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Chen L, Yao Y. Emerging Trends and Research Hotspots of Remote Ischemic Preconditioning in Cardiac Surgery: A Bibliometric Analysis. J Eval Clin Pract 2025; 31:e70111. [PMID: 40344270 DOI: 10.1111/jep.70111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 03/21/2025] [Accepted: 04/06/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND Remote ischemic preconditioning (RIPC) is a key area in cardiovascular research, but inconsistent findings have made it hard to fully understand. Bibliometrics, using mathematics and statistics, can track trends and progress in research over time. This study uses bibliometrics to assess RIPC trends and hotspots in cardiac surgery, aiming to better understand future research. METHODS AND RESULTS Studies on RIPC were retrieved from the Web of Science Core Collection, with 104 studies included contributing countries, collaborative countries, institutions, authors, journals, keywords, research topics, citation patterns, and the current state of research. in this field were visually analyzed by using R platform, VOS viewer, and Microsoft Excel. These publications mainly came from 29 countries and 65 institutions. All experiments were clinical studies, and the type of surgery involved was cardiac surgery. A significant percentage of publications occurred during the period from 2010 to 2020 (75; 72.11%). Germany made the most significant contribution to this field with 27 (25.96%) papers and had the highest total citation count (2314). J Thorac Cardiovasc Surg published the most studies (n = 6), followed by Basic Res Cardiol (n = 5). We identified 89 authors, among which Patrick Meybohm, Juergen Peters, and Matthias Thielmann had the most studies (n = 10). CONCLUSIONS RIPC has significant research value and potential in cardiac surgery, mainly focusing on organ protection during adult heart surgeries, especially myocardial protection. Although Germany and China are leading, more international cooperation is needed. Large-scale, standardized randomized controlled trials on RIPC are essential to provide higher-level evidence-based medical research.
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Affiliation(s)
- Linlin Chen
- Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Yuntai Yao
- Department of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Keim C, Wiedenmann L, Schubert T, Rothe M, Dobre BC, Kaess BM, Ehrlich JR, Boehmer AA. Remote Ischemic Preconditioning for Electrical Cardioversion of Atrial Fibrillation-the Prospective Randomized PRECON-AF Study. CJC Open 2025; 7:571-578. [PMID: 40433224 PMCID: PMC12105482 DOI: 10.1016/j.cjco.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 03/05/2025] [Indexed: 05/29/2025] Open
Abstract
Background Electrical cardioversion (ECV) is highly effective in restoring sinus rhythm in patients with atrial fibrillation (AF), but it does not influence long-term rhythm control. Remote ischemic preconditioning (RIPC) has demonstrated various cardioprotective effects. Combining ECV with RIPC could provide a promising approach to minimizing AF recurrences after successful ECV. Methods This prospective, randomized, single-blinded, single-centre study investigated the impact of RIPC on early AF recurrence following successful ECV (defined as sinus rhythm ≥ 30 seconds). Patients were randomized in a 1:1 ratio to receive either RIPC or sham preconditioning before ECV. RIPC was performed in a standardized manner, with 3 cycles of 5-minute forearm ischemia followed by 5 minutes of reperfusion. The primary efficacy endpoint was AF recurrence after 30 days. Safety endpoints included death, stroke, and procedure-related complications. Secondary endpoints were acute ECV success, mean energy, and number of shocks required to restore sinus rhythm. Results A total of 240 patients were enrolled. Of these, 214 (89%) had successful ECV. At follow-up, the RIPC group did not show a lower AF recurrence rate, compared to that in the sham group (39% vs 36%, P = 0.63), and no effect of RIPC on cardioversion parameters was seen. One stroke occurred in the RIPC group. The study was terminated before the number of prespecified follow-up visits was reached, due to determination of futility. Conclusions RIPC did not impact the short-term rhythm-control or cardioversion procedure in patients with AF undergoing ECV. Clinical Trial Registration NCT05342220.
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Affiliation(s)
- Christoph Keim
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Lilli Wiedenmann
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Tim Schubert
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
- Department of Pediatric Cardiology and Congenital Heart Disease, Heidelberg University Hospital, Heidelberg, Germany
| | - Moritz Rothe
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Bianca C. Dobre
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Bernhard M. Kaess
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Joachim R. Ehrlich
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Andreas A. Boehmer
- Department of Cardiology, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
- Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada
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Wang DD, Xu B, Sun JJ, Sui M, Li SP, Chen YJ, Zhang YL, Wu JB, Teng SY, Pang QF, Hu CX. MOTS-c mimics remote ischemic preconditioning in protecting against lung ischemia-reperfusion injury by alleviating endothelial barrier dysfunction. Free Radic Biol Med 2025; 229:127-138. [PMID: 39827923 DOI: 10.1016/j.freeradbiomed.2025.01.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/08/2025] [Accepted: 01/09/2025] [Indexed: 01/22/2025]
Abstract
Remote ischemic preconditioning (RIPC) induces the expression of unidentified protective cytokines that mitigate lung ischemia-reperfusion injury (LIRI). This study hypothesizes that MOTS-c, a mitokine with potent protective effects against mitochondrial damage, contributes to RIPC-mediated protection by alleviating endothelial barrier dysfunction. In human lung transplantation patients, serum levels of MOTS-c significantly decreased following IR injury but were markedly increased when RIPC was performed prior to transplantation. Similarly, in a mouse model of LIRI, RIPC restored serum MOTS-c levels and improved lung injury outcomes. Intravenous administration of MOTS-c in mice replicated the protective effects observed with RIPC. Mechanistic studies demonstrated that repeated hypoxia in human primary skeletal muscle immortalized cells (HPSMIC) led to the secretion of conditioned media that protected HUVECs from OGD/R-induced injury; silencing MOTS-c abolished these protective effects. Further investigations using nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice and the Nrf2 inhibitor ML385 revealed that MOTS-c exerts its protective function by increasing Nrf2 protein levels, thereby maintaining endothelial barrier integrity. In conclusion, this study identifies MOTS-c as a novel mediator of RIPC's protective effects against LIRI and highlights its potential as a therapeutic alternative for preventing lung injury and preserving vascular endothelial function.
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Affiliation(s)
- Dan-Dan Wang
- Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu province, China; Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China
| | - Bo Xu
- Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China
| | - Jiao-Jiao Sun
- Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu province, China; Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China
| | - Meng Sui
- Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China
| | - Sheng-Peng Li
- Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu province, China
| | - Yi-Jing Chen
- Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu province, China
| | - Yan-Li Zhang
- Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu province, China
| | - Jin-Bo Wu
- Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China
| | - Shi-Yong Teng
- Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China
| | - Qing-Fang Pang
- Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu province, China.
| | - Chun-Xiao Hu
- Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China.
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Jia P, Ji Q, Zou Z, Zeng Q, Ren T, Chen W, Yan Z, Shen D, Li Y, Peng F, Su Y, Xu J, Shen B, Luo Z, Wang C, Ding X. Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial. Circulation 2024; 150:1366-1376. [PMID: 39319450 PMCID: PMC11495536 DOI: 10.1161/circulationaha.124.071408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/04/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery. METHODS This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. RESULTS A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47-1.00]; P=0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. CONCLUSIONS Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI. REGISTRATION URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000035568.
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Affiliation(s)
- Ping Jia
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Qiang Ji
- Department of Cardiovascular Surgery (Q.J., C.W.), Zhongshan Hospital, Fudan University, Shanghai
| | - Zhouping Zou
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Qi Zeng
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Ting Ren
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Weize Chen
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Zhixin Yan
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Daoqi Shen
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Yang Li
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Fangyuan Peng
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Ying Su
- Cardiac Intensive Care Center (Y.S., Z.L.), Zhongshan Hospital, Fudan University, Shanghai
| | - Jiarui Xu
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Bo Shen
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
| | - Zhe Luo
- Cardiac Intensive Care Center (Y.S., Z.L.), Zhongshan Hospital, Fudan University, Shanghai
| | - Chunsheng Wang
- Department of Cardiovascular Surgery (Q.J., C.W.), Zhongshan Hospital, Fudan University, Shanghai
| | - Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., Z.Z., Q.Z., T.R., W.C., Z.Y., D.S., Y.L., F.P., B.S., J.X., X.D.)
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Pham PNV, Yahsaly L, Ochsenfarth C, Giebel B, Schnitzler R, Zahn P, Frey UH. Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease. Int J Mol Sci 2024; 25:9304. [PMID: 39273253 PMCID: PMC11395148 DOI: 10.3390/ijms25179304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/26/2024] [Accepted: 08/26/2024] [Indexed: 09/15/2024] Open
Abstract
Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.
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Affiliation(s)
- Phuong N V Pham
- Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany
| | - Loubna Yahsaly
- Department of Cardiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Crista Ochsenfarth
- Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany
| | - Bernd Giebel
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Romina Schnitzler
- Department of Anesthesiology, Intensive Care and Pain Medicine, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany
| | - Peter Zahn
- Department of Anesthesiology, Intensive Care and Pain Medicine, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany
| | - Ulrich H Frey
- Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany
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Sabe SA, Harris DD, Broadwin M, Sellke FW. Cardioprotection in cardiovascular surgery. Basic Res Cardiol 2024; 119:545-568. [PMID: 38856733 DOI: 10.1007/s00395-024-01062-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 05/31/2024] [Accepted: 06/01/2024] [Indexed: 06/11/2024]
Abstract
Since the invention of cardiopulmonary bypass, cardioprotective strategies have been investigated to mitigate ischemic injury to the heart during aortic cross-clamping and reperfusion injury with cross-clamp release. With advances in cardiac surgical and percutaneous techniques and post-operative management strategies including mechanical circulatory support, cardiac surgeons are able to operate on more complex patients. Therefore, there is a growing need for improved cardioprotective strategies to optimize outcomes in these patients. This review provides an overview of the basic principles of cardioprotection in the setting of cardiac surgery, including mechanisms of cardiac injury in the context of cardiopulmonary bypass, followed by a discussion of the specific approaches to optimizing cardioprotection in cardiac surgery, including refinements in cardiopulmonary bypass and cardioplegia, ischemic conditioning, use of specific anesthetic and pharmaceutical agents, and novel mechanical circulatory support technologies. Finally, translational strategies that investigate cardioprotection in the setting of cardiac surgery will be reviewed, with a focus on promising research in the areas of cell-based and gene therapy. Advances in this area will help cardiologists and cardiac surgeons mitigate myocardial ischemic injury, improve functional post-operative recovery, and optimize clinical outcomes in patients undergoing cardiac surgery.
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Affiliation(s)
- Sharif A Sabe
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA
| | - Dwight D Harris
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA
| | - Mark Broadwin
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA
| | - Frank W Sellke
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA.
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Hadebe N, Cour M, Imamdin A, Petersen T, Pennel T, Scherman J, Snowball J, Ntsekhe M, Zilla P, Swanevelder J, Lecour S. Cardioprotection with Intralipid During Coronary Artery Bypass Grafting Surgery on Cardiopulmonary Bypass: A Randomized Clinical Trial. Cardiovasc Drugs Ther 2024:10.1007/s10557-024-07594-w. [PMID: 38864969 DOI: 10.1007/s10557-024-07594-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/30/2024] [Indexed: 06/13/2024]
Abstract
PURPOSE Coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB) is associated with myocardial ischemia-reperfusion injury (IRI), which may limit the benefit of the surgery. Both experimental and clinical studies suggest that Intralipid, a lipid emulsion commonly used for parenteral nutrition, can limit myocardial IRI. We therefore aimed to investigate whether Intralipid administered at reperfusion can reduce myocardial IRI in patients undergoing CABG on CPB. METHODS We conducted a randomized, double-blind, pilot trial in which 29 adult patients scheduled for CABG were randomly assigned (on a 1:1 basis) to receive either 1.5 ml/kg Intralipid 20% or Ringer's Lactate 3 min before aortic cross unclamping. The primary endpoint was the 72-h area under the curve (AUC) for troponin I. RESULTS Of the 29 patients randomized, 26 were included in the study (two withdrew consent and one was excluded before surgery). The 72-h AUC for troponin I did not significantly differ between the control and Intralipid group (546437 ± 205518 versus 487561 ± 115724 arbitrary units, respectively; P = 0.804). Other outcomes (including 72-h AUC for CK-MB, C-reactive protein, need for defibrillation, time to extubation, length of ICU and hospital stay, and serious adverse events) were similar between the two groups. CONCLUSION In patients undergoing CABG on CPB, Intralipid did not limit myocardial IRI compared to placebo. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02807727 (registration date: 16 June 2016).
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Affiliation(s)
- Nkanyiso Hadebe
- Cardioprotection Group, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Anzio Road, Cape Town, 7925, Observatory, South Africa
- Department of Anaesthesia, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Martin Cour
- Cardioprotection Group, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Anzio Road, Cape Town, 7925, Observatory, South Africa
| | - Aqeela Imamdin
- Cardioprotection Group, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Anzio Road, Cape Town, 7925, Observatory, South Africa
| | - Tarra Petersen
- Cardioprotection Group, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Anzio Road, Cape Town, 7925, Observatory, South Africa
| | - Timothy Pennel
- Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Cape Town, South Africa
| | - Jacques Scherman
- Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Cape Town, South Africa
| | - Jane Snowball
- Cardioprotection Group, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Anzio Road, Cape Town, 7925, Observatory, South Africa
| | - Mpiko Ntsekhe
- Division of Cardiology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Peter Zilla
- Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Cape Town, South Africa
| | - Justiaan Swanevelder
- Department of Anaesthesia, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Sandrine Lecour
- Cardioprotection Group, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Anzio Road, Cape Town, 7925, Observatory, South Africa.
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Milne B, John M, Evans R, Robertson S, Ó Scanaill P, Murphy GJ, Landoni G, Marber M, Clayton T, Kunst G. Comparison between propofol and total inhalational anaesthesia on cardiovascular outcomes following on-pump cardiac surgery in higher-risk patients: a randomised controlled pilot and feasibility study. Open Heart 2024; 11:e002630. [PMID: 38724266 PMCID: PMC11086547 DOI: 10.1136/openhrt-2024-002630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 04/14/2024] [Indexed: 05/12/2024] Open
Abstract
OBJECTIVES Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. METHODS In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. RESULTS All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. CONCLUSIONS It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. TRIAL REGISTRATION NUMBER NCT04039854.
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Affiliation(s)
- Benjamin Milne
- Department of Anaesthetics and Pain Therapy, King's College Hospital NHS Foundation Trust, London, UK
| | - Martin John
- Department of Anaesthesia, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | - Richard Evans
- London School of Hygiene and Tropical Medicine, Medical Statistics, 1 Keppel Street, London WC1E 7HT, UK
| | - Steven Robertson
- London School of Hygiene and Tropical Medicine, Medical Statistics, 1 Keppel Street, London WC1E 7HT, UK
| | - Pádraig Ó Scanaill
- Department of Anaesthetics and Pain Therapy, King's College Hospital NHS Foundation Trust, London, UK
| | - Gavin J Murphy
- Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester, UK
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Michael Marber
- School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK
| | - Tim Clayton
- London School of Hygiene and Tropical Medicine, Medical Statistics, 1 Keppel Street, London WC1E 7HT, UK
| | - Gudrun Kunst
- Department of Anaesthetics and Pain Therapy, King's College Hospital NHS Foundation Trust, London, UK
- School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK
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9
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Drury NE, van Doorn C, Woolley RL, Amos-Hirst RJ, Bi R, Spencer CM, Morris KP, Montgomerie J, Stickley J, Crucean A, Gill A, Hill M, Weber RJ, Najdekr L, Jankevics A, Southam AD, Lloyd GR, Jaber O, Kassai I, Pelella G, Khan NE, Botha P, Barron DJ, Madhani M, Dunn WB, Ives NJ, Kirchhof P, Jones TJ. Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery. JTCVS OPEN 2024; 18:193-208. [PMID: 38690427 PMCID: PMC11056492 DOI: 10.1016/j.xjon.2024.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 01/30/2024] [Accepted: 02/20/2024] [Indexed: 05/02/2024]
Abstract
Objective The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.
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Affiliation(s)
- Nigel E. Drury
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - Carin van Doorn
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Rebecca L. Woolley
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Rebecca J. Amos-Hirst
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Rehana Bi
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - Collette M. Spencer
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Kevin P. Morris
- Department of Paediatric Intensive Care, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - James Montgomerie
- Department of Paediatric Cardiac Anesthesia, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - John Stickley
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - Adrian Crucean
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - Alicia Gill
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Matt Hill
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Ralf J.M. Weber
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Lukas Najdekr
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Andris Jankevics
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Andrew D. Southam
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Gavin R. Lloyd
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Osama Jaber
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Imre Kassai
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Giuseppe Pelella
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Natasha E. Khan
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - Phil Botha
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - David J. Barron
- Division of Cardiovascular Surgery, Hospital for Sick Children, Toronto, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - Melanie Madhani
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Warwick B. Dunn
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular, and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Natalie J. Ives
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Paulus Kirchhof
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- Department of Cardiology, University Heart and Vascular Centre, UKE Hamburg, Hamburg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - Timothy J. Jones
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
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10
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Chang H, Chen E, Zhu T, Liu J, Chen C. Communication Regarding the Myocardial Ischemia/Reperfusion and Cognitive Impairment: A Narrative Literature Review. J Alzheimers Dis 2024; 97:1545-1570. [PMID: 38277294 PMCID: PMC10894588 DOI: 10.3233/jad-230886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/07/2023] [Indexed: 01/28/2024]
Abstract
Coronary artery disease is a prevalent ischemic disease that results in insufficient blood supply to the heart muscle due to narrowing or occlusion of the coronary arteries. Various reperfusion strategies, including pharmacological thrombolysis and percutaneous coronary intervention, have been developed to enhance blood flow restoration. However, these interventions can lead to myocardial ischemia/reperfusion injury (MI/RI), which can cause unpredictable complications. Recent research has highlighted a compelling association between MI/RI and cognitive function, revealing pathophysiological mechanisms that may explain altered brain cognition. Manifestations in the brain following MI/RI exhibit pathological features resembling those observed in Alzheimer's disease (AD), implying a potential link between MI/RI and the development of AD. The pro-inflammatory state following MI/RI may induce neuroinflammation via systemic inflammation, while impaired cardiac function can result in cerebral under-perfusion. This review delves into the role of extracellular vesicles in transporting deleterious substances from the heart to the brain during conditions of MI/RI, potentially contributing to impaired cognition. Addressing the cognitive consequence of MI/RI, the review also emphasizes potential neuroprotective interventions and pharmacological treatments within the MI/RI model. In conclusion, the review underscores the significant impact of MI/RI on cognitive function, summarizes potential mechanisms of cardio-cerebral communication in the context of MI/RI, and offers ideas and insights for the prevention and treatment of cognitive dysfunction following MI/RI.
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Affiliation(s)
- Haiqing Chang
- Department of Anesthesiology, West China Hospital, Sichuan University, Sichuan, China
- Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Erya Chen
- Department of Anesthesiology, West China Hospital, Sichuan University, Sichuan, China
- Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tao Zhu
- Department of Anesthesiology, West China Hospital, Sichuan University, Sichuan, China
- Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jin Liu
- Department of Anesthesiology, West China Hospital, Sichuan University, Sichuan, China
- Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chan Chen
- Department of Anesthesiology, West China Hospital, Sichuan University, Sichuan, China
- Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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11
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Anttila T, Herajärvi J, Laaksonen H, Mustonen C, Honkanen HP, Y Dimova E, Piuhola J, Koivunen P, Juvonen T, Anttila V. Remote ischemic preconditioning and hypoxia-induced biomarkers in acute myocardial infarction: study on a porcine model. SCAND CARDIOVASC J 2023; 57:2251730. [PMID: 37641930 DOI: 10.1080/14017431.2023.2251730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/19/2023] [Accepted: 08/18/2023] [Indexed: 08/31/2023]
Abstract
Objectives. Remote ischemic preconditioning (RIPC) mitigates acute myocardial infarction (AMI). We hypothesized that RIPC reduces the size and severity of AMI and explored molecular mechanisms behind this phenomenon. Design. In two series of experiments, piglets underwent 60 min of the circumflex coronary artery occlusion, resulting in AMI. Piglets were randomly assigned into the RIPC groups (n = 7 + 7) and the control groups (n = 7 + 7). The RIPC groups underwent four 5-min hind limb ischemia-reperfusion cycles before AMI. In series I, the protective efficacy of RIPC was investigated by using biomarkers and echocardiography with a follow-up of 24 h. In series II, the heart of each piglet was harvested for TTC-staining to measure infarct size. Muscle biopsies were collected from the hind limb to explore molecular mechanisms of RIPC using qPCR and Western blot analysis. Results. The levels of CK-MBm (p = 0.032) and TnI (p = 0.007) were lower in the RIPC group. Left ventricular ejection fraction in the RIPC group was greater at the end of the follow-up. The myocardial infarct size in the RIPC group was smaller (p = 0.033). Western blot indicated HIF1α stabilization in the skeletal muscle of the RIPC group. PCR analyses showed upregulation of the HIF target mRNAs for glucose transporter (GLUT1), glucose transporter 4 (GLUT4), phosphofructokinase 1 (PFK1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase 1 (ENO1), lactate dehydrogenase (LDHA) and endothelial nitric oxidate synthase (eNOS). Conclusions. Biochemical, physiologic, and histologic evidence confirms that RIPC decreases the size of AMI. The HIF pathway is likely involved in the mechanism of the RIPC.
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Affiliation(s)
- Tuomas Anttila
- Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Johanna Herajärvi
- Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Henna Laaksonen
- Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Caius Mustonen
- Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Hannu-Pekka Honkanen
- Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Elitsa Y Dimova
- Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
| | - Jarkko Piuhola
- Department of Cardiology, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Peppi Koivunen
- Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
| | - Tatu Juvonen
- Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
- Department of Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Vesa Anttila
- Heart Center, Turku University Hospital, University of Turku, Turku, Finland
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12
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Xing J, Loh SKN. Perioperative acute kidney injury: Current knowledge and the role of anaesthesiologists. PROCEEDINGS OF SINGAPORE HEALTHCARE 2023. [DOI: 10.1177/20101058231163406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023] Open
Abstract
Background Among the different types of perioperative organ injury, acute kidney injury (AKI) occurs frequently and is consistently associated with increased rates of mortality and mortality. Despite development of many clinical trials to assess perioperative interventions, reliable means to prevent or reverse AKI are still lacking. Objectives This narrative review discusses recent literature on modifiable risk factors, current approaches to prevention and potential directions for future research. Methods A Pubmed search with the relevant keywords was done for articles published in the last 10 years. Results New insights into preoperative identification and optimisation, intraoperative strategies, including the choice of anaesthetic, haemodynamic and fluid management, have been made, with the aim of preventing perioperative AKI. Conclusion A patient-centric multidisciplinary approach is essential to protect kidney function of patients going for surgery. Much can be done by anaesthesiologists perioperatively, to reduce the risk of development of AKI, especially in susceptible patients. There is a need for further multicentred trials to enhance the currently generic perioperative recommendations.
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Affiliation(s)
- Jieyin Xing
- Division of Anaesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore
| | - Samuel Kent Neng Loh
- Division of Anaesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore
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13
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Kotani Y, Pruna A, Landoni G. Mechanisms of Action of the Detrimental Effects of Propofol on Survival. J Cardiothorac Vasc Anesth 2023; 37:2176-2180. [PMID: 37586953 DOI: 10.1053/j.jvca.2023.07.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/19/2023] [Accepted: 07/22/2023] [Indexed: 08/18/2023]
Abstract
Due to its favorable pharmacologic features, propofol is the most commonly used hypnotic agent in perioperative and intensive care settings. However, it also has adverse effects like propofol infusion syndrome and an increased risk of infection. Growing evidence suggests that propofol may worsen clinical outcomes by inhibiting the organ-protective properties of other interventions, such as volatile anesthetics or remote ischemic preconditioning. This editorial describes possible mechanisms underlying the detrimental effects of propofol, and provides an overview of the results of clinical trials evaluating the effects of propofol in various settings.
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Affiliation(s)
- Yuki Kotani
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Japan
| | - Alessandro Pruna
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
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14
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Hariri G, Collet L, Duarte L, Martin GL, Resche-Rigon M, Lebreton G, Bouglé A, Dechartres A. Prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis of non-pharmacological interventions. Crit Care 2023; 27:354. [PMID: 37700297 PMCID: PMC10498585 DOI: 10.1186/s13054-023-04640-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 09/06/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. METHODS We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I2 = 0%; Phet = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I2 = 23%; Phet = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I2 = 53%; Phet < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; Phet = 0.67; I2 = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; Phet = 0.25; I2 = 26%). CONCLUSIONS Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.
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Affiliation(s)
- Geoffroy Hariri
- Département de Santé Publique, UMR-S 1136, AP-HP, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France.
- Département d'anesthésie et réanimation, GRC 29, DMU DREAM, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013, Paris, France.
| | - Lucie Collet
- Département de Santé Publique, UMR-S 1136, AP-HP, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Lucie Duarte
- Département d'anesthésie et réanimation, GRC 29, DMU DREAM, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013, Paris, France
| | - Guillaume L Martin
- Département de Santé Publique, UMR-S 1136, AP-HP, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Matthieu Resche-Rigon
- ECSTRRA - CRESS UMR1153, INSERM and SBIM, AP-HP, Hôpital Saint-Louis, Université de Paris, Paris, France
| | - Guillaume Lebreton
- AP-HP, Service de Chirurgie Cardiaque, Institut de Cardiologie, Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013, Paris, France
| | - Adrien Bouglé
- Département d'anesthésie et réanimation, GRC 29, DMU DREAM, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013, Paris, France
| | - Agnès Dechartres
- Département de Santé Publique, UMR-S 1136, AP-HP, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France
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15
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Li Z, Cheng Q, He Y, Wang S, Xie J, Zheng Y, Liu Y, Li L, Gao S, Yu C. Effect of Dan-Lou tablets on coronary heart disease revealed by microarray analysis integrated with molecular mechanism studies. Heliyon 2023; 9:e15777. [PMID: 37305453 PMCID: PMC10256850 DOI: 10.1016/j.heliyon.2023.e15777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 06/13/2023] Open
Abstract
Dan-Lou tablets (DLT) effectively treat coronary heart disease (CHD). However, its pharmacological mechanism in CHD treatment requires further investigation. This study aimed to elucidate the underlying pharmacological mechanisms of DLT in the treatment of CHD through clinical trials, microarray research, bioinformatics analysis, and molecular mechanism research. In this study, DLT improved coagulation function, endothelial injury, and levels of lipids, metalloproteases, adhesion molecules, inflammatory mediators, and homocysteine. The results of molecular biology research demonstrated that DLT can increase the gene and protein expressions of meningioma expressed antigen 5 (MGEA5) and mouse doubleminute 2 (MDM2) and inhibited the gene and protein expressions of signal transcription and transcription activator 5 B (STAT5B), tropomyosin-1 (TPM1), and aromatic hydrocarbon receptor nuclear transpose (ARNT). The results indicate that DLT reduced the extent of vascular endothelial damage in CHD rats by reducing the expressions of STAT5B, TPM1, and MDM2; inhibiting the inflammatory reaction; and increasing the expressions of ARNT and MGEA5.
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Affiliation(s)
| | | | | | | | | | | | | | - Lin Li
- Corresponding author. No. 10, Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin, China.
| | - Shan Gao
- Corresponding author. No. 10, Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin, China.
| | - Chunquan Yu
- Corresponding author. No. 10, Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin, China.
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16
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Leung CH, Rizoli SB, Trypcic S, Rhind SG, Battista AP, Ailenberg M, Rotstein OD. Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial. Sci Rep 2023; 13:7025. [PMID: 37120600 PMCID: PMC10148877 DOI: 10.1038/s41598-023-33681-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 04/17/2023] [Indexed: 05/01/2023] Open
Abstract
Resuscitation induced ischemia/reperfusion predisposes trauma patients to systemic inflammation and organ dysfunction. We investigated the effect of remote ischemic conditioning (RIC), a treatment shown to prevent ischemia/reperfusion injury in experimental models of hemorrhagic shock/resuscitation, on the systemic immune-inflammatory profile in trauma patients in a randomized trial. We conducted a prospective, single-centre, double-blind, randomized, controlled trial involving trauma patients sustaining blunt or penetrating trauma in hemorrhagic shock admitted to a Level 1 trauma centre. Patients were randomized to receive RIC (four cycles of 5-min pressure cuff inflation at 250 mmHg and deflation on the thigh) or a Sham intervention. The primary outcomes were neutrophil oxidative burst activity, cellular adhesion molecule expression, and plasma levels of myeloperoxidase, cytokines and chemokines in peripheral blood samples, drawn at admission (pre-intervention), 1 h, 3 h, and 24 h post-admission. Secondary outcomes included ventilator, ICU and hospital free days, incidence of nosocomial infections, 24 h and 28 day mortality. 50 eligible patients were randomized; of which 21 in the Sham group and 18 in the RIC group were included in the full analysis. No treatment effect was observed between Sham and RIC groups for neutrophil oxidative burst activity, adhesion molecule expression, and plasma levels of myeloperoxidase and cytokines. RIC prevented significant increases in Th2 chemokines TARC/CCL17 (P < 0.01) and MDC/CCL22 (P < 0.05) at 24 h post-intervention in comparison to the Sham group. Secondary clinical outcomes were not different between groups. No adverse events in relation to the RIC intervention were observed. Administration of RIC was safe and did not adversely affect clinical outcomes. While trauma itself modified several immunoregulatory markers, RIC failed to alter expression of the majority of markers. However, RIC may influence Th2 chemokine expression in the post resuscitation period. Further investigation into the immunomodulatory effects of RIC in traumatic injuries and their impact on clinical outcomes is warranted.ClinicalTrials.gov number: NCT02071290.
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Affiliation(s)
- C H Leung
- The Keenan Research Centre for Biomedical Science and the Department of Surgery, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Li Ka Shing Knowledge Institute 3-305, Toronto, ON, M5B 1W8, Canada
| | - S B Rizoli
- The Keenan Research Centre for Biomedical Science and the Department of Surgery, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Li Ka Shing Knowledge Institute 3-305, Toronto, ON, M5B 1W8, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - S Trypcic
- The Keenan Research Centre for Biomedical Science and the Department of Surgery, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Li Ka Shing Knowledge Institute 3-305, Toronto, ON, M5B 1W8, Canada
| | - S G Rhind
- The Defence Research and Development Canada, Toronto Research Centre, Toronto, Canada
| | - A P Battista
- The Defence Research and Development Canada, Toronto Research Centre, Toronto, Canada
| | - M Ailenberg
- The Keenan Research Centre for Biomedical Science and the Department of Surgery, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Li Ka Shing Knowledge Institute 3-305, Toronto, ON, M5B 1W8, Canada.
| | - O D Rotstein
- The Keenan Research Centre for Biomedical Science and the Department of Surgery, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Li Ka Shing Knowledge Institute 3-305, Toronto, ON, M5B 1W8, Canada.
- Department of Surgery, University of Toronto, Toronto, Canada.
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Kotani Y, Pruna A, Turi S, Borghi G, Lee TC, Zangrillo A, Landoni G, Pasin L. Propofol and survival: an updated meta-analysis of randomized clinical trials. Crit Care 2023; 27:139. [PMID: 37046269 PMCID: PMC10099692 DOI: 10.1186/s13054-023-04431-8] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 04/05/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Propofol is one of the most widely used hypnotic agents in the world. Nonetheless, propofol might have detrimental effects on clinically relevant outcomes, possibly due to inhibition of other interventions' organ protective properties. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate if propofol reduced survival compared to any other hypnotic agent in any clinical setting. METHODS We searched eligible studies in PubMed, Google Scholar, and the Cochrane Register of Clinical Trials. The following inclusion criteria were used: random treatment allocation and comparison between propofol and any comparator in any clinical setting. The primary outcome was mortality at the longest follow-up available. We conducted a fixed-effects meta-analysis for the risk ratio (RR). Using this RR and 95% confidence interval, we estimated the probability of any harm (RR > 1) through Bayesian statistics. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022323143). RESULTS We identified 252 randomized trials comprising 30,757 patients. Mortality was higher in the propofol group than in the comparator group (760/14,754 [5.2%] vs. 682/16,003 [4.3%]; RR = 1.10; 95% confidence interval, 1.01-1.20; p = 0.03; I2 = 0%; number needed to harm = 235), corresponding to a 98.4% probability of any increase in mortality. A statistically significant mortality increase in the propofol group was confirmed in subgroups of cardiac surgery, adult patients, volatile agent as comparator, large studies, and studies with low mortality in the comparator arm. CONCLUSIONS Propofol may reduce survival in perioperative and critically ill patients. This needs careful assessment of the risk versus benefit of propofol compared to other agents while planning for large, pragmatic multicentric randomized controlled trials to provide a definitive answer.
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Affiliation(s)
- Yuki Kotani
- Department of Anesthesia and Intensive Care, San Raffaele Hospital, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Japan
| | - Alessandro Pruna
- Department of Anesthesia and Intensive Care, San Raffaele Hospital, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy
| | - Stefano Turi
- Department of Anesthesia and Intensive Care, San Raffaele Hospital, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy
| | - Giovanni Borghi
- Department of Anesthesia and Intensive Care, San Raffaele Hospital, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy
| | - Todd C Lee
- Division of Infectious Diseases, Department of Medicine, McGill University, Montreal, QC, Canada
| | - Alberto Zangrillo
- Department of Anesthesia and Intensive Care, San Raffaele Hospital, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, San Raffaele Hospital, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy.
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
| | - Laura Pasin
- Anesthesia and Intensive Care Unit, Padua University Hospital, Padua, Italy
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Li J, Wang X, Liu W, Wen S, Li X. Remote ischemic preconditioning and clinical outcomes after pediatric cardiac surgery: a systematic review and meta-analysis. BMC Anesthesiol 2023; 23:105. [PMID: 37005591 PMCID: PMC10067320 DOI: 10.1186/s12871-023-02064-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/22/2023] [Indexed: 04/04/2023] Open
Abstract
BACKGROUND The benefit of remote ischemia preconditioning (RIPreC) in pediatric cardiac surgery is unclear. The objective of this systematic review and meta-analysis was to examine the effectiveness of RIPreC in reducing the duration of mechanical ventilation and intensive care unit (ICU) length of stay after pediatric cardiac surgery. METHODS We searched PubMed, EMBASE and the Cochrane Library from inception to December 31, 2022. Randomized controlled trials comparing RIPreC versus control in children undergoing cardiac surgery were included. The risk of bias of included studies was assessed using the Risk of Bias 2 (RoB 2) tool. The outcomes of interest were postoperative duration of mechanical ventilation and ICU length of stay. We conducted random-effects meta-analysis to calculate weighted mean difference (WMD) with 95% confidence interval (CI) for the outcomes of interest. We performed sensitivity analysis to examine the influence of intraoperative propofol use. RESULTS Thirteen trials enrolling 1,352 children were included. Meta-analyses of all trials showed that RIPreC did not reduce postoperative duration of mechanical ventilation (WMD -5.35 h, 95% CI -12.12-1.42) but reduced postoperative ICU length of stay (WMD -11.48 h, 95% CI -20.96- -2.01). When only trials using propofol-free anesthesia were included, both mechanical ventilation duration (WMD -2.16 h, 95% CI -3.87- -0.45) and ICU length of stay (WMD -7.41 h, 95% CI -14.77- -0.05) were reduced by RIPreC. The overall quality of evidence was moderate to low. CONCLUSIONS The effects of RIPreC on clinical outcomes after pediatric cardiac surgery were inconsistent, but both postoperative mechanical ventilation duration and ICU length of stay were reduced in the subgroup of children not exposed to propofol. These results suggested a possible interaction effect of propofol. More studies with adequate sample size and without intraoperative propofol use are needed to define the role of RIPreC in pediatric cardiac surgery.
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Affiliation(s)
- Jianwen Li
- Departments of Anesthesiology, DongGuan SongShan Lake Tungwah Hospital, DongGuan, China
| | - Xiwen Wang
- Departments of Anesthesiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wengui Liu
- Departments of Anesthesiology, DongGuan SongShan Lake Tungwah Hospital, DongGuan, China
| | - Shihong Wen
- Departments of Anesthesiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Xueping Li
- Departments of Anesthesiology, DongGuan SongShan Lake Tungwah Hospital, DongGuan, China.
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19
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Processed Electroencephalographic Use During Anesthesia and Outcomes: Analysis of The Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg 2022; 114:1688-1694. [PMID: 34717905 DOI: 10.1016/j.athoracsur.2021.09.049] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 08/12/2021] [Accepted: 09/20/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND This study assessed associations between processed electroencephalographic (pEEG) use during anesthesia, surgery- and anesthesia-related risk factors, and neurologic outcomes and mortality after cardiac surgery. METHODS Drawing from The Society of Thoracic Surgeons Adult Cardiac Surgery Database and its Adult Cardiac Anesthesiology Section, we identified 42 932 records for elective, urgent, and emergency cardiac surgical procedures between July 1, 2017 and December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the associations between pEEG use during anesthesia on the primary outcome, postoperative delirium (POD), and secondary outcomes of stroke, encephalopathy, coma, and operative mortality. RESULTS The rate of pEEG use during anesthesia use was 32.8% (n = 14 086), and its use was not associated with decreased odds for POD (odds ratio [OR], 0.88; 95% CI, 0.78-1.02) or encephalopathy (OR, 0.85; 95% CI, 0.70-1.03). Intraoperative pEEG monitoring use was also not associated with increased odds for stroke (OR, 1.17; 95% CI, 0.97-1.42) or coma (OR, 1.44; 95% CI, 0.82-2.52). In contrast, pEEG use during anesthesia was associated with higher odds for operative mortality (OR, 1.23; 95% CI, 1.05-1.44). This association remained significant after adjusting for POD (OR, 1.21; 95% CI, 1.03-1.41), stroke (OR, 1.21; 95% CI, 1.04-1.42), and encephalopathy (OR, 1.28; 95% CI, 1.07-1.52). CONCLUSIONS This large retrospective database study found no association between pEEG use during cardiac surgery and postoperative neurologic outcomes such as POD, stroke, encephalopathy, or coma. However, patients who underwent pEEG monitoring during anesthesia experienced higher mortality, even after adjustment for neurologic outcomes.
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20
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Assad RS, Guedes MGA, Aiello VD, Thomaz PG, Zanoni FL, Saito M, da Silva APN, Coutinho E Silva RDS, Pinto MV, Jatene MB, Moreira LFP. Ischemic preconditioning does not prevent placental dysfunction induced by fetal cardiac bypass. J Card Surg 2022; 37:2592-2599. [PMID: 35775747 DOI: 10.1111/jocs.16718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/05/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. METHODS Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-min period, followed by a 2-min reperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. RESULTS The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2 , mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1 in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1 (VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-α, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-min post-bypass (p > .133). CONCLUSION Although rIPC allowed increased blood flow during fetal CB and decreased IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.
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Affiliation(s)
- Renato S Assad
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Marcelo G A Guedes
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Vera D Aiello
- Division of Pathology, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Petronio G Thomaz
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Fernando L Zanoni
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Mauricio Saito
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Ana Paula N da Silva
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | | | - Marcelo V Pinto
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Marcelo B Jatene
- Division of Pediatric Cardiac Surgery, Heart Institute University of São Paulo, São Paulo, Brazil
| | - Luiz Felipe P Moreira
- Laboratory of Cardiovascular Research, Heart Institute University of São Paulo, São Paulo, Brazil
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21
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Penna C, Comità S, Tullio F, Alloatti G, Pagliaro P. Challenges facing the clinical translation of cardioprotection: 35 years after the discovery of ischemic preconditioning. Vascul Pharmacol 2022; 144:106995. [PMID: 35470102 DOI: 10.1016/j.vph.2022.106995] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/17/2022] [Accepted: 04/16/2022] [Indexed: 12/19/2022]
Abstract
Since coronary reperfusion was introduced into clinical practice in the late 1970s, the further translation of several successful animal experiments on cardioprotection into clinical practice has been disappointing to date. Animal experiments are often performed on young, healthy animals lacking the risk factors, co-morbidities and co-medications characteristic of acute myocardial infarction patients. Many hopes were kindled in 1986 when ischemic preconditioning was discovered. However, it is not yet known how long ischemia can last and what is the best modality for additional cardioprotection through conditioning to obtain benefits. There is a lack of experimental studies on the long-term effects of additional cardioprotection, in addition to the reduction in infarct size; in particular, there is a lack of studies on vessel protection, repair, inflammation, remodeling, and mortality. The reproducibility and robustness of experimental studies are often limited by species differences, the role of co-morbidities, vascular damage, inflammatory processes, and co-medications, which are not adequately considered. In particular, inflammatory processes, including NLRP3 inflammasome, play an important role in the long-term effects. Future studies should focus on interventions/agents with robust preclinical data and should recruit patients who truly have the potential to benefit from further cardioprotection. Here we focus on the main mechanisms and targets of cardioprotection during remote conditioning and their alteration by one of the most common co-morbidities, namely diabetes, in which microvascular lesions and inflammatory processes play extremely important roles.
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Affiliation(s)
- Claudia Penna
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043 Torino, TO, Italy; National Institute for Cardiovascular Research (INRC), Bologna, Italy
| | - Stefano Comità
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043 Torino, TO, Italy
| | - Francesca Tullio
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043 Torino, TO, Italy
| | | | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043 Torino, TO, Italy; National Institute for Cardiovascular Research (INRC), Bologna, Italy.
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22
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Hamarneh A, Ho AFW, Bulluck H, Sivaraman V, Ricciardi F, Nicholas J, Shanahan H, Hardman EA, Wicks P, Ramlall M, Chung R, McGowan J, Cordery R, Lawrence D, Clayton T, Kyle B, Xenou M, Ariti C, Yellon DM, Hausenloy DJ. Negative interaction between nitrates and remote ischemic preconditioning in patients undergoing cardiac surgery: the ERIC-GTN and ERICCA studies. Basic Res Cardiol 2022; 117:31. [PMID: 35727392 PMCID: PMC9213287 DOI: 10.1007/s00395-022-00938-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/21/2022] [Accepted: 05/23/2022] [Indexed: 01/31/2023]
Abstract
Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2-5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413-0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.
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Affiliation(s)
- Ashraf Hamarneh
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - Andrew Fu Wah Ho
- Department of Emergency Medicine, Singapore General Hospital, Singapore, Singapore
- Pre-Hospital and Emergency Research Centre, Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - Heerajnarain Bulluck
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Vivek Sivaraman
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - Federico Ricciardi
- Department of Statistical Science, University College London, London, UK
| | - Jennifer Nicholas
- Clinical Trials Unit and Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
| | - Hilary Shanahan
- University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Peter Wicks
- University Hospital Southampton NHS Foundation Trust, London, UK
| | - Manish Ramlall
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - Robin Chung
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - John McGowan
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - Roger Cordery
- Barts Heart Centre, King's College London, London, UK
| | - David Lawrence
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Tim Clayton
- Clinical Trials Unit and Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
| | - Bonnie Kyle
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Maria Xenou
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - Cono Ariti
- University Hospital of Wales, Heath Park, Cardiff, CF14 4YS, UK
| | - Derek M Yellon
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK
| | - Derek J Hausenloy
- Institute of Cardiovascular Sciences, The Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK.
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore.
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.
- Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taichung City, Taiwan.
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23
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Remote ischemic preconditioning can extend the tolerance to extended drug-coated balloon inflation time by reducing myocardial damage during percutaneous coronary intervention. Int J Cardiol 2022; 353:3-8. [DOI: 10.1016/j.ijcard.2022.01.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 01/18/2022] [Accepted: 01/24/2022] [Indexed: 11/24/2022]
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Long YQ, Feng XM, Shan XS, Chen QC, Xia Z, Ji FH, Liu H, Peng K. Remote Ischemic Preconditioning Reduces Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg 2021; 134:592-605. [PMID: 34748518 DOI: 10.1213/ane.0000000000005804] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.
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Affiliation(s)
- Yu-Qin Long
- From the Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiao-Mei Feng
- Department of Anesthesiology, University of Utah Health, Salt Lake City, Utah.,Transitional Residency Program, Intermountain Medical Center, Murray, Utah
| | - Xi-Sheng Shan
- From the Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qing-Cai Chen
- From the Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhengyuan Xia
- Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, California
| | - Fu-Hai Ji
- From the Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hong Liu
- Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, California
| | - Ke Peng
- From the Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China
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25
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Comità S, Femmino S, Thairi C, Alloatti G, Boengler K, Pagliaro P, Penna C. Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function. Basic Res Cardiol 2021; 116:56. [PMID: 34642818 PMCID: PMC8510947 DOI: 10.1007/s00395-021-00898-0] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 09/23/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022]
Abstract
Ischemia–reperfusion injury (IRI) is one of the biggest challenges for cardiovascular researchers given the huge death toll caused by myocardial ischemic disease. Cardioprotective conditioning strategies, namely pre- and post-conditioning maneuvers, represent the most important strategies for stimulating pro-survival pathways essential to preserve cardiac health. Conditioning maneuvers have proved to be fundamental for the knowledge of the molecular basis of both IRI and cardioprotection. Among this evidence, the importance of signal transducer and activator of transcription 3 (STAT3) emerged. STAT3 is not only a transcription factor but also exhibits non-genomic pro-survival functions preserving mitochondrial function from IRI. Indeed, STAT3 is emerging as an influencer of mitochondrial function to explain the cardioprotection phenomena. Studying cardioprotection, STAT3 proved to be crucial as an element of the survivor activating factor enhancement (SAFE) pathway, which converges on mitochondria and influences their function by cross-talking with other cardioprotective pathways. Clearly there are still some functional properties of STAT3 to be discovered. Therefore, in this review, we highlight the evidence that places STAT3 as a promoter of the metabolic network. In particular, we focus on the possible interactions of STAT3 with processes aimed at maintaining mitochondrial functions, including the regulation of the electron transport chain, the production of reactive oxygen species, the homeostasis of Ca2+ and the inhibition of opening of mitochondrial permeability transition pore. Then we consider the role of STAT3 and the parallels between STA3/STAT5 in cardioprotection by conditioning, giving emphasis to the human heart and confounders.
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Affiliation(s)
- Stefano Comità
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043, Torino, TO, Italy
| | - Saveria Femmino
- Department of Medical Sciences, University of Turin, Torino, Italy
| | - Cecilia Thairi
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043, Torino, TO, Italy
| | | | - Kerstin Boengler
- Institute of Physiology, University of Giessen, Giessen, Germany
| | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043, Torino, TO, Italy.
| | - Claudia Penna
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043, Torino, TO, Italy.
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Abel F, Giebel B, Frey UH. Agony of choice: How anesthetics affect the composition and function of extracellular vesicles. Adv Drug Deliv Rev 2021; 175:113813. [PMID: 34029645 DOI: 10.1016/j.addr.2021.05.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 04/22/2021] [Accepted: 05/20/2021] [Indexed: 02/07/2023]
Abstract
The choice of the anesthetic regime is suggested to affect clinical outcomes following major surgery. Propofol was shown to exert beneficial effects on different cancer outcomes, while volatile anesthetics may be favorable in cardiac surgery. Recently, extracellular vesicles (EVs) were discovered as essential signal mediators in physiological and pathophysiological processes including carcinogenesis and metastasis. Furthermore, depending on their cell source, EVs fulfill therapeutic functions. In addition to extracorporally produced EVs, appropriate systemic intervention such as remote ischemic preconditioning (RIPC) is considered to promote endogenous release of therapeutically active EVs to mediate cardioprotective effects. EVs are assembled in cell-type specific manners and the composition of EVs is not only affected by the disease, but also by the applied anesthetic of anesthetized patients. Here, we compare known impacts of anesthetic agents on outcomes in cancer surgery and cardioprotection and link these effects to the composition and therapeutic potential of EVs.
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Affiliation(s)
- Frederik Abel
- Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Bernd Giebel
- Institut für Transfusionsmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany.
| | - Ulrich H Frey
- Klinik für Anästhesiologie, operative Intensivmedizin, Schmerz- und Palliativmedizin, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Hölkeskampring 40, 44625 Herne, Germany
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27
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Myocardial remote ischemic preconditioning: from cell biology to clinical application. Mol Cell Biochem 2021; 476:3857-3867. [PMID: 34125317 DOI: 10.1007/s11010-021-04192-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 05/26/2021] [Indexed: 12/25/2022]
Abstract
Remote ischemic preconditioning (rIPC) is a cardioprotective phenomenon where brief periods of ischemia followed by reperfusion of one organ/tissue can confer subsequent protection against ischemia/reperfusion injury in other organs, such as the heart. It involves activation of humoral, neural or systemic communication pathways inducing different intracellular signals in the heart. The main purpose of this review is to summarize the possible mechanisms involved in the rIPC cardioprotection, and to describe recent clinical trials to establish the efficacy of these strategies in cardioprotection from lethal ischemia/reperfusion injury. In this sense, certain factors weaken the subcellular mechanisms of rIPC in patients, such as age, comorbidities, medication, and anesthetic protocol, which could explain the heterogeneity of results in some clinical trials. For these reasons, further studies, carefully designed, are necessary to develop a clearer understanding of the pathways and mechanism of early and late rIPC. An understanding of the pathways is important for translation to patients.
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Lassen TR, Hjortbak MV, Hauerslev M, Tonnesen PT, Kristiansen SB, Jensen RV, Bøtker HE. Influence of strain, age, origin, and anesthesia on the cardioprotective efficacy by local and remote ischemic conditioning in an ex vivo rat model. Physiol Rep 2021; 9:e14810. [PMID: 33818005 PMCID: PMC8020046 DOI: 10.14814/phy2.14810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 03/01/2021] [Accepted: 03/03/2021] [Indexed: 02/07/2023] Open
Abstract
Background Local ischemic preconditioning (IPC) and remote ischemic conditioning (RIC) induced by brief periods of ischemia and reperfusion protect against ischemia‐reperfusion injury. Methods We studied the sensitivity to IR‐injury and the influence of strain, age, supplier, and anesthesia upon the efficacy of IPC and RIC in 7‐ and 16‐weeks‐old Sprague‐Dawley and Wistar rats from three different suppliers. The influence of sedation with a hypnorm and midazolam mixture (rodent mixture) and pentobarbiturate was compared. Results IPC attenuated infarct size in both 7‐weeks‐old Sprague–Dawley (48.4 ± 17.7% vs. 20.3 ± 6.9, p < 0.001) and 7‐weeks‐old Wistar (55.6 ± 10.9% vs. 26.8 ± 5.0%, p < 0.001) rats. Infarct size was larger in 16‐weeks‐old Sprague–Dawley rats, however, IPC still lowered infarct size (78.8 ± 9.2% vs. 58.3 ± 12.3%, p < 0.01). RIC reduced infarct sizes in 7‐weeks‐old Sprague–Dawley (75.3 ± 11.8% vs. 58.6 ± 8.9%, p < 0.05), but not in 7‐weeks‐old Wistar rats (31.7 ± 17.6% and 24.0 ± 12.6%, p = 0.2). In 16‐weeks‐old Sprague–Dawley rats, RIC did not induce protection (76.4 ± 5.5% and 73.2 ± 14.7%, p = 0.6). However, RIC induced protection in 16‐weeks‐old Wistar rats (45.2 ± 8.5% vs. 14.7 ± 10.8%, p < 0.001). RIC did not reduce infarct size in 7‐weeks‐old Sprague–Dawley rats from Charles River (62.0 ± 13.5% and 69.4 ± 10.4% p = 0.3) or 16‐weeks‐old Wistar rats from Janvier (50.7 ± 11.3 and 49.2 ± 16.2, p = 0.8). There was no difference between sedation with rodent mixture or pentobarbiturate. Conclusion The cardioprotective effect of IPC is consistent across rat strains independent of age, strain, and supplier. RIC seems to be less reproducible, but still yields protection across different rat strains. However, age, animal supplier, and anesthetics may modulate the sensitivity of IR‐injury and the response to RIC.
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Affiliation(s)
- Thomas Ravn Lassen
- Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Marie Vognstoft Hjortbak
- Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Marie Hauerslev
- Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Pernille Tilma Tonnesen
- Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | | | | | - Hans Erik Bøtker
- Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
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Abstract
Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with high morbidity and mortality. Although the number of cardiac surgical procedures is constantly growing worldwide, incidence of cardiac surgery-associated AKI is still around 40% and has a significant impact on global health care costs. Numerous trials attempted to identify strategies to prevent AKI and attenuate its detrimental consequences. Effective options remained elusive. Current evidence supports a multimodal risk-stratification approach with biomarker-guided management of high-risk patients, perioperative administration of dexmedetomidine, and implementation of a care bundle as recommended by the Kidney Disease: Improving Global Outcomes group.
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30
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Weir P, Maguire R, O'Sullivan SE, England TJ. A meta-analysis of remote ischaemic conditioning in experimental stroke. J Cereb Blood Flow Metab 2021; 41:3-13. [PMID: 32538284 PMCID: PMC7747156 DOI: 10.1177/0271678x20924077] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD -2.0; 95% CI -2.38, -1.61; p < 0.00001) and permanent (SMD -1.54; 95% CI -2.38, -1.61; p < 0.00001) focal models of ischaemia and improved neurological deficit (SMD -1.63; 95% CI -1.97, -1.29, p < 0.00001). In meta-regression, cycle length and number, dose and limb number did not interact with infarct volume, although country and physiological monitoring during anaesthesia did. In all studies, RIC was ineffective if the dose was <10 or ≥50 min. Median study quality was 7 (range 4-9/10); Egger's test suggested publication bias (p < 0.001). RIC is most effective in experimental stroke using a dose between 10 and 45 min. Further studies using repeated dosing in animals with co-morbidities are warranted.
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Affiliation(s)
- Philippa Weir
- Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine, University of Nottingham, Derby, UK
| | - Ryan Maguire
- Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine, University of Nottingham, Derby, UK
| | - Saoirse E O'Sullivan
- Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine, University of Nottingham, Derby, UK
| | - Timothy J England
- Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine, University of Nottingham, Derby, UK.,University Hospitals of Derby and Burton NHS Foundation Trust, Royal Derby Hospital, Derby, UK
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31
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Cho YJ, Nam K, Yoo SJ, Lee S, Bae J, Park JY, Kim HR, Kim TK, Jeon Y. Effects of remote ischemic preconditioning on platelet activation and reactivity in patients undergoing cardiac surgery using cardiopulmonary bypass: a randomized controlled trial. Platelets 2020; 33:123-131. [PMID: 33307907 DOI: 10.1080/09537104.2020.1856362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
During cardiopulmonary bypass (CPB), platelet activation and dysfunction are associated with adverse outcomes. Remote ischemic preconditioning (RIPC) has been shown to attenuate platelet activation. We evaluated the effects of RIPC on platelet activation during CPB in patients undergoing cardiac surgery. Among 58 randomized patients, 26 in the RIPC group and 28 in the sham-RIPC group were analyzed. RIPC consisted of 4 cycles of 5-min ischemia induced by inflation of pneumatic cuff pressure to 200 mmHg, followed by 5-min reperfusion comprising deflation of the cuff on the upper arm. Platelet activation was assessed using flow cytometry analysis of platelet activation markers. The primary endpoint was the AUC of CD62P expression during the first 3 h after initiation of CPB. Secondary outcomes were the AUC of PAC-1 expression and monocyte-platelet aggregates (MPA) during 3 h of CPB. The AUCs of CD62P expression during 3 h after initiation of CPB were 219.4 ± 43.9 and 211.0 ± 41.2 MFI in the RIPC and sham-RIPC groups, respectively (mean difference, 8.42; 95% CI, -14.8 and 31.7 MFI; p =.471). The AUCs of PAC-1 expression and MPA did not differ between groups. RIPC did not alter platelet activation and reactivity during CPB in patients undergoing cardiac surgery.
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Affiliation(s)
- Youn Joung Cho
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Karam Nam
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sol Ji Yoo
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seohee Lee
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jinyoung Bae
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ji-Young Park
- FACS Core Facility, Seoul National University College of Medicine, Seoul, Korea
| | - Hang-Rae Kim
- Department of Biomedical Sciences, BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Korea
| | - Tae Kyong Kim
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Yunseok Jeon
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Kleinbongard P, Bøtker HE, Ovize M, Hausenloy DJ, Heusch G. Co-morbidities and co-medications as confounders of cardioprotection-Does it matter in the clinical setting? Br J Pharmacol 2020; 177:5252-5269. [PMID: 31430831 PMCID: PMC7680006 DOI: 10.1111/bph.14839] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 07/26/2019] [Accepted: 08/15/2019] [Indexed: 02/06/2023] Open
Abstract
The translation of cardioprotection from robust experimental evidence to beneficial clinical outcome for patients suffering acute myocardial infarction or undergoing cardiovascular surgery has been largely disappointing. The present review attempts to critically analyse the evidence for confounders of cardioprotection in patients with acute myocardial infarction and in patients undergoing cardiovascular surgery. One reason that has been proposed to be responsible for such lack of translation is the confounding of cardioprotection by co-morbidities and co-medications. Whereas there is solid experimental evidence for such confounding of cardioprotection by single co-morbidities and co-medications, the clinical evidence from retrospective analyses of the limited number of clinical data is less robust. The best evidence for interference of co-medications is that for platelet inhibitors to recruit cardioprotection per se and thus limit the potential for further protection from myocardial infarction and for propofol anaesthesia to negate the protection from remote ischaemic conditioning in cardiovascular surgery. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.
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Affiliation(s)
- Petra Kleinbongard
- Institute for Pathophysiology, West German Heart and Vascular CenterUniversity of Essen Medical SchoolEssenGermany
| | - Hans Erik Bøtker
- Department of CardiologyAarhus University Hospital SkejbyAarhusDenmark
| | - Michel Ovize
- INSERM U1060, CarMeN Laboratory, Université de Lyon and Explorations Fonctionnelles Cardiovasculaires, Hôpital Louis Pradel, Hospices Civils de LyonLyonFrance
| | - Derek J. Hausenloy
- Cardiovascular and Metabolic Disorders ProgramDuke‐National University of Singapore Medical SchoolSingapore
- National Heart Research Institute SingaporeNational Heart CentreSingapore
- Yong Loo Lin School of MedicineNational University SingaporeSingapore
- The Hatter Cardiovascular InstituteUniversity College LondonLondonUK
- Research and DevelopmentThe National Institute of Health Research University College London Hospitals Biomedical Research CentreLondonUK
- Tecnologico de MonterreyCentro de Biotecnologia‐FEMSAMonterreyNuevo LeonMexico
| | - Gerd Heusch
- Institute for Pathophysiology, West German Heart and Vascular CenterUniversity of Essen Medical SchoolEssenGermany
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Oliván-Viguera A, Pérez-Zabalza M, García-Mendívil L, Mountris KA, Orós-Rodrigo S, Ramos-Marquès E, Vallejo-Gil JM, Fresneda-Roldán PC, Fañanás-Mastral J, Vázquez-Sancho M, Matamala-Adell M, Sorribas-Berjón F, Bellido-Morales JA, Mancebón-Sierra FJ, Vaca-Núñez AS, Ballester-Cuenca C, Marigil MÁ, Pastor C, Ordovás L, Köhler R, Diez E, Pueyo E. Minimally invasive system to reliably characterize ventricular electrophysiology from living donors. Sci Rep 2020; 10:19941. [PMID: 33203905 PMCID: PMC7673124 DOI: 10.1038/s41598-020-77076-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 11/03/2020] [Indexed: 01/03/2023] Open
Abstract
Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratome-sliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verified viability. Optically mapped transmembrane potentials confirmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.
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Affiliation(s)
- Aida Oliván-Viguera
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain.
| | - María Pérez-Zabalza
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain
| | - Laura García-Mendívil
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain
| | - Konstantinos A Mountris
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain
| | - Sofía Orós-Rodrigo
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain
| | - Estel Ramos-Marquès
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain
| | - José María Vallejo-Gil
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza, Spain
| | | | - Javier Fañanás-Mastral
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza, Spain
| | - Manuel Vázquez-Sancho
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza, Spain
| | - Marta Matamala-Adell
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza, Spain
| | | | | | | | | | | | | | | | - Laura Ordovás
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain.,Aragón Agency for Research and Development (ARAID), Zaragoza, Spain
| | - Ralf Köhler
- Aragón Institute of Health Sciences (IACS), Zaragoza, Spain.,Aragón Agency for Research and Development (ARAID), Zaragoza, Spain
| | - Emiliano Diez
- Institute of Experimental Medicine and Biology of Cuyo (IMBECU), CONICET, Mendoza, Argentina
| | - Esther Pueyo
- Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón, Institute of Engineering Research (I3A) and Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Edificio I+D+i, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain.,Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain
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Drury NE, Bi R, Woolley RL, Stickley J, Morris KP, Montgomerie J, van Doorn C, Dunn WB, Madhani M, Ives NJ, Kirchhof P, Jones TJ. Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: protocol for a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery. BMJ Open 2020; 10:e042176. [PMID: 33033035 PMCID: PMC7542918 DOI: 10.1136/bmjopen-2020-042176] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Myocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection. The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial will assess whether remote ischaemic preconditioning, applied to both lower limbs immediately prior to surgery, reduces myocardial injury in cyanotic and acyanotic young children. METHODS AND ANALYSIS The BRICC trial is a two-centre, double-blind, randomised controlled trial recruiting up to 120 young children (age 3 months to 3 years) undergoing primary repair of tetralogy of Fallot or surgical closure of an isolated ventricular septal defect. Participants will be randomised in a 1:1 ratio to either bilateral remote ischaemic preconditioning (3×5 min cycles) or sham immediately prior to surgery, with follow-up until discharge from hospital or 30 days, whichever is sooner. The primary outcome is reduction in area under the time-concentration curve for high-sensitivity (hs) troponin-T release in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include peak hs-troponin-T, vasoactive inotrope score, arterial lactate and central venous oxygen saturations in the first 12 hours, and lengths of stay in the paediatric intensive care unit and the hospital. ETHICS AND DISSEMINATION The trial was approved by the West Midlands-Solihull National Health Service Research Ethics Committee (16/WM/0309) on 5 August 2016. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a local charity. TRIAL REGISTRATION NUMBER ISRCTN12923441.
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Affiliation(s)
- Nigel E Drury
- Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, West Midlands, UK
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, West Midlands, UK
| | - Rehana Bi
- Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, West Midlands, UK
- Paediatric Intensive Care, Birmingham Children's Hospital, Birmingham, West Midlands, UK
| | - Rebecca L Woolley
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, West Midlands, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, West Midlands, UK
| | - John Stickley
- Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, West Midlands, UK
| | - Kevin P Morris
- Paediatric Intensive Care, Birmingham Children's Hospital, Birmingham, West Midlands, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, West Midlands, UK
| | - James Montgomerie
- Paediatric Cardiac Anaesthesia, Birmingham Children's Hospital, Birmingham, West Midlands, UK
| | - Carin van Doorn
- Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, West Yorkshire, UK
| | - Warwick B Dunn
- School of Biosciences, University of Birmingham, Birmingham, West Midlands, UK
- Phenome Centre Birmingham, University of Birmingham, Birmingham, West Midlands, UK
| | - Melanie Madhani
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, West Midlands, UK
| | - Natalie J Ives
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, West Midlands, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, West Midlands, UK
| | - Paulus Kirchhof
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, West Midlands, UK
- Cardiology, University Heart and Vascular Center, UKE, Hamburg, Germany
| | - Timothy J Jones
- Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, West Midlands, UK
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, West Midlands, UK
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Bellis A, Mauro C, Barbato E, Di Gioia G, Sorriento D, Trimarco B, Morisco C. The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction. Cells 2020; 9:cells9092134. [PMID: 32967374 PMCID: PMC7565478 DOI: 10.3390/cells9092134] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 12/11/2022] Open
Abstract
During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients. Myocardial ischemia-reperfusion injury (MIRI) prevention represents the main goal to reach in order to reduce STEMI mortality. There is currently no effective therapy for MIRI prevention in STEMI patients. A significant reason for the weak and inconsistent results obtained in this field may be the presence of multiple, partially redundant, mechanisms of cell death during ischemia-reperfusion, whose relative importance may depend on the conditions. Therefore, it is always more recognized that it is important to consider a "multi-targeted cardioprotective therapy", defined as an additive or synergistic cardioprotective agents or interventions directed to distinct targets with different timing of application (before, during, or after pPCI). Given that some neprilysin (NEP) substrates (natriuretic peptides, angiotensin II, bradykinin, apelins, substance P, and adrenomedullin) exert a cardioprotective effect against ischemia-reperfusion injury, it is conceivable that antagonism of proteolytic activity by this enzyme may be considered in a multi-targeted strategy for MIRI prevention. In this review, by starting from main pathophysiological mechanisms promoting MIRI, we discuss cardioprotective effects of NEP substrates and the potential benefit of NEP pharmacological inhibition in MIRI prevention.
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Affiliation(s)
- Alessandro Bellis
- Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy; (A.B.); (E.B.); (G.D.G.); (D.S.); (B.T.)
- Unità Operativa Complessa Cardiologia con UTIC ed Emodinamica—Dipartimento Emergenza Accettazione, Azienda Ospedaliera “Antonio Cardarelli”, 80131 Napoli, Italy;
| | - Ciro Mauro
- Unità Operativa Complessa Cardiologia con UTIC ed Emodinamica—Dipartimento Emergenza Accettazione, Azienda Ospedaliera “Antonio Cardarelli”, 80131 Napoli, Italy;
| | - Emanuele Barbato
- Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy; (A.B.); (E.B.); (G.D.G.); (D.S.); (B.T.)
| | - Giuseppe Di Gioia
- Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy; (A.B.); (E.B.); (G.D.G.); (D.S.); (B.T.)
- Cardiac Catheterization Laboratory, Montevergine Clinic, 83013 Mercogliano (AV), Italy
| | - Daniela Sorriento
- Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy; (A.B.); (E.B.); (G.D.G.); (D.S.); (B.T.)
| | - Bruno Trimarco
- Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy; (A.B.); (E.B.); (G.D.G.); (D.S.); (B.T.)
| | - Carmine Morisco
- Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy; (A.B.); (E.B.); (G.D.G.); (D.S.); (B.T.)
- Correspondence: ; Tel.: +39-081-746-2253; Fax: +39-081-746-2256
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Chen Y, Wang G, Zhou H, Yang L, Zhang C, Yang X, Lei G. 90 days impacts of remote ischemic preconditioning on patients undergoing open total aortic arch replacement: a post-hoc analysis of previous trial. BMC Anesthesiol 2020; 20:169. [PMID: 32646379 PMCID: PMC7346644 DOI: 10.1186/s12871-020-01085-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 07/05/2020] [Indexed: 12/21/2022] Open
Abstract
Background In the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II–III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear. Methods This study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement. Results In this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046). Conclusions At 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial. Trial registration This study was approved by the Ethics Committee of Fuwai Hospital (No. 2016–835) and our previous study was registered at clinicaltrials.gov before patient enrollment (NCT03141385; principal investigator: G.W.; date of registration: March 5, 2017).
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Affiliation(s)
- Yimeng Chen
- Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Belishi road 167, Xicheng District, Beijing, 100037, China
| | - Guyan Wang
- Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Belishi road 167, Xicheng District, Beijing, 100037, China. .,Department of Anesthesiology, Beijng Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, China.
| | - Hui Zhou
- Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Lijing Yang
- Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Belishi road 167, Xicheng District, Beijing, 100037, China
| | - Congya Zhang
- Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Belishi road 167, Xicheng District, Beijing, 100037, China
| | - Xiying Yang
- Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Belishi road 167, Xicheng District, Beijing, 100037, China
| | - Guiyu Lei
- Department of Anesthesiology, Beijng Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, China
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Abstract
Despite the increasing use and success of interventional coronary reperfusion strategies, morbidity and mortality from acute myocardial infarction are still substantial. Myocardial infarct size is a major determinant of prognosis in these patients. Therefore, cardioprotective strategies aim to reduce infarct size. However, a perplexing gap exists between the many preclinical studies reporting infarct size reduction with mechanical and pharmacological interventions and the poor translation into better clinical outcomes in patients. This Review revisits the pathophysiology of myocardial ischaemia-reperfusion injury, including the role of autophagy and forms of cell death such as necrosis, apoptosis, necroptosis and pyroptosis. Other cellular compartments in addition to cardiomyocytes are addressed, notably the coronary microcirculation. Preclinical and clinical research developments in mechanical and pharmacological approaches to induce cardioprotection, and their signal transduction pathways, are discussed. Additive cardioprotective interventions are advocated. For clinical translation into treatments for patients with acute myocardial infarction, who typically are of advanced age, have comorbidities and are receiving several medications, not only infarct size reduction but also attenuation of coronary microvascular obstruction, as well as longer-term targets including infarct repair and reverse remodelling, must be considered to improve patient outcomes. Future clinical trials must focus on patients who really need adjunct cardioprotection, that is, those with severe haemodynamic alterations.
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Hausenloy DJ, Bøtker HE, Ferdinandy P, Heusch G, Ng GA, Redington A, Garcia-Dorado D. Cardiac innervation in acute myocardial ischaemia/reperfusion injury and cardioprotection. Cardiovasc Res 2020; 115:1167-1177. [PMID: 30796814 DOI: 10.1093/cvr/cvz053] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 12/21/2018] [Accepted: 02/21/2019] [Indexed: 12/13/2022] Open
Abstract
Acute myocardial infarction (AMI) and the heart failure (HF) that often complicates this condition, are among the leading causes of death and disability worldwide. To reduce myocardial infarct (MI) size and prevent heart failure, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). In this regard, targeting cardiac innervation may provide a novel therapeutic strategy for cardioprotection. A number of cardiac neural pathways mediate the beneficial effects of cardioprotective strategies such as ischaemic preconditioning and remote ischaemic conditioning, and nerve stimulation may therefore provide a novel therapeutic strategy for cardioprotection. In this article, we provide an overview of cardiac innervation and its impact on acute myocardial IRI, the role of extrinsic and intrinsic cardiac neural pathways in cardioprotection, and highlight peripheral and central nerve stimulation as a cardioprotective strategy with therapeutic potential for reducing MI size and preventing HF following AMI. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
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Affiliation(s)
- Derek J Hausenloy
- Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore.,National Heart Research Institute Singapore, National Heart Centre, Singapore.,Yong Loo Lin School of Medicine, National University Singapore, Singapore.,The Hatter Cardiovascular Institute, University College London, London, UK.,The National Institute of Health Research University College London Hospitals Biomedical Research Centre, Research & Development, London, UK.,Tecnologico de Monterrey, Centro de Biotecnologia-FEMSA, Nuevo Leon, Mexico
| | - Hans Erik Bøtker
- Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark
| | - Peter Ferdinandy
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.,Pharmahungary Group, Szeged, Hungary
| | - Gerd Heusch
- Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Essen, Germany
| | - G André Ng
- Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, UK
| | - Andrew Redington
- Cincinnati Children's Hospital Medical Center, Heart Institute, Cincinnati, OH, USA.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - David Garcia-Dorado
- Department of Cardiology, Vascular Biology and Metabolism Area, Vall d'Hebron University Hospital and Research Institute (VHIR), Universitat Autónoma de Barcelona, Spain.,Instituto CIBER de Enfermedades Cardiovasculares (CIBERCV): Instituto de Salud Carlos III, Madrid, Spain
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Abel F, Murke F, Gaida M, Garnier N, Ochsenfarth C, Theiss C, Thielmann M, Kleinbongard P, Giebel B, Peters J, Frey UH. Extracellular vesicles isolated from patients undergoing remote ischemic preconditioning decrease hypoxia-evoked apoptosis of cardiomyoblasts after isoflurane but not propofol exposure. PLoS One 2020; 15:e0228948. [PMID: 32059016 PMCID: PMC7021285 DOI: 10.1371/journal.pone.0228948] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 01/26/2020] [Indexed: 12/27/2022] Open
Abstract
Remote ischemic preconditioning (RIPC) can evoke cardioprotection following ischemia/reperfusion and this may depend on the anesthetic used. We tested whether 1) extracellular vesicles (EVs) isolated from humans undergoing RIPC protect cardiomyoblasts against hypoxia-induced apoptosis and 2) this effect is altered by cardiomyoblast exposure to isoflurane or propofol. EVs were isolated before and 60 min after RIPC or Sham from ten patients undergoing coronary artery bypass graft surgery with isoflurane anesthesia and quantified by Nanoparticle Tracking Analysis. Following EV-treatment for 6 hours under exposure of isoflurane or propofol, rat H9c2 cardiomyoblasts were cultured for 18 hours in normoxic or hypoxic atmospheres. Apoptosis was detected by flow cytometry. Serum nanoparticle concentrations in patients had increased sixty minutes after RIPC compared to Sham (2.5x1011±4.9x1010 nanoparticles/ml; Sham: 1.2x1011±2.0x1010; p = 0.04). Hypoxia increased apoptosis of H9c2 cells (hypoxia: 8.4%±0.6; normoxia: 2.5%±0.1; p<0.0001). RIPC-EVs decreased H9c2 cell apoptosis compared to control (apoptotic ratio: 0.83; p = 0.0429) while Sham-EVs showed no protection (apoptotic ratio: 0.97). Prior isoflurane exposure in vitro even increased protection (RIPC-EVs/control, apoptotic ratio: 0.79; p = 0.0035; Sham-EVs/control, apoptotic ratio:1.04) while propofol (50μM) abrogated protection by RIPC-EVs (RIPC-EVs/control, Apoptotic ratio: 1.01; Sham-EVs/control, apoptotic ratio: 0.94; p = 0.602). Thus, EVs isolated from patients undergoing RIPC under isoflurane anesthesia protect H9c2 cardiomyoblasts against hypoxia-evoked apoptosis and this effect is abrogated by propofol. This supports a role of human RIPC-generated EVs in cardioprotection and underlines propofol as a possible confounder in RIPC-signaling mediated by EVs.
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Affiliation(s)
- Frederik Abel
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Florian Murke
- Institut für Transfusionsmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Morten Gaida
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Nicolas Garnier
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Crista Ochsenfarth
- Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerz- und Palliativmedizin, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Bochum, Germany
| | - Carsten Theiss
- Institut für Anatomie, Abteilung für Cytologie, Ruhr-Universität-Bochum, Bochum, Germany
| | - Matthias Thielmann
- Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Petra Kleinbongard
- Institut für Pathophysiologie, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Bernd Giebel
- Institut für Transfusionsmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Jürgen Peters
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
| | - Ulrich H. Frey
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Essen, Germany
- Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerz- und Palliativmedizin, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Bochum, Germany
- * E-mail:
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Yoon HK, Oh H, Lee HC, Cho WS, Kim JE, Park JW, Choi H, Park HP. Effect of Sevoflurane Postconditioning on the Incidence of Symptomatic Cerebral Hyperperfusion After Revascularization Surgery in Adult Patients with Moyamoya Disease. World Neurosurg 2020; 134:e991-e1000. [DOI: 10.1016/j.wneu.2019.11.055] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 11/10/2019] [Indexed: 01/04/2023]
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Kim TK, Nam K, Cho YJ, Choi S, Row HS, Jeon Y. Effect of remote ischaemic conditioning on coagulation function as measured by whole blood impedance aggregometry and rotational thromboelastometry in off-pump coronary artery bypass surgery: A randomised controlled trial. Thromb Res 2020; 187:72-78. [PMID: 31972380 DOI: 10.1016/j.thromres.2020.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 12/26/2019] [Accepted: 01/08/2020] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Remote ischaemic conditioning (RIC) has been shown to prevent platelet activation during ablation for atrial fibrillation. RIC has also been associated with more postoperative transfusion in the off-pump coronary artery bypass graft surgery (OPCAB) patients. We evaluated the effects of RIC on coagulation function in OPCAB patients. METHODS A total of 58 patients undergoing OPCAB were randomised to the RIC or control group. In the RIC group, four cycles of 5 min of ischaemia and 5 min of reperfusion were applied twice to the upper arm after the induction of anaesthesia (preconditioning), and after the completion of coronary anastomoses (postconditioning). Whole blood impedance aggregometry (Multiplate®) and rotational thromboelastometry (ROTEM®) were performed before the induction of anaesthesia, at the end of surgery, and at postoperative day 1. RESULTS The trend towards a decrease in adenosine diphosphate-induced whole blood aggregation at the end of surgery was greater in the RIC group than in the control group, but this effect was not statistically significant (-10.4 [18.1] vs. -5.7 [24.8] U, P = 0.424). In ROTEM® analysis, the EXTEM area under the velocity curve was lower in the RIC group than in the control group at the end of surgery (3567 [1399-5794] vs. 5693 [4718-6179] mm∗100, respectively; P = 0.030). A tendency of larger perioperative blood loss was identified in the RIC group. CONCLUSIONS Although some parameters indicated a tendency for hypocoagulation in the RIC group at the end of surgery, most effects were not statistically significant. RIC does not significantly affect perioperative platelet aggregability and coagulation in patients undergoing OPCAB.
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Affiliation(s)
- Tae Kyong Kim
- Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Anaesthesiology and Pain Medicine, SMG-SNU Boramae Medical Centre, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Karam Nam
- Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Youn Joung Cho
- Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seungeun Choi
- Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Anaesthesiology and Pain Medicine, SMG-SNU Boramae Medical Centre, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyung Sang Row
- Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Anaesthesiology and Pain Medicine, SMG-SNU Boramae Medical Centre, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yunseok Jeon
- Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Bergmann A, Jovanovska E, Schilling T, Hedenstierna G, Föllner S, Schreiber J, Hachenberg T. Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers. Respir Physiol Neurobiol 2020; 271:103287. [DOI: 10.1016/j.resp.2019.103287] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/06/2019] [Accepted: 09/05/2019] [Indexed: 12/14/2022]
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Tyagi S, Kaur S, Singh N, Jaggi AS. Investigating the role of acute and repeated stress on remote ischemic preconditioning-induced cardioprotection. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2020; 23:111-116. [PMID: 32395208 PMCID: PMC7206844 DOI: 10.22038/ijbms.2019.36416.8678] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 07/31/2019] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To study the effect of acute and repeated stress on cardioprotection-induced by remote ischemic preconditioning (RIPC). MATERIALS AND METHODS RIPC was induced by giving 4 short cycles of ischemia and reperfusion, each consisting of five min. The Langendorff's apparatus was used to perfuse the isolated rat hearts by subjecting the hearts to global ischemia of 30 min and reperfusion of 120 min. The coronary effluent was collected to measure the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) for the assessment of injury to the myocardium. Myocardial infarct size was measured by the use of triphenyl tetrazolium chloride. Acute stress was induced by subjecting the animals to cold immersion stress for 5 min. However, in the case of stress adaptation, rats were exposed to a homotypic stressor (cold-water immersion stress) each of 5 min duration for five consecutive days. RESULTS RIPC demonstrated a significant decrease in ischemia-reperfusion-induced myocardial injury in terms of decrease in LDH, CK, and infarct size. However, acute stress for five minutes prior to RIPC significantly abolished its cardioprotective effects. Exogenous administration of adenosine restored RIPC-induced cardioprotective effects in the presence of acute stress. On repeated stress exposure for 5 days, stress adaptation was noted, and there was no effect of repeated stress exposure on RIPC-induced cardioprotection. However, the cardioprotective effects of adenosine were absent in the case of rats subjected to repeated episodes of stress. CONCLUSION Acute stress, but not repeated stress exposure, may alter the release of adenosine during RIPC, which may be manifested in the form of reduced cardioprotection during ischemic-reperfusion injury.
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Affiliation(s)
- Sakshi Tyagi
- Department of Pharmaceutical Sciences and Drug Research Punjabi University, Patiala, India
| | - Simranjot Kaur
- Department of Pharmaceutical Sciences and Drug Research Punjabi University, Patiala, India
| | - Nirmal Singh
- Department of Pharmaceutical Sciences and Drug Research Punjabi University, Patiala, India
| | - Amteshwar Singh Jaggi
- Department of Pharmaceutical Sciences and Drug Research Punjabi University, Patiala, India
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Wu Q, Wang T, Chen S, Zhou Q, Li H, Hu N, Feng Y, Dong N, Yao S, Xia Z. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J 2019; 39:1028-1037. [PMID: 28329231 PMCID: PMC6018784 DOI: 10.1093/eurheartj/ehx030] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 01/17/2017] [Indexed: 01/17/2023] Open
Abstract
Aims Remote ischaemic preconditioning (RIPC) by inducing brief ischaemia in distant tissues protects the heart against myocardial ischaemia-reperfusion injury (IRI) in children undergoing open-heart surgery, although its effectiveness in adults with comorbidities is controversial. The effectiveness and mechanism of RIPC with respect to myocardial IRI in children with tetralogy of Fallot (ToF), a severe cyanotic congenital cardiac disease, undergoing open heart surgery are unclear. We hypothesized that RIPC can confer cardioprotection in children undergoing ToF repair surgery. Methods and results Overall, 112 ToF children undergoing radical open cardiac surgery using cardiopulmonary bypass (CPB) were randomized to either a RIPC group (n = 55) or a control group (n = 57). The RIPC protocol consisted of three cycles of 5-min lower limb occlusion and 5-min reperfusion using a cuff-inflator. Serum inflammatory cytokines and cardiac injury markers were measured before surgery and after CPB. Right ventricle outflow tract (RVOT) tissues were collected during the surgery to assess hypoxia-inducible factor (Hif)-1α and other signalling proteins. Cardiac mitochondrial injury was assessed by electron microscopy. The primary results showed that the length of stay in the intensive care unit (ICU) was longer in the control group than in the RIPC group (52.30 ± 13.43 h vs. 47.55 ± 10.34 h, respectively, P = 0.039). Patients in the control group needed longer post-operative ventilation time compared to the RIPC group (35.02 ± 6.56 h vs. 31.96 ± 6.60 h, respectively, P = 0.016). The levels of post-operative serum troponin-T at 12 and 18 h, CK-MB at 24 h, as well as the serum h-FABP levels at 6 h, after CPB were significantly lower, which was coincident with significantly higher protein expression of cardiac Hif-1α, p-Akt, p-STAT3, p-STAT5, and p-eNOS and less vacuolization of mitochondria in the RIPC group compared to the control group. Conclusion In ToF children undergoing open heart surgery, RIPC attenuates myocardial IRI and improves the short-term prognosis.
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Affiliation(s)
- Qingping Wu
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Tingting Wang
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Shiqiang Chen
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Quanjun Zhou
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Haobo Li
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, 21 Sassoon Road, Hong Kong, China.,Department of Anaesthesiology, University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China
| | - Na Hu
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Yinglu Feng
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Nianguo Dong
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Shanglong Yao
- Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Zhengyuan Xia
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, 21 Sassoon Road, Hong Kong, China.,Department of Anaesthesiology, University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China
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Cho YJ, Kim WH. Perioperative Cardioprotection by Remote Ischemic Conditioning. Int J Mol Sci 2019; 20:ijms20194839. [PMID: 31569468 PMCID: PMC6801656 DOI: 10.3390/ijms20194839] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 09/11/2019] [Accepted: 09/27/2019] [Indexed: 12/24/2022] Open
Abstract
Remote ischemic conditioning has been investigated for cardioprotection to attenuate myocardial ischemia/reperfusion injury. In this review, we provide a comprehensive overview of the current knowledge of the signal transduction pathways of remote ischemic conditioning according to three stages: Remote stimulus from source organ; protective signal transfer through neuronal and humoral factors; and target organ response, including myocardial response and coronary vascular response. The neuronal and humoral factors interact on three levels, including stimulus, systemic, and target levels. Subsequently, we reviewed the clinical studies evaluating the cardioprotective effect of remote ischemic conditioning. While clinical studies of percutaneous coronary intervention showed relatively consistent protective effects, the majority of multicenter studies of cardiac surgery reported neutral results although there have been several promising initial trials. Failure to translate the protective effects of remote ischemic conditioning into cardiac surgery may be due to the multifactorial etiology of myocardial injury, potential confounding factors of patient age, comorbidities including diabetes, concomitant medications, and the coadministered cardioprotective general anesthetic agents. Given the complexity of signal transfer pathways and confounding factors, further studies should evaluate the multitarget strategies with optimal measures of composite outcomes.
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Affiliation(s)
- Youn Joung Cho
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Won Ho Kim
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.
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46
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Affiliation(s)
- Gerd Heusch
- From the Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School
| | - Andreas Skyschally
- From the Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School
| | - Petra Kleinbongard
- From the Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School
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Deferrari G, Bonanni A, Bruschi M, Alicino C, Signori A. Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials. Nephrol Dial Transplant 2019; 33:813-824. [PMID: 28992285 DOI: 10.1093/ndt/gfx210] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 04/28/2017] [Indexed: 12/20/2022] Open
Abstract
Background The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. Methods Randomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned. Results Thirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74-0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics. Conclusions RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.
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Affiliation(s)
- Giacomo Deferrari
- Department of Cardionephrology, Istituto Clinico Di Alta Specialità (ICLAS), Rapallo (GE), Italy.,Department of Internal Medicine (Di.MI), University of Genoa, Genoa, Italy
| | - Alice Bonanni
- Department of Cardionephrology, Istituto Clinico Di Alta Specialità (ICLAS), Rapallo (GE), Italy.,Division of Nephrology, Dialysis and Transplantation and Laboratory on Pathophysiology of Uremia, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Maurizio Bruschi
- Division of Nephrology, Dialysis and Transplantation and Laboratory on Pathophysiology of Uremia, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Cristiano Alicino
- Department of Health Science (Di.S.Sal), University of Genoa, Genoa, Italy
| | - Alessio Signori
- Department of Health Science (Di.S.Sal), University of Genoa, Genoa, Italy
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Yu J, Chen K, Wu L, Liu X, Lu Y. Anesthetic propofol blunts remote preconditioning of trauma-induced cardioprotection via the TRPV1 receptor. Biomed Pharmacother 2019; 118:109308. [PMID: 31401396 DOI: 10.1016/j.biopha.2019.109308] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/28/2019] [Accepted: 07/31/2019] [Indexed: 01/07/2023] Open
Abstract
Remote preconditioning of trauma (RPCT) by surgical incision is an effective cardioprotective strategy via the transient receptor potential vanilloid 1 (TRPV1) channel as a form of remote ischemic preconditioning (RIPC). However, cardioprotection by RIPC has been shown to be completely blocked by propofol. We thus hypothesized that propofol may interfere with RPCT induced cardioprotection, and that RPCT induces cardioprotection via the cardiac TRPV1 channel. Male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia followed by 2 h of reperfusion. RPCT was achieved by a transverse abdominal incision. Additionally, propofol or the TRPV1 receptor inhibitor capsazepine (CPZ) was given before RPCT. Infarct size was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RPCT significantly reduced infarct size compared to control treatment (45.6 ± 4% versus 65.4 ± 2%, P < 0.01). This protective effect of RPCT was completely abolished by propofol and CPZ. TRPV1 channels are present in the heart. Therefore, cardioprotection by RPCT is also abolished by propofol, and cardiac TRPV1 mediates this cardioprotection.
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Affiliation(s)
- Junma Yu
- Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei, 230027, PR China; Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230061, PR China
| | - Ke Chen
- Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China
| | - Lining Wu
- Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230061, PR China
| | - Xuesheng Liu
- Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China
| | - Yao Lu
- Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China.
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Deja MA, Piekarska M, Malinowski M, Wiaderkiewicz R, Czekaj P, Machej L, Węglarzy A, Kowalówka A, Kołodziej T, Czech E, Plewka D, Mizia M, Latusek T, Szurlej B. Can human myocardium be remotely preconditioned? The results of a randomized controlled trial. Eur J Cardiothorac Surg 2019; 55:1086-1094. [PMID: 30649238 DOI: 10.1093/ejcts/ezy441] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 11/02/2018] [Accepted: 11/17/2018] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study. RESULTS The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3-48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1-53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0-13.5) to 19.1% (13.2-23.8) (P < 0.001) after 1 h of ischaemia and 2 h of reperfusion in vitro. The amount of activated Caspase 3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells also significantly increased. No difference was observed between the remotely preconditioned and sham-treated myocardium. In the in vivo trial, the area under the curve for postoperative concentration of troponin T over 72 h was 16.4 ng⋅h/ml (95% confidence interval 14.2-18.9) for the remote ischaemic preconditioning and 15.5 ng⋅h/ml (13.4-17.9) for the control group in the intention-to-treat analysis. This translated into an area under the curve ratio of 1.06 (0.86-1.30; P = 0.586). CONCLUSIONS Remote ischaemic preconditioning with 3 cycles of 5-min ischaemia/reperfusion of the upper limb before cardiac surgery does not make human myocardium more resistant to ischaemia/reperfusion injury. CLINICAL TRIAL REGISTRATION NUMBER NCT01994707.
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Affiliation(s)
- Marek A Deja
- Department of Cardiac Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.,Department of Cardiac Surgery, Upper-Silesian Heart Center, Katowice, Poland
| | - Magda Piekarska
- Department of Cardiac Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.,Department of Cardiac Surgery, Upper-Silesian Heart Center, Katowice, Poland
| | - Marcin Malinowski
- Department of Cardiac Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.,Department of Cardiac Surgery, Upper-Silesian Heart Center, Katowice, Poland
| | - Ryszard Wiaderkiewicz
- Department of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Piotr Czekaj
- Department of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Leszek Machej
- Department of Anesthesia and Intensive Care Nursing, School of Health Sciences, Medical University of Silesia, Katowice, Poland
| | - Andrzej Węglarzy
- Department of Cardiac Anesthesia, Upper-Silesian Heart Center, Katowice, Poland
| | - Adam Kowalówka
- Department of Cardiac Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.,Department of Cardiac Surgery, Upper-Silesian Heart Center, Katowice, Poland
| | - Tadeusz Kołodziej
- Department of Cardiac Surgery, Upper-Silesian Heart Center, Katowice, Poland
| | - Ewa Czech
- Department of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Danuta Plewka
- Department of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Magdalena Mizia
- 1 Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Tomasz Latusek
- Department of Cardiac Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Bartosz Szurlej
- Department of Cardiac Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
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Behmenburg F, van Caster P, Bunte S, Brandenburger T, Heinen A, Hollmann MW, Huhn R. Impact of Anesthetic Regimen on Remote Ischemic Preconditioning in the Rat Heart In Vivo. Anesth Analg 2019; 126:1377-1380. [PMID: 29077609 DOI: 10.1213/ane.0000000000002563] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Remote ischemic preconditioning (RIPC) seems to be a promising cardioprotective strategy with contradictive clinical data suggesting the anesthetic regimen influencing the favorable impact of RIPC. This study aimed to investigate whether cardio protection by RIPC is abolished by anesthetic regimens. Male Wistar rats were randomized to 6 groups. Anesthesia was either maintained by pentobarbital (Pento) alone or a combination of sevoflurane (Sevo) and remifentanil or propofol (Prop) and remifentanil in combination with and without RIPC. RIPC reduced infarct size in Pento- and Sevo-anesthetized rats (Pento-RIPC: 30% ± 9% versus Pento-control [Con]: 65% ± 6%, P < .001; Sevo-RIPC: 31% ± 6% versus Sevo-Con: 61% ± 8%, P < .001), but RIPC did not initiate cardio protection in Prop-anesthetized animals (Prop-RIPC: 59% ± 6% versus Prop-Con: 59% ± 8%, P = 1.000). Cardio protection by RIPC is abolished by Prop.
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Affiliation(s)
- Friederike Behmenburg
- From the Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Patrick van Caster
- From the Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Sebastian Bunte
- From the Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Timo Brandenburger
- From the Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany
| | - André Heinen
- Institute of Cardiovascular Physiology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Markus W Hollmann
- Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands
| | - Ragnar Huhn
- From the Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany
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