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Sandroni C, Scquizzato T, Cacciola S, Bonizzoni MA, West S, D'Arrigo S, Soar J, International Liaison Committee on Resuscitation ILCOR Advanced Life Support Task Force. Does cardiopulmonary resuscitation before donor death affect solid organ transplant function? A systematic review and meta-analysis. Resuscitation 2025:110654. [PMID: 40409674 DOI: 10.1016/j.resuscitation.2025.110654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Revised: 05/04/2025] [Accepted: 05/14/2025] [Indexed: 05/25/2025]
Abstract
INTRODUCTION Patients who die after cardiopulmonary resuscitation (CPR) are an important source of solid organs, but ischaemia-reperfusion injury may lead to worse recipient outcomes. This systematic review and meta-analysis assessed if solid organs transplanted from donors who underwent CPR had worse outcomes compared to organs from donors who did not receive CPR. METHODS PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched until January 1, 2025. The primary outcome (graft survival at the longest follow-up) and secondary outcomes (30-day and 1-year graft survival) were calculated separately for each organ and pathway (brain/circulatory death). RESULTS We included 33 studies (26 in adults; 72,994 donors), of which three compared multiple organs and pathways. In 24 studies comparing brain-dead donors with vs without CPR in all organs, outcomes did not differ between groups. In nine studies, donation after uncontrolled circulatory death compared to donation after brain death showed a lower long-term survival for livers (OR 0.51 [0.32-0.83]) and lower short-term but not long-term survival (OR 0.64[0.36-1.15]) for kidneys. Two studies in kidneys compared donation in controlled vs uncontrolled circulatory death showing no different long-term survival (OR 0.73[0.27-1.99]). CONCLUSIONS Organs transplanted from donors who received CPR demonstrated comparable outcomes at the longest follow-up compared to organs from donors who did not receive CPR. Kidneys and livers after uncontrolled donation after circulatory death showed worse outcomes compared to donation after brain death.
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Affiliation(s)
- Claudio Sandroni
- Department of Intensive Care, Emergency Medicine and Anaesthesiology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy; Institute of Anaesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Tommaso Scquizzato
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sofia Cacciola
- Department of Intensive Care, Emergency Medicine and Anaesthesiology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
| | - Matteo Aldo Bonizzoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stephen West
- Intensive Care Unit, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK
| | - Sonia D'Arrigo
- Department of Intensive Care, Emergency Medicine and Anaesthesiology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
| | - Jasmeet Soar
- Intensive Care Unit, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK
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Mei S, Xiang J, Wang L, Xu Y, Li Z. Impact of Resuscitated Cardiac Arrest in the Brain-dead Donors on the Outcome of Liver Transplantation: A Retrospective and Propensity Score Matching Analysis. ANNALS OF SURGERY OPEN 2024; 5:e522. [PMID: 39711659 PMCID: PMC11661731 DOI: 10.1097/as9.0000000000000522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 10/18/2024] [Indexed: 12/24/2024] Open
Abstract
Objective To evaluate the impact of cardiac arrest time (CAT) in brain-dead donors on graft and recipient outcomes following liver transplantation. Background The outcome of livers from brain-dead donors with a history of cardiac arrest (CA) remains controversial, and the duration of the CAT has never been evaluated. Methods A retrospective review of data from the Scientific Registry of Transplant Recipients between 2003 and 2022 was conducted. Propensity score matching was performed to minimize confounding effects. Results A total of 115,202 recipients were included, 7364 (6.4%) and 107,838 (93.6%) of whom were of the CA and non-CA group, respectively. After 1:1 propensity score matching, each group consisted of 7157 cases. The CA group demonstrated shorter hospital stay (15.5 ± 20.0 days vs. 16.2 ± 21.3 days, P = 0.041), with comparable incidence of early graft failure (EGF, 5.8% vs. 6.2%, P = 0.161). The CA group demonstrated slightly higher graft survival rates (1 year, 90% vs. 88%; 5 years, 76% vs. 74%; and 10 years, 61% vs. 58%, P < 0.001). CAT positively correlated with EGF [odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.02-1.04, P < 0.001], with a sensitivity and specificity of 73% and 86% at a cutoff of 30 minutes. The CAT <30 minutes group demonstrated significantly lower incidence of EGF (5.0%), compared with 7.8% of the CAT >30 minutes group and 6.2% of the non-CA group (P < 0.001). Conclusions The use of brain-dead donors with a history of CA did not increase the risk of liver graft failure in our study. A downtime of <30 minutes may confer protective effects on transplanted grafts.
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Affiliation(s)
- Shengmin Mei
- From the Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jie Xiang
- From the Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Li Wang
- From the Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuan Xu
- Department of Surgery, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Zhiwei Li
- From the Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Wilson EA, Weinberg DL, Patel GP. Intraoperative Anesthetic Strategies to Mitigate Early Allograft Dysfunction After Orthotopic Liver Transplantation: A Narrative Review. Anesth Analg 2024; 139:1267-1282. [PMID: 38442076 DOI: 10.1213/ane.0000000000006902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.
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Affiliation(s)
- Elizabeth A Wilson
- From the Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia
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Zheng M, Wu Y, Xiang J, Wang L, Li Z, Gao F. Impact of Preprocurement Cardiac Arrest in Brain-Dead Donors on the Outcome of Pancreas Transplantation. Transplant Proc 2024; 56:2255-2262. [PMID: 39609177 DOI: 10.1016/j.transproceed.2024.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/10/2024] [Accepted: 11/11/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND This study aimed to determine the risk factors and whether cardiac arrest (CA) in brain-death donors (DBD) could affect pancreas transplantation outcomes. METHODS We analyzed data from the Scientific Registry of Transplant Recipients (2000-2020). The study included 21,499 pancreas transplantations, divided into CA-DBD and noCA-DBD groups based on whether the DBD had a history of CA. RESULTS There were 1129 CA-DBD (5.3%) transplantations. The principal donor death cause for both groups was head trauma. Graft and patient survival rates were similar in both groups. CA time (CAT) was a risk factor for pancreatic graft survival in the univariate analysis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.03-1.08; P = .010) and multivariate Cox regression model (HR, 1.03; 95% CI, 1.02-1.04; P =.015). Pancreas graft survival in those with CAT ≥30 minutes was significantly lower than in those with CAT <30 minutes and the noCA-DBD group (log-rank P = .018 and P = .014, respectively), which were comparable (log-rank P = .711). No relationships were found among the various transplantation types. CONCLUSIONS CA in donors did not affect the pancreatic graft prognosis. However, pancreatic donors with CAT ≥30 minutes should be meticulously evaluated.
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Affiliation(s)
- Minyan Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yue Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Li Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Feng Gao
- Department of Urological Surgery, Weifang People's Hospital, Shandong, China.
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Philipoff A, Lin Y, Teixeira-Pinto A, Gately R, Craig JC, Opdam H, Chapman JC, Pleass H, Rogers NM, Davies CE, McDonald S, Yang J, Lopez P, Wong G, Lim WH. Antecedent Cardiac Arrest Status of Donation After Circulatory Determination of Death (DCDD) Kidney Donors and the Risk of Delayed Graft Function After Kidney Transplantation: A Cohort Study. Transplantation 2024; 108:2117-2126. [PMID: 38685196 DOI: 10.1097/tp.0000000000005022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
BACKGROUND The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF). METHODS Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF. RESULTS A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF. CONCLUSIONS This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.
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Affiliation(s)
- Adam Philipoff
- Department of Transplant Surgery, Western Australian Kidney and Liver Transplant Surgery, Sir Charles Gairdner Hospital, Perth, WA, Australia
| | - Yingxin Lin
- Public Health, Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Sydney Precision Data Science, Faculty of Science, School of Mathematics and Science, University of Sydney, Sydney, NSW, Australia
| | - Armando Teixeira-Pinto
- Public Health, Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Centre for Kidney Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Ryan Gately
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Jonathan C Craig
- Centre for Kidney Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Helen Opdam
- Department of Intensive Care, Austin Health, Melbourne, VIC, Australia
- DonateLife, Organ and Tissue Authority, Canberra, ACT, Australia
| | - Jeremy C Chapman
- The Westmead Institute for Medical Research, Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - Henry Pleass
- Specialty of Surgery, University of Sydney, Sydney, NSW, Australia
| | - Natasha M Rogers
- The Westmead Institute for Medical Research, Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney, NSW, Australia
| | - Christopher E Davies
- Australia and New Zealand Dialysis and Transplant Registry, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- Faculty of Health and Medical Sciences, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
| | - Stephen McDonald
- Australia and New Zealand Dialysis and Transplant Registry, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- Faculty of Health and Medical Sciences, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Department of Renal Medicine, Central Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Jean Yang
- Sydney Precision Data Science, Faculty of Science, School of Mathematics and Science, University of Sydney, Sydney, NSW, Australia
| | - Pedro Lopez
- Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia
- Pleural Medicine Unit, Institute for Respiratory Health, Perth, WA, Australia
- Grupo de Pesquisa em Exercício para Populações Clínicas (GPCLIN), Universidade de Caxias do Sul, Caxias do Sul, Rio Grande do Sul, Brazil
| | - Germaine Wong
- Public Health, Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Centre for Kidney Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney, NSW, Australia
| | - Wai H Lim
- Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
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Ehrsam JP, Benden C, Immer FF, Inci I. Current status and further potential of lung donation after circulatory death. Clin Transplant 2021; 35:e14335. [PMID: 33948997 DOI: 10.1111/ctr.14335] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 04/22/2021] [Accepted: 04/27/2021] [Indexed: 12/13/2022]
Abstract
Chronic organ shortage remains the most limiting factor in lung transplantation. To overcome this shortage, a minority of centers have started with efforts to reintroduce donation after circulatory death (DCD). This review aims to evaluate the experimental background, the current international clinical experience, and the further potential and challenges of the different DCD categories. Successful strategies have been implemented to reduce the problems of warm ischemic time, thrombosis after circulatory arrest, and difficulties in organ assessment, which come with DCD donation. From the currently reported results, controlled-DCD lungs are an effective and safe method with good mid-term and even long-term survival outcomes comparable to donation after brain death (DBD). Primary graft dysfunction and onset of chronic allograft dysfunction seem also comparable. Thus, controlled-DCD lungs should be ceased to be treated as marginal and instead be promoted as an equivalent alternative to DBD. A wide implementation of controlled-DCD-lung donation would significantly decrease the mortality on the waiting list. Therefore, further efforts in establishment of legislation and logistics are crucial. With regard to uncontrolled DCD, more data are needed analyzing long-term outcomes. To help with the detailed assessment and improvement of uncontrolled or otherwise questionable grafts after retrieval, ex-vivo lung perfusion is promising.
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Affiliation(s)
- Jonas P Ehrsam
- Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.,Department of Thoracic Surgery, Cantonal Hospital Aarau, Zurich, Switzerland
| | | | | | - Ilhan Inci
- Department of Thoracic Surgery, Cantonal Hospital Aarau, Zurich, Switzerland.,University of Zurich Faculty of Medicine, Zurich, Switzerland
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De Carlis R, Buscemi V, Checchini G, Frassoni S, Bagnardi V, Pagnanelli M, Lauterio A, De Carlis L. Liver transplantation from brain-dead donors on mechanical circulatory support: a systematic review of the literature. Transpl Int 2021; 34:5-15. [PMID: 33037727 DOI: 10.1111/tri.13766] [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: 07/25/2020] [Revised: 08/18/2020] [Accepted: 10/05/2020] [Indexed: 12/14/2022]
Abstract
Mechanical circulatory support (MCS) refers to a range of rescue devices to assist circulation for the treatment of heart failure, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and ventricular assist devices (VADs). This review aims at evaluating the transplant outcome of the livers procured from brain-dead donors on MCS, who are currently considered as having extended criteria. We identified 22 records (17 on VA-ECMO and 5 on VADs), most of which (68.2%) were case reports. We performed a meta-analysis only when the outcome was reported homogeneously among studies; otherwise, we illustrated the results with narrative synthesis. A total of 156 liver transplants (LTs) have been reported, where VA-ECMO was initiated in the donor with resuscitative intent or as a bridge to donation. Early graft survival approached 100% in most studies. The pooled rate of primary nonfunction was 1% (95% CI: 0-3%). Only three successful LTs from VAD donors have been reported. Particular attention should be paid to cardiological history, biochemical tests, and imaging, as well as MCS parameters, to determine graft eligibility for transplantation. Although further analysis is needed in this field, the results of this review advocate a more systematic consideration of brain-dead patients on MCS as potential liver donors.
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Affiliation(s)
- Riccardo De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Vincenzo Buscemi
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giuliana Checchini
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Surgical Sciences, University of Pavia, Pavia, Italy
| | - Samuele Frassoni
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | - Michele Pagnanelli
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of General Surgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Schroering JR, Hathaway TJ, Kubal CA, Ekser B, Mihaylov P, Mangus RS. Impact of donor preprocurement cardiac arrest on clinical outcomes in pediatric deceased donor liver transplantation. Pediatr Transplant 2020; 24:e13701. [PMID: 32415910 DOI: 10.1111/petr.13701] [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] [Received: 11/12/2019] [Accepted: 02/05/2020] [Indexed: 11/29/2022]
Abstract
PPCA has historically been considered detrimental to donor quality in LT, but transplantation of grafts from this group of donors is now routine. Our study aims to evaluate the outcomes associated with use of donors with a history of PPCA in the pediatric population. This study is a single-center retrospective analysis of all pediatric LTs performed over an 18-year period. Donors and recipients were stratified by the presence and length of donor PPCA time. Preprocurement donor and post-transplant recipient laboratory values were collected to assess the degree of ischemic liver injury associated with each donor group. Cox regression analysis was used to compare survival. The records for 130 deceased pediatric LT donors and corresponding recipients were reviewed. There were 73 (56%) non-PPCA donors and 57 (44%) PPCA donors. Donors that experienced a PPCA event demonstrated a higher median, pretransplant peak alanine aminotransferase (ALT) level (P < .001). When comparing post-transplant recipient median ALT levels, donors with any PPCA had lower median peak ALT (P = .15) and day 3 ALT (P = .43) levels than the non-PPCA group. Rates of early graft loss did not differ. The PPCA group with >40 minutes of ischemia had markedly lower survival at 10 years, but this finding did not reach statistical significance. Liver grafts from donors with or without PPCA demonstrated no statistically significant differences in function or survival. A history of donor PPCA alone should not be used as an exclusionary criterion in pediatric liver transplantation.
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Affiliation(s)
- Joel R Schroering
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Taylor J Hathaway
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Chandrashekhar A Kubal
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Burcin Ekser
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Plamen Mihaylov
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Richard S Mangus
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
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Mehdiani A, Immohr MB, Sipahi NF, Boettger C, Dalyanoglu H, Scheiber D, Westenfeld R, Aubin H, Lichtenberg A, Boeken U, Akhyari P. Successful Heart Transplantation after Cardiopulmonary Resuscitation of Donors. Thorac Cardiovasc Surg 2020; 69:504-510. [PMID: 32674179 DOI: 10.1055/s-0040-1713351] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Heart transplantation (HTx) is the best therapy for end-stage heart failure. Unfortunately, death on the waiting list remains a problem. Decreasing the number of rejected organs could increase the donor pool. METHODS A total of 144 patients underwent HTx at our department between 2010 and 2019. Of them, 27 patients received organs of donors with cardiopulmonary resuscitation (CPR) prior to organ donation (donor CPR) and were compared with patients who received organs without CPR (control; n = 117). RESULTS We did not observe any disadvantage in the outcome of the donor CPR group compared with the control group. Postoperative morbidity and 1-year survival (control: 72%; donor CPR: 82%; p = 0.35) did not show any differences. We found no impact of the CPR time as well as the duration between CPR and organ donation, but we found an improved survival rate for donors suffering from anoxic brain injury compared with cerebral injury (p = 0.04). CONCLUSIONS Donor organs should not be rejected for HTx due to resuscitation prior to donation. The need for CPR does not affect the graft function after HTx in both short- and mid-term outcomes. We encourage the use of these organs to increase the donor pool and preserve good results.
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Affiliation(s)
- Arash Mehdiani
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | | | - Nihat Firat Sipahi
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Charlotte Boettger
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Hannan Dalyanoglu
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Daniel Scheiber
- Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Medical School, Moorenstrasse 5, Duesseldorf, Germany
| | - Ralf Westenfeld
- Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Medical School, Moorenstrasse 5, Duesseldorf, Germany
| | - Hug Aubin
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Artur Lichtenberg
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Udo Boeken
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Payam Akhyari
- Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
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Hinzmann J, Grzella S, Lengenfeld T, Pillokeit N, Hummels M, Vaihinger HM, Westhoff TH, Viebahn R, Schenker P. Impact of donor cardiopulmonary resuscitation on the outcome of simultaneous pancreas-kidney transplantation-a retrospective study. Transpl Int 2020; 33:644-656. [PMID: 32012375 DOI: 10.1111/tri.13588] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/04/2019] [Accepted: 01/28/2020] [Indexed: 11/29/2022]
Abstract
Previous cardiac arrest in brain-dead donors has been discussed as a potential risk factor in pancreas transplantation (PT), leading to a higher rate of organ refusal. This study aimed to assess the impact of cardiopulmonary resuscitation (CPR) in brain-dead donors on pancreas transplant outcome. A total of 518 type 1 diabetics underwent primary simultaneous pancreas-kidney (SPK) transplantation at our center between 1994 and 2018. Patients were divided into groups, depending on whether their donor had been resuscitated or not. A total of 91 (17.6%) post-CPR donors had been accepted for transplantation (mean duration of cardiac arrest, 19.4 ± 15.6 min). Those donors were younger (P < 0.001), had lower pancreas donor risk index (PDRI, P = 0.003), and had higher serum creatinine levels (P = 0.021). With a median follow-up of 167 months (IQR 82-229), both groups demonstrated comparable short- and long-term patient and graft survival. The resuscitation time (<20 min vs. ≥20 min) also showed no impact, with similar survival rates for both groups. A multivariable Cox regression analysis suggested no statistically significant association between donor CPR and patient or graft survival. Our results indicate that post-CPR brain-dead donors are suitable for PT without increasing the risk of complications.
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Affiliation(s)
- Jannik Hinzmann
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Sascha Grzella
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Thorsten Lengenfeld
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Nina Pillokeit
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Marielle Hummels
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Hans-Martin Vaihinger
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Timm H Westhoff
- Medical Department I, University Hospital Marienhospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Richard Viebahn
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Peter Schenker
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
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12
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Mangus RS, Schroering JR, Fridell JA, Kubal CA. Impact of Donor Pre-Procurement Cardiac Arrest (PPCA) on Clinical Outcomes in Liver Transplantation. Ann Transplant 2018; 23:808-814. [PMID: 30455411 PMCID: PMC6259573 DOI: 10.12659/aot.910387] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background Transplantation of liver grafts from deceased donors who experienced cardiac arrest prior to liver procurement is now common. This single-center study analyzed the impact of pre-donation arrest time on clinical outcomes in liver transplantation. Material/Methods Records of all orthotopic liver transplants performed at a single center over a 15-year period were reviewed. Donor records were reviewed and total arrest time was calculated as cumulative minutes. Post-transplant liver graft function was assessed using laboratory values. Graft survival was assessed with Cox regression analysis. Results Records for 1830 deceased donor transplants were reviewed, and 521 donors experienced pre-procurement cardiac arrest (28%). Median arrest time was 21 min (mean 25 min, range 1–120 min). After transplant, the peak alanine aminotransferase and bilirubin levels for liver grafts from donors with arrest were lower compared to those for donors without arrest (p<0.001). Early allograft dysfunction occurred in 25% (arrest) and 28% (no arrest) of patients (p=0.22). There were no differences in risk of early graft loss (3% vs. 3%, p=0.84), length of hospital stay (10 vs. 10 days, p=0.76), and 1-year graft survival (89% vs. 89%, p=0.94). Cox regression analysis comparing 4 groups (no arrest, <20 min, 20–40 min, and >40 min arrest) demonstrated no statistically significant difference in survival at 10 years. Subgroup analysis of 93 donation after cardiac death grafts showed no significant difference for these same outcomes. Conclusions These results support the use of select deceased liver donors who experience pre-donation cardiac arrest. Pre-donation arrest may be associated with less early allograft dysfunction, but had no impact on long-term clinical outcomes. The results for donation after cardiac death donors were similar.
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Affiliation(s)
- Richard S Mangus
- Transplant Division, Department of Surgery, Indiana University, School of Medicine, Indianapolis, IN, USA
| | - Joel R Schroering
- Transplant Division, Department of Surgery, Indiana University, School of Medicine, Indianapolis, IN, USA
| | - Jonathan A Fridell
- Transplant Division, Department of Surgery, Indiana University, School of Medicine, Indianapolis, IN, USA
| | - Chandrashekhar A Kubal
- Transplant Division, Department of Surgery, Indiana University, School of Medicine, Indianapolis, IN, USA
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Jafari A, Matthaei H, Branchi V, Bölke E, Tolba RH, Kalff JC, Manekeller S. Donor liver quality after hypovolemic shock and venous systemic oxygen persufflation in an experimental animal model. Eur J Med Res 2018; 23:51. [PMID: 30352629 PMCID: PMC6198357 DOI: 10.1186/s40001-018-0346-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 10/13/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The ever growing demand for liver transplantation inevitably necessitates an expansion of the donor pool. Utilization of "shock organs" is considered suboptimal to date while the associated outcome has hardly been investigated. MATERIALS AND METHODS Male Wistar rats underwent a period of 30 min of hypovolemic shock. After 24 h livers were explanted and prior to reperfusion underwent either 18 h of cold storage (CS; N = 6) or 17 h of CS followed by 60 min venous systemic oxygen persufflation (VSOP; N = 6). The outcome of "shock organs (SHBD)" was compared to heart-beating donor (HBD; N = 12) as positive control and non-heart-beating donor (NHBD; N = 12) as negative control animal groups. Liver function was assessed by measuring enzyme release (AST, ALT, LDH), bile production, portal vein pressure and hepatic oxygen uptake during reperfusion. For reperfusion, the isolated perfused rat liver system was used. RESULTS Liver function was severely limited in NHBD group compared to HBD organs after 18 h of CS (e.g., AST; HBD: 32.25 ± 7.25 U/l vs. NHBD: 790 ± 414.56 U/l; p < 0.005). VSOP improved liver function of NHBD organs significantly (AST; NHBD + VSOP: 333.6 ± 149.1 U/l; p < 0.005). SHBD organs showed a comparable outcome to HBD and clearly better results than NHBD organs after 18 h of CS (AST; SHBD: 76.4 ± 21.9 U/l). After 17 h of CS accompanied by 60 min VSOP, no improvement concerning liver function and integrity of SHBD organs was observed while the results were severely deteriorated by VSOP resulting in higher enzyme release (AST; SHBD + VSOP: 213 ± 61 U/l, p < 0.001), higher portal vein pressure (SHBD: 10.8 ± 1.92 mm Hg vs. SHBD + VSOP: 21.6 ± 8.8 mm Hg; p < 0.05) and lower hepatic oxygen uptake (SHBD: 321.75 ± 3.87 ml/glw/min vs. SHBD + VSOP: 395.8 ± 46.64 ml/glw/min, p < 0.05) at 24 h. CONCLUSIONS Our data suggest that the potential of "shock organs" within liver transplantation may be underestimated. If our findings are reproducable in humans, SHBD grafts should be considered as a valuable source for expanding the thus far limited donor pool.
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Affiliation(s)
- Azin Jafari
- Department of Surgery, Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freudstr. 25, 53127 Bonn, Germany
| | - Hanno Matthaei
- Department of Surgery, Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freudstr. 25, 53127 Bonn, Germany
| | - Vittorio Branchi
- Department of Surgery, Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freudstr. 25, 53127 Bonn, Germany
| | - Edwin Bölke
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine, Heinrich-Heine-Universität, Düsseldorf, Germany
| | - Rene H. Tolba
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany
| | - Jörg C. Kalff
- Department of Surgery, Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freudstr. 25, 53127 Bonn, Germany
| | - Steffen Manekeller
- Department of Surgery, Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freudstr. 25, 53127 Bonn, Germany
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14
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Schroering JR, Mangus RS, Powelson JA, Fridell JA. Impact of Deceased Donor Cardiac Arrest Time on Postpancreas Transplant Graft Function and Survival. Transplant Direct 2018; 4:e381. [PMID: 30234150 PMCID: PMC6133408 DOI: 10.1097/txd.0000000000000813] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 06/04/2018] [Indexed: 12/18/2022] Open
Abstract
Introduction Transplantation of pancreas allografts from donors that have experienced preprocurement cardiopulmonary arrest (PPCA) is not common, though use of PPCA grafts is routine in liver and kidney transplantation. This article reviews a large number of PPCA pancreas grafts at a single center and reports posttransplant outcomes including early graft dysfunction, length of hospital stay, rejection, and early and late graft survival. Methods Preprocurement cardiopulmonary arrest, arrest time, and donor and recipient pancreatic enzyme levels were collected from electronic and written medical records. The PPCA donors were stratified into 4 groups: none, less than 20 minutes, 20-39 minutes, and 40 minutes or greater. Graft survival was assessed at 7 and 90 days and at 1 year. Long-term graft survival was assessed by Cox regression analysis. Results The records of 606 pancreas transplants were reviewed, including 328 (54%) simultaneous pancreas and kidney transplants. Preprocurement cardiopulmonary arrest occurred in 176 donors (29%; median time, 20 minutes). Median peak donor lipase was higher in PPCA donors (40 μ/L vs 29 μ/L, P = 0.02). Posttransplant, peak recipient amylase, and lipase levels were similar (P = 0.63). Prolonged arrest time (>40 minutes) was associated with higher donor peak lipase and lower recipient peak amylase (P = 0.05 for both). Stratified by donor arrest time, there was no difference in 7-day, 90-day, or 1-year graft survival. Cox regression comparing the 4 groups demonstrated no statistical difference in 10-year survival. Conclusions These results support transplantation of pancreas allografts from PPCA donors. Prolonged asystole was associated with higher peak donor serum lipase but lower peak recipient serum amylase. There were no differences in allograft survival.
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Affiliation(s)
- Joel R Schroering
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Richard S Mangus
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - John A Powelson
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Jonathan A Fridell
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
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15
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Assalino M, Majno P, Toso C, Berney T, Giraud R, Dutkowski P, Andres A, Wildhaber B, Elkrief L. In situ liver splitting under extracorporeal membrane oxygenation in brain-dead donor. Am J Transplant 2018; 18:258-261. [PMID: 28801937 DOI: 10.1111/ajt.14461] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 07/21/2017] [Accepted: 08/01/2017] [Indexed: 01/25/2023]
Abstract
Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs, and four kidneys. Refractory cardiac arrest and hemodynamic instability corrected by VA-ECMO should not be considered as a contraindication to in situ liver splitting.
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Affiliation(s)
- Michela Assalino
- Division of Transplantation, Department of Surgery, University Hospitals, Geneva, Switzerland
| | - Pietro Majno
- Division of Transplantation, Department of Surgery, University Hospitals, Geneva, Switzerland.,HPB Center, University Hospitals of Geneva, Geneva, Switzerland
| | - Christian Toso
- Division of Transplantation, Department of Surgery, University Hospitals, Geneva, Switzerland
| | - Thierry Berney
- Division of Transplantation, Department of Surgery, University Hospitals, Geneva, Switzerland
| | - Raphaël Giraud
- Intensive Care University Hospitals, Geneva, Switzerland
| | - Philipp Dutkowski
- Division of Transplantation, University Hospital, Zurich, Switzerland
| | - Axel Andres
- Division of Transplantation, Department of Surgery, University Hospitals, Geneva, Switzerland
| | - Barbara Wildhaber
- University Center of Pediatric Surgery of Western Switzerland, University Hospitals, Geneva, Switzerland
| | - Laure Elkrief
- Division of Transplantation, Department of Surgery, University Hospitals, Geneva, Switzerland
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16
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Abstract
Publications are reviewed that identify factors during donor care and characteristics of the donor liver that may be associated with outcome following liver transplantation. The procurement coordinator has the opportunity to influence cold ischemia time, blood pressure, the serum sodium concentration and, perhaps, liver glycogen reserves. These variables may significantly affect postimplantation graft performance and graft or recipient survival. Summaries of those publications comprising this database are presented, and several limitations in their interpretation are discussed.
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Affiliation(s)
- David J Powner
- Vivian L. Smith Center for Neurologic Research, University of Texas Health Science Center at Houston, Tex, USA
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17
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Abstract
Organ procurement coordinators must treat various cardiac dysrhythmias (arrhythmias), including rhythm disturbances that may cause or follow a cardiac arrest, in about 15% to 50% of donors. Treatment decisions should be based on the particular dysrhythmia and its effect on donor blood pressure. Medications selected should be effective but short acting. In this article, data available in publications located through a PubMed search are reviewed and specific dysrhythmias that are likely to occur during donor care are described. Treatment recommendations are based on guidelines from the American Heart Association.
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Affiliation(s)
- David J Powner
- The University of Texas Health Science Center at Houston, USA
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18
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Hoyer DP, Paul A, Saner F, Gallinat A, Mathé Z, Treckmann JW, Schulze M, Kaiser GM, Canbay A, Molmenti E, Sotiropoulos GC. Safely expanding the donor pool: brain dead donors with history of temporary cardiac arrest. Liver Int 2015; 35:1756-63. [PMID: 25522767 DOI: 10.1111/liv.12766] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 12/09/2014] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors. METHODS We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest. RESULTS We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1-150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors. CONCLUSION This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors.
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Affiliation(s)
- Dieter P Hoyer
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Andreas Paul
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Fuat Saner
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Anja Gallinat
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Zoltan Mathé
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Juergen W Treckmann
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Maren Schulze
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Gernot M Kaiser
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Ali Canbay
- Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Ernesto Molmenti
- Department of Surgery, North Shore University Hospital, Manhasset, NY, USA
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20
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Krutsinger D, Reed RM, Blevins A, Puri V, De Oliveira NC, Zych B, Bolukbas S, Van Raemdonck D, Snell GI, Eberlein M. Lung transplantation from donation after cardiocirculatory death: a systematic review and meta-analysis. J Heart Lung Transplant 2014; 34:675-84. [PMID: 25638297 DOI: 10.1016/j.healun.2014.11.009] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Revised: 10/14/2014] [Accepted: 11/04/2014] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Lung transplantation (LTx) can extend life expectancy and enhance the quality of life for select patients with end-stage lung disease. In the setting of donor lung shortage and waiting list mortality, the interest in donation after cardiocirculatory death (DCD) is increasing. We performed a systematic review and meta-analysis to compare outcomes between DCD and conventional donation after brain death (DBD). METHODS PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were searched. We identified original research studies with 1-year post-transplant survival data involving >5 DCD transplants. We performed meta-analyses examining 1-year survival, primary graft dysfunction, and acute rejection after LTx. RESULTS We identified 519 citations; 11 observational cohort studies met our inclusion criteria for systematic review, and 6 met our inclusion criteria for meta-analysis. There were no differences found in 1-year mortality after LTx between DCD and DBD cohorts in individual studies or in the meta-analysis (DCD [n = 271] vs DBD [n = 2,369], relative risk [RR] 0.88, 95% confidence interval [CI] 0.59-1.31, p = 0.52, I(2) = 0%). There was also no difference between DCD and DBD in a pooled analysis of 5 studies reporting on primary graft dysfunction (RR 1.09, 95% CI 0.68-1.73, p = 0.7, I(2) = 0%) and 4 studies reporting on acute rejection (RR 0.72, 95% CI 0.49-1.05, p = 0.09, I(2) = 0%). CONCLUSIONS Survival after LTx from DCD is comparable to survival after LTx from DBD in observational cohort studies. DCD appears to be a safe and effective method to expand the donor pool.
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Affiliation(s)
| | - Robert M Reed
- Division of Pulmonary and Critical Care Medicine, University of Maryland, Baltimore, Maryland
| | - Amy Blevins
- Hardin Library for the Health Sciences, University of Iowa, Iowa City, Iowa
| | - Varun Puri
- Department of Surgery, Washington University, St. Louis, Missouri
| | - Nilto C De Oliveira
- Division of Cardiothoracic Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Bartlomiej Zych
- Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, London, United Kingdom
| | - Servet Bolukbas
- Department of Thoracic Surgery, Dr. Korst Schmidt Klinik, Wiesbaden, Germany
| | - Dirk Van Raemdonck
- Department of Thoracic Surgery and Lung Transplant Unit, University Hospitals Leuven, Leuven, Belgium
| | - Gregory I Snell
- Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia
| | - Michael Eberlein
- Department of Medicine, University of Iowa, Iowa City, Iowa; Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, Iowa.
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Castleberry AW, Worni M, Osho AA, Snyder LD, Palmer SM, Pietrobon R, Davis RD, Hartwig MG. Use of lung allografts from brain-dead donors after cardiopulmonary arrest and resuscitation. Am J Respir Crit Care Med 2014; 188:466-73. [PMID: 23777361 DOI: 10.1164/rccm.201303-0588oc] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
RATIONALE Patients who progress to brain death after resuscitation from cardiac arrest have been hypothesized to represent an underused source of potential organ donors; however, there is a paucity of data regarding the viability of lung allografts after a period of cardiac arrest in the donor. OBJECTIVES To analyze postoperative complications and survival after lung transplant from brain-dead donors resuscitated after cardiac arrest. METHODS The United Network for Organ Sharing database records donors with cardiac arrest occurring after brain death. Adult recipients of lung allografts from these arrest/resuscitation donors between 2005 and 2011 were compared with nonarrest donors. Propensity score matching was used to reduce the effect of confounding. Postoperative complications and overall survival were assessed using McNemar's test for correlated binary proportions and Kaplan-Meier methods. MEASUREMENTS AND MAIN RESULTS A total of 479 lung transplant recipients from arrest/resuscitation donors were 1:1 propensity matched from a cohort of 9,076 control subjects. Baseline characteristics in the 1:1-matched cohort were balanced. There was no significant difference in perioperative mortality, airway dehiscence, dialysis requirement, postoperative length of stay (P ≥ 0.38 for all), or overall survival (P = 0.52). A subanalysis of the donor arrest group demonstrated similar survival when stratified by resuscitation time quartile (P = 0.38). CONCLUSIONS There is no evidence of inferior outcomes after lung transplant from brain-dead donors who have had a period of cardiac arrest provided that good lung function is preserved and the donor is otherwise deemed acceptable for transplantation. Potential expansion of the donor pool to include cardiac arrest as the cause of brain death requires further study.
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23
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Fernández V, Tapia G, Videla LA. Recent advances in liver preconditioning: Thyroid hormone, n-3 long-chain polyunsaturated fatty acids and iron. World J Hepatol 2012; 4:119-28. [PMID: 22567184 PMCID: PMC3345536 DOI: 10.4254/wjh.v4.i4.119] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Revised: 11/08/2011] [Accepted: 04/24/2012] [Indexed: 02/06/2023] Open
Abstract
Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T(3)), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T(3), n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.
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Affiliation(s)
- Virginia Fernández
- Virginia Fernández, Gladys Tapia, Luis A Videla, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70000, Santiago-7, Chile
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24
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Levesque E, Hoti E, Khalfallah M, Salloum C, Ricca L, Vibert E, Azoulay D. Impact of reversible cardiac arrest in the brain-dead organ donor on the outcome of adult liver transplantation. Liver Transpl 2011; 17:1159-66. [PMID: 21744468 DOI: 10.1002/lt.22372] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Several donor and graft characteristics are associated with higher failure rates for deceased donor liver transplantation (LT). The influence of reversible cardiac arrest in the donor on these failure rates is unclear because of scarce and inconsistent data. The aim of this study was to determine whether reversible cardiac arrest in the donor could affect the early postoperative outcome of LT. From January 2008 to February 2010, 165 patients underwent LT, and they were retrospectively divided into 2 groups: a cardiac arrest group (34 patients who received grafts from donors who had experienced reversible cardiac arrest before organ procurement) and a control group (131 patients who received grafts from donors without a history of reversible cardiac arrest). The postoperative complications and the graft and recipient outcomes were prospectively recorded for all the patients. Graft failure was defined as death or the need for retransplantation within 90 days of LT. Donors in the cardiac arrest group displayed higher serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than donors in the control group [AST: 104 (19-756) versus 42 IU/L (10-225 IU/L), P < 0.001; ALT: 73 (13-869) versus 29 IU/L (6-549 IU/L), P < 0.001]. However, no difference in the graft failure rates was found between the 2 groups (11.8% versus 8.4%, P = 0.51). The biological parameters 5 and 7 days after LT and the peak AST/ALT levels were similar for the 2 groups. Furthermore, the 2 groups had similar graft and patient survival rates at the 6-month mark (87% and 88%, respectively). In conclusion, our study shows that brief and reversible cardiac arrest in organ donors does not affect post-LT allograft survival and function, even though liver function test values are higher for these donors. However, the risk of using these grafts needs to be balanced against the potential benefits for the recipients.
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Affiliation(s)
- Eric Levesque
- Hepatobiliary Center, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Villejuif, France
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Sandroni C, Adrie C, Cavallaro F, Marano C, Monchi M, Sanna T, Antonelli M. Are patients brain-dead after successful resuscitation from cardiac arrest suitable as organ donors? A systematic review. Resuscitation 2010; 81:1609-14. [DOI: 10.1016/j.resuscitation.2010.08.037] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2010] [Revised: 07/24/2010] [Accepted: 08/29/2010] [Indexed: 01/21/2023]
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26
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Videla LA. Hormetic responses of thyroid hormone calorigenesis in the liver: Association with oxidative stress. IUBMB Life 2010; 62:460-6. [PMID: 20503439 DOI: 10.1002/iub.345] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Thyroid hormone (L-3,3',5-triiodothyronine, T(3)) exerts calorigenic effects by accelerating mitochondrial O(2) consumption through transcriptional activation of respiratory genes, with consequent increased reactive oxygen species (ROS) production. In the liver, ROS generation occurs at different sites of hepatocytes and in the respiratory burst of Kupffer cells, triggering the activation of the transcription factors nuclear factor-kappaB, signal transducer and activator of transcription 3, and activating protein 1. Under these conditions, the redox upregulation of Kupffer cell-dependent expression of cytokines [tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6] is achieved, which upon interaction with specific receptors in hepatocytes trigger the expression of antioxidant enzymes (manganese superoxide dismutase, inducible nitric oxide synthase), antiapoptotic proteins (Bcl-2), and acute-phase proteins (haptoglobin, beta-fibrinogen). These responses and the promotion of hepatocyte and Kupffer cell proliferation observed represent hormetic effects re-establishing redox homeostasis, promoting cell survival, and protecting the liver against ischemia-reperfusion (IR) injury. It is proposed that hormesis underlying T(3) action may constitute a novel preconditioning strategy for IR injury during liver surgery in man or in liver transplantation using reduced-size grafts from living donors, considering that (i) with the exception of the controversial ischemic preconditioning, all other studied strategies have failed to reach the clinical setting and (ii) T(3) is a well-tolerated therapeutic agent that either lacks major adverse effects or has minimal and controlled side effects.
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Affiliation(s)
- Luis A Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
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Andreani P, Hoti E, de la Serna S, degli Esposti D, Sebagh M, Lemoine A, Ichai P, Saliba F, Castaing D, Azoulay D. Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia-reperfusion injury and clinical relevance. HPB (Oxford) 2010; 12:439-46. [PMID: 20815852 PMCID: PMC3030752 DOI: 10.1111/j.1477-2574.2010.00194.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). OBJECTIVE To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. PATIENTS AND METHODS Alternate patients were transplanted with right lobe grafts that were (n = 22; Group (Precond)) or were not (n = 22; Group (Control)) subjected to IPC in the living donor. Liver ischaemia-reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. RESULTS Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P = 0.8) and alanine aminotransferase (ALT) peaks (P = 0.6) were similar in both groups (307 +/- 189 and 437 +/- 302 vs. 290 +/- 146 and 496 +/- 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P = 0.003) and pre-operative bilirubin concentration (P = 0.004) were significantly predictive of minimum prothrombin time post-transplantation. CONCLUSIONS Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain.
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Affiliation(s)
- Paola Andreani
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
| | - Emir Hoti
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
| | - Sofia de la Serna
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
| | | | - Mylène Sebagh
- Département d'Anatomopathologie, Hôpital Paul BrousseVillejuif, France
| | | | - Philippe Ichai
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
| | - Fauzi Saliba
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
| | - Denis Castaing
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
| | - Daniel Azoulay
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-BiliaireIFR 89.9
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Utilization of donors who have suffered cardiopulmonary arrest and resuscitation in intestinal transplantation. Transplantation 2008; 86:941-6. [PMID: 18852660 DOI: 10.1097/tp.0b013e3181852f9a] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Cardiopulmonary resuscitation (CPR) of a person destined to become an organ donor has been associated with overall poor donor quality, especially for the intestinal donor, as splanchnic vasoconstriction that is intended to preserve coronary and cerebral blood flow may result in clinically relevant intestinal ischemia. Outcomes of recipients who receive intestine grafts that have suffered CPR are unknown. We sought to analyze our clinical experience in using intestinal grafts from donors who suffered cardiopulmonary arrest and resuscitation and to evaluate the outcome of recipients of organs coming from resuscitated donors when compared with recipients of nonresuscitated donors. METHODS We retrospectively analyzed the donor and recipient charts of all of our intestinal transplants with regard to the performance of donor CPR. RESULTS Sixty-seven intestinal transplants were performed in 65 patients from November 2003 to December 2007. Twelve donors (18%) were identified as having suffered cardiac arrest and subsequent CPR. Mean duration of CPR was 19.3+/-12.7 min. Terminal laboratory profiles of CPR donors and non-CPR donors were similar. Of the 12 resuscitated grafts, two were used for multivisceral, one for a modified multivisceral, seven for liver-intestine, and two for isolated intestinal transplant. There were no significant differences in outcome parameters such as operative time, blood use, ventilation days, length of stay, time to enteral independence, rejection, enteric bacteremia, and survival between the 12 resuscitated grafts and the 55 nonresuscitated grafts. CONCLUSION A donor history of cardiac arrest should not automatically exclude the use of the intestine graft for transplantation.
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Rescue of Acute Complete Portal Vein Occlusion With Doppler Ultrasound Findings After Liver Transplantation. Transplantation 2008; 85:778-80. [DOI: 10.1097/tp.0b013e31816616eb] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Jovanović B, Bumbasirević V, Pavlović A, Palibrk I, Pandurović M. [Management of cadaveric organ donors]. ACTA CHIRURGICA IUGOSLAVICA 2008; 55:99-105. [PMID: 18510069 DOI: 10.2298/aci0801099j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Because the supply of cadaveric organ donors is limited and their ICU management is complex, a multidisciplinary, well-coordinated, and institutionally supported approach to management is essential to ensure the maintenance of the current supply and to increase the future supply of organs and tissues that are suitable for transplantation. The potential organ donor is at high risk for instability as a direct consequence of the loss of physiologic homeostatic mechanisms that are dependent on functioning of the central nervous system. The keys to successful ICU management of the potential organ donor include a team approach that is focused on the anticipation of complications, appropriate physiologic monitoring, aggressive life support, with frequent reassessment and titration of therapy.
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Affiliation(s)
- B Jovanović
- Institut za anesteziologiju i reanimaciju. KC Srbije, Beograd
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Powner DJ. Brain Death: Compliance, Consequences and Care of the Adult Donor. Intensive Care Med 2007. [DOI: 10.1007/978-0-387-49518-7_89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Abstract
The purpose of this review is to describe in more detail ischemia reperfusion injury and preconditioning, and to speculate on the potential role of preconditioning in the care of critically ill patients. Current hemodynamic treatment of hypotension and hypoperfusion in critically ill patients is directed at ensuring essential organ perfusion by maintaining intravascular volume and cardiac output, and ensuring adequate oxygen delivery by maintaining arterial oxygen partial pressure and hemoglobin levels. However, morbidity and mortality remain high and new approaches to critically ill patients are required. Treatments are needed that can protect against organ ischemia during periods of low blood flow. In recent years, there has been a growing appreciation of the importance of ischemia reperfusion injury. Ischemia associated with reperfusion may result in greater injury than ischemia alone. Ischemic preconditioning is used to describe the protective effect of short periods of ischemia to an organ or tissue against longer periods of ischemia. Although first described in the myocardium, there is now evidence that this phenomenon occurs in a wide variety of organs and tissues, including the brain and other nervous tissue such as the retina and spinal cord, liver, stomach, intestines, kidney, and the lungs. Preconditioning therapy may offer a new avenue of treatment in critically ill patients. Both traditional preconditioning methods and pharmacologic agents that mimic or induce such preconditioning may be used in the future. Clinical trials of pharmacologic agents are underway in patients with coronary artery disease. Further trials of such methods and agents are needed in critically ill patients suffering from sepsis or multiorgan system failure.
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Affiliation(s)
- Peter Rock
- Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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Xu MQ, Shuai XR, Yan ML, Zhang MM, Yan LN. Nuclear factor-kappaB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft. World J Gastroenterol 2006; 11:6960-7. [PMID: 16437600 PMCID: PMC4717038 DOI: 10.3748/wjg.v11.i44.6960] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the protective effect of NF-kappaB decoy oligodeoxynucleotides (ODNs) on ischemia/reperfusion (I/R) injury in rat liver graft. METHODS Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold preservation of liver graft in University of Wisconsin solution containing phosphorothioated double-stranded NF-kappaB decoy ODNs or scrambled ODNs. NF-kappaB decoy ODNs or scrambled ODNs were injected intravenously into donor and recipient rats 6 and 1 h before operation, respectively. Recipients were killed 0 to 16 h after liver graft reperfusion. NF-kappaB activity in the liver graft was analyzed by electrophoretic mobility shift assay (EMSA). Hepatic mRNA expression of TNF-alpha, IFN-gamma and intercellular adhesion molecule-1 (ICAM-1) were determined by semiquantitative RT-PCR. Serum levels of TNF-alpha and IFN-gamma were measured by enzyme-linked immunosorbent assays (ELISA). Serum level of alanine transaminase (ALT) was measured using a diagnostic kit. Liver graft myeloperoxidase (MPO) content was assessed. RESULTS NF-kappaB activation in liver graft was induced in a time-dependent manner, and NF-kappaB remained activated for 16 h after graft reperfusion. NF-kappaB activation in liver graft was significant at 2 to 8 h and slightly decreased at 16 h after graft reperfusion. Administration of NF-kappaB decoy ODNs significantly suppressed NF-kappaB activation as well as mRNA expression of TNF-alpha, IFN-gamma and ICAM-1 in the liver graft. The hepatic NF-kappaB DNA binding activity [presented as integral optical density (IOD) value] in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (2.16+/-0.78 vs 36.78+/-6.35 and 3.06+/-0.84 vs 47.62+/- 8.71 for IOD value after 4 and 8 h of reperfusion, respectively, P<0.001). The hepatic mRNA expression level of TNF-alpha, IFN-gamma and ICAM-1 [presented as percent of beta-actin mRNA (%)] in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (8.31+/-3.48 vs 46.37+/-10.65 and 7.46+/- 3.72 vs 74.82+/-12.25 for hepatic TNF-alpha mRNA, 5.58+/-2.16 vs 50.46+/-9.35 and 6.47+/-2.53 vs 69.72+/-13.41 for hepatic IFN-gamma mRNA, 6.79+/-2.83 vs 46.23+/-8.74 and 5.28+/-2.46 vs 67.44+/-10.12 for hepatic ICAM-1 mRNA expression after 4 and 8 h of reperfusion, respectively, P<0.001). Administration of NF-kappaB decoy ODNs almost completely abolished the increase of serum level of TNF-alpha and IFN-gamma induced by hepatic ischemia/reperfusion, the serum level (pg/mL) of TNF-alpha and IFN-gamma in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (42.7+/-13.6 vs 176.7+/-15.8 and 48.4+/-15.1 vs 216.8+/-17.6 for TNF-alpha level, 31.5+/-12.1 vs 102.1+/-14.5 and 40.2+/-13.5 vs 118.6+/-16.7 for IFN-gamma level after 4 and 8 h of reperfusion, respectively, P<0.001). Liver graft neutrophil recruitment indicated by MPO content and hepatocellular injury indicated by serum ALT level were significantly reduced by NF-kappaB decoy ODNs, the hepatic MPO content (A655) and serum ALT level (IU/L) in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (0.17+/-0.07 vs 1.12+/-0.25 and 0.46+/-0.17 vs 1.46+/-0.32 for hepatic MPO content, 71.7+/-33.2 vs 286.1+/-49.6 and 84.3+/-39.7 vs 467.8+/-62.3 for ALT level after 4 and 8 h of reperfusion, respectively, P<0.001). CONCLUSION The data suggest that NF-kappaB decoy ODNs protects against I/R injury in liver graft by suppressing NF-kappaB activation and subsequent expression of proinflammatory mediators.
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Affiliation(s)
- Ming-Qing Xu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
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Cescon M, Grazi GL, Grassi A, Ravaioli M, Vetrone G, Ercolani G, Varotti G, D'Errico A, Ballardini G, Pinna AD. Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study. Liver Transpl 2006; 12:628-635. [PMID: 16555338 DOI: 10.1002/lt.20640] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC- group, n = 24) IPC (10-min ischemia + 15-min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC- group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC- group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC-, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits.
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Affiliation(s)
- Matteo Cescon
- Liver and Multiorgan Transplant Unit, Department of Surgery and Transplantation, University of Bologna, Bologna, Italy
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Powner D, Allison T. Cardiac dysrhythmias during donor care. Prog Transplant 2006. [DOI: 10.7182/prtr.16.1.66593806h44n853p] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Azoulay D, Del Gaudio M, Andreani P, Ichai P, Sebag M, Adam R, Scatton O, Min BY, Delvard V, Lemoine A, Bismuth H, Castaing D. Effects of 10 minutes of ischemic preconditioning of the cadaveric liver on the graft's preservation and function: the ying and the yang. Ann Surg 2005; 242:133-9. [PMID: 15973111 PMCID: PMC1357714 DOI: 10.1097/01.sla.0000167848.96692.ad] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
SUMMARY BACKGROUND DATA Although extensively studied in animal models, ischemic preconditioning has not yet been studied in clinical transplantation. OBJECTIVE To compare the results of cadaveric liver transplantation with and without ischemic liver preconditioning in the donor. PATIENTS AND METHODS Alternate patients were transplanted with liver grafts that had (n = 46, GroupPrecond) or had not (n = 45, GroupControl) been subjected to ischemic preconditioning. Liver ischemia-reperfusion injury, liver and kidney function, morbidity, and in-hospital mortality rates were compared in the 2 groups. Initial poor function was defined as a minimal prothrombin time within 10 days of transplantation <30% of normal and/or bilirubin >200 micromol/L. RESULTS The postoperative peaks of ASAT (IU/L) and ALAT (IU/L) were significantly lower in GroupPrecond (556 +/- 968 and 461+/-495, respectively) than in the GroupControl (1073 +/- 1112 and 997+/-1071, respectively). The rate of technical morbidity and the incidence of acute rejection were similar in both groups. Initial poor function was significantly more frequent in the GroupPrecond (10 of 46 cases) than in the GroupControl (3 of 45 cases). Hospital mortality rates were similar in the 2 groups. In multivariate analysis, body mass index of the donor, graft steatosis, and ischemic preconditioning were significantly predictive of the posttransplant peak of ASAT. In univariate analysis, only preconditioning was significantly associated with initial poor function. CONCLUSIONS Compared with standard orthotopic liver transplant, ischemic preconditioning of the liver graft in the donor is associated with better tolerance to ischemia. However, this is at the price of decreased early function. Until further studies are available, the clinical value of preconditioning liver grafts remains uncertain.
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Affiliation(s)
- Daniel Azoulay
- Centre Hépato-Biliaire, Département de Chirurgie Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France.
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Compagnon P, Lindell S, Ametani MS, Gilligan B, Wang HB, D'Alessandro AM, Southard JH, Mangino MJ. Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals. Transplantation 2005; 79:1393-400. [PMID: 15912109 DOI: 10.1097/01.tp.0000164146.21136.0b] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND In the rodent, ischemic preconditioning (IPC) has been shown to improve the tolerance of the liver to ischemia-reperfusion under normothermic or hypothermic conditions. The aim of the present study was to test this hypothesis in a dog model, which may be more relevant to the human. METHODS Beagle dogs were used in two distinct animal models of hepatic warm ischemia and orthotopic liver transplantation (hypothermic ischemia). IPC consisted of 10 minutes of ischemia followed by 10 minutes of reperfusion. In the first model, livers were exposed to 55 minutes prolonged warm ischemia and reperfused for 3 days (n = 6). In the second model, livers were retrieved and preserved for 48 hours at 4 degrees C in University of Wisconsin solution, transplanted, and reperfused without immunosuppression for 7 days (n = 5). In each model, nonpreconditioned animals served as controls (n = 5 in each group). Also, isolated dog hepatocytes were subjected to warm and cold storage ischemia-reperfusion to model the animal transplant studies using IPC. RESULTS In the first model (warm ischemia), IPC significantly decreased serum aminotransferase activity at 6 and 24 hours post-reperfusion. After 1 hour of reperfusion, preconditioned livers contained more adenosine triphosphate and produced more bile and less myeloperoxidase activity (neutrophils) relative to controls. In the second model (hypothermic preservation), IPC was not protective. Finally, IPC significantly attenuated hepatocyte cell death after cold storage and warm reperfusion in vitro. CONCLUSIONS IPC is effective in large animals for protecting the liver against warm ischemia-reperfusion injury but not injury associated with cold ischemia and reperfusion (preservation injury). However, the IPC effect observed in isolated hepatocytes suggests that preconditioning for preservation is theoretically possible.
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Affiliation(s)
- Philippe Compagnon
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine, Madison, WI 53792, USA
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Banga NR, Homer-Vanniasinkam S, Graham A, Al-Mukhtar A, White SA, Prasad KR. Ischaemic preconditioning in transplantation and major resection of the liver. Br J Surg 2005; 92:528-38. [PMID: 15852422 DOI: 10.1002/bjs.5004] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Ischaemia-reperfusion injury (IRI) contributes significantly to the morbidity and mortality of transplantation and major resection of the liver. Its severity is reduced by ischaemic preconditioning (IP), the precise mechanisms of which are not completely understood. This review discusses the pathophysiology and role of IP in this clinical setting. METHODS A Medline search was performed using the keywords 'ischaemic preconditioning', 'ischaemia-reperfusion injury', 'transplantation' and 'hepatic resection'. Additional articles were obtained from references within the papers identified by the Medline search. RESULTS AND CONCLUSION The mechanisms underlying hepatic IRI are complex, but IP reduces the severity of such injury in several animal models and in recent human trials. Increased understanding of the cellular processes involved in IP is of importance in the development of treatment strategies aimed at improving outcome after liver transplantation and major hepatic resection.
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Affiliation(s)
- N R Banga
- Department of Hepatobiliary Surgery and Transplantation, St James's University Hospital, Leeds, UK
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Koneru B, Fisher A, He Y, Klein KM, Skurnick J, Wilson DJ, de la Torre AN, Merchant A, Arora R, Samanta AK. Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy. Liver Transpl 2005; 11:196-202. [PMID: 15666380 DOI: 10.1002/lt.20315] [Citation(s) in RCA: 102] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.
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Affiliation(s)
- Baburao Koneru
- Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
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Corradini SG, Elisei W, De Marco R, Siciliano M, Iappelli M, Pugliese F, Ruberto F, Nudo F, Pretagostini R, Bussotti A, Mennini G, Eramo A, Liguori F, Merli M, Attili AF, Muda AO, Natalizi S, Berloco P, Rossi M. Preharvest donor hyperoxia predicts good early graft function and longer graft survival after liver transplantation. Liver Transpl 2005; 11:140-51. [PMID: 15666381 DOI: 10.1002/lt.20339] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A total of 44 donor/recipient perioperative and intraoperative variables were prospectively analyzed in 89 deceased-donor liver transplantations classified as initial good graft function (IGGF) or initial poor graft function (IPGF) according to a scoring system based on values obtained during the 1st 72 postoperative hours from the serum alanine aminotransferase (ALT) concentration, bile output, and prothrombin activity. The IGGF compared with the IPGF group showed: 1) longer graft (P = .002) and patient (P = .0004) survival; 2) at univariate analysis, a higher (mean [95% confidence interval]) preharvest donor arterial partial pressure of oxygen (PaO(2)) (152 [136-168] and 104 [91-118] mmHg, respectively; P = .0008) and arterial hemoglobin oxygen saturation (97.9 [97.2-98.7] and 96.7 [95.4-98.0]%, respectively; P = .0096), a lower percentage of donors older than 65 years (13 and 33%, respectively; P = .024), a lower percentage of donors treated with noradrenaline (16 and 41%, respectively; P = .012). At multivariate analysis, IGGF was associated positively with donor PaO(2) and negatively with donor age greater than 65 years and with donor treatment with noradrenaline. Independently from the grouping according to initial graft function, graft survival was longer when donor PaO(2) was >150 mmHg than when donor PaO(2) was < or =150 mmHg (P = .045). In conclusion, preharvest donor hyperoxia predicts IGGF and longer graft survival.
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Abstract
Publications are reviewed that identify factors during donor care and characteristics of the donor liver that may be associated with outcome following liver transplantation. The procurement coordinator has the opportunity to influence cold ischemia time, blood pressure, the serum sodium concentration and, perhaps, liver glycogen reserves. These variables may significantly affect postimplantation graft performance and graft or recipient survival. Summaries of those publications comprising this database are presented, and several limitations in their interpretation are discussed.
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Affiliation(s)
- David J Powner
- Vivian L. Smith Center for Neurologic Research, University of Texas Health Science Center at Houston, Tex, USA
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He XS, Ma Y, Wu LW, Ju WQ, Wu JL, Hu RD, Chen GH, Huang JF. Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors. World J Gastroenterol 2004; 10:3157-60. [PMID: 15457563 PMCID: PMC4611261 DOI: 10.3748/wjg.v10.i21.3157] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To explore the dynamical changes of histology, histochemistry, energy metabolism, liver microcirculation, liver function and posttransplant survival of liver graft in rats under different warm ischemia times (WIT) and predict the maximum limitation of liver graft to warm ischemia.
METHODS: According to WIT, the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60 min, respectively. The recovery changes of above-mentioned indices were observed or measured after liver transplantation. The graft survival and postoperative complications in each subgroup were analyzed.
RESULTS: Liver graft injury was reversible and gradually resumed normal structure and function after reperfusion when WIT was less than 30 min. In terms of graft survival, there was no significant difference between subgroups within 30 min WIT. When WIT was prolonged to 45 min, the recipients’ long-term survival was severely insulted, and both function and histological structure of liver graft developed irreversible damage when WIT was prolonged to 60 min.
CONCLUSION: The present study indicates that rat liver graft can be safely subjected to warm ischemia within 30 min. The levels of ATP, energy charge, activities of glycogen, enzyme-histochemistry of liver graft and its recovery potency after reperfusion may serve as the important criteria to evaluate the quality of liver graft.
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Affiliation(s)
- Xiao-Shun He
- Organ Transplantation Center, First Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
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Tsai BM, Wang M, March KL, Turrentine MW, Brown JW, Meldrum DR. Preconditioning: evolution of basic mechanisms to potential therapeutic strategies. Shock 2004; 21:195-209. [PMID: 14770032 DOI: 10.1097/01.shk.0000114828.98480.e0] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Preconditioning describes the phenomenon by which a traumatic or stressful stimulus confers protection against subsequent injury. Originally recognized in dog heart subjected to ischemic challenges, preconditioning has been demonstrated in multiple species, can be induced by various stimuli, and is applicable in different organ systems. Tremendous progress has been made elucidating the signal transduction cascade of preconditioning. Preconditioning represents a potent tissue-protective condition, and mechanistic understanding may allow safe clinical application. This review recalls the history of preconditioning and how it relates to the history of the investigation of endogenous adaptation; summarizes the current mechanistic understanding of acute preconditioning; outlines the signal transduction cascade leading to the development of delayed preconditioning; discusses preconditioning in noncardiac tissue; and explores the potential of using preconditioning clinically.
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Affiliation(s)
- Ben M Tsai
- Section of Cardiothoracic Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
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Totsuka E, Fung JJ, Hakamada K, Ohashi M, Takahashi K, Nakai M, Morohashi S, Morohashi H, Kimura N, Nishimura A, Ishizawa Y, Ono H, Narumi S, Sasaki M. Synergistic effect of cold and warm ischemia time on postoperative graft function and outcome in human liver transplantation. Transplant Proc 2004; 36:1955-8. [PMID: 15518710 DOI: 10.1016/j.transproceed.2004.08.068] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Prolonged cold ischemia time (CIT) during graft preservation and warm ischemia time (WIT) during rewarming time have been reported to cause postoperative graft dysfunction after orthotopic liver transplantation (OLT). However, the effects of both CIT and WIT in combination on patient and graft survivals are not yet defined. The aim of this study was to determine whether simultaneously prolonged CIT and WIT were associated with early graft outcomes after clinical OLT. For analysis of liver graft survival within 90 days of OLT and postoperative graft function, 186 consecutive OLT cases were divided into four groups as follows: group A, CIT < 12 hours and WIT < 45 minutes; group B, CIT > 12 hours and WIT < 45 minutes; group C, CIT < 12 hours and WIT > 45 minutes; and group D, CIT > 12 hours and WIT > 45 minutes. The graft loss rates were 5.4% in group A, 9.8% in group B, 11.1% in group C, and 42.9% in group D. The mean highest aspartate aminotransferase (AST) value after OLT in group D (3352.3 +/- 569.4 U/L) was significantly greater than those in groups A (1411.7 +/- 169.2 U/L) and B (1931.3 +/- 362.6 U/L). The simultaneously prolonged cold and warm ischemia times significantly caused hepatic allograft injury and failure, suggesting some cumulative effects of CIT and WIT on postoperative graft function.
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Affiliation(s)
- E Totsuka
- Second Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan.
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Drognitz O, Liu X, Obermaier R, Neeff H, Dobschuetz E, Hopt UT, Benz S. Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation. Transpl Int 2004. [DOI: 10.1111/j.1432-2277.2004.tb00449.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Obermaier R, von Dobschuetz E, Drognitz O, Hopt UT, Benz S. Ischemic preconditioning attenuates capillary no-reflow and leukocyte adherence in postischemic pancreatitis. Langenbecks Arch Surg 2004; 389:511-6. [PMID: 14716491 DOI: 10.1007/s00423-003-0443-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2003] [Accepted: 10/29/2003] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Ischemic preconditioning (IPC) has been shown to protect several organs from ischemia-reperfusion injury. Postischemic microvascular dysfunction is considered to be the key mechanism of early graft pancreatitis after transplantation. The aim of the study was to determine whether brief ischemia and reperfusion before prolonged ischemia followed by reperfusion is protective in respect to microcirculatory derangement in postischemic pancreatitis. METHODS In an in-situ model of ischemia-reperfusion was induced in the isolated pancreatic tail segment. Wistar rats were randomized to one group ( n=7/group) with 2-h ischemia and reperfusion (I/R) and another group with 10-min ischemia and 10-min reperfusion (IPC) before the prolonged ischemia time. Microcirculation was observed for 2 h by intravital-fluorescence microscopy that analyzed functional capillary density and leukocyte adherence in postcapillary venules. Histological damage was quantified by a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). RESULTS IPC resulted in a significant improvement of functional capillary density (248+/-20 vs 372+/-8 cm(-1), P<0.001), a significant reduction in leukocyte adherence in postcapillary venules (476+/-79 vs 179+/-15 cells/mm(2), P<0.001) and in significantly lower histological damage (score 9+/-0.8 vs 5+/-1.4, P<0.001), when compared with the ischemia-reperfusion group. CONCLUSION IPC reduces pancreatic inflammatory reaction by preservation of postischemic microcirculation. Therefore, it might become a useful procedure before organ procurement in pancreas transplantation.
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Affiliation(s)
- R Obermaier
- Department of General and Visceral Surgery, Albert-Ludwigs-University, Hugstetter Strasse 55, 79106 Freiburg, Germany.
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Abstract
Ischemia/reperfusion is the main cause of hepatic damage consequent to temporary clamping of the hepatoduodenal ligament during liver surgery as well as graft failure after liver transplantation. In recent years, a number of animal studies have shown that pre-exposure of the liver to transient ischemia, hyperthermia, or mild oxidative stress increases the tolerance to reperfusion injury, a phenomenon known as hepatic preconditioning. The development of hepatic preconditioning can be differentiated into 2 phases. An immediate phase (early preconditioning) occurs within minutes and involves the direct modulation of energy supplies, pH regulation, Na(+) and Ca(2+) homeostasis, and caspase activation. The subsequent phase (late preconditioning) begins 12-24 hours after the stimulus and requires the synthesis of multiple stress-response proteins, including heat shock proteins HSP70, HSP27, and HSP32/heme oxygenase 1. Hepatic preconditioning is not limited to parenchymal cells but ameliorates sinusoidal perfusion, prevents postischemic neutrophil infiltration, and decreases the production of proinflammatory cytokines by Kupffer cells. This latter effect is important in improving systemic disorders associated with hepatic ischemia/reperfusion. The signals triggering hepatic preconditioning have been partially characterized, showing that adenosine, nitric oxide, and reactive oxygen species can activate multiple protein kinase cascades involving, among others, protein kinase C and p38 mitogen-activated protein kinase. These observations, along with preliminary studies in humans, give a rationale to perform clinical trials aimed at verifying the possible application of hepatic preconditioning in preventing ischemia/reperfusion injury during liver surgery.
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Affiliation(s)
- Rita Carini
- Department of Medical Sciences, A. Avogdro University of East Piedmont, Via Solaroli 17, 28100 Novara, Italy
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48
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Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol 2003; 18:891-902. [PMID: 12859717 DOI: 10.1046/j.1440-1746.2003.03056.x] [Citation(s) in RCA: 299] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This review highlights recent advances in our understanding of mechanisms underlying reperfusion injury to the liver after warm hepatic ischemia. Sinusoidal endothelial cells and hepatocytes are targets of injury in the early 'cytotoxic' phase, although participation of apoptosis in the cell-death process remains contentious. Kupffer cells may play an important role as the initial cytotoxic cell type and are likely a source of reactive oxygen species and proinflammatory mediators, particularly tumor necrosis factor (TNF)-alpha. The latter are involved with subsequent neutrophil activation and recruitment. Microcirculatory disruption results from an imbalance between the actions of vasoconstrictors and vasodilators, such as nitric oxide, and also has a major impact on reperfusion injury. There is growing evidence that a brief prior ischemia-reperfusion period, termed 'ischemic preconditioning', is hepatoprotective. This can be mimicked by drugs that produce oxidative stress, and by interleukin-6 and TNF-alpha; both these cytokines are involved with priming hepatocytes to enter the cell cycle. Several mechanisms have been implicated including mobilization of adenosine and activation of adenosine type 2 receptors, nitric oxide, abrogation of TNF synthesis, preservation of energy metabolism, protection of the microcirculation and accelerated cell-cycle entry. A better understanding of preconditioning mechanisms will lead to novel approaches to improve outcomes of liver surgery.
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Affiliation(s)
- Narci C Teoh
- Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
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Wilson DJ, Fisher A, Das K, Goerlitz F, Holland BK, De La Torre AN, Merchant A, Seguel J, Samanta AK, Koneru B. Donors with cardiac arrest: improved organ recovery but no preconditioning benefit in liver allografts. Transplantation 2003; 75:1683-7. [PMID: 12777856 DOI: 10.1097/01.tp.0000064542.63798.6b] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Historically, organ recovery rates in donors with cardiac arrest (CA) have been low, presumably from hemodynamic instability. We hypothesized that donor resuscitation has improved hemodynamic stability and organ recovery in CA donors, and that CA triggers ischemic preconditioning (IP) in liver grafts. METHODS A total of 131 donor pairs with and without CA were matched in age, gender, and year of recovery. Hemodynamic stability was determined by vasopressor use. Abdominal and thoracic organs recovered and livers transplanted were compared between the groups. Liver graft function, injury, and IP benefit were examined by comparing liver chemistries after transplantation and postperfusion biopsies between recipients of grafts from both groups (n=40 each). RESULTS Hemodynamic stability was similar in both groups, but recovery of thoracic organs was significantly lower in CA versus non-CA donors (35 vs. 53%, P<0.01). On the other hand, recovery rates of three or more abdominal organs from CA donors approached those of non-CA donors (77 vs. 87%, not significant). Although significantly fewer livers were transplanted from CA donors (69 vs. 85%, P<0.01), posttransplantation graft function and injury parameters were similar between the two groups, and CA did not appear to trigger IP. CONCLUSION Compared with historical data, cardiovascular stability and abdominal organ recovery rates have improved considerably in CA donors. Liver grafts from CA donors function similarly to grafts from non-CA donors with no IP from CA. Our data support the increased use of livers and other organs from donors with CA.
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Affiliation(s)
- Dorian J Wilson
- Department of Surgery, New Jersey Medical School, Newark, New Jersey, USA
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Pastor CM, Frossard JL, Mentha G, Mastrangelo D, Quadri R, Hadengue A. Effect of hyperthermic preconditioning on cold preserved rat portal veins. J Hepatol 2002; 37:640-7. [PMID: 12399231 DOI: 10.1016/s0168-8278(02)00242-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS Little information is available regarding the effect of cold storage and hyperthermic preconditioning on the contractile responses of hepatic vessels. We then studied, after cold preservation, the in vitro contractile responses of rat portal veins (RPV) isolated from normal rats or from rats previously subjected to hyperthermia. METHODS Rats were or were not subjected to hyperthermia 24 h before the RPV isolation. Then, RPV were stored at 4 degrees C in Krebs-Henseleit bicarbonate (KHB) or University of Wisconsin solution or conserved at 20 degrees C in KHB solution. Control RPV were tested after rat sacrifice. RESULTS The contractile responses were importantly decreased in RPV conserved at room temperature. The morphology of the vessels was altered and the heat shock protein 70 (Hsp70) protein expression disappeared. These abnormalities were prevented by cold preservation. The type of preservation solution did not interfere with the beneficial effect. Hyperthermic preconditioning increased the expression of Hsp70 protein in freshly isolated and cold preserved RPV but decreased the contractile responses. In RPV conserved at room temperature, hyperthermic preconditioning further worsened the decreased contractile response. CONCLUSIONS Thus, hyperthermic preconditioning, which is beneficial in protecting hepatic injury following cold preservation, alters the contractile responses of RPV.
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Affiliation(s)
- Catherine M Pastor
- Division d'Hépatologie et de Gastro-entérologie, Hôpital Cantonal Universitaire de Genève, Rue Micheli-du-Crest, 24, 1211 Geneva 14, Switzerland.
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