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Ji Z, Zheng J, Ma Y, Lei H, Lin W, Huang J, Yang H, Zhang G, Li B, Shu B, Du X, Zhang J, Lin H, Liao Y. Emergency Treatment and Photoacoustic Assessment of Spinal Cord Injury Using Reversible Dual-Signal Transform-Based Selenium Antioxidant. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2207888. [PMID: 37127878 DOI: 10.1002/smll.202207888] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 04/08/2023] [Indexed: 05/03/2023]
Abstract
Spinal cord injury (SCI), following explosive oxidative stress, causes an abrupt and irreversible pathological deterioration of the central nervous system. Thus, preventing secondary injuries caused by reactive oxygen species (ROS), as well as monitoring and assessing the recovery from SCI are critical for the emergency treatment of SCI. Herein, an emergency treatment strategy is developed for SCI based on the selenium (Se) matrix antioxidant system to effectively inhibit oxidative stress-induced damage and simultaneously real-time evaluate the severity of SCI using a reversible dual-photoacoustic signal (680 and 750 nm). Within the emergency treatment and photoacoustic severity assessment (ETPSA) strategy, the designed Se loaded boron dipyrromethene dye with a double hydroxyl group (Se@BDP-DOH) is simultaneously used as a sensitive reporter group and an excellent antioxidant for effectively eliminating explosive oxidative stress. Se@BDP-DOH is found to promote the recovery of both spinal cord tissue and locomotor function in mice with SCI. Furthermore, ETPSA strategy synergistically enhanced ROS consumption via the caveolin 1 (Cav 1)-related pathways, as confirmed upon treatment with Cav 1 siRNA. Therefore, the ETPSA strategy is a potential tool for improving emergency treatment and photoacoustic assessment of SCI.
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Affiliation(s)
- Zhisheng Ji
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P. R. China
| | - Judun Zheng
- Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China
| | - Yanming Ma
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P. R. China
| | - Hongyi Lei
- Department of Anesthesiology, Longgang District Central Hospital of Shenzhen, Shenzhen, 518100, P. R. China
| | - Weiqiang Lin
- Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China
| | - Jialin Huang
- Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China
| | - Hua Yang
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P. R. China
| | - Guowei Zhang
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P. R. China
| | - Bin Li
- Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China
| | - Bowen Shu
- Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China
| | - Xianjin Du
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China
| | - Jian Zhang
- Department of Biomedical Engineering, School of Basic Medical Science, Guang-zhou Medical University, Guangzhou, 511436, P. R. China
| | - Hongsheng Lin
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P. R. China
| | - Yuhui Liao
- Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China
- Department of Anesthesiology, Longgang District Central Hospital of Shenzhen, Shenzhen, 518100, P. R. China
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, 750004, P. R. China
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Xia W, Singh N, Goel S, Shi S. Molecular Imaging of Innate Immunity and Immunotherapy. Adv Drug Deliv Rev 2023; 198:114865. [PMID: 37182699 DOI: 10.1016/j.addr.2023.114865] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 04/17/2023] [Accepted: 05/03/2023] [Indexed: 05/16/2023]
Abstract
The innate immune system plays a key role as the first line of defense in various human diseases including cancer, cardiovascular and inflammatory diseases. In contrast to tissue biopsies and blood biopsies, in vivo imaging of the innate immune system can provide whole body measurements of immune cell location and function and changes in response to disease progression and therapy. Rationally developed molecular imaging strategies can be used in evaluating the status and spatio-temporal distributions of the innate immune cells in near real-time, mapping the biodistribution of novel innate immunotherapies, monitoring their efficacy and potential toxicities, and eventually for stratifying patients that are likely to benefit from these immunotherapies. In this review, we will highlight the current state-of-the-art in noninvasive imaging techniques for preclinical imaging of the innate immune system particularly focusing on cell trafficking, biodistribution, as well as pharmacokinetics and dynamics of promising immunotherapies in cancer and other diseases; discuss the unmet needs and current challenges in integrating imaging modalities and immunology and suggest potential solutions to overcome these barriers.
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Affiliation(s)
- Wenxi Xia
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, United States
| | - Neetu Singh
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, United States
| | - Shreya Goel
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, United States; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, United States; Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84112, United States
| | - Sixiang Shi
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, United States; Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84112, United States.
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Cortese S, López Baena JÁ, Pérez Peña JM, Matilla AM, Olmedilla L, Morales Taboada Á, Fernández Vázquez ML, Fernández Martínez M, Asencio JM. Usefulness of Indocyanine Green Plasma Disappearance Rate in Liver Donors and Recipients: A Prospective Observational Study. Transplant Proc 2022; 54:2545-2548. [DOI: 10.1016/j.transproceed.2022.07.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/22/2022] [Accepted: 07/22/2022] [Indexed: 12/07/2022]
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Malhotra S, Dumoga S, Singh N. Red blood cells membrane-derived nanoparticles: Applications and key challenges in their clinical translation. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2022; 14:e1776. [PMID: 35106966 DOI: 10.1002/wnan.1776] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 08/16/2021] [Accepted: 10/12/2021] [Indexed: 12/20/2022]
Abstract
Cellular membrane-derived nanoparticles, particularly of red blood cells (RBCs), represent an emerging class of drug delivery systems. The lack of nucleus and organelles in these cells makes them easy to process and empty out intracellular contents. The empty vesicle membranes can then be either used as a coating on nanoparticles or can be reassembled into a nanovesicle. Engineered RBCs membrane has unique ability to retain its lipid bilayer architecture with host's proteins during top-down approach, thus allowing it to form stable nanoformulations mimicking RBCs stealth properties. In addition, its core-shell structure allows loading of different drug molecules, and its surface chemistry can be manipulated by facile conjugation with ligands on the shell. The remarkable ability of RBCs membrane to fuse with membranes of other cells enables the formation of hybrid nanovesicles. In this review, we highlight the biomedical applications of such vesicles and discuss the potential challenges related to its clinical translation. Although nano-RBCs retain much of the host's proteins, which may give an edge over synthetic nanoparticles in terms of lower immunogenicity, its production at industrial level is more challenging. This review gives the critical analysis of barriers involved in the translation of RBCs-derived nanoparticles from preclinical to clinical level. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.
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Affiliation(s)
- Sahil Malhotra
- Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India
| | - Shweta Dumoga
- Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India
| | - Neetu Singh
- Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.,Biomedical Engineering unit, All India Institute of Medical Sciences New Delhi, New Delhi, India
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Malhotra S, Dumoga S, Mehta S, Rao EP, Mohanty S, Singh N. Engineering Cellular Membrane for Dual Mode Therapy Using NIR Responsive Photosensitizer and Reversible Topoisomerase Inhibition Activity. ACS APPLIED BIO MATERIALS 2022; 5:570-582. [PMID: 35040623 DOI: 10.1021/acsabm.1c01070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Extensive research over past few decades has highlighted the challenges of chemotherapy and prompted the need for multimodality therapy because chemotherapy alone cannot fully eradicate the tumor due to physiological barriers in its effective delivery and systemic side effects. It can be mitigated by adopting nanoparticles as more effective delivery method, but none of them completely prevents drug toxicities. Utilizing multiple therapeutic modes such as phototherapy that can act synergistically with chemotherapy in controlling tumor growth, while reducing the overall dosage, could become a preferred route for cancer management. Careful selection of nanoparticle system, which can simultaneously deliver both drug and photosensitizer, can significantly enhance the therapeutic outcome. Therefore, in this paper, we report development and potential of immune-compatible and long circulating nanoerythrosomes for enhancing the therapeutic potential of camptothecin and indocyanine green against murine cancer model. The RBCs membrane simultaneously loaded the nonpolar drug and amphiphilic photosensitizer in its lipid bilayer, which self-assembled to form stable nanoparticles. These nano constructs absorbed light in the near-infrared region and hence are suitable for targeting deep seated tissues. The dual chemo-phototherapy had great effect on cell viability and had therapeutic value.
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Affiliation(s)
- Sahil Malhotra
- Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India
| | - Shweta Dumoga
- Meerut Institute of Engineering and Technology, Meerut 250005, India
| | - Supriya Mehta
- Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India
| | - E Pranshu Rao
- Stem Cell Facility, DBT-Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
| | - Sujata Mohanty
- Stem Cell Facility, DBT-Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
| | - Neetu Singh
- Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.,Biomedical Engineering Unit, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
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Abstract
Indocyanine green (ICG) is a fluorescent dye taken up and almost exclusively cleared by the liver. Measurement of its clearance and visualization of its fluorescence make it suitable for a number of potential applications in liver transplantation including assessment of liver function and real-time assessment of arterial, venous, and biliary structures. ICG clearance can be used to assess donor graft quality before procurement and graft metabolic function before transplant using normothermic ex vivo machine perfusion. ICG clearance in the post-liver transplantation period is able to predict recipient outcomes with correlations to early allograft dysfunction and postoperative complications. After absorbing light in the near-infrared spectrum, ICG also emits fluorescence at 835 nm. This allows the assessment of vascular patency after reconstruction and patterns of liver perfusion in real time. ICG perfusion patterns after revascularization are also associated with posttransplant graft function and survival. ICG fluorescence cholangiography is routine in a number of centers and acts as an aid to identifying the optimal point of bile duct division during living donor liver transplantation to optimize safety for both donor and recipient. In summary, ICG is a versatile tool and has a number of useful applications in the liver transplantation journey including assessment of liver function, perfusion assessment, and cholangiography. Further research and clinical trials are required to validate and standardize its routine use in liver transplantation.
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Cherchi V, Vetrugno L, Terrosu G, Zanini V, Ventin M, Pravisani R, Tumminelli F, Brollo PP, Boscolo E, Peressutti R, Lorenzin D, Bove T, Risaliti A, Baccarani U. Association between the donor to recipient ICG-PDR variation rate and the functional recovery of the graft after orthotopic liver transplantation: A case series. PLoS One 2021; 16:e0256786. [PMID: 34449820 PMCID: PMC8396715 DOI: 10.1371/journal.pone.0256786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/15/2021] [Indexed: 12/23/2022] Open
Abstract
Background Despite current advances in liver transplant surgery, post-operative early allograft dysfunction still complicates the patient prognosis and graft survival. The transition from the donor has not been yet fully understood, and no study quantifies if and how the liver function changes through its transfer to the recipient. The indocyanine green dye plasma disappearance rate (ICG-PDR) is a simple validated tool of liver function assessment. The variation rate between the donor and recipient ICG-PDR still needs to be investigated. Materials and methods Single-center retrospective study. ICG-PDR determinations were performed before graft retrieval (T1) and 24 hours after transplant (T2). The ICG-PDR relative variation rate between T1 and T2 was calculated to assess the graft function and suffering/recovering. Matched data were compared with the MEAF model of graft dysfunction. Objective To investigate whether the variation rate between the donor ICG-PDR value and the recipient ICG-PDR measurement on first postoperative day (POD1) can be associated with the MEAF score. Results 36 ICG-PDR measurements between 18 donors and 18 graft recipients were performed. The mean donor ICG-PDR was 22.64 (SD 6.35), and the mean receiver’s ICG-PDR on 1st POD was 17.68 (SD 6.60), with a mean MEAF value of 4.51 (SD 1.23). Pearson’s test stressed a good, linear inverse correlation between the ICG-PDR relative variation and the MEAF values, correlation coefficient -0.580 (p = 0.012). Conclusion The direct correlation between the donor to recipient ICG-PDR variation rate and MEAF was found. Measurements at T1 and T2 showed an up- or downtrend of the graft performance that reflect the MEAF values.
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Affiliation(s)
- Vittorio Cherchi
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
| | - Luigi Vetrugno
- Department of Anesthesia and Intensive Care, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Giovanni Terrosu
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Victor Zanini
- Department of Anesthesia and Intensive Care, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Marco Ventin
- Department of Medicine, University of Udine, Udine, Italy
- * E-mail:
| | - Riccardo Pravisani
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Francesco Tumminelli
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Pier Paolo Brollo
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Erica Boscolo
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | | | - Dario Lorenzin
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
| | - Tiziana Bove
- Department of Anesthesia and Intensive Care, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | | | - Umberto Baccarani
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
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Luo X, Hu D, Gao D, Wang Y, Chen X, Liu X, Zheng H, Sun M, Sheng Z. Metabolizable Near-Infrared-II Nanoprobes for Dynamic Imaging of Deep-Seated Tumor-Associated Macrophages in Pancreatic Cancer. ACS NANO 2021; 15:10010-10024. [PMID: 34060821 DOI: 10.1021/acsnano.1c01608] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as pancreatic cancer. Herein, we aim to develop metabolizable dextran-indocyanine green (DN-ICG) nanoprobes in the second near-infrared window (NIR-II, 1 000-1 700 nm) for dynamic imaging of TAMs in pancreatic cancer. Compared to free ICG, the NIR-II fluorescence intensity of DN-ICG nanoprobes increased by 279% with significantly improved stability. We demonstrated that DN-ICG nanoprobes could specifically target TAMs through the interaction of dextran with specific ICAM-3-grabbing nonintegrin related 1 (SIGN-R1), which were highly expressed in TAMs. Subsequently, DN-ICG nanoprobes gradually metabolized in the liver yet remained in pancreatic tumor stroma in mouse models, achieving a high signal-to-background ratio (SBR = 7) in deep tissue (∼0.5 cm) NIR-II imaging of TAMs. Moreover, DN-ICG nanoprobes could detect dynamic changes of TAMs induced by low-dose radiotherapy and zoledronic acid. Therefore, the highly biocompatible and biodegradable DN-ICG nanoprobes harbor great potential for precision therapy in pancreatic cancer.
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Affiliation(s)
- Xinping Luo
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, P. R. China
- Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Dehong Hu
- Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Duyang Gao
- Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Yuenan Wang
- Department of Radiaton Oncology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong Province 518036, P. R. China
| | - Xinhua Chen
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, P. R. China
| | - Xin Liu
- Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Hairong Zheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Minjie Sun
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Zonghai Sheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China
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Cherchi V, Vetrugno L, Zanini V, Pravisani R, Ventin M, Lorenzin D, Adani GL, Clocchiatti L, Boscolo E, Vit A, Sponza M, D'Alì L, Di Loreto C, Bove T, Terrosu G, Risaliti A, Baccarani U. Association between indocyanine green clearance test and ischemic type biliary lesions within one year after orthotopic liver transplantation. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:687-695. [PMID: 34023468 DOI: 10.1016/j.gastrohep.2021.03.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 03/03/2021] [Accepted: 03/29/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. OBJECTIVE Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. METHODS This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. RESULTS ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. LIMITATIONS Retrospective, single-center study. CONCLUSIONS The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.
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Affiliation(s)
- Vittorio Cherchi
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Luigi Vetrugno
- Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy; Department of Anesthesia and Intensive Care, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Victor Zanini
- Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy; Department of Anesthesia and Intensive Care, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Riccardo Pravisani
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy; Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy
| | - Marco Ventin
- Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy.
| | - Dario Lorenzin
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Gian Luigi Adani
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Lucrezia Clocchiatti
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy; Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy
| | - Erica Boscolo
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy; Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy
| | - Alessandro Vit
- Division of Vascular and Interventional Radiology, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Massimo Sponza
- Division of Vascular and Interventional Radiology, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Lorenzo D'Alì
- Anatomic Pathology Institute, ASUFC University Hospital, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Carla Di Loreto
- Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy; Anatomic Pathology Institute, ASUFC University Hospital, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Tiziana Bove
- Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy; Department of Anesthesia and Intensive Care, University-Hospital of Udine, P.le S. Maria della, Misericordia n° 15, 33100 Udine, Italy
| | - Giovanni Terrosu
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy; Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy
| | - Andrea Risaliti
- Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy
| | - Umberto Baccarani
- General Surgery Clinic and Liver Transplant Center, University-Hospital of Udine, P.le S. Maria della Misericordia 15, 33100 Udine, Italy; Department of Medicine, University of Udine, Via Colugna n° 50, 33100 Udine, Italy
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Marants R, Qirjazi E, Lai KB, Szeto CC, Li PKT, Li F, Lee TY, McIntyre CW. Exploring the Link Between Hepatic Perfusion and Endotoxemia in Hemodialysis. Kidney Int Rep 2021; 6:1336-1345. [PMID: 34013112 PMCID: PMC8116762 DOI: 10.1016/j.ekir.2021.02.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/25/2021] [Accepted: 02/01/2021] [Indexed: 01/18/2023] Open
Abstract
Introduction The liver receives gut-derived endotoxin via the portal vein, clearing it before it enters systemic circulation. Hemodialysis negatively impacts the perfusion and function of multiple organs systems. Dialysate cooling reduces hemodialysis-induced circulatory stress and protects organs from ischemic injury. This study examined how hemodialysis disrupts liver hemodynamics and function, its effect on endotoxemia, and the potential protective effect of dialysate cooling. Methods Fifteen patients were randomized to receive either standard (36.5°C dialysate temperature) or cooled (35.0°C) hemodialysis first in a two-visit crossover trial. We applied computed tomography (CT) liver perfusion imaging to patients before, 3 hours into and after each hemodialysis session. We measured hepatic perfusion and perfusion heterogeneity. Hepatic function was measured by indocyanine green (ICG) clearance. Endotoxin levels in blood throughout dialysis were also measured. Results During hemodialysis, overall liver perfusion did not significantly change, but portal vein perfusion trended towards increasing (P = 0.14) and perfusion heterogeneity significantly increased (P = 0.038). In addition, ICG clearance decreased significantly during hemodialysis (P = 0.016), and endotoxin levels trended towards increasing during hemodialysis (P = 0.15) and increased significantly after hemodialysis (P = 0.037). Applying dialysate cooling trended towards abrogating these changes but did not reach statistical significance compared to standard hemodialysis. Conclusion Hemodialysis redistributes liver perfusion, attenuates hepatic function, and results in endotoxemia. Higher endotoxin levels in end-stage renal disease (ESRD) patients may result from the combination of decreased hepatic clearance function and increasing fraction of liver perfusion coming from toxin-laden portal vein during hemodialysis. The protective potential of dialysate cooling should be explored further in future research studies.
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Affiliation(s)
- Raanan Marants
- Department of Medical Biophysics, Western University, London, Ontario, Canada.,Robarts Research Institute, Western University, London, Ontario, Canada
| | - Elena Qirjazi
- The Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada.,Division of Nephrology, Alberta Health Sciences, Calgary, Alberta, Canada
| | - Ka-Bik Lai
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Cheuk-Chun Szeto
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Philip K T Li
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Fiona Li
- Department of Medical Biophysics, Western University, London, Ontario, Canada.,Robarts Research Institute, Western University, London, Ontario, Canada.,Lawson Health Research Institute, London, Ontario, Canada
| | - Ting-Yim Lee
- Department of Medical Biophysics, Western University, London, Ontario, Canada.,Robarts Research Institute, Western University, London, Ontario, Canada.,Lawson Health Research Institute, London, Ontario, Canada
| | - Christopher W McIntyre
- Department of Medical Biophysics, Western University, London, Ontario, Canada.,The Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada.,Lawson Health Research Institute, London, Ontario, Canada.,Division of Nephrology, London Health Sciences Centre, London, Ontario, Canada
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11
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Gonzalez EH, Nacif LS, Flores Cassenote AJ, Pinheiro RS, Rocha-Santos V, Bronze de Martino R, Waisberg DR, Arantes RM, Ducatti L, Haddad L, Galvão F, Andraus W, D'Albuquerque LC. Early Graft Dysfunction Evaluation by Indocyanine Green Plasma Clearance Rate in the Immediate Postoperative Period After Liver Transplantation. Transplant Proc 2020; 52:1336-1339. [PMID: 32178927 DOI: 10.1016/j.transproceed.2020.02.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 02/07/2020] [Accepted: 02/13/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND Liver transplantation (LT) has evolved to improve graft and patient survival. Early graft dysfunction (EGD) and primary nonfunction are an important cause of morbi-mortality. We had formulated the scientific hypothesis that the liver function can be evaluated by the indocyanine green (IG) after LT. The aim was to evaluate the EGD by plasma disappearance rate (PDR) of IG after LT. METHOD Prospective and observational clinical study, from July 2014 to June 2015. IG evaluation by pulse densitometry, Limon system. Degree analysis of ischemia and reperfusion injury in groups as follows: 1 (G0/G1/G2) and 2 (G3/G4). Donor risk index (DRI), Wagener and Olthoff criteria, and prognostic predictors were evaluated. All tests were performed with bidirectional α of 0.05 and a confidence interval of 95% and support by IBM SPSS 25. RESULTS A total of 40 patients, mean age 53.3 ± 14.0 years and a majority of men and hepatitis C virus. PDR were more relevant with high degrees of ischemia and reperfusion injury grades G3/G4 (P = .030). The PDR related to the donor risk index showed positive significance at DRI >1.5 (P = .066). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death (P = .063). CONCLUSION EGD can be assessed by PDR with high degrees of ischemia and reperfusion injury (G3/G4) and with marginal donors (DRI >1.5). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death of the patient.
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Affiliation(s)
- Esteban Horacio Gonzalez
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Lucas Souto Nacif
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
| | - Alex Jones Flores Cassenote
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Rafael Soares Pinheiro
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Vinicius Rocha-Santos
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Rodrigo Bronze de Martino
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Daniel Reis Waisberg
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Rubens Macedo Arantes
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Liliana Ducatti
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Luciana Haddad
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Flávio Galvão
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Wellington Andraus
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Luiz Carneiro D'Albuquerque
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
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12
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Indocyanine green dye clearance test: early graft (dys)-function and long-term mortality after liver transplant. Should we continue to use it? An observational study. J Clin Monit Comput 2020; 35:505-513. [PMID: 32166552 DOI: 10.1007/s10877-020-00493-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 03/04/2020] [Indexed: 12/27/2022]
Abstract
Early allograft dysfunction (EAD) can be a serious complication in the immediate postoperative period following liver transplantation. Our aim was to study the prognostic role of the indocyanine green plasma disappearance rate (ICG-PDR) in predicting early and late EAD and mortality at 3 and 12 months and 5 years after liver transplantation. ICG-PDR values were also assessed for association with the Donor Risk Index (DRI). 220 patients underwent orthotopic liver transplantation. In 77 patients, ICG-PDR was assessed on the 1st post-operative (PO) day. ICG, a water-soluble dye almost entirely excreted into the bile, was measured by spectrophotometry to evaluate graft (dys)-function. DRI was calculated in all patients. The primary study outcomes were the presence (or absence) of EAD after transplant and the results of mortality risk factor analysis. EAD occurred in 18 patients. 1st PO day ICG-PDR was significantly associated with EAD (p < 0.005). A threshold ICG-PDR value < 16%/min on the 1st PO day was also associated with patient probability to survive at 3 and 12 months and 5 years. The sensitivity and specificity of the AUC was good in predicting EAD, being 83% and 56%, respectively, for a 1st PO day ICG-PDR cut-off value < 16%/min. In this study, ICG-PDR on the 1st PO day following OLT can reliably predict EAD and survival at 3 and 12 months and 5 years. ICG-PDR should, therefore, be routinely performed on the 1st PO day following OLTx in all patients in light of its important prognostic role.
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13
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Aguree S, Gernand AD. An efficient method for measuring plasma volume using indocyanine green dye. MethodsX 2019; 6:1072-1083. [PMID: 31193322 PMCID: PMC6526294 DOI: 10.1016/j.mex.2019.05.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 05/04/2019] [Indexed: 01/09/2023] Open
Abstract
Plasma volume (PV) can be an important marker of health status and may affect the interpretation of plasma biomarkers, but is rarely measured due to the complexity and time required. Indocyanine green (ICG) is a water-soluble tricarbocyanine dye with a circulatory half-life of 2–3 min, allowing for quick clearance and repeated use. It is used extensively in medical diagnostic tests including ophthalmologic imaging, liver function, and cardiac output, particularly in critical care. ICG has been validated for measuring PV in humans, however previous work has provided minimal published details or has focused on a single aspect of the method. We aimed to develop a detailed, optimal protocol for the use of ICG to measure PV in women of reproductive age. We combined best practices from other studies and optimized the protocol for efficiency.
This method reduces the time from blood collection to PV determination to ˜2 h and the amount of plasma required to estimate PV to 2.5 mL (1.5 mL before ICG injection and 1.0 mL post-injection). Participant inconvenience is reduced by inserting an intravenous (IV) catheter in only one arm, not both arms. Five post-injection plasma samples (2–5 min after ICG bolus) are enough to accurately develop the decay curve for plasma ICG concentration and estimate PV by extrapolation.
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Affiliation(s)
- Sixtus Aguree
- Department of Nutritional Sciences, The Pennsylvania State University, 110 Chandlee Laboratory, University Park, PA, 16802, United States
| | - Alison D Gernand
- Department of Nutritional Sciences, The Pennsylvania State University, 110 Chandlee Laboratory, University Park, PA, 16802, United States
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14
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Lozano P, Orue-Echebarria MI, Asencio JM, Sharma H, Lisbona CJ, Olmedilla L, Pérez Peña JM, Salcedo MM, Skaro A, Velasco E, Colón A, Díaz-Zorita B, Rodríguez L, Ferreiroa J, López-Baena JÁ. Donor Risk Index Has an Impact in Intraoperative Measure of Hepatic Artery Flow and in Clearance of Indocyanine Green: An Observational Cohort Study. Transplant Proc 2019; 51:50-55. [PMID: 30655145 DOI: 10.1016/j.transproceed.2018.03.138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 03/15/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increase in indications for liver transplantation has led to acceptance of donors with expanded criteria. The donor risk index (DRI) was validated with the aim of being a predictive model of graft survival based on donor characteristics. Intraoperative arterial hepatic flow and indocyanine green clearance (plasma clearance rate of indocyanine green [ICG-PDR]) are easily measurable variables in the intraoperative period that may be influenced by graft quality. Our aim was to analyze the influence of DRI on intraoperative liver hemodynamic alterations and on intraoperative dynamic liver function testing (ICG-PDR). METHODS This investigation was an observational study of a single-center cohort (n = 228) with prospective data collection and retrospective data analysis. Measurement of intraoperative flow was made with a VeriQ flowmeter based on measurement of transit time (MFTT). The ICG-PDR was obtained from all patients with a LiMON monitor (Pulsion Medical Systems AG, Munich, Germany). DRI was calculated using a previously validated formula. Normally distributed variables were compared using Student's t test. Otherwise, the Mann-Whitney U test or Kruskal-Wallis test was applied, depending on whether there were 2 or more comparable groups. The qualitative variables and risk measurements were analyzed using the chi-square test. P < .05 was considered statistically significant. RESULTS DRI score (mean ± SD) was 1.58 ± 0.31. The group with DRI >1.7 (poor quality) had an intraoperative arterial flow of 234.2 ± 121.35 mL/min compared with the group having DRI < 1.7 (high quality), with an intraoperative arterial flow of 287.24 ± 156.84 mL/min (P = .02). The group with DRI >1.70 had an ICG-PDR of 14.75 ± 6.52%/min at 60 minutes after reperfusion compared to the group with DRI <1.70, with an ICG-PDR of 16.68 ± 6.47%/min at 60 minutes after reperfusion (P = .09). CONCLUSION Poor quality grafts have greater susceptibility to ischemia-reperfusion damage. Decreased intraoperative hepatic arterial flow may represent an increase in intrahepatic resistance early in the intraoperative period.
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Affiliation(s)
- P Lozano
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
| | - M I Orue-Echebarria
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - J M Asencio
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - H Sharma
- Department of Multi-Organ Transplant Surgery, Ochsner Medical Center, New Orleans, Louisiana, USA
| | - C J Lisbona
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - L Olmedilla
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - J M Pérez Peña
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - M M Salcedo
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - A Skaro
- Department of Multi-Organ Transplant Surgery, University of Western Ontario, London, Ontario, Canada
| | - E Velasco
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - A Colón
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - B Díaz-Zorita
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - L Rodríguez
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - J Ferreiroa
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - J Á López-Baena
- Liver Transplant Unit, Hospital Universitario Gregorio Marañón de Madrid, Madrid, Spain; Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
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15
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Abstract
Modern radiotherapy techniques have enabled high focal doses of radiation to be delivered to patients with primary and secondary malignancies of the liver. The current clinical practice of radiation oncology has benefitted from decades of research that have informed how to achieve excellent local control and survival outcomes with minimal toxicities. Still, one of the most devastating consequences of radiation to the liver remains a challenge: radiation-induced liver disease (RILD). Here, we will review the current understanding of classic and nonclassic RILD from a clinical perspective, the evaluation and management of patients who are at risk of developing RILD, methods to reduce the likelihood of RILD using modern radiation techniques, and the diagnosis and treatment of radiation-related liver toxicities.
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16
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Sun Y, Yu L, Liu Y. Predictive Value of Indocyanine Green Plasma Disappearance Rate on Liver Function and Complications After Liver Transplantation. Med Sci Monit 2018; 24:3661-3669. [PMID: 29855460 PMCID: PMC6007494 DOI: 10.12659/msm.907783] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate the correlation between indocyanine green plasma disappearance rate (ICG-PDR) and allograft function as well as postoperative complications after liver transplantation. MATERIAL AND METHODS In this prospective study, 115 cases of adult liver transplantation performed from 1 June 2016 to 1 December 2016 were enrolled. These 115 patients were divided into a group of PDR <18%/min (50 cases) and a group of PDR ≥18%/min (65 cases). The rates of liver recovery, postoperative complications, and survival were compared between these 2 groups. RESULTS Among the total of 115 patients, 111 patients recovered well and were discharged, whereas 4 patients died during the first month after the operation. Between the 2 groups, significant differences were observed in terms of the model for end-stage liver disease (MELD) score, intraoperative bleeding volume, and the level of hemoglobin (Hb), pre-albumin (PA) and total bilirubin (TB) the first week after the operation. Overall, the incidence of hepatic arterial complications and pneumonia was much higher in the PDR<18%/min group (P<0.05). CONCLUSIONS The early postoperative value of ICG-PDR was closely related to graft function and could act as a good predictor for the incidence of postoperative arterial complications.
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Affiliation(s)
- Yan Sun
- Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China (mainland)
| | - Lixin Yu
- Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China (mainland)
| | - Yihe Liu
- Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China (mainland)
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17
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Levesque E, Martin E, Dudau D, Lim C, Dhonneur G, Azoulay D. Current use and perspective of indocyanine green clearance in liver diseases. Anaesth Crit Care Pain Med 2015; 35:49-57. [PMID: 26477363 DOI: 10.1016/j.accpm.2015.06.006] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 06/12/2015] [Indexed: 02/06/2023]
Abstract
Indocyanine green (ICG) is a water-soluble anionic compound that binds to plasma proteins after intravenous administration. It is selectively taken up at the first pass by hepatocytes and excreted unchanged into the bile. With the development of ICG elimination measurement by spectrophotometry, the ICG retention test has become a safe, rapid, reproducible, inexpensive and noninvasive tool for the assessment of liver function. Clinical evidence suggests that the ICG retention test can enable the establishment of tailored management strategies by providing prognostic information. In particular, this method has been evaluated as a prognostic marker in patients with advanced cirrhosis or awaiting liver transplantation. In addition, it is used as a marker of portal hypertension in cirrhotic patients, as a prognostic factor in intensive care units and for the assessment of liver function in patients undergoing liver surgery. Since recent technology enables ICG-PDR to be measured noninvasively at the bedside, this parameter is an attractive addition to liver function and regional haemodynamic monitoring. However, the current state-of-the-art as concerns this technology remains at a low level of evidence and thorough assessment is required.
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Affiliation(s)
- Eric Levesque
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France.
| | - Eléonore Martin
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France
| | - Daniela Dudau
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France
| | - Chetana Lim
- AP-HP, Hôpital Henri-Mondor, Service de Chirurgie Digestive, Hépatobiliaire, Pancréatique et Transplantation Hépatique, 94000 Créteil, France
| | - Gilles Dhonneur
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France
| | - Daniel Azoulay
- AP-HP, Hôpital Henri-Mondor, Service de Chirurgie Digestive, Hépatobiliaire, Pancréatique et Transplantation Hépatique, 94000 Créteil, France
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18
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Gerega A, Zolek N, Soltysinski T, Milej D, Sawosz P, Toczylowska B, Liebert A. Wavelength-resolved measurements of fluorescence lifetime of indocyanine green. JOURNAL OF BIOMEDICAL OPTICS 2011; 16:067010. [PMID: 21721831 DOI: 10.1117/1.3593386] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
We study fluorescence lifetime of indocyanine green (ICG) using femtosecond laser and sensitive detection based on time-correlated single-photon counting. A time-resolved multichannel spectral system is constructed and applied for determination of the fluorescence lifetime of the ICG in different solvents. Emission properties of ICG in water, milk, and 1% intralipid solution are investigated. Fluorescence of the fluorophore of different concentrations (in a range of 1.7-160 μM) dissolved in different solutions is excited by femtosecond pulses generated with the use of Ti:Sa laser tuned within the range of 740-790 nm. It is observed that fluorescence lifetime of ICG in water is 0.166 ± 0.02 ns and does not depend on excitation and emission wavelengths. We also show that for the diffusely scattering solvents (milk and intralipid), the lifetime may depend on the dye concentration (especially for large concentrations of ICG). This effect should be taken into account when analyzing changes in the mean time of arrival of fluorescence photons excited in ICG dissolved in such optically turbid media.
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Affiliation(s)
- Anna Gerega
- Polish Academy of Sciences, Institute of Biocybernetics and Biomedical Engineering, Trojdena 4, 02-109 Warsaw, Poland.
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19
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Merle U, Sieg O, Stremmel W, Encke J, Eisenbach C. Sensitivity and specificity of plasma disappearance rate of indocyanine green as a prognostic indicator in acute liver failure. BMC Gastroenterol 2009; 9:91. [PMID: 19954554 PMCID: PMC2791758 DOI: 10.1186/1471-230x-9-91] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2009] [Accepted: 12/03/2009] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND In patients presenting with acute liver failure (ALF) prediction of prognosis is vital to determine the need of transplantation. Based on the evidence that plasma disappearance rate of indocyanine green (ICG-PDR) correlates with liver cell function, we evaluated the ability of ICG-PDR measured by pulse dye densitometry to predict outcome in patients with acute liver failure. METHODS Prospectively markers of hepatocellular injury, synthesis and excretion, including ICG-PDR were measured daily until liver transplantation, death, discharge from intensive care unit, or up to 7 days in 25 patients with acute liver failure. Receiver operating curve (ROC) analysis was performed to assess the value of ICG-PDR to predict outcome in ALF. RESULTS The 25 patients analyzed included 18 that recovered spontaneously and 7 that underwent liver transplantation (n = 6) or died (n = 1). Causes of ALF included viral hepatitis (n = 4), toxic liver injury (n = 15), ischemic liver injury (n = 2), and cryptogenic liver failure (n = 4). King's college criteria were fulfilled in 85.7% of patients not recovering spontaneously and in 16.7% of patients recovering spontaneously. The mean ICG-PDR measured on day 1 in patients recovering spontaneously was 12.0 +/- 7.8%/min and in patients not recovering spontaneously 4.3 +/- 2.0%/min (P = 0.002). By ROC analysis the sensitivity and specificity of an ICG-PDR value <or= 6.3%/min on study day 1 were 85.7% and 88.9%, respectively, for predicting a non spontaneous outcome in ALF. CONCLUSION ICG-PDR allows early and sensitive bedside assessment of liver dysfunction in ALF. Measurement of ICG-PDR might be helpful in predicting the outcome in acute liver failure. TRIAL REGISTRATION Clinicaltrials.gov, NCT 00245310.
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Affiliation(s)
- Uta Merle
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany.
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Miller M, Kahraman A, Ross B, Beste M, Gerken G. Evaluation of quantitative liver function tests in HIV-positive patients under anti-retroviral therapy. Eur J Med Res 2009; 14:369-77. [PMID: 19748856 PMCID: PMC3351969 DOI: 10.1186/2047-783x-14-9-369] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Background and aims Quantitative tests of liver function (QTLF) which are based on the hepatic metabolism or clearance of test substances have been successfully used to predict prognosis of a variety of different liver diseases. Still sufficient data in HIV-patients under anti-retroviral therapy (ART) are lacking. Therefore, the aim of this prospective study was to investigate if and to what extent ART influences a broad panel of quantitative tests of liver function in patients with HIV-infection. Patients and methods Nineteen patients (14 males, 5 females, mean age 40 years) with HIV-infection underwent QTLF including lidocaine half-life test (LHT), galactose elimination capacity (GEC), and indocyanine green clearance (IGC). These tests were performed before and 3 to 6 months after initiation of anti-retroviral therapy. Twenty age-matched healthy, medication-and virus-free adults served as controls. Results Lidocaine half-life was significantly lower in HIV-patients without ART. Combining anti-retroviral therapies shifted cytochrome p450 activity back into standard ranges. Galactose elimination capacity as a parameter of cytosolic liver function and indocyanine green clearance as a parameter of liver perfusion were not affected by ART. Conclusions QTLF may be a tool to predict prognosis or hepatic complications in HIV-infected patients with liver disease. Early determination of lidocaine half-life seems to be useful - this should be considered during the treatment of HIV-positive individuals.
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Affiliation(s)
- M Miller
- Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany
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21
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Stauber RE, Wagner D, Stadlbauer V, Palma S, Gurakuqi G, Kniepeiss D, Iberer F, Smolle KH, Haas J, Trauner M. Evaluation of indocyanine green clearance and model for end-stage liver disease for estimation of short-term prognosis in decompensated cirrhosis. Liver Int 2009; 29:1516-20. [PMID: 19732329 DOI: 10.1111/j.1478-3231.2009.02104.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Indocyanine green (ICG) clearance has been proposed as a quantitative liver function test several decades ago. Interest in this method has been renewed following the development of finger pulse densitometry for noninvasive estimation of the ICG plasma disappearance rate (PDR). On the other hand, the model for end-stage liver disease (MELD), which is based on routine laboratory parameters, is widely used for estimation of short-term survival in cirrhosis, but its prognostic value in critically ill cirrhotic patients is unclear. AIMS The aim of the present study was to compare the diagnostic accuracy of ICG PDR vs. MELD for estimation of short-term prognosis in cirrhotic patients. METHODS Ninety consecutive cirrhotic patients who were admitted for decompensated disease or were being evaluated for liver transplantation were screened. Patients who underwent liver transplantation within the following 90 days and those with hepatocellular carcinoma were excluded. In the remaining 70 patients, routine laboratory parameters and ICG clearance were analysed. Following an injection of ICG 0.25 mg/kg, PDR was measured by finger pulse densitometry. The diagnostic accuracy of ICG PDR and MELD for prediction of 90-day survival was assessed by receiver-operating characteristic (ROC) curve analysis. RESULTS ROC curve analysis revealed superior diagnostic accuracy for MELD as compared with ICG PDR in predicting 90-day survival (area under the ROC curve 0.89 vs. 0.71). A MELD cut-off of 22 provided the best discrimination for prediction of 90-day survival. CONCLUSIONS MELD is superior to ICG PDR for estimation of short-term survival in patients with decompensated cirrhosis.
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Affiliation(s)
- Rudolf E Stauber
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
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Endothelin-1 contributes to hemoglobin glutamer-200-mediated hepatocellular dysfunction after hemorrhagic shock. Shock 2009; 32:179-89. [PMID: 19106820 DOI: 10.1097/shk.0b013e318199352b] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Hemoglobin glutamer-200 (HbG) might be an alternative to human blood. However, artificial oxygen carriers are initially successful to restore oxygen supply but may induce organ dysfunction and increase mortality several days after application in terms of delayed side effects. Impairment of microcirculation and an inflammatory cytokine response through induction of endothelin (ET) 1 may contribute. We investigated the role of HbG for the therapy of hemorrhagic shock and for delayed side effects in a model of hemorrhagic shock and reperfusion (H/R). To analyze early effects, Sprague-Dawley rats (n = 8/group) were resuscitated after hemorrhagic shock (1 h) with shed blood or HbG followed by reperfusion (2 h). Hemorrhagic shock and reperfusion decreased liver microcirculation and hepatic function in both shock groups to the same extent. Thus, HbG was not superior to shed blood regarding resuscitation end points after hemorrhagic shock. To determine delayed effects, rats (n = 8/group) were pretreated with Ringer's solution (vehicle) or HbG (1 g/kg) 24 h before H/R. Endothelin receptors were blocked with bosentan. Subsequently, ET-1 expression, inflammatory response, sinusoidal perfusion, hepatocellular function (plasma disappearance rate of indocyanine green [PDRICG]), and redox state [NAD(P)H] were analyzed. After vehicle pretreatment, H/R increased ET-1, hepatocellular injury, NAD(P)H, and cytokine levels. Sinusoidal perfusion and PDRICG decreased. After HbG pretreatment, a further increase of ET-1 and hepatocellular injury was observed, whereas PDRICG further decreased. Application of bosentan after HbG but not after vehicle pretreatment significantly improved PDRICG and liver perfusion, whereas NAD(P)H and hepatocellular injury decreased. Furthermore, cytokine release changed to an anti-inflammatory response. These data suggest an HbG-dependent increase of ET-1, which may contribute to delayed side effects under shock conditions.
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Levesque E, Saliba F, Benhamida S, Ichaï P, Azoulay D, Adam R, Castaing D, Samuel D. Plasma disappearance rate of indocyanine green: a tool to evaluate early graft outcome after liver transplantation. Liver Transpl 2009; 15:1358-64. [PMID: 19790157 DOI: 10.1002/lt.21805] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Indocyanine green clearance (Cl-ICG) has been used to assess liver function and hepatic blood flow mainly before and after hepatic surgery. Cl-ICG (invasive method) has been reported to be a good marker of early graft function after liver transplantation (LT). The goal of this study was to determine if the indocyanine green plasma disappearance rate (PDR-ICG), measured by a noninvasive technique (LiMON, Impulse Medical System, Munich, Germany), is predictive of complications and graft outcome after LT. From September 2005 to June 2006, 72 LT recipients were included in the study. PDR-ICG was measured daily (from day 0 to day 5 after LT) with a digital sensor after patients were injected with 0.25 mg/kg indocyanine green. A PDR-ICG cutoff level of 12.85%/minute was predictive of the development of a serious postoperative complication. The sequential changes of PDR-ICG enabled us to differentiate 2 groups: (1) patients with early severe complications (hepatic artery thrombosis, primary graft nonfunction, or sepsis) who had a low value of PDR-ICG during the first 5 posttransplantation days (average, 8.8 +/- 4.5%/minute) and (2) patients who developed acute rejection and who had a progressive reduction of PDR-ICG between days 0 and 5 (from 25.5 +/- 4.8 to 10.3 +/- 2.5%/minute; P < 0.002). In conclusion, after LT, PDR-ICG (a noninvasive technique), measured regularly during the first 5 postoperative days, is a safe technique that can predict early postoperative complications.
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Affiliation(s)
- Eric Levesque
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
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Olmedilla L, Pérez-Peña JM, Ripoll C, Garutti I, de Diego R, Salcedo M, Jiménez C, Bañares R. Early noninvasive measurement of the indocyanine green plasma disappearance rate accurately predicts early graft dysfunction and mortality after deceased donor liver transplantation. Liver Transpl 2009; 15:1247-53. [PMID: 19790138 DOI: 10.1002/lt.21841] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Early diagnosis of graft dysfunction in liver transplantation is essential for taking appropriate action. Indocyanine green clearance is closely related to liver function and can be measured noninvasively by spectrophotometry. The objectives of this study were to prospectively analyze the relationship between the indocyanine green plasma disappearance rate (ICGPDR) and early graft function after liver transplantation and to evaluate the role of ICGPDR in the prediction of severe graft dysfunction (SGD). One hundred seventy-two liver transplants from deceased donors were analyzed. Ten patients had SGD: 6 were retransplanted, and 4 died while waiting for a new graft. The plasma disappearance rate was measured 1 hour (PDRr60) and within the first 24 hours (PDR1) after reperfusion, and it was significantly lower in the SGD group. PDRr60 and PDR1 were excellent predictors of SGD. A threshold PDRr60 value of 10.8%/minute and a PDR1 value of 10%/minute accurately predicted SGD with areas under the receiver operating curve of 0.94 (95% confidence interval, 0.89-0.97) and 0.96 (95% confidence interval, 0.92-0.98), respectively. In addition, survival was significantly lower in patients with PDRr60 values below 10.8%/minute (53%, 47%, and 47% versus 95%, 94%, and 90% at 3, 6, and 12 months, respectively) and with PDR1 values below 10%/minute (62%, 62%, and 62% versus 94%, 92%, and 88%). In conclusion, very early noninvasive measurement of ICGPDR can accurately predict early severe graft dysfunction and mortality after liver transplantation.
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Affiliation(s)
- Luis Olmedilla
- Department of Anesthesiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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25
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Quantitative assessment of hepatic function and its relevance to the liver surgeon. J Gastrointest Surg 2009; 13:374-85. [PMID: 18622661 DOI: 10.1007/s11605-008-0564-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2008] [Accepted: 06/04/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND Standard evaluation of patients undergoing hepatic surgery has been through radiological and quantitative determination of liver function. As more complex and extensive surgery is now being performed, often in the presence of cirrhosis/fibrosis or following administration of chemotherapy, it is questioned whether additional assessment may be required prior to embarking on such surgery. The aim of this review was to determine the current knowledge base in relation to the performance of quantitative assessment of hepatic function both pre- and post-operatively in patients undergoing hepatic resectional surgery and liver transplantation. METHODS An electronic search was performed of the medical literature using the MEDLINE database to identify relevant articles with cross-referencing of all identified papers to ensure full literature capture. RESULTS AND CONCLUSIONS The review has identified a number of different methods of dynamically assessing hepatic function, the most frequently performed being through the use of indocyanine green clearance. With the recent and further anticipated developments in hepatic resectional surgery, it is likely that quantitative assessment will become more widely practiced in order to reduce post-operative hepatic failure and improve outcome.
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Non-isotopic tyrosine kinetics using an alanyl-tyrosine dipeptide to assess graft function in liver transplant recipients - a pilot study. Wien Klin Wochenschr 2008; 120:19-24. [PMID: 18239987 DOI: 10.1007/s00508-007-0908-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2006] [Accepted: 09/28/2007] [Indexed: 10/22/2022]
Abstract
BACKGROUND Although accurate assessment of liver function in liver transplant recipients is of crucial importance for optimal timing of the procedure and for determining graft viability, none of the many available methods has proven reliable in the clinical routine. Thus, a novel non-isotopic assay of tyrosine kinetics using the tyrosine-containing dipeptide L-alanyl-L-tyrosine (Ala-Tyr) was tested for its clinical feasibility in patients undergoing orthotopic liver transplantation (OLT). METHODS Plasma levels of tyrosine and clearance of tyrosine released after infusion of the dipetide Ala-Tyr were assessed before and one day after OLT in 10 liver transplant recipients with normal graft function, also in three organ donors and in three recipients showing poor graft function. Standard laboratory parameters (e.g. aminotransferases) and the plasma disappearance rate of indocyanine green were also measured. RESULTS Following uneventful OLT, tyrosine plasma levels (before 127 +/- 15 micromol/vs. post-OLT 52 +/- 6 micromol/l, P < 0.05) and kinetics (tyrosine clearance: before 206 +/- 77 ml/min vs. post-OLT 371 +/- 109 ml/min, P < 0.05) were normalized. In cases of severe graft dysfunction, tyrosine kinetics (tyrosine clearance: 238 +/- 61 ml/min) resembled the situation in end-stage liver disease, whereas no such correlation was seen with conventional markers of liver function. Organ preservation had only a minor impact on tyrosine kinetics (n.s.). CONCLUSION OLT rapidly normalizes both the plasma levels and the kinetics of tyrosine. Graft failure is associated with an immediate rise in plasma tyrosine levels and a delay in tyrosine elimination. Our results show that tyrosine clearance using the dipetide Ala-Tyr is a suitable non-isotopic, non-invasive indicator of graft viability in the early postoperative course following OLT.
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Parker BM, Cywinski JB, Alster JM, Irefin SA, Popovich M, Beven M, Fung JJ. Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation. Liver Transpl 2008; 14:46-52. [PMID: 18161838 DOI: 10.1002/lt.21308] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Twenty adult patients undergoing orthotopic liver transplantation (OLT) were enrolled in this study, with the noninvasive indocyanine green plasma disappearance rate (ICG-PDR) measured both during and after OLT to assess the relationship between ICG-PDR and the ability of patients to achieve therapeutic postoperative tacrolimus immunosuppressant blood levels. Liver function was determined at both 2 and 18 hours post reperfusion with the ICG-PDR k value (1/min). Postoperative standard serum measures of liver function as well as liver biopsies were also collected and analyzed. The median ICG-PDR k value for the study group at 2 hours post reperfusion was 0.20 (0.16, 0.27), whereas at 18 hours post reperfusion, it was 0.22 (0.18, 0.35). The median change in the k value between the two ICG-PDR measurements was 0.05 (-0.02, 0.07) with P = 0.02. There was an interaction between the postoperative day 1 (18 hours post reperfusion) ICG-PDR k value and the linear increase in the tacrolimus blood level, such that the greater the k value was, the more gradual the observed rise was in tacrolimus over time [that is, the longer it took to achieve a therapeutic blood level (>12 ng/mL), P = 0.003]. Of the 16 patients that received tacrolimus, comparable dosing on a per kilogram body weight basis was observed. Also, no significant association between ICG-PDR k values and postoperative liver biopsy results was seen. This study demonstrates that the ICG-PDR measurement is a modality with the potential to assist in achieving adequate blood levels of tacrolimus following OLT.
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Affiliation(s)
- Brian M Parker
- Department of General Anesthesiology, Cleveland Clinic, Cleveland, OH 44195, USA.
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Scheingraber S, Richter S, Igna D, Girndt M, Flesch S, Kleinschmidt S, Schilling MK. Indocyanine green elimination but not bilirubin indicates improvement of graft function during MARS therapy. Clin Transplant 2007; 21:689-95. [DOI: 10.1111/j.1399-0012.2007.00706.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
The presence of hepatic dysfunction significantly affects the length of hospital stay and the outcome in critically ill patients. Considering the important partial hepatic functions of metabolism, synthesis, detoxification, and excretion, the worse clinical course of patients suffering from hepatic dysfunction is not surprising. The most often used indicator of hepatic dysfunction is bilirubin. However, bilirubin and other commonly used static laboratory tests provide only indirect measures of hepatic function. In contrast to these static tests, dynamic liver tests, such as indocyanine green (ICG) disappearance rate should provide better direct measures of the actual functional state of the liver at the time of assessment. The ICG is a water-soluble inert compound that is injected intravenously. It mainly binds to albumin in the plasma. ICG is then selectively taken up by hepatocytes, independent of adenosine triphosphate (ATP), and later excreted unchanged into the bile via an ATP-dependent transport system. The ICG is not metabolized; it does not undergo enterohepatic recirculation. Thus, ICG excretion rate in bile reflects the hepatic excretory function and hepatic energy status. Because of these features, ICG has been found to be useful to assess liver function in liver donors and transplant recipients, in patients with chronic liver failure, and as a prognostic factor in critically ill patients. Further trials concerning liver dysfunction have applied the noninvasive bedside assessment of ICG among other clinical variables to monitor the progress and/or the reversal of liver dysfunction.
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Affiliation(s)
- P Faybik
- Medical university of Vienna, Vienna, Austria.
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31
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Raddatz A, Kubulus D, Winning J, Bauer I, Pradarutti S, Wolf B, Kreuer S, Rensing H. Dobutamine Improves Liver Function after Hemorrhagic Shock through Induction of Heme Oxygenase-1. Am J Respir Crit Care Med 2006; 174:198-207. [PMID: 16627864 DOI: 10.1164/rccm.200508-1221oc] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Induction of heme oxygenase-1 (HO-1) protects the liver against reperfusion injury after hemorrhagic shock. Previous data suggest that the beta(1)-adrenoceptor agonist dobutamine induces HO-1 in hepatocytes. OBJECTIVES To investigate the functional significance of dobutamine pretreatment for liver function after hemorrhagic shock in vivo. METHODS Anesthetized rats received either Ringer's (Vehicle/Shock), 10 microg/kg/min of the beta(1)-adrenoceptor agonist dobutamine (Dob/Shock), or 10 microg/kg/min dobutamine and 500 microg/kg/min of the beta(1)-adrenoceptor antagonist esmolol (Dob/Esmolol/Shock) for 6 h. Hemorrhagic shock was induced thereafter (mean arterial pressure, 35 mm Hg for 90 min). Animals were resuscitated with shed blood and Ringer's. In addition, the HO pathway was blocked after dobutamine pretreatment with 10 micromol/kg tin-mesoporphyrin-IX (Dob/SnMP/Shock) or animals received 100 mg/kg of the carbon monoxide donor dichloromethane (DCM/Shock). MEASUREMENTS Hepatocellular metabolism and liver blood flow were measured by plasma disappearance rate of indocyanine green (PDR(ICG)) as a sensitive marker of liver function. MAIN RESULTS Pretreatment with dobutamine induced HO-1 in pericentral hepatocytes and improved PDR(ICG) (Vehicle/Shock: 11.7 +/- 8.12%/min vs. Dob/Shock: 19.7 +/- 2.46%/min, p = 0.006). Blockade of the HO pathway after preconditioning and the combined pretreatment with dobutamine and esmolol decreased PDR(ICG) (Dob/SnMP/Shock: 12.6 +/- 4.24%/min, p = 0.011; Dob/Esmolol/Shock: 10.2 +/- 4.34%/min, p = 0.008). Pretreatment with a carbon monoxide donor improved PDR(ICG) (DCM/Shock: 18 +/- 3.19%/min, p = 0.022) compared with Vehicle/Shock. CONCLUSIONS These results suggest a beta(1)-adrenoceptor-dependent hepatic up-regulation of HO-1 and a better maintained hepatocellular function after hemorrhagic shock in animals pretreated with dobutamine. The improved hepatocellular function may be in part mediated by carbon monoxide because of up-regulation of HO-1. Pretreatment with dobutamine might be a potential means of pharmacologic preconditioning before ischemia-reperfusion of the liver.
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Affiliation(s)
- Alexander Raddatz
- Klinik für Anaesthesiologie und Intensivmedizin, Universität des Saarlandes, D-66421 Homburg/Saar, Germany
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Kanoria S, Jalan R, Davies NA, Seifalian AM, Williams R, Davidson BR. Remote ischaemic preconditioning of the hind limb reduces experimental liver warm ischaemia-reperfusion injury. Br J Surg 2006; 93:762-8. [PMID: 16609953 DOI: 10.1002/bjs.5331] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Direct ischaemic preconditioning of the liver reduces ischaemia-reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) of a limb has been shown to reduce IRI to the heart. This study determined the effect of brief remote ischaemia to the limb in reducing early liver warm IRI. METHODS Twenty-eight male rabbits were allocated to four groups: sham operated, RIPC alone, IRI alone, and RIPC plus IRI. RIPC was induced in the leg with a tourniquet, before liver IRI, by three alternate cycles of 10 min ischaemia followed by 10 min reperfusion. Liver IRI was produced by total inflow occlusion for 25 min. Markers of liver injury and systemic and hepatic haemodynamics were measured for 2 h after reperfusion. RESULTS At 2 h, IRI alone was associated with increased serum levels of aminotransferases, and reduced mean arterial blood pressure, hepatic blood flow and peripheral oxygen saturation. There was significant improvement in these variables in animals that had RIPC before liver IRI, and hepatic venous nitrate/nitrite levels were also significantly higher. CONCLUSION In this experimental model RIPC appeared to reduce liver IRI.
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Affiliation(s)
- S Kanoria
- Hepatopancreatobiliary and Liver Transplant Unit, University Department of Surgery, Royal Free Hospital, London, UK
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Dinant S, van Veen SQ, Roseboom HJ, van Vliet AK, van Gulik TM. Liver protection by hypothermic perfusion at different temperatures during total vascular exclusion. Liver Int 2006; 26:486-93. [PMID: 16629653 DOI: 10.1111/j.1478-3231.2006.01248.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
INTRODUCTION In situ hypothermic perfusion (HP) can be applied to attenuate ischemia and reperfusion (I/R) injury during liver resection under total vascular exclusion (TVE). This study examines the protective effect of cooling by HP at 20 and 28 degrees C as compared with no HP during TVE in a porcine liver I/R model. METHODS Twenty-one pigs underwent 60 min TVE of the liver followed by 24 h reperfusion. HP was performed via the portal vein using ringerlactate solution of 4 degrees C. Pigs were assigned to three groups: TVE without HP (no-HP, n=9), TVE with HP at 28 degrees C (HP-28, n=6) and TVE with HP at 20 degrees C (HP-20, n=6). RESULTS Perfusion volumes during TVE were 5.1+/-0.5 and 17.3+/-1.7 l in HP-28 and HP-20, respectively (P<0.05). Aspartate aminotransferase (AST) after 24 h reperfusion was 1172+/-440 U/l in no-HP as compared with 223+/-69 and 180+/-22 U/l in HP-28 and HP-20, respectively (P<0.05). No differences in liver function or histopathology were found between the HP-28 and HP-20 groups. CONCLUSIONS HP at 20 degrees C is equally effective in preserving liver function and preventing hepatocellular injury under TVE as compared with HP at 28 degrees C. HP at 28 degrees C is advised, because of the lesser perfusion volume necessary for cooling of the liver.
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Affiliation(s)
- Sander Dinant
- Department of Surgery (Surgical Laboratory), Academic Medical Center, Amsterdam, the Netherlands
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Silva MA, Richards DA, Bramhall SR, Adams DH, Mirza DF, Murphy N. A Study of the Metabolites of Ischemia-Reperfusion Injury and Selected Amino Acids in the Liver Using Microdialysis during Transplantation. Transplantation 2005; 79:828-35. [PMID: 15818326 DOI: 10.1097/01.tp.0000153156.38617.97] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND Preservation and ischemia-reperfusion injury still impact the outcome of orthotopic liver transplantation. The authors used microdialysis with a view to monitoring its effect on graft function. METHODS A microdialysis catheter was inserted into the graft immediately after reperfusion and perfused with an isotonic solution for 48 hr. Metabolites of the ischemia-reperfusion injury and selected amino acids were studied. There were 18 patients, with a median age of 52 years (range, 38-62 years), 8 of whom were men. Lactate, pyruvate, glycerol, and glucose levels were measured. In addition, alanine, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glutamine, glycine, and taurine were determined. RESULTS All grafts functioned well. High lactate, pyruvate, and glycerol levels were observed in the immediate postoperative period. These showed a significant rapid decrease and stabilized to baseline levels. Alanine, glutamate, GABA, and taurine levels declined significantly to baseline values. Arginine levels were low immediately postreperfusion and then increased, reaching significantly higher values beyond 19 hr. CONCLUSIONS These data may represent "normal" changes seen in the immediate posttransplant period because all grafts functioned well. Two important metabolic fates of arginine in the liver are in the detoxification of ammonia by means of the urea cycle, and in the synthesis of nitric oxide (NO). Low extracellular arginine may reflect influx of the amino acid into hepatocytes, resulting in formation of NO in the presence of inducible NO synthase or conversion to ornithine in the presence of arginase in the urea cycle. As the organ stabilizes, restriction of arginine uptake may give rise to the observed increase in extracellular arginine.
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Affiliation(s)
- Michael A Silva
- Liver Unit, University Hospital Birmingham NHS Trust, Queen Elizabeth, Edgbaston, Birmingham B15 2TH, UK.
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Hsieh CB, Chen CJ, Chen TW, Yu JC, Shen KL, Chang TM, Liu YC. Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients. World J Gastroenterol 2004; 10:2394-6. [PMID: 15285026 PMCID: PMC4576295 DOI: 10.3748/wjg.v10.i16.2394] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.8] [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 investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation.
METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated.
RESULTS: The correlation between these two methods was excellent (r2 = 0.977).
CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients.
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Affiliation(s)
- Chung-Bao Hsieh
- Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
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Faybik P, Krenn CG, Baker A, Lahner D, Berlakovich G, Steltzer H, Hetz H. Comparison of invasive and noninvasive measurement of plasma disappearance rate of indocyanine green in patients undergoing liver transplantation: a prospective investigator-blinded study. Liver Transpl 2004; 10:1060-4. [PMID: 15390334 DOI: 10.1002/lt.20205] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Plasma disappearance rate of indocyanine green (PDRICG) has been proposed for assessment of liver function in liver transplants donors and recipients, in patients with chronic liver failure, and as a prognostic factor in critically ill patients. The assessment of PDRICG using a newly developed noninvasive digital pulse densitometry method was simultaneously compared to invasive aortic fiber-optic method in patients undergoing orthotopic liver transplantation (OLT). Fourteen consecutive liver transplant candidates (11 male, 3 female) were prospectively enrolled into the study. A 4F aortic catheter with an integrated fiber-optic device and a thermistor was inserted via a femoral artery sheath for invasive aortic (INV) PDRICG assessment in all patients. The fiber-optic device was connected to a computer system (COLD-Z021, PULSION Medical Systems, Munich, Germany). A finger-piece sensor was used for non-invasive (NINV) pulse-densitometric PDRICG assessment. For the PDRICG assessment.5 mg/kg of ICG in cooled saline (10-15 mL) was injected through a central venous catheter. The assessments of PDRICG were performed after induction of anesthesia, after clamping of the hepatic artery, after clamping of the inferior vena cava, after reperfusion of the graft, and on the first postoperative day. During the PDRICG measurements, the investigators were blinded for the results of the noninvasive monitoring. Seventy-one pairs of measurements were performed successfully. PDRICG ranged from 0%/min to 43.8 %/min (11.6%/min +/- 9.6 %/min, mean +/- SD) for invasive and from 2.6%/min to 36.1 %/min (10%/min +/- 7.6 %/min, mean +/- SD) for noninvasive assessment method. The linear regression analysis yielded the equation: PDRICG(NINV) = 1.493 +/- 0.735 x PDRICG(INV), with a correlation coefficient of r = 0.93 (P <.0001). The analysis according to Bland and Altman showed a good agreement between the PDRICG(NINV) and PDRICG(INV) with a mean bias 1.5 +/- 3.8 for all measurements. In conclusion, according to these results, the noninvasive transcutaneous pulse-densitometric method correlates well with the invasive aortic fiber-optic method and thus can be used in patients undergoing liver transplantation.
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Affiliation(s)
- Peter Faybik
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Vienna, Austria.
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Fuson AL, Cowan DF, Kanatous SB, Polasek LK, Davis RW. Adaptations to diving hypoxia in the heart, kidneys and splanchnic organs of harbor seals (Phoca vitulina). ACTA ACUST UNITED AC 2004; 206:4139-54. [PMID: 14555753 DOI: 10.1242/jeb.00654] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Pinnipeds (seals and sea lions) have an elevated mitochondrial volume density [VV(mt)] and elevated citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HOAD) activities in their swimming muscles to maintain an aerobic, fat-based metabolism during diving. The goal of this study was to determine whether the heart, kidneys and splanchnic organs have an elevated VV(mt) and CS and HOAD activities as parallel adaptations for sustaining aerobic metabolism and normal function during hypoxia in harbor seals (Phoca vitulina). Samples of heart, liver, kidney, stomach and small intestine were taken from 10 freshly killed harbor seals and fixed in glutaraldehyde for transmission electron microscopy or frozen in liquid nitrogen for enzymatic analysis. Samples from dogs and rats were used for comparison. Within the harbor seal, the liver and stomach had the highest VV(mt). The liver also had the highest CS activity. The kidneys and heart had the highest HOAD activities, and the liver and heart had the highest lactate dehydrogenase (LDH) activities. Mitochondrial volume densities scaled to tissue-specific resting metabolic rate [VV(mt)/RMR] in the heart, liver, kidneys, stomach and small intestine of harbor seals were elevated (range 1.2-6.6x) when compared with those in the dog and/or rat. In addition, HOAD activity scaled to tissue-specific RMR in the heart and liver of harbor seals was elevated compared with that in the dog and rat (3.2x and 6.2x in the heart and 8.5x and 5.5x in the liver, respectively). These data suggest that organs such as the liver, kidneys and stomach possess a heightened ability for aerobic, fat-based metabolism during hypoxia associated with routine diving. However, a heightened LDH activity in the heart and liver indicates an adaptation for the anaerobic production of ATP on dives that exceed the animal's aerobic dive limit. Hence, the heart, liver, kidneys and gastrointestinal organs of harbor seals exhibit adaptations that promote an aerobic, fat-based metabolism under hypoxic conditions but can provide ATP anaerobically if required.
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Affiliation(s)
- Amanda L Fuson
- Department of Marine Biology, Texas A&M University at Galveston, 5007 Avenue U, Galveston, TX 77551, USA.
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Erdogan D, Heijnen BHM, Bennink RJ, Kok M, Dinant S, Straatsburg IH, Gouma DJ, van Gulik TM. Preoperative assessment of liver function: a comparison of 99mTc-Mebrofenin scintigraphy with indocyanine green clearance test. Liver Int 2004; 24:117-23. [PMID: 15078475 DOI: 10.1111/j.1478-3231.2004.00901.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS The indocyanine green (ICG) clearance test is the most frequently used test for preoperative assessment of liver parenchymal function but has its limitations. The aim of this study was to investigate the correlation between ICG clearance test and the liver uptake of 99-Technetium-labelled (99mTc)-Mebrofenin (99mTc-Mebrofenin) as measured with hepatobiliary scintigraphy. METHODS Fifty-four patients were diagnosed as hepatocellular carcinoma (n=9), hilar tumours (n=20) and 25 patients with non-parenchymal tumours including colorectal metastasis (n=15) and miscellaneous tumours (n=10). One day prior to operation, hepatobiliary 99mTc-Mebrofenin scintigraphy was performed after intravenous injection of 85 MBq and the 15-min clearance rate of ICG (ICG-C15) was measured. RESULTS The mean ICG-C15 was 86.86+/-1.19% (SEM). The mean 99mTc-Mebrofenin uptake rate was 12.87+/-0.52%/min. A significant correlation was obtained between 99mTc-Mebrofenin uptake rate by scintigraphy and ICG-C15 (r=0.73, P<0.0001). The mean clearance capacity of the right liver segments (79.83+/-1.63, range 47.75-95.97%) was larger than that of the left segments (20.24+/-1.55, range 6.51-52.51%). CONCLUSION 99mTc-Mebrofenin uptake rate as assessed by scintigraphy is an efficient method for determining liver function and correlates well with ICG clearance. At the same time, 99mTc-Mebrofenin scintigraphy provides information of segmental functional liver tissue, which is of additional use when planning liver resection.
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Affiliation(s)
- Deha Erdogan
- Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands
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Dimicoli JL, Patry J, Poupon J, Volk A. On the use of R1 and R2* for measurement of contrast agent concentration in isolated perfused rat liver. NMR IN BIOMEDICINE 2003; 16:276-285. [PMID: 14648888 DOI: 10.1002/nbm.846] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
We present experimental MRI protocols at 4.7 T for quantitative determination of the Dotarem distribution volume in isolated perfused rat liver. The procedures involved either constant contrast agent (CA) concentration or bolus administration conditions. R1 and R2* effects of the CA in liver and perfusate were measured using gradient echo fast imaging (GEFI) experiments by varying either the excitation angle or the echo time. CA concentrations in liver and perfusate were also measured after MRI by inductively coupled plasma atomic emission spectroscopy, in order to determine in situ relaxivities in the perfusate (r1=4.2 +/- 0.1 s(-1) mm(-1), r2*=17 +/- 2 s(-1) mm(-1)) and in the liver (r1=7.2 +/- 0.2 s(-1) mm(-1), r2*=99 +/- 5 s(-1) mm(-1)). When CA concentrations were estimated from R1 measurements and r1, the CA distribution volume estimations in liver resulting from bolus (0.31 +/- 0.01) and stationary (0.32 +/- 0.05) experiments were not significantly different. In contrast, after a bolus, CA concentrations derived from R2* and r2* were overestimated in liver and even more in perfusate. However, with R1 and R2* being measured before CA bolus administration, zero echo time signal intensities computed from multiple TE measurements during multiple boli yielded good estimations of R1 and thus correct CA concentrations in liver and in perfusate. Under these conditions, a single multi-echo GEFI acquisition should be sufficient to determine the concentration-time curves. Consequently, this protocol should be appropriate to rapidly estimate the distribution volume in vivo when multiple boli have to be avoided.
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Affiliation(s)
- Jean-Luc Dimicoli
- U350 INSERM, Institut Curie, Centre Universitaire, Bâtiment 112, F91405 Orsay Cédex, France.
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Herold C, Ganslmayer M, Ocker M, Zopf S, Gailer B, Hahn EG, Schuppan D. Inducibility of microsomal liver function may differentiate cirrhotic patients with maintained compared with severely compromised liver reserve. J Gastroenterol Hepatol 2003; 18:445-449. [PMID: 12653894 DOI: 10.1046/j.1440-1746.2003.03007.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIM Quantitative tests of liver function (QTLF) can be modulated by enzyme-inducing agents. The objective of the study was to examine changes in QTLF after treatment with Phenobarbital, a potent cytochrome P450-inducing agent. METHODS Forty-six consecutive patients with liver cirrhosis Child-Pugh score B and C (34 alcoholic, 12 hepatitis C) and a compromised aminopyrine breath test (ABT) were included. Thirty-six patients (group I) received phenobarbitone (150 mg) for 7 days. Ten patients (group II) received a placebo. The QTLF, which included ABT (microsomal liver function), galactose elimination capacity (GEC, cytosolic liver function), sorbitol clearance (SCl, liver plasma flow) and indocyanine green clearance (ICG, liver perfusion) was carried out before and after pharmacological induction. RESULTS Group I showed a basal ABT of 0.18 +/- 0.11% dose.kg/mmol CO2 (normal >0.6%), which increased significantly after induction (172%, P < 0.05), whereas in group II the ABT values did not change. In group IB, a subgroup of group I which exceeded the basal threshold value of 0.30% after stimulation (n = 22), the ABT values increased significantly to 0.44 +/- 0.17% (244%, P < 0.01). The GEC, SCl and ICG remained unchanged before and after induction. CONCLUSIONS After pharmacological induction, microsomal liver function increased significantly in a subgroup of patients with liver cirrhosis, whereas the GEC, SCl and ICG remained unchanged. Inducibility of the microsomal liver function could be used as a novel parameter of functional hepatic reserve and prognosis in cirrhosis.
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Affiliation(s)
- Chirstoph Herold
- Department of Medicine I, Unviersity of Erlangen-Nuernberg, Erlangen Germany.
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41
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Van Beers BE, Materne R, Annet L, Hermoye L, Sempoux C, Peeters F, Smith AM, Jamart J, Horsmans Y. Capillarization of the sinusoids in liver fibrosis: noninvasive assessment with contrast-enhanced MRI in the rabbit. Magn Reson Med 2003; 49:692-9. [PMID: 12652540 DOI: 10.1002/mrm.10420] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Sinusoidal capillarization induces microcirculatory changes in liver cirrhosis and fibrosis. The purpose of this study was to assess whether contrast-enhanced MRI can be used to demonstrate the effects of sinusoidal capillarization in liver fibrosis. Dynamic MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd-DOTA), and two high-molecular-weight contrast agents of 6.47 kDa and 52 kDa (P792 and P717) was performed in rabbits with liver fibrosis induced by cholesterol and diethylstilbestrol. The hepatic distribution volume accessible to the high-molecular-weight agents decreased in the rabbits with liver fibrosis (P792: 7.8% +/- 1.7% vs. 10.1% +/- 1.8% in normal rabbits, P =.038; P717: 6.2% +/- 2.1% vs. 9.7% +/- 1.6% in normal rabbits, P =.007), whereas the hepatic mean transit time (MTT) of the low-molecular-weight agent was increased (15.9 +/- 8.0 s vs. 8.8 +/- 2.6 s in normal rabbits, P =.015). In rabbits with liver fibrosis, the clearance of indocyanine green (ICG) was correlated with the volume accessible to the high-molecular-weight agents (P792: r = 0.810, P =.015; P717: r = 0.857, P =.007). The collagen content of the liver was inversely correlated with the distribution volume of P717 (r = -.833, P =.010) and with the ICG clearance (r = -.810, P =.015). It was concluded that the microcirculatory changes induced by sinusoidal capillarization in liver fibrosis can be demonstrated noninvasively with MRI.
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Affiliation(s)
- Bernard E Van Beers
- Department of Radiology, Université Catholique de Louvain, St-Luc University Hospital, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
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Díaz S, Pérez-Peña J, Sanz J, Olmedilla L, Garutti I, Barrio JM. Haemodynamic monitoring and liver function evaluation by pulsion cold system Z-201 (PCS) during orthotopic liver transplantation. Clin Transplant 2003; 17:47-55. [PMID: 12588322 DOI: 10.1034/j.1399-0012.2003.02072.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] [Indexed: 11/23/2022]
Abstract
Pulsion cold system (PCS, COLD) is a haemodynamic monitoring system that allows measurement of cardiac output (CO), partial blood volumes, lung water, and liver function. The aim of the study was to evaluate this monitoring system during human orthotopic liver transplantation (OLT) for the following: (a) to determine agreement between CO measurements via pulmonary artery thermodilution (CO TDpa), and aortic transpulmonary thermodilution (CO TDa); (b) to compare the preload dates obtained with the COLD with central venous pressure (CVP) and pulmonary capillary wedge (PCWP); and (c) to assess the use of the plasma disappearance rate (PDR) of indocyanine green (ICG) as a measure of graft function. Fifteen consecutive patients undergoing OLT were studied. Each patient received a pulmonary artery catheter and a 5F aortic catheter with an integrated thermistor. The thermistor of the aortic catheter were connected to one computer system (COLD-Z201, Pulsion Medical Systems, Munich, Germany). Haemodynamic data were registered an all the phases of OLT. PDR was measured during surgery in 12 patients. Correlations between PDR and the other markers of graft function (transaminases, protrombine time, and bile production) were sought. The correlation coefficient between CO TDa (COLD) and CO TDpa was r = 0.766 (p < 0.001), and an additional analysis according to Bland-Altman was also performed. There was a better correlation between the cardiac index (determined by two monitoring systems) and the volume measurements than the correlation observed with pressure preload parameters. The best correlations were found between the cardiac index in the femoral artery and intrathoracic blood volume index (ITBVI) and pulmonary blood volume index (PBVI) (r = 0.79 and r = 0.72, respectively; p < 0.01). PDR measured in the group patients with bad early graft function were lower (13.6 +/- 2.7) than those in the group with a good graft function (21.6 +/- 9) (p < 0.05). The degree of discrepancy between femoral and pulmonary thermodilution cardiac output measures is very wide during OLT so as to make the techniques using the COLD machine clinically useless. On the other hand, the volumes measured by COLD, specially ITBVI and PBVI, are more useful to asses the pre-load than pressure measurements. In OLT, the PDR measured within the first few hours after liver reperfusion may become a useful tool for early diagnosis of primary graft dysfunction (PDF).
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Affiliation(s)
- Susana Díaz
- Department of Anesthesiology and Reanimation, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Niemann CU, Roberts JP, Ascher NL, Yost CS. Intraoperative hemodynamics and liver function in adult-to-adult living liver donors. Liver Transpl 2002; 8:1126-32. [PMID: 12474151 DOI: 10.1053/jlts.2002.36493] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Indocyanine green (ICG) can be used to measure cardiac output (CO), hepatic function, and blood volume. We used ICG to describe the effect of right hepatectomy for living liver donation on intraoperative hemodynamics and perioperative liver function. ICG disposition was determined in 12 healthy adult living liver donors during the dissection phase and immediately after removal of the right hepatic lobe. In addition, measurements were repeated postoperative day 5. After injecting ICG, plasma concentrations were obtained for approximately 10 minutes by noninvasive pulse dye densitometry. CO was significantly higher and systemic vascular resistance was significantly lower immediately after removal of the right lobe compared with those obtained before resection (6.02 +/- 1.12 v 10.28 +/- 3.84 L/min; P < .05; 639 +/- 254 v 1,007 +/- 264 dyn x s x cm(-5); P < .05). Heart rate also increased significantly after removal of the right lobe from 62 +/- 10 to 83 +/- 9 beats/min (P < .05). Mean arterial pressure and central venous pressure were not different between measurements. The average elimination rate constant of ICG (K(ICG)) was reduced by more than 50% immediately after resection of the right lobe in comparison to baseline (0.25 +/- 0.096 v 0.12 +/- 0.03; P < .05). Day 5, K(ICG) was still decreased from baseline (0.25 +/- 0.096 v 0.16 +/- 0.04; P < .05), but approximately 25% greater than the immediate postresection K(ICG) (0.16 +/- 0.04 v 0.12 +/- 0.03; P > .05). Findings show profound intraoperative hemodynamic changes during living liver donation. In addition, we show that functional recovery of the liver is likely to be slower than morphological recovery, and such clinical parameters as coagulation profile may not be a good index of fully restored hepatic function.
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Affiliation(s)
- Claus U Niemann
- Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143-0648, USA.
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Mandell MS, Wachs M, Niemann CU, Henthorn TK. Elimination of indocyanine green in the perioperative evaluation of donor liver function. Anesth Analg 2002; 95:1182-4, table of contents. [PMID: 12401588 DOI: 10.1097/00000539-200211000-00010] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
IMPLICATIONS The authors describe the intraoperative use of indocyanine green dye elimination to detect critical reductions in donor liver function.
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Affiliation(s)
- M Susan Mandell
- Department of Anesthesiology, Division of Transplantation, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA.
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Niemann CU, Yost CS, Mandell S, Henthorn TK. Evaluation of the splanchnic circulation with indocyanine green pharmacokinetics in liver transplant patients. Liver Transpl 2002; 8:476-81. [PMID: 12004348 DOI: 10.1053/jlts.2002.33218] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Although indocyanine green (ICG) can be used to estimate cardiac output (CO) and blood volume independently, a recirculatory multicompartmental ICG model enables description of these and additional intravascular factors. This model was used to describe the effect of end-stage liver disease (ESLD) on systemic and splanchnic hemodynamics in patients undergoing orthotopic liver transplantation. ICG disposition was determined during the dissection phase in six patients with ESLD undergoing orthotopic liver transplantation and six healthy adult living liver donors. After injecting ICG, plasma concentrations were obtained for approximately 10 to 12 minutes by noninvasive pulse dye densitometry. The recirculatory model characterizes three distinct intravascular circuits: lumped parallel fast (presumably nonsplanchnic circulation) and slow peripheral (splanchnic) circuits and a central circuit (central blood volume). Mean transit time (MTT) in the fast peripheral circuit was not different in patients with ESLD and controls. However, ESLD resulted in a significant decrease in MTT in the central (0.11 +/- 0.028 [SD] v 0.24 +/- 0.094 minutes in controls; P <.001) and slow peripheral circuit (0.67 +/- 0.41 v 1.37 +/- 0.37 minutes in controls; P <.001) because of increased flows to the central and slow peripheral circuits. These findings are consistent with the described hyperdynamic systemic and splanchnic circulations in patients with ESLD. In conclusion, the ICG model is able to derive estimates of not only blood volume and CO, but also splanchnic hemodynamics under different physiological conditions. This model can be a useful tool to evaluate the effect of pharmacological manipulation of splanchnic hemodynamics.
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Affiliation(s)
- Claus U Niemann
- Department of Anesthesia and Perioperative Care, University of California, San Francisco 94143-0648, USA.
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Sadler KM, Walsh TS, Garden OJ, Lee A. Comparison of hepatic artery and portal vein reperfusion during orthotopic liver transplantation. Transplantation 2001; 72:1680-4. [PMID: 11726832 DOI: 10.1097/00007890-200111270-00019] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND During orthotopic liver transplantation (OLT), it is standard procedure to reperfuse the liver via the portal vein (PV) despite having a lower oxygen content and perfusion pressure than the hepatic artery (HA). There are no published studies that describe graft function and outcome when the HA is used for reperfusion. We report a retrospective comparison of graft outcome after HA or PV reperfusion when the piggyback technique was used. METHODS We identified 26 patients who had undergone OLT with HA reperfusion and 26 patients reperfused via the PV. Demographics, primary diagnosis, surgeon, warm and cold ischemic times, and blood product use were recorded. In each patient, whole blood lactate concentration, prothrombin time (PT), and alanine aminotransferase (ALT) were measured at defined time points during and after surgery as indices of graft lactate metabolism, synthetic function, and reperfusion injury, respectively. Thirty-day and 1-year outcome data were recorded. Data were compared between the HA and PV groups. RESULTS Demographics, blood product use, primary diagnosis, cold ischemic time, and surgeon were similar between the groups. Warm ischemic time was longer in the HA group (mean [SD] HA 51.2 [14.7], PV 40 [9.1] min, P=0.002). Blood lactate concentrations were similar at all time points. There was no difference in 24-hr postoperative PT between the groups (median [InterQuartile (IQ) range] HA 17.5 [16-28.3], PV 19 [16-24] sec, P=0.85). Peak postoperative ALT values were comparable (median [IQ range] HA 1031 [668-1701], PV 1107 [754-1824] IU/ml, P=0.78). There were no statistically significant differences in 30-day or 1-year mortality, but more early deaths occurred in the HA group. Using our data, we calculated that a prospective randomized trial would need approximately 300 patients to be sure that mortality was the same with both techniques. CONCLUSION We have demonstrated no clinically or statistically significant differences in indices of graft function, reperfusion injury, or outcome between primary HA or PV reperfusion.
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Affiliation(s)
- K M Sadler
- Department of Anesthesia, Royal Infirmary of Edinburgh, 1 Lauriston Place, Edinburgh EH3 9YW, Scotland, UK.
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Herold C, Heinz R, Niedobitek G, Schneider T, Hahn EG, Schuppan D. Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C. LIVER 2001; 21:260-5. [PMID: 11454189 DOI: 10.1034/j.1600-0676.2001.021004260.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND/AIM Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. METHODS Three hundred and sixty-seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. CONCLUSIONS In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.
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Affiliation(s)
- C Herold
- Dept. of Medicine I and Institute of Pathology, University of Erlangen-Nuernberg, Erlangen, Germany
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Pascolo L, Petrovic S, Cupelli F, Bruschi CV, Anelli PL, Lorusso V, Visigalli M, Uggeri F, Tiribelli C. Abc protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles. Biochem Biophys Res Commun 2001; 282:60-6. [PMID: 11263971 DOI: 10.1006/bbrc.2001.4318] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The mechanism of excretion into bile of hepatospecific magnetic resonance imaging (MRI) contrast media employed labeled Gd-reagents EOB.DTPA, BOPTA, B 20790 (iopanoate-linked), and B 21690 (glycocholate-linked) for measurement in rat liver canalicular plasma membrane vesicles and yeast vacuoles. The presence of ATP gave threefold greater transport of B 20790 and B 21690 than of EOB.DTPA and BOPTA. In yeast vacuoles the ATP stimulatory effect was eightfold with B 20790 and fivefold greater for B 21690, whereas in YCF1- or YLLO115w-deleted yeast cells the transport was significantly reduced and absent from double mutants, YCF1 and YLLO15w. The transport was similar in wild-type and deletant cells for B 21690; taurocholate gave 85% inhibition. These data suggest that bilary secretion of structurally related MRI agents depend on molecular structure. The findings are suggestive as of possible value for clinical diagnosis of inherited hyperbilirubinemias and other liver disorders.
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Affiliation(s)
- L Pascolo
- CSF-Department BBC, University of Trieste, Via Giorgeri 1, Trieste, 34127, Italy
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Della Rocca G, Passariello M, Costa MG, Coccia C, Pompei L, Pierconti F, Venuta F, De Giacomo T, Pietropaoli P, Cortesini R. Volumetric monitoring in multiorgan donor and related lung transplant recipients. Transplant Proc 2001; 33:1637-9. [PMID: 11267452 DOI: 10.1016/s0041-1345(00)02624-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- G Della Rocca
- Istituto di Anestesiologia e Rianimazione, University of Rome "La Sapienza," Azienda Ospedaliera Policlinico Umberto I, Rome, Italy.
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Abstract
The success of liver transplantation has resulted in its widespread use for end-stage liver disease; 1- and 5-year survival rates of 70-90% and 60-80% respectively have been reported. Indications for assessment for liver transplantation are now evidence-based and early referral is recommended, correlating with improved patient survival. The management of patients on the waiting list for liver transplantation is designed to prevent complications of liver disease and to avoid therapeutic misadventures. Following transplantation, rejection and infection dominate post-operative complications, and improvements in their prevention and treatment have also correlated with improved patient survival. The development and introduction into clinical practice of a variety of immunosuppressive agents has offered a bewildering array of therapeutic options but with a lack of evidence on which to select optimal immunosuppression. Similarly, difficulties remain in the treatment of some of the complications arising from liver transplantation such as recurrence of disease and complications of immunosuppression.
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Affiliation(s)
- G H Haydon
- Department of Medicine, University of Birmingham Medical School, Birmingham, UK
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