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Shen C, Cheng H, Zong T, Zhu H. The role of normothermic machine perfusion (NMP) in the preservation of ex-vivo liver before transplantation: A review. Front Bioeng Biotechnol 2023; 11:1072937. [PMID: 36845187 PMCID: PMC9947506 DOI: 10.3389/fbioe.2023.1072937] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/31/2023] [Indexed: 02/11/2023] Open
Abstract
The discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. There is a limited access to liver transplantation, as a result, it is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. However, there are still many unknown risks associated with the use of ECD, among which preservation before liver transplantation is important in determining whether patients would experience complications survive after liver transplantation. In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion (NMP) may reduce preservation injury, improve graft viability, and potentially ex vivo assessment of graft viability before transplantation. Data seem to suggest that NMP can enhance the preservation of liver transplantation to some extent and improve the early outcome after transplantation. In this review, we provided an overview of NMP and its application in ex vivo liver preservation and pre-transplantation, and we summarized the data from current clinical trials of normothermic liver perfusion.
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Affiliation(s)
- Chuanyan Shen
- The College of Life Sciences, Northwest University, Xi’an, Shaanxi, China
| | - Hongwei Cheng
- The College of Life Sciences, Northwest University, Xi’an, Shaanxi, China
| | - Tingting Zong
- The College of Life Sciences, Northwest University, Xi’an, Shaanxi, China
| | - Hongli Zhu
- The College of Life Sciences, Northwest University, Xi’an, Shaanxi, China,National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi’an, China,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi’an, China,*Correspondence: Hongli Zhu,
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Blundell J, Shahrestani S, Lendzion R, Pleass HJ, Hawthorne WJ. Risk Factors for Early Pancreatic Allograft Thrombosis Following Simultaneous Pancreas-Kidney Transplantation: A Systematic Review. Clin Appl Thromb Hemost 2021; 26:1076029620942589. [PMID: 33052066 PMCID: PMC7573738 DOI: 10.1177/1076029620942589] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1 diabetes with renal failure. Thrombosis of the pancreatic vasculature continues to contribute significantly to early graft failure and loss. We compared the rate of thrombosis to graft loss and systematically reviewed risk factors impacting early thrombosis of the pancreas allograft following SPK transplantation. We searched the MEDLINE, EMBASE, The Cochrane Library, and PREMEDLINE databases for studies reporting thrombosis following pancreas transplantation. Identified publications were screened for inclusion and synthesized into a data extraction sheet. Sixty-three studies satisfied eligibility criteria: 39 cohort studies, 22 conference abstracts, and 2 meta-analyses. Newcastle-Ottawa Scale appraisal of included studies demonstrated cohort studies of low bias risk; 1127 thrombi were identified in 15 936 deceased donor, whole pancreas transplants, conferring a 7.07% overall thrombosis rate. Thrombosis resulted in pancreatic allograft loss in 83.3% of reported cases. This review has established significant associations between donor and recipient characteristics, procurement and preservation methodology, transplantation technique, postoperative management, and increased risk of early thrombosis in the pancreas allograft. Further studies examining the type of organ preservation fluid, prophylactic heparin protocol, and exocrine drainage method and early thrombosis should also be performed.
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Affiliation(s)
- Jian Blundell
- Sydney Medical School, University of Sydney, New South Wales, Australia
| | - Sara Shahrestani
- Sydney Medical School, University of Sydney, New South Wales, Australia.,Department of Surgery, University of Sydney at Westmead Hospital, New South Wales, Australia
| | - Rebecca Lendzion
- Department of Surgery, University of Sydney at Westmead Hospital, New South Wales, Australia
| | - Henry J Pleass
- Sydney Medical School, University of Sydney, New South Wales, Australia.,Department of Surgery, University of Sydney at Westmead Hospital, New South Wales, Australia
| | - Wayne J Hawthorne
- Sydney Medical School, University of Sydney, New South Wales, Australia.,Department of Surgery, University of Sydney at Westmead Hospital, New South Wales, Australia.,The Centre for Transplant & Renal Research, Westmead Institute for Medical Research, New South Wales, Australia
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Chen Y, Shi J, Xia TC, Xu R, He X, Xia Y. Preservation Solutions for Kidney Transplantation: History, Advances and Mechanisms. Cell Transplant 2019; 28:1472-1489. [PMID: 31450971 PMCID: PMC6923544 DOI: 10.1177/0963689719872699] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Solid organ transplantation was one of the greatest medical advances during the past few
decades. Organ preservation solutions have been applied to diminish ischemic/hypoxic
injury during cold storage and improve graft survival. In this article, we provide a
general review of the history and advances of preservation solutions for kidney
transplantation. Key components of commonly used solutions are listed, and effective
supplementations for current available preservation solutions are discussed. At cellular
and molecular levels, further insights were provided into the pathophysiological
mechanisms of effective ingredients against ischemic/hypoxic renal injury during cold
storage. We pay special attention to the cellular and molecular events during
transplantation, including ATP depletion, acidosis, mitochondrial dysfunction, oxidative
stress, inflammation, and other intracellular mechanisms.
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Affiliation(s)
- Yimeng Chen
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Jian Shi
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Terry C Xia
- The University of Connecticut, Storrs, CT, USA
| | - Renfang Xu
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Xiaozhou He
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Ying Xia
- Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai, China
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Jing L, Yao L, Zhao M, Peng LP, Liu M. Organ preservation: from the past to the future. Acta Pharmacol Sin 2018; 39:845-857. [PMID: 29565040 DOI: 10.1038/aps.2017.182] [Citation(s) in RCA: 115] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 12/31/2017] [Indexed: 12/13/2022]
Abstract
Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservation. However, preservation time with SCS is limited as prolonged cold storage increases the risk of early graft dysfunction that contributes to chronic complications. Furthermore, the growing demand for the use of marginal donor organs requires methods for organ assessment and repair. Machine perfusion has resurfaced and dominates current research on organ preservation. It is credited to its dynamic nature and physiological-like environment. The development of more sophisticated machine perfusion techniques and better perfusates may lead to organ repair/reconditioning. This review describes the history of organ preservation, summarizes the progresses that has been made to date, and discusses future directions for organ preservation.
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Kazemi K, Nikeghbalian Z, Yaghmaei S, Nikeghbalian S, Shamsaeifar A, Asgharnia Y, Dehghankhalili M, Golchini A, Malekhosseini SA. University of Wisconsin vs normal saline solutions for preservation of blood vessels of brain dead donors: A histopathological study. Clin Transplant 2018; 32:e13241. [PMID: 29573462 DOI: 10.1111/ctr.13241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2018] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To compare the cellular changes of harvested arteries which were preserved in normal saline (NS) and the standard and routinely used University of Wisconsin (UW) solution. METHODS This experimental study was conducted on 20 brain dead patients. The femoral and iliac arteries were bilaterally removed and were placed in NS and UW solutions. The vascular change indices including endothelial detachment (ED), medial detachment (MD), and internal elastic membrane disruption (IEMD) were surveyed for each preserver in the first, 5th, 10th, and 21st day. RESULTS The mean age of the included patients was 32.28 ± 8.88 years, and there were 13 (65.0%) men and 7 (35.0%) women among the patients. The NS and UW preservation solutions were comparable regarding the indices of vascular changes at first, 5th, and 10th day of the study. Only in 21st day of the study, there was a significant difference between 2 group regarding MD changes (P = .049). CONCLUSION The results of this in vitro study demonstrated that NS can be used as a worthy preserver for harvested vessels for up to 21 days, especially in resource-limited transplantation centers.
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Affiliation(s)
- Kourosh Kazemi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Nikeghbalian
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shekoofeh Yaghmaei
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saman Nikeghbalian
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Shamsaeifar
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Yasaman Asgharnia
- Student Research Committee, Guilan University of Medical Sciences, Rasht, Iran
| | - Maryam Dehghankhalili
- Resident of General Surgery, Department of General Surgery, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Golchini
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
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Teh ES, Zal F, Polard V, Menasché P, Chambers DJ. HEMO2life as a protective additive to Celsior solution for static storage of donor hearts prior to transplantation. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2017; 45:717-722. [DOI: 10.1080/21691401.2016.1265974] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Elaine S. Teh
- Cardiac Surgical Research/Cardiothoracic Surgery, the Rayne Institute (King’s College London), Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London, UK
| | - Franck Zal
- Biotechnopôle, Hemarina SA, Aéropôle Centre, Morlaix, France
| | - Valérie Polard
- Biotechnopôle, Hemarina SA, Aéropôle Centre, Morlaix, France
| | - Philippe Menasché
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery, Université Paris Descartes, Sorbonne Paris Cité; INSERM U 970, Paris, France
| | - David J. Chambers
- Cardiac Surgical Research/Cardiothoracic Surgery, the Rayne Institute (King’s College London), Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London, UK
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A multidrug cocktail approach attenuates ischemic-type biliary lesions in liver transplantation from non-heart-beating donors. Med Hypotheses 2016; 91:47-52. [DOI: 10.1016/j.mehy.2016.04.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 12/20/2015] [Accepted: 04/08/2016] [Indexed: 02/06/2023]
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Latchana N, Peck JR, Whitson BA, Henry ML, Elkhammas EA, Black SM. Preservation solutions used during abdominal transplantation: Current status and outcomes. World J Transplant 2015; 5:154-164. [PMID: 26722644 PMCID: PMC4689927 DOI: 10.5500/wjt.v5.i4.154] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/01/2015] [Accepted: 11/11/2015] [Indexed: 02/05/2023] Open
Abstract
Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate (HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.
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Abstract
PURPOSE OF REVIEW To summarize the history of organ preservation and place into this context the current trends in preservation. RECENT FINDINGS Multiple large retrospective studies have analyzed cold preservation solutions in an attempt to determine superiority with largely negative results. Experimental and some clinical studies have examined machine perfusion of procured grafts, in both hypothermic and normothermic contexts with variable, but promising, results. Lastly, there are experimental efforts to evaluate mesenchymal stem cell therapy on rehabilitation of marginal donor organs. SUMMARY New trends in organ preservation may soon translate into more efficient use of the limited donor pool.
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Tabka D, Bejaoui M, Javellaud J, Roselló-Catafau J, Achard JM, Abdennebi HB. Effects of Institut Georges Lopez-1 and Celsior preservation solutions on liver graft injury. World J Gastroenterol 2015; 21:4159-4168. [PMID: 25892865 PMCID: PMC4394076 DOI: 10.3748/wjg.v21.i14.4159] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 12/30/2014] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To compare Institut Georges Lopez (IGL-1) and Celsior preservation solutions for hepatic endothelium relaxation and liver cold ischemia reperfusion injury (IRI). METHODS Two experimental models were used. In the first one, acetylcholine-induced endothelium-dependent relaxation (EDR) was measured in isolated ring preparations of rat hepatic arteries preserved or not in IGL-1 or Celsior solutions (24 h at 4 °C). To determine nitric oxide (NO) and cyclooxygenase EDR, hepatic arteries were incubated with L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of endothelium nitric oxide synthase (eNOS), or with L-NAME plus indomethacin, an inhibitor of cyclooxygenase. In the second experiment, rat livers were cold-stored in IGL-1 or Celsior solutions for 24 h at 4 °C and then perfused "ex vivo" for 2 h at 37 °C. Liver injury was assessed by transaminase measurements, liver function by bile production and bromosulfophthalein clearance, oxidative stress by malondialdehyde levels and catalase activity and alterations in cell signaling pathways by pAkt, pAMPK, eNOS and MAPKs proteins level. RESULTS After cold storage for 24 h with either Celsior or IGL-1, EDR was only slightly altered. In freshly isolated arteries, EDR was exclusively mediated by NO. However, cold-stored arteries showed NO- and COX-dependent relaxation. The decrease in NO-dependent relaxation after cold storage was significantly more marked with Celsior. The second study indicated that IGL-1 solution obtained better liver preservation and protection against IRI than Celsior. Liver injury was reduced, function was improved and there was less oxidative stress. IGL-1 solution activated Akt and AMPK, which was concomitant with increased eNOS expression and nitrite/nitrate levels. Furthermore, MAPKs kinases were regulated in livers preserved with IGL-1 solution since reductions in p-p38, p-ERK and p-JNK protein levels were observed. CONCLUSION IGL-1 solution preserved NO-dependent relaxation better than Celsior storage solution and enhanced liver graft preservation.
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12
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Preservation solutions for static cold storage of abdominal allografts: which is best? Curr Opin Organ Transplant 2014; 19:100-7. [PMID: 24553501 DOI: 10.1097/mot.0000000000000063] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW To update the reader on the recent literature in liver, kidney, pancreas, and intestine static cold preservation, and to identify which solutions are most advantageous for each organ. RECENT FINDINGS The comparison of randomized trials of histidine-tryptophan-ketoglutarate (HTK), Celsior, and University of Wisconsin solutions has shown equivalent risk of delayed graft function after kidney transplantation. Similar outcomes have been observed after pancreas preservation with University of Wisconsin, HTK, and Celsior solution. In live-donor liver transplantation, University of Wisconsin and HTK solution have shown equivalent results, whereas in the recent trials of deceased-donor liver transplantation, University of Wisconsin, HTK, and Celsior solutions have shown equivalence. Contrary to the most clinical trials, national registry data in kidney, pancreas, and liver transplantation demonstrate more detrimental effects and earlier graft loss after preservation with HTK versus University of Wisconsin solution. Early outcomes after intestinal transplantation with University of Wisconsin or HTK solution have shown no significant difference and animal studies indicate intraluminal preservation may be beneficial. SUMMARY The University of Wisconsin solution is the standard criterion static cold preservation for the procurement of liver, kidney, pancreas, and intestine. University of Wisconsin, HTK, and Celsior solutions all provide similar allograft outcomes in most clinical trials, but subtle differences have become more apparent in the recent studies and registry reports.
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Gohrbandt B, Avsar M, Warnecke G, Sommer SP, Haverich A, Strueber M. Initial topical cooling followed by backtable Celsior flush perfusion provides excellent early graft function in porcine single lung transplantation after 24 hours of cold ischemia. J Heart Lung Transplant 2013; 32:832-8. [PMID: 23856220 DOI: 10.1016/j.healun.2013.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Revised: 05/20/2013] [Accepted: 06/04/2013] [Indexed: 10/26/2022] Open
Abstract
BACKGROUND Topical in situ cooling of the donor lungs is a prerequisite for procurement of non-heart-beating donor lungs and may be of interest for living related lung donation. METHODS Twenty-four single lung transplants were performed in 4 groups of Landrace pigs (6 per group). Control LPD, control Celsior and topical cooling in situ, followed by LPD (exLPD) or Celsior (exCel) ex situ flush, were employed. All lungs were perfused antegrade with 1 liter of solution at 4°C. Lungs were stored immersed in preservation solution for 24 hours at 4°C. After transplantation of the left lung, the right recipient bronchus and pulmonary artery were clamped. RESULTS Four of 6 animals each in the LPD and Celsior groups and all 6 animals in both the exLPD and the exCel groups survived the 7-hour reperfusion. The mean oxygenation index was favorably preserved in the exCel group at 7 hours after reperfusion (417 ± 81) over all other groups (LPD 341 ± 133, Celsior 387 ± 86, exLPD 327 ± 76; p < 0.0001). Pulmonary vascular resistance showed significantly lower values in the Celsior and exCel groups (LPD 1,310 ± 620, Celsior 584 ± 194, exLPD 1,035 ± 361, exCel 650 ± 116 dyn/s/cm(5) at 7 hours after reperfusion; p < 0.0001). Consistently, the wet-to-dry lung weight ratio also indicated beneficial graft protection in the exCel group (LPD 8.1 ± 0.8, Celsior 8.4 ± 0.8, exLPD 7.5 ± 1.0, exCel 3.1 ± 0.9; p < 0.0001). CONCLUSION Initial topical cooling followed by backtable perfusion is a sufficient technique for pulmonary graft preservation providing excellent post-transplant function. Celsior subsequent to in-situ topical cooling revealed the most beneficial results in this setting. This combined technique could advance non-heart-beating, living related lung lobe donation and, potentially, regular heart-beating lung donation.
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Affiliation(s)
- Bernhard Gohrbandt
- Hannover Thoracic Transplant Program, Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany
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García-Gil FA, Serrano MT, Fuentes-Broto L, Arenas J, García JJ, Güemes A, Bernal V, Campillo A, Sostres C, Araiz JJ, Royo P, Simón MA. Celsior versus University of Wisconsin preserving solutions for liver transplantation: postreperfusion syndrome and outcome of a 5-year prospective randomized controlled study. World J Surg 2011; 35:1598-607. [PMID: 21487851 DOI: 10.1007/s00268-011-1078-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Celsior solution (CS) is a high-sodium, low-potassium, low-viscosity extracellular solution that has been used for liver graft preservation in recent years, although experience with it is still limited. We performed an open-label randomized active-controlled trial comparing CS with the University of Wisconsin solution (UW) for liver transplantation (LT), with a follow-up period of 5 years. METHODS Adult transplant recipients (n=102) were prospectively randomized to receive either CS (n=51) or UW (n=51). The two groups were comparable with respect to donor and recipient characteristics. The primary outcome measure was the incidence of postreperfusion syndrome (PRS). Secondary outcome measures included primary nonfunction (PNF) or primary dysfunction (PDF), liver retransplantation, and graft and patient survival. Other secondary outcome measures were days in the intensive care unit (ICU) and the rates of acute rejection, chronic rejection, infectious complications, postoperative reoperations, and vascular and biliary complications. RESULTS In all, 14 posttransplant variables revealed no significant differences between the groups. There were no cases of PNF or PDF. The incidence of PRS was 5.9% in the CS group and 21.6% in the UW group (P=0.041). After reperfusion, CS revealed greater control of serum potassium (P=0.015), magnesium levels (P=0.005), and plasma glucose (P=0.042) than UW. Respective patient survivals at 3, 12, and 60 months were 95.7, 87.2, and 82.0% for the CS group and 95.7, 83.3, and 66.6% for the UW group (P=0.123). CONCLUSIONS While retaining the same degree of safety and effectiveness as UW for LT, CS may yield postliver graft reperfusion benefits, as shown in this study by a significant reduction in the incidence of PRS and greater metabolic control.
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Affiliation(s)
- Francisco A García-Gil
- Department of Surgery, University of Zaragoza, Domingo Miral s/n, 50009, Zaragoza, Spain.
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Boudjema K, Grandadam S, Compagnon P, Salamé E, Wolf P, Ducerf C, Le Treut P, Soubrane O, Cherqui D, Mouchel C, Renault A, Bellissant E. Efficacy and safety of Celsior preservation fluid in liver transplantation: one-year follow up of a prospective, multicenter, non-randomized study. Clin Transplant 2011; 26:199-207. [PMID: 21517997 DOI: 10.1111/j.1399-0012.2011.01447.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The purpose of this prospective, nine-center, non-randomized study was to assess the efficacy and safety of Celsior preservation fluid in liver transplantation using unselected donors. As data comparing allograft outcomes following liver transplantation using Celsior and University of Wisconsin (UW) preservation fluids are limited, we also compared our cohort with matched controls selected from the European Liver Transplant Registry (ELTR) who received total liver grafts preserved with UW solution during the same period. One hundred and forty patients who received livers preserved with Celsior were included. The primary endpoint, graft loss at one-yr post-transplantation, was observed in 24 patients (17.1%) which was not significantly different from the 20.0% pre-defined threshold rate (95% confidence interval [CI] 10.9, 23.4; p=0.398). Predictive factors for graft loss on univariate analysis were moderate-to-severe steatosis on the donor graft (5/22 patients with graft loss vs. 8/107 patients without, p=0.046) and duration of warm ischemia (1.4±1.1 h in patients with graft loss vs. 0.9±0.5 h in patients without, p=0.034). Hepatic artery thrombosis and stenosis occurred in seven (5.0%) and six (4.3%) patients, respectively. The comparison of our patients to 420 ELTR controls showed that one-yr graft survival rates (Celsior: 82.9%, 95% CI 75.8, 88.2; UW: 78.6%, 95% CI 74.4, 82.2) and Kaplan-Meier one-yr graft survival distributions (p=0.285) were similar. Within the cold ischemia time achieved in our study, liver preservation with Celsior appeared efficient and safe. Comparison with ELTR patients suggested that liver allograft survival was similar using Celsior or UW solution for preservation of unselected donor grafts.
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Affiliation(s)
- Karim Boudjema
- Service de Chirurgie Hépatobiliaire et Digestive, Hôpital de Pontchaillou, Centre Hospitalier Universitaire de Rennes & Université de Rennes 1, Rennes, France.
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Teng PN, Rungruang BJ, Hood BL, Sun M, Flint MS, Bateman NW, Dhir R, Bhargava R, Richard SD, Edwards RP, Conrads TP. Assessment of buffer systems for harvesting proteins from tissue interstitial fluid for proteomic analysis. J Proteome Res 2010; 9:4161-9. [PMID: 20518575 DOI: 10.1021/pr100382v] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Tissue interstitial fluid (TIF) bathes cells in tissues, and it is hypothesized that TIF proximal to a developing tumor may contain an enriched population of tumor-specific shed and secreted proteins relative to peripheral blood. Extraction of TIF proteins is typically accomplished through passive incubation of surgically resected tissues in phosphate buffered saline (PBS); however, its influence on cellular activity and viability has not been fully explored. The present investigation sought to characterize whether different buffer systems influence the recovered TIF proteome. Five TIF buffer systems were investigated including PBS, Dulbecco's modified Eagle medium (DMEM), and three organ transplantation preservative solutions: Celsior solution S (CS), histidine-tryptophan-ketoglutarate (HTK), and University of Wisconsin (UW). Kidney tumor, adjacent normal kidney, and ovarian tumor tissues were incubated in each of the buffer systems, and the harvested TIF proteins were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the present results indicate that no significant differences exist in the recovered proteins from these two neoplasms between the five solution groups, additional sample preparative steps are required prior to LC-MS/MS for TIF proteins harvested from DMEM, UW, CS, and HTK. These data support that PBS is a suitable and convenient solution for harvesting TIF proteins for MS-based proteomics.
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Affiliation(s)
- Pang-ning Teng
- Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, USA
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Liver transplantation using University of Wisconsin or Celsior preserving solutions in the portal vein and Euro-Collins in the aorta. Transplant Proc 2010; 42:429-34. [PMID: 20304157 DOI: 10.1016/j.transproceed.2010.01.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Orthotopic liver transplantation (OLT) is today the gold standard treatment of the end-stage liver disease. Different solutions are used for graft preservation. Our objective was to compare the results of cadaveric donor OLT, preserved with the University of Wisconsin (UW) or Celsior solutions in the portal vein and Euro-Collins in the aorta. METHODS We evaluated retrospectively 72 OLT recipients, including 36 with UW solution (group UW) and 36 with Celsior (group CS). Donors were perfused in situ with 1000 mL UW or Celsior in the portal vein of and 3000 mL of Euro-Collins in the aortia and on the back table managed with 500 mL UW or Celsior in the portal vein, 250 mL in the hepatic artery, and 250 mL in the biliary duct. We evaluated the following variables: donor characteristics, recipient features, intraoperative details, reperfusion injury, and steatosis via a biopsy after reperfusion. We noted grafts with primary nonfunction (PNF), initial poor function (IPF), rejection episodes, biliary duct complications, hepatic artery complications, re-OLT, and recipient death in the first year after OLT. RESULTS The average age was 33.6 years in the UW group versus 41 years in the CS group (P = .048). There was a longer duration of surgery in the UW group (P = .001). The other recipient characteristics, ischemia-reperfusion injury, steatosis, PNF, IPF, rejection, re-OLT, and recipient survival were not different. Stenosis of the biliary duct occured in 3 (8.3%) cases in the UW group and 8 (22.2%) in the CS (P = .19) with hepatic artery thrombosis in 4 (11.1%) CS versus none in the UW group (P = .11). CONCLUSION Cadaveric donor OLT showed similar results with organs preserved with UW or Celsior in the portal vein and Euro-Collins in the aorta.
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Zaouali MA, Ben Abdennebi H, Padrissa-Altés S, Mahfoudh-Boussaid A, Roselló-Catafau J. Pharmacological strategies against cold ischemia reperfusion injury. Expert Opin Pharmacother 2010; 11:537-555. [PMID: 20163266 DOI: 10.1517/14656560903547836] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
IMPORTANCE OF THE FIELD Good organ preservation is a determinant of graft outcome after revascularization. The necessity of increasing the quality of organ preservation, as well as of extending cold storage time, has made it necessary to consider the use of pharmacological additives. AREAS COVERED IN THIS REVIEW The complex physiopathology of cold-ischemia-reperfusion (I/R) injury--and in particular cell death, mitochondrial injury and endoplasmic reticulum stress--are reviewed. Basic principles of the formulation of the different preservation solutions are discussed. WHAT THE READER WILL GAIN Current strategies and new trends in static organ preservation using additives such as trimetazidine, polyethylene glycols, melatonin, trophic factors and endothelin antagonists in solution are presented and discussed. The benefits and mechanisms responsible for enhancing organ protection against I/R injury are also discussed. Graft preservation was substantially improved when additives were added to the preservation solutions. TAKE HOME MESSAGE Enrichment of preservation solutions by additives is clinically useful only for short periods. For longer periods of cold ischemia, the use of such additives becomes insufficient because graft function deteriorates as a result of ischemia. In such conditions, the preservation strategy should be changed by the use of machine perfusion in normothermic conditions.
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Affiliation(s)
- Mohamed Amine Zaouali
- Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, C/Rosselló 161, 7th floor, E-08036-Barcelona, Spain.
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Multifactorial biological modulation of warm ischemia reperfusion injury in liver transplantation from non-heart-beating donors eliminates primary nonfunction and reduces bile salt toxicity. Ann Surg 2009; 250:808-17. [PMID: 19826248 DOI: 10.1097/sla.0b013e3181bdd787] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To design a multifactorial biological modulation approach targeting ischemia reperfusion injury to augment viability of porcine liver grafts from non-heart-beating donors (NHBD). BACKGROUND DATA Liver Transplantation (LTx) from NHBD is associated with an increased risk of primary nonfunction (PNF) and biliary complications. In porcine NHBD-LTx, we previously reported a 50% risk of PNF and toxic bile formation in grafts exposed to > or =30' warm ischemia (WI). METHODS Porcine livers exposed to 45' WI were cold stored, transplanted and either modulated (n = 6) or not (controls, n = 9). In the modulation group, donor livers were flushed with warm Ringers (avoiding cold-induced vasoconstriction), streptokinase (eliminating stagnating thrombi), and epoprostenol (vasodilator, platelet aggregation inhibitor) prior to cold storage. In recipients, glycine (Kupffer cell stabilizer), alpha1-acid-glycoprotein (anti-inflammatory protein), MAPKinase-inhibitor (pro-inflammatory cytokine generation inhibitor), alpha-tocopherol and glutathione (anti-oxidants), and apotransferrin (iron chelator) were administrated intravenously. PNF, survival, lactate, transaminase, TNF-alpha, redox-active iron, and biliary bile salt-to-phospholipid ratio were monitored. RESULTS No PNF was observed in modulated versus 55% in control pigs (P = 0.025). Survival was 83% in modulated versus 22% in control pigs (P = 0.02). At 180' postreperfusion, lactate was lower in modulated (5.4 +/- 1.9 mmol/L) versus control pigs (9.4 +/- 2.2 mmol/L; P = 0.011). At 60' postreperfusion, there was a trend for lower AST in modulated versus control pigs at 60' (939 +/- 578 vs. 1683 +/- 873 IU/L; P = 0.089). Postreperfusion, TNF-alpha remained stable in modulated pigs (49 +/- 27 pg/mL at 15' and 85 +/- 26 pg/mL at 180'; P = 0.399) but increased in control pigs (107 +/- 36 pg/mL at 15' and 499 +/- 216 pg/mL at 180'; P = 0.023). At 180' postreperfusion, redox-active iron was higher in control pigs versus modulated pigs (0.21+/-0.18 vs. 0.042+/-0.062 mum; P = 0.038). Biliary bile salt-to-phospholipid ratio post-LTx was lower in modulated versus control pigs (1128 +/- 447 vs. 4836 +/- 4619; P = 0.05). CONCLUSIONS A multifactorial biological modulation eliminates PNF, improves liver function and increases survival. Biochemically, TNF-alpha and redox-active iron are suppressed and biliary bile salt toxicity is reduced. Translating this strategy clinically may lead to wider and safer use of NHBD.
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Dramatic Improvement in Survival After Lung Transplantation Over Time: A Single Center Experience. Transplant Proc 2009; 41:687-91. [DOI: 10.1016/j.transproceed.2008.12.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Kóbori L, Kõhalmy K, Porrogi P, Sárváry E, Gerlei Z, Fazakas J, Nagy P, Járay J, Monostory K. Drug-induced liver graft toxicity caused by cytochrome P450 poor metabolism. Br J Clin Pharmacol 2008; 65:428-36. [PMID: 18070218 PMCID: PMC2291242 DOI: 10.1111/j.1365-2125.2007.03056.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2007] [Accepted: 09/18/2007] [Indexed: 12/15/2022] Open
Abstract
UNLABELLED What is already known about this subject. The activity of drug-metabolizing enzymes, primarily cytochrome P450 enzymes, can determine a patient's response to a drug. Therapeutic failure or drug toxicity in the postoperative period after liver transplantation is influenced by the drug metabolizing capacity of the graft. Dose adjustment or selection of an alternative drug, which is not a substrate for the polymorphic enzyme may prevent the development of side-effects in recipients of poor metabolizer liver grafts. What this study adds. A validated analytical system with metabolomic tools has been developed to estimate the drug-metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates the improvement of individual recipient therapy. In the test of drug-metabolizing status, one of the liver grafts was found to be a CYP2C9 poor metabolizer, while the other was a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week. AIMS The drug-metabolizing capacity of transplanted liver highly influences drug efficacy or toxicity, particularly in the early postoperative period. The aim of our study was to predict therapeutic failures or severe adverse drug reactions by phenotyping for cytochrome P450 (P450) polymorphism resulting in reduced or no activity of the key drug-metabolizing enzymes. METHODS A validated analytical system with metabolomic tools has been developed for estimation of the drug-metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates improvement of the individual recipient therapy. RESULTS Of the 109 liver donors in Hungary, the frequency of poor metabolizers was found to be 0.92%, 5.5% and 8.3% for CYP2C9, CYP2C19 and CYP2D6, respectively. In the present study, two liver grafts transplanted in paediatric recipients were reported to be poor metabolizer phenotypes. The liver grafts presented normal function in the early postoperative days; 2 weeks after transplantation, however, increasing liver enzymes were detected. Histological investigation of a liver biopsy suggested drug toxicity. The test of drug metabolizing status showed one of the liver grafts to be a CYP2C9 poor metabolizer, and the other was found to be a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week. CONCLUSIONS Prospective investigation of the P450 status may lead to the optimization of drug choice and/or dose for a more effective therapy, avoid serious adverse effects, and decrease medical costs. Phenotyping donor livers and tailored medication can contribute to the improvement of graft and recipient survival.
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Affiliation(s)
- László Kóbori
- Transplantation and Surgical Clinic, Semmelweis UniversityBaross 23-25, H-1082 Budapest, Hungary
| | - Krisztina Kõhalmy
- Chemical Research Center, Hungarian Academy of SciencesPusztaszeri 59-67, H-1025 Budapest, Hungary
| | - Pálma Porrogi
- Chemical Research Center, Hungarian Academy of SciencesPusztaszeri 59-67, H-1025 Budapest, Hungary
| | - Enikõ Sárváry
- Transplantation and Surgical Clinic, Semmelweis UniversityBaross 23-25, H-1082 Budapest, Hungary
| | - Zsuzsa Gerlei
- Transplantation and Surgical Clinic, Semmelweis UniversityBaross 23-25, H-1082 Budapest, Hungary
| | - János Fazakas
- Transplantation and Surgical Clinic, Semmelweis UniversityBaross 23-25, H-1082 Budapest, Hungary
| | - Péter Nagy
- Ist Pathology and Experimental Cancer Research, Semmelweis UniversityÜllõi 26, H-1085 Budapest, Hungary
| | - Jenõ Járay
- Transplantation and Surgical Clinic, Semmelweis UniversityBaross 23-25, H-1082 Budapest, Hungary
| | - Katalin Monostory
- Chemical Research Center, Hungarian Academy of SciencesPusztaszeri 59-67, H-1025 Budapest, Hungary
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Crutchley TA, Pearce JD, Craven TE, Edwards MS, Dean RH, Hansen KJ. Branch renal artery repair with cold perfusion protection. J Vasc Surg 2007; 46:405-412; discussion 412. [PMID: 17681711 DOI: 10.1016/j.jvs.2007.04.036] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2007] [Accepted: 04/11/2007] [Indexed: 11/28/2022]
Abstract
PURPOSE This retrospective review describes the use and clinical outcome of cold perfusion protection during branch renal artery (RA) repair in 77 consecutive patients. METHODS From July 1987 through November 2006, 874 patients had open operative RA repair to 1312 kidneys. Seventy-seven patients (62 women, 15 men; mean age, 44 +/- 17 years) had branch RA reconstruction using ex vivo or in situ cold perfusion protection for 78 kidneys. Demographic data and surgical technique were examined. Blood pressure response and renal function were estimated. Patency of repair was determined by angiography and renal duplex ultrasound (RDUS) imaging. Primary RA patency was estimated by life-table methods. RESULTS Seventy-eight RAs were repaired using ex vivo (49 kidneys) or in situ (29 kidneys) cold perfusion protection. Bilateral RA repair was performed in eight patients, with 13 repairs to solitary kidneys. RA disease included aneurysm (RAA) in 50, fibromuscular dysplasia (FMD) in 37, atherosclerosis in 5, and arteritis in 2; 16 patients had both FMD and RAA. Hypertension was present in 93.5% (mean blood pressure, 184 +/- 35/107 +/- 19 mm Hg; mean of 1.9 +/- 1.1 drugs). RA repair included bypass using saphenous vein in 69, hypogastric artery in 3, polytetrafluoroethylene (PTFE) in 2, composite vein/PTFE in 2, cephalic vein in 1, or aneurysmorrhaphy in 1. The eight bilateral RA repairs were staged. One patient required bilateral cold perfusion protection. One planned nephrectomy was performed at the time of contralateral ex vivo reconstruction. No primary nephrectomies were required for intended reconstruction. Each RA reconstruction required branch dissection and reconstruction (mean of 2.8 +/- 1.6 branches were repaired). Mean cold ischemia time was 125 +/- 40 minutes. Each kidney was reconstructed in an orthotopic fashion. Five early failures of repair required three nephrectomies and one operative revision. Based on postoperative angiography or RDUS, or both, primary patency of RA repair at 12 months was 85% +/- 5%; assisted primary patency was 93% +/- 4%. Among patients with preoperative hypertension, 15% were cured, 65% were improved, and 20% were considered failed. Early renal function was improved in 35%, unchanged in 48%, and worse in 17%. Four patients had perioperative acute tubular necrosis. No patient progressed to dialysis-dependence. CONCLUSION Both ex vivo and in situ cold perfusion protection extend the safe renal ischemia time for complex branch RA repair and avoid the need for nephrectomy.
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Affiliation(s)
- Teresa A Crutchley
- Division of Surgical Sciences, Section on Vascular and Endovascular Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1095, USA
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Abstract
Maintaining organ viability after donation until transplantation is critically important for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in every day clinical practice. Although simple and effective, it is questionable whether this method is able to prevent deterioration of organ quality in the present era with increasing numbers of organs retrieved from older, more marginal, and even non-heart-beating donors. This review describes principles involved in effective preservation and focuses on some basic components and methods of abdominal organ preservation in clinical and experimental transplantation. Concepts and developments to reduce ischemia related injury are discussed, including hypothermic machine perfusion. Despite the fact that hypothermic machine perfusion might be superior to static cold storage preservation, organs are still exposed to hypothermia induced damage. Therefore, recently some groups have pointed at the beneficial effects of normothermic machine perfusion as a new perspective in organ preservation and transplantation.
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Affiliation(s)
- Mark-Hugo J Maathuis
- Department of Surgery, Surgical Research Laboratory, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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Lisik W, Gontarczyk G, Kosieradzki M, Lagiewska B, Pacholczyk M, Adadyński L, Kobryń A, Kwiatkowski A, Chmura A, Kahan B, Rowiński W. Intraoperative Blood Flow Measurements in Organ Allografts Can Predict Postoperative Function. Transplant Proc 2007; 39:371-2. [PMID: 17362732 DOI: 10.1016/j.transproceed.2007.01.046] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
A reliable method to recognize the extent of ischemia/reperfusion injury in transplantation is needed in order to tailor the immunosuppressive scheme to the needs of a damaged organ. This study sought to assess the correlation between the total and the parenchymal blood flow into a transplanted kidney (n = 71) or liver (n = 15) shortly after revascularization with the early function of the organ after transplantation. The total blood flow in the renal artery in kidney recipients or in the hepatic artery and portal vein in liver recipients was measured by an electromagnetic flowmeter. The parenchymal blood flow (in several parts of the transplanted organ) was assessed using a laser-Doppler flowmeter. Two measurements were always taken after revascularization (5 to 60 minutes apart). Vascular resistance (VR) as calculated by the difference between the mean arterial pressure (MAP) and the central venous pressure (CVP) was correlated with immediate kidney or liver function parameters. Neither total renal blood flow (RBF) nor VR was different between the immediate function (IF) and delayed graft function (DGF) groups of kidney transplant patients. However, the cortical (parenchymal) blood flow was significantly greater in the IF than the DGF group at 5 minutes: 29.98 +/- 6.13 mL/min/100 g vs 23.56 +/- 6.46 mL/min/100 g (P < .001). The difference was even more significant at 35 minutes: 33.94 +/- 7.47 mL/min/100 g vs 15.47 +/- 3.34 mL/min/100 g (P < .0001). Among liver transplant patients, the results suggested a correlation between hepatic arterial blood flow and early graft viability and function. The most reliable predictor of early graft function was the portal blood flow, which correlated with the volume of secreted bile as well as the bilirubin, and transaminase levels and coagulation profile. Further studies must confirm the value of measurements of total and parenchymal blood flow in organ transplant recipients.
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Affiliation(s)
- W Lisik
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
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Hubert T, Gmyr V, Arnalsteen L, Jany T, Triponez F, Caiazzo R, Vandewalle B, Vantyghem MC, Kerr-Conte J, Pattou F. Influence of Preservation Solution on Human Islet Isolation Outcome. Transplantation 2007; 83:270-6. [PMID: 17297400 DOI: 10.1097/01.tp.0000251723.97483.16] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The influence of the preservation solution used for in situ perfusion of the donor and pancreas storage on islet isolation has received little attention. METHODS In this prospective controlled trial, we compared the outcome of human islet isolation from pancreata perfused with University of Wisconsin (UW) solution or Celsior, an alternative colloid-free extracellular solution. RESULTS At the 1-year interim analysis, the viability and insulin secretion of islets isolated from donors perfused with UW (n=19) or Celsior (n=5) were identical. However, total islet recovery (IEQ) and isolation yield (IEQ/g) were 1.8-fold and 2.1-fold inferior in the Celsior group (P<0.05 vs. UW). Overall, 13 (68%) of islet preparations were effectively transplanted from the UW group vs. none from the Celsior group (P=0.01). The clinical study was discontinued and the causes of these differences were further explored in the pig (n=14). In contrast to UW, Celsior induced cell swelling and pancreas edema after only four hours of cold storage. These abnormalities were delayed when the donor was perfused with Solution de Conservation d'Organes et de Tissus (SCOT), an extracellular solution containing polyethylene glycol. CONCLUSIONS Our results suggest that colloid-free preservation solutions might be suboptimal for pancreas perfusion and cold storage prior to islet isolation and transplantation. Because pancreata are now frequently recovered for islet transplantation, preliminary experimental and clinical data about islet isolation should be obtained prior to the routine implementation of new preservation solutions for abdominal perfusion during multiorgan recovery.
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Affiliation(s)
- Thomas Hubert
- Inserm U859, Diabetes Cell Therapy, Faculty of Medicine, Lille 2 University, Lille, France
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