Non-heart-beating donor porcine livers: The adverse effect of cooling

Reddy, Srikanth; Greenwood, Joanne; Maniakin, N; Bhattacharjya, Shantanu; Zilvetti, Miguel; Brockmann, Jens; James, Tim; Pigott, David; Friend, Peter J.

doi:10.1002/lt.20287

Cited by 83 publications

(83 citation statements)

References 13 publications

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“…In both situations the whole cascade of I/R injury will be activated without a conditioning or protective effect of MP. [33][34][35] Another limitation of our study is the ex situ reperfusion model. Although this model, which has also been used by other groups, 9,12,14,15 allowed us to assess viability and injury of hepatocytes and cholangiocytes, we did not confirm our findings in a transplantation model.…”

Section: Discussionmentioning

confidence: 99%

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Westerkamp

Mahboub²,

Meyer

et al. 2015

Liver Transpl

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A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation. Liver Transpl 21:1300-1311, 2015. V C 2015 AASLD.Received March 17, 2015; accepted June 8, 2015.Ischemic cholangiopathy, also known as nonanastomotic biliary strictures (NAS), is one of the most prevalent and troublesome complications after liver transplantation. During NAS formation, in particular, the large (extrahepatic) bile ducts become fibrotic and/or necrotic. Patients with NAS may suffer from recurrent jaundice and episodes of cholangitis, and retransplantation may be the only curative treatment. 1 The combination of ischemia and ischemia/ reperfusion (I/R) injury has been shown to be a major Additional supporting information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Westerkamp

Mahboub²,

Meyer

et al. 2015

Liver Transpl

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“…Therefore, organs from non heart beating donors (NHBD) can be suitable for transplantation, regardless of a worse first year graft survival outcome 1,2,4,9 . Contemporary aspects of organ donation after cardiac death have stimulated the development of experimental models aiming the improvement of preservation and organ dysfunction 2,6,7 .…”

Section: Introductionmentioning

confidence: 99%

Non heart beating organ donor: new experimental model in pigs

Morais¹,

Júnior²,

Moreno

et al. 2012

Acta Cir. Bras.

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PURPOSE:To describe technical aspects of a new experimental model that simulates a non heart beating organ donor. METHODS:Landrace pigs were operated on and cardiac arrest was obtained by means of myocardial infarction and interruption of ventilator support. RESULTS:Mean cardiac frequency, systolic and diastolic blood pressure levels, central venous pressure, oxygen saturation and concentration of expired CO 2 dropout occurred at seven minutes after cardiac arrest. CONCLUSION:The procedure was easily reproduced and a homogeneous circulatory failure could de obtained by the end of seven minutes. The model is suitable for further studies regarding abdominal organ transplantation.Key words: Transplantation. Models, Animal. Experimental Development. Heart Arrest. Swine. RESUMO OBJETIVO:Descrever os aspectos técnicos de um novo modelo experimental que simula um doador de órgãos após a parada cardíaca. MÉTODOS:Suínos da raça Landrace foram operados e a parada cardíaca foi obtida por meio de infarto do miocárdio e interrupção do suporte ventilatório. RESULTADOS:Freqüência cardíaca, pressão arterial sistólica e diastólica, pressão venosa central, saturação de oxigênio e concentração parcial de CO 2 são consistentes com falência hemodinâmica ao final de sete minutos. CONCLUSÕES:O procedimento foi facilmente executado e uma falência circulatória pode ser obtida ao final de sete minutos. Este modelo é adequado para estudos posteriores com respeito a preservação e tranplantes de órgãos abdominais.

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“…Therefore, ECD grafts have been associated with a higher risk of posttransplant complications such as primary graft nonfunction and chronic cholangiopathy. (1)(2)(3)(4) Machine perfusion has been investigated both as a preservation method to reduce IRI in ECD livers and as a method to assess the viability and function of suboptimal grafts prior to transplantation. (5)(6)(7) Currently, there are 3 variants of liver machine perfusion that are distinguished by the perfusate temperature: hypothermic, subnormothermic, and normothermic.…”

mentioning

confidence: 99%

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Banan¹,

Watson²,

Xu³

et al. 2016

Liver Transpl

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Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. The major limiting factor of using extended criteria donor (ECD) grafts is their greater susceptibility to injury during cold preservation and lower tolerance for ischemia/reperfusion injury (IRI) upon reperfusion. Therefore, ECD grafts have been associated with a higher risk of posttransplant complications such as primary graft nonfunction and chronic cholangiopathy.(1-4) Machine perfusion has been investigated both as a preservation method to reduce IRI in ECD livers and as a method to assess the viability and function of suboptimal grafts prior to transplantation.(5-7)Currently, there are 3 variants of liver machine perfusion that are distinguished by the perfusate temperature: hypothermic, subnormothermic, and normothermic.

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Non-heart-beating donor porcine livers: The adverse effect of cooling

Cited by 83 publications

References 13 publications

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Non heart beating organ donor: new experimental model in pigs

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

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