scholarly journals Cytochrome P450 2E1 Predicts Liver Retrieval from Donation After Circulatory Death Using Air-Ventilated Normothermic Machine Perfusion

2021 ◽  
Author(s):  
Ji-Hua Shi ◽  
Dong-Jing Yang ◽  
Qiang Jin ◽  
Nuo Cheng ◽  
Yuan-Bin Shi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Ex Vivo ◽  
Liver Perfusion ◽  
Molecular Networks ◽  
Machine Perfusion ◽  
Cytochrome P450 2E1 ◽  
Donation After Circulatory Death ◽  
Pparγ Agonist ◽  
Normothermic Machine Perfusion ◽  
Circulatory Death

Abstract The optimal oxygen concentration is unclear for normothermic machine perfusion (NMP) of livers from donation after circulatory death donors (DCD). Our purposes were to investigate the effect of air-ventilated NMP on liver retrieval from DCD rats, and to analyze the underlying mechanism. Normothermic liver perfusion was performed using the NMP system with either air ventilation or oxygen ventilation for 2h in the rat liver following warm ischemia and cold ischemia preservation. Proteomics and metabolomics were used to reveal the significant molecular networks. The bioinformation analysis was validated by administering peroxisome proliferator activator receptor-γ (PPARγ) antagonist and agonist via ex vivo perfusion circuit in the air-ventilated NMP. Results showed that air-ventilated NMP conferred a better functional retrieval and a less inflammatory response in the rat DCD liver; integrated proteomics and metabolomics analysis indicated that intrahepatic docosapentaenoic acid (DPA) downregulation and upregulation of cytochrome P450 2E1 (CYP2E1) expression and activity were associated with DCD liver retrieval with air-ventilated NMP; PPARγ antagonist worsened liver function under air-oxygenated NMP whereas PPARγ agonist played the opposite role. In conclusion, air-ventilated NMP confers a better liver retrieval from DCD rats through the DAP-PPARγ-CYP2E1 axis; CYP2E1 activity provides a biomarker of liver retrieval from DCD.

scholarly journals Twenty-four hour ex-vivo normothermic machine perfusion in rat livers

TECHNOLOGY ◽  
2020 ◽  
pp. 1-10
Author(s):  
Omar Haque ◽  
Casie A. Pendexter ◽  
Stephanie E.J. Cronin ◽  
Siavash Raigani ◽  
Reiner J. de Vries ◽  
...  
Keyword(s):  
Rat Liver ◽  
Ex Vivo ◽  
Liver Perfusion ◽  
Therapeutic Interventions ◽  
Liver Graft ◽  
Large Animal ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion ◽  
Organ Quality ◽  
Rat Livers

Ex-vivo liver perfusion (EVLP) is an ideal platform to study liver disease, therapeutic interventions, and pharmacokinetic properties of drugs without any patient risk. Rat livers are an ideal model for EVLP due to less organ quality variability, ease of hepatectomy, well-defined molecular pathways, and relatively low costs compared to large animal or human perfusions. However, the major limitation with rat liver normothermic machine perfusion (NMP) is maintaining physiologic liver function on an ex-vivo machine perfusion system. To address this need, our research demonstrates 24-hour EVLP in rats under normothermic conditions. Early (6 hour) perfusate transaminase levels and oxygen consumption of the liver graft are shown to be good markers of perfusion success and correlate with viable 24-hour post-perfusion histology. Finally, we address overcoming challenges in long-term rat liver perfusions such as rising intrahepatic pressures and contamination, and offer future directions necessary to build upon our work.

scholarly journals Normothermic Ex Vivo Machine Perfusion for Liver Grafts Recovered from Donors after Circulatory Death: A Systematic Review and Meta-Analysis

HPB Surgery ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jordan J. Nostedt ◽  
Daniel T. Skubleny ◽  
A. M. James Shapiro ◽  
Sandra Campbell ◽  
Darren H. Freed ◽  
...  
Keyword(s):  
Cold Storage ◽  
Meta Analysis ◽  
Mean Difference ◽  
Large Animal ◽  
Machine Perfusion ◽  
Donation After Circulatory Death ◽  
Economic Implications ◽  
Normothermic Perfusion ◽  
Normothermic Machine Perfusion ◽  
Circulatory Death

As a result of donation after circulatory death liver grafts’ poor tolerance to cold storage, there has been increasing research interest in normothermic machine perfusion. This study aims to systematically review the current literature comparing normothermic perfusion to cold storage in donation after circulatory death liver grafts and complete a meta-analysis of published large animal and human studies. A total of nine porcine studies comparing cold storage to normothermic machine perfusion for donation after circulatory death grafts were included for analysis. There was a significant reduction in AST (mean difference −2291 U/L, CI (−3019, −1563); P ≤ 0.00001) and ALT (mean difference −175 U/L, CI (−266, −85); P=0.0001), for normothermic perfusion relative to static cold storage, with moderate (I2 = 61%) and high (I2 = 96%) heterogeneity, respectively. Total bile production was also significantly higher (mean difference = 174 ml, CI (155, 193); P≤0.00001). Further research focusing on standardization, performance of this technology following periods of cold storage, economic implications, and clinical trial data focused on donation after circulatory death grafts will be helpful to advance this technology toward routine clinical utilization for these grafts.

Pushing the Limits in Donation After Circulatory Death Donor Selection: Optimizing Graft Rehabilitation With Ex Vivo Machine Perfusion

2020 ◽  
Vol 26 (10) ◽  
pp. 1368-1372
Author(s):  
Paolo Magistri ◽  
Tiziana Olivieri ◽  
Cristiano Guidetti ◽  
Gian Piero Guerrini ◽  
Vanni Agnoletti ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Donor Selection ◽  
Machine Perfusion ◽  
Donation After Circulatory Death ◽  
Circulatory Death

scholarly journals Donation after Circulatory Death in Paediatric Liver Transplantation: Current Status and Future Perspectives in the Machine Perfusion Era

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Roberta Angelico ◽  
M. Thamara P. R. Perera ◽  
Tommaso Maria Manzia ◽  
Alessandro Parente ◽  
Chiara Grimaldi ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Perfusion ◽  
Current Status ◽  
Machine Perfusion ◽  
Donation After Circulatory Death ◽  
Future Perspectives ◽  
Donor Pool ◽  
Donor Support ◽  
Paediatric Liver Transplantation ◽  
Circulatory Death

Efforts have been made by the transplant community to expand the deceased donor pool in paediatric liver transplantation (LT). The growing experience on donation after circulatory death (DCD) for adult LT has encouraged its use also in children, albeit in selective cases, opening new perspectives for paediatric patients. Even though there has recently been a slight increase in the number of DCD livers transplanted in children, with satisfactory graft and patient outcomes, the use of DCD grafts in paediatric recipients is still controversial due to morbid outcomes associated with DCD grafts. In this context, recent advances in the optimization of donor support by extracorporeal membrane oxygenation and in the graft preservation by liver machine perfusion could find application in order to expand the donor pool in paediatric LT. In the present study we review the current literature on DCD liver grafts transplanted in children and on the use of extracorporeal donor support and liver perfusion machines in paediatrics, with the aim of defining the current status and future perspectives of paediatric LT.

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