Subnormothermic Machine Perfusion at Both 20°C and 30°C Recovers Ischemic Rat Livers for Successful Transplantation

Abstract

Background Utilizing livers from donors after cardiac death could significantly expand the donor pool. We have previously shown that normothermic (37°C) extracorporeal liver perfusion significantly improves transplantation outcomes of ischemic rat livers. Here we investigate whether recovery of ischemic livers is possible using sub-normothermic machine perfusion at 20°C and 30°C. Methods Livers from male Lewis rats were divided into five groups after 1 h of warm ischemia (WI): (1) WI only, (2) 5 h of static cold storage (SCS), or 5 h of MP at (3) 20°C, (4) 30°C, and (5) 37°C. Long-term graft performance was evaluated for 28 d post-transplantation. Acute graft performance was evaluated during a 2 h normothermic sanguineous reperfusion ex vivo. Fresh livers with 5 h of SCS were positive transplant controls while fresh livers were positive reperfusion controls. Results Following machine perfusion (MP) (Groups 3, 4, and 5), ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 100% survival (N ≥ 4) after 4 wk. On the other hand, animals from WI only, or WI + SCS groups all died within 24 h of transplantation. Fresh livers preserved using SCS had the highest alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the lowest bile production during reperfusion, while at 28 d post-transplantation, livers preserved at 20°C and 30°C had the highest total bilirubin values. Conclusions MP at both 20°C and 30°C eliminated temperature control in perfusion systems and recovered ischemically damaged rat livers. Postoperatively, low transaminases suggest a beneficial effect of subnormothermic perfusion, while rising total bilirubin levels suggest inadequate prevention of ischemia- or hypothermia-induced biliary damage.

Technique of Subnormothermic <em>Ex Vivo</em> Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts

“…At the same time, it provides a decreased oxygen demand in comparison to normothermic perfusion settings which provides additional safety against ischemic injury. In general, perfusion temperatures above 30 °C have shown to minimize cold ischemic injury and provide sufficient metabolic activity 31 .…”

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

“…5,6 Although recent data from animal models and (discarded) human donor livers have provided promising results suggesting that endischemic MP has relevant protective effects on the bile ducts of donation after cardiac death (DCD) liver grafts, the most optimal perfusion temperature during end-ischemic MP has not been investigated. [7][8][9][10][11][12][13][14][15][16][17] The aim of this study was, therefore, to assess the optimal perfusion temperature during end-ischemic oxygenated MP for protection of the large bile ducts against I/R injury in a DCD rat liver model.…”

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“…66 Likewise, several other groups have suggested that subnormothermic machine perfusion can recover and allow transplant of ischemic livers with promising results. 64,67 Notably, successful preservation of rat livers for up to 4 days can be achieved using supercooling and subsequent subnormothermic machine perfusion. 68 This method has the potential to prolong transport of DCD livers by 3-to 4-fold.…”