Anti-apoptotic treatment of warm ischemic male rat livers in machine perfusion improves symptoms of ischemia-reperfusion injury

Abstract

Abstract Liver donation after cardiac death (DCD) makes up a small percentage of the donor pool and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis at the cellular level. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia. Livers procured from male lewis rats were subjected to 90 minutes of warm ischemia, followed by 6 hours of NMP where they were treated with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives. The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular functions associated with the hepatic parenchyma, biliary epithelium and especially the sinusoidal endothelium. This study’s findings provide useful insight for further investigation of the extent of apoptotic contribution to ischemia reperfusion injury (IRI).