Novel First Report - Extended Normothermic Machine Perfusion (E-NMP) Achieves Recovery of ECD Livers Not Obtained by Short Duration NMP

Abstract

Introduction: Normothermic machine perfusion (NMP) for a few hours successfully assesses functionality of extended criteria (ECD) livers. Lactate of<2.5mmol/L, and appropriate vascular flows in first 4hrs of NMP have been suggested as markers of functionality (VITTAL study). However, liver cell cycle initiation occurs at 12-24hrs and cell recovery, proliferation peaks at∼40–48hrs. Extended NMP is a novel concept with sporadic reporting but has not been used to rehabilitate ECD livers that do not achieve early markers of function. Methods: Five discarded ECD human livers were obtained. All 5 organs had cold ischemia times>10hrs. Machine perfusion was started at 1250rpms and gradually titrated to achieve physiological pressures in artery and vein. Flow, pressure and resistance parameters were recorded. Lactate was serially measured. Biopsy of the liver was repeated daily and stained with H&E, Ki67 and TUNEL staining. Results: Organ cold times, lactate levels, flows, pressures and duration of NMP are noted in Table below. Lactate reduction was identified in four out of five livers. With lactate reduction taking a mean of over 14 hrs (below) and being associated with a serial reduction in apoptosis and cellular congestion. Apoptosis reduced at 2hrs, >24hrs,>48hrshrs of NMP from 76+/-40% to 17+/-14% to 15+/-16%. Cellular congestion showed a similar trend. Conclusions: These data show that extended normothermic machine perfusion is associated with cellular recovery and lactate clearance with recovery of vascular flows. Therefore, we conclude that Extended NMP can be used to rehabilitate ECD liver that would not meet early functionality on short duration NMP.