The effects of various organ preservation solutions on hepatocyte membranepotentials, intracellular calcium concentrations, and outcome following liver transplantation

BACKGROUND: Hepatocyte membrane potential differences (PDs) may be altered by the preservation solutions used in liver transplantation. Such alteratio ns could impact on the survival of the donor liver, extent of biochemical i njury, and flux of important ionic compounds, The purpose of the present st udy was to document these outcomes in the presence of four different presen tation solutions. METHODS: Livers of adult male Sprague-Dawley rats (N = 3 to 4 per group) we re impaled with intracellular microelectrodes prior to and at various time periods for 6 hours following complete hepatic resection, Just prior to res ection, each liver was perfused with preservation solutions associated with high (normal saline [NS]), moderate (Euro-Collins [EC]), and low (Universi ty of Wisconsin solution [UW]) risks of reperfusion injury. RESULTS: Baseline (in situ) PDs were similar in all groups (-37 +/- 4 mV, m ean +/- SD). Ten minutes postresection, hepatic PDs were as follows: NS, -2 3.8 +/- 3.5 mV; EC, -11.4 +/- 0.4 mV; and UW, -8.7 +/- 0.3 mV (P <0.01 for all groups). Maximum depolarization occurred at 6 hours postresection (NS, -8.1 +/- 1.1 mV; EC, -7.7 +/- 1.3 mV; and UW, -8.6 +/- 1.0 mV), To determin e whether these changes are of pathophysiologic importance, the NS solution was modified (addition of 0.1% ethanol) to achieve similar PD changes as t hose observed with UW. Liver transplants were then performed where the dono r livers had been perfused and preserved for 6 hours with either NS or the modified NS (MNS) solution. Posttransplant (10 day) survival was 1 of 6 (17 %) in the NS group and 4 of 6 (67%) in the MNS group (P <0.05), Regarding t he effects of PD changes on ionic flux, intracellular calcium levels were d ocumented for up to 4 hours by fluorescence video microscopy using Fura-a i n isolated hepatocytes exposed to NS, UW, and MNS solutions. Intracellular calcium levels were similar in all solutions at each time point studied. CONCLUSIONS: The results of this study indicate that hepatocytes undergo pr ompt and marked depolarization following hepatic resection, and the extent of the depolarization correlates with survival following transplantation. A m J Surg. 2000;179:154-160. (C) 2000 by Excerpta Medica, Inc.