EFFECTS OF DIFFERENT COLD PRESERVATION SOLUTIONS ON RESTORATION OF HEPATIC ENERGY-METABOLISM DURING COLD REPERFUSION

Rat livers were flushed with different preservation solutions and stor ed at 4 degrees C for 24 h before being reperfused with a synthetic ai r-equilibrated, water-based solution. Four solutions were tested using this isolated rat liver model: Marshall's hypertonic citrate (HC); mo dified University of Wisconsin solution (Mod UW); a histidine based so lution (HIS); and a histidine-lactobionate-raffinose-based solution (H LR). After storage, livers were perfused at 4 degrees C for a period o f 2 h and biopsy samples taken, at different time points, to investiga te energy metabolism. Livers stored in HLR and HIS had higher 24-h sto rage levels of ATP (0.41 and 0.24 mu mol/g respectively; P < 0.05) tha n those stored in Mod UW and HC. On reperfusion, all groups regenerate d ATP by 1-2 h. However, significantly greater levels of ATP regenerat ion occurred in livers stored in the HLR (1.6 +/- 0.08 mu mol/g) and M od UW (1.3 +/- 0.18) than HC (0.58 +/- 0.19) and HIS (0.96 +/- 0.12); P < 0.05. Energy charge (1) (EC) recovered in all groups but was signi ficantly higher in HLR and Mod UW (0.79 and 0.68, respectively; P < 0. 05) than HC and HIS. These represent 95% (HLR) and 80% (Mod UW) of val ues observed in FIL. During the reperfusion period, total adenine nucl eotide levels CTA) did not vary significantly within each storage grou p, except in the HIS solution. However, TAs were greater with livers s tored for 24 h in HLR (2.5 +/- 0.25) and Mod UW (2.7 +/- 0.20) than th ose the other two storage groups (P < 0.05 in each case). This study h as demonstrated that it was possible to resuscitate liver energetics a fter prolonged hypothermic ischemia by a period of cold reperfusion, a nd the method can differentiate between preservation solutions. The li vers stored in each solution showed varying degrees of success in rege neration of ATP and EC, demonstrating that oxygen was not a limiting f actor when using an air-equilibrated perfusate. The solutions providin g the better preservation conditions gave the greater resuscitation of liver energetics (Mod UW and HLR). Overall, livers stored in HLR had the greatest resuscitation of energy metabolism, which correlates with survival data from other studies (29-31, 33). (C) 1996 Academic Press , Inc.