THE POSSIBILITY OF RESUSCITATING LIVERS AFTER WARM ISCHEMIC-INJURY

The number of clinical liver transplants that can be performed is limi ted by the availability of suitable donor organs. If it were possible to harvest and use livers after cardiac arrest, the supply could be im proved. The mechanisms of damage in warm ischemia are not yet well und erstood and the consequences of transplanting a liver that is unable t o provide immediate life-support are unacceptable. This study aims to identify areas for more detailed study in an attempt to improve the qu ality of livers harvested after significant warm ischemia, and to sele ct acceptable organs for transplantation. Porcine livers were subjecte d to 75 min of warm ischemia and then perfused at 37-degrees-C for 3 h r, during which period biochemical monitoring was carried out. At the end of the perfusion, histological and transmission electron microscop ical studies were made. Large amounts of the intracellular enzymes ALT , AST, and LDH were released into the perfusate during the first 30 mi n of perfusion, but this-and the further amounts released during the s ubsequent 2.5 hr-was influenced by the composition of the perfusate. T he inclusion of the substrates fructose and oleate, plus amino acids, substantially reduced this release and also improved the ability of th e livers to metabolize ammonia. Oxygen free-radical scavengers had a s ignificant, but smaller, beneficial effect. Electron microscopy confir med the value of perfusion in improving cell morphology, and the addit ional value of including metabolic substrates. This study shows that h epatocellular structure and function can be improved by appropriate pe rfusion methods that also provide a simple means of monitoring some im portant functions. Both metabolic support and neutralization of oxygen free-radical action have a role to play in this approach to rendering ischemically injured livers acceptable for clinical use.