OXIDANT STRESS AND POTENTIATION OF ISCHEMIA REPERFUSION INJURY TO THEPERFUSED-RAT-LIVER BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES/

The accumulation and activation of polymorphonuclear leukocytes in the liver may play an important role in liver damage following ischemia a nd reperfusion. To study the effects of polymorphonuclear leukocytes o n hepatic function, human polymorphonuclear leukocytes were infused in to perfused rat livers. Infusion of polymorphonuclear leukocytes into continuously oxygenated livers led to an increased consumption of oxyg en by the perfused liver which paralleled the production of superoxide anion radicals by activated polymorphonuclear leukocytes. The increas ed use of oxygen was followed by a decrease in the sinusoidal efflux o f glutathione and a marked increase in the biliary excretion of glutat hione disulfide, indicating that polymorphonuclear leukocytes were act ivated within the liver, and created a potentially deleterious oxidant stress. When polymorphonuclear leukocytes were infused into rat liver s that had been subjected to 45 min of warm ischemia followed by reper fusion, the release of lactate dehydrogenase upon reperfusion of ische mic liver was significantly higher from livers exposed to polymorphonu clear leukocytes than from livers subjected to the same period of isch emia without leukocytes. This indicates that polymorphonuclear leukocy tes potentiate ischemia/reperfusion injury. The present in vitro syste m provides a model to study pharmacological interventions designed to modulate the potentially deleterious interactions of polymorphonuclear leukocytes with the liver. (C) Journal of Hepatology.