Warm ischemia and reperfusion injury in diet-induced canine fatty livers

Background Fatty liver is associated with primary nonfunction after liver t ransplantation, contributing a shortage of suitable liver grafts. Because e xtensive investigation of mechanisms underlying such non-function has been limited largely to rodents, we made a new fatty liver model in dogs and stu died primary nonfunction after warm ischemia. Methods. We developed a diet rich in fat but deficient in choline to induce fatty change in canine liver and investigated effects of 60 min of warm is chemia and reperfusion in dogs with such fatty livers, Results. Microscopically evident steatosis increased with duration of dieta ry manipulation (up to12 weeks), as did hepatic total lipid and triglycerid e levels. No dog with >30% of steatotic hepatocytes, >445 mg/g hepatic tota l lipid or >145 mg/g hepatic triglyceride survived after 60 min of warm isc hemia. Arterial ketone body ratios decreased and blood endotoxin increased after reperfusion in nonsurvivors, The main histologic finding in fivers of nonsurvivors was marked sinusoidal congestion. Conclusions. Damage to hepatocytes and nonparenchymal cells after warm isch emia and reperfusion was thought 60 be closely related to sinusoidal microc irculatory disturbances in fatty livers. The canine fatty liver model repor ted here may be useful in studying the pathology of primary nonfunction and in establishing criteria for allowable degrees of fatty change in potentia l liver grafts.