Ischemia-reperfusion injury in rat fatty liver: Role of nutritional status

Fatty livers are more sensitive to the deleterious effects of ischemia-repe rfusion than normal livers. Nutritional status greatly modulates this injur y in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats w ith normal or fatty liver induced by a choline deficient diet underwent 1 h our of lobar ischemia and reperfusion. Rat survival was determined for 7 da ys. Serum transaminases, liver histology and cell ultrastructure were asses sed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion, Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced surviva l in rats with fatty liver (14% vs. 64%, P <.01), Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. M itochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survi val to 45%. These data indicate that rat fatty livers exposed to normotherm ic ischemia-reperfusion injury are much more sensitive to fasting than hist ologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion proc edure may be part of a treatment strategy aimed to prevent ischemia-reperfu sion injury in fatty livers.