Mild hypothermia protects obese rats from fulminant hepatic necrosis induced by ischemia-reperfusion

BackgroundObese Zucker rats demonstrate increased susceptibility to hepatic ischemia–reperfusion injury. This study evaluates the effect of mild systemic hypothermia on ischemia-induced acute fulminant necrosis during warm ischemia and reperfusion, and investigates blood metabolic profiles under normothermic and mildly hypothermic conditions.MethodsThe left and median hepatic lobes of male, obese, Zucker rats were exposed to 75 minutes of ischemia under either normothermic (36.9 ± 0.3°C) or mildly hypothermic (33.3 ± 0.1°C) conditions followed by 8 hours of reperfusion. Animals were killed and tissue and blood were harvested for analysis of histology, liver enzymes, and metabolic 1H-NMR spectroscopy.ResultsLiver enzyme activities were significantly higher in the normothermic group when compared with mildly hypothermic animals. Histologic analysis showed greater than 75% necrosis in the normothermic group, whereas in the mildly hypothermic group necrosis was less than 25%. Blood from normothermic animals contained greater concentrations of lactate (190%, P = .001) and lower concentrations of glucose (60%, P = .01) than hypothermic animals; hepatic osmolyte betaine was also increased in blood from the normothermic group (220%, P = .0002). In addition, normothermic rats had increased concentrations of circulating fatty acids, triglycerides, glutamate, succinate, and acetate when compared with the hypothermic.ConclusionMild hypothermia decreased hepatic necrosis in obese rats. NMR blood profiles indicate that hypothermia protects hepatic metabolism.