Mild Hypothermia Provides Significant Protection Against Ischemia/Reperfusion Injury in Livers of Obese and Lean Rats

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Abstract
To evaluate the effect of anesthesia induced mild systemic hypothermia on hepatic injury in lean and obese rats during warm ischemia. Hepatic warm ischemia during surgery remains a significant problem, particularly in organs with presumed baseline dysfunction. The left and median lobes of male lean and obese Zucker rats were exposed to 75 minutes of ischemia under either mild hypothermic or normothermic conditions. After 75 minutes of ischemia, the organs were reperfused and animals were observed for 24 hours. Surviving animals were killed and blood and tissue was harvested to determine liver enzymes and examine the histology. Mild hypothermia significantly decreased hepatocellular injury in both lean and obese rats. Biochemical markers of hepatic injury were significantly reduced in hypothermic groups (P < 0.01). Survival in normo- and hypothermic lean groups were not different at 24 hours of reperfusion. However, hypothermia profoundly increased survival in obese rats when compared with normothermic obese rats (100% versus 20%, P < 0.01). Necrosis was more pronounced in both normothermic lean and obese animals who experienced more than >75% necrosis when compared with hypothermic animals. In contrast, mild hypothermia reduced necrosis in lean rats to less than 25% and in obese rats to less than 50%. We demonstrated in a clinically relevant model that mild hypothermia significantly reduces hepatic injury in a warm ischemia model in lean and obese rats and significantly improved 24-hour survival in obese rats.