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Updated: Jul 20, 2026
Short-Duration Hypothermia Induction in Rats using Models for Studies examining Clinical Relevance and Mechanisms
Published on: March 3, 2021
Mild hypothermia protects obese rats from fulminant hepatic necrosis induced by ischemia-reperfusion
Claus U Niemann1, Soojinna Choi, Matthias Behrends
1Anesthesia and Perioperative Care, Division of Liver Transplantation, University of California San Francisco, San Francisco, CA 94143-0648, USA. niemannc@anesthesia.ucsf.edu
Background:
Obese 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.
Methods:
The left and median hepatic lobes of male, obese, Zucker rats were exposed to 75 minutes of ischemia under either normothermic (36.9 +/- 0.3 degrees C) or mildly hypothermic (33.3 +/- 0.1 degrees 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.
Results:
Liver 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.
Conclusion:
Mild hypothermia decreased hepatic necrosis in obese rats. NMR blood profiles indicate that hypothermia protects hepatic metabolism.
