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

Surgery. 2006 Sep;140(3):404-12. doi: 10.1016/j.surg.2006.01.021. Epub 2006 Jul 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Blood Glucose / analysis
  • Hypothermia, Induced*
  • Lactates / blood
  • Liver / enzymology
  • Liver / pathology
  • Liver / physiopathology
  • Liver Failure, Acute / etiology*
  • Liver Failure, Acute / pathology
  • Liver Failure, Acute / prevention & control*
  • Male
  • Necrosis
  • Obesity / physiopathology*
  • Rats
  • Rats, Zucker
  • Reperfusion Injury / complications*
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control

Substances

  • Blood Glucose
  • Lactates
  • Aspartate Aminotransferases
  • Alanine Transaminase