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


CONCLUSIONS
Mild hypothermia decreased hepatic necrosis in obese rats. NMR blood profiles indicate that hypothermia protects hepatic metabolism.
Niemann
Claus U
CU
Anesthesia and Perioperative Care, Division of Liver Transplantation, University of California San Francisco, San Francisco, CA 94143-0648, USA. niemannc@anesthesia.ucsf.edu
Choi
Soojinna
S
Behrends
Matthias
M
Hirose
Ryutaro
R
Noh
Joonhwa
J
Coatney
John L
JL
Roberts
John P
JP
Serkova
Natalie J
NJ
Maher
Jacquelyn J
JJ
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D007036:Hypothermia, Induced; D007773:Lactates / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control
D001786:Blood Glucose; D007773:Lactates; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase