Mild hypothermia reduces the inflammatory response and hepatic ischemia/reperfusion injury in rats.
OBJECTIVE
Hypothermia is known to protect against ischemia/reperfusion (I/R) injury. The mechanisms of protection are incompletely understood and a temperature threshold for protection has not been established.


METHODS
In anesthetized Wistar rats, partial (70%) hepatic ischemia was applied for 45 min. Three study groups were used. Group T31 (n = 6) spontaneously cooled to 31.3 +/- 0.8 degrees C, while group T34 (n = 6) spontaneously cooled to 34 degrees C and was then maintained at 34.0 +/- 0.1 degrees C using a heat lamp. The normothermic group (T37, n = 6) was maintained at 37.1 +/- 0.3 degrees C. Hepatic injury, inflammation, lipid peroxidation and metabolic function (using quantitative 1H-NMR) were assessed 24 h after reperfusion.


RESULTS
At 24 h following reperfusion, alanine aminotransferase and aspartate aminotransferase increased to 5101 +/- 2378 and 6409 +/- 4202 U/l in the normothermic T37 group (P < 0.05 vs. T34 and T31), whereas transaminases in hypothermic groups (T31 and T34) were significantly lower. Severe liver necrosis was only noted with T37. Myeloperoxidase activity was increased in the T37 group when compared with hypothermic groups (223 +/- 161 (T37) vs. 16 +/- 10 (T31) and 8 +/- 5 (T34) mU/min/mg of tissue, P<0.05 vs. T31 and T34). 1H-NMR analysis of the blood of normothermic animals revealed metabolic changes consistent with increased ischemic injury, which was almost completely ameliorated in T34 and T31 groups.


CONCLUSIONS
Mild hypothermia of 34 degrees C is sufficient to reduce I/R injury by inhibiting the inflammatory response. Further spontaneous cooling to 31 degrees C did not demonstrate any additional protective effect.
Behrends
Matthias
M
Department of Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco, CA 94143-0648, USA. behrendsm@anesthesia.ucsf.edu
Hirose
Ryutaro
R
Serkova
Natalie J
NJ
Coatney
John L
JL
Bedolli
Melanie
M
Yardi
Jason
J
Park
Yeon Ho
YH
Niemann
Claus U
CU
D000818:Animals; D007036:Hypothermia, Induced; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*