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  • Title: Mechanisms of hypothermic protection against ischemic liver injury in mice.
    Author: Kato A, Singh S, McLeish KR, Edwards MJ, Lentsch AB.
    Journal: Am J Physiol Gastrointest Liver Physiol; 2002 Apr; 282(4):G608-16. PubMed ID: 11897619.
    Abstract:
    Hepatic hypothermia can safely prolong the duration of hepatic inflow occlusion during complex liver resectional surgeries. The mechanism(s) by which hypothermia protects against this form of liver ischemia-reperfusion injury are not completely understood. In this study, we sought to determine whether hypothermia protects against ischemia-reperfusion injury by altering the hepatic inflammatory response. Mice undergoing 90 min of partial hepatic ischemia followed by up to 8 h of reperfusion had their body temperatures regulated at 35-37 degrees C (normothermic) or unregulated, in which rectal temperature dropped as low as 25 degrees C by the end of ischemia (hypothermic). Hypothermic mice had less liver injury vs. normothermic mice, as assessed histologically, by serum transaminase levels (89% decrease), and by liver wet-to-dry weight ratios (91% decrease). Neutrophil accumulation was absent in hypothermic mice (99% reduction vs. normothermic mice). Production of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and macrophage inflammatory protein-2 were reduced by up to 92%. Activation of the transcription factor nuclear factor-kappa B was not reduced in hypothermic mice, but activation of c-Jun NH(2)-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 were greatly diminished. These data suggest that hypothermia suppresses the hepatic inflammatory response through selective inhibition of JNK and AP-1.
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