Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines.
BACKGROUND
Prolonged hepatic warm ischemia during surgery remains a significant problem, particularly in the setting of liver resection and reduced remaining liver mass. The goal of the present study is to evaluate the effect of passive cooling caused by exposure to ambient conditions on hepatic injury in rats during warm ischemia followed by hepatectomy.


METHODS
The left and median lobes of male rats were exposed to 75 min of ischemia under either normothermic (37 degrees C) or mildly hypothermic (34 degrees C) conditions. After 75 min of ischemia, the right lobe was resected, leaving the animal with only the remaining ischemic lobes. Animals were allowed to survive indefinitely or sacrificed at 4 h after reperfusion for determination of injury and inflammatory gene expression.


RESULTS
Survival was already markedly higher in mildly hypothermic rats than normothermic rats at 24 h. Short passive cooling for the time course of the ischemic event significantly increased the hepatic induction of heat shock proteins 70 and 32 (both 3-fold versus normothermia, P<0.05) in response to ischemia/reperfusion whereas it significantly decreased the induction of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) in the liver. Biochemical markers of hepatic injury were significantly lower in the passive cooling group than in normothermic animals: aspartate aminotransferase (AST) serum concentrations were 9277+/-3461IU/L versus 15106+/-4104IU/L (P<0.01), and alanine aminotransferase (ALT) levels 5986+/-2246IU/L versus 9429+/-3643IU/L (P<0.01).


CONCLUSIONS
We demonstrated in a clinically relevant model of hepatic ischemia/reperfusion that mild hypothermia significantly reduces hepatic injury and improves survival.
Niemann
Claus U
CU
Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California 94143-0648, USA. niemannc@anesthesia.ucsf.edu
Xu
Fengyun
F
Choi
Soojinna
S
Behrends
Matthias
M
Park
Yeonho
Y
Hirose
Ryutaro
R
Maher
Jacquelyn J
JJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006498:Hepatectomy / Q000379:methods / Q000401:mortality; D007036:Hypothermia, Induced; D008099:Liver / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000517:prevention & control
D016207:Cytokines; D006360:Heat-Shock Proteins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3