Short Passive Cooling Protects Rats During Hepatectomy by Inducing Heat Shock Proteins and Limiting the Induction of Pro-Inflammatory Cytokines

Niemann, Claus U.; Xu, Fengyun; Choi, Soojinna; Behrends, Matthias; Park, Yeonho; Hirose, Ryutaro; Maher, Jacquelyn J.

doi:10.1016/j.jss.2008.08.030

« Previous Next »Journal of Surgical Research
Volume 158, Issue 1 , Pages 43-52, January 2010

Short Passive Cooling Protects Rats During Hepatectomy by Inducing Heat Shock Proteins and Limiting the Induction of Pro-Inflammatory Cytokines

Claus U. Niemann, M.D.
- Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California
- Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, California
- To whom correspondence and reprint requests should be addressed at Department of Anesthesia and Perioperative Care and Surgery, University of California at San Francisco, 521 Parnassus Avenue, C 450, San Francisco, CA 94143-0648.
Fengyun Xu, Ph.D.
- Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, California
Soojinna Choi, M.D.
- Chonnam National University Medical School, Gwangju, Korea
Matthias Behrends, M.D.
- Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California
Yeonho Park, M.D.
- Department of Surgery, Gachon Medical School, Gil Medical Center, Incheon, Korea
Ryutaro Hirose, M.D.
- Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, California
Jacquelyn J. Maher, M.D.
- Rice Liver Center Laboratory and Department of Medicine, University of California, San Francisco, California

Received 19 May 2008 published online 16 October 2008.

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°C) or mildly hypothermic (34°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-α (TNF-α) 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).

Conclusion

We demonstrated in a clinically relevant model of hepatic ischemia/reperfusion that mild hypothermia significantly reduces hepatic injury and improves survival.

Key Words: warm ischemia, rats, hypothermic preconditioning, hepatectomy, hepatic injury, survival