The Effect of Antagonism of Adenosine A1 Receptor Against Ischemia and Reperfusion Injury of the Liver

Magata, Shinichiro; Taniguchi, Masahiko; Suzuki, Tomomi; Shimamura, Tsuyoshi; Fukai, Moto; Furukawa, Hiroyuki; Fujita, Miri; Todo, Satoru

doi:10.1016/j.jss.2006.09.021

« Previous Next »Journal of Surgical Research
Volume 139, Issue 1 , Pages 7-14, 1 May 2007

The Effect of Antagonism of Adenosine A1 Receptor Against Ischemia and Reperfusion Injury of the Liver

Shinichiro Magata, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- To whom correspondence and reprint requests should be addressed at Department of Surgery, Hokkaido University, Hokkaido, Japan.
Masahiko Taniguchi, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Tomomi Suzuki, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Tsuyoshi Shimamura, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Moto Fukai, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Hiroyuki Furukawa, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Miri Fujita, M.D.
- Department of Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Satoru Todo, M.D.
- Department of Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

Received 11 November 2005 published online 09 March 2007.

Background

Adenosine is known to exert protective roles in hepatic ischemia and reperfusion injury, while all adenosine receptors do not play the cytoprotective roles. We have tested our hypothesis that blockage of adenosine binding to A₁ receptor by its antagonist, KW3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] attenuates hepatic ischemia-reperfusion injury.

Methods

Adult female beagle dogs underwent a 2 h total hepatic vascular exclusion (THVE) with a venovenous bypass. Nontreated animals that underwent THVE with a venovenous bypass alone were used as the control (Group CT, n = 6). KW3902 was given to the animals by continuous intraportal infusion for 60 min before ischemia at a dose of 1μg/kg/min (Group KW, n = 6). Two wk survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, energy metabolism, cAMP concentration, and histopathological findings were studied.

Results

Two wk animal survival was significantly improved in group KW compared with that in group CT (group CT: 16.7% versus group KW: 83.3%). HTBF, liver function, and hepatic adenine nucleotide concentration were remarkably better in group KW than group CT. In addition, cAMP concentration in group KW was maintained significantly higher than group CT. Histopathological examination revealed preservation of hepatic architecture and suppression of neutrophil infiltration into hepatic tissue in group KW.

Conclusion

Administration of adenosine A₁ receptor antagonist before ischemia attenuates hepatic ischemia-reperfusion injury. To elicit the beneficial effect of adenosine against ischemia and reperfusion injury of the liver, it is important to oppose adenosine A1 receptor activation.

Key Words: liver, ischemia and reperfusion injury, adenosine, adenosine A₁ receptor antagonist, KW3902, dog