The effect of antagonism of adenosine A1 receptor against ischemia and reperfusion injury of the liver
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概要
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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.
- Elsevierの論文
- 2007-05-01
著者
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Todo Satoru
First Department Of Surgery Hokkaido University Hospital
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Todo Satoru
Department Of First Surgery Hokkaido University Graduate School Of Medicine
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Todo Satoru
University Of Pittsburgh
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Furukawa Hiroyuki
First Department Of Surgery Hokkaido University Hospital
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Shimamura Tsuyoshi
First Department Of Surgery Hokkaido University Hospital
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Shimamura Tsuyoshi
University Of Pittsburgh
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FUKAI Moto
Department of Molecular Surgery, Hokkaido University School of Medicine
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Fukai Moto
Department Of Molecular Surgery Hokkaido University School Of Medicine
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Todo S
Department Of General Surgery Hokkaido University
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Todo Satoru
Department Of Pediatric Surgery First Surgery Endoscopy And Pathology Hokkaido University School Of
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Todo Satoru
Division Of Cardiovascular Surgery Jichi Medical University
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Taniguchi Masahiko
Department Of Organ Transplantation And Regenerative Medicine Hokkaido University School Of Medicine
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Suzuki Tomomi
Department Of Organ Transplantation And Regenerative Medicine Hokkaido University School Of Medicine
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Shimamura Tsuyoshi
First Department Of Surgery Hokkaido University School Of Medicine
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