2002 Fiscal Year Final Research Report Summary
Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats
| Project/Area Number |
13671295
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
NAKAMURA Satoshi Hamamatsu University School of Medicine Second Dept. of Surgery, Professor, 医学部, 教授 (00090027)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Shohachi Hamamatsu University School of Medicine University Hospital, Assistant Professor, 医学部附属病院, 講師 (20196827)
YOKOI Yoshihiro Hamamatsu University School of Medicine University Hospital, Instructor, 医学部附属病院, 助手 (80313956)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Endothelin-1 / Liver cirrhosis / Hepatectomy / Microcirculation / Ischemia / Pringle's maneuver / Reperfusion injury / Time-resolved spectroscopy |
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| Research Abstract |
Endothelin (ET)-1 contributes to hepatic ischemia and reperfusion (HIR) injury in normal liver. This study was conducted to clarify the role of ET-1 in HIR injury in cirrhotic state. Hepatic ET-1 levels in cirrhotic rats were significantly higher than those in non-cirrhotic rats. Plasma and hepatic ET-1 levels at 1, 3 and 6 hours of reperfusion animals subjected to intermittent hepatic ischemia, the elevation of plasma AST levels at 1, 3 and 6 hours of reperfusion and the decline in hepatic SO2 at the end of 60-minute hepatic ischemia and after reperfusion were significantly suppressed when compared to those subjected to continuous hepatic ischemia. Pretreatment with a non-selective endothelin receptor antagonist in continuous hepatic ischemia significantly ameliorated plasma AST levels and hepatic SO2 values with less hepatic sinusoidal congestion, resulting in an improvement in the 7-day survival rate. Continuous hepatic ischemia in the cirrhotic liver has disadvantages relating to microcirculatory derrangement with more ET-1 production in partial hepatectomy. In liver surgery, pharmacological regulation of ET-1 production may lead to attenuation of reperfusion injuries for ischemically damaged cirrhotic liver.
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[Publications] Tsuchiya, Y., Suzuki, S., Inaba, K., Sakaguchi, T., Baba, S., Miwa, M., Konno, H., Nakamura, S.: "Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats."J.Surg.Res.. (in press).
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