| Project/Area Number |
06671176
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
SAWA Masayuki Asahikawa Medical College, Assistant, 医学部, 助手 (70226059)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Tetsu Asahikawa Medical College, Assistant Professor, 医学部, 講師 (50125415)
KASAI Shinichi Asahikawa Medical College, Associate Professor, 医学部, 助教授 (40091566)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Liver Transplantation / Warm ischemia / Procurement / DBcAMP |
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| Research Abstract |
Recent increasing frequency of organ transplantation has caused severe shortage of donor organ from heart-beating cadavers. Organ donation from nonheart-beating cadavers has been attempted to recover these situation, however, it involves a prolonged period of warm ischemia, which causes first functional impairment, then to structural changes, and ultimately to cell death. Dibutyryl cAMP (DBcAMP) has a high membrane permeability, and maintenance of the intracellular cAMP concentration may improve the viability of organs. In this study, the effect of DBcAMP pretreatment on warm ischemic injury of rat livers was evaluated. Warm ischemic liver injury was induced in adult Wistar rats weighing 250-280 g by leaving them at room temperature (22-25ﾟC) after cardiac arrest. The hepatic cAMP concentration, %ATP,and trypan blue-positive nuclear ratio were determined after different durations of warm ischemia. In addition, transaminase and endothelin (ET-1) release into the perfusate were examined during 60 min of isolated liver perfusion with Krebs-Henseleit solution. The optimal dose and time of DBcAMP pretreatment were determined to be 15 mg/kg and 60 min prior to warm ischemia, respectively. Data on the trypan blue-positive nuclear ratio, and the release of transaminases and ET-1 revealed that warm ischemia first damaged the endothelial cells and then the hepatocytes. DBcAMP pretreatment appeared to protect the liver from warm ischemic injury by increasing the intracellular cAMP concentration and stabilizing the cell membranes of endothelial cells and hepatocytes.
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