| Project/Area Number |
06454613
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | HOKKAIDO KALLEGE OF PHARMACY |
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Principal Investigator |
ICHIHARA Kazuo HOKKAIDO COLLEGE OF PHARMACY,DEPARTMENT OF PHARMACOLOGY,PROFESSOR, 薬学部, 教授 (20041832)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Kumi HOKKAIDO COLLEGE OF PHARMACY,DEPARTMENT OF PHARMACOLOGY,RESEARCH ASSISTANT, 薬学部, 助手 (00235334)
NAKAI Tohru HOKKAIDO COLLEGE OF PHARMACY,DEPARTMENT OF PHARMACOLOGY,RESEARCH ASSISTANT, 薬学部, 助手 (40237201)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Ischemic myocardium / Failing heart / Liposome / Adenine nucleotides / 8-Bromo-AMP / OG-VI / アデニンヌクレオチド / 心筋虚血 / エネルギー代謝 |
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| Research Abstract |
High-energy phosphate depletion due to ischemia may cause myocardial mechanical dysfunction during ischemia and reperfusion. It is well known that creatine phosphate (CP) content which has been lowered by brief ischemia can be completely restored or restored beyond the preischemic level during reperfusion. This result indicates that the mitochondria can produce enough ATP to restore or elevate CP after reperfusion, although the total ATP content is still low. We speculate that loss of adenine nucleotides during ischemia may occur from the ADP store near the contractile elements. We have tested several agents as energy ameliorants to fill ADP stores with ADP during ischemia and reperfusion. The candidates for energy ameliorants are 1) some precursors of adenine nucleotide, such as adenosine, inosine, AICAr and OG-VI ; 2) membrane permeable adenine nucleotide analogues, such as tributyryl-AMP and 8-bromo-AMP ; and 3) liposome-entrapped adenine nucleotides. Some of these agents may protect the myocardium against ischemic/reperfused damage through restoration of ADP where it is required in the cell.
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