| Project/Area Number |
07670814
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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 |
Circulatory organs internal medicine
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| Research Institution | The First Department of Internal Medicine, Nippon Medical School |
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Principal Investigator |
IBUKI Chikao Nippon Medical School ; The First Department of Internal Medicine ; Research Fellow, 医学部, 助手 (80193639)
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| Co-Investigator(Kenkyū-buntansha) |
KUSAMA Yoshiki Nippon Medical School ; The First Department of Internal Medicine ; Research Fel, 医学部, 助手 (40169983)
HOSHINO Kimihiko Nippon Medical School ; The First Department of Internal Medicine ; Research Fel, 医学部, 助手 (00238734)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | ischemia / reperfusion / preconditioning / angiotensin / arrhythmia / contractile dysfunction / myocardium / arrhythmia / contractile dycfunction / 再灌流不整脈 / 細胞内pH / Na^+ / H^+交換系 / Ca^<2+>交換系 |
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| Research Abstract |
Intracellular Ca^<2+> overload contributes to development of reperfusion-induced arrhythmias. As the mechanism intracellular H^+ accumulated during ischemia has been shown to result in influx of Na^+ and Ca^<2+> via Na^+/H^+ and N^+/Ca^<2+> exchange systems. We have shown delayd normalization of extracellular pH using acidic solution, acidic reperfusion, inhibits reperfusion-induced ventricular fibrillation (VF) in the isolated perfused rat heart model. In those studies, when the perfusate pH was normalized to 7.4 within 2min of reperfusion most hearts developed VF after the switching, while such the normalization did not induce new onset of VF when acidic reperfusion persisted for more than 2min. We analyzed myocardial Na^+/K^+-ATPase, another modulating mechenism of intracellular Na^+, histochemically in ischemic area of left ventricular (LV) free wall. The enzyme activity extremely diminished during ischemia, and after commencement of reperfusion its acitivity gradulally increased with significant recovery obtained after 2min. This fact suggests that Na^+ influx via Na^+/H^+ exchange may act as arrhythmogenic factor only when Na^+/K^+ pump activity is not yet recoverd. We have finally focused on ischemic preconditioning (IP) to examine pathologic involvement of Ca^<2+> overload. IP with cycles of brief ischemia-reperfusion prior to sustained ischemia resulted in improvment of recovery of LV developed pressure. Perfusion with several concentartion of angiotensin (AT) substituted for IP mimicked the protective effect while the effect is not dose-dependent manner. These results implies that preconditioning is the multifactorial phenomenon. Precise mechanisms of IP remain to be clarified in future.
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