1999 Fiscal Year Final Research Report Summary
The Study on the Mechanism of Ischemic Preconditioning of the Myocardium
| Project/Area Number |
09670738
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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 | Wakayama Medical College |
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Principal Investigator |
BABA Akira Wakayama Medical College, Department of Medicine, Assistant Professor of Medicine, 医学部, 講師 (00228678)
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| Co-Investigator(Kenkyū-buntansha) |
HANO Takuzo Wakayama Medical College, Department of Medicine, Associate Professor of Medicine, 医学部, 助教授 (90156381)
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| Project Period (FY) |
1997 – 1999
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| Keywords | ischemic preconditioning / hypoxia-reperfusion injury / ATP-sensitive K channel / mitochondria / diazoxide / intracellular hydrogen concentration |
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| Research Abstract |
ATP-sensitive K channel (KィイD2ATPィエD2 channel) have been reported to play a major role in ischemic preconditioning. The present study was designed to clarify the effect of mitochondrial KィイD2ATPィエD2 channel opener on the hypoxia-reperfusion injury. Ventricular myocytes isolated from Sprague-Dawley rat were studied. Cardiomyocytes were superfused with anoxic glucose-free Tyrode solution, which was equilibrated with 99.99% nitrogen under positive pressure, for 15 minutes followed by normoxic Tyrode solution for 40 minutes. Diazoxide (30 μM), a specific mitochondrial KィイD2ATPィエD2 channel opener was administered to the diazoxide group (D group) 5 minutes prior to anoxic perfusion until the end of anoxic perfusion. Intracellular pH measured by BCECF and the shape of myocytes were recorded by microscopic fluorometric system ARGUS 200 (Hamamatsu Photonics, Hamamatsu, Japan). Rod-shaped cell was considered to be alive. The viability of cardiomyocytes at the end of anoxia-reoxygenation perfusion was significantly higher in D group compared with control group (59.3±10.6 vs 22.0±13.3% ; n=8,6 rats ; <0.05). The pH of myocytes was similar between two groups at the end of anoxic perfusion. Most of the killed cells of the control group showed round cells but the half of the killed cell of D group showed rigor contracture (control group : round cells 62.3%, rigor contracture 10.7% ; D group : round cells 20.3%, rigor contracture 19.5%). When isolated cardiomyocytes were made skinned by saponin after washing by EGTA-containing solution, and suspended in ATP-depleted solution, myocytes became rigor contracture. Mitochondrial KィイD2ATPィエD2 channel opener showed the protective effect on the anoxia-reoxygenation injury of the isolated cardiomyocyte of rat without any change of intracellular pH. This protective effect might be due to reducing Ca overload during anoxia-reoxygenation perfusion.
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Research Products
(12 results)
