| Project/Area Number |
11670085
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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 |
General pharmacology
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| Research Institution | Yamanashi Medical University |
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Principal Investigator |
HASHIMOTO Keitaro Yamanashi Medical University, Faculty of Medicine Professor, 医学部, 教授 (10004665)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Kouich University of Shizuoka, Facultu of Pharmaceutical Sciences Professor, 薬学部, 教授 (50112769)
KOMORI Sadayoshi Yamanashi Medical University, Faculty of Medicine Professor, 医学部, 教授 (30162069)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | arrhythmia / Na / H exchange / ischemia / animal model / H交換抑制薬 / 心筋梗塞 / イヌ / 心室性不整脈 / 心室細動 |
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| Research Abstract |
Selective Na^+/H^+ exchange inhibitors have been shown to have cardioprotective effects in animal models of myocardial ischemia. Among them, cariporide, KB-R9032, SMP-300 and FR168888 suppressed coronary ligation/reperfusion induced VF in dogs and rats, which might have been induced by Ca^<2+> overload after extrusion of H^+. KB-R9032 also decreased the number of PVCs during coronary occlusion in dogs. They had no effects on cardiohemodynamic parameters of in vivo dogs and rats, nor had no significant effects on other Ca^<2+> overload induced arrhythmias by digitalis or adrenaline. In rats, cariporide did not suppress antiarrhythmic effects of ischemic preconditioning. Though there were almost no ECG changes to explain antiarrhythmic effects, metabolically favorable effects, such as blunting creatine phosphate overshoot during reperfusion in rat myocardium were observed. Regardless of these favorable animal data, a preliminary clinical trial of cariporide did not show marked protective effect in acute coronary diseases. A new selective Na^+/Ca^+ exchange inhibitor, KB-R7943, did not show protective effect against against reperfusion VF and digitalis arrhythmias in dogs, though favorable effects have been reported in.
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