Pravastatin Prevents Arrhythmias Induced by Coronary Artery Ischemia/Reperfusion in Anesthetized Normocholesterolemic Rats
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概要
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HMG-CoA reductase inhibitors (statins) have been shown to decrease cardiovascular mortality. Since ventricular tachyarrhythmias are closely related to cardiovascular mortality, we tested effects of the hydrophilic statin pravastatin and the lipophilic statin fluvastatin in a rat arrhythmia model of ischemia/reperfusion and simultaneously measured serum total cholesterol level. Anesthetized rats were subjected to 5-min ischemia and 10-min reperfusion after chronic administration of oral pravastatin (0.02, 0.2, or 2 mg/kg), fluvastatin (0.2, 2, or 4 mg/kg), or vehicle for 22 days, once daily. The acute effect of pravastatin (0.2 or 2 mg/kg, once orally) was also observed. Chronically administrated pravastatin significantly reduced the incidence of ischemia-induced ventricular tachycardia (VT) from 70% (control) to 9% at 2 mg/kg, and it reduced the incidence of reperfusion-induced lethal ventricular fibrillation (VF) from 90% (control) to 20% at 0.2 mg/kg. Acute pravastatin and chronically administrated fluvastatin had no significant effect on these arrhythmias. There were no significant changes in blood pressure, heart rate, QT interval, and serum cholesterol among pravastatin-, fluvastatin-, and vehicle-treated groups. Hydrophilic pravastatin prevented reperfusion-induced lethal VF in anesthetized rats by chronic administration independent of its cholesterol lowering effect. This may be a new beneficial role of pravastatin in decreasing cardiovascular mortality.
- 2003-09-01
著者
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Harada Ken-ichi
Department Of Human Pathology Kanazawa University Graduate School Of Medicine
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HASHIMOTO Keitaro
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, Universit
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Fujimura Akio
Department Of Clinical Pharmacology Jichi Medical School
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OHMORI Masami
Department of Clinical Pharmacology, Jichi Medical School
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Zhu Bing-mei
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Ohmori Masami
Department Of Clinical Pharmacology Jichi Medical School
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NAGASAWA Yoshinobu
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, Universit
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CHEN Jianguang
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, Universit
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Chen Jianguang
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Harada Ken-ichi
Department Of Clinical Pharmacology Jichi Medical School
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Hashimoto Keitaro
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Hashimoto Keitaro
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Hashimoto Keitaro
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Hashimoto Keitaro
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Nagasawa Yoshinobu
Department Of Pharmacology Interdisciplinary Graduate School Of Medicine And Engineering University
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Nagasawa Yoshinobu
Department Of Human Science And Fundamentals Of Nursing
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Zhu Bing-Mei
Department of Pharmacology and Department of Human Science, Yamanashi Medical University
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HASHIMOTO Keitaro
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
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HASHIMOTO Keitaro
Department of Phamacology, Yamanashi Medical University
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