Pravastatin Inhibits Arrhythmias Induced by Coronary Artery Ischemia in Anesthetized Rats

Journal of Pharmacological Sciences

Kazuhiro Mitsui²  Hua Shen²  Yoshinobu Nagasawa¹  Keitaro Hashimoto¹  Jianguang Chen¹  Kunio Tsurugi² 

[1] Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan;Department of Biochemistry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan

关键词: pravastatin;    fluvastatin;    ischemia;    arrhythmia;    myeloperoxidase;   

DOI  :  10.1254/jphs.FP0061235

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(13)We have reported that chronically administered pravastatin prevented coronary artery reperfusion-induced lethal ventricular fibrillation (VF) in anesthetized rats without lowering the serum cholesterol level. The present study was undertaken to evaluate whether pravastatin prevents ischemia-induced lethal VF, simultaneously examining myeloperoxidase (MPO) activity in ischemic myocardial tissues. Anesthetized rats were subjected to 30-min ischemia and 60-min reperfusion after chronic administration of pravastatin (0.02, 0.2, and 2 mg/kg), fluvastatin (2 and 4 mg/kg), or vehicle for 22 days, orally, once daily. ECG and blood pressure were continually recorded, and MPO was measured by a spectrophotometer. Pravastatin and fluvastatin significantly (P<0.05) decreased MPO activities, but only pravastatin decreased the incidence of ischemia-induced lethal VF. Both statins had no significant effects on body weight, blood pressure, heart rate, and QT interval as we reported earlier. Our results prove further that pravastatin has benefits to decrease cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in prevention of arrhythmias. A decrease in the neutrophil infiltration may be partly involved in the inhibitory effect of pravastatin on the ischemia-induced VF.

【 授权许可】

Unknown