Pravastatin inhibits arrhythmias induced by coronary artery ischemia in anesthetized rats.
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.
Chen
Jianguang
J
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. chenjg621@yahoo.com.cn
Shen
Hua
H
Nagasawa
Yoshinobu
Y
Mitsui
Kazuhiro
K
Tsurugi
Kunio
K
Hashimoto
Keitaro
K
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000517:prevention & control*; D003331:Coronary Vessels / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000627:therapeutic use; D000077340:Fluvastatin; D006903:Hydroxymethylglutaryl CoA Reductases / Q000008:administration & dosage / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D007511:Ischemia / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D009195:Peroxidase; D017035:Pravastatin