Chen Jianguang, Shen Hua, Nagasawa Yoshinobu, Mitsui Kazuhiro, Tsurugi Kunio, Hashimoto Keitaro
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
J Pharmacol Sci. 2007 Mar;103(3):317-22. doi: 10.1254/jphs.fp0061235. Epub 2007 Mar 7.
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.
我们曾报道，长期给予普伐他汀可预防麻醉大鼠冠状动脉再灌注诱导的致死性室颤（VF），且不降低血清胆固醇水平。本研究旨在评估普伐他汀是否能预防缺血诱导的致死性VF，并同时检测缺血心肌组织中的髓过氧化物酶（MPO）活性。将麻醉大鼠连续22天每日口服给予普伐他汀（0.02、0.2和2mg/kg）、氟伐他汀（2和4mg/kg）或赋形剂，随后进行30分钟的缺血和60分钟的再灌注。持续记录心电图和血压，并用分光光度计测量MPO。普伐他汀和氟伐他汀均显著（P<0.05）降低MPO活性，但只有普伐他汀降低了缺血诱导的致死性VF的发生率。如我们之前报道的那样，两种他汀类药物对体重、血压、心率和QT间期均无显著影响。我们的结果进一步证明，普伐他汀除了具有降胆固醇作用外，还有助于降低心血管死亡率。在预防心律失常方面，普伐他汀比氟伐他汀更有效。中性粒细胞浸润的减少可能部分参与了普伐他汀对缺血诱导的VF的抑制作用。
