Minocycline attenuates ischemia-induced ventricular arrhythmias in rats

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• 作者：Xiaorong Hu^a ; ¹ ; Bing Wu^a ; ^b ; ¹ ; Xin Wang^a ; Changwu Xu^a ; Bo He^a ; Bo Cui^a ; Zhibing Lu^a ; Hong Jiang^a ; ^{jianghwurm@163.com}
• 关键词：Minocycline ; Ventricular arrhythmia ; Myocardial ischemia ; PI3K/Akt ; Mitochondrial ATP-sensitive potassium ; L-type Ca²⁺ channel
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：11 March 2011
• 年：2011
• 卷：654
• 期：3
• 页码：274-279
• 全文大小：1408 K

文摘

Minocycline has been shown to protect against myocardial ischemia–reperfusion injury. This study investigated the effects of minocycline on ischemia-induced ventricular arrhythmias in rats. Anesthetized male rats were once treated with minocycline (45 mg/kg, i.p.) 1 h before ischemia in the absence and/or presence of 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002, 0.3 mg/kg, i.v., a PI3K inhibitor) and 5-hydroxydecanoic acid [5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium (K_ATP) channels] which were once injected 10 min before ischemia and then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed. L-type Ca²⁺ current was measured by the patch-clamp technique. During the 30-minute ischemia, minocycline significantly reduced the incidence of ventricular fibrillation (VF) (P < 0.05). The duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by minocycline compared to those in myocardial ischemia group (P < 0.05 for all). Administration of LY294002 or 5-HD abolished the protective effects of minocycline on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (P < 0.05 for all). In addition, minocycline inhibited L-type Ca²⁺ currents of normal myocardial cell membrane in a dose-dependent manner. This study suggested that minocycline could attenuate ischemia-induced ventricular arrhythmias in rats in which PI3K/Akt signaling pathway, mitochondrial K_ATP channels and L-type Ca²⁺ channels may be involved_.