The effects of mebudipine on myocardial arrhythmia induced by ischemia-reperfusion injury in isolated rat heart.

Abstract

Reperfusion of the heart after an ischemic insult may lead to potentially lethal arrhythmias and cardimyocyte cell death via apoptosis and necrosis. In addition, previous studies showed that calcium channel blockers may have a protective role in the myocardium against arrhythmia and irreversible tissue injury. Therefore, this study was aimed to investigate the effects of mebudipine on myocardial arrhythmias and tissue injury induced by ischemia/reperfusion injury in isolated rat hearts. Male Wistar rats (250?300g) were randomly divided to Sham group (without ischemia), control group (ischemia without drug), drug group (ischemia with mebudipine 0.1nM) and vehicle group (ischemia with ethanol 0.01%). The hearts of anaesthetized rats were removed and mounted on Langendorff apparatus and perfused by Krebs?Henseleit solution under constant pressure of 75 mmHg at 37°C. Impulsive heart rate was monitored with bipolar golden electrodes. The electrocardiographs were recorded throughout the experiment and interpreted using the Lambeth convention. LDH and CPK activities in coronary effluent were analyzed spectrophotometrically. Hematoxilin & Eosin staining was performed for evaluation of microscopic architecture of the myocardium and tissue injury. Pretreatment with mebudipine significantly decreased the number of ventricular premature beats (VPB) as compared with control group. The similar findings were seen in the number of ventricular tachycardia (VT) and fibrillation (VF) among groups. In addition, mebudipine significantly reduced the severity of arrhythmias in comparison with control hearts. Moreover, the drug group demonstrated marked improvement in edema and infiltration of inflammatory cells especially with regard to the degree of myonecrosis and cell lysis.Mebudipine diminished the number and the incidence of myocardial arrhythmias induced by reperfusion injury and the severity of tissue injury.