Ghiasi R, Mohammadi M, Majidinia M, Yousefi B, Ghiasi A, Badalzadeh R
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Urmia University Medical Sciences, Urmia, Iran.
Cell Mol Biol (Noisy-le-grand). 2016 Nov 30;62(13):15-20. doi: 10.14715/cmb/2016.62.13.4.
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.
缺血性损伤后心脏再灌注可能会通过凋亡和坏死导致潜在致命性心律失常和心肌细胞死亡。此外，先前的研究表明钙通道阻滞剂可能对心肌具有抗心律失常和防止不可逆组织损伤的保护作用。因此，本研究旨在探讨美贝地尔对离体大鼠心脏缺血/再灌注损伤所致心肌心律失常和组织损伤的影响。将雄性Wistar大鼠（250 - 300g）随机分为假手术组（无缺血）、对照组（缺血但未用药）、药物组（缺血且使用0.1nM美贝地尔）和溶剂组（缺血且使用0.01%乙醇）。将麻醉大鼠的心脏取出，安装在Langendorff装置上，并在37℃、75mmHg恒压下用Krebs-Henseleit溶液灌注。用双极金电极监测冲动心率。在整个实验过程中记录心电图，并根据Lambeth标准进行解读。用分光光度法分析冠状动脉流出液中的乳酸脱氢酶（LDH）和肌酸磷酸激酶（CPK）活性。进行苏木精和伊红染色以评估心肌的微观结构和组织损伤。与对照组相比，美贝地尔预处理显著减少了室性早搏（VPB）的数量。各组在室性心动过速（VT）和心室颤动（VF）的数量上也有类似发现。此外，与对照心脏相比，美贝地尔显著降低了心律失常的严重程度。而且，药物组在水肿和炎性细胞浸润方面表现出明显改善，尤其是在心肌坏死和细胞溶解程度方面。美贝地尔减少了再灌注损伤所致心肌心律失常的数量和发生率以及组织损伤的严重程度。
