Sandmann S, Claas R, Cleutjens J P, Daemen M J, Unger T
Institute of Pharmacology, Christian-Albrechts-University of Kiel, Germany.
J Cardiovasc Pharmacol. 2001 Jan;37(1):64-77. doi: 10.1097/00005344-200101000-00008.
Calcium channel antagonists (CCAs) have been proposed to prevent cardiac events after myocardial infarction (MI). However, unwanted effects, such as negative inotropy, limit their use in many cases. The aim of this study was to compare the effects of long-term treatment with the CCAs, mibefradil, verapamil, and amlodipine, administered before and after chronic MI on myocardial remodeling and cardiac function. MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Infarcted animals were treated with placebo, mibefradil (10 mg/kg/d po), verapamil (8 mg/kg bid po), or amlodipine (4 mg/kg/d po). Treatment was started 7 days before or 3 h after MI induction. Six weeks after MI, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), and cardiac contractility (dP/dt(max)) were measured. Morphometric parameters such as infarct size (IS), left ventricular dilation (LVD), septal thickness (ST), and cardiac fibrosis were determined in picrosirius red-stained hearts. Six weeks after MI, MAP and dP/dt(max) were decreased, whereas LVEDP and HR were increased in placebo-treated controls. The hearts featured an IS of 45%, left ventricular dilation, cardiac fibrosis, and septal thinning. MAP of all CCA-treated animals was increased, whereas LVEDP was decreased and dP/dt(max) increased 7-day pre- and 3-h post-MI started in mibefradil- and amlodipine-treated animals, but not in verapamil-treated animals. In contrast to amlodipine treatment, before and after MI started mibefradil and verapamil treatment decreased HR. Pretreatment with all CCA reduced IS and increased ST, whereas only mibefradil and amlodipine pretreatment prevented LVD and cardiac fibrosis. After MI started treatment with mibefradil and amlodipine reduced IS and cardiac fibrosis, and increased ST. Long-term treatment with the CCAs mibefradil, verapamil, and amlodipine reduced myocardial remodeling and improved cardiac function in MI-induced heart failure in rats.
钙通道拮抗剂（CCAs）已被提议用于预防心肌梗死（MI）后的心脏事件。然而，诸如负性肌力等不良作用在许多情况下限制了它们的使用。本研究的目的是比较长期使用CCAs（米贝拉地尔、维拉帕米和氨氯地平）在慢性心肌梗死后给药对心肌重塑和心脏功能的影响。通过永久性结扎雄性Wistar大鼠的左冠状动脉诱导心肌梗死。梗死动物接受安慰剂、米贝拉地尔（10 mg/kg/d口服）、维拉帕米（8 mg/kg每日两次口服）或氨氯地平（4 mg/kg/d口服）治疗。治疗在心肌梗死诱导前7天或诱导后3小时开始。心肌梗死后6周，测量平均动脉血压（MAP）、心率（HR）、左心室舒张末期压力（LVEDP）和心脏收缩力（dP/dt(max)）。在天狼星红染色的心脏中测定梗死面积（IS）、左心室扩张（LVD）、室间隔厚度（ST）和心脏纤维化等形态学参数。心肌梗死后6周，安慰剂治疗的对照组中MAP和dP/dt(max)降低，而LVEDP和HR升高。心脏的梗死面积为45%，伴有左心室扩张、心脏纤维化和室间隔变薄。所有接受CCAs治疗的动物的MAP升高，而LVEDP降低，米贝拉地尔和氨氯地平治疗组在心肌梗死前7天和后3小时开始治疗时dP/dt(max)升高，但维拉帕米治疗组未升高。与氨氯地平治疗相反，米贝拉地尔和维拉帕米治疗在心肌梗死前后开始降低HR。所有CCAs预处理均降低梗死面积并增加室间隔厚度，而只有米贝拉地尔和氨氯地平预处理可预防左心室扩张和心脏纤维化。心肌梗死后开始用米贝拉地尔和氨氯地平治疗可降低梗死面积和心脏纤维化，并增加室间隔厚度。长期使用CCAs米贝拉地尔、维拉帕米和氨氯地平可减少大鼠心肌梗死后心力衰竭中的心肌重塑并改善心脏功能。
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