Opie L H
Ischaemic Heart Disease Research Unit of the Medical Research Council, Cape Town, South Africa.
Cardiovasc Drugs Ther. 1992 Feb;6(1):19-24. doi: 10.1007/BF00050912.
The use of calcium antagonists for postinfarct cardioprotection remains controversial. Several major trials have failed to show benefit, despite positive expectations based on promising experimental data. A clue to the problem with the calcium antagonists was provided by the diltiazem trial, in which an adverse effect in the presence of congestive heart failure masked a benefit in those without heart failure. Accordingly, the most recent trial, DAVIT-II, was carried out in patients in whom preexisting left ventricular failure had been excluded. One of the interesting byproducts of that study was the possibility that verapamil prevented postinfarct sudden death, which implies a potential antiarrhythmic mechanism. It is proposed that cytosolic calcium overload could play a role in ischemic ventricular fibrillation. Experimentally, calcium antagonists are most effective antifibrillatory agents when catecholamine stimulation is combined with acute ischemia, as would be the situation in the acute phase of myocardial infarction. This potential benefit of calcium antagonists may be offset in the presence of congestive heart failure because left ventricular dilation is directly arrhythmogenic. The ideal calcium antagonist, aimed at preventing postinfarct ischemic arrhythmias, but without a significant negative inotropic effect, could be based on 1 of 2 principles. First, the agent could be highly selective for the ischemic but not the nonischemic zone of the myocardium (ischemic-selective agent). Second, the agent could be highly vascular selective, so that left ventricular dilation would be avoided. A comparative study of these two types of calcium antagonists should be undertaken in postinfarct patients.
钙拮抗剂用于心肌梗死后心脏保护的作用仍存在争议。尽管基于有前景的实验数据有积极预期，但几项主要试验均未显示出益处。地尔硫䓬试验为钙拮抗剂存在的问题提供了线索，在该试验中，充血性心力衰竭患者出现的不良反应掩盖了无心力衰竭患者的益处。因此，最近的DAVIT-II试验是在已排除既往存在左心室衰竭的患者中进行的。该研究的一个有趣副产品是维拉帕米可能预防心肌梗死后猝死，这意味着存在潜在的抗心律失常机制。有人提出，细胞溶质钙超载可能在缺血性心室颤动中起作用。在实验中，当儿茶酚胺刺激与急性缺血相结合时，钙拮抗剂是最有效的抗纤颤药物，心肌梗死急性期就是这种情况。在存在充血性心力衰竭时，钙拮抗剂的这种潜在益处可能会被抵消，因为左心室扩张直接会导致心律失常。理想的钙拮抗剂旨在预防心肌梗死后缺血性心律失常，但又无明显的负性肌力作用，可基于以下两个原则之一。第一，该药物对心肌的缺血区而非非缺血区具有高度选择性（缺血选择性药物）。第二，该药物具有高度的血管选择性，从而避免左心室扩张。应在心肌梗死后患者中对这两种类型的钙拮抗剂进行比较研究。
