Effects of calcium-channel blockers on myocardial preservation during experimental acute myocardial infarction

Abstract

Calcium antagonists have become accepted agents for the attenuation of myocardial ischemia when it becomes manifest as angina pectoris. However, it is not known whether these agents can protect ischemic myocardium during the early evolution of an acute myocardial infarct. Calcium antagonists could potentially improve myocardial perfusion, by relieving coronary spasm or improving collateral blood flow, and reduce the energy demands of the ischemic myocardium either directly or by reducing heart rate or contractility. In some studies, calcium antagonists have decreased the rate of adenosine triphosphate depletion in ischemia and reduced functional or structural indexes of ischemic injury after relatively brief periods (up to 2 hours) of injury. We have assessed the ability of verapamil to protect severely ischemic myocardium in dogs with a 40-minute test period of circumflex occlusion followed by reperfusion. After 4 days of recovery, infarcts were sized by histologic methods. Untreated dogs had subendocardial infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with verapamil reduced the size of these subendocardial infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed (anatomic area at risk). Thus, verapamil prevented cell death in a substantial proportion of the severely ischemic subendocardial region that otherwise would have died as a result of the 40-minute test period of ischemia. To establish whether verapamil could prevent cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion with reperfusion was studied.