Reduction of the size of acute, experimental myocardial infarction by Verapamil

Abstract

The effect of 0.1 mg/kg Verapamil on the extent of the ischemic area following ligation of a branch of the left descending coronary artery was studied in anesthetized open chest dogs. The sum of the ST-segment elevation during the entire period of occlusion in the epicardial ECG was 15 mV in control infarction compared to 9 mV (p smaller than 0.0005) when Verapamil was infused after ligation. Mean flow in the left descending coronary artery was reduced by coronary ligation alone on the average by 23%, but augmented by Verapamil for 5% above pre-occlusion control flow. Corresponding to the rise in the coronary flow and the drop in perfusion pressure under the influence of Verapamil, the increase of left coronary artery resistance induced by coronary occlusion was diminished. The positive effect of Verapamil on the size of myocardial infarction as estimated from the epicardial ST-segment changes is probably not induced by coronary vasodilatation, but by the Ca-antagonizing effect of this drug, as described by other authors.

Autoradiographic method for measuring the ischemic myocardium at risk: effects of verapamil on infarct size aftr experimental coronary artery occlusion.

“…Reduction of calcium flux reduces myocardial contractility and hence myocardial oxygen consumption. It can also result in systemic vasodilation with afterload reduction and vasodilation of coronary collateral vessels supplying the ischemic zone (20)(21)(22).…”

The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium.

“…The observation that verapamil and cardioplegia do not directly inhibit calcium entry on reperfusion is in contrast to many studies (Wende et al, 1975;Reimer et al, 1977;Smith et al, 1977;Lefer et al, 1979) which have shown that, when given prior to a period of ischemia, calcium antagonists delay or prevent tissue damage, and also reduce calcium accumulation Witts et al, 1979;Lefer et al, 1979;Nayler et al, 1980). There are fewer reports of the effects of calcium antagonists given after the onset of ischemia.…”

“…Verapamil and other calcium antagonists block the slow calcium current of the action potential (Kohlhardt et al, 1972a(Kohlhardt et al, , 1972bCranefield et al, 1974;Kohlhardt and Mnich, 1978;Henry, 1980). When these drugs are given prior to or at the onset of a period of ischemia, they have been shown to preserve tissue ultrastructure (Reimer et al, 1977), to reduce enzyme release (Wende et al, 1975;Smith et al, 1977;Lefer et al, 1979), to diminish S-T elevation (Lefer et al, 1979;Selwyn et al, 1979), to improve hemodynamic function (Magee et al, 1979;Clark et al, 1979), to maintain tissue ATP (Lefer et al, 1979;Watts et al, 1979;Nayler et al, 1980;Weishaar and Bing, 1980), and to prevent calcium accumulation in whole tissue and isolated mitochondria Watts et al, 1979;Lefer et al, 1979;Nayler et al, 1980). The uniformly beneficial results obtained in such experiments are in sharp contrast to the results of experiments in which calcium antagonists have been administered, not prior to ischemia, but either after the ischemic myocardium has ceased to contract or at the time of reperfusion.…”

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…As a consequence, the early conceptual approaches to infarct limitation in the 1970s centered on agents to reduce myocardial oxygen demand or vasodilators to increase oxygen and metabolic substrate delivery (Maroko et al, 1971;Braunwald and Maroko, 1975). Hence, agents such as ␤-adrenoceptor antagonists Reynolds et al, 1981;Downey et al, 1982); calcium channel blockers (Reimer and Jennings, 1984;Reimer et al, 1985;Wende et al, 1975); and glyceryl trinitrate (Bleifeld et al, 1973;Malm et al, 1979;Fukuyama et al, 1980) were extensively investigated with no consistently reproducible evidence of infarct limitation.…”