Protective effects of slow channel calcium antagonists on noradrenaline induced myocardial necrosis

Catecholamine excess results in two distinct forms of coagulative myocytolysis, apparently due to increased membrane permeability followed by a large influx of calcium. To determine if three slow channel calcium antagonists, verapamil, nifedipine, and diltiazem, could reduce the calcium overload and prevent the development of noradrenaline induced acute myocardial contraction band lesions, 48 adult mongrel dogs in eight groups (n = 6) were continuously infused with saline alone, noradrenaline alone (4 micrograms X kg-1 X min-1), nifedipine (1 microgram X kg-1 X min-1), or other calcium blockers (10 micrograms X kg-1 X min-1) with saline or noradrenaline. After 15 minutes of pretreatment with a calcium antagonist, the antagonists were simultaneously infused with either saline or noradrenaline for 60 minutes. Nifedipine increased heart rate to the same degree as noradrenaline alone, whereas verapamil and diltiazem significantly suppressed the noradrenaline induced increases in heart rate. All three calcium antagonists reduced the increases in blood pressure and frequency of ventricular arrhythmias seen with noradrenaline alone. Only nifedipine produced a moderate increase in contractility (dP/dtmax) within 5 min and a pronounced synergistic increase when combined with noradrenaline. The effect of the other antagonists with noradrenaline was no different than the effect with noradrenaline alone. Contraction band lesions in the hearts of dogs in the saline and saline plus calcium antagonist groups were rare. The group receiving noradrenaline alone showed large numbers of the two predominant lesions: small paradiscal contraction band lesions and large holocytic contraction band lesions.(ABSTRACT TRUNCATED AT 250 WORDS)