The pharmacologic and hemodynamic effects of verapamil are the result of its selective inhibitory action on the slow channel in cardiac muscle and its propensity to block transmembrane calcium influx in vascular smooth muscle and to nonspecifically antagonize sympathetic excitation. In patients with normal or moderately reduced ventricular function, verapamil's ability to reduce afterload counteracts its intrinsic negative inotropic effects and therefore a reduction in ventricular performance is not seen. In patients with a severely reduced ventricular ejection fraction and high ventricular filling pressures, however, the drug may produce clinical and hemodynamic deterioration. Computer-assisted angiographic analysis shows that verapamil dilates normal as well as narrowed epicardial coronary vessels and reverses ergonovineand sympathetically provoked coronary vasoconstriction. Intravenous administration of verapamil reduces coronary arterial resistance and enhances coronary sinus flow with variable effects on myocardial oxygen consumption. The drug prevents the ischemic consequences of angina produced by atrial pacing; after verapamil administration, pacing-induced lactate production is lessened, and ischemia-related declines in left ventricular ejection fraction are prevented. During chronic therapy the effects of verapamil on regional and global ventricular function are similar to those of propranolol during supine bicycle exercise. However, verapamil has significantly less effect on rate-pressure product at rest and during exercise, which suggests that its antianginal mechanism of action, unlike that of beta-blocking agents, may not be related solely to a reduction in oxygen demand. These data indicate that the mechanisms underlying the antianginal effects of verapamil are complex and are likely to be multifactorial.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine