Serotonin and the heart: effects of ketanserin on myocardial function, heart rate, and arrhythmias.

Serotonergic receptors have been identified in the blood vessels of the heart and in myocardial tissue. We indirectly examined the potential significance of these receptors by studying the properties of ketanserin, an S2-serotonergic antagonist. In an isolated rat heart preparation, ketanserin at 10(-6) M slowed the heart rate, whereas at 10(-5) M it also decreased the cardiac output. Because the stroke volume rose, a negative inotropic effect could be excluded. Electrophysiologically, ketanserin (10(-7) M or more) increased the action potential duration of the superfused guinea-pig papillary muscle preparation. This Class III effect may account for the antiarrhythmic action of ketanserin (5 X 10(-6) M-10(-5) M) in an ischemic-reperfused rat heart preparation. The possibility of nonspecific effects of ketanserin such as an interaction with alpha 1-adrenergic receptors merits careful evaluation, but in the case of the Class III effect, ketanserin was approximately 100 times more active than prazosin in widening the action potential duration. These data suggest that even high concentrations of ketanserin are unlikely to have harmful effects on the myocardium and might, on the contrary, have beneficial effects in the context of myocardial ischemia.