Because ergonovine appears to produce coronary contractions by a serotonergic (5-HT) mechanism, we attempted to prevent ergonovine-induced ischemia in patients with vasospastic angina by pretreatment with ketanserin, a new selective 5-HT blocker. We studied seven patients with consistently positive results of ergonovine testing (ST segment elevation in three and ST segment depression in four). Ergonovine testing was performed before and after a bolus of 10 mg of ketanserin (all patients) and infusion of 2 to 4 mg/hr for 8 hr (six patients). To assess 5-HT blockade during ketanserin infusion, the constrictor response of hand veins to 5-HT was tested before and after ketanserin. Despite evidence of 5-HT blockade in hand veins, ergonovine-induced ischemia was not prevented by ketanserin in any patient, and there was no significant change in the dose of ergonovine required to provoke ischemia. In one patient, four spontaneous episodes of ST segment elevation occurred during infusion of ketanserin. The plasma concentrations of ketanserin at the time of ergonovine testing ranged from 61 to 127 ng/ml (mean 102) and were well above those that completely inhibit canine coronary 5-HT contractions in vitro. Although human coronary arteries may differ in their responsiveness to 5-HT or ketanserin, these data suggest that ischemia from ergonovine-induced coronary vasospasm is not mediated by 5-HT receptors. Circulation 70, No. 2, 178-183, 1984. CORONARY arterial spasm is now recognized as an important cause of ischemia in patients with all degrees of severity of coronary artery disease,' but the mechanisms responsible for its occurrence are still unknown. Ergonovine is the vasoconstrictor that most consistently provokes spasm in patients with angina at rest, 2 3 whose arteries appear hypersensitive to the drug at the site of spasm.4 Therefore the mechanism of ergonovine's action may be related to the cause (or causes) of spontaneously occurring spasm. Recent work in experimental animals has shown that coronary arterial contractions induced by ergonovine are mediated by serotonergic (5-HT) receptors5-7 and that the increased sensitivity of atherosclerotic rabbit aortas to ergonovine is at least partially mediated by a 5-HT mechanism. 178 tagonist with no partial agonist activity,'" provides an opportunity to test whether ergonovine-induced vasospasm in patients with angina is mediated by 5-HT receptors. In this study we attempted to block the effects of ergonovine by pretreatment with ketanserin in seven patients with ergonovine-induced ischemia. In six of the patients we also assessed the level of 5-HT blockade in peripheral veins during infusion of ketanserin by a test of venoconstriction in the hand.
MethodsPatient selection. Seven patients with angina pectoris and an ischemic electrocardiographic response to ergonovine maleate formed the study group. Their clinical, electrocardiographic, and angiographic findings are summarized in table 1. In five patients angina occurred both at rest and during exertion, whil...
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