Abstract

Numerous reports have documented the existence and significance of coronary artery spasm in patients with Prinzmetal's variant angina, with or without associated obstructive coronary artery disease. The mechanisms whereby spontaneous coronary arterial spasm is precipitated in variant angina, particularly in patients without high-grade obstructive lesions, is far from clear, but certain facts suggest the possibility of cyclic increases in neural stimulation of epicardial coronary arteries through alpha and beta receptors. A hypothesis to explain the biochemical mechanism of coronary spasm is postulated. This hypothesis is based on accumulated experimental and limited clinical evidence suggesting that increased cyclic AMP concentration appears to be an important factor in the process of arteriolar vasodilatation and that reduction of cyclic AMP content of vascular smooth muscle seems to be an initial event associated with arteriolar vasoconstriction. Previous reports have documented the ability to provoke the attack of angina accompanied by elevation of the ST segment by the administration of the parasympathomimetic drug, methacholine. Methacholine causes coronary vasodilatation by direct action; however, it also causes release of norepinephrine from the postganglionic sympathetic nerve terminals in the heart. Since the epicardial coronary arteries are supplied predominantly by alpha receptors (vasoconstriction), the resulting effect is intense vasoconstriction resulting in coronary arterial spasm. Preliminary results have shown that intravascular administration of ergonovine in patients with suspected Prinzmetal's angina may result in focal as well as diffuse coronary arterial spasm. The effects of this sympathomimetic agent are promptly reversed by sublingual nitroglycerin, without clinical, hemodynamic, or angiographic complications. A large series of patients with variant angina needs to be studied with the use of these provocative agents to confirm their diagnostic specificity as well as sensitivity.