Acetylcholine and coronary artery spasm: important insight or squeeze play?

For over 100 years, ergot alkaloids have been known to be powerful vasoconstrictor agents, even capable of causing gangrene (1). In the late 1940s, intravenous administration of ergotamine to patients with "organic heart disease" s found to cause electrocardiographic (ECG) changes and chest pain, believed to represent a direct vasoconstrictor effect of ergotamine on the coronary arteries, Stein and Weinstein (2) reported the responses of 30 patients. 15 of whom had a clinical diagnosis of coronary artery disease, to ergonovine, 0.5 to 0.6 mg in incremental doses . In 6 of these 15 patients, prior exercise testing had failed to produce ST segment depression. In all 15 . ergonovine administration resulted in ST segment depression or chest pain . or both . Chest pain was relieved by nitroglycerin . and repeat administration of ergonovine after nitroglycerin produced no or less prominent ECG changes in 10 patients . No chest pain or ECG changes were induced in 15 "controls ." Thus, ergonovine administration appeared to show promise as a diagnostic agent for coronary artery disease . Ergonovine for provocalion of coronary spasm. in 1959 Prinzmetal described 32 patients, with angina primarily at rest, whose ECG showed striking ST segment elevation during episodes of pain (3) . He hypothesized that these findings represented severe, transient coronary artery vasoconstriction, superimposed on atherosclerotic plaque. "Prinzmetal's" or "variant-" angina gained credibility with the angfographic demonstration of spontaneous episodes of coronary artery spasm in patients with rest pain primarily associated with ST segment elevation (4-6) . However, such events were rarely seen during a rteriography . in part because of the common practice of premeditation with nitrates to avoid catheter-induced spasm of the coronary (especially right) artery . In 1975, Heupler et al . (7) reported the use of