VARIANT ANGINA Induction of coronary artery spasm by acetylcholine in patients with variant angina : possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm

We injected acetylcholine (ACh), the neurotransmitter of the parasympathetic nervous system, into the coronary arteries of 28 patients with variant angina. Injection of 10 to 80 gg ACh into the coronary artery responsible for the attack induced spasm together with chest pain and ST segment elevation or depression on the electrocardiogram in 30 of the 32 arteries of 25 of the 27 patients. The injection of 20 to 100 gg ACh into the coronary artery not responsible for the attack in 18 patients resulted in various degrees of constriction in most of them, but no spasm in any of them. After intravenous injection of 1.0 to 1.5 mg atropine sulfate, the injection of ACh into the coronary artery responsible for the attack did not induce spasm or attack in any of the nine coronary arteries injected in eight patients. We conclude that the intracoronary injection of ACh induces coronary spasm and attack in patients with variant angina and that the activity of the parasympathetic nervous system may play a role in the pathogenesis of coronary spasm. We also conclude that the intracoronary injection ofACh is a useful test for provocation of coronary spasm. Circulation 74, No. 5, 955-963, 1986. IT IS NOW widely accepted that spasm of an epicardial coronary artery (coronary spasm) plays an important role in the pathogenesis, not only of variant angina, but also of other forms of resting angina, some types of exertional angina, and types of acute myocardial infarction. 1-3 However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm occurs most often when patients are at rest, and is usually not provoked by exercise in the daytime."6 We have shown that an attack of variant angina or coronary spasm can be induced by subcutaneous injection of methacholine, an analogue of acetylcholine (ACh), which is the neurotransmitter of the parasympathetic nervous system, and that the attack can be suppressed by atropine, a parasympatholytic agent, in some patients with variant angina.7-9 SubseFrom the Division of Cardiology, Kumamoto University School of Medicine, Kumamoto City, Japan. Address for correspondence: Hirofumi Yasue, M.D., Division of Cardiology, Kumamoto University School of Medicine, 1-1-1, Honjou, Kumamoto City 860, Japan. Received Oct. 3, 1985; revision accepted June 10, 1986. Vol. 74, No. 5, November 1986 quently Endo et al.'0 confirmed our results. On the basis of this fact and the fact that the activity of the parasympathetic nervous system is enhanced at rest and is suppressed by physical activity," we postulated that the activity of parasympathetic nervous system might be related to the pathogenesis of variant angina or coronary spasm.7 It has been shown that stimulation of the parasympathetic (vagus) nerve or intracoronary injection of ACh causes coronary vasodilatation, as demonstrated by an increase in coronary blood flow in dogs,'2-'5 and that ACh dilates isolated epicardial coronary arteries in dogs'6 and monkeys. 17 In humans subcutaneous injection of methacholine causes profound dilatation of systemic vasculature, resulting in a transient fall in blood pressure and compensatory tachycardia due to reflex sympathetic discharge.7 We therefore speculated that coronary spasm might be induced by sympathetic discharge by way of a-adrenergic stimulation.7 Recently, however, reports have appeared that show that ACh contracts strips of human coronary arteries obtained from hearts of transplant recipients'8 or cadav955 by gest on N ovem er 6, 2017 http://ciajournals.org/ D ow nladed from