Effects of parasympathetic blockade on ischemic threshold in patients with exercise-induced myocardial ischemia

Abstract

In patients with coronary artery disease (CAD), an abnormal coronary vasoconstriction superimposed to organic stenosis may further limit coronary flow reserve. 1 This functional factor can modulate flow availability to the ischemic region and be responsible for the variability of ischemic threshold frequently observed in patients with effort angina pectoris. 2 An imbalance between dilatatory and constrictor stimuli has been postulated in these patients, possibly related to the impairment of the endothelium-mediated regulation of smooth muscle tone. 3 In normal subjects, coronary infusion of acetylcholine produces coronary vasodilation that appears to be mediated by the endothelium-derived relaxing factors, whereas in patients with CAD, it reduces large coronary artery diameter and decreases coronary flow velocity 4 (in animal experiments this latter effect seems to be independent of both α and β blockade, and is promptly reversed by intravenous injection of atropine). 5 A similar phenomenon can be observed during exercise. Compared with normal subjects, patients with CAD have a paradoxical vasoconstriction of large epicardial coronary arteries that can be prevented by treatment with isosorbide dinitrate. 6,7 It can be hypothesized that in normal conditions the parasympathetic system opposes vasoconstriction during exercise, whereas in the absence of endothelium its effect is reversed to coronary vasoconstriction. The aim of this study was to evaluate the effect of atropine, a parasympathetic blocker, compared with that of isosorbide dinitrate, an endothelial independent vasodilating drug, on the ischemic threshold of patients with exercise-induced ischemia.