Relief of myocardial ischemia with nitroglycerin: what is the mechanism?

THE PHYSIOLOGIC EFFECT of nitroglycerin in patients with ischemic heart disease has been a focus of intense clinical investigation. However, some disagreement about the mechanisms by which nitroglycerin relieves myocardial ischemia still exists,' for several reasons. The action of nitroglycerin may vary, depending on the dose or route of administration. Also, parenteral nitroglycerin can be given by bolus or slow infusion into the systemic or coronary circulation. To further complicate the issue, the patient population is not homogeneous. Myocardial ischemia may result from a fixed coronary stenosis that prevents an increase in coronary flow when myocardial oxygen requirements are increased, from coronary artery spasm, or from a combination of spasm and fixed coronary stenosis. The preceding article by Brown and colleagues2 focuses on the effect of nitroglycerin on coronary stenosis diameter. These investigators used both sublingual and intracoronary nitroglycerin and made quantitative coronary angiographic measurements of coronary stenoses. In 46 patients, they showed that sublingual nitroglycerin dilates both the coronary stenosis and the adjacent artery. They then administered low-dose intracoronary nitroglycerin by infusion (25 gg/min) to other patients and found similar coronary dilatation and improvement in left ventricular performance in selected patients. None of these latter patients were reported to have coronary artery spasm, yet almost all patients showed dilatation of the coronary stenosis. These observations were interpreted to show that vasodilatation of epicardial coronary stenoses is usually a major component of the beneficial response to nitroglycerin in patients with coronary artery disease. The observation that nitroglycerin may dilate coronary stenoses agrees with previous results using sublingual nitroglycerin.3 4 However, data in these reports conflict with those of Brown et al., i.e., although many coronary artery stenoses dilate after nitroglycerin, stenoses with the smallest luminal diameter often did not dilate.4 For example, when coronary stenoses were measured, only 14% (two of 14) of those 1.2 mm or smaller dilated at least 0.1 mm after nitroglycerin. In contrast, 59% (16 of 27) of stenoses greater than 1.2 mm dilated an average of 1 1% after nitroglycerin. The stenoses in which the diameter was