The effect of risk factors for coronary atherosclerosis on the change in resting coronary vascular tone with N^G-monomethyl-L-arginine (L-NMMA), an antagonist of nitric oxide (NO) synthesis. The percent change in the coronary vascular resistance, flow, and proximal and distal epicardial diameters with L-NMMA are compared in patients with 1 risk factor (open circles) and in patients without risk factors (solid circles). Results expressed as mean ± SEM. p < 0.02 denotes differences in the response to L-NMMA by repeat-measures analysis of variance between patients with and patients without risk factors. *p < 0.05 and **p < 0.01 denote differences between rest and post–L-NMMA measurements in each group. Reprinted, with permission, from Quyyumi et al. (31).

The impact of risk factors for coronary atherosclerosis on the vascular effects of acetylcholine before and after inhibition of nitric oxide synthesis with N^G-monomethyl-L-arginine (L-NMMA). The percent change in the coronary vascular resistance, flow, and proximal and distal epicardial diameters with acetylcholine are compared in patients with 1 risk factor (open circles) and in patients without risk factors (solid circles) for atherosclerosis. Responses to the peak dose of acetylcholine are compared before and after L-NMMA in the 2 groups. Results expressed as mean ± SEM. p < 0.03 denotes differences in the response to acetylcholine between patients with and patients without risk factors. *p < 0.05 and **p < 0.01 denote differences between control and post–L-NMMA measurements in each group. Reprinted, with permission, from Quyyumi et al. (31).

Comparison of the quantitative myocardial response to the infusion of incremental doses of dobutamine in healthy control subjects (open circles) and in patients with chest pain and normal coronary angiograms (solid circles). Results expressed as mean ± SEM. The p value corresponds to comparison of the different responses by repeat-measures analysis of variance. Reprinted, with permission, from Panza et al. (56). NS = not significant.

Prevalence of typical chest pain experienced during cardiac catheterization in 36 patients with chest pain and normal coronary angiograms (CPNCA), 44 patients with coronary artery disease (CAD), and 10 patients with valvular heart disease (VHD) provoked by pacing from apex of right ventricle at 5 beats over resting heart rate and/or injection of contrast media into the left coronary artery. Adapted and reprinted with permission from Cannon et al. (64).

Future research should establish a coherent pathophysiology that links coronary microvascular dysfunction with myocardial ischemia. For the diagnosis to be clinically relevant, testing that separates those patients whose symptoms are caused by myocardial ischemia from those whose pain is nonischemic should be validated by multiple groups, and strategies for effective management must be supported by randomized clinical trials. CV = cardiovascular.