Metabolic coronary-flow regulation and exogenous nitric oxide in human coronary artery disease: Assessment by intravenous administration of nitroglycerin

We sought to evaluate the effect of intravenous administration of the nitri c oxide-donor substance nitroglycerin (NTG) on metabolic coronary-flow regu lation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen sup ply and consumption (MVo(2)) at sinus rhythm and during atrial pacing (30 b eats/min above sinus rate), both at control and during infusion of NTG, 1 m u g/kg/min, and NTG, 2 mu g/kg/min. To study metabolic coronary vasodilatio n, changes in myocardial oxygen supply were related to pacing-induced chang es in MVo(2), by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control , characterizing physiological metabolic coronary flow regulation) was comp ared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 mu g/kg/min, and NTG, 2 mu g/kg/min, attenuated pacin g-induced increases in MVo(2) by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/ demand rat io of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 mu g/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 mu g/kg/min, thi s ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p < 0.01). Intr avenous administration of high-dose NTG, a donor of exogenous NO, blunts pa cing-induced increases in MVo(2) and may increase metabolic coronary vasodi lation in patients with CAD.