Nitric Oxide Spares Myocardial Oxygen Consumption Through Attenuation of Contractile Response to β-Adrenergic Stimulation in Patients With Idiopathic Dilated Cardiomyopathy

Abstract

Background —The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to β-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to β-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. Methods and Results —We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E max , the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MV̇ o 2 ), and mechanical efficiency (measured as EW/MV̇ o 2 ) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8±0.3 μg · kg −1 · min −1 IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N G -monomethyl- l -arginine (L-NMMA; 200 μmol). DOB increased E max , EW, and MV̇ o 2 (by 77±17%, 39±5%, and 21±5%, respectively), leading to an increase in mechanical efficiency (25.4±3.1% to 29.6±4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased E max , EW, and MV̇ o 2 (by 140±21%, 64±9%, and 35±5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3±3.3% to 29.5±4.5%) because EW and MV̇ o 2 increased in parallel. Conclusions —These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MV̇ o 2 through attenuation of LV contractile response to β-adrenergic stimulation while maintaining LV energy-converting efficiency.