Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy

Article

关键词: TUMOR-NECROSIS-FACTOR;    HEART-FAILURE;    SYNTHASE;    MODULATION;    RELAXATION;    ENERGETICS;    VENTRICLE;   

DOI  :  10.1161/01.CIR.101.16.1925

来源: SCIE

【 摘 要 】

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 beta-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 beta-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 (M(V) over dot O-2), and mechanical efficiency (measured as EW/M(V) over dot 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 mu g . 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 mu mol). DOE increased E-max, EW, and M(V) over dot 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 M(V) over dot O-2 (by 140+/-21%, 64+/-9%, and 35+/-5%, respectively) more than DOE alone, mechanical efficiency did not increase further (24.3+/-3.3% to 29.5+/-4.5%) because EW and M(V) over dot O-2, increased in parallel. Conclusions-These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares M(V) over dot O-2 through attenuation of LV contractile response to beta-adrenergic stimulation while maintaining LV energy-converting efficiency.

【 授权许可】

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