INCREASED SENSITIVITY TO NITRIC-OXIDE SYNTHASE INHIBITION IN PATIENTSWITH HEART-FAILURE - POTENTIATION OF BETA-ADRENERGIC INOTROPIC RESPONSIVENESS

Background-We previously showed that cardiac nitric oxide (NO) inhibit s the positive inotropic response to beta-adrenergic stimulation in hu mans with left ventricular (LV) dysfunction. Whether this effect is sp ecific to heart failure per se or is a generalized feature of normal h uman myocardium is unknown. We therefore tested the hypothesis that in hibition of cardiac NO potentiates the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure bu t not in subjects with normal LV function. Methods and Results-We stud ied 11 patients with LV failure due to idiopathic dilated cardiomyopat hy and 7 control subjects with normal LV function. The beta-adrenergic agonist dobutamine was infused via a peripheral vein before and durin g concurrent intracoronary artery infusion of acetylcholine, which act ivates the agonist-coupled isoforms of NO synthase, and N-G-monomethyl -L-arginine, which inhibits all isoforms of NO synthase. Changes in co ntractility were assessed by measuring the peak rate of rise of LV pre ssure (+dP/dt). Dobutamine increased +dP/dt by 40+/-6% and 73+/-14% in patients with heart failure and control subjects, respectively. Acety lcholine inhibited the +dP/dt response to dobutamine to a similar degr ee in patients with heart failure and control subjects (-39+/-8% and - 31+/-4%, respectively; P=NS). infusion of N-G-monomethyl-L-arginine po tentiated the +dP/dt response to dobutamine by 51+/-15% (P=.01 versus dobutamine) in patients with heart failure but had no effect in contro l subjects (-6+/-4%; P=NS versus dobutamine; P=.0002 versus heart fail ure patients). Conclusions-Inhibition of cardiac NO augments the posit ive inotropic response to beta-adrenergic receptor stimulation in pati ents with heart failure due to idiopathic dilated cardiomyopathy but n ot in control subjects with normal LV function.