Key result
Inhibition of cardiac NO with N(G)-monomethyl-L-arginine potentiated the +dP/dt response to dobutamine by 51% in heart failure patients compared to -6% in normal controls (P=0.0002).
Why the study?
Does inhibition of cardiac nitric oxide synthase potentiate the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure compared to subjects with normal LV function?
Does inhibition of cardiac nitric oxide synthase potentiate the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure compared to subjects with normal LV function?
Inhibition of cardiac nitric oxide synthase augments the positive inotropic response to beta-adrenergic stimulation specifically in patients with heart failure due to idiopathic dilated cardiomyopathy, but not in normal hearts.
May support NOS inhibition to augment beta-adrenergic inotropy in HF; hypothesis-generating, requires randomized confirmation before practice change.
BACKGROUND: We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular (LV) dysfunction. Whether this effect is specific to heart failure per se or is a generalized feature of normal human myocardium is unknown. We therefore tested the hypothesis that inhibition of cardiac NO potentiates the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure but not in subjects with normal LV function. METHODS AND RESULTS: We studied 11 patients with LV failure due to idiopathic dilated cardiomyopathy and 7 control subjects with normal LV function. The beta-adrenergic agonist dobutamine was infused via a peripheral vein before and during concurrent intracoronary artery infusion of acetylcholine, which activates the agonist-coupled isoforms of NO synthase, and N(G)-monomethyl-L-arginine, which inhibits all isoforms of NO synthase. Changes in contractility were assessed by measuring the peak rate of rise of LV pressure (+dP/dt). Dobutamine increased +dP/dt by 40+/-6% and 73+/-14% in patients with heart failure and control subjects, respectively. Acetylcholine inhibited the +dP/dt response to dobutamine to a similar degree in patients with heart failure and control subjects (-39 +/- 8% and -31 +/- 4%, respectively; P=NS). Infusion of N(G)-monomethyl-L-arginine potentiated the +dP/dt response to dobutamine by 51+/-15% (P=.01 versus dobutamine) in patients with heart failure but had no effect in control subjects (-6 +/- 4%; P=NS versus dobutamine; P=.0002 versus heart failure patients). CONCLUSIONS: Inhibition of cardiac NO augments the positive inotropic response to beta-adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.
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Hare et al. (1998) studied Heart failure due to idiopathic dilated cardiomyopathy (n=18). N(G)-monomethyl-L-arginine (NO synthase inhibitor) during dobutamine infusion vs. Control subjects with normal LV function was evaluated on Change in peak rate of rise of LV pressure (+dP/dt) in response to dobutamine during N(G)-monomethyl-L-arginine infusion (p=0.0002). Inhibition of cardiac NO with N(G)-monomethyl-L-arginine potentiated the +dP/dt response to dobutamine by 51% in heart failure patients compared to -6% in normal controls (P=0.0002).
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