From the Cardiomyopathy Programs and Cardiovascular Divisions, Boston
Medical Center, Boston, Mass (M.M.G., W.S.C.); Johns Hopkins Medical
Institutions, Baltimore, Md (J.M.H.); Brigham and Women's Hospital,
Boston, Mass (M.M.G., W.S.C.); Boston University School of Medicine, Boston,
Mass (M.A.C.); Johns Hopkins School of Medicine, Baltimore, Md (J.M.H.); and
Harvard Medical School, Boston, Mass (M.A.C.).
Correspondence to Wilson S. Colucci, MD, Cardiomyopathy Program, Boston Medical Center, 88 E Newton St, Boston, MA 02118. E-mail wcolucci{at}acs.bu.edu
Background—We previously showed that
cardiac nitric oxide (NO) inhibits the positive inotropic response to
ß-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
ß-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 ß-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
NG-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
NG-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 ß-adrenergic receptor stimulation in patients
with heart failure due to idiopathic dilated
cardiomyopathy but not in control subjects with
normal LV function.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Increased Sensitivity to Nitric Oxide Synthase Inhibition in Patients With Heart Failure
Potentiation of ß-Adrenergic Inotropic Responsiveness
Key Words: nitric oxide • heart failure • cardiomyopathy • contractility • receptors, adrenergic, beta
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