(Circulation. 1995;92:1793-1800.)
© 1995 American Heart Association, Inc.
Articles |
Functional Significance of Presynaptic 
-Adrenergic Receptors in Failing and Nonfailing Human Left Ventricle
From the Cardiovascular Division (J.D.P., G.E.N., J.S.F.), Departments of Medicine, Mount Sinai Hospital and the Toronto Hospital, University of Toronto, Toronto, Ontario, Canada; and the Cardiovascular Division (J.S.L., W.S.C.), Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to John D. Parker, MD, Cardiovascular Division, Rm 1609, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada M5G 1X5.
Background There are 
-adrenergic receptors on human
myocardium that exert positive inotropic effects. The
effect of -adrenergic receptor blockade on human left
ventricular (LV) performance has not been fully
explored. Although -adrenergic receptor blockade might have effects
on LV function that are mediated via blockade of postsynaptic
myocardial -adrenergic receptors, it is also possible that blockade
of presynaptic 2-adrenergic receptors and subsequent
increased release of norepinephrine would have effects on
LV performance. In the present study, we explored the
effects of nonselective -adrenergic receptor blockade on LV
performance and transcardiac
norepinephrine concentrations in a group of patients with
normal LV function and in a group of patients with congestive heart
failure secondary to dilated cardiomyopathy.
Methods and Results Using an intracoronary drug
infusion technique, we administered the nonselective -adrenergic
antagonist phentolamine to 13 patients with normal
LV function and 19 patients with congestive heart failure secondary to
dilated cardiomyopathy. With a high-fidelity LV
catheter, the systolic (+dP/dt) and diastolic (-dP/dt and
Tau) LV function responses to intracoronary infusion of
phentolamine (0.2 mg/minx5 minutes) were assessed. In 8
patients with normal ventricular function and 10 patients
with congestive heart failure, arterial and
coronary sinus blood samples were drawn to determine the
effects of phentolamine on catecholamine
concentrations. Phentolamine had no measurable effect on LV
performance or catecholamine concentrations in the
normal ventricular function group. In patients with
congestive heart failure, intracoronary
phentolamine caused a significant increase in +dP/dt and the
rate of isovolumic LV relaxation (-dP/dt and Tau). These
hemodynamic effects were accompanied by a significant
increase in coronary sinus norepinephrine
concentration but no change in arterial
norepinephrine concentration.
Conclusions Myocardial -adrenergic receptor blockade causes
significant inotropic and lusitropic effects in the failing but not the
nonfailing human LV. These effects appear to be mediated by increased
release of norepinephrine from cardiac nerves secondary to
blockade of presynaptic 2-adrenergic receptors.
Differences in the responses of the failing and nonfailing human LV
appear to reflect the higher level of sympathetic activation that is
seen in the group with congestive heart failure. This suggests that the
presynaptic 2-adrenergic receptor exerts a tonic
inhibitory effect on the release of
norepinephrine from cardiac nerves in patients with
congestive heart failure.
Key Words: receptors • adrenergic • alpha • diastole • cardiomyopathy
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