Circulation, Vol 79, 483-490, Copyright © 1989 by American Heart Association
SM Heilbrunn, P Shah, MR Bristow, HA Valantine, R Ginsburg and MB Fowler
Severe heart failure is associated with a reduction in myocardial beta-
adrenergic receptor density and an impaired contractile response to
catecholamine stimulation. Metoprolol was administered during a 6-month
period to 14 patients with dilated cardiomyopathy to examine its effects on
these abnormalities. The mean daily dose of metoprolol for the group was
105 mg (range, 75-150 mg). Myocardial beta-receptor density, resting
hemodynamic output, and peak left ventricular dP/dt response to dobutamine
infusions were compared in 9, 14, and 7 patients, respectively, before and
after 6 months of metoprolol therapy while the patients were on therapy.
The second hemodynamic study was performed 1-2 hours after the morning dose
of metoprolol had been given. Myocardial beta-receptor density increased
from 39 +/- 7 to 80 +/- 12 fmol/mg (p less than 0.05). Resting hemodynamic
output showed a rise in stroke work index from 27 +/- 4 to 43 +/- 3 g/m/m2,
p less than 0.05, and ejection fraction rose from 0.26 +/- 0.03 to 0.39 +/-
0.03 after 6 months of metoprolol therapy, p less than 0.05. Before
metoprolol therapy, dobutamine caused a 21 +/- 4% increase in peak positive
left ventricular dP/dt; during metoprolol therapy, the same dobutamine
infusion rate increased peak positive dP/dt by 74 +/- 18% (p less than
0.05). Thus, long-term metoprolol therapy is associated with an increase in
myocardial beta-receptor density, significant improvement in resting
hemodynamic output, and improved contractile response to catecholamine
stimulation. These changes indicate a restoration of beta-adrenergic
sensitivity associated with metoprolol therapy, possibly related to the
observed up-regulation of beta- adrenergic receptors.
ARTICLES
Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy
Cardiology Division, Stanford University School of Medicine, CA.
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