title: Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy.
abstract: 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.
authors.affiliation: Cardiology Division, Stanford University School of Medicine, CA.
authors.forename: S M
authors.initials: SM
authors.lastname: Heilbrunn
authors.forename: P
authors.initials: P
authors.lastname: Shah
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
authors.forename: H A
authors.initials: HA
authors.lastname: Valantine
authors.forename: R
authors.initials: R
authors.lastname: Ginsburg
authors.forename: M B
authors.initials: MB
authors.lastname: Fowler
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000188:drug therapy*; D004280:Dobutamine; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors
chemical_list: D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D008790:Metoprolol