Increased a-Receptor Density and Improved Hemodynamic Response to Catecholamine Stimulation During Long-term Metoprolol Therapy in Heart Failure From Dilated Cardiomyopathy

Severe heart failure is associated with a reduction in myocardial P3-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 efrects on these abnormalities. The mean daily dose of metoprolol for the group was 105 mg (range, 75150 mg). Myocardial ,B-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 f-receptor density increased from 39±7 to 80±12 fmol/mg (p<0.05). Resting hemodynamic output showed a rise in stroke work index from 27±4 to 43±3 g/m/m2, p <0.05, and ejection fraction rose from 0.26± 0.03 to 0.39± 0.03 after 6 months of metoprolol therapy, p <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<0.05). Thus, long-term metoprolol therapy is associated with an increase in myocardial X-receptor density, significant improvement in resting hemodynamic output, and improved contractile response to catecholamine stimulation. These changes indicate a restoration of f3-adrenergic sensitivity associated with metoprolol therapy, possibly related to the observed up-regulation of j3-adrenergic receptors. (Circulation 1989;79: 483-490)