Effects of the beta 1-adrenergic receptor partial agonist xamoterol on left ventricular diastolic function. An evaluation after 1-6 years of oral therapy

Abstract

Acute intravenous administration of the new beta 1-adrenergic receptor partial agonist xamoterol lowers left ventricular end-diastolic pressure and improves the isovolumic indexes of inotropic state and relaxation. To determine if these hemodynamic changes were maintained after prolonged administration, the dose-response relation to cumulative doses of xamoterol was determined in a group of 14 patients with mild (n = 6)-to-serve (n = 8) ischemic left ventricular dysfunction. These patients had been treated with xamoterol (200 mg, b.i.d.) for a mean of 51 +/- 17 months, and the drug had been stopped for 72 hours before testing the responsiveness to xamoterol. In these patients, xamoterol administration still induced dose-dependent decreases in left ventricular end-diastolic pressure from 21.4 +/- 8.2 to 15.8 +/- 7.7 mm Hg (p less than 0.01, vs. baseline and vs. the control data 51 +/- 17 months before). Peak positive dP/dt and dP/dt normalized to a developed pressure of 40 mm Hg [( dP/dt]/DP40) increased by 14% and 23%, respectively (p less than 0.01), whereas the rate of isovolumic pressure decrease improved by 12% (p less than 0.01). It is concluded that the myocardial response to xamoterol is maintained after years of continuous therapy, and that in patients with heart failure, this response was expressed mainly as a reduction in left ventricular end-diastolic pressure.