Abstract 10553: APD418, A Selective Beta3-Adrenergic Receptor Antagonist Enhances Cardiac Positive Inotropic and Lusitropic Responses to Dobutamine in Conscious, Chronically-Instrumented Dogs With Pacing-Induced Heart Failure: Assessment by Pressure-Volume Analysis

Background: Attenuation of heart failure (HF) response to positive inotropic agents such as dobutamine (DOB) represents a major clinical problem. The regulation of cardiac function by catecholamine involves 3 populations of β-adrenergic receptors (AR). β1-and β2-AR stimulation produces an increase in contractility, and β3-AR stimulation mediates a negative inotropic effect. In HF, β3-AR-mediated negative action is increased due to β3-AR upregulation. Since DOB is a non-selective β-AR agonist, the diminished response of DOB in HF patients may be caused by DOB-induced β3-AR stimulation. Therefore, we tested the hypothesis that APD418, a novel, potent, selective, human β3-AR antagonist (β3-ANT), may restore cardiac positive responses to DOB in HF. Methods: We compared the effect of APD418 treatment (1.9 mg/kg, iv, 10 min) on left ventricular (LV) systolic and diastolic performance and LV contractile response to DOB (6 μg/kg/min, iv, 10 min) in 5 chronically-instrumented, conscious dogs after pacing-induced H...