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Background— Studies in isolated cardiac myocytes have demonstrated that signaling via specific β₁-adrenergic receptor subtypes (β₁ARs) promotes but that signaling via β₂ARs protects from cell death. We hypothesized that prolonged β₂AR stimulation or β₁AR blockade would each protect myocytes from death and thereby ameliorate cardiac remodeling in chronic heart failure.

Methods and Results— A large myocardial infarction (MI) induced in rats by coronary artery ligation resulted in a dilated cardiomyopathy (DCM) characterized by infarct expansion and a progressive increase in left ventricular (LV) end-diastolic volume, accompanied by a reduction in ejection fraction (EF), as assessed by repeated echocardiography. Pressure-volume analysis at 8 weeks after ligation showed that diastolic stiffness (Eed) and arterial elastance (Ea) were increased, end-systolic elastance (Ees) was decreased, and …