In vivo and in vitro cardiac responses to beta-adrenergic stimulation in volume-overload heart failure

► A decline in LV contractility in VO HF is coincident with that of LV myocytes. ► [Ca2 +]i levels were offset by EC coupling proteins with no net effect on function. ► Changes in myofilament proteins contribute to reduced contractility in HF. ► β-AR responsiveness was decreased in vivo HF but preserved in isolated myocytes. ► Reduced connexin-43 contributes to altered basal and β-AR responsiveness in VO HF.