Abstract 5306: Cardiac Resynchronization Therapy Restores β-Adrenergic Reserve of Ca2+ Homeostasis in a Canine Model of Dyssynchronous Heart Failure
Alterations in L-type calcium channel properties, Ca2+ homeostasis and their contribution to the blunted adrenergic responsiveness in dyssynchronous heart failure (DHF) and recovery after cardiac resynchronization therapy (CRT) remain largely unexplored. Adult dogs underwent LBB ablation and right atrial pacing (190–200 bpm) for either 6 weeks (DHF dogs: n=7) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT dogs: n=7). Myocytes were isolated from the LV anterior (ANT) and lateral (LTR) walls in non-failing (NF), DHF and CRT dogs. L-type Ca2+ current (ICa,L) and [Ca2+]i transients (CaT) were measured in absence (baseline) and presence of 200 nmol/L isoproterenol (ISO) using the whole-cell patch clamp and indo-1 fluorescence, respectively. DHF reduced baseline ICa,L density in the LTR but not ANT cells, and CRT restored the DHF-induced reduction of ICa,L density. DHF significantly reduced the ISO responsiveness of ICa,L in both ANT and LTR cells, but CRT completely restored the ISO responsiveness of ICa,L. ISO produced a significant leftward shift (≈ −5mV) of the ICa,L activation curve in NF and CRT but not in DHF myocytes (Figure A). DHF reduced baseline and ISO-induced CaT amplitude especially in the LTR cells, and CRT partially restored the DHF-induced reduction of CaT at baseline and with ISO (Figure B). CRT restores DHF-induced reduction of ICa,L at baseline and β-adrenergic responsiveness, as well as improves Ca handling, which may contribute to improvement in contractility and restoration of adrenergic responsiveness of the failing heart.