The electrical remodeling occurring after CAVB predisposes the heart to acquired TdP, whereas the structural changes (hypertrophy) are successfully aimed at maintaining cardiac function.

Background-Ventricular arrhythmias are a major cause of sudden death in patients with heart failure and hypertrophy.The dog with chronic complete atrioventricular block (CAVB) has biventricular hypertrophy and ventricular arrhythmias and is a useful model to study underlying cellular mechanisms. We investigated whether changes in Ca 2ϩ homeostasis are part of the contractile adaptation to CAVB and might contribute to arrhythmogenesis. Methods and Results-In enzymatically isolated myocytes, cell shortening, Ca 2ϩ release from the sarcoplasmic reticulum (SR), and SR Ca 2ϩ content were enhanced at low stimulation frequencies. Ca 2ϩ influx through L-type Ca 2ϩ channels was unchanged, but Ca 2ϩ influx via the Na/Ca exchanger was increased and contributed to Ca 2ϩ loading of the SR. Inward Na/Ca exchange currents were also larger. Changes in Ca 2ϩ fluxes were less pronounced in the right versus left ventricle. Conclusions-Enhanced Na/Ca exchange activity may improve contractile adaptation to CAVB but at the same time facilitate arrhythmias by (1) increasing the propensity to Ca 2ϩ overload, (2) providing more inward current leading to (nonhomogeneous) action potential prolongation, and (3)

Background-Amiodarone is an effective antiarrhythmic drug rarely associated with torsade de pointes arrhythmias (TdP).The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired long-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment. Methods and Results-Amiodarone (nϭ7, 40 mg · kg Ϫ1 · d

The alterations responsible for improvement in systolic contractile function in CAVB dogs predispose the hypertrophied heart to DAD-dependent triggered arrhythmias during positive inotropic interventions.