Enhanced Ca2+ release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes - Potential link between contractile adaptation and arrhythmogenesis

Background-Ventricular arrhythmias are a major cause of sudden death in pat ients with heart failure and hypertrophy. The dog with chronic complete atr ioventricular block (CAVB) has biventricular hypertrophy and ventricular ar rhythmias and is a useful model to study underlying cellular mechanisms. We investigated whether changes in Ca2+ homeostasis are part of the contracti le adaptation to CAVE and might contribute to arrhythmogenesis. Methods and Results-In enzymatically isolated myocytes, cell shortening, Ca 2+ release from the sarcoplasmic reticulum (SR), and SR Ca2+ content were e nhanced at low stimulation frequencies; Ca2+ influx through L-type Ca2+ cha nnels was unchanged, but Ca2+ influx via the Na/Ca exchanger was increased and contributed to Ca2+ loading of the SR. Inward Na/Ca exchange currents w ere also larger. Changes in Ca2+ fluxes were less pronounced in the right v ersus left ventricle. Conclusions-Enhanced Na/Ca exchange activity may improve contractile adapta tion to CAVE but at the same time facilitate arrhythmias by (1) increasing the propensity to Ca2+ overload, (2) providing more inward current leading to (nonhomogeneous) action potential prolongation, and (3) enhancing (arrhy thmogenic) currents during spontaneous Ca2+ release.