Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, I: Experimental Studies

Pacing-induced heart failure in the dog recapitulates many of the electrophysiological and hemodynamic abnormalities of the human disease; however, the mechanisms underlying altered Ca handling have not been investigated in this model. We now show that left ventricular midmyocardial myocytes isolated from dogs subjected to 3 to 4 weeks of rapid pacing have prolonged action potentials and Ca transients with reduced peaks, but durations [approximate]3-fold longer than controls. To discriminate between action potential effects on Ca kinetics and direct changes in Ca regulatory processes, voltage-clamp steps were used to examine the time constant for cytosolic Ca removal (tauCa). tauCa was prolonged by just 35% in myocytes from failing hearts after fixed voltage steps in physiological solutions (tauCa control, 216 +/- 25 ms, n = 17; tau (Ca) failing, 292 +/- 23 ms, n = 22; P