Ionic remodeling of cardiac Purkinje cells by congestive heart failure

Background-Cardiac Purkinje cells (PCs) are important for the generation of triggered arrhythmias, particularly in association with abnormal repolariz ation. The effects of congestive heart failure (CHF) on the ionic propertie s of PCs are unknown. Methods and Results-PCs were isolated from false tendons of control dogs an d dogs with ventricular tachypacing-induced CHF. CHF PCs were hypertrophied (capacitance, mean +/- SEM, 149 +/-4 pF, n= 130; versus 128 +/-3 pF, n= 15 0, control; P +/-0.001). Transient outward current density was reduced in C HF PCs without change in voltage dependence or kinetics. CHF also reduced i nward-rectifier current density, with no change in form of the current-volt age relationship. Densities of L- and T-type calcium, rapid and slow delaye d rectifier, and Na+-Ca2+ exchange currents were unaltered by CHF, but L-ty pe calcium current inactivation was slowed at positive potentials. Purkinje fiber action potentials from CHF dogs showed decreased phase I amplitudes and elevated plateau voltages and demonstrated twice as much prolongation o n exposure to the rapid delayed rectifier blocker E-4031 as control Purkinj e fibers. Conclusions-CHF causes remodeling of important K+ and Ca2+ currents in card iac PCs, decreasing repolarization reserve and causing an exaggerated repol arization delay in response to a class III drug. These results have importa nt potential implications regarding ventricular arrhythmogenesis, particula rly related to triggered activity in PCs, in patients with CHF.