ALTERATIONS OF K-FAILURE( CURRENTS IN ISOLATED HUMAN VENTRICULAR MYOCYTES FROM PATIENTS WITH TERMINAL HEART)

Prolongation of the action potential has been postulated to be a major reason for the altered diastolic relaxation of the heart in patients with severe heart failure. To investigate the electrophysiological bas is for this action potential prolongation in terminal heart failure, K + currents were recorded in single ventricular myocytes isolated from 16 explanted hearts of patients undergoing transplantation. Results fr om diseased hearts were compared with ventricular cells isolated from six undiseased donor hearts. Action potential duration was significant ly prolonged in cells from patients with heart failure. A delayed rect ifier K+ current was hardly detectable in most cells, and if it could be recorded, it was very small in both diseased and undiseased cells. When currents were normalized for cell surface area, the average curre nt density of the inward rectifier K+ current was significantly reduce d in diseased cells when compared with normal control cells (hyperpola rization at -100 mV, -15.9+/-2.2 vs -9.0+/-1.2 muA/cm2; P<.01). In add ition, a large transient outward K+ current could be recorded in human myocytes. The average current density of the time-dependent component of this transient outward K+ current was significantly reduced in hea rt failure (depolarization at +40 mV, 9.1+/-1.0 vs 5.8+/-0.64 muA/cm2; p<.01). Action potential prolongation in severe heart failure may par tially be explained by a reduction in current densities of the inward rectifier K+ current and of the transient outward K+ current. These al terations may thereby have a significant effect on cardiac relaxation.