Cellular electrophysiologic abnormalities of diseased human ventricular myocardium.

Using standard microelectrode techniques, the cellular electrophysiologic features of ventricular myocardium resected from 8 patients with refractory arrhythmias were studied in vitro. Action potentials from damaged myocardium compared with normal myocardium had reduced resting membrane potential, amplitude, and maximal upstroke velocity. Tetrodotoxin, but not verapamil, suppressed 3 action potentials with resting potentials of -60 to -64 mV and Vmax less than 70 V/s. Verapamil, but not tetrodotoxin, suppressed 4 action potentials with resting potentials of -44 to -57 mV and Vmax less than 20 V/s. Unidirectional block, Wenckebach block, and summation occurred in damaged zones. Exit block from and frequency-dependent entrance block into an ectopic focus were noted. Subthreshold responses in the focal area induced by action potentials in the surrounding myocardium and by subthreshold current pulses injected through the recording microelectrode altered the spontaneous discharge rate of the focus, as previously described for modulated parasystole. Pulses early in the spontaneous cycle delayed the next expected discharge, and later pulses accelerated the subsequent discharge. Pulses injected at the singular point completely suppressed automaticity (annihilation). Tetrodotoxin and verapamil suppressed automaticity in some fibers. Single action potentials induced in quiescent fibers triggered and terminated sustained rhythmic activity. These data suggest that depressed fast responses, slow responses, and subthreshold potentials can generate and modulate ectopic activity in damaged human ventricle and that fast- and slow-channel blocking agents and single premature stimuli can terminate such activity.