Electroporation of the cardiac cell membrane may result from intense electric fields applied to cardiac muscle, associated for example with defibrillation and cardioversion. We analyzed the distribution of voltage levels sufficient to cause electroporation in enzymatically isolated frog cardiac cells, using the cell-attached patch-clamp technique with rectangular pulses similar to those used in experimental studies of cardiac defibrillation. Five-millisecond monophasic or ten-millisecond biphasic symmetric (1/1) and asymmetric (1/0.5) rectangular pulses of either polarity were applied to the cell membrane in 100-mV steps from 0.2 to 0.8 V. The membrane conductance was continuously monitored by a low-voltage pulse train. In a total of 77 cells, we observed a step increase in conductance, occurring in 21% of cells at a transmembrane potential of 0.3 V, 52% at 0.4 V, 14% at 0.5 V, and 13% at 0.6-0.8 V. Electroporation occurred with this voltage distribution regardless of pulse shape, polarity, or the presence of all of the following ionic channel blockers: tetrodotoxin, barium, tetraethylammonium, 4-aminopyridine, cadmium, nickel, and gadolinium. The time course of membrane recovery was highly variable. The maintenance of a high membrane conductance after the shock pulse was associated with irreversible cell contracture provided that Ca2+ was included in the patch-pipette solution. However, with biphasic asymmetric pulses, the conductance recovered very quickly (< or = 37 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

During defibrillation, cardioversion, and electrocution trauma, heart cells are exposed to potential gradients that increase the transmembrane potential (Vm). At sufficiently high Vm, pathological increases in cell permeability can occur. With enzymatically isolated frog heart cells (n = 29) we investigated the voltage and time sufficient for electroporation or cardiac cell membranes with rectangular voltage pulses, particularly with 5-msec monophasic, and 5- or 10-msec biphasic pulses. The rectangular voltage pulse (monophasic 0.1-1.5 V, 0.1-100 msec or symmetric biphasic 0.1-1 V, 0.4-10 msec [total duration]) was applied to the cell membrane using the cell-attached patch clamp technique, and a low voltage pulse train was added so that membrane conductance could be monitored continuously. Step increases in membrane conductance (breakdown) were observed, indicative of electroporation, and occurred with different combinations of pulse amplitude and duration; for example, for monophasic square pulses: (1 V, 0.2 msec) or (0.5 V, 0.5 msec), and for biphasic pulses: (1 V, 0.4 msec total duration) or (0.5 V, 0.8 msec). Using 5- or 10-msec rectangular pulses, breakdown occurred at a voltage around 0.4 V independent of polarity or waveform. The recovery of the permeabilized cell membrane after the voltage pulse was highly variable, in some cases not recovering at all while in other cases recovering after a lapse of seconds to minutes. These results suggest that monophasic and biphasic pulses of approximately 1 V, 0.2-0.4 msec and approximately 0.4 V, 5 msec can permeabilize the heart cell membrane even for minutes, time enough to cause an alteration in the cellular ionic composition leading to depressed or unexcitable tissue, a precursor for cardiac arrhythmia.

This study demonstrates that thousands of patients have been affected by pacemaker and ICD malfunctions, the pacemaker malfunction replacement rate has decreased, the ICD malfunction replacement rate increased during the latter half of the study, and the ICD malfunction replacement rate is significantly higher than that for pacemakers. Although pacemakers and ICDs are important life-sustaining devices that have saved many lives, careful monitoring of device performance is still required.

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These results show a rapid and progressive electrophysiological deterioration during fibrillation, leading to electrical diastole between fibrillation action potentials. This rapid deterioration may explain the decreased probability of successful resuscitation after prolonged fibrillation. Therefore, a greater understanding of cellular deterioration during fibrillation may lead to improved resuscitation methods, including development of specific defibrillator waveforms for out-of-hospital cardiac arrest.