Postcountershock fibrillation in digitalized myocardial cells in vitro.

Postcountershock arrhythmias are potentiated in patients receiving digitalis; and these arrhythmias frequently lead to irreversible ventricular fibrillation and death. The mechanisms underlying this potentiation are largely unknown. The purpose of this study was to determine whether an accentuation of electric shock induced arrhythmias was produced in in vitro myocardial cells by ouabain, a fast-acting digitalis glycoside. Such an accentuation would suggest that the in vivo potentiation occurred in the individual myocardial cell rather than through some secondary mechanism such as action on the nervous system as had been previously suggested. Myocardial cells grown in vitro were subjected to 5 msec square wave electric field stimulation of varying intensity. Pre- and postshock arrhythmias were evaluated using a photovoltaic cell mounted on a closed-circuit television monitor. The photocell converted the change in light intensity produced by cellular contraction to an electrical signal which was then processed and displayed on a strip chart recorder. Fibrillation of the cell sheet and of portions of individual myocardial cells could be observed visually on the television monitor. "Therapeutic" (antiarrhythmic) concentrations of ouabain were observed in the range of 1 x 10(-6)M to 5 x 10(-6)M; "toxic" (arrhythmia producing) concentrations were above 1 x 10(-5)M. Electric shocks of intensities which produced a short postshock arrest in nondigitalized cells, produced an increased duration of arrest proportional to the ouabain concentration in the range of 5 x 10(-8)M to 7 x 10(-6)M. Cellular fibrillation has been previously observed in in vitro myocardial cells after extremely high shock intensities in the absence of ouabain or after toxic concentrations of ouabain in the absence of electric shock. Similar cellular fibrillation was observed in this study after low intensity electric shocks in cells exposed to low concentrations of ouabain, neither of which produced cellular fibrillation alone. Because this cellular fibrillation in vitro appears to be related to "irreversible" fibrillation in vivo, these results suggest that the deleterious interactions between digitalis and electric countershock occur directly in the myocardial cell and that postshock cellular fibrillation may be the basis for the "unmasking" of digitalis toxicity by electric countershock which has been of clinical concern.