Experimental evidence of improved transthoracic defibrillation with electroporation-enhancing pulses

There is considerable work on defibrillation wave form optimization. This paper determines the impedance changes during defibrillation, then uses that information to derive the optimum defibrillation wave form. Methods Part I: Twelve guinea pigs and six swine were used to measure the current wave form for square voltage pulses of a strength which would defibrillate about 50% of the time. In guinea pigs, electrodes were placed thoracically, abdominally and subcutaneously using two electrode materials (zinc and steel) and two electrode pastes (Core-gel and metallic paste). Results Part I: The measured current wave form indicated an exponentially increasing conductance over the first 3 ms, consistent with enhanced electroporation or another mechanism of time-dependent conductance. We fit this current with a parallel conductance composed of a time-independent component (g(0) = 1.22 +/- 0.28 mS) and a time-dependent component described by g(Delta) (1 - e(-t/tau)), where g(Delta) = 0.95 +/- 0.20 mS and tau = 0.82 +/- 0.17 ms in guinea pigs using zinc and Cor-gel. Different electrode placements and materials had no significant effect on this fit. From our fit, we determined the stimulating wave form that would theoretically charge the myocardial membrane to a given threshold using the least energy from the defibrillator. The solution was a very short, high voltage pulse followed immediately by a truncated ascending exponential tail. Methods PART II: The optimized wave forms and similar nonoptimized wave forms were tested for efficacy in 25 additional guinea pigs and six additional swine using methods similar to Part I. Results Part II: Optimized wave forms were significantly more efficacious than similar nonoptimized wave forms. In swine, a wave form with the short pulse was 41% effective while the same wave form without the short pulse was 8.3% effective (p < .0.03) despite there being only a small difference in energy (111 J versus 116 J). Conclusions: We conclude that a short pulse preceding a defibrillation pulse significantly improves efficacy, perhaps by enhancing electroporation.