Genesis of sigmoidal dose-response curve during defibrillation by random shock: a theoretical model based on experimental evidence for a vulnerable window during ventricular fibrillation.

The sigmoidal dose-response curve (percent success vs shock energy) suggests a probabilistic nature of defibrillation. The mechanism is still largely unknown, however, random variation in the excitable state during ventricular fibrillation (VF) is suspected. A canine defibrillation study was designed to determine whether random variation in absolute VF voltage (AVFV) (a crude marker of number of excitable cells) was related to success of defibrillation, using a DC shock successful at the 50% level. The results were: (a) transmyocardial resistance (73.4 +/- 1.4 vs 73.6 +/- 1.5 ohms) and delivered energy (6.1 +/- 1.2 vs 6.2 +/- 1.2 joules) were similar; however, (b) AVFV 2 msec prior to DC shock was greater for successful as compared to unsuccessful attempts (0.5 +/- 0.1 vs 0.3 +/- 0.0 mV, P less than 0.01). A mathematical model was subsequently developed based on fluctuation in the number of excitable cells. Variation in the state of excitability resulted in a cyclic window potentially vulnerable to defibrillation. The vulnerable window occurred at a point when the number of excitable cells was low, i.e., a higher state of total depolarization, which was in agreement with the experimental finding. For a given VF pattern, duration of the vulnerable window was regulated by the shock energy. A larger shock energy generated a wider vulnerable window and, in turn, a higher success rate. Finally, the sigmoidal dose-response curve of defibrillation was theoretically constructed by calculating the variable chances of a random DC shock occurring either in a vulnerable window or elsewhere during VF. It is concluded that a vulnerable window susceptible to defibrillation can be demonstrated in the early stages (10 sec) of VF. The mathematical model provides a theoretical basis for the vulnerable window and helps elucidate the probabilistic nature of defibrillation.