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 (VFJ is suspected. A canine defibrillation study was designed to determine whether random variation in absolute VF voltage (AVFVJ of crude marker of number of excitable cells) was related to success of defibrillufion, using a DC shock successful at the 50% level. The results were: (a) fransmyocardial 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 < 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 defibrillafion 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.