The ventricular defibrillation and upper limit of vulnerability dose-response curves.
INTRODUCTION: A stimulus delivered in the T wave of a paced cardiac cycle can induce ventricular fibrillation (VF). If the stimulus strength is increased, the probability of inducing VF decreases. This study determines an ideal mathematical model (a dose-response curve) for the relationship between the shock strength and the probability of inducing VF or defibrillating. METHODS AND RESULTS: Defibrillating electrodes were implanted in the right ventricle and superior vena cava in 16 pigs. The electrode in the vena cava was electrically connected to a cutaneous patch. The same electrodes were used for both VF induction and defibrillation. T wave stimuli were given at the peak of the T wave according to a modified up-down protocol (40 V up, 20 V down). When a T wave stimulus induced VF, a defibrillation stimulus was delivered 10 seconds later, also according to the modified up-down protocol. Exponential, logistic, log-dose logistic, piecewise linear and Box-Tiao dose-response curves were fit to the resulting data using the maximum likelihood method. For the defibrillation data, it was found that only the logistic and Box-Tiao curves fit all of the animals (P < 0.05). For VF induction, only the Box-Tiao curve fit all of the animals (P < 0.05). Extrapolating along a dose-response curve that did not fit to a shock strength with a very low probability of inducing VF or a very high probability of defibrillating yielded errors as great as 610 V. CONCLUSION: The Box-Tiao dose-response curve is the best single choice for fitting VF induction or defibrillation datasets.
Malkin, RA; Souza, JJ; Ideker, RE
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