Effects of premature responses on vulnerability to fibrillation in a computer model

The purpose of this study was to determine the effects of premature responses on vulnerability to fibrillation using a computer model based on the wavelet hypothesis. The model simulated propagation, nonuniform recovery of excitability, and slow propagation during incomplete recovery. Vulnerability was assessed as the fibrillation threshold, which was defined as the duration of train stimulation required to initiate self-sustained reentrant excitation with multiple excitation fronts. The fibrillation threshold was determined at various premature cycle lengths in the presence of refractory periods of varied range and duration, at various rates, and after compensatory pauses and varied patterns of consecutive premature responses. The fibrillation threshold was found to be reduced by premature responses, and with increasing premature cycle length, there was an initial decrease followed by an increase of fibrillation threshold. The fibrillation threshold was directly related to the duration and indirectly related to the range of the refractory period. The time phase of curves relating premature cycle length and fibrillation threshold was such that premature responses at some cycle lengths were associated with a lower fibrillation threshold in the presence of longer refractory periods, with slower rates, and with an immediately preceding compensatory pause. The mechanism may be important in the proarrhythmia effects of drugs that prolong repolarization and in the bradycardia-tachycardia syndrome. Consecutive premature responses at a constant rate increased the fibrillation threshold in comparison with the initial response, while consecutive responses at an accelerating rate decreased the fibrillation threshold.