Mechanisms in Adrenergic Dependent Onset of Torsades de Pointes

Pause dependent onset of torsades de pointes is characteristic in acquired long QT syndromes, and the probable mechanism is reentry facilitated by increased disparity of refractoriness following a long cycle. Adrenergic dependent onset is usual in familial long QT syndromes, and the mechanism is uncertain. In this study with a computer simulation of torsades de pointes, possible mechanisms of adrenergic dependent onset have been identified. Decreased refractory periods facilitated the initiation of torsades de pointes by permitting earlier premature excitation and allowing reentry in the presence of the shorter refractory period that had been further shortened by the earlier excitation. In addition, accelerating rate resulted in responses occurring in the presence of refractory periods set by the prior response so each response was premature with respect to the preceding one. The difference between cycle lengths and refractory period decreased with increasing rate leading to the functional block required for initiation of simulated torsades de pointes. Findings define possible mechanisms by which the adrenergic effects of reduced refractory period duration and increased rate may lead to the initiation of torsades de pointes.