Determinants of slowed conduction in premature ventricular beats induced during programmed stimulations in perfused guinea-pig heart

What is the central question of this study? Is the slowed conduction upon premature ventricular activations during clinical electrophysiological testing attributable to the prolonged activation latency, or increased impulse propagation time, or both? What is the main finding and its importance? Prolonged activation latency at the stimulation site is the critical determinant of conduction slowing and associated changes in the ventricular response intervals in premature beats initiated during phase 3 repolarization in perfused guinea-pig heart. These relations are likely to have an effect on arrhythmia induction and termination independently of the presence of ventricular conduction defects or the proximity of the stimulation site to the re-entrant circuit.

During cardiac electrophysiological testing, slowed conduction upon premature ventricular activation can limit the delivery of the closely coupled impulses from the stimulation site to the region of tachycardia origin. In order to examine the contributing factors, in this study, cardiac conduction intervals and refractory periods were determined from left ventricular (LV) and the right ventricular (RV) monophasic action potential recordings obtained in perfused guinea-pig hearts. A premature activation induced immediately after the termination of the refractory period was associated with conduction slowing. The latter was primarily accounted for by the markedly increased (+54%) activation latency at the LV stimulation site, with only negligible changes (+12%) noted in the LV-to-RV delay. The prolonged activation latency was acting to limit the shortest interval at which two successive action potentials can be induced in the LV and RV chambers. The prolongation of the activation latency in premature beats was accentuated upon an increase in the stimulating current intensity, or during hypokalaemia. This change was related to the reduced ratio of the refractory period to the action potential duration, which allowed extrastimulus capture to occur earlier during phase 3 repolarization. Flecainide, a Na⁺ channel blocker, prolonged both the activation latency and the LV-to-RV delay, without changing their relative contributions to conduction slowing. In summary, these findings suggest that the activation latency is the critical determinant of conduction slowing and associated changes in the ventricular response intervals upon extrastimulus application during phase 3 of the action potential.