Abstract 5337: Sympathetic Stimulation Initiates Dynamic Triggered Activity that Degenerates into pVT and VF in LQT1 Rabbits
Sympathetic stimulation is a known trigger for polymorphic ventricular tachycardia (pVT) in long QT syndrome (LQTS). pVT is initiated by different stimuli (physical activity or startle) in different genotypes of LQTS. We exposed transgenic LQT1 and LQT2 rabbits to isoproterenol (ISO) infusion (to mimic physical activity) or bolus (to mimic sudden sympathetic surge) to assess the differential effects of these sympathetic stimulation modes on arrhythmia and refractoriness. In vivo electrophysiological studies (EPS) were performed at baseline and with ISO infusion. Early afterdepolarizations (EADs) and pVT were mapped in Langendorff perfused hearts after AV node ablation and ISO bolus (140 nM) or infusion (40nM) using optical mapping. In vivo ISO infusion shortened the ventricular effective refractoriness (VERP) in LQT2 (n=8, p<0.01). However, in LQT1 rabbits ISO infusion failed to shorten VERP. In isolated hearts, bolus injection of ISO triggered EADs in LQT2 rabbits (2/6) and in one case pVT and VF. However, continuous ISO infusion shortened APD and did not trigger pVT. In contrast, in LQT1 both infusion and bolus of ISO did not alter APD and triggered EADs in multiple dynamic foci that generated pVT and VF (4/4). No pVT occurred during ISO infusion in vivo in either genotype. In conclusion, sympathetic stimulation mode is critical in triggering EADs and pVT in different LQTS genotypes. Furthermore, continuous sympathetic stimulation shortens refractoriness in LQT2, failing to generate EADs. By contrast, in LQT1 rabbits, continuous stimulation generates dynamic triggered activity in multiple sites that degenerated into VF in the absence of change in cardiac refractoriness.