Abstract 17882: Complex Dynamics of Multiple Early After Depolarizations (eads) and Their Propagation Underlie Polymorphic Vts (pvt) in Transgenic Rabbit Model of Lqt1
Long QT syndrome type 1 (LQT1) is a congenital disease arising from a loss of function in the slowly activating delayed potassium current (IKs), which causes EADs and pVTs under sympathetic stimulation. We investigated mechanisms underlying pVT initiation and maintenance using a transgenic rabbit model of LQT1. Hearts were perfused in a Langendorff perfusion system and AV node was ablated to control the heart rate. Cardiac action potentials from the anterior surface were recorded using a voltage sensitive dye and CMOS cameras (2х2 cm2 field of view). Bolus injection of isoproterenol (140 nM) increased APD dispersion, most notably between RV/LV at slow heart rates, and induced pVTs (n=9 out of 10 hearts). pVTs were initiated by EADs from the RV (n=16 out of 18 pVTs), which subsequently trigger series of focal activities associated with the oscillating QRS complex in the ECGs. The average nearest neighbor ratio of foci to random events was 0.9, indicating a relatively uniform distribution of focal activities across the ventricles. This suggests that foci slowly move around the heart to produce the shifting QRS axis of pVTs. The histogram of [dV/dt]max shows two populations of action potentials: mainly driven by INa or ICa (panel A). Addition of 2 μM TTX to block INa reduces the number of focal activities and constrains the focal sites to the RV region (panel B), corroborating the importance of INa in maintaining pVTs. In conclusion, our data revealed that continuously re-triggered focal activities, heavily influenced by INa, play a significant role in maintaining pVTs in the LQT1 model.
- © 2013 by American Heart Association, Inc.