Abstract 11020: Multi Array Mapping Demonstrates both Conduction Delay and Repolarization Abnormalities in a Murine Model of Brugada Syndrome
Introduction: Both right ventricular (RV) conduction delays and increased RV repolarization heterogeneities are implicated in arrhythmogenesis in Brugada Syndrome (BrS). We use contact mapping to investigate these mechanisms in a genetic mouse Scn5a+/− model.
Methods: Left (LV) and RV electrograms were obtained from a 64-channel multi-electrode recording array in spontaneously beating Langendorff-perfused wild type (WT) and Scn5a+/− hearts. Activation times (AT) and activation recovery intervals (ARIs) were measured and their dispersions calculated.
Results: AT dispersions were larger in RV than LV in Scn5a+/− (18.0 +/− 1.7 vs 12.1 +/− 1.5 ms). They were larger in RVs, but not LVs, of Scn5a+/− than WT (18.0 +/− 1.7 vs 5.0 +/− 1.8 ms), and further lengthened, particularly in the RV, by flecainide (to 37.0 +/− 1.4 ms). Isochronal propagation maps showed (A) ordered impulse propagation from apex to base in WT, (B) lines of partial conduction block in Scn5a+/− leading to (C) conduction spreading around the block to form macro-re-entrant loops. Electrograms along the diagonal axis of the multi-electrode array in (A) and (C) respectively showed (D) clear lines of impulse propagation in one direction only and (E) initial fast propagation followed by conduction delay with double potentials in regions of latest activation. Scn5a+/− hearts showed smaller ARIs but greater dispersions than WT (23.1 +/− 1.1 vs 25.7 +/− 1.0 ms and 11.6+/−0.8 vs 4.1 +/− 0.7 ms in RV). Flecainide further reduced mean ARI values (to 18.4 +/− 1.6 ms in Scn5a+/− in RV), but increased their dispersion (to 19.1 +/− 2.0 ms). Quinidine increased mean ARI (to 36.3 +/− 2.1 ms) but decreased dispersion (to 5.7 +/− 2.1 ms). N =12 in all cases.
Conclusions: Scn5a+/− hearts demonstrate both depolarization and repolarization abnormalities specifically in the RV exacerbated by flecainide. The conduction delay leads to lines of functional block, which can produce arrhythmias through initiation of re-entrant circuits.
- © 2010 by American Heart Association, Inc.