Abstract 13806: Enhanced Atrial Automaticity Causes Ca Triggered Atrial Fibrillation in a Casq2-linked CPVT Mouse Model
Introduction Patients affected by catecholaminergic polymorphic ventricular tachycardia (CPVT), a familiar arrhythmogenic disorder, exhibit an increased risk for atrial fibrillation (AF). Although Casq2-/-mice represent a well established CPVT model for ventricular arrhythmias, AF inducibility in these animals has never been reported. Here we assess AF susceptibility in Casq2-/- mice and explore its underlying electrophysiological mechanisms.
Methods Atrial burst pacing (50Hz, 2s) was used to quantify AF susceptibility in Langendorff perfused hearts from Casq2-/- and wild-type (WT) littermates. Optical voltage and Ca maps were obtained from the posterior wall and pulmonary vein region of atria during sinus rhythm and during AF (Figure) and anatomical origin of AF determined.
Results AF was induced in 10 out of 11 Casq2-/- but not in WT hearts ( 0/7, p<0.01). In Casq2-/- hearts, atrial activation during AF occurred almost simultaneously from multiple independent sites separated by electrical silence (Figure). Action potential duration (ADP) and atrial conduction velocity (CV) were unaltered (Casq2-/-: ADP90: 32.7±1.2ms vs WT: 33.5±1.3ms, p=0.2; Casq2-/-: CV 60±2 cm/s vs. WT: 58±3 cm/s, p=0.5). Optical Ca maps showed that subthreshold diastolic Ca waves preceeded AF induction in all Casq2-/- atria. Diastolic Ca waves were never observed in WT atria. Conclusions Casq2-/- hearts are susceptible to AF. The multifocal pattern of activation during AF together with the increased Ca wave frequency in Casq2-/- intact atria is most consistent with a Ca triggered mechanism of AF.
- © 2012 by American Heart Association, Inc.