Abstract 8520: Total beta-Adrenoceptor Knockout Slows Conduction and Reduces Inducible Arrhythmias in the Mouse Heart
Introduction: Beta-Adrenocepors (ß-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (ß1, ß2 and ß3) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. We assessed the hypothesis that TKO leads to considerable changes in electrophysiological parameters.
Methods: We performed in vivo electrophysiological studies using right heart catheterisation in 10 TKO mice at the age of 14 weeks. As controles served 10 wild type mice (WT) with identical genetic background (129SV). We analyzed standard ECG- and electrophysiological parameters and arrhythmia inducibility.
Results: The surface ECG of TKO mice revealed a reduced heart rate (359.2 ± 20.9bpm vs. 461.1 ± 33.3bpm; p <0.001) as well as prolonged P wave (17.5 ± 3.0ms vs. 15.1 ± 1.2ms; p=0.019) and PQ time (40.8 ± 2.4ms vs. 37.3 ± 3.0ms; p=0.013) compared to WT. Intracardiac ECG revealed a significantly prolonged infrahisian conductivity (12.9 ± 1.4ms vs. 6.8 ± 1.0ms; p <0.001). Functional testing showed extended atrial and ventricular refractory periods in TKO (40.5 ± 15.5ms vs. 21.3 ± 5.8ms; p = 0.004; and 41.0 ± 9.7ms vs. 28.3 ± 6.6; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p < 0.001) and the probability of induction of ventricular tachycardias (0% vs. 26%; p < 0.001) were reduced.
Conclusion: TKO results in significant prolongation in cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. This finding confirms the importance of ß-AR in arrhythmogenesis and their role as therapeutic target.
- © 2011 by American Heart Association, Inc.