Clin Res Cardiol 96: Suppl 1 (2007)

V1116 -  Effect of parasympathetic stimulation on heart rate and rhythm in deltaKPQ-SCN5A mice with Long QT Syndrome 3

D. Damke1, L. Fabritz1, S. Laakmann1, L. Fortmüller1, A. Blana1, Chr. Waldeyer1, N. Kreienkamp1, D. Volkery1, M. Tekook1, G. Breithardt1, P. Carmeliet2, E. Carmeliet3, P. Kirchhof1

1Medizinische Klinik und Poliklinik C, Universitätsklinikum Münster, Münster; 2Center for Transgenic Technology and Gene Therapy, KU Leuven, Leuven; 3Lab of Experimental Cardiology, Katholieke Universiteit Leuven, Leuven, Belgien;

Arrhythmias in long QT 3 (LQT3) occur predominantly at rest. Increased vagal tone during sleep has been suggested as an arrhythmogenic trigger in LQT3 but studies in LQT3 patients are scarce.  Methods: Telemetry Holter ECGs were recorded in freely roaming adult mice with the knock-in deletion ΔKPQ SCN5A LQT3 and in WT littermates at baseline, during stress protocols, and during administration of carbachol 0.5 mg/kg with or without chronic oral propranolol. During sedation with isoflurane, 6 lead surface ECGs were recorded. Action potential duration (APD) was measured in isolated, beating hearts in monophasic action potential recorded both at fix RV pacing frequency and during spontaneous rhythm at baseline and during infusion with Carbachol 10-7 to 10-5.  Results: During administration of carbachol, ΔKPQ (6/6) but not WT (0/6) developed prolonged ventricular bigemini or runs of ventricular tachycardia in vivo. In contrast, arrhythmias were not documented during stress tests. Chronic oral propranolol did not protect from carbachol induced arrhythmias in ΔKPQ, p<0.05. Carbachol did not prolong APD at fix pacing frequency, but induced bradycardia and thereby prolonged APD in ΔKPQ LQT3 compared to WT APD and compared to ΔKPQ LQT3 APD at faster heart rate, p<0.05. Conclusions: Parasympathetic stimulation is proarrhythmic and ß-adrenoreceptor block does not protect from arrhythmias induced by parasympathetic stimulation in the ΔKPQ SCN5A LQT3 mouse model.

http://www.abstractserver.de/dgk2007/ft/abstracts/V1116.htm