Session S71.6

Circadian Pattern to Ventricular Arrhythmias in Mouse Models of Heart Failure and Arrhythmia

V Shusterman*, CF McTiernan, H Mehdi, B London

University of Pittsburgh
Pittsburgh, PA, USA

Introduction: Arrhythmias and sudden cardiac death are more frequent during the morning hours in humans. Transgenic and gene-targeted mouse models have been used to identify the molecular basis of cardiac ionic currents and arrhythmia mechanisms. It is not known whether a circadian pattern of arrhythmias is present in mice.
Methods: Mice with cardiac-specific overexpression of tumor necrosis factor alpha (TNF1.6mice) develop a dilated cardiomyopathy, atrial/ventricular arrhythmias (VA) and heart failure. Mice heterozygous for a targeted deletion of Merg1 (Merg1+/-mice) have QT prolongation and VA. Animals were maintained on a 12hr light/dark cycle (7AM on - 7PM off).
Radio-telemetry monitors (DSI) were implanted and 24hr, ambulatory, single-lead ECG was recorded = 5 days later at 400 Hz sampling rate. VA were grouped into 3hr intervals and normalized by total ectopy. ECG analysis was performed using custom software.
Results: TNF1.6 (n=7) and Merg1+/-mice (n=3) had more frequent PVCs and complex ectopy (couplets, nonsustained VA) during the evening (p=0.01). The circadian pattern of ectopy in TNF1.6mice peaked before the onset of activity period (p=0.049). Complex ectopy occurred more often between 3PM and midnight (TNF1.6mice: 204/231; Merg1+/-mice: 37/40).
Conclusions: Genetic mouse models of heart failure and long QT syndrome develop arrhythmias with circadian variation. Similar to humans, arrhythmias are more frequent shortly before or during the interval of increased activity (human, diurnal; rodents, nocturnal). These models may be useful for the study of the molecular/genetic basis for the circadian variation in arrhythmias and sudden death using continuous electrocardiographic telemetry monitoring.

(Abstract Control Number: 120)