Abstract 10433: Accentuated Circadian Pattern to Ventricular Arrhythmias in Calsequestrin-2 Knockout Mice
Introduction: The incidence of ventricular arrhythmias (VA) in humans shows a major peak at the beginning of the activity period, in the morning hours. This pattern has been attributed to the changes in autonomic nervous system (ANS) activity and local cardiac sensitivity to ANS stimulation. A number of molecularly engineered mouse models have been developed for the study of VA mechanisms. However, their relevance for the study of circadian VA triggers is unknown. Our goal was to examine the 24h pattern of VA in Calsequestrin-2 knockout on C57BL6 background (KO) mice and to compare with that in a transgenic model of heart failure consequent to cardiac-specific overexpression of the proinflammatory cytokine TNF1.6 on FVB background (TNF) mice.
Methods: Continuous telemetry ECG was recorded in 3-month-old (mo) KO males (N=5) and 12-mo TNF females (N=6). The hours of occurrence of arrhythmias were combined into 3h windows and fitted to a 24h-periodic cosine function.
Results: KO mice had multiple VA (≥3 beats), PVCs and junctional (J) beats. The incidence of VA surged in the evening, at the beginning of activity period in rodents; this pattern of VA was well explained by the fitted function (R2=.75; p=.006; Figure). KO mice had a 4x higher VA frequency compared with TNF mice (p<.001) and a 2x greater variation in the incidence of VA over 24h. In contrast, the incidence of PVCs or J-beats in KO mice did not show any circadian pattern.
Conclusions: The VA frequency increases at the beginning of the activity period in mice; the magnitude of such increases varies among the mouse models, which could be useful for studying cardiac responses to ANS stimulation.
- © 2011 by American Heart Association, Inc.