Abstract
BackgroundElectrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice.ResultsWe examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography.ConclusionsWe provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies.
Highlights
Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects
We found heart rate variability to be lower in neonates than adults, initially being very low at PND2-4 before rising with age through 9 weeks (Figure 3A)
The approach described and data reported should be useful to other investigators in designing and implementing studies that investigate the development of tachy- and brady-arrhythmias, heart block, conduction deficits, and modulation of heart rate by the autonomic nervous system in mouse models of human disease
Summary
Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. Studies in the nmd mouse model revealed a previously unobserved cardiomyopathy and arrhythmia later uncovered in spinal muscular atrophy with respiratory distress (SMARD) patients with extended survival [16]. Conduction defects such as ventricular pre-excitation displayed in Wolff-ParkinsonWhite syndrome are faithfully reproduced in PRKAG2 and Alk transgenic mice [17,18]. Mutant mice that reproduce AV block and congenital heart defects were vital in elucidating a molecular pathway, encompassing Nkx2.5, Tbx and Id2, that is essential for development of the cardiac conduction system and is compromised in Holt-Oram syndrome [19,20,21]
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