Heier Christopher R, Hampton Thomas G, Wang Deli, Didonato Christine J
Human Molecular Genetics Program, Children's Memorial Research Center, 2300 Children's Plaza, PO Box 211, Chicago, IL 60614, USA.
BMC Physiol. 2010 Aug 24;10:16. doi: 10.1186/1472-6793-10-16.
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. 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.
We 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.
We 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.
心电图仍然是诊断一系列涉及心脏或自主神经系统缺陷的儿科疾病的最佳工具和治疗生物标志物。随着与这些疾病的遗传联系得以确立,并且为了理解和治疗这些疾病而构建了转基因小鼠模型,令人惊讶的是,关于新生小鼠心电图(ECG)及ECG异常的信息却非常匮乏。这可能是由于许多传统的小鼠心电图记录方法需要造成创伤并使用麻醉,而许多突变新生小鼠的脆弱性又加剧了这一问题。在此,我们使用一种非侵入性系统来描述清醒的新生FVB/N小鼠在整个生长过程中心率和心电图的发育情况。
我们最早在出生后两天就对心电图波形进行了检查。此时,雄性和雌性小鼠的心率相当,比成年小鼠低50%。新生小鼠的心率变异性非常低。在出生后的12天内,PR、QRS和QTc间期持续时间接近成年值,而心率持续增加直至断奶。断奶后,FVB/N雌性小鼠的心率很快比雄性小鼠慢,不过在较晚年龄之前,两性之间的PR间期相当。这表明不同的发育事件可能导致了心电图中的这些性别差异。
我们为新生小鼠心率建立的自然过程提供了新的详细见解。现在可以方便且重复地在新生小鼠中使用心电图。这应该具有广泛的用途,有助于在临床前小鼠研究中进一步研究多种疾病的发展和治疗方法。