Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
Children's National Heart Institute, Children's National Hospital, Washington, DC, USA.
Europace. 2024 Jul 2;26(7). doi: 10.1093/europace/euae158.
Electroanatomical adaptations during the neonatal to adult phase have not been comprehensively studied in preclinical animal models. To explore the impact of age as a biological variable on cardiac electrophysiology, we employed neonatal and adult guinea pigs, which are a recognized animal model for developmental research.
Electrocardiogram recordings were collected in vivo from anaesthetized animals. A Langendorff-perfusion system was employed for the optical assessment of action potentials and calcium transients. Optical data sets were analysed using Kairosight 3.0 software. The allometric relationship between heart weight and body weight diminishes with age, it is strongest at the neonatal stage (R2 = 0.84) and abolished in older adults (R2 = 1E-06). Neonatal hearts exhibit circular activation, while adults show prototypical elliptical shapes. Neonatal conduction velocity (40.6 ± 4.0 cm/s) is slower than adults (younger: 61.6 ± 9.3 cm/s; older: 53.6 ± 9.2 cm/s). Neonatal hearts have a longer action potential duration (APD) and exhibit regional heterogeneity (left apex; APD30: 68.6 ± 5.6 ms, left basal; APD30: 62.8 ± 3.6), which was absent in adults. With dynamic pacing, neonatal hearts exhibit a flatter APD restitution slope (APD70: 0.29 ± 0.04) compared with older adults (0.49 ± 0.04). Similar restitution characteristics are observed with extrasystolic pacing, with a flatter slope in neonates (APD70: 0.54 ± 0.1) compared with adults (younger: 0.85 ± 0.4; older: 0.95 ± 0.7). Neonatal hearts display unidirectional excitation-contraction coupling, while adults exhibit bidirectionality.
Postnatal development is characterized by transient changes in electroanatomical properties. Age-specific patterns can influence cardiac physiology, pathology, and therapies for cardiovascular diseases. Understanding heart development is crucial to evaluating therapeutic eligibility, safety, and efficacy.
在临床前动物模型中，尚未全面研究新生儿到成年期的电解剖适应。为了探索年龄作为生物变量对心脏电生理学的影响，我们使用了新生和成年豚鼠，它们是发育研究的公认动物模型。
从麻醉动物体内采集心电图记录。采用 Langendorff 灌注系统进行动作电位和钙瞬变的光学评估。使用 Kairosight 3.0 软件分析光学数据集。心脏重量与体重的比例关系随年龄而减小，在新生儿期最强（R2=0.84），在老年时消失（R2=1E-06）。新生儿心脏呈圆形激活，而成年人呈典型的椭圆形。新生儿的传导速度（40.6±4.0cm/s）比成年人慢（年轻：61.6±9.3cm/s；年老：53.6±9.2cm/s）。新生儿心脏的动作电位持续时间较长（APD），并表现出区域性异质性（左心尖；APD30：68.6±5.6ms，左基底；APD30：62.8±3.6），成年人则不存在。动态起搏时，新生儿心脏的 APD 复极斜率较平坦（APD70：0.29±0.04），而老年心脏较平坦（0.49±0.04）。心脏 extrasystolic 起搏时也观察到相似的复极特征，新生儿的斜率较平坦（APD70：0.54±0.1），而成年人的斜率较平坦（年轻：0.85±0.4；年老：0.95±0.7）。新生儿心脏表现为单向兴奋-收缩偶联，而成年人则表现为双向性。
出生后发育的特征是电解剖特性的短暂变化。特定年龄的模式会影响心血管疾病的心脏生理学、病理学和治疗。了解心脏发育对于评估治疗的适用性、安全性和疗效至关重要。
