关键词: Cardiac electrophysiology Developmental biology Optical mapping Pediatric models

Mesh : Animals Guinea Pigs Action Potentials Animals, Newborn Adaptation, Physiological Age Factors Heart Rate / physiology Electrocardiography Aging / physiology Isolated Heart Preparation Calcium Signaling Male Heart / physiology Voltage-Sensitive Dye Imaging Time Factors Body Weight Heart Conduction System / physiology Female

来  源:   DOI:10.1093/europace/euae158

Abstract:
OBJECTIVE: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要:
目的:在临床前动物模型中尚未全面研究新生儿至成人阶段的电解剖适应。探讨年龄作为生物学变量对心脏电生理的影响,我们雇佣了新生和成年豚鼠,这是一种公认的发展研究动物模型。
结果:从麻醉动物体内收集心电图记录。使用Langendorff灌注系统对动作电位和钙瞬变进行光学评估。使用Kairosight3.0软件分析光学数据集。心脏重量和体重之间的异速关系随着年龄的增长而减弱,它在新生儿期最强(R2=0.84),在老年人中消失(R2=1E-06)。新生儿心脏表现出圆形激活,而成年人则表现出典型的椭圆形。新生儿传导速度(40.6±4.0cm/s)比成人慢(年龄:61.6±9.3cm/s;年龄:53.6±9.2cm/s)。新生儿心脏的动作电位持续时间(APD)较长,并表现出区域异质性(左心尖;APD30:68.6±5.6ms,左基底;APD30:62.8±3.6),这在成年人中是不存在的。动态起搏,与老年人(0.49±0.04)相比,新生儿心脏表现出更平坦的APD恢复斜率(APD70:0.29±0.04)。在收缩前起搏中观察到类似的恢复特征,与成年人(年轻:0.85±0.4;年龄:0.95±0.7)相比,新生儿的斜率更平坦(APD70:0.54±0.1)。新生儿心脏显示单向兴奋-收缩耦合,而成年人表现出双向性。
结论:产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脏生理学,病理学,和心血管疾病的治疗。了解心脏发育对评估治疗资格至关重要,安全,和功效。
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