Europace. 2024 Jun 12:euae158. doi: 10.1093/europace/euae158. Online ahead of print.
ABSTRACT
BACKGROUND: 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.
METHODS: Electrocardiogram (ECG) recordings were collected in vivo from anesthetized animals. A Langendorff-perfusion system was employed for optical assessment of action potentials and calcium transients. Optical data sets were analyzed using Kairosight 3.0.
RESULTS: 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 to 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 to adults (younger: 0.85±0.4; older: 0.95±0.7). Neonatal hearts display unidirectional excitation-contraction coupling, while adults exhibit bidirectionality.
CONCLUSION: 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.
PMID:38864516 | DOI:10.1093/europace/euae158
