Electroanatomical adaptations in the guinea pig heart from neonatal to adulthood

Author:

Haq Kazi T12,McLean Kate1ORCID,Salameh Shatha123ORCID,Swift Luther M12ORCID,Posnack Nikki Gillum1234ORCID

Affiliation:

1. Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital , 111 Michigan Avenue, NW, Washington, DC 20010 , USA

2. Children’s National Heart Institute, Children’s National Hospital , Washington, DC , USA

3. Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences , Washington, DC , USA

4. Department of Pediatrics, The George Washington University School of Medicine and Health Sciences , Washington, DC , USA

Abstract

Abstract Aims 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 and 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. 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.

Funder

National Institutes of Health

American Heart Association and The Children’s Heart Foundation

Publisher

Oxford University Press (OUP)

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