Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction and Natural Heart Regeneration in Newborn Piglets

Abstract

Newborn mammals, including piglets, exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). The electrophysiologic properties of this naturally regenerated myocardium have not been examined. We hypothesized that epicardial conduction is preserved after P1 MI in piglets. Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation at age P1 (n = 6) or P7 (n = 7), After 7 weeks, cardiac magnetic resonance imaging was performed with late gadolinium enhancement for analysis of fibrosis. Epicardial conduction mapping was performed using custom 3D-printed high-resolution mapping arrays. Age- and weight-matched healthy pigs served as controls (n = 6). At the study endpoint, left ventricular (LV) ejection fraction was similar for controls and P1 pigs (46.4 ± 3.0% vs. 40.3 ± 4.9%, p = 0.132), but significantly depressed for P7 pigs (30.2 ± 6.6%, p < 0.001 vs. control). The percentage of LV myocardial volume consisting of fibrotic scar was 1.0 ± 0.4% in controls, 9.9 ± 4.4% in P1 pigs (p = 0.002 vs. control), and 17.3 ± 4.6% in P7 pigs (p < 0.001 vs. control, p = 0.007 vs. P1). Isochrone activation maps and apex activation time were similar between controls and P1 pigs (9.4 ± 1.6 vs. 7.8 ± 0.9 ms, p = 0.649), but significantly prolonged in P7 pigs (21.3 ± 5.1 ms, p < 0.001 vs. control, p < 0.001 vs. P1). Conduction velocity was similar between controls and P1 pigs (1.0 ± 0.2 vs. 1.1 ± 0.4 mm/ms, p = 0.852), but slower in P7 pigs (0.7 ± 0.2 mm/ms, p = 0.129 vs. control, p = 0.052 vs. P1). Overall, our data suggest that epicardial conduction dynamics are conserved in the setting of natural heart regeneration in piglets after P1 MI.

Electrophysiological mapping of the epicardium via 3D‐printed flexible arrays

“…Comparison between activation isochrones during sinus rhythm (Figure 5h) and PVC (Figure 5i) highlights the different origins of epicardial activation, with PVC activation occurring along the left ventricular border. The whole‐chamber array format allows for measurement of beat‐to‐beat changes in epicardial activation and precise localization of PVC sources, without the need for repositioning 21 …”

“…The whole-chamber array format allows for measurement of beat-to-beat changes in epicardial activation and precise localization of PVC sources, without the need for repositioning. 21…”

“…The specific platform reported here allows for conformal contact with the epicardial surface and provides the option for concurrent delivery of energy for the purpose of electrical stimulation and radiofrequency (RF) ablation (RFA). The devices are deployed and tested in the cardiac surgical environment for their ability to aid surgeons in arrhythmia interventions 21 …”

“…The devices are deployed and tested in the cardiac surgical environment for their ability to aid surgeons in arrhythmia interventions. 21 2 | RESULTS…”

The origin, progress, and application of cell‐based cardiac regeneration therapy

“…Such hydrogels have biological activity and influence cell behavior (Liguori et al, 2021). In the mouse model of infarction, the use of dECM hydrogel as a medium has a longer retention time, higher stiffness, and slow protein release, which enables the persistence of cell‐secreted paracrine factors, promotes vascular density, and reduces left ventricular remodeling, which can be used as an alternative for cardiovascular regeneration (Wang, Pong, et al, 2022).…”