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.
Highlights
Ischemic heart disease affects 200 million people and results in 10 million deaths globally each year [1]
left ventricular (LV) ejection fraction (EF) for postnatal day 1 (P1) pigs was mildly decreased compared to controls (46.4 ± 3.0 vs. 40.3±4.9%, p = 0.132, Figure 2E), postnatal day 7 (P7) pigs exhibited significantly depressed LV EF (30.2 ± 6.6%, p < 0.001 vs. control, p = 0.007 vs. P1)
P7 pigs developed LV dysfunction and formed large scars after left anterior descending (LAD) ligation, in association with aberrant epicardial activation, prolonged apex activation time, slower conduction velocity, and lengthened QRS interval. These results suggest that natural heart regeneration is able to conserve native epicardial conduction dynamics after myocardial infarction (MI)
Summary
Ischemic heart disease affects 200 million people and results in 10 million deaths globally each year [1]. Revascularization techniques have improved early survival after acute myocardial infarction (MI), many survivors develop heart failure despite receiving optimal management [2]. In the healthy mammalian heart, electrical impulses are transmitted from the sinoatrial node to the atrioventricular node to the bundle of His. Electrical conduction passes rapidly within the interventricular septum via the right and left bundle branches, emerging epicardially first as two wavefront foci on the free walls of the right and left ventricles, respectively, before radiating and converging to activate the mid-ventricle and apex via the Purkinje fiber network, and reaching the basal posterolateral region last [6, 7]. After MI, the development of fibrotic scar alters impulse propagation within and around the infarct [8]. Anteroseptal MI resulting from occlusion of the proximal left anterior descending (LAD) coronary artery may result in more global ventricular conduction delays and an increased QRS interval on electrocardiography, as the blood supply of the right bundle branch, the anterior fascicle of the left bundle branch, and, to a lesser extent, the posterior fascicle of the left bundle branch, may all depend on septal perforators from the LAD [9]
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