Abstract 153: Dexamethasone Inhibits Regeneration and Causes Ventricular Aneurysm in the Neonatal Porcine Heart After Myocardial Infarction

Abstract

Background: The adult mammalian heart has limited ability to repair itself following injury. Zebrafish, newts and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. More recently, we demonstrated that the hearts of neonatal pigs (2-day old) have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth. The current study aims to determine whether acute inflammation is required for CM regeneration after myocardial infarction (MI). Methods: We examined the role of acute inflammation on regenerative capacity of the neonatal pig heart (ages: 2 days postnatal) by intramuscular injection of dexamethasone (Dex) during the first week post-MI surgery. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance (CMR) imaging. Bromodeoxyuridine pulse-chase labeling, histology, and immunohistochemistry were performed to study CM cytokinesis and to quantify myocardial fibrosis. Results: After MI, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day old pigs. In contrast, piglets received Dex injection developed ventricular aneurysm and did not recover function. Dex limited CM cytokinesis via inhibiting aurora-B protein expression and caused mature scar and thinned walls at infarct site. Conclusions: Dex suppresses acute inflammation, inhibits CM regeneration, and causes ventricular aneurysm in neonatal pig hearts after MI.