Neonatal dexamethasone exposure causes the early maturation of cardiomyocytes in rats (862.4)

Dexamethasone (Dex) is a synthetic glucocorticoid commonly administered to preterm infants for the maturation of the lung. However, it is also associated with adverse effects in increasing cardiovascular disease later in life. In the present study we investigated the involvement of Dex in phenotypical and functional changes in the developing heart. The hypothesis of this study is that neonatal Dex treatment will result in an early terminal differentiation of the heart marked by the transition of mononucleate cardiomyocytes to binucleate phenotype and reduced proliferation in cardiomyocytes. To test this hypothesis neonatal rats were treated with tapered doses of Dex on day 1 (0.5 µg/g), 2 (0.3 µg/g) and 3 (0.1 µg/g) by intraperitoneal injection. Control animals received either saline or no injections. Primary cardiomyocytes were isolated at day 4, 7, and 14. The results revealed that Dex‐treated animals tended to have higher the heart to body ratio compared to controls. Immunocytochemistry analysis revealed Ki‐67, a proliferation marker, was unchanged at day 4 then significantly decreased at day 7 and 14. A significant increase in binucleation of cardiomyocytes was noted in day 4 animals with no subsequent changes for later days. These findings suggest that Dex treatment caused a premature exit of the cell cycle and terminal differentiation of cardiomyocytes in the developing heart, which may lead to a reduction in cardiomyocyte number and ultimately compromise cardiac health later in life.