Model Systems for the Study of Integrative Physiology: The Rebirth of Translational Biology: Chronic maternal hypercortisolemia in late gestation alters fetal cardiac function at birth

摘要

Studies in our laboratory have shown that modest chronic increases in maternal cortisol concentrations over the last 0.20 of gestation impair maternal glucose metabolism and increase the incidence of perinatal stillbirth. Previous studies had found that an increase in maternal cortisol concentrations from 115 to 130 days of gestation in sheep increased both proliferation in fetal cardiomyocytes and apoptosis in the fetal cardiac Purkinje fibers. We hypothesized that the adverse effects of excess cortisol may result in defects in cardiac conduction during labor and delivery. In the present study, we infused cortisol (1 mg·kg⁻¹·day⁻¹) into late gestation pregnant ewes and continuously monitored fetal aortic pressure and ECG through labor and delivery. We found that, although the fetuses of cortisol infused ewes had normal late gestation patterns of arterial pressure and heart rate, there was a significant decrease in fetal aortic pressure and heart rate on the day of birth, specifically in the final hour before delivery. Significant changes in the fetal ECG were also apparent on the day of birth, including prolongation of the P wave and P-R interval. We speculate that chronic exposure to glucocorticoids alters cardiac metabolism or ion homeostasis, contributing to cardiac dysfunction, precipitated by active labor and delivery.