Role of α-adrenergic activation during the hemodynamic response to maternal hyperoxygenation in fetal sheep†.

Normal neurodevelopment relies on effective placental oxygen transfer and the specialized circulatory shunts that direct oxygen-rich blood to key fetal organs. The tone of these shunts, particularly the ductus venosus, is critical for routing oxygen and nutrient-rich blood towards the fetal brain. However, these shunts are sensitive to both oxygenation status and sympathetic innervation. Notably, fetal hypoxia increases shunting through the ductus venosus via enhanced hepatic sympathetic activation, a mechanism that redistributes oxygen rich blood toward vital organs. Thus, we hypothesized that hyperoxygenation may decrease shunting through the ductus venosus via hepatic sympathetic regulation but may be reversed if combined with an α-adrenergic agonist. Pregnant ewes (n = 8) underwent fetal catheterization surgery at 116-117 days gestation. At 120-124 days gestation, ewes were anaesthetized, and magnetic resonance imaging (MRI) scans were performed during normoxia, hyperoxia, and hyperoxia + phenylephrine infusion to measure blood flow and oxygenation within the major fetal vessels using phase-contrast and T2 oximetry MRI techniques, respectively. Hyperoxia had minimal effects on fetal hemodynamics. However, with the addition of phenylephrine, there was increased flow through the ductus venosus and ascending aorta but decreased flow toward the brain via the carotid arteries. Hyperoxia + phenylephrine increased overall fetal oxygen delivery but decreased cerebral oxygen delivery, despite no change in ductus venosus shunting (ductus venosus/umbilical vein flow ratio). There was no change in fetal or cerebral oxygen consumption. In conclusion, hyperoxia + phenylephrine reduced cerebral oxygenation, indicating that increased ductus venosus flow does not translate to improved cerebral oxygen delivery when carotid vascular resistance is elevated.