α‐Adrenergic blockade impairs ductus venosus shunting during an acute period of fetal hypoxaemia without further deficits to cerebral oxygen delivery

The fetal circulation has unique shunts, including the ductus venosus (DV), the tone of which dictates how much substrate-rich blood returning from the placenta is streamed preferentially away from the liver and instead towards the heart. Herein, we aimed to use clinically relevant MRI techniques in sheep to measure indirectly induced changes in DV tone and the consequences of this on DV shunting, expressed as a ratio of umbilical vein (UV) flow [DV:UV (as a percentage)], and its impact on oxygen delivery to the fetal brain. At 116-117 days gestational age (term = 150 days), fetal sheep (n = 11) underwent surgery to implant vascular catheters. Fetal MRI scans were performed at 120-123 days gestational age. Phase contrast MRI and T₂ MRI oximetry were performed to measure blood flow and oxygen saturation within the fetal circulation during states of fetal normoxaemia, hypoxaemia and hypoxaemia + systemic α-adrenergic blockade (fetal infusion of the α-adrenergic antagonist, phentolamine). Hypoxaemia reduced both overall fetal and cerebral oxygen delivery but did not impact either systemic or cerebral oxygen consumption. Fetal hypoxaemia alone did not impact DV shunting. However, addition of α-adrenergic blockade to acute hypoxaemia significantly decreased DV shunting. Neither fetal hypoxaemia nor the addition of the α-adrenergic blockade impacted left ventricular cardiac output or blood flow to the brain and the placenta. At the gestational age studied, systemic α-adrenergic signalling is required to maintain DV shunting during fetal hypoxaemia. However, reduced DV shunting during the systemic α-adrenergic blockade was not accompanied by a further deficit in cerebral oxygen delivery_.