Fetal and placental haemodynamic responses to hypoxaemia, maternal hypotension and vasopressor therapy in a chronic sheep model

Abstract Knowledge of the effects of maternally administered vasopressors on human fetal and placental haemodynamics is sparse and limited to elective Caesarean deliveries in uncomplicated pregnancies. We hypothesized that, after short-term fetal hypoxaemia, which activates fetal cardiovascular compensatory mechanisms, treatment of maternal hypotension with ephedrine or phenylephrine results in divergent responses in fetal and placental haemodynamics. Chronically instrumented near-term sheep fetuses with either normal placental function or increased placental vascular resistance following placental embolization were exposed to two subsequent periods of decreased fetal oxygenation caused by maternal hypoxaemia and epidural-induced hypotension. The fetuses that underwent placental embolization were also chronically hypoxaemic. Fetal and placental haemodynamics were assessed by invasive techniques and by noninvasive Doppler ultrasonography. Our results show that umbilical artery blood flow velocity waveforms cannot be used to derive information of fetal cardiac function. Furthermore, the changes in placental volume blood flows and vascular resistances caused by maternal vasopressor treatment cannot be reliably recognized based on uterine and umbilical artery pulsatility index values. In response to acute hypoxaemia, a fetus with normal placental function redistributes its right ventricular cardiac output from the pulmonary to the systemic circulation and is able to increase its combined cardiac output, with a concomitant relative decrease in the net forward flow through the aortic isthmus. However, fetal haemodynamic responses to subsequent hypoxaemic insults may vary. Furthermore, the compensatory responses of fetuses with increased placental vascular resistance differ from those of normal fetuses. In these fetuses, repeated episodes of a further decrease in oxygenation lead to lactataemia. The effects of ephedrine on uteroplacental and umbilicoplacental circulations were more favourable than those of phenylephrine. Ephedrine restored the changes in fetal cardiovascular haemodynamics caused by maternal hypotension to the baseline conditions in both embolized and nonembolized fetuses. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus. Moreover, fetal left ventricular function was impaired by phenylephrine. Although no significant differences in fetal acid-base status were observed in fetuses with normal placental function, the lactate concentrations of the embolized fetuses increased further when maternal hypotension was treated with phenylephrine