Fetal cardiovascular response to acute hypoxia during maternal anesthesia

Abstract

Preclinical imaging studies of fetal hemodynamics require anesthesia to immobilize the animal. This may induce cardiovascular depression and confound measures under investigation. We compared the impact of four anesthetic regimes upon maternal and fetal blood gas and hemodynamics during baseline periods of normoxia, and in response to an acute hypoxic challenge in pregnant sheep. Merino ewes were surgically prepared with maternal and fetal vascular catheters and a fetal femoral artery flow probe at 105–109 days gestation. At 110–120 days gestation, ewes were anesthetized with either isoflurane (1.6%), isoflurane (0.8%) plus ketamine (3.6 mg·kg−1·h−1), ketamine (12.6 mg·kg−1·h−1) plus midazolam (0.78 mg·kg−1·h−1), propofol (30 mg·kg−1·h−1), or remained conscious. Following 60 min of baseline recording, nitrogen was administered directly into the maternal trachea to displace oxygen and induce maternal and thus fetal hypoxemia. During normoxia, maternal PaO2 was ~30 mmHg lower in anesthetized ewes compared to conscious controls, regardless of the type of anesthesia (p < .001). There was no effect of anesthesia on fetal mean arterial blood pressure (MAP; p > .05), but heart rate was 32 ± 8 bpm lower in fetuses from ewes administered isoflurane (p = .044). During maternal hypoxia, fetal MAP increased, and peripheral blood flow decreased in all fetuses except those administered propofol (p < .05). Unexpectedly, hypoxemia also induced fetal tachycardia regardless of the anesthetic regime (p < .05). These results indicate that despite maternal anesthesia, the fetus can mount a cardiovascular response to acute hypoxia by increasing blood pressure and reducing peripheral blood flow, although the heart rate response may differ from when no anesthesia is present.

Impact of resveratrol‐mediated increase in uterine artery blood flow on fetal haemodynamics, blood pressure and oxygenation in sheep

“…This might be attributable to the transport of glucose across the placenta being tightly regulated by the concentration of glucose transporters across the membrane surface (Hay, 2006). (Varcoe et al, 2020). However, in the present study there was a greater fall in pH and rise in P CO 2 in the RSV compared with the VEH fetuses, which indicates metabolic acidosis despite normal maternal arterial S O 2 (93−99%).…”

“…Additionally, there are known haemodynamic effects of isoflurane on the fetal circulation, such as increased cerebral blood flow (Gelman et al, 1984;Reinstrup et al, 1995). Prolonged exposure to isoflurane is also associated with decreased fetoplacental perfusion, CVO and fetal pH, but the fetus remains capable of mounting a cardiovascular response to acute hypoxia (Biehl et al, 1983;Varcoe et al, 2020).…”

Umbilical vein infusion of prostaglandin I2 increases ductus venosus shunting of oxygen‐rich blood but does not increase cerebral oxygen delivery in the fetal sheep

“…Although anaesthesia itself is known to impact on cardiovascular parameters and should be considered as a potentially confounding factor when interpreting fetal haemodynamics, our previous studies suggest that the fetus is capable of mounting a cardiovascular response during this anaesthesia regime (Varcoe et al . 2020). In addition, anaesthesia reduces fetal movement and thus reduces motion artefact, which increases image quality.…”

An MRI approach to assess placental function in healthy humans and sheep

“…Maternal anaesthesia was required in our sheep subjects to alleviate the stress of isolation and to restrict movements during MRI. Isoflurane was used as the aesthetic agent, which has known suppressive cardiovascular effects (Bachman et al 1986;Brett et al 1987;Okutomi et al 2009); although the fetus can still mount a cardiovascular response to hypoxia (Varcoe et al 2020). Fetal health being the priority, the ewe was mildly hyperoxygenated to achieve fetal normoxemia as indicated by higher maternal jugular venous P O 2 and S O 2 during MRI compared to the pre-anaesthesia/conscious state (Table 2).…”