Magnesium sulfate and sex differences in cardiovascular and neural adaptations during normoxia and asphyxia in preterm fetal sheep

Robert Galinsky, Simerdeep K. Dhillon, Christopher A. Lear, Kyohei Yamaguchi, Guido Wassink, Alistair J Gunn, Laura Bennet

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Magnesium sulfate (MgSO4) is recommended for preterm neuroprotection, preeclampsia and preterm labor prophylaxis. There is an important unmet need to carefully test clinical interventions in both sexes. Therefore, we aimed to investigate cardiovascular and neurophysiological adaptations to MgSO4 during normoxia and asphyxia in preterm male and female fetal sheep. Fetuses were instrumented at 98{plus minus}1 days of gestation (d; term=147 d). At 104 d, unanaesthetised fetuses were randomly assigned to intravenous MgSO4 (n=12 F, 10 M) or saline (n=13 F, 10 M). At 105 d fetuses underwent umbilical cord occlusion for up to 25 minutes. Occlusions were stopped early if MAP fell below 8 mmHg or asystole occurred for > 20 seconds. During normoxia, MgSO4 was associated with similar reductions in FHR, EEG power and movement in both sexes (P<0.05 vs. saline-controls) and suppression of alpha and beta spectral band power in males (P<0.05 vs. saline-controls). During occlusion, similar FHR and MAP responses occurred in MgSO4-treated males and females compared to saline-controls. Recovery of FHR and MAP after release of occlusion was more prolonged in MgSO4-treated males (P<0.05 vs. saline-controls). During and after occlusion, EEG power was lower in MgSO4-treated females (P<0.05 vs. saline-controls). In conclusion, MgSO4 infusion was associated with subtle sex-specific effects on EEG spectral power and cardiac responses to asphyxia in utero, possibly reflecting sex-specific differences in inter-neuronal connectivity and regulation of cardiac output.
Original languageEnglish
Pages (from-to)R205-R217
Number of pages13
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2
Publication statusPublished - Aug 2018
Externally publishedYes

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