Abstract
Background:
Cardiac dysfunction is reported to occur after severe perinatal asphyxia. We hypothesized that anesthesia of the mother with propofol during emergency cesarean section (c-section) would result in less cardiac injury (troponin T) in preterm fetuses exposed to global severe asphyxia in utero than anesthesia with isoflurane. We tested whether propofol decreases the activity of proapoptotic caspase-3 by activating the antiapoptotic AKT kinase family and the signal transducer and activator of transcription-3 (STAT-3).
Methods:
Pregnant ewes were randomized to receive either propofol or isoflurane anesthesia. A total of 44 late-preterm lambs were subjected to in utero umbilical cord occlusion (UCO), resulting in asphyxia and cardiac arrest, or sham treatment. After emergency c-section, each fetus was resuscitated, mechanically ventilated, and supported under anesthesia for 8 h using the same anesthetic as the one received by its mother.
Results:
At 8 h after UCO, the fetuses whose mothers had received propofol anesthesia had lower plasma troponin T levels, and showed a trend toward a higher median left ventricular ejection fraction (LVEF) of 84% as compared with 74% for those whose mothers had received isoflurane. Postasphyxia activation of caspase-3 was lower in association with propofol anesthesia than with isoflurane. Postasphyxia levels of STAT-3 and the AKT kinase family rose 655% and 500%, respectively with the use of propofol anesthesia for the mother.
Conclusion:
The use of propofol for maternal anesthesia results in less cardiac injury in late-preterm lambs subjected to asphyxia than the use of isoflurane anesthesia. The underlying mechanism may be activation of the antiapoptotic STAT-3 and AKT pathways.
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Acknowledgements
We thank Monique Engel for her advice and for making the technical equipment available to us. We also thank Claudia Lorefice, Elke Kuypers, Lotte van den Heuij, and the staff of the central animal facility of Maastricht University for their excellent technical help.
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Seehase, M., Houthuizen, P., Jellema, R. et al. Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest. Pediatr Res 73, 427–434 (2013). https://doi.org/10.1038/pr.2013.10
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DOI: https://doi.org/10.1038/pr.2013.10
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