title: Propofol administration to the fetal-maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Paediatrics, Maastricht University Medical Center, School of Oncology, Maastricht, The Netherlands.
authors: Matthias
authors: M
authors: Seehase
authors: Patrick
authors: P
authors: Houthuizen
authors: Reint K
authors: RK
authors: Jellema
authors: Jennifer J P
authors: JJ
authors: Collins
authors: Otto
authors: O
authors: Bekers
authors: Johannes
authors: J
authors: Breuer
authors: Boris W
authors: BW
authors: Kramer
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D002585:Cesarean Section; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D005865:Gestational Age; D006323:Heart Arrest / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007231:Infant, Newborn; D007530:Isoflurane / Q000008:administration & dosage; D008026:Ligation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011247:Pregnancy; D047928:Premature Birth; D015742:Propofol / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012121:Respiration, Artificial; D012151:Resuscitation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D020107:Troponin T / Q000097:blood; D014463:Ultrasonography; D014470:Umbilical Cord / Q000601:surgery; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D015415:Biomarkers; D050796:STAT3 Transcription Factor; D020107:Troponin T; D007530:Isoflurane; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D015742:Propofol