title: Isoflurane/nitrous oxide anesthesia and stress-induced procedures enhance neuroapoptosis in intrauterine growth-restricted piglets.
abstract: OBJECTIVE
  There is compelling evidence that interference of various anesthetics with synaptic functions and stress-provoking procedures during critical periods of brain maturation results in increased neuroapoptotic cell death. The hypothesis is that adverse intrauterine environmental conditions leading to intrauterine growth restriction (IUGR) with altered brain development may result in enhanced susceptibility to developmental anesthetic neurotoxicity.
  
  
  METHODS
  This was a prospective, randomized, blinded animal study performed in a university laboratory involving 20 normal-weight (NW) and 19 IUGR newborn piglets. General inhalation anesthesia with isoflurane and nitrous oxide at clinically comparable dosages were administered for about 10 h. Surgical and monitoring procedures were accompanied by appropriate stage of general anesthesia. Resulting effects on developmental anesthetic and stress-induced neurotoxicity were assessed by estimation of apoptotic rates in untreated piglets and piglets after 10-h general anesthesia with MAC 1.0 isoflurane in 70 % nitrous oxide and 30 % oxygen.
  
  
  RESULTS
  IUGR piglets exposed to different levels of isoflurane inhalation exhibited a significant increased apoptosis rate (TUNEL-positive neuronal cells) compared to NW animals of similar condition (P < 0.05). Cardiovascular and metabolic monitorings revealed similar effects of general anesthesia together with similar effects on brain electrical activity and broadly a similar dose-dependent gradual restriction in brain oxidative metabolism in NW and IUGR piglets.
  
  
  CONCLUSIONS
  There is no indication that the increased rate in neuroapoptosis in IUGR piglets is confounded by additional adverse systemic or organ-specific impairments resulting from administered mixed inhalation anesthesia. Developmental anesthetic and stress-induced neuroapoptosis presumably originated in response to fetal adaptations to adverse conditions during prenatal life and should be considered in clinical interventions on infants having suffered from fetal growth restriction.
authors.affiliation: Institute of Laboratory Animal Science and Welfare, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schubert
authors.forename: Michael
authors.initials: M
authors.lastname: Eiselt
authors.forename: Bernd
authors.initials: B
authors.lastname: Walter
authors.forename: Harald
authors.initials: H
authors.lastname: Fritz
authors.forename: Michael
authors.initials: M
authors.lastname: Brodhun
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
mesh_terms: D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D004195:Disease Models, Animal; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000633:toxicity*; D011446:Prospective Studies; D013312:Stress, Physiological / Q000187:drug effects; D013552:Swine; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D009609:Nitrous Oxide