title: Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain.
abstract: BACKGROUND
  Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs.
  
  
  METHODS
  Twenty-six healthy pigs (<24-h old) were randomized into four groups: (1) 24  h of 50% inhaled xenon with fentanyl at hypothermia (Trec = 33.5 °C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 °C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions.
  
  
  RESULTS
  For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5- to 10-fold increase of immunostained cells.
  
  
  CONCLUSIONS
  At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.
authors.affiliation: School of Clinical Sciences, University of Bristol, St. Michael's Hospital, Bristol, UK.
authors.forename: Hemmen
authors.initials: H
authors.lastname: Sabir
authors.forename: Sarah
authors.initials: S
authors.lastname: Bishop
authors.forename: Nicki
authors.initials: N
authors.lastname: Cohen
authors.forename: Elke
authors.initials: E
authors.lastname: Maes
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: John
authors.initials: J
authors.lastname: Dingley
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001831:Body Temperature; D001921:Brain / Q000187:drug effects*; D004195:Disease Models, Animal; D005283:Fentanyl / Q000494:pharmacology*; D007036:Hypothermia, Induced; D018696:Neuroprotective Agents / Q000494:pharmacology; D013552:Swine; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D018696:Neuroprotective Agents; D014978:Xenon; D005283:Fentanyl