title: Neuroprotection by argon ventilation after perinatal asphyxia: a safety study in newborn piglets.
abstract: Hypothermia is ineffective in 45% of neonates with hypoxic-ischemic encephalopathy. Xenon has additive neuroprotective properties, but is expensive, and its application complicated. Argon gas is cheaper, easier to apply, and also has neuroprotective properties in experimental settings. The aim was to explore the safety of argon ventilation in newborn piglets.
  
  
  METHODS
  Eight newborn piglets (weight 1.4-3.0 kg) were used. Heart rate, blood pressure, regional cerebral saturation, and electrocortical brain activity were measured continuously. All experiments had a 30 min. baseline period, followed by three 60 min. periods of argon ventilation alternated with 30 min argon washout periods. Two animals were ventilated with increasing concentrations of argon (1h 30%, 1 h 50%, and 1 h 80%), two were subjected to 60 min. hypoxia (FiO2 0.08) before commencing 50% argon ventilation, and two animals received hypothermia following hypoxia as well as 50% argon ventilation. Two animals served as home cage controls and were terminated immediately.
  
  
  RESULTS
  Argon ventilation did not result in a significant change of heart rate (mean ± s.d. -3.5 ± 3.6 bpm), blood pressure (-0.60 ± 1.11 mmHg), cerebral oxygen saturation (0.3 ± 0.9%), electrocortical brain activity (-0.4 ± 0.7 µV), or blood gas values. Argon ventilation resulted in elevated argon concentrations compared to the home cage controls (34.5, 25.4, and 22.4 vs. 7.3 µl/ml).
  
  
  CONCLUSIONS
  Ventilation with up to 80% argon during normoxia, and 50% argon after hypoxia did not affect heart rate, blood pressure, cerebral saturation and electrocortical brain activity. Clinical safety studies of argon ventilation in humans seem justified.
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alderliesten
authors.affiliation: Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Laurent M A
authors.initials: LM
authors.lastname: Favie
authors.affiliation: Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Neijzen
authors.affiliation: Department of Forensic Toxicology, Institute of Forensic Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cora H A
authors.initials: CH
authors.lastname: Nijboer
authors.affiliation: Department of Medical Technology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Roland E J
authors.initials: RE
authors.lastname: Marges
authors.affiliation: Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Carin M A
authors.initials: CM
authors.lastname: Rademaker
authors.affiliation: Department of Forensic Toxicology, Institute of Forensic Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kempf
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001128:Argon / Q000008:administration & dosage* / Q000009:adverse effects; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007035:Hypothermia / Q000188:drug therapy* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000503:physiopathology; D007231:Infant, Newborn; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine; D014691:Ventilation
chemical_list: D018696:Neuroprotective Agents; D001128:Argon