title: Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by K(ATP)-channel opening.
abstract: OBJECTIVE
  Argon at a dosage of 70% is neuroprotective when given 1 h after cardiac arrest (CA) in rats. In a rodent model, we investigated if the neuroprotective effects of argon are dose dependent and mediated by adenosine triphosphate dependent potassium (K(ATP)) channels.
  
  
  METHODS
  Forty-seven male Sprague-Dawley rats were subjected to 7 min of CA and 3 min of cardiopulmonary resuscitation (CPR). In protocol I animals were randomized to receive either 70% or 40% argon ventilation 1 h after successful CPR or no argon-treatment. Animals of the second protocol also received 1 h of 70% argon ventilation or no argon treatment but were randomized to a group receiving the K(ATP) channel blocker 5-hydroxydecanoate (5-HD). For all animals a neurological deficit score (NDS) was calculated daily for seven days following the experiment before the animals were killed and the brains harvested for histopathological analyses.
  
  
  RESULTS
  All animals survived. Control animals exhibited severe neurologic dysfunction at all points in time as measured with the NDS. Argon treated animals showed significant improvements in the NDS through all postoperative days in a dose dependent fashion. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region. Administration of 5-HD neither abolished the positive effects on functional recovery nor on histopathologic changes observed in the argon group.
  
  
  CONCLUSIONS
  Our study demonstrates a dose dependent neuroprotective effect of argon administration in this rodent model, which is not mediated via ATP dependent potassium channels.
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany. Electronic address: abruecken@ukaachen.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Brücken
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Pinar
authors.initials: P
authors.lastname: Kurnaz
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Derwall
authors.affiliation: Institute for Neuropathology; University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.affiliation: Institute for Neuropathology; University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Nolte
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fries
mesh_terms: D000818:Animals; D001128:Argon / Q000008:administration & dosage*; D001927:Brain Diseases / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006323:Heart Arrest / Q000150:complications*; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054086:KATP Channels; D018696:Neuroprotective Agents; D001128:Argon
keywords: Argon; Brain; Cardiopulmonary resuscitation; Hypoxia-ischaemia; Neuroprotective agents; Reperfusion injury