title: Strain differences in cortical electroencephalogram associated with isoflurane-induced loss of consciousness.
abstract: BACKGROUND
  Previously observed increased sensitivity to noxious stimulation in the Dahl salt-sensitive rat strain (SS/JrHsdMcwi, abbreviated as SS) compared to Brown Norway rats (BN/NhsdMcwi abbreviated as BN) is mediated by genes on a single chromosome. The current study used behavioral and electrocortical data to determine if differences also exist between SS and BN rats in loss of consciousness.
  
  
  METHODS
  Behavioral responses, including loss of righting, (a putative index of consciousness) and concurrent electroencephalogram recordings, in 12 SS and BN rats were measured during isoflurane at inhaled concentrations of 0, 0.3, 0.6, 0.8, 1.0 and 1.2%.
  
  
  RESULTS
  In SS compared to BN rats, the mean ± SEM EC50 for righting was significantly less (0.65 ± 0.01% vs. 0.74 ± 0.02% inhaled isoflurane) and delta fraction in parietal electroencephalogram was enhanced 50-100% at all isoflurane levels during emergence. The frequency decay constant of an exponential fit of the parietal electroencephalogram spectrum graphed as a function of isoflurane level was three times less steep (mean ± SEM slope -57 ± 13 vs. -191 ± 38) and lower at each level of isoflurane in SS versus BN rats (i.e., shifted toward low frequency activity). Electroencephalogram differences between strains were larger during emergence than induction.
  
  
  CONCLUSIONS
  Sensitivity is higher in SS compared to BN rats leading to unconsciousness at lower levels of isoflurane. This supports using additional strains in this animal model to study the genetic basis for differences in anesthetic action on mechanisms of consciousness. Moreover, induction and emergence appear to involve distinct pathways.
authors.affiliation: Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McCallum
authors.forename: Siveshigan
authors.initials: S
authors.lastname: Pillay
authors.forename: Jeannette A
authors.initials: JA
authors.lastname: Vizuete
authors.forename: Gary
authors.initials: G
authors.lastname: Mouradian
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Hudetz
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Stekiel
mesh_terms: D000465:Algorithms; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography; D007530:Isoflurane / Q000097:blood; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D013045:Species Specificity; D014474:Unconsciousness / Q000139:chemically induced* / Q000235:genetics*
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane