Strain Differences in Cortical Electroencephalogram Associated with Isoflurane-induced Loss of Consciousness

• Published in: Anesthesiology (Philadelphia) 2013-02, Vol.118 (2), p.350-360
• Main Authors: BRUCE MCCALLUM, J, PILLAY, Siveshigan, VIZUETE, Jeannette A, MOURADIAN, Gary, HUDETZ, Anthony G, STEKIEL, Thomas A
• Format: Article
• Language: English
• Subjects: Algorithms; Anesthesia; Anesthesia, Inhalation; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Inhalation - blood; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Dose-Response Relationship, Drug; Electrodes, Implanted; Electroencephalography; Isoflurane - blood; Male; Medical sciences; Rats; Rats, Inbred BN; Rats, Inbred Dahl; Species Specificity; Unconsciousness - chemically induced; Unconsciousness - genetics
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0b013e31827ddfed

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. 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%. 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. 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.