title: Temporal summation governs part of the minimum alveolar concentration of isoflurane anesthesia.
abstract: BACKGROUND
  General anesthesia may delay the onset of movement in response to noxious stimulation. The authors hypothesized that the production of immobility could involve depression of time-related processes involved in the generation of movement.
  
  
  METHODS
  The delays (latencies) between onset of tail clamp (n = 16) or 50-Hz continuous electrical stimulation (n = 8) and movement were measured in rats equilibrated at 0.1-0.2% increasing steps of isoflurane. In other rats (n = 8), the isoflurane concentrations just permitting and preventing movement (crossover concentrations) in response to trains of 0.5-ms 50-V square-wave pulses of interstimulus intervals of 10, 3, 1, 0.3, or 0.1 s during the step increases were measured. These measures were again made during administration of intravenous MK801, an N-methyl-D-aspartate receptor antagonist that can block temporal summation (n = 6). Temporal summation refers to the cumulative effect of repeated stimuli. Crossover concentrations to 10- and 0.1-s interstimulus interval pulses ranging in voltage from 0.25-50 V were also measured (n = 4).
  
  
  RESULTS
  The increase in concentrations from 0.6 to nearly 1.0 minimum alveolar concentration progressively increased latency from less than 1 s to 58 s. Shortening the interstimulus interval (50 V) pulses from 10 to 0.1 s progressively increased crossover concentrations from 0.6 to 1.0 minimum alveolar concentration. In contrast, during MK801 administration shortening interstimulus intervals did not change crossover concentrations, producing a flat response to change in the interstimulus interval. Increasing the voltage of interstimulus interval pulses increased the crossover concentrations but did not change the response to change in interstimulus intervals for pulses greater than 1 V.
  
  
  CONCLUSIONS
  Increasing the duration or frequency (interstimulus interval) of stimulation increases the concentration of isoflurane required to suppress movement by a 0.4 minimum alveolar concentration MK801 blocks this effect, a finding consistent with temporal summation (which requires intact N-methyl-D-aspartate receptor activity) at concentrations of up to 1 minimum alveolar concentration isoflurane.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California 94143-0464, USA. duttonr@anesthesia.ucsf.edu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Dutton
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Caroline R
authors.initials: CR
authors.lastname: Stabernack
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Laster
authors.forename: James M
authors.initials: JM
authors.lastname: Sonner
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
mesh_terms: D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004576:Electromyography; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007530:Isoflurane / Q000493:pharmacokinetics*; D009068:Movement / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D007530:Isoflurane