title: Increasing the duration of isoflurane anesthesia decreases the minimum alveolar anesthetic concentration in 7-day-old but not in 60-day-old rats.
abstract: BACKGROUND
  While studying neurotoxicity in rats, we observed that the anesthetic minimum alveolar anesthetic concentration (MAC) of isoflurane decreases with increasing duration of anesthesia in 7-day-old but not in 60-day-old rats. After 15 min of anesthesia in 7-day-old rats, MAC was 3.5% compared with 1.3% at 4 h. We investigated whether kinetic or dynamic factors mediated this decrease.
  
  
  METHODS
  In 7-day-old rats, we measured inspired and cerebral partial pressures of isoflurane at MAC as a function of duration of anesthesia. In 60-day-old rats, we measured inspired partial pressures of isoflurane at MAC as a function of duration of anesthesia. Finally, we determined the effect of administering 1 mg/kg naloxone and of delaying the initiation of the MAC determination (pinching the tail) on MAC in 7-day-old rats.
  
  
  RESULTS
  In 7-day-old rats, both inspired and cerebral measures of MAC decreased from 1 to 4 h. The inspired MAC decreased 56%, whereas the cerebral MAC decreased 33%. At 4 h, the inspired MAC approximated the cerebral MAC (i.e., the partial pressures did not differ appreciably). Neither administration of 1 mg/kg naloxone nor delaying tail clamping until 3 h reversed the decrease in MAC. In 60-day-old rats, inspired MAC of isoflurane was stable from 1 to 4 h of anesthesia.
  
  
  CONCLUSIONS
  MAC of isoflurane decreases over 1-4 h of anesthesia in 7-day-old but not in 60-day-old rats. Both pharmacodynamic and a pharmacokinetic components contribute to the decrease in MAC in 7-day-old rats. Neither endorphins nor sensory desensitization mediate the pharmacodynamic component.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, USA. stratman@anesthesia.ucsf.edu
authors.forename: Greg
authors.initials: G
authors.lastname: Stratmann
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Sall
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Laster
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bell
authors.forename: Laura D V
authors.initials: LD
authors.lastname: May
authors.forename: Helge
authors.initials: H
authors.lastname: Eilers
authors.forename: Martin
authors.initials: M
authors.lastname: Krause
authors.forename: Frank v d
authors.initials: Fv
authors.lastname: Heusen
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Gonzalez
mesh_terms: D000465:Algorithms; D000758:Anesthesia / Q000379:methods*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects; D000077335:Desflurane; D004723:Endorphins / Q000378:metabolism; D005740:Gases; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology*; D007700:Kinetics; D008738:Methyl Ethers / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D004723:Endorphins; D005740:Gases; D008738:Methyl Ethers; D009270:Naloxone; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane