Circadian Variations For Potency Of Inhaled Anesthetics And Its Mechanism

Objective:This study explored whether induction and recovery in mice that received volatile anesthetics,mainly sevoflurane and isoflurane showed circadian variations.And circadian rhythm dependent variations for immobility were also tested.Methods:1.Study of circadian rhythm dependent variations for induction and recovery from isoflurane and sevoflurane anesthesiaWe used loss of righting reflex?LORR?as an endpoint for loss of consciousness and recovery of righting reflex?RORR?as the symbol for recovery of consciousness.1.1 Determination of time to loss of righting reflex and time to recovery for isoflurane and sevoflurane at day phase and night phase respectively in mice.Forty male mice were randomly divided into four groups to determine Time _LORR?Time to loss of righting reflex?and Time_RORR?Time to recovery of righting reflex?for isoflurane and sevoflurane at day phase and night phase respectively.All tests for day phase group were conducted during 9:00-14:00,and night phase tests were made during 21:00-02:00.Time _LORRORR and Time_RORR for isoflurane and sevoflurane were defined as the time to loss of righting reflex under 1 Minimum alveolar concentration?MAC?of isoflurane and sevoflurane anesthesia and the time elapsed from discontinuation of an anesthetic until the return of the righting reflex after 30 minutes anesthesia.1.2.Determination of MAC_LORR,MAC_RORR and MAC of isoflurane and sevoflurane for mice at day phase and night phase.To determine MAC_LORR?the anesthetic dose at which half of the mice lost their righting reflex?,MAC_RORR?the anesthetic dose at which half of the mice recover their righting reflex?and MAC?the anesthetic dose at which half of the mice lost response to noxious stimulation?along with their corresponding 95%confidence intervals?95%CI?,the log of inhaled anesthetics concentration versus loss of righting reflex,recovery of righting reflex and immobility were fit with nonlinear dose-response curves.All day phase tests were conducted during 9:00-14:00,and night phase tests were made during 21:00-02:00.2.Characteristics of electroencephalogram?EEG?signals during isoflurane and sevoflurane anesthesia at day phase and night phaseEEG electrodes were implanted surgically at least 14 days before experiments.16 mice were used to record EEG signals during isoflurane anesthesia and 14 mice were used to record EEG signals during isoflurane anesthesia.Results:1.Study of circadian rhythm dependent variations for induction and recovery from isoflurane and sevoflurane anesthesia1.1 There was no significant difference for Time _LORR under 1 MAC of isoflurane and sevoflurane anesthesia between day phase group and night phase group,while Time _RORRORR showed phase-dependent variations,with night phase group being shorter than day phase group for isoflurane?p<0.05?.Time_RORR for sevoflurane anesthesia showed no significant difference.1.2 MAC_RORR of isoflurane was significantly higher?0.490%,95%confidence interval=0.469-0.513%vs.0.414%,95%confidence interval=0.389-0.440%,p<0.01?at night phase compared to that at day phase.There was no significant difference for MAC_LORRORR and MAC of isoflurane between day phase and night phase.Circadian rhythm had no significantly effect on MAC_LORR and MAC of sevoflurane,while MAC_RORR showed phase-dependent variation,with night phase group?0.938%,95%CI=0.918-0.959%?being higher than day phase group?0.799%,95%CI=0.789-0.809%,p<0.01?.2.The delta wave relative power of EEG was increased and theta wave relative power was decreased after isoflurane or sevoflurane anesthesia.There was no difference in rate of descent for the theta/delta ratio during induction in isoflurane or sevoflurane anesthesia.The theta/delta ratio at night phase was trend to recover more quickly than that at day phase during recovery from isoflurane and sevofluraneConclusion:For isoflurane and sevoflurane anesthesia,mice were much easier to recovery at night phase than that at day phase.That activity of cortex was trend to recover more quickly at night phase than that at day phase might explain this phenomenon.