title: Inhibition of voltage-gated sodium channels by emulsified isoflurane may contribute to its subarachnoid anesthetic effect in beagle dogs.
abstract: BACKGROUND
  Volatile anesthetics, in addition to their general anesthesia action, have been proven to produce regional anesthetic effect in various animal models. The major aim of this study was to examine whether emulsified isoflurane (EI) could also produce subarachnoid anesthesia and to investigate its possible mechanism.
  
  
  METHODS
  Beagle dogs were randomly assigned into 5 groups (n = 6/group): intrathecally receiving 1% lidocaine 0.1 mL/kg, 30% intralipid 0.1 mL/kg (control), or 8% EI at doses of 0.05, 0.075, or 0.1 mL/kg, respectively. Consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. The effect of EI on voltage-gated Na channel was recorded from isolated spinal neurons of rats, using the whole-cell patch-clamp technique. Inhibition of peak sodium currents and effect of EI on Na channel gating were analyzed.
  
  
  RESULTS
  Emulsified isoflurane produced subarachnoid anesthesia in a dose-dependent manner, and at the dose of 0.1 mL/kg, the effect of 8% EI was similar to 1% lidocaine. Sodium channel currents were inhibited by EI at clinically relevant concentrations, with the IC50 (median inhibitory concentration) at 0.69 ± 0.08 mM. Voltage activation of Na channels was positive, shifted by isoflurane at the concentration of 0.77 mM, and V½ of activation (voltage for half-maximal activation) shifted from -12.4 ± 2.7 mV to -7.3 ± 2.3 mV (P < 0.01).
  
  
  CONCLUSIONS
  Emulsified isoflurane produced dose-dependent subarachnoid anesthesia, and this effect might be mediated by inhibition of EI on voltage-gated Na channels in the spinal cord.
authors: Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Cheng
authors: C
authors: Zhou
authors: Wei
authors: W
authors: Wu
authors: Jin
authors: J
authors: Liu
authors: Da-qing
authors: DQ
authors: Liao
authors: Yi
authors: Y
authors: Kang
authors: Xiang-dong
authors: XD
authors: Chen
mesh_terms: D000767:Anesthesia, Epidural / Q000379:methods*; D000818:Animals; D000831:Animals, Newborn; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D007278:Injections, Spinal; D007530:Isoflurane / Q000008:administration & dosage* / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000008:administration & dosage*; D015222:Sodium Channels / Q000502:physiology*; D013346:Subarachnoid Space / Q000187:drug effects / Q000502:physiology
chemical_list: D004655:Emulsions; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D007530:Isoflurane