Inhibition of voltage-gated sodium channels by emulsified isoflurane may contribute to its subarachnoid anesthetic effect in beagle dogs

Reg Anesth Pain Med. 2011 Nov-Dec;36(6):553-9. doi: 10.1097/AAP.0b013e3182324d18.

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.

Publication types

  • Comparative Study

MeSH terms

  • Anesthesia, Epidural / methods*
  • Animals
  • Animals, Newborn
  • Dogs
  • Dose-Response Relationship, Drug
  • Emulsions
  • Injections, Spinal
  • Isoflurane / administration & dosage*
  • Isoflurane / chemistry
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers / administration & dosage*
  • Sodium Channels / physiology*
  • Subarachnoid Space / drug effects
  • Subarachnoid Space / physiology

Substances

  • Emulsions
  • Sodium Channel Blockers
  • Sodium Channels
  • Isoflurane