Optical imaging of propofol-induced central respiratory depression in medulla-spinal cord preparations from newborn rats

Clin Exp Pharmacol Physiol. 2011 Mar;38(3):186-91. doi: 10.1111/j.1440-1681.2011.05480.x.

Abstract

1. Propofol (2,6-diisopropylphenol) is an intravenous anaesthetic used for the induction and maintenance of general anaesthesia; it also potently and dose-dependently depresses respiration. The aim of the present study was to analyse propofol-induced changes in spatiotemporal patterns of inspiratory-related neural activity and to investigate the involvement of the GABAA receptor by using an optical imaging technique. 2. The brain stems and spinal cords of 0-1-day-old Wistar rats were isolated and stained using a fluorescent voltage-sensitive dye. Neuronal activity in the preparation was detected using an optical recording apparatus containing a charge-coupled device (CCD)-based camera. 3. Bath-applied propofol (7.5 μmol/L) decreased the C4 burst rate to 45.9% of baseline. Although optical signals corresponding to membrane depolarization during the pre-inspiratory phase in the parafacial region of the ventral medulla decreased to 28.7% of baseline following propofol application, those during the inspiratory phase in the caudal part of the rostral ventrolateral medulla did not. 4. The inhibitory effect of bath-applied propofol was reversed by 2 μmol/L bicuculline. 5. Changes in optical signals corresponding to the population activity of pre-inspiratory neurons were parallel to changes in the C4 burst rate. 6. The results suggest that propofol decreases the inspiratory burst rate by reducing the activity of pre-inspiratory neurons and that GABAA receptor activation plays a role in propofol-induced central respiratory depression. These results are consistent with those of previous electrophysiological studies.

Keywords: medulla oblongata; newborn rat; optical recordings; propofol; respiratory rhythm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Animals, Newborn
  • Medulla Oblongata / drug effects*
  • Medulla Oblongata / metabolism
  • Medulla Oblongata / pathology
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Optical Imaging
  • Propofol / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • Respiration / drug effects*
  • Respiratory Insufficiency / chemically induced*
  • Respiratory Insufficiency / metabolism
  • Respiratory Insufficiency / pathology
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism

Substances

  • Anesthetics, Intravenous
  • Receptors, GABA-A
  • Propofol