Optical imaging of propofol-induced central respiratory depression in medulla-spinal cord preparations from newborn rats.
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.
Department of Anaesthesiology, Kitasato Institute Hospital, Kitasato UniversityDepartment of Physiology, Showa University School of MedicineDepartment of Anaesthesiology, School of Medicine, Keio University, Tokyo, Japan.
Masanori
M
Kashiwagi
Yoshimune
Y
Osaka
Hiroshi
H
Onimaru
Junzo
J
Takeda
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061848:Optical Imaging; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D012119:Respiration / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D015742:Propofol