Neural mechanisms of sevoflurane-induced respiratory depression in newborn rats.
BACKGROUND
Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of gamma-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression.


METHODS
In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the gamma-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques.


RESULTS
Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons.


CONCLUSIONS
Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.
Kuribayashi
Junya
J
Department of Anesthesiology, Keio University School of Medicine, Japan.
Sakuraba
Shigeki
S
Kashiwagi
Masanori
M
Hatori
Eiki
E
Tsujita
Miki
M
Hosokawa
Yuki
Y
Takeda
Junzo
J
Kuwana
Shun-Ichi
S
D018685:Anesthetics, Inhalation / Q000134:cerebrospinal fluid / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D004347:Drug Interactions; D058787:GABA-A Receptor Antagonists; D008526:Medulla Oblongata / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000134:cerebrospinal fluid / Q000633:toxicity*; D009046:Motor Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced*; D000077149:Sevoflurane; D013116:Spinal Cord / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D058787:GABA-A Receptor Antagonists; D008738:Methyl Ethers; D010852:Picrotoxin; D011963:Receptors, GABA-A; D000077149:Sevoflurane