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PEDIATRIC ANESTHESIA

A Neuronal Mechanism of Propofol-Induced Central Respiratory Depression in Newborn Rats

Masanori Kashiwagi, MD^*, Yasumasa Okada, MD, Shun-ichi Kuwana, PhD, Shigeki Sakuraba, MD^*, Ryoichi Ochiai, MD^*, and Junzo Takeda, MD^*

*Department of Anesthesiology, School of Medicine, Keio University; Department of Physiology, Teikyo University School of Medicine, Tokyo; and Department of Medicine, Keio University Tsukigase Rehabilitation Center, Shizuoka-ken, Japan

Address correspondence and reprint requests to Masanori Kashiwagi, MD, Department of Anesthesiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. Address e-mail to mkashiwagi{at}1990.jukuin.keio.ac.jp

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of -aminobutyric acid (GABA)_A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABA_A antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABA_A receptors. It is likely that the GABA_A receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.

IMPLICATIONS: We analyzed the effects of propofol on medullary respiratory neurons in brainstem-spinal cord preparations from newborn rats in vitro using a perforated patch-clamp technique. Our findings suggest that the -aminobutyric acid (GABA)_A receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999