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Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells

[Les effets différentiels des anesthésiques intraveineux sur la motilité ciliaire de cellules cultivées d’épithélium trachéal de rat]

From the Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.

Address correspondence to: Dr. G. Shirakami, Department of Anesthesia, Kyoto University Hospital, Kyoto 606-8507, Japan. Phone: 81-75-751-3516; Fax: 81-75-752-3259; E-mail: gshi{at}kuhp.kyoto-u.ac.jp

Purpose: It has been shown that airway ciliary function is impaired by several anesthetic or sedative drugs, which may predispose anesthetized or intensive care patients to respiratory complications, such as hypoxemia, atelectasis and pulmonary infection. We studied the effects of midazolam, propofol, dexmedetomidine, ketamine, fentanyl, thiopental and pentobarbital on ciliary beat frequency (CBF) in isolated and cultured rat tracheal epithelial (RTE) cells, to investigate their direct CBF action removing influences of non-epithelial cells.

Methods: Rat tracheal epithelial cells were purely isolated from tracheas of adult male Sprague-Dawley rats. After 14 to 21 days of culture, the images of motile cilia were videotaped using a phase-contrast microscope. Baseline CBF and CBF 30 or 50 min after administration of vehicle or one of the above agents were computer-analyzed.

Results: Midazolam (0.3–10 µM), propofol (1–100 µM), dexmedetomidine (1–100 nM), fentanyl (0.1–10 nM) and thiopental (30–300 µM) had no effect on CBF. Ketamine at a supraclinical dose (1000 µM) increased CBF (22 ± 13, mean ± standard deviation, % increase from baseline; baseline = 100%) significantly (P < 0.01). Fentanyl at a high clinical dose (100 nM) increased CBF significantly (10 ± 9%). Pentobarbital decreased CBF dose-dependently (100 µM, –2 ± 6%; 300 µM, –14 ± 18%; 1000 µM, –75 ± 5%) and reversibly (P < 0.01).

Conclusion: These results show that midazolam, propofol, dexmedetomidine and thiopental have no direct action on CBF in isolated RTE cells, whereas high doses of ketamine and fentanyl have direct ciliostimulatory actions and pentobarbital has a direct cilioinhibitory action.