Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells.
OBJECTIVE
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 microM), propofol (1-100 microM), dexmedetomidine (1-100 nM), fentanyl (0.1-10 nM) and thiopental (30-300 microM) had no effect on CBF. Ketamine at a supraclinical dose (1000 microM) 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 microM, -2 +/- 6%; 300 microM, -14 +/- 18%; 1000 microM, -75 +/- 5%) and reversibly (P < 0.01).


CONCLUSIONS
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.
Iida
Hiroko
H
Department of Anesthesia, Kyoto University Hospital, Kyoto 606-8507, Japan.
Matsuura
Shogo
S
Shirakami
Gotaro
G
Tanimoto
Keiji
K
Fukuda
Kazuhiko
K
D000700:Analgesics / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects*; D005283:Fentanyl / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009038:Motion; D010424:Pentobarbital / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*; D013874:Thiopental / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000166:cytology
D000700:Analgesics; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D007649:Ketamine; D010424:Pentobarbital; D013874:Thiopental; D008874:Midazolam; D005283:Fentanyl; D015742:Propofol