Skip to main content
SpringerLink
Log in

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 ďépithélium trachéal de rat

  • Published:
Canadian Journal of Anesthesia Aims and scope Submit manuscript

Abstract

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.

Résumé

Objectif

La fonction ciliaire des voies aériennes est affectée par certains anesthésiques ou sédatifs qui peuvent prédisposer des patients anesthésiés, ou en soins intensifs, à ľhypoxémie, ľatélectasie et ľinfection pulmonaire. Les effets des midazolam, propofol, dexmédétomidine, kétamine, fentanyl, thiopental et pentobarbital sur la fréquence des battements ciliaires (FBC) de cellules épithéliales trachéales de rat (ETR), isolées et cultivées, ont été étudiés pour vérifier leur action directe sur la FBC tout en écartant ľinfluence des cellules non épithéliales.

Méthode

Des cellules épithéliales de trachée de rats, mâles adultes Sprague-Dawley, ont été isolées. Après 14 à 21 jours de culture, les images vidéo de cils mobiles ont été enregistrées en utilisant un microscope à contraste de phase. La FBC de base, et celle de 30 ou 50 min après ľadministration du véhicule, ou ďun des médicaments, ont été analysées par ordinateur.

Résultats

Les midazolam (0,3–10 μM), propofol (1–100 μM), dexmédétomidine (1–100 nM), fentanyl (0,1–10 nM) et thiopental (30–300 μM) n’ont pas eu ďeffet sur la FBC. La kétamine, à dose supraclinique (1000 μM), a augmenté la FBC (22 ± 13, moyenne ± écart type, % ďaugmentation; données de base = 100 %) de manière significative (P < 0,01). Le fentanyl, à forte dose (100 nM), a significativement augmenté la FBC (10 ± 9 %). Le pentobarbital a diminué la FBC en fonction de la dose (100 μM, -2 ± 6 %; 300 μM, -14 ± 18 %; 1000 μM, -75 ± 5 %) et de façon réversible (P < 0,01).

Conclusion

Les midazolam, propofol, dexmédétomidine et thiopental n’ont pas ďaction directe sur la FBC de cellules ETR isolées, tandis que de fortes doses de kétamine et de fentanyl ont une action ciliostimulante directe et que le pentobarbital a une action clio-inhibitrice directe.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lee RM, Forrest JB. Structure and function of cilia.In: Crystal RG, West JB (Eds) The Lung, Scientific Foundations, 2nd ed. Philadelphia: Lippincott-Raven; 1997: 459–78.

    Google Scholar 

  2. Wanner A, Salathé M, O’Riordan TG. Mucociliary clearance in the airways. Am J Respir Crit Care Med 1996; 154: 1868–902.

    Article  PubMed  CAS  Google Scholar 

  3. Farber NE, Pagel PS, Warltier DC. Pulmonary pharmacology.In: Miller RD (Ed.) Miller’s Anesthesia, 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005: 155–89.

    Google Scholar 

  4. Forbes AR, Horrigan RW. Mucociliary flow in the trachea during anesthesia with enflurane, ether, nitrous oxide, and morphine. Anesthesiology 1977; 46: 319–21.

    Article  PubMed  CAS  Google Scholar 

  5. Forbes AR, Gamsu G. Depression of lung mucociliary clearance by thiopental and halothane. Anesth Analg 1979; 58: 387–9.

    PubMed  CAS  Google Scholar 

  6. Patrick G, Stirling C. Measurement of mucociliary clearance from the trachea of conscious and anesthetized rats. J Appl Physiol 1977; 42: 451–5.

    PubMed  CAS  Google Scholar 

  7. Raphael JH, Selwyn DA, Mottram SD, Langton JA, O’Callaghan C. Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro. Br J Anaesth 1996; 76: 116–21.

    Article  PubMed  CAS  Google Scholar 

  8. Raphael JH, Butt MW. Comparison of isoflurane with propofol on respiratory cilia. Br J Anaesth 1997; 79: 473–5.

    Article  PubMed  CAS  Google Scholar 

  9. Hasani A, Spiteri MA, Pavia D, Lopez-Vidriero MT, Agnew JE, Clarke SW. Effect of temazepam on tracheobronchial mucus clearance. Thorax 1992; 47: 298–300.

    Article  PubMed  CAS  Google Scholar 

  10. Johnston M, Watts S, Drake-Lee A. In vitro effects of diazepam on human ciliary function. Acta Otolaryngol (Stockh) 1997; 117: 856–9.

    Article  CAS  Google Scholar 

  11. Konrad F, Schraag S, Marx T, Kilian J, Goertz A. Effect of total intravenous anaesthesia with propofol, alfentanil, vecuronium on bronchial mucus transport velocity (German). Anästhesiol Intensivmed Notfallmed Schmerzther 1998; 33: 171–6.

    Article  PubMed  CAS  Google Scholar 

  12. Dormehl IC, Jacobs L, Maree M, Ras G, Hugo N, Beverley G. A baboon model for in vivo assessment of mucociliary lung clearance. J Med Primatol 1991; 20: 235–9.

    PubMed  CAS  Google Scholar 

  13. Iravani J, Melville GN. Effects of drugs and environmental factors on ciliary movement (authors’s transl, German). Respiration 1975; 32: 157–64.

    Article  PubMed  CAS  Google Scholar 

  14. Karttunen P, Silvasti M, Saano V, et al. Effect of codeine on rat and guinea pig tracheal ciliary beat frequency. Arzneim-Forsch Drug Res 1991; 41: 1095–7.

    CAS  Google Scholar 

  15. Wang L, Tiniakov RL, Yeates DB. Peripheral opioidergic regulation of the tracheobronchial mucociliary transport system. J Appl Physiol 2003; 94: 2375–83.

    PubMed  CAS  Google Scholar 

  16. Landa JF, Hirsh JA, Lebeaux MI. Effects of topical and general anesthetic agents on tracheal mucous velocity of sheep. J Appl Physiol 1975; 38: 946–8.

    PubMed  CAS  Google Scholar 

  17. King M, Engel LA, Macklem PT. Effect of pentobarbital anesthesia on rheology and transport of canine tracheal mucus. J Appl Physiol 1979; 46: 504–9.

    PubMed  CAS  Google Scholar 

  18. Kaartinen L, Nettesheim P, Adler KB, Randell SH. Rat tracheal epithelial cell differentiation in vitro. In Vitro Cell Dev Biol 1993; 29A: 481–92.

    Article  CAS  Google Scholar 

  19. Ostrowski LE, Randell SH, Clark AB, Gray TE, Nettesheim P. Ciliogenesis of rat tracheal epithelial cells in vitro. Methods Cell Biol 1995; 47: 57–63.

    Article  PubMed  CAS  Google Scholar 

  20. Ohmoto N, Tokiwano K, Tanaka Y, Sumi A, Terachi S, Konno H. Exponential characteristics of power spectral densities caused by chaotic phenomena. J Phys Soc Jpn 1995; 64: 1104–13.

    Article  Google Scholar 

  21. Hann HC, Hall AP, Rahael JH, Langton JA. An investigation into the effects of midazolam and propofol on human respiratory cilia beat frequency in vitro. Intensive Care Med 1998; 24: 791–4.

    Article  PubMed  CAS  Google Scholar 

  22. Reves JG, Glass PS, Lubarsky DA, McEvoy MD. Intravenous nonopioid anesthetics.In: Miller RD (Ed.). Miller’s Anesthesia, 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005: 317–78.

    Google Scholar 

  23. Shirakami G, Li D, Zhan X, Johns RA. Propofol stimulates ciliary motility via the nitric oxide-cyclic GMP pathway in cultured rat tracheal epithelial cells. Anesthesiology 2000; 93: 482–8.

    Article  PubMed  CAS  Google Scholar 

  24. Phillips PP, McCaffrey TV, Kern EB. The in vivo and in vitro effect of phenylephrine (neo synephrine) on nasal ciliary beat frequency and mucociliary transport. Otolaryngol Head Neck Surg 1990; 103: 558–65.

    PubMed  CAS  Google Scholar 

  25. Ingels KJ, Meeuwsen F, Graamans K, Huizing EH. Influence of sympathetic and parasympathetic substances in clinical concentrations on human nasal ciliary beat. Rhinology 1992; 30: 149–60.

    PubMed  CAS  Google Scholar 

  26. Curtis LN, Carson JL. Computer-assisted video measurement of inhibition of ciliary beat frequency of human nasal epithelium in vitro by xylometazoline. J Pharmacol Toxicol Meth 1992; 28: 1–7.

    Article  CAS  Google Scholar 

  27. Boek WM, Romeijn SG, Graamans K, Verhoef JC, Merkus FW, Huizing EH. Validation of animal experiments on ciliary function in vitro. I. The influence of substances used clinically. Acta Otolaryngol (Stockh) 1999; 119: 93–7.

    Article  CAS  Google Scholar 

  28. Salathe M. Effects of ß-agonists on airway epithelial cells. J Allergy Clin Immunol 2002; 110: S275–81.

    Article  PubMed  CAS  Google Scholar 

  29. Selwyn DA, Raphael JH, Lambert DG, Langton JA. Effects of morphine on human nasal cilia beat frequency in vitro. Br J Anaesth 1996; 76: 274–7.

    Article  PubMed  CAS  Google Scholar 

  30. Fukuda K. Intravenous opioid anesthetics.In: Miller RD (Ed.). Miller’s Anesthesia, 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005: 379–437.

    Google Scholar 

  31. Henthorn TK. Pharmacokinetics of intravenous induction agents.In: Bowdle TA, Horita A, Kharasch ED (Eds). The Pharmacologic Basis of Anesthesiology. New York: Churchill-Livingstone; 1994: 307–18.

    Google Scholar 

  32. Bullock R, Ward JD. Management of head trauma.In: Ayres SM, Grenvik A, Holbrook PR, Shoemaker WC (Eds). Textbook of Critical Care, 3rd ed. Philadelphia: W.B. Saunders; 1995: 1449–57.

    Google Scholar 

  33. Sato M, Hirakata H, Nakagawa T, Arai K, Fukuda K. Thiamylal and pentobarbital have opposite effects on human platelet aggregation in vitro. Anesth Analg 2003; 97: 1353–9.

    Article  PubMed  CAS  Google Scholar 

  34. Moriyama S, Nakamura K, Hatano Y, Harioka T, Mori K. Responses to barbiturates of isolated dog cerebral and mesenteric arteries contracted with KCl and prostaglandin F2á. Acta Anaesthesiol Scand 1990; 34: 523–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesia, Kyoto University Hospital, 606-8507, Kyoto, Japan

    Hiroko Iida, Shogo Matsuura, Gotaro Shirakami, Keiji Tanimoto & Kazuhiko Fukuda

Authors
  1. Hiroko Iida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shogo Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gotaro Shirakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keiji Tanimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuhiko Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gotaro Shirakami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iida, H., Matsuura, S., Shirakami, G. et al. Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells. Can J Anesth 53, 242–249 (2006). https://doi.org/10.1007/BF03022209

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03022209

Search

Navigation