Effects of anaesthetic and sedative agents on human respiratory cilia in vitro.

Chest infections developing after surgery and in patients in the intensive care unit occur commonly, and the incidence has been largely unchanged over the years. This has occurred despite the widespread use of antibiotics and of methods to improve mucus clearance through more effective coughing. One of the most important defences against respiratory infections is mucociliary clearance. A variety of anaesthetic and sedative drugs impair this and therefore may be a factor in the development of these respiratory infections. The mechanisms by which these agents impair mucociliary clearance have not been elucidated. The presence of cilia and their beating frequency is one of the most important determinants and the investigation of anaesthetic and sedative agents upon these factors forms the subject of this thesis. We have developed an in vitro method for investigating the effects of anaesthetic and sedative agents on ciliary beat frequency. This comprises a perfusion system together with new techniques of ciliated tissue sample preparation. The inhalation anaesthetic agents, halothane, enflurane and isoflurane caused a reversible dose-dependent reduction in ciliary beat frequency that was significant at clinical concentrations. In contrast, short term exposure to intravenously administered anaesthetics and sedatives, propofol, midazolam and morphine, did not cause any significant change in ciliary beat frequency. The long term effects of intensive care sedatives gave differing results. 48-72 hours exposure to a sedative concenfration of isoflurane did not affect ciliary beat frequency or cilia survival. In contrast 72 hours incubation with either propofol or midazolam impaired cilia survival. In the case of propofol the effect was only apparent with tissue that had been stored for several days and with fr'esh tissue there was no effect on cilia survival. In the case of midazolam there was a dose-dependent reduction in the number of functioning cilia following incubation of fresh tissue although this effect was significant only above clinical concentrations.