Recovery of respiratory ciliary function after depression by inhalation anaesthetic agents: an in vitro study using nasal turbinate explants.

We have developed a human tissue preparation suitable for measurement of cilia beat frequency derived from nasal turbinates. Cilia beat frequency of turbinate explants from 11 patients did not change significantly over a 10-day observation period while maintained in an incubator, with mean cilia beat frequency of 13.1 (SEM 0.3) Hz to 14.4 (0.2) Hz (ANOVA for repeated measures, P = 0.168). We have used this preparation to investigate recovery of ciliary function after depression by inhalation anaesthetic agents. Eight or nine turbinate explants were exposed to three times the minimum alveolar concentration (MAC) of halothane, enflurane or isoflurane for a period of 1 h and thereafter to a period of air washout. After exposure to the inhalation agent there was a significant reduction in cilia beat frequency with all three agents: halothane 14.3 (0.4) Hz to 9.5 (0.3) Hz; enflurane 13.7 (0.6) Hz to 10.5 (0.5) Hz;isoflurane 15.9 (0.6) Hz to 10.6 (0.3) Hz. Cilia beat frequency returned to values after air washout that were not significantly different from baseline after 90 min of washout of halothane and 60 min of washout of enflurane and isoflurane (repeated measures ANOVA, unpaired t test; P = 0.01 at 60 min and P = 0.31 at 90 min washout for halothane; P = 0.83 at 60 min washout for enflurane; P = 0.26 at 60 min washout for isoflurane).

Effects of morphine on human nasal cilia beat frequency in vitro.

Using human nasal cytological brushings, we have investigated the effects of morphine on ciliary function by measurement of cilia beat frequency in vitro, and we have also determined opioid receptor binding in these specimens. We obtained ciliated samples from seven volunteers, and measured cilia beat frequency using the transmitted light technique during exposure to morphine 10 mumol litre-1 for 4 h. Mean cilia beat frequency of the samples exposed to morphine was 11.1 (95% confidence interval 10.9-11.5) Hz and that of the controls 11.3 (11.1-11.7) Hz. There was no significant effect of morphine on human cilia beat frequency in vitro (MANOVA for repeated measures and nested, F = 0.61, P = 0.66). In a separate study, we obtained nasal brushings from 20 patients and measured the binding of the opioid antagonist tritiated diprenorphine ([3H]DPN). Mean disintegrations per minute (dpm) for total and non-specific binding were 9036 (8105-9967) dpm and 9130 (8054-10206) dpm, respectively. These values did not differ significantly (paired t test, t = 0.22, P = 0.83). We conclude that morphine had no effect on cilia beat frequency in vitro and we were unable to demonstrate any significant numbers of opioid receptors on nasal ciliated epithelium.

A perfusion system for in vitro measurement of human cilia beat frequency.

We have designed and built a perfusion system and perfusion chamber to allow investigation of the effects of anaesthetic agents on human cilia in vitro. Using this system, samples of human respiratory cilia can be maintained in a stable and controlled environment for several hours. We measured cilia beat frequency of nasal respiratory epithelium from 10 healthy volunteers; cilia beat frequency was constant over a 4-h period, and measurements were found to be in good agreement with previously published work [1]. In a separate study we investigated the effect of a sleep dose of propofol on cilia beat frequency in samples from six patients undergoing minor surgery; samples were obtained before and immediately after induction of anaesthesia with propofol 2-3 mg kg-1. There was no statistically significant difference in cilia beat frequency between data obtained before and after induction with propofol.

Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro.

We have measured the effects of three times the minimum alveolar concentration (MAC) of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelial brushings from 18 healthy adult patients. Using the transmitted light technique and paired perfusion chambers, the cilia were exposed to 2.25% halothane, 5% enflurane or 3.6% isoflurane in air, or air alone, in a controlled and blinded manner. Over a 4-h observation period, cilia beat frequency of the samples exposed to inhalation anaesthetic agents demonstrated a significant reduction in frequency compared with controls exposed to air alone. Mean cilia beat frequency for the samples exposed to halothane was 9.3 (SEM 1.3) compared with its controls of 11.4 (1.0); for the samples exposed to enflurane, 10.9 (1.3) compared with its controls of 11.6 (1.2); and for the samples exposed to isoflurane, 10.8 (1.1) compared with its controls of 11.6 (1.2). There was a statistically significant difference between the samples exposed to all three volatile agents and their associated controls (halothane, P = 0.01; enflurane, P = 0.03; isoflurane, P = 0.01; nested repeated measures analysis of variance utilizing polynomial contrasts).