The Effects of Temperature and Anesthetic Agents on Ciliary Function in Murine Respiratory Epithelia

Abstract

Background: Mucus transport mediated by motile cilia in the airway is an important defense mechanism for prevention of respiratory infections. As cilia motility can be depressed by hypothermia or exposure to anesthetics, in this study, we investigated the individual and combined effects of dexmedetomidine (dex), fentanyl (fen), and/or isoflurane (iso) at physiologic and low temperatures on cilia motility in mouse tracheal airway epithelia. These anesthetic combinations and low temperature conditions are often used in the setting of cardiopulmonary bypass surgery, surgical repair of congenital heart disease, and cardiac intensive care.Methods: C57BL/6J mouse tracheal epithelia were excised and cilia dynamics were captured by videomicroscopy following incubation at 15, 22–24, and 37°C with different combinations of therapeutic concentrations of dex (10 nM), fen (10 nM), and iso (0.01%). Airway ciliary motion was assessed and compared across conditions by measuring ciliary beat frequency and ciliary flow velocity. Statistical analysis was carried out using unpaired t-tests, analysis of variance, and multivariate linear regression.Results: There was a linear correlation between cilia motility and temperature. Fen exerted cilia stimulatory effects, while dex and iso each had ciliodepressive effects. When added together, fen + iso, dex + iso, and dex + fen + iso were all cilia inhibitory. In contrast fenl + dex did not significantly alter ciliary function.Conclusion: We show that ciliary motility is stimulated by fen, but depressed by dex or iso. However, when used in combination, ciliary motility showed changes indicative of complex drug–drug and drug–temperature interactions not predicted by simple summation of their individual effects. Similar studies are needed to examine the human airway epithelia and its response to anesthetics.

Measurement of ciliary beat frequency using Doppler optical coherence tomography

“…The VCSEL D‐OCT device measured a CBF value at physiologic temperature of approximately 9 Hz, which is similar to that reported in other ex vivo tissue studies . Pharmacologic agents and temperature are known to augment CBF in ex vivo mucosal samples; although we diminished CBF using 10% formalin, we also expect D‐OCT to reproduce the known correlation between temperature or pharmacological agents and CBF reported in the literature . In the future, the ability of D‐OCT to monitor changes in CBF due to these conditions will be evaluated ex vivo and in vivo.…”

Quantifying hyperoxia-mediated damage to mammalian respiratory cilia-driven fluid flow using particle tracking velocimetry optical coherence tomography

“…2). Consistent with prior literature, 22 flow speeds increase as temperature increases from room to body temperature. Interestingly, after returning the temperature to a normal range of 36 to 38°C from febrile temperatures, flow velocities do not recover to baseline values for that temperature range.…”

The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood

“…Memarzadeh et al reported higher water intake in ventilated cages compared with CCs in a mouse study but did not address the gender of the animals or the temperature 13. It has also been observed that the temperature inside the cages tends to be higher than that outside the cages 14. Therefore, the temperature in the IVCs may be higher than that in the CCs because the lids of IVCs are closed, unlike those of CCs.…”