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Updated: Nov 15, 2025
In vivo Evaluation of Mucociliary Clearance in Mice
Published on: December 18, 2020
Differential effect of anesthetics on mucociliary clearance in vivo in mice
Kyle S Feldman1, Eunwon Kim1, Michael J Czachowski2
1Department of Developmental Biology, Rangos Research Center, University of Pittsburgh School of Medicine, 530 45th St., Pittsburgh, PA, 15201, USA.
Abstract:
Respiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice received intra-tracheal installation of 99mTc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 h to measure baseline MCC (n = 8). Mice were challenged for one hour with inhalational 1.5% isoflurane, or intraperitoneal ketamine (100 mg/kg)/xylazine (20 mg/kg), ketamine (0.5 mg/kg)/dexmedetomidine (50 mg/kg), fentanyl (0.2 mg/kg)/1.5% isoflurane, propofol (120 mg/Kg), or fentanyl/midazolam/dexmedetomidine (0.025 mg/kg/2.5 mg/kg/0.25 mg/kg) prior to MCC assessment. The baseline MCC was 6.4%, and was significantly reduced to 3.7% (p = 0.04) and 3.0% (p = 0.01) by ketamine/xylazine and ketamine/dexmedetomidine challenge respectively. Importantly, combinations of drugs containing fentanyl, and propofol in isolation did not significantly depress MCC. Although no change in cilia length or percent ciliation was expected, we tried to correlate ex-vivo tracheal cilia ciliary beat frequency and cilia-generated flow velocities with MCC and found no correlation. Our results indicate that anesthetics containing ketamine (ketamine/xylazine and ketamine/dexmedetomidine) significantly depress MCC, while combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol do not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations.
Insights
Ketamine-based anesthetics significantly impair respiratory mucociliary clearance (MCC) in mice. However, fentanyl-containing combinations and propofol did not affect MCC, suggesting safer anesthetic options for lung function.
Area of Science:
- Pulmonary Physiology
- Pharmacology
- Anesthesiology
Background:
- Respiratory mucociliary clearance (MCC) is crucial for lung defense against inhaled substances.
- In vitro studies suggest anesthetics can depress ciliary function.
- The in vivo effects of various anesthetic agents on MCC require further investigation.
Purpose of the Study:
- To evaluate the impact of different anesthetic regimens on MCC in a mouse model.
- To identify anesthetic combinations that preserve MCC function.
- To assess the utility of a SPECT/CT imaging method for MCC assessment.
Main Methods:
- 99mTc-Sulfur colloid was instilled intratracheally in mice.
- Mucociliary clearance (MCC) was measured using dual-modality SPECT/CT imaging at baseline and after 6 hours.
- Mice were challenged with various anesthetics including ketamine/xylazine, ketamine/dexmedetomidine, fentanyl/isoflurane, propofol, and fentanyl/midazolam/dexmedetomidine.
Main Results:
- Ketamine/xylazine and ketamine/dexmedetomidine significantly reduced MCC by 42% and 53% respectively.
- Anesthetic combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol did not significantly depress MCC.
- No correlation was found between ex-vivo ciliary beat frequency/flow velocities and in vivo MCC.
Conclusions:
- Anesthetics containing ketamine significantly impair respiratory mucociliary clearance.
- Fentanyl-containing anesthetic combinations and propofol appear to preserve MCC function.
- The SPECT/CT method is a reproducible tool for studying drug effects on MCC.
