Abstract
Background
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.
Methods
Wild-type C57BL/6J mice received intra-tracheal 99mTc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 hours to measure baseline MCC (n = 8). Mice were challenged for one hour with 1.5% isoflurane, 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.
Results
The baseline MCC ranged from 5.2 to 7.2%, 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. The CBF, cilia length, percent ciliation, and flow velocity did not correlate with the post-study baseline measurements.
Conclusions
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 alone did not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations.