Differential effect of anesthetics on mucociliary clearance in vivo in mice

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.

Using the Intranasal Route to Administer Drugs to Treat Neurological and Psychiatric Illnesses: Rationale, Successes, and Future Needs

“…atropine) [ 67 , 68 ] or inhibit ciliary movement (e.g. local anesthetics such as ketamine/xylazine and fentanyl) [ 69 ], increasing the potential for adverse effects.…”

Anesthesia and analgesia for common research models of adult mice

“…As reported, intraperitoneal injection of pentobarbital sodium/ketamine [ 70 ], urethane/alpha-chloralose [ 71 ], and ketamine/xylazine [ 72 ], as well as inhaled isoflurane have been applied as anesthetic agents in this surgical procedure. The combination of pentobarbital/Ketamine/xylazine decreases the tracheal mucociliary clearance [ 73 ]. However, isoflurane, propofol, or fentanyl/dexmedetomidine/midazolam do not seem to change the tracheal mucociliary clearance values [ 73 ].…”

“…The combination of pentobarbital/Ketamine/xylazine decreases the tracheal mucociliary clearance [ 73 ]. However, isoflurane, propofol, or fentanyl/dexmedetomidine/midazolam do not seem to change the tracheal mucociliary clearance values [ 73 ]. Opioid analgesics such as buprenorphine should be used as intra-operative analgesics.…”

Mucus Clearance Strategies in Mechanically Ventilated Patients

“…We define direct effects as those resulting directly from the mechanical ventilation circuit (including epithelial damage from endotracheal tube and cuff, anesthetics, lack of humidification, direct cough impairment) vs. indirect effects resulting from comorbid critical illness (inflammation, immobility, atelectasis) ( Sackner et al, 1975a ; Konrad et al, 1994 ). Anesthetic medications, specifically dexmedetomidine and ketamine, have been shown in in vitro models to directly decrease mucociliary clearance ( Feldman et al, 2021 ). High FiO2 is known to decrease tracheal mucus velocity, likely through impaired ciliary function ( Sackner et al, 1975b ).…”