Differential Effect of Anesthetics on Mucociliary Clearance in Vivo in Mice

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.

Transnasal-brain delivery of nanomedicines for neurodegenerative diseases

“…Repeated delivery of the drug to the nasal cavity can cause nasal pruritus, nasal bleeding, reduced or altered sense of smell and taste, sinusitis, and nasal epithelial damage (Musumeci et al, 2019). Some drugs also alter ciliary beating frequency (e.g., atropine) (Ukai et al, 1985) and inhibit ciliary motility (e.g., ketamine) (Feldman et al, 2021), and enhancing long-term patient compliance is a challenge that requires further evaluation.…”

Methods for the assessment of human airway ciliary function

“…ALI-cultures may be washed in processing to reduce mucus build-up before use [22]. Inhaled anaesthetics depress ciliary function [25,26], therefore anaesthetic or topical nasal agents that potentially modify ciliary function should be avoided or washed out before baseline measurements. Sampling and infection damage increase SCD [27,28].…”

Anesthesia and analgesia for common research models of adult mice

“…As reported, intraperitoneal injection of pentobarbital sodium/ketamine [70], urethane/ Ahmadi-Noorbakhsh et al Laboratory Animal Research (2022) 38:40 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.…”