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Research Article
Differential Effect of Anesthetics on Mucociliary Clearance in Vivo in Mice
Maliha Zahid
University of Pittsburgh
Corresponding Author
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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.
Keywords
Cilia, Mucociliary Clearance, Fentanyl, Isoflurane, Ketamine, Xylazine, Dexmedetomidine, Propofol
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CURRENT STATUS: Under Review
Version 1
Posted 22 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 12 Jan, 2021
Review #4 received
Received 31 Dec, 2020
Review #3 received
Received 31 Dec, 2020
Review #2 received
Received 31 Dec, 2020
Review #1 received
Received 31 Dec, 2020
Reviewer #6 agreed
On 24 Dec, 2020
Reviewer #3 agreed
On 24 Dec, 2020
Reviewer #10 agreed
On 24 Dec, 2020
Reviewer #9 agreed
On 24 Dec, 2020
Reviewer #8 agreed
On 24 Dec, 2020
Reviewer #7 agreed
On 24 Dec, 2020
Reviewer #4 agreed
On 24 Dec, 2020
Reviewer #1 agreed
On 24 Dec, 2020
Reviewer #2 agreed
On 24 Dec, 2020
Reviewers invited
Invitations sent on 23 Dec, 2020
Editor assigned
On 18 Dec, 2020
Editor invited
On 18 Dec, 2020
Submission checks complete
On 18 Dec, 2020
First submitted
On 02 Dec, 2020
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Differential Effect of Anesthetics on Mucociliary Clearance in Vivo in Mice
Maliha Zahid
University of Pittsburgh
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 22 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 12 Jan, 2021
Review #4 received
Received 31 Dec, 2020
Review #3 received
Received 31 Dec, 2020
Review #2 received
Received 31 Dec, 2020
Review #1 received
Received 31 Dec, 2020
Reviewer #6 agreed
On 24 Dec, 2020
Reviewer #3 agreed
On 24 Dec, 2020
Reviewer #10 agreed
On 24 Dec, 2020
Reviewer #9 agreed
On 24 Dec, 2020
Reviewer #8 agreed
On 24 Dec, 2020
Reviewer #7 agreed
On 24 Dec, 2020
Reviewer #4 agreed
On 24 Dec, 2020
Reviewer #1 agreed
On 24 Dec, 2020
Reviewer #2 agreed
On 24 Dec, 2020
Reviewers invited
Invitations sent on 23 Dec, 2020
Editor assigned
On 18 Dec, 2020
Editor invited
On 18 Dec, 2020
Submission checks complete
On 18 Dec, 2020
First submitted
On 02 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5