Differential Effect of Anesthetics on Mucociliary Clearance in Vivo in Mice
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/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.
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.
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.
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Posted 22 Dec, 2020
On 12 Jan, 2021
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On 24 Dec, 2020
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On 18 Dec, 2020
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Differential Effect of Anesthetics on Mucociliary Clearance in Vivo in Mice
Posted 22 Dec, 2020
On 12 Jan, 2021
Received 31 Dec, 2020
Received 31 Dec, 2020
Received 31 Dec, 2020
Received 31 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
On 24 Dec, 2020
Invitations sent on 23 Dec, 2020
On 18 Dec, 2020
On 18 Dec, 2020
On 18 Dec, 2020
On 02 Dec, 2020
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/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.
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.
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