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Front. Neurol. | doi: 10.3389/fneur.2018.00985

A Novel Non-invasive Approach for Measuring Upper Airway Collapsibility in Mice

 Yoichi Nishimura1*, Rafael S. Arias2,  Huy Pho2, Luu V. Pham2, Thomaz Fleury Curado,2,  Vsevolod Y. Polotsky2 and  Alan R. Schwartz2
  • 1The Johns Hopkins Hospital, Johns Hopkins Medicine, United States
  • 2Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, United States

ABSTRACT
Introduction: Invasive procedures were previously developed for measuring pharyngeal collapsibility in rodents during expiration, when declining neuromuscular activity makes the airway unstable. We developed a non-invasive approach for streamlining collapsibility measurements by characterizing responses in physiologic markers of dynamic expiratory airflow obstruction to negative nasal pressure challenges.
Methods: Anesthetized mice were instrumented to monitor upper airway pressure-flow relationships with head-out plethysmography while nasal pressure was ramped down from ~+5 to -20 cmH2O over several breaths. Inspiratory and expiratory flow, volume and timing characteristics were assessed breath-wise. Pcrit was estimated at transitions in expiratory amplitude and timing parameters, and compared to gold standard PCRIT measurements when nasal and tracheal pressures diverged during expiration. Predictions equations were constructed in a development data set (n=8) and applied prospectively to a validation data set (n=16) to estimate gold standard PCRIT.
Results: The development data demonstrated that abrupt reversals in expiratory duration and tidal volume during nasal pressure ramps predicted gold standard PCRIT measurements. After applying regression equations from the development to a validation dataset, we found that a combination of expiratory amplitude and timing parameters proved to be robust predictors of gold standard PCRIT with minimal bias and narrow confidence intervals.
Conclusions: Markers of expiratory airflow obstruction can be used to model upper airway collapsibility, and can provide sensitive measures of changes in airway collapsibility in rodents. This approach streamlines repeated non-invasive PCRIT measurements, and facilitates studies examining the impact of genetic, environmental and pharmacologic factors on upper airway control.

Keywords: obstructive sleep apnea, Upper airway collapsibility, Critical pressure, Pharynx, Mice

Received: 03 Oct 2018; Accepted: 31 Oct 2018.

Edited by:

Thomas Penzel, Charité Universitätsmedizin Berlin, Germany

Reviewed by:

Ramon Farre, University of Barcelona, Spain
Irma Rukhadze, UCLA David Geffen School of Medicine, United States  

Copyright: © 2018 Nishimura, Arias, Pho, Pham, Fleury Curado,, Polotsky and Schwartz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yoichi Nishimura, The Johns Hopkins Hospital, Johns Hopkins Medicine, Baltimore, United States, ny41west@yahoo.co.jp