A closed-loop model of the respiratory system: focus on hypercapnia and active expiration.

Authors:
Yaroslav I Molkov
Yaroslav I Molkov
Drexel University College of Medicine
Natalia A Shevtsova
Natalia A Shevtsova
Drexel University College of Medicine
Choongseok Park
Choongseok Park
Indiana University Purdue University Indianapolis
United States
Jeffrey C Smith
Jeffrey C Smith
National Institute of Neurological Disorders and Stroke
Bethesda | United States
Jonathan E Rubin
Jonathan E Rubin
University of Pittsburgh
Dr. Ilya A Rybak, PhD
Dr. Ilya A Rybak, PhD
Drexel University College of Medicine
Professor
Neuroscience
Philadelphia, Pennsylvania | Afghanistan

PLoS One 2014 10;9(10):e109894. Epub 2014 Oct 10.

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109894PLOSFound
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193835PMCFound
June 2015
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9 PubMed Central Citations(source)
3.23 Impact Factor

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