Abstract
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.
Highlights
IntroductionIt establishes the automatic rhythm that produces periodic contraction of respiratory muscles, resulting in rhythmic inflation and deflation of the lungs that underlie the exchange of gases between the lungs and air
The neural control of ventilation in mammals serves two major functions
Our work may represent the first model of the closed-loop respiratory system incorporating both mechanical and chemical feedback that simulates the transition to breathing with active expiration during hypercapnia
Summary
It establishes the automatic rhythm that produces periodic contraction of respiratory muscles, resulting in rhythmic inflation and deflation of the lungs that underlie the exchange of gases between the lungs and air It adjusts the rhythm and pattern of breathing to current metabolic demands (defined by the levels of carbon dioxide and oxygen in blood and tissues) and mechanical conditions (execution of various movements, maintenance of posture, and so on) as well as to various non-ventilatory behaviors (such as speaking, sniffing, and eating). The feedforward neural connections from the CPG involve the bulbospinal neurons in the brainstem projecting to phrenic motoneurons in the spinal cord that control rhythmic contractions of the diaphragm (the principal respiratory muscle) and to other motoneurons that control abdominal and intercostal muscles The latter can, in some conditions, be involved in active expiration by contributing to pumping air out of the lungs
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