Control of Breathing During Exercise

Abstract

During exercise by healthy mammals, alveolar ventilation and alveolar-capillary diffusion increase in proportion to the increase in metabolic rate to prevent PaCO2 from increasing and PaO2 from decreasing. There is no known mechanism capable of directly sensing the rate of gas exchange in the muscles or the lungs; thus, for over a century there has been intense interest in elucidating how respiratory neurons adjust their output to variables which can not be directly monitored. Several hypotheses have been tested and supportive data were obtained, but for each hypothesis, there are contradictory data or reasons to question the validity of each hypothesis. Herein, we report a critique of the major hypotheses which has led to the following conclusions. First, a single stimulus or combination of stimuli that convincingly and entirely explains the hyperpnea has not been identified. Second, the coupling of the hyperpnea to metabolic rate is not causal but is due to of these variables each resulting from a common factor which link the circulatory and ventilatory responses to exercise. Third, stimuli postulated to act at pulmonary or cardiac receptors or carotid and intracranial chemoreceptors are not primary mediators of the hyperpnea. Fourth, stimuli originating in exercising limbs and conveyed to the brain by spinal afferents contribute to the exercise hyperpnea. Fifth, the hyperventilation during heavy exercise is not primarily due to lactacidosis stimulation of carotid chemoreceptors. Finally, since volitional exercise requires activation of the CNS, neural feed-forward (central command) mediation of the exercise hyperpnea seems intuitive and is supported by data from several studies. However, there is no compelling evidence to accept this concept as an indisputable fact.

Ventilation and Respiratory Mechanics

“…First, negative feedback might be of vital importance during infancy whereby having successfully corrected errors the CNS "learns" how to prevent them. Central command or spinal afferents might activate these neural networks (166,490,576). This hypothesis is largely unproven, but recent work in human infants (9 months) shows that the rhythm generated for stepping and/or its afferent feedback have strong influences on the rhythm generator for breathing (392).…”

“…Despite these caveats, important advances have been made using both human and animal models, and some general conclusions can be made regarding the question of how exercise ventilation is initiated and subsequently controlled. Extensive reviews have been presented on this topic (128,166). Rather than restate what has been detailed elsewhere, we have taken a broad view of the vast number of studies, many of which provide contradictory support for a given hypothesis.…”

Autonomic Adjustments to Exercise in Humans

“…However, during exercise, the influence of the chemoreflex has primarily focused on respiratory adjustments, which are reviewed in detail elsewhere (92,211), and investigations on chemoreflex-mediated cardiovascular control are sparse. Recently, Stickland, Dempsey, and colleagues conducted a series of experiments to examine the role of the chemoreflex in modulating SNA and blood flow during exercise.…”

Atropine microdialysis within or near the pre-Bötzinger Complex increases breathing frequency more during wakefulness than during NREM sleep

“…It is well known that V I is coupled to metabolic rate (15,22) during exercise, changes in body weight, and other conditions. Thus, it is possible that changes in metabolic rate contributed to the atropine-induced changes in breathing.…”