Theories on the nature of the coupling between ventilation and gas exchange during exercise☆
Introduction
One of the most challenging questions in respiratory physiology is certainly that of the mechanisms of arterial control during muscular dynamic exercise (Krogh and Lindhard, 1913, Grodins, 1950, Kao, 1956, Dejours et al., 1957a, Dejours, 1963). When the metabolic – and thus the pulmonary gas exchange – rate increases as a result of muscular activity, ventilation appears to rise in proportion and prevents hypercapnia (and hypoxia) from occurring (Whipp and Ward, 1991, Whipp and Ward, 1998).
Extensive and numerous reviews have been written on this subject (Dejours, 1959, Wasserman et al., 1979, Dempsey et al., 1984, Eldridge and Waldrop, 1991, Whipp and Ward, 1991), and the search for the mechanisms coupling ventilatory control to factors proportional or related to the gas exchange rate has triggered, for many decades, creative and fascinating debates. The discussion on this subject is still very vivid, not only because it is one of the most controversial, and as of yet unanswered, questions in physiological regulation but also because many types of patients suffering from dyspnea on exertion would benefit from a better understanding of the structures involved in the –metabolism coupling.
The literature in this domain is so vast that one may find published studies which support a given concept and an equal number of experiments apparently supporting just the opposite. This may cause perplexity to many readers. Besides, the control of exercise hyperpnea covers very different domains of research with their specific techniques and language, from fundamental neurophysiology to mathematical analysis of the responses in exercising humans. The fact that studies published in one given domain are at odds with the results obtained in another field is often ignored simply because they belong to a different area of research. For instance, whether a concept imagined from a reduced preparation is compatible with the simple description of the dynamic of the ventilatory response to exercise in humans should be systematically tested. Finally, the primary control systems could be affected by “external” factors with long lasting effects, a phenomenon which has been overlooked (see Mitchell and Johnson, 2003 for discussion) and which makes the study of such control mechanisms more complicated. This implies that observation in “intact” animals and in humans should dictate the direction taken by the most fundamental research and not the opposite.
This short review will focus primarily on the possible sites of mediation between gas exchange and ventilation. First, we will try to explain the reasons why so many physiologists have believed (and still believe) that there is a ventilatory–metabolism coupling, independent of the motor component of exercise. We will illustrate that when the work load or the frequency of movements are dissociated from the gas exchange rate, ventilation follows factors related or proportional to the changes in gas exchange and not to the motor act, regardless of the magnitude of the centrally or peripherally mediated signal related to the locomotion. Secondly, we will examine the most important attempts to understand the nature of such a coupling in exercise. Finally, we will try to discuss whether new ideas have emerged to answer this question.
Section snippets
Is ventilation linked to factors related to motor and locomotor activity or to gas exchange during dynamic exercise?
Dynamic exercise is a complex situation which combines an increase in metabolic rate and a motor act. The increase in metabolic rate certainly changes the local chemical environment of the muscle, the composition of the venous blood and the rate of change in alveolar gas composition through the respiratory cycle, and is associated with systemic and local circulatory responses (increase in blood flow).
The motor act requires the voluntary and automatic control of movements and produces
Kao's experiments
Kao (1963) and Kao et al. (1963) probably contributed the most impressive series of observations on the role of somatic information during exercise as fundamental factors for homeostasis in animal preparations. In a sophisticated series of experiments, he studied the response in dogs in which the circulatory systems were connected in such a way that the blood leaving the exercising muscles of one dog (the neural dog) was infused into the venous system of another animal (the humoral
Conclusions
Studies attempting to dissociate in the frequency domain factors related to the motor act from those related to the gas exchange have shown that the main part of the response to exercise follows the latter (Casaburi et al., 1978). This approach has revealed a fundamental property of the respiratory control system during exercise, i.e. that not all the inputs to the respiratory neurons are taken into account. The strategy adopted by the respiratory control system is to follow factors related
References (74)
- et al.
Characteristics of the ventilatory exercise stimulus
Respir. Physiol.
(1985) - et al.
Ventilatory control characteristics of the exercise hyperpnea as discerned from dynamic forcing techniques
Chest
(1978) - et al.
Vascular distension in muscles contributes to respiratory control in sheep
Respir. Physiol.
(1995) - et al.
Femoral vascular occlusion and ventilation during recovery from heavy exercise
Respir. Physiol.
(1993) - et al.
Responses of group IV and group III muscle afferents to thermal stimuli.
Brain Res.
(1976) - et al.
Role of muscle perfusion and baroreception in the hyperpnea following muscle contraction in dog
Respir. Physiol.
(1993) Group III and IV receptors in skeletal muscle: are they specific or polymodal?
Prog. Brain Res.
(1996)- et al.
The early circulatory and ventilatory response to voluntary and electrically induced exercise in man
J. Physiol.
(1987) - et al.
Responses of group III and IV muscle afferents to dynamic exercise
J. Appl. Physiol.
(1997) - et al.
Respiratory oscillations in arterial carbon dioxide tension as a control signal in exercise
Nature
(1980)
Ventilatory and circulatory responses at the onset of exercise in man following heart or heart-lung transplantation
J. Physiol.
Gain of the ventilatory exercise stimulus: definition and meaning
J. Appl. Physiol.
Role of in control of breathing of awake exercising dogs
J. Appl. Physiol.
Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise
J. Appl. Physiol.
Ventilatory and gas exchange dynamics in response to sinusoidal work
J. Appl. Physiol.
Regional cerebral blood flow during volitional breathing in man
J. Physiol.
The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog
J. Physiol.
La regulation de la ventilation au cours de l’exercise musculaire chez l’homme
J. Physiol. (Paris)
The regulation of breathing during muscular exercise in man: a neuro-humoral theory
Neurogenic factors in the control of ventilation during exercise
Circ. Res.
Stimulus oxygene chemoreflexe de la ventilation a basse altitude (50 m) chez l’homme - I au repos
J. Physiol. (Paris)
Evidence against the existence of specific ventilatory chemoreceptors in the legs
J. Appl. Physiol.
Attempt to demonstrate venous chemoreceptors of ventilation
J. Physiol. (Paris)
Exercise and chemoreception
Am. Rev. Resp. Dis.
Exercise hyperpnea and locomotion: parallel activation from the hypothalamus
Science
Neural control of breathing during exercise
Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement
J. Physiol.
Ventilatory responses to intraventous and airway CO2 administration in anesthetized dogs
J. Appl. Physiol.
Hyperpnea of exercise at various PIO2 in normal and carotid body-denervated ponies
J. Appl. Physiol.
Temporal pattern of arterial CO2 partial pressure during exercise in humans
J. Appl. Physiol.
Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs
J. Appl. Physiol.
Analysis of factors concerned in the regulation of breathing in exercise
Physiol. Rev.
Regulation of breathing during electrically-induced muscular work in anesthetized dogs following transection of spinal cord
Am. J. Physiol.
The control of ventilation is dissociated from locomotion during walking in sheep
J. Physiol.
Sensing vascular distension in skeletal muscle by slow conducting afferent fibers: neurophysiological basis and implication for respiratory control
J. Appl. Physiol.
Responses of group III and IV muscle afferents to distension of the peripheral vascular bed
J. Appl. Physiol.
Venous return and ventilatory control
Cited by (53)
Differences in the point of optimal ventilatory efficiency and the anaerobic threshold in untrained adults aged 50 to 60 years
2020, Respiratory Physiology and NeurobiologyCitation Excerpt :Thereby, POE is determined by identifying the first disproportional increase of VE related to VO2 (Hollmann, 2001, 1959), while the AT is determined by the first disproportional rise of expired carbon dioxide (VCO2) related to VO2 (v-slope method; Beaver et al., 1986; Wasserman et al., 2011). Although the increase in VE is closely linked to a rise in CO2 production especially during the transition from moderate to heavy exercise intensity (Haouzi, 2006; Wasserman et al., 2011), other factors may explain differences between work rates at POE compared to AT. Reasons for that variation in the ventilatory response to incremental testing are factors like psychogenic stress, inter-individual differences in the alveolar gas pressure of carbon dioxide (PaCO2), the sensitivity of the chemoreceptors to PaCO2, or the dead space to tidal volume ratio (Meyer et al., 2005; Sun et al., 2002; Wasserman et al., 2011).
Exercise physiology: exercise hyperpnea
2019, Current Opinion in PhysiologyThe cessation of breathing in the chicken embryo during cold-hypometabolism
2017, Respiratory Physiology and NeurobiologyLimb movement frequency is a significant modulator of the ventilatory response during submaximal cycling exercise in humans
2016, Respiratory Physiology and NeurobiologyCitation Excerpt :The sudden increase in ventilation at the onset of exercise is termed the ‘fast neural drive’ (Mateika and Duffin, 1995; Duffin, 2014), because this response occurs too rapidly for a metabolic signal to travel through the blood and increase ventilation through central or peripheral chemoreception (Barr et al., 1964). The fast neural drive originates from peripheral feedback from the muscles of exercising limbs that can be mechnoreceptive (Amann et al., 2011) or metaboreceptive (Haouzi, 2006). Additionally, central command generation from higher brain centres contributes to the fast neural drive to breathe (Bell, 2006).
Ventilatory control in infants, children, and adults with bronchopulmonary dysplasia
2013, Respiratory Physiology and NeurobiologyCitation Excerpt :For example, group III and IV muscle afferents are stimulated by metabolic byproducts, vasoactive mediators, muscle stretch, and temperature (Hertel et al., 1976; Mense and Stahnke, 1983; Haouzi et al., 1999; Kaufman et al., 2002) and increase ventilation in response to stimuli, In humans, the hyperpneic response to exercise is associated with increased activity in the superomedial and superolateral primary motor cortices, suggesting motor cortex involvement in the ventilatory response (Fink et al., 1995; Thornton et al., 2001). While we again note that the precise mechanisms governing the ventilatory response to exercise are unclear (Haouzi, 2006), animal and human studies strongly support a role for higher brain centers in the initiation and maintenance of exercise hyperpnea (Waldrop et al., 2010). As we note in our discussion of sleep (see Section 4.2), individuals with BPD may have cortical and subcortical brain lesions.
Uncoupling mitochondrial activity maintains body VO2 during hemorrhage-induced O<inf>2</inf> deficit in the anesthetized rat
2013, Respiratory Physiology and Neurobiology
- ☆
This paper is part of the Special Issue entitled “New Directions in Exercise Physiology”, guest-edited by Susan Hopkins and Peter D. Wagner.