Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Control of Breathing During Exercise

Hubert V. Forster, Philippe Haouzi, Jerome A. Dempsey

10.1002/cphy.c100045

Source: Volume 2, Issue 1, January 2012

Published online: January 2012

Full Article on Wiley Online Library



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. © 2012 American Physiological Society. Compr Physiol 2:743‐777, 2012.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

Schematic depicting multiple structures contributing to the control of breathing. It is hypothesized that respiratory rhythm originates within a brainstem oscillator which activates brainstem pattern generating neurons that provide for the proper sequential activation of respiratory pump (diaphragm, intercostal, and abdominal) and airway (laryngeal and pharyngeal) muscles. These brainstem neurons receive excitatory and inhibitory input from multiple sources including hypothesized supramedullary central command and mecho/metaboreceptor initiated spinal afferents from limb and respiratory skeletal muscles. In addition, the brainstem controller neurons receive carotid and intracranial chemoreceptor (retrotrapezoid nucleus, RTN) and vagal mechanoreceptor input critical to meet the proper ventilatory response to exercise. The figure is, with permission, from Dempsey et al. 86.
Figure 2. Figure 2.

Steady‐state arterial blood gas and pH status during spontaneous exercise in humans and ponies. Exercise intensity is depicted by heart rate rather than metabolic rate to avoid use of a mask or breathing valve which that can affect the ventilatory response. Note in humans arterial homeostasis is maintained from rest to a heart rate of about 150 and thereafter pH and PaCO2 decrease. In ponies, PaCO2 is inversely related to exercise intensity from rest to maximum irrespective of initially an alkaline but then an acid pH. In both species, Pao2 homeostasis is maintained throughout exercise. Data are, with permission, from Forster et al. 119,124,126.
Figure 3. Figure 3.

Effect of steady‐state exercise intensity (expressed as CO2 excretion, ) in humans on pulmonary (E) and alveolar (A) ventilation, breathing frequency (fb), tidal volume (VT), and dead space (VD) to VT ratio. Note E and A increase linearly as increases to about 2.5 l/min but thereafter E and A increase relatively more than . Adapted, with permission, from Dempsey et al. 86.
Figure 4. Figure 4.

Temporal pattern of ventilatory responses during and after exercise by healthy humans. Panel A shows the normal fast (phase I) and slow (phase II) responses to mild exercise and also shows that occlusion of blood flow to the muscles during the recovery hastens the return of ventilation to control levels [data, with permission, from Dejours 84]. In panel B are data during and after heavy constant work rate cycloergometer exercise. Between the two arrows, cuffs around the legs were inflated to occlude blood flow (open symbols) and these data are compared to unoccluded flow (closed symbols). Note again that the ventilatory decline during recovery was increased during cuff occlusion despite expected accumulation of metabolites in the muscle circulation [data, with permission, from Haouzi et al. 158].
Figure 5. Figure 5.

Temporal pattern of PaCO2 in humans (n = 10) from rest to work and work‐to‐work submaximal levels of exercise. All data were obtained without the subjects encumbered by a breathing valve system. Note the transient hypocapnia in the exercise transitions. The data are, with permission, from Forster et al. 126.
Figure 6. Figure 6.

Temporal pattern of PaCO2 in normal and carotid body denervated (CBD) ponies in rest to work and work‐to‐work transitions. The data were obtained without a mask needed to measure ventilatory parameters. Note the hypocapnia in rest to work transitions with some but not complete recovery, the changes in work‐to‐work transitions, and the exacerbation of the PaCO2 disruptions after CBD. The data are, with permission, from Pan et al. 263.
Figure 7. Figure 7.

Recording of inspiration (upward deflection) and expiration in a human subject at rest and during moderate bicycle exercise. Onset of exercise indicated by x. Volume change indicated on right side and marks on the bottom indicate seconds. Adapted, with permission, from Krogh and Linehard 202.
Figure 8. Figure 8.

The ventilatory (E/) response to exercise is increased as muscle strength is progressively weakened (decrease in handgrip strength) by injection of tubocurare. Adapted, with permission, from Asmussen et al. 14.
Figure 9. Figure 9.

Data supporting concept that suprapontine mechanisms “central command” stimulates breathing. Shown (panel a) is a decorticate cat preparation used in studies when respiration (phrenic nerve activity) was measured during spontaneous locomotion and locomotion was induced by stimulation in the subthalamic locomotor region (panel b). Shown in panel c is decorticate paralyzed preparation used for spontaneous fictive locomotion which as shown in panel d elicited a respiratory response. Data are, with permission, from Eldridge et al. 109.
Figure 10. Figure 10.

Effect of voluntary (circles) and electrically (x) induced exercise on pulmonary ventilation (vent) and alveolar PCO2 (PCO2 alv) relative to metabolic rate (l O2 min). Note the near identical responses to the two exercise tasks interpreted as indicating “central command” is not obligatory for ventilatory response to exercise. Data are, with permission, from Asmussen et al. 14.
Figure 11. Figure 11.

Schematics depicting multiple supramedullary structures potentially contributing to cardiovascular and respiratory control during exercise. The cardiovascular schematic was developed by Green and Paterson 139 and presented here with their permission. To our knowledge, no comparable schematic has been published for respiratory control; thus, since the cardiovascular and respiratory responses to exercise are usually qualitatively the same, we assume the supramedullary components are the same or at least similar for both responses. As detailed in the text, evidence suggests medullary respiratory neurons receive excitatory exercise‐related inputs from suprapontine pathways that include the cortex, anterior (AHN) and lateral (LHA) hypothalamic nuclei, paraventricular nucleus (PVN), and periaqueductal gray (PAG). The respiratory rhythm originates within a brainstem oscillator which activates pattern generating neurons that provide for proper sequential activation of respiratory pump and airway muscles. The pre‐Bötzinger (PBC) is the core site of rhythm and pattern generation with important contributions from the parafacial respiratory group (pFRG)/retrotrapezoid nucleus (RTN) as well as the pontine respiratory group including the lateral parabrachial nucleus (LPBN) 2,303.
Figure 12. Figure 12.

Anatomical distribution of the afferent innervation of the cat skeletal muscle. Most of the group III and IV afferents fibers are found in association with arterioles (a.) and the venous and venular structures (v.) of the muscles. Data are, with permission, from Stacey et al. 308.
Figure 13. Figure 13.

Exercise activates group III and group IV muscles afferents. Shown are cumulative histograms for 24 group III afferents (A) and 10 group IV afferents (B) before, during, and after time that cats performed dynamic exercise, which was induced by stimulation of mesencephalic locomotor region. Exercise period is denoted by horizontal bars. Note maintained response to dynamic exercise by both group III and group IV afferent impulses. Data are, with permission, from Adreani et al. 4.
Figure 14. Figure 14.

Increased muscle blood flow activates group III and group IV afferents. Shown in the top panel are the temporal profiles of cumulative histogram of the activity of 15 group IV (open bars) and 3 group III (solid bars) fibers of the cat triceps surae, responding to papaverine (top) and mean popliteal blood flow (bottom). Shown in the bottom are the effects of venous obstruction on the discharge of a group IV muscle afferent fiber originating in the triceps surae of the cat at different flow levels after an injection of isoproterenol. The higher the level of flow before occlusion the greater the neural response to venous distension. Data are, with permission, from Haouzi et al. 156.
Figure 15. Figure 15.

The time course of pulmonary ventilation (E), oxygen consumption (), and the E/ ration (EO2) in an anesthetized (neural) dog when the hindlimb muscles were induced electrically to contract and the venous blood from the hindlimbs was delivered to another non exercise (humoral) dog. Note the brisk hyperpnea at the onset of contraction in the neural dog and the delayed response in the humoral dog. Data are, with permission, from Kao et al. 189.
Figure 16. Figure 16.

Blood flow in muscles has an effect on ventilation. Shown in panel A are the effects of the occlusion of the iliac arteries on the E and responses at the onset of electrically induced muscle contractions in anesthetized dogs. The arrow indicates the onset of exercise. The arterial occlusion was maintained during the period depicted by the horizontal bar. Responses in control condition are depicted with open symbols while the responses to occlusion and release are shown using closed symbols. Note that impediment of the arterial supply to the contracting muscles prevented the normal increase in and reduced dramatically the magnitude of the normal E response to exercise. Shown in panel B are the E effects of the occlusion of the lower abdominal aorta and inferior vena cava at the cessation of electrically induced hindlimb muscle contractions in an anesthetized dog. At the cessation of the contractions (second vertical arrow), both the arterial and venous balloons were inflated (first and second horizontal bar, respectively). The arterial balloon was deflated at the first vertical line, whereas venous return from the hindlimb remained blocked. This change caused E to increase despite the drop in PETCO2 and the lack of sustained change in systemic blood pressure (BP). When the venous balloon was deflated, note that E decreased despite the ensuing hypercapnia. Data are, with permission, from Huszczuk et al. 174.
Figure 17. Figure 17.

Rapid muscle blood flow response to exercise. Shown are oxygen consumption (dotted line, ) and leg blood flow (solid line) response to constant work rate exercise in supine position (40 W). Note the immediate increase in blood flow (as soon as the exercise starts) and the exponential increase in blood flow preceding phase II and reaching a steady state within 2 min. The ventilatory responses have been added based on the characteristics presented by MacDonald et al. 220.
Figure 18. Figure 18.

The isocapnic ventilatory response (right panel) to exercise does not correlate with changes in cardiac output and mixed venous CO2 content (left panel) during ramp‐like exercise in healthy humans. Note that as cardiac output and ventilation increase dramatically, there is only a small change in mixed venous CO2 content; thus, it is unlikely CO2 content provides a major signal for the blood flow and ventilatory responses. Data are, with permission, from Sun et al. 316.
Figure 19. Figure 19.

Effect of blockage of μ‐opioid sensitive type III‐IV muscle afferents via intrathecal Fentanyl on the steady‐state ventilatory response to 3 min of cycling exercise at each of four work rates. (*P<0.05, P<0.8). The Fentanyl‐induced hypoventilation was due to a reduced breathing frequency. Heart rate and mean arterial blood pressure (data not shown) along with E were significantly reduced at each work rate. Taking into account the reduced exercise E with Fentanyl plus the ventilatory equivalent of the concomitant rise in PETCO2, it is estimated that the partial blockage of muscle afferents accounted for 47%, 45%, and 15% of the total exercise hyperpnea at 100, 150, and 325 W, respectively. Data adapted, with permission, from Amann et al. 7.
Figure 20. Figure 20.

Example of changes in oxygen consumption (O2), CO2 excretion (), and ventilation when the period of sinusoidal changes in treadmill speed is shortened from 5 to 2 and then to 1 min. The fundamental component of the responses computed by Fourier analysis is superimposed on the raw data. Note that the changes in walking frequency are in phase with the sinusoidal changes in the speed of the treadmill and that there is no reduction in amplitude when the frequency of oscillations of the treadmill speed increases. There is a clear reduction in amplitude of both pulmonary gas exchange and ventilation when the oscillation period decreases whereas the phase lag between walking frequency and the respiratory parameters increases. Data are, with permission, from Haouzi et al. 151.
Figure 21. Figure 21.

Ventilatory sensitivity to increases in PaCO2 at rest and during two levels of bicycle exercise in a normal human. Note that exercise did not change the slope of the relationship indicating an unchanged sensitivity to CO2 during exercise. Data are, with permission, from studies by Asmussen et al, 17.
Figure 22. Figure 22.

Effect of exercise on ventilatory (E) sensitivity to hypoxia in a normal human. The closed symbols were obtained at rest and the additional data were obtained during two levels of submaximal exercise. Note that exercise increased the response to hypoxia. Data are, with permission, from Asmussen et al. 17.


Figure 1.

Schematic depicting multiple structures contributing to the control of breathing. It is hypothesized that respiratory rhythm originates within a brainstem oscillator which activates brainstem pattern generating neurons that provide for the proper sequential activation of respiratory pump (diaphragm, intercostal, and abdominal) and airway (laryngeal and pharyngeal) muscles. These brainstem neurons receive excitatory and inhibitory input from multiple sources including hypothesized supramedullary central command and mecho/metaboreceptor initiated spinal afferents from limb and respiratory skeletal muscles. In addition, the brainstem controller neurons receive carotid and intracranial chemoreceptor (retrotrapezoid nucleus, RTN) and vagal mechanoreceptor input critical to meet the proper ventilatory response to exercise. The figure is, with permission, from Dempsey et al. 86.



Figure 2.

Steady‐state arterial blood gas and pH status during spontaneous exercise in humans and ponies. Exercise intensity is depicted by heart rate rather than metabolic rate to avoid use of a mask or breathing valve which that can affect the ventilatory response. Note in humans arterial homeostasis is maintained from rest to a heart rate of about 150 and thereafter pH and PaCO2 decrease. In ponies, PaCO2 is inversely related to exercise intensity from rest to maximum irrespective of initially an alkaline but then an acid pH. In both species, Pao2 homeostasis is maintained throughout exercise. Data are, with permission, from Forster et al. 119,124,126.



Figure 3.

Effect of steady‐state exercise intensity (expressed as CO2 excretion, ) in humans on pulmonary (E) and alveolar (A) ventilation, breathing frequency (fb), tidal volume (VT), and dead space (VD) to VT ratio. Note E and A increase linearly as increases to about 2.5 l/min but thereafter E and A increase relatively more than . Adapted, with permission, from Dempsey et al. 86.



Figure 4.

Temporal pattern of ventilatory responses during and after exercise by healthy humans. Panel A shows the normal fast (phase I) and slow (phase II) responses to mild exercise and also shows that occlusion of blood flow to the muscles during the recovery hastens the return of ventilation to control levels [data, with permission, from Dejours 84]. In panel B are data during and after heavy constant work rate cycloergometer exercise. Between the two arrows, cuffs around the legs were inflated to occlude blood flow (open symbols) and these data are compared to unoccluded flow (closed symbols). Note again that the ventilatory decline during recovery was increased during cuff occlusion despite expected accumulation of metabolites in the muscle circulation [data, with permission, from Haouzi et al. 158].



Figure 5.

Temporal pattern of PaCO2 in humans (n = 10) from rest to work and work‐to‐work submaximal levels of exercise. All data were obtained without the subjects encumbered by a breathing valve system. Note the transient hypocapnia in the exercise transitions. The data are, with permission, from Forster et al. 126.



Figure 6.

Temporal pattern of PaCO2 in normal and carotid body denervated (CBD) ponies in rest to work and work‐to‐work transitions. The data were obtained without a mask needed to measure ventilatory parameters. Note the hypocapnia in rest to work transitions with some but not complete recovery, the changes in work‐to‐work transitions, and the exacerbation of the PaCO2 disruptions after CBD. The data are, with permission, from Pan et al. 263.



Figure 7.

Recording of inspiration (upward deflection) and expiration in a human subject at rest and during moderate bicycle exercise. Onset of exercise indicated by x. Volume change indicated on right side and marks on the bottom indicate seconds. Adapted, with permission, from Krogh and Linehard 202.



Figure 8.

The ventilatory (E/) response to exercise is increased as muscle strength is progressively weakened (decrease in handgrip strength) by injection of tubocurare. Adapted, with permission, from Asmussen et al. 14.



Figure 9.

Data supporting concept that suprapontine mechanisms “central command” stimulates breathing. Shown (panel a) is a decorticate cat preparation used in studies when respiration (phrenic nerve activity) was measured during spontaneous locomotion and locomotion was induced by stimulation in the subthalamic locomotor region (panel b). Shown in panel c is decorticate paralyzed preparation used for spontaneous fictive locomotion which as shown in panel d elicited a respiratory response. Data are, with permission, from Eldridge et al. 109.



Figure 10.

Effect of voluntary (circles) and electrically (x) induced exercise on pulmonary ventilation (vent) and alveolar PCO2 (PCO2 alv) relative to metabolic rate (l O2 min). Note the near identical responses to the two exercise tasks interpreted as indicating “central command” is not obligatory for ventilatory response to exercise. Data are, with permission, from Asmussen et al. 14.



Figure 11.

Schematics depicting multiple supramedullary structures potentially contributing to cardiovascular and respiratory control during exercise. The cardiovascular schematic was developed by Green and Paterson 139 and presented here with their permission. To our knowledge, no comparable schematic has been published for respiratory control; thus, since the cardiovascular and respiratory responses to exercise are usually qualitatively the same, we assume the supramedullary components are the same or at least similar for both responses. As detailed in the text, evidence suggests medullary respiratory neurons receive excitatory exercise‐related inputs from suprapontine pathways that include the cortex, anterior (AHN) and lateral (LHA) hypothalamic nuclei, paraventricular nucleus (PVN), and periaqueductal gray (PAG). The respiratory rhythm originates within a brainstem oscillator which activates pattern generating neurons that provide for proper sequential activation of respiratory pump and airway muscles. The pre‐Bötzinger (PBC) is the core site of rhythm and pattern generation with important contributions from the parafacial respiratory group (pFRG)/retrotrapezoid nucleus (RTN) as well as the pontine respiratory group including the lateral parabrachial nucleus (LPBN) 2,303.



Figure 12.

Anatomical distribution of the afferent innervation of the cat skeletal muscle. Most of the group III and IV afferents fibers are found in association with arterioles (a.) and the venous and venular structures (v.) of the muscles. Data are, with permission, from Stacey et al. 308.



Figure 13.

Exercise activates group III and group IV muscles afferents. Shown are cumulative histograms for 24 group III afferents (A) and 10 group IV afferents (B) before, during, and after time that cats performed dynamic exercise, which was induced by stimulation of mesencephalic locomotor region. Exercise period is denoted by horizontal bars. Note maintained response to dynamic exercise by both group III and group IV afferent impulses. Data are, with permission, from Adreani et al. 4.



Figure 14.

Increased muscle blood flow activates group III and group IV afferents. Shown in the top panel are the temporal profiles of cumulative histogram of the activity of 15 group IV (open bars) and 3 group III (solid bars) fibers of the cat triceps surae, responding to papaverine (top) and mean popliteal blood flow (bottom). Shown in the bottom are the effects of venous obstruction on the discharge of a group IV muscle afferent fiber originating in the triceps surae of the cat at different flow levels after an injection of isoproterenol. The higher the level of flow before occlusion the greater the neural response to venous distension. Data are, with permission, from Haouzi et al. 156.



Figure 15.

The time course of pulmonary ventilation (E), oxygen consumption (), and the E/ ration (EO2) in an anesthetized (neural) dog when the hindlimb muscles were induced electrically to contract and the venous blood from the hindlimbs was delivered to another non exercise (humoral) dog. Note the brisk hyperpnea at the onset of contraction in the neural dog and the delayed response in the humoral dog. Data are, with permission, from Kao et al. 189.



Figure 16.

Blood flow in muscles has an effect on ventilation. Shown in panel A are the effects of the occlusion of the iliac arteries on the E and responses at the onset of electrically induced muscle contractions in anesthetized dogs. The arrow indicates the onset of exercise. The arterial occlusion was maintained during the period depicted by the horizontal bar. Responses in control condition are depicted with open symbols while the responses to occlusion and release are shown using closed symbols. Note that impediment of the arterial supply to the contracting muscles prevented the normal increase in and reduced dramatically the magnitude of the normal E response to exercise. Shown in panel B are the E effects of the occlusion of the lower abdominal aorta and inferior vena cava at the cessation of electrically induced hindlimb muscle contractions in an anesthetized dog. At the cessation of the contractions (second vertical arrow), both the arterial and venous balloons were inflated (first and second horizontal bar, respectively). The arterial balloon was deflated at the first vertical line, whereas venous return from the hindlimb remained blocked. This change caused E to increase despite the drop in PETCO2 and the lack of sustained change in systemic blood pressure (BP). When the venous balloon was deflated, note that E decreased despite the ensuing hypercapnia. Data are, with permission, from Huszczuk et al. 174.



Figure 17.

Rapid muscle blood flow response to exercise. Shown are oxygen consumption (dotted line, ) and leg blood flow (solid line) response to constant work rate exercise in supine position (40 W). Note the immediate increase in blood flow (as soon as the exercise starts) and the exponential increase in blood flow preceding phase II and reaching a steady state within 2 min. The ventilatory responses have been added based on the characteristics presented by MacDonald et al. 220.



Figure 18.

The isocapnic ventilatory response (right panel) to exercise does not correlate with changes in cardiac output and mixed venous CO2 content (left panel) during ramp‐like exercise in healthy humans. Note that as cardiac output and ventilation increase dramatically, there is only a small change in mixed venous CO2 content; thus, it is unlikely CO2 content provides a major signal for the blood flow and ventilatory responses. Data are, with permission, from Sun et al. 316.



Figure 19.

Effect of blockage of μ‐opioid sensitive type III‐IV muscle afferents via intrathecal Fentanyl on the steady‐state ventilatory response to 3 min of cycling exercise at each of four work rates. (*P<0.05, P<0.8). The Fentanyl‐induced hypoventilation was due to a reduced breathing frequency. Heart rate and mean arterial blood pressure (data not shown) along with E were significantly reduced at each work rate. Taking into account the reduced exercise E with Fentanyl plus the ventilatory equivalent of the concomitant rise in PETCO2, it is estimated that the partial blockage of muscle afferents accounted for 47%, 45%, and 15% of the total exercise hyperpnea at 100, 150, and 325 W, respectively. Data adapted, with permission, from Amann et al. 7.



Figure 20.

Example of changes in oxygen consumption (O2), CO2 excretion (), and ventilation when the period of sinusoidal changes in treadmill speed is shortened from 5 to 2 and then to 1 min. The fundamental component of the responses computed by Fourier analysis is superimposed on the raw data. Note that the changes in walking frequency are in phase with the sinusoidal changes in the speed of the treadmill and that there is no reduction in amplitude when the frequency of oscillations of the treadmill speed increases. There is a clear reduction in amplitude of both pulmonary gas exchange and ventilation when the oscillation period decreases whereas the phase lag between walking frequency and the respiratory parameters increases. Data are, with permission, from Haouzi et al. 151.



Figure 21.

Ventilatory sensitivity to increases in PaCO2 at rest and during two levels of bicycle exercise in a normal human. Note that exercise did not change the slope of the relationship indicating an unchanged sensitivity to CO2 during exercise. Data are, with permission, from studies by Asmussen et al, 17.



Figure 22.

Effect of exercise on ventilatory (E) sensitivity to hypoxia in a normal human. The closed symbols were obtained at rest and the additional data were obtained during two levels of submaximal exercise. Note that exercise increased the response to hypoxia. Data are, with permission, from Asmussen et al. 17.

References
 1. Aaker A, Laughlin MH. Diaphragm arterioles are less responsive to alpha1‐adrenergic constriction than gastrocnemius arterioles. J Appl Physiol 92: 1808‐1816, 2002.
 2. Abdala AP, Rybak IA, Smith JC, Zoccal DB, Machado BH, St‐John WM, Paton JF. Multiple pontomedullary mechanisms of respiratory rhythmogenesis. Respir Physiol Neurobiol 168: 19‐25, 2009.
 3. Adams L, Frankel H, Garlick J, Guz A, Murphy K, Semple SJ. The role of spinal cord transmission in the ventilatory response to exercise in man. JPhysiol 355: 85‐97, 1984.
 4. Adreani CM, Hill JM, Kaufman MP. Responses of group III and IV muscle afferents to dynamic exercise. J Appl Physiol 82: 1811‐1817, 1997.
 5. Agostoni E, D'Angelo E. The effect of limb movements on the regulation of depth and rate of breathing. RespirPhysiol 27: 33‐52, 1956.
 6. Ainsworth DM, Smith CA, Johnson BD, Eicker SW, Henderson KS, Dempsey JA. Vagal modulation of respiratory muscle activity in awake dogs during exercise and hypercapnia. J Appl Physiol 72: 1362‐1367, 1992.
 7. Amann M, Blain GM, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans. J Appl Physiol 109: 966‐976, 2010.
 8. Amann M, Dempsey JA. Locomotor muscle fatigue modifies central motor drive in healthy humans and imposes a limitation to exercise performance. J Physiol 586: 161‐173, 2008.
 9. Amann M, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Opioid‐mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J Physiol 587: 271‐283, 2009.
 10. Amann M, Secher NH. Point: Afferent feedback from fatigued locomotor muscles is an important determinant of endurance exercise performance. J Appl Physiol 108: 452‐454; discussion 457; author reply 470, 2010.
 11. Andrezik JA, Dormer KJ, Foreman RD, Person RJ. Fastigial nucleus projections to the brain stem in beagles: Pathways for autonomic regulation. Neuroscience 11: 497‐507, 1984.
 12. Annerbrink K, Olsson M, Melchior LK, Hedner J, Eriksson E. Serotonin depletion increases respiratory variability in freely moving rats: Implications for panic disorder. Int J Neuropsychopharmacol 6: 51‐56, 2003.
 13. Armour JA, Wurster RD, Randall WC. Cardiac reflexes. In: Randall WC, editor. Neural Regulation of the Heart. Oxford Univ Press, 1977, p. 157‐186.
 14. Asmussen E. Muscular exercise. In: Fenn WO, Rahn H, editors. Handbook of Physiology, Respiration. Washington, D.C.: Am Physiol Soc, 1965, p. 631‐648.
 15. Asmussen E, Johansen SH, Jorgensen M, Nielsen M. On the nervous factors controlling respiration and circulation during exercise. Experiments with curarization. Acta Physiol Scand 63: 343‐350, 1965.
 16. Asmussen E, Nielsen M. Studies on the regulation of respiration in heavy work. Acta Physiol Scand 12: 171‐188, 1946.
 17. Asmussen E, Nielsen M. Ventilatory response to CO2 during work at normal and at low oxygen tensions. Acta Physiol Scand 39: 27‐35, 1957.
 18. Asmussen E, Nielsen M. Experiments on nervous factors controlling respiration and circulation during exercise employing blocking of the blood flow. Acta Physiol Scand 60: 103‐111, 1964.
 19. Asmussen E, Nielsen M, Weith‐Pedersen G. Cortical or reflex control of respiration during muscular work? Acta Physiol Scand 6: 168‐175, 1943.
 20. Bach KB, Lutcavage ME, Mitchell GS. Serotonin is necessary for short‐term modulation of the exercise ventilatory response. Respir Physiol 91: 57‐70, 1993.
 21. Ballion B, Morin D, Viala D. Forelimb locomotor generators and quadrupedal locomotion in the neonatal rat. Eur J Neurosci 14: 1727‐1738, 2001.
 22. Band DM, Cameron IR, Semple SJ. Oscillations in arterial pH with breathing in the cat. JApplPhysiol 26: 261‐267, 1969.
 23. Bandler R, Keay KA. Columnar organization in the midbrain periaqueductal gray and the integration of emotional expression. Prog Brain Res 107: 285‐300, 1996.
 24. Bandler R, Keay KA, Floyd N, Price J. Central circuits mediating patterned autonomic activity during active vs. passive emotional coping. Brain Res Bull 53: 95‐104, 2000.
 25. Bandler R, Shipley MT. Columnar organization in the midbrain periaqueductal gray: Modules for emotional expression? Trends Neurosci 17: 379‐389, 1994.
 26. Banner N, Guz A, Heaton R, Innes JA, Murphy K, Yacoub M. Ventilatory and circulatory responses at the onset of exercise in man following heart or heart‐lung transplantation. JPhysiol 399: 437‐449, 1988.
 27. Barr PO, Beckman M, Bjurstedt H, Brismar J, Hesser CM, Matell G. Time courses of blood gas changes provoked by light and moderate exercise in man. Acta Physiol Scand 60: 1‐17, 1964.
 28. Bartlett D Jr, Sant'ambrogio G. Effects of local and systemic hypercapnia on the discharge of stretch receptors in the airways of the dog. Respir Physiol 26: 91‐99, 1976.
 29. Basnayake SD, Hyam JA, Pereira EA, Schweder PM, Brittain JS, Aziz TZ, Green AL, Paterson DJ. Identifying cardiovascular neurocircuitry involved in the exercise pressor reflex in humans using functional neurosurgery. J Appl Physiol 110: 881‐891, 2010.
 30. Bassal M, Bianchi AL. Inspiratory onset or termination induced by electrical stimulation of the brain. Respir Physiol 50: 23‐40, 1982.
 31. Bayly WM, Grant BD, Breeze RG, Kramer JW, Snow DH, Persson SG, Rose RJ. The effects of maximal exercise on acid‐base balance and arterial blood gas tensions in thoroughbred horses. In: Snow DH, Persson SGB, Rose RJ, editors. Equine Exercise Physiology. Cambridge UK: Granta Editions, 1983, p. 400‐417.
 32. Bechbache RR, Duffin J. The entrainment of breathing frequency by exercise rhythm. JPhysiol 272: 553‐561, 1977.
 33. Bedford TG, Loi PK, Crandall CC. A model of dynamic exercise: The decerebrate rat locomotor preparation. JApplPhysiol 72: 121‐127, 1992.
 34. Bell HJ. Respiratory control at exercise onset: An integrated systems perspective. RespirPhysiol Neurobiol 152: 1‐15, 2006.
 35. Bell HJ, Duffin J. Rapid increases in ventilation accompany the transition from passive to active movement. Respir Physiol Neurobiol 152: 128‐142, 2006.
 36. Bell HJ, Feenstra W, Duffin J. The initial phase of exercise hyperpnoea in humans is depressed during a cognitive task. Exp Physiol 90: 357‐365, 2005.
 37. Bennett F, Reischl P, Grodins FS, Yamashiro SM, Fordyce WE. Dynamics of ventilatoy response to exercise in humans. J Appl Physiol 51: 194‐203, 1981.
 38. Bennett FM. A role for neural pathways in exercise hyperpnea. JApplPhysiol 56: 1559‐1564, 1984.
 39. Bennett FM, Tallman RD Jr, Grodins FS. Role of VCO2 in control of breathing of awake exercising dogs. J Appl Physiol 56: 1335‐1339, 1984.
 40. Bernard, Claude. Introduction a I'etude de la medicine experimentale. Paris‐Leipzig: J.B. Baillere, Jung‐Treuttel, 1974.
 41. Bernard JF, Bandler R. Parallel circuits for emotional coping behaviour: New pieces in the puzzle. J Comp Neurol 401: 429‐436, 1998.
 42. Bessou P, Dejours P, Laporte Y. Effets ventilatoires reflexes de la stimulation de fibres afferents de grand diametre, d'origine musculaire chez le chat. Compt Rend Soc Biol 153: 477‐480, 1959a.
 43. Bessou P, Dejours P, Laporte Y. Reflex ventilatory action of large diameter afferent fibers of muscular origin in the cat. J Physiol (Paris) 51: 400‐401, 1959b.
 44. Bessou P, Laporte Y. Activation des fibres afferentes amyeliniques d'origine musculaire. CR Acad Sci Ser 3: 1587‐1590, 1958.
 45. Biscoe T, Purves, M. Factors affecting the cat carotid chemoreceptor and cervical sympathetic activity with special reference to passive hind‐limb movement. J Physiol (London) 190: 425‐441, 1967.
 46. Bisgard GE, Forster HV, Byrnes B, Stanek K, Klein J, Manohar M. Cerebrospinal fluid acid‐base balance during muscular exercise. J Appl Physiol 45: 94‐101, 1978.
 47. Bisgard GE, Forster HV, Mesina J, Sarazin RG. Role of the carotid body in hyperpnea of moderate exercise in goats. J Appl Physiol 52: 1216‐1222, 1982.
 48. Bisgard GE, Forster HV, Orr JA, Buss DD, Rawlings CA, Rasmussen B. Hypoventilation in ponies after carotid body denervation. J Appl Physiol 40: 184‐190, 1976.
 49. Blain GM, Smith CA, Henderson KS, Dempsey JA. Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetized dog. J Appl Physiol 106: 1564‐1573, 2009.
 50. Blain GM, Smith CA, Henderson KS, Dempsey JA. Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO(2). J Physiol 588: 2455‐2471, 2010.
 51. Bouverot P, Collin R, Favier R, Flandrois R, Sebert P. Carotid chemoreceptor function in ventilatory and circulatory O2 convection of exercising dogs at low and high altitude. Respir Physiol 43: 147‐167, 1981.
 52. Brack KE, Jeffery SM, Lovick TA. Cardiovascular and respiratory responses to a panicogenic agent in anaesthetised female Wistar rats at different stages of the oestrous cycle. Eur J Neurosci 23: 3309‐3318, 2006.
 53. Bramble DM, Carrier DR. Running and breathing in mammals. Science 219: 251‐256, 1983.
 54. Brice AG, Forster HV, Pan LG, Brown DR, Forster AL, Lowry TF. Effect of cardiac denervation on cardiorespiratory responses to exercise in goats. J Appl Physiol 70: 1113‐1120, 1991.
 55. Brice AG, Forster HV, Pan LG, Funahashi A, Hoffman MD, Murphy CL, Lowry TF. Is the hyperpnea of muscular contractions critically dependent on spinal afferents? J Appl Physiol 64: 226‐233, 1988.
 56. Brice AG, Forster HV, Pan LG, Funahashi A, Lowry TF, Murphy CL, Hoffman MD. Ventilatory and PaCO2 responses to voluntary and electrically induced leg exercise. J Appl Physiol 64: 218‐225, 1988.
 57. Brown DR, Forster HV, Pan LG, Brice AG, Murphy CL, Lowry TF, Gutting SM, Funahashi A, Hoffman M, Powers S. Ventilatory response of spinal cord‐lesioned subjects to electrically induced exercise. J Appl Physiol 68: 2312‐2321, 1990.
 58. Brown HV, Wasserman K, Whipp BJ. Effect of beta‐adrenergic blockade during exercise on ventilation and gas exchange. J Appl Physiol 41: 886‐892, 1976.
 59. Carrive P. The periaqueductal gray and defensive behavior: Functional representation and neuronal organization. Behav Brain Res 58: 27‐47, 1993.
 60. Carrive P, Bandler R. Viscerotopic organization of neurons subserving hypotensive reactions within the midbrain periaqueductal grey: A correlative functional and anatomical study. Brain Res 541: 206‐215, 1991.
 61. Carrive P, Bandler R, Dampney RA. Anatomical evidence that hypertension associated with the defence reaction in the cat is mediated by a direct projection from a restricted portion of the midbrain periaqueductal grey to the subretrofacial nucleus of the medulla. Brain Res 460: 339‐345, 1988.
 62. Carrive P, Bandler R, Dampney RA. Viscerotopic control of regional vascular beds by discrete groups of neurons within the midbrain periaqueductal gray. Brain Res 493: 385‐390, 1989.
 63. Casaburi R, Barstow TJ, Robinson T, Wasserman K. Influence of work rate on ventilatory and gas exchange kinetics. J Appl Physiol 67: 547‐555, 1989.
 64. Casaburi R, Whipp BJ, Wasserman K, Beaver WL, Koyal SN. Ventilatory and gas exchange dynamics in response to sinusoidal work. J Appl Physiol 42: 300‐301, 1977.
 65. Casaburi R, Whipp BJ, Wasserman K, Koyal SN. Ventilatory and gas exchange responses to cycling with sinusoidally varying pedal rate. JApplPhysiol 44: 97‐103, 1978.
 66. Casaburi R, Whipp BJ, Wasserman K, Stremel RW. Ventilatory control characteristics of the exercise hyperpnea as discerned from dynamic forcing techniques. Chest 73: 280‐283., 1978.
 67. Casey K, Duffin J, Kelsey CJ, McAvoy GV. The effect of treadmill speed on ventilation at the start of exercise in man. J Physiol 391: 13‐24, 1987.
 68. Casey K, Duffin J, McAvoy GV. The effect of exercise on the central‐chemoreceptor threshold in man. J Physiol 383: 9‐18, 1987.
 69. Clark JM, Sinclair RD, Lenox JB. Chemical and nonchemical components of ventilation during hypercapnic exercise in man. J Appl Physiol 48: 1065‐1076, 1980.
 70. Clifford PS, Litzow JT, Coon RL. Arterial hypocapnia during exercise in beagle dogs. J Appl Physiol 61: 599‐602, 1986.
 71. Clifford PS, Litzow JT, von Colditz JH, Coon RL. Effect of chronic pulmonary denervation on ventilatory responses to exercise. J Appl Physiol 61: 603‐610, 1986.
 72. Colebatch JG, Adams L, Murphy K, Martin AJ, Lammertsma AA, Tochon‐Danguy HJ, Clark JC, Friston KJ, Guz A. Regional cerebral blood flow during volitional breathing in man. J Physiol 443: 91‐103, 1991.
 73. Coleridge HM, Coleridge JC, Banzett RB II. Effect of CO2 on afferent vagal endings in the canine lung. Respir Physiol 34: 135‐151, 1978.
 74. Comroe JH, Schmidt CF. Reflexes from the limbs as a factor in the hyerpnea of muscular exercise. Am J Physiol 138: 536‐547, 1943.
 75. Corda M, von Euler C, Lennerstrand G. Reflex and cerebellar influences on alpha and on ‘rhythmic’ and ‘tonic’ gamma activity in the intercostal muscle. J Physiol 184: 898‐923, 1966.
 76. Cropp GJ, Comroe JH Jr. Role of mixed venous blood PCO2 in respiratory control. J Appl Physiol 16: 1029‐1033, 1961.
 77. Cross BA, Davey A, Guz A, Katona PG, MacLean M, Murphy K, Semple SJ, Stidwill R. The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog. J Physiol 329: 37‐55, 1982.
 78. D'Angelo E, Torelli G. Neural stimuli increasing respiration during different types of exercise. J Appl Physiol 30: 116‐121, 1971.
 79. da Silva LG Jr, Menezes RC, Villela DC, Fontes MA. Excitatory amino acid receptors in the periaqueductal gray mediate the cardiovascular response evoked by activation of dorsomedial hypothalamic neurons. Neuroscience 139: 1129‐1139, 2006.
 80. Dean JB, Mulkey DK, Henderson RA III, Potter SJ, Putnam RW. Hyperoxia, reactive oxygen species, hyperventilation: Oxygen sensitivity of brain stem neurons. J Appl Physiol 96: 784‐791, 2004.
 81. Decima EE, von Euler C. Intercostal and cerebellar influences on efferent phrenic activity in the decerebrate cat. Acta Physiol Scand 76: 148‐158, 1969.
 82. Dejours P. Regulation of ventilation during muscular exercise in man. JPhysiol (Paris) 51: 163‐261, 1959.
 83. Dejours P, Chemoreflexes in breathing. Physiologic Reviews, European Editorial Committee. American Physiologic Society. 42: 335‐358, 1962.
 84. Dejours P. Control of respiration during muscular exercise. In: Handbook of Physiology; Respiration. Washington, D.C.: American Physiologic Society, 1964, p. 631‐648.
 85. Dejours P, Mithoefer JC, Raynaud J. Evidence against the existence of specific ventilatory chemoreceptors in the legs. J Appl Physiol 10: 367‐371, 1957.
 86. Dempsey JA, Miller JS, Roman LM. The respiratory system. In: Tipton CM, Sawka CN, Tate CA, Terjing RJ, editors. American College of Sport's Medicine Advanced Exercise Physiology. Lippincott, Williams, and Wilkins: Philadelphia, 2006, p. 246‐299.
 87. Dempsey JA, Forster HV, Birnbaum ML, Reddan WG, Thoden J, Grover RF, Rankin J. Control of exercise hyperpnea under varying durations of exposure to moderate hypoxia. Respir Physiol 16: 213‐231, 1972.
 88. Dempsey JA, Gledhill N, Reddan WG, Forster HV, Hanson PG, Claremont AD. Pulmonary adaptation to exercise: Effects of exercise type and duration, chronic hypoxia and physical training. Ann N Y Acad Sci 301: 243‐261, 1977.
 89. Dempsey JA, Hanson PG, Henderson KS. Exercise‐induced arterial hypoxaemia in healthy human subjects at sea level. J Physiol 355: 161‐175, 1984.
 90. Dempsey JA, Rankin J. Physiologic adaptations of gas transport systems to muscular work in health and disease. Am J Phys Med 46: 582‐647, 1967.
 91. Dempsey JA, Reddan WG, Birnbaum ML, Forster HV, Thoden JS, Grover RF, Rankin J. Effects of acute through life‐long hypoxic exposure on exercise pulmonary gas exchange. Respir Physiol 13: 62‐89, 1971.
 92. Dempsey JA, Vidruk EH, Mitchell GS. Pulmonary control systems in exercise: Update. Fed Proc 44: 2260‐2270, 1985.
 93. DiMarco AF, Romaniuk JR, von EC, Yamamoto Y. Immediate changes in ventilation and respiratory pattern associated with onset and cessation of locomotion in the cat. J Physiol 343: 1‐16, 1983.
 94. Dormer KJ. Modulation of cardiovascular response to dynamic exercise by fastigial nucleus. J Appl Physiol 56: 1369‐1377, 1984.
 95. Dormer KJ, Foreman RD, Ohata CA. Fastigial nucleus stimulation and excitatory spinal sympathetic activity in dog. Am J Physiol 243: R25‐R33, 1982.
 96. Douglas CG, Haldane JS. The regulation of normal breathing. J Physiol 38: 420‐440, 1909.
 97. Dubayle D, Viala D. Entrainment of the medullary respiratory generators by electrical stimulation in the cervical grey matter on in vitro preparations of newborn rat. Neurosci Lett 248: 204‐208, 1998.
 98. Duffin J, Bechbache RR, Goode RC, Chung SA. The ventilatory response to carbon dioxide in hyperoxic exercise. Respir Physiol 40: 93‐105, 1980.
 99. Duffin J, McAvoy GV. The peripheral‐chemoreceptor threshold to carbon dioxide in man. J Physiol 406: 15‐26, 1988.
 100. Eccles JC, Provini L, Strata P, Taborikova H. Analysis of electrical potentials evoked in the cerebellar anterior lobe by stimulation of hindlimb and forelimb nerves. Exp Brain Res 6: 171‐194, 1968.
 101. Ehrman J, Keteyian S, Fedel F, Rhoads K, Levine TB, Shepard R. Cardiovascular responses of heart transplant recipients to graded exercise testing. J Appl Physiol 73: 260‐264, 1992.
 102. Eiken O, Bjurstedt H. Cardiorespiratory responses to supine leg exercise during lower body negative pressure (LBNP). Physiologist 30: S70‐S71, 1987.
 103. Eldridge FL. Posthyperventilation breathing: Different effects of active and passive hyperventilation. J Appl Physiol 34: 422‐430, 1973.
 104. Eldridge FL. Expiratory effects of brief carotid sinus nerve and carotid body stimulations. Respir Physiol 26: 395‐410, 1976.
 105. Eldridge FL. Maintenance of respiration by central neural feedback mechanisms. Fed Proc 36: 2400‐2404, 1977.
 106. Eldridge FL, Gill‐Kumar P. Central neural respiratory drive and afterdischarge. Respir Physiol 40: 49‐63, 1980.
 107. Eldridge FL, Gill‐Kumar P. Central respiratory effects of carbon dioxide, and carotid sinus nerve and muscle afferents. J Physiol 300: 75‐87, 1980.
 108. Eldridge FL, Millhorn DE, Kiley JP, Waldrop TG. Stimulation by central command of locomotion, respiration and circulation during exercise. RespirPhysiol 59: 313‐337, 1985.
 109. Eldridge FL, Millhorn DE, Waldrop TG. Exercise hyperpnea and locomotion: Parallel activation from the hypothalamus. Science 211: 844‐846, 1981.
 110. Erickson BK, Forster HV, Pan LG, Lowry TF, Brown DR, Forster MA, Forster AL. Ventilatory compensation for lactacidosis in ponies: Role of carotid chemoreceptors and lung afferents. J Appl Physiol 70: 2619‐2626, 1991.
 111. Favier R, Desplanches D, Frutoso J, Grandmontagne M, Flandrois R. Ventilatory and circulatory transients during exercise: New arguments for a neurohumoral theory. J Appl Physiol 54: 647‐653, 1983a.
 112. Favier R, Desplanches D, Frutoso J, Grandmontagne M, Flandrois R. Ventilatory transients during exercise: Peripheral or central control? Pflugers Arch 396: 269‐276, 1983b.
 113. Favier R, Kepenekian G, Desplanches D, Flandrois R. Effects of chronic lung denervation on breathing pattern and respiratory gas exchanges during hypoxia, hypercapnia and exercise. RespirPhysiol 47: 107‐119, 1982.
 114. Fernandes A, Galbo H, Kjaer M, Mitchell JH, Secher NH, Thomas SN. Cardiovascular and ventilatory responses to dynamic exercise during epidural anaesthesia in man. J Physiol 420: 281‐293, 1990.
 115. Fink GR, Adams L, Watson JD, Innes JA, Wuyam B, Kobayashi I, Corfield DR, Murphy K, Jones T, Frackowiak RS. Hyperpnoea during and immediately after exercise in man: Evidence of motor cortical involvement. J Physiol 489(Pt 3): 663‐675, 1995.
 116. Flandrois R, Lacour JR, Eclache JP. Control of respiration in exercising dog: Interaction of chemical and physical stimuli. Respir Physiol 21: 169‐181, 1974.
 117. Flynn C, Forster HV, Pan LG, Bisgard GE. Role of hilar nerve afferents in hyperpnea of exercise. J Appl Physiol 59: 798‐806, 1985.
 118. Fordyce WE, Grodins FS. Ventilatory responses to intravenous and airway CO2 administration in anesthetized dogs. J Appl Physiol 48: 337‐346, 1980.
 119. Forster HV, Dunning MB, Lowry TF, Erickson BK, Forster MA, Pan LG, Brice AG, Effros RM. Effect of asthma and ventilatory loading on arterial PCO2 of humans during submaximal exercise. J Appl Physiol 75: 1385‐1394, 1993.
 120. Forster HV, Erickson BK, Lowry TF, Pan LG, Korducki MJ, Forster AL. Effect of helium‐induced ventilatory unloading on breathing and diaphragm EMG in awake ponies. J Appl Physiol 77: 452‐462, 1994.
 121. Forster HV, Klausen K. The effect of chronic metabolic acidosis and alkalosis on ventilation during exercise and hypoxia. RespirPhysiol 17: 336‐346, 1973.
 122. Forster HV, Lowry TF, Murphy CL, Pan LG. Role of elevated plasma [K+] and carotid chemoreceptors in hyperpnea of exercise in ponies. J Physiol (London) 417: 112P, 1989.
 123. Forster HV, Lowry TF, Pan LG, Erickson BK, Korducki MJ, Forster MA. Diaphragm and lung afferents contribute to inspiratory load compensation in awake ponies. J Appl Physiol 76: 1330‐1339, 1994.
 124. Forster HV, Pan LG, Bisgard GE, Flynn C, Dorsey SM, Britton MS. Independence of exercise hypocapnia and limb movement frequency in ponies. J Appl Physiol 57: 1885‐1893, 1984.
 125. Forster HV, Pan LG, Bisgard GE, Kaminski RP, Dorsey SM, Busch MA. Hyperpnea of exercise at various PIO2 in normal and carotid body‐denervated ponies. J Appl Physiol 54: 1387‐1393, 1983.
 126. Forster HV, Pan LG, Funahashi A. Temporal pattern of arterial CO2 partial pressure during exercise in humans. JApplPhysiol 60: 653‐660, 1986.
 127. Forster HV, Pan LG, Lowry TF, Serra A, Wenninger J, Martino P. Important role of carotid chemoreceptor afferents in control of breathing of adult and neonatal mammals. Respir Physiol 119: 199‐208, 2000.
 128. Fortuna MG, Stornetta RL, West GH, Guyenet PG. Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation. J Physiol 587: 5121‐5138, 2009.
 129. Frappell PB, Dotta A, Mortola JP. Metabolism during normoxia, hyperoxia, and recovery in newborn rats. Can J Physiol Pharmacol 70: 408‐411, 1992.
 130. Fregosi RF, Dempsey JA. Arterial blood acid‐base regulation during exercise in rats. J Appl Physiol 57: 396‐402, 1984.
 131. Fujihara Y, Hildebrandt JR, Hildebrandt J. Cardiorespiratory transients in exercising man. II. Linear models. J Appl Physiol 35: 68‐76, 1973a.
 132. Fujihara Y, Hildebrandt JR, Hildebrandt J. Cardiorespiratory transients in exercising man. I. Tests of superposition. J Appl Physiol 35: 58‐67, 1973b.
 133. Galbo H, Kjaer M, Secher NH. Cardiovascular, ventilatory and catecholamine responses to maximal dynamic exercise in partially curarized man. J Physiol 389: 557‐568, 1987.
 134. Gautier H, Bonora M. Ventilatory and metabolic responses to cold and hypoxia in intact and carotid body‐denervated rats. JApplPhysiol 73: 847‐854, 1992.
 135. Gesell R, Brassfield, C, Hamilton M. An acid‐neurohumoral mechanism of nerve cell activation. Am J Physiol 136: 604‐608, 1942.
 136. Gladwell VF, Coote JH. Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: A role for mechanoreceptors. J Physiol 540: 1095‐1102, 2002.
 137. Goodman NW, Nail BS, Torrance RW. Oscillations in the discharge of single carotid chemorecptor fibers of the cat. Respir Physiol 20: 251‐269, 1974.
 138. Greco EC Jr, Fordyce WE, Gonzalez F Jr, Reischl P, Grodins FS. Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs. J Appl Physiol 45: 109‐114, 1978.
 139. Green AL, Paterson DJ. Identification of neurocircuitry controlling cardiovascular function in humans using functional neurosurgery: Implications for exercise control. Exp Physiol 93: 1022‐1028, 2008.
 140. Green AL, Wang S, Owen SL, Xie K, Liu X, Paterson DJ, Stein JF, Bain PG, Aziz TZ. Deep brain stimulation can regulate arterial blood pressure in awake humans. Neuroreport 16: 1741‐1745, 2005.
 141. Green AL, Wang S, Purvis S, Owen SL, Bain PG, Stein JF, Guz A, Aziz TZ, Paterson DJ. Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans. J Physiol 578: 605‐612, 2007.
 142. Green JF, Sheldon MI. Ventilatory changes associated with changes in pulmonary blood flow in dogs. J Appl Physiol 54: 997‐1002, 1983.
 143. Griffiths TL, Henson LC, Whipp BJ. Influence of inspired oxygen concentration on the dynamics of the exercise hyperpnoea in man. J Physiol 380: 387‐403, 1986.
 144. Grodins FS. Analysis of factors concerned in regulation of breathing in exercise. Physiol Rev 30: 220‐239, 1950.
 145. Gruart A, Delgado‐Garcia JM. Respiration‐related neurons recorded in the deep cerebellar nuclei of the alert cat. Neuroreport 3: 365‐368, 1992.
 146. Guenette JA, Querido JS, Eves ND, Chua R, Sheel AW. Sex differences in the resistive and elastic work of breathing during exercise in endurance‐trained athletes. Am J Physiol Regul Integr Comp Physiol 297: R166‐R175, 2009.
 147. Guyton A, Organization of the nervous system, basic functions of synapses and transmitter substances. In: Guyton A, editor. Textbook of Medical Physiology. 7th ed. Saunders: Philadelphia, 447‐494, 1991.
 148. Guz A. Brain, breathing and breathlessness. Respir Physiol 109: 197‐204, 1997.
 149. Haldane JS, Priestley JG. The regulation of the lung‐ventilation. J Physiol 32: 225‐266, 1905.
 150. Hanson P, Claremont A, Dempsey J, Reddan W. Determinants and consequences of ventilatory responses to competitive endurance running. J Appl Physiol 52: 615‐623, 1982.
 151. Haouzi P. Theories on the nature of the coupling between ventilation and gas exchange during exercise. Respir Physiol Neurobiol 151: 267‐279, 2006.
 152. Haouzi P, Allioui EM, Gille JP, Bedez Y, Tousseul B, Chalon B. Stimulation of ventilation by normobaric hyperoxia in exercising dogs. Exp Physiol 85: 829‐838, 2000.
 153. Haouzi P, Chenuel B. Control of arterial PCO2 by somatic afferents in sheep. J Physiol 569: 975‐987, 2005.
 154. Haouzi P, Chenuel B, Chalon B. The control of ventilation is dissociated from locomotion during walking in sheep. J Physiol 559: 315‐325, 2004.
 155. Haouzi P, Chenuel B, Huszczuk A. Sensing vascular distension in skeletal muscle by slow conducting afferent fibers: Neurophysiological basis and implication for respiratory control. J Appl Physiol 96: 407‐418, 2004.
 156. Haouzi P, Hill JM, Lewis BK, Kaufman MP. Responses of group III and IV muscle afferents to distension of the peripheral vascular bed. J Appl Physiol 87: 545‐553, 1999.
 157. Haouzi P, Huszczuk A, Gille JP, Chalon B, Marchal F, Crance JP, Whipp BJ. Vascular distension in muscles contributes to respiratory control in sheep. Respir Physiol 99: 41‐50, 1995.
 158. Haouzi P, Huszczuk A, Porszasz J, Chalon B, Wasserman K, Whipp BJ. Femoral vascular occlusion and ventilation during recovery from heavy exercise. Respir Physiol 94: 137‐150, 1993.
 159. Harms CA, Babcock MA, McClaran SR, Pegelow DF, Nickele GA, Nelson WB, Dempsey JA. Respiratory muscle work compromises leg blood flow during maximal exercise. J Appl Physiol 82: 1573‐1583, 1997.
 160. Harms CA, Wetter TJ, McClaran SR, Pegelow DF, Nickele GA, Nelson WB, Hanson P, Dempsey JA. Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise. J Appl Physiol 85: 609‐618, 1998.
 161. Heigenhauser GJ, Sutton JR, Jones NL. Effect of glycogen depletion on the ventilatory response to exercise. JApplPhysiol 54: 470‐474, 1983.
 162. Hernandez JP, Xu F, Frazier DT. Medial vestibular nucleus mediates the cardiorespiratory responses to fastigial nuclear activation and hypercapnia. J Appl Physiol 97: 835‐842, 2004.
 163. Hertel HC, Howaldt B, Mense S. Responses of group IV and group III muscle afferents to thermal stimuli. Brain Res 113: 201‐205, 1976.
 164. Heymans J, Heymans C. Sur les modifications directes et sur la regulation reflexe de l'activite du centre respiratoir de la tete isolee du chien. Arch intern Pharmacodynamie 33: 273‐372, 1927.
 165. Hill JM. Discharge of group IV phrenic afferent fibers increases during diaphragmatic fatigue. Brain Res 856: 240‐244, 2000.
 166. Hobbs S. Central command during exercise: Parallel activation of the cardiovascular and motor systems by descending command signals. Circ Neurobiol Behav 217‐231, 1982.
 167. Hodges MR, Opansky C, Qian B, Davis S, Bonis JM, Krause K, Pan LG, Forster HV. Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe. JApplPhysiol 98: 1234‐1242, 2005.
 168. Holmgren A, Linderholm H. Oxygen and carbon dioxide tensions of arterial blood during heavy and exhaustive exercise. Acta Physiol Scand 44: 203‐215, 1958.
 169. Honda Y, Myojo S, Hasegawa S, Hasegawa T, Severinghaus JW. Decreased exercise hyperpnea in patients with bilateral carotid chemoreceptor resection. J Appl Physiol 46: 908‐912, 1979.
 170. Hornbein TF, Sorensen SC, Parks CR. Role of muscle spindles in lower extremities in breathing during bicycle exercise. J Appl Physiol 27: 476‐479, 1969.
 171. Huszczuk A, Jones PW, Oren A, Shores EC, Nery LE, Whipp BJ, Wasserman K. Venous return and ventilatory control. In: Whipp BJ, Wiberg DM, editors. Modeling and control of breathing. Oxford UK: Elsevier, 1983, p. 78‐85.
 172. Huszczuk A, Whipp BJ, Adams TD, Fisher AG, Crapo RO, Elliott CG, Wasserman K, Olsen DB. Ventilatory control during exercise in calves with artificial hearts. J Appl Physiol 68: 2604‐2611, 1990.
 173. Huszczuk A, Whipp BJ, Oren A, Shors EC, Pokorski M, Nery LE, Wasserman K. Ventilatory responses to partial cardiopulmonary bypass at rest and exercise in dogs. J Appl Physiol 61: 575‐583, 1986.
 174. Huszczuk A, Yeh E, Innes JA, Solarte I, Wasserman K, Whipp BJ. Role of muscle perfusion and baroreception in the hyperpnea following muscle contraction in dog. Respir Physiol 91: 207‐226, 1993.
 175. Ichiyama RM, Gilbert AB, Waldrop TG, Iwamoto GA. Changes in the exercise activation of diencephalic and brainstem cardiorespiratory areas after training. Brain Res 947: 225‐233, 2002.
 176. Innes JA, Solarte I, Huszczuk A, Yeh E, Whipp BJ, Wasserman K. Respiration during recovery from exercise: Effects of trapping and release of femoral blood flow. J Appl Physiol 67: 2608‐2613, 1989.
 177. Iscoe S. Respiratory and stepping frequencies in conscious exercising cats. J Appl Physiol 51: 835‐839, 1981.
 178. Iwamoto GA, Wappel SM, Fox GM, Buetow KA, Waldrop TG. Identification of diencephalic and brainstem cardiorespiratory areas activated during exercise. Brain Res 726: 109‐122, 1996.
 179. Jasinskas CL, Wilson BA, Hoare J. Entrainment of breathing rate to movement frequency during work at two intensities. Respir Physiol 42: 199‐209, 1980.
 180. Jeyaranjan R, Goode R, Beamish S, Duffin J. The contribution of peripheral chemoreceptors to ventilation during heavy exercise. Respir Physiol 68: 203‐213, 1987.
 181. Jeyaranjan R, Goode R, Duffin J. Changes in ventilation at the end of heavy exercise of different durations. Eur J Appl Physiol Occup Physiol 59: 385‐389, 1989a.
 182. Jeyaranjan R, Goode R, Duffin J. The effect of metabolic acid‐base changes on the ventilatory changes at the end of heavy exercise. Eur J Appl Physiol Occup Physiol 58: 405‐410, 1989b.
 183. Johansson JE. Uber die einwirkung der muskeltaetigkeit auf die atmung ung herztaegkeit. Skand Arch Physiol 5: 20‐66, 1893.
 184. Johnson BD, Babcock MA, Suman OE, Dempsey JA. Exercise‐induced diaphragmatic fatigue in healthy humans. J Physiol 460: 385‐405, 1993.
 185. Johnson BD, Reddan WG, Pegelow DF, Seow KC, Dempsey JA. Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respir Dis 143: 960‐967, 1991.
 186. Johnson BD, Reddan WG, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in a fit aging population. Am Rev Respir Dis 143: 968‐977, 1991.
 187. Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol 73: 874‐886, 1992.
 188. Jones P, Huszczuk A, Wasserman K. Cardiac output as a contgroller of ventilation through changes in right ventricular load. J Appl Physiol 53: 218‐224, 1982.
 189. Kao FF. An experimental study of the pathways involved in exercise hyperpnea employing cross‐circulation techniques. In: Cunningham DJC, Lloyd BB, editors. Regulation of Human Respiration, Philadelphia. F.A. Davis Company, 1963, p. 461‐502.
 190. Kaufman MP, Hayes SG, Adreani CM, Pickar JG. Discharge properties of group III and IV muscle afferents. Adv Exp Med Biol 508: 25‐32, 2002.
 191. Kaufman MP, Rybicki KJ. Discharge properties of group III and IV muscle afferents: Their responses to mechanical and metabolic stimuli. Circ Res 61: I60‐I65, 1987.
 192. Kaufman MP, Rybicki KJ, Waldrop TG, Ordway GA. Effect of ischemia on responses of group III and IV afferents to contraction. J Appl Physiol 57: 644‐650, 1984.
 193. Kay JD, Petersen ES, Vejby‐Christensen H. Breathing in man during steady‐state exercise on the bicycle at two pedalling frequencies, and during treadmill walking. J Physiol 251: 645‐656, 1975.
 194. Kelsey CJ, Duffin J. Changes in ventilation in response to ramp changes in treadmill exercise load. Eur J Appl Physiol Occup Physiol 65: 480‐484, 1992.
 195. Kiley JP, Kuhlmann WD, Fedde MR. Arterial and mixed venous blood gas tensions in exercising ducks. Poult Sci 59: 914‐917, 1980.
 196. King AB, Menon RS, Hachinski V, Cechetto DF. Human forebrain activation by visceral stimuli. J Comp Neurol 413: 572‐582, 1999.
 197. Knuttgen HG, Emerson K Jr. Physiological response to pregnancy at rest and during exercise. J Appl Physiol 36: 549‐553, 1974.
 198. Koehle M, Duffin J. The effect of exercise duration on the fast component of exercise hyperpnoea at work rates below the first ventilatory threshold. Eur J Appl Physiol Occup Physiol 74: 548‐552, 1996.
 199. Kostreva DR, Hopp FA, Zuperku EJ, Igler FO, Coon RL, Kampine JP. Respiratory inhibition with sympathetic afferent stimulation in the canine and primate. J Appl Physiol 44: 718‐724, 1978.
 200. Kostreva DR, Hopp FA, Zuperku EJ, Kampine JP. Apnea, tachypnea, and hypotension elicited by cardiac vagal afferents. J Appl Physiol 47: 312‐318, 1979.
 201. Kramer JM, Waldrop TG. Neural control of the cardiovascular system during exercise. An integrative role for the vestibular system. J Vestib Res 8: 71‐80, 1998.
 202. Krogh A, Lindhard J. The regulation of respiration and circulation during the initial stages of muscular work. J Physiol 47: 112‐136, 1913.
 203. Kuhlmann WD, Hodgson DS, Fedde MR. Respiratory, cardiovascular, and metabolic adjustments to exercise in the Hereford calf. J Appl Physiol 58: 1273‐1280, 1985.
 204. Lahiri S. Physiologic responses: Peripheral chemoreflexes. In: Crystal RG, West JB, Weibel ER, Barnes PJ, editors. The Lung: Scientific Foundations Lippincott‐Raven: Phiadelphia‐New York, 1991, p. 1333‐1340.
 205. Lahiri S, de Laney RG. Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers. Respir Physiol 24: 249‐266, 1975.
 206. Lamb TW. Ventilatory responses to intravenous and inspired carbon dioxide in anesthetized cats. Respir Physiol 2: 99‐104, 1966.
 207. Lamb TW. Ventilatory responses to hind limb exercise in anesthetized cats and dogs. Respir Physiol 6: 88‐104, 1968.
 208. Levine S. Ventilatory response to muscular exercise: Observations regarding a humoral pathway. J Appl Physiol 47: 126‐137, 1979.
 209. Lewis S. Awake baboon's ventilatory response to venous and inhaled CO2 loading. J Appl Physiol 39: 417‐422, 1975.
 210. Li J, Mitchell JH. c‐Fos expression in the midbrain periaqueductal gray during static muscle contraction. Am J Physiol Heart Circ Physiol 279: H2986‐H2993, 2000.
 211. Li P, Lovick TA. Excitatory projections from hypothalamic and midbrain defense regions to nucleus paragigantocellularis lateralis in the rat. Exp Neurol 89: 543‐553, 1985.
 212. Linnarsson D. Dynamics of pulmonary gas exchange and heart rate changes at start and end of exercise. Acta Physiol Scand Suppl 415: 1‐68, 1974.
 213. Linnarsson D, Lindborg B. Breath‐by‐breath measurement of respiratory gas exchange using on‐line analog computation. Scand J Clin Lab Invest 34: 219‐224, 1974.
 214. Linton R, Miller, R, Cameron R. Ventilatory response to CO2 inhalation and intravenous infusion of hypercapnic blood. Respir Physiol 26: 383‐394, 1976.
 215. Lloyd TC Jr. Effect on breathing of acute pressure rise in pulmonary artery and right ventricle. J Appl Physiol 57: 110‐116, 1984.
 216. Lovick TA. Ventrolateral medullary lesions block the antinociceptive and cardiovascular responses elicited by stimulating the dorsal periaqueductal grey matter in rats. Pain 21: 241‐252, 1985.
 217. Lugliani R, Whipp BJ, Seard C, Wasserman K. Effect of bilateral carotid‐body resection on ventilatory control at rest and during exercise in man. N Engl J Med 285: 1105‐1111, 1971.
 218. Lutherer LO, Williams JL. Stimulating fastigial nucleus pressor region elicits patterned respiratory responses. Am J Physiol 250: R418‐R426, 1986.
 219. Lutherer LO, Williams JL, Everse SJ. Neurons of the rostral fastigial nucleus are responsive to cardiovascular and respiratory challenges. J Auton Nerv Syst 27: 101‐111, 1989.
 220. MacDonald MJ, Shoemaker JK, Tschakovsky ME, Hughson RL. Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans. J Appl Physiol 85: 1622‐1628, 1998.
 221. MacDougall JD, Reddan WG, Layton CR, Dempsey JA. Effects of metabolic hyperthermia on performance during heavy prolonged exercise. J Appl Physiol 36: 538‐544, 1974.
 222. Manohar M. Blood flow in respiratory muscles during maximal exertion in ponies with laryngeal hemiplegia. J Appl Physiol 62: 229‐237, 1987.
 223. Martin PA, Mitchell GS. Long‐term modulation of the exercise ventilatory response in goats. J Physiol 470: 601‐617, 1993.
 224. Martino PF, Davis S, Opansky C, Krause K, Bonis JM, Czerniak SG, Pan LG, Qian B, Forster HV. Lesions in the cerebellar fastigial nucleus have a small effect on the hyperpnea needed to meet the gas exchange requirements of submaximal exercise. J Appl Physiol 101: 1199‐1206, 2006.
 225. Martino PF, Davis S, Opansky C, Krause K, Bonis JM, Pan LG, Qian B, Forster HV. The cerebellar fastigial nucleus contributes to CO2‐H+ ventilatory sensitivity in awake goats. Respir Physiol Neurobiol 157: 242‐251, 2007.
 226. Martino PF, Hodges MR, Davis S, Opansky C, Pan LG, Krause K, Qian B, Forster HV. CO2/H+ chemoreceptors in the cerebellar fastigial nucleus do not uniformly affect breathing of awake goats. J Appl Physiol 101: 241‐248, 2006.
 227. Masuda A, Paulev, P, Honda Y. Estimation of peripheral chemoreceptor contribution to exercise hyhperpnea in man. Jpn J Physiol 38: 607‐618, 1988.
 228. Mateika JH, Duffin J. Coincidental changes in ventilation and electromyographic activity during consecutive incremental exercise tests. Eur J Appl Physiol Occup Physiol 68: 54‐61, 1994.
 229. McClaran SR, Harms CA, Pegelow DF, Dempsey JA. Smaller lungs in women affect exercise hyperpnea. J Appl Physiol 84: 1872‐1881, 1998.
 230. McClaran SR, Wetter TJ, Pegelow DF, Dempsey JA. Role of expiratory flow limitation in determining lung volumes and ventilation during exercise. J Appl Physiol 86: 1357‐1366, 1999.
 231. McCloskey DI, Mitchell JH. Reflex cardiovascular and respiratory responses originating in exercising muscle. J Physiol 224: 173‐186, 1972.
 232. McMurray RG, Ahlborn SW. Respiratory responses to running and walking at the same metabolic rate. Respir Physiol 47: 257‐265, 1982.
 233. Menna TM, Mortola JP. Metabolic control of pulmonary ventilation in the developing chick embryo. Respir Physiol Neurobiol 130: 43‐55, 2002.
 234. Mense S. Group III and IV receptors in skeletal muscle: Are they specific or polymodal? Prog Brain Res 113: 83‐100, 1996.
 235. Mense S, Meyer H. Different types of slowly conducting afferent units in cat skeletal muscle and tendon. J Physiol 363: 403‐417, 1985.
 236. Miller JD, Hemauer SJ, Smith CA, Stickland MK, Dempsey JA. Expiratory threshold loading impairs cardiovascular function in health and chronic heart failure during submaximal exercise. J Appl Physiol 101: 213‐227, 2006.
 237. Miller JD, Pegelow DF, Jacques AJ, Dempsey JA. Skeletal muscle pump versus respiratory muscle pump: Modulation of venous return from the locomotor limb in humans. J Physiol 563: 925‐943, 2005.
 238. Miller JD, Smith CA, Hemauer SJ, Dempsey JA. The effects of inspiratory intrathoracic pressure production on the cardiovascular response to submaximal exercise in health and chronic heart failure. Am J Physiol Heart Circ Physiol 292: H580‐H592, 2007.
 239. Mitchell, GS, Bach KB, Martin, PA, Foley KT. Modulation and plasticity of the exercise ventilatory response. Functionsanalyse Biologischer System 23: 269‐277, 1993.
 240. Mitchell GS, Babb TG. Layers of exercise hyperpnea: Modulation and plasticity. Respir Physiol Neurobiol 151: 251‐266, 2006.
 241. Mitchell GS, Gleeson TT, Bennett AF. Ventilation and acid‐base balance during graded activity in lizards. AmJPhysiol 240: R29‐R37, 1981.
 242. Mitchell GS, Smith CA, Dempsey JA. Changes in the VI‐VCO2 relationship during exercise in goats: Role of carotid bodies. J Appl Physiol 57: 1894‐1900, 1984.
 243. Mitchell JH, Reardon WC, McCloskey DI. Reflex effects on circulation and respiration from contracting skeletal muscle. Am J Physiol 233: H374‐H378, 1977.
 244. Morikawn T, Ono t, Honda Y. Afferent and cardiodynamic drives in the early phase of exercise hyperpnea in humans. J Appl Physiol 67: 2006‐2013, 1989.
 245. Morin D, Viala D. Coordinations of locomotor and respiratory rhythms in vitro are critically dependent on hindlimb sensory inputs. J Neurosci 22: 4756‐4765, 2002.
 246. Mortola JP. Correlations between the circadian patterns of body temperature, metabolism and breathing in rats. Respir Physiol Neurobiol 155: 137‐146, 2007.
 247. Mortola JP, Gautier H. Interaction between metabolism and ventilation; Effects of respiratory gases and temperature. In: Dempsey JA, Pack AI, editors. Regulation of Breathing, New York: Marcel Dekker, 1995, p. 1011‐1064.
 248. Mortola JP, Seifert EL. Circadian patterns of breathing. RespirPhysiol Neurobiol 131: 91‐100, 2002.
 249. Moruzzi G. paleocerebellar inhibition of vasomotor and respiratory carotid sinus reflexes. J Neurophysiol 3: 15‐23, 1940.
 250. Nobrega AC, Araujo CG. Heart rate transient at the onset of active and passive dynamic exercise. Med Sci Sports Exerc 25: 37‐41, 1993.
 251. Nourry C, Deruelle F, Fabre C, Baquet G, Bart F, Grosbois JM, Berthoin S, Mucci P. Exercise flow‐volume loops in prepubescent aerobically trained children. J Appl Physiol 99: 1912‐1921, 2005.
 252. Nybo L, Rasmussen P. Inadequate cerebral oxygen delivery and central fatigue during strenuous exercise. Exerc Sport Sci Rev 35: 110‐118, 2007.
 253. Nye P. Identification of peripheral chemoreceptor stimuli. Med Sci Sports Exerc 26: 311‐318, 1994.
 254. Ogoh S, Ainslie PN. Cerebral blood flow during exercise: Mechanisms of regulation. J Appl Physiol 107: 1370‐1380, 2009.
 255. Oldenburg FA, McCormack DW, Morse JL, Jones NL. A comparison of exercise responses in stairclimbing and cycling. J Appl Physiol 46: 510‐516, 1979.
 256. Olsson M, Ho HP, Annerbrink K, Melchior LK, Hedner J, Eriksson E. Association between estrus cycle‐related changes in respiration and estrus cycle‐related aggression in outbred female Wistar rats. Neuropsychopharmacology 28: 704‐710, 2003.
 257. Olsson M, Ho HP, Annerbrink K, Thylefors J, Eriksson E. Respiratory responses to intravenous infusion of sodium lactate in male and female Wistar rats. Neuropsychopharmacology 27: 85‐91, 2002.
 258. Ordway GA, Waldrop TG, Iwamoto GA, Gentile BJ. Hypothalamic influences on cardiovascular response of beagles to dynamic exercise. Am J Physiol 257: H1247‐H1253, 1989.
 259. Oren A, Whipp BJ, Wasserman K. Effect of acid‐base status on the kinetics of the ventilatory response to moderate exercise. JApplPhysiol 52: 1013‐1017, 1982.
 260. Oscarsson, O. Functional organization of spinocerebellar paths. In: Lggo A, editor. Handbook of Sensory Physiology Vol II. Somatosensory System, Berlin‐Heidelberg‐New York: Springer Verlage, 1973 p. 339‐380.
 261. Paintal AS. Functional analysis of group III afferent fibres of mammalian muscles. J Physiol 152: 250‐270, 1960.
 262. Pan LG, Forster HV, Bisgard GE, Dorsey SM, Busch MA. Cardiodynamic variables and ventilation during treadmill exercise in ponies. J Appl Physiol 57: 753‐759, 1984.
 263. Pan LG, Forster HV, Bisgard GE, Kaminski RP, Dorsey SM, Busch MA. Hyperventilation in ponies at the onset of and during steady‐state exercise. J Appl Physiol 54: 1394‐1402, 1983.
 264. Pan LG, Forster HV, Bisgard GE, Murphy CL, Lowry TF. Independence of exercise hyperpnea and acidosis during high‐intensity exercise in ponies. J Appl Physiol 60: 1016‐1024, 1986.
 265. Pan LG, Forster HV, Martino P, Strecker PJ, Beales J, Serra A, Lowry TF, Forster MM, Forster AL. Important role of carotid afferents in control of breathing. J Appl Physiol 85: 1299‐1306, 1998.
 266. Pan LG, Forster HV, Wurster RD, Brice AG, Lowry TF. Effect of multiple denervations on the exercise hyperpnea in awake ponies. J Appl Physiol 79: 302‐311, 1995.
 267. Pan LG, Forster HV, Wurster RD, Murphy CL, Brice AG, Lowry TF. Effect of partial spinal cord ablation on exercise hyperpnea in ponies. J Appl Physiol 69: 1821‐1827, 1990.
 268. Panda A, Senapati JM, Parida B, Fahim M. Role of cerebellum on ventilatory change due to muscle‐receptor stimulation in the dog. J Appl Physiol 47: 1062‐1065, 1979.
 269. Paterson DJ. Potassium and ventilation in exercise. J Appl Physiol 72: 811‐820, 1992.
 270. Paterson DJ, Friedland JS, Bascom DA, Clement ID, Cunningham DA, Painter R, Robbins PA. Changes in arterial K+ and ventilation during exercise in normal subjects and subjects with McArdle's syndrome. JPhysiol 429: 339‐348, 1990.
 271. Paterson DJ, Wood GA, Marshall RN, Morton AR, Harrison AB. Entrainment of respiratory frequency to exercise rhythm during hypoxia. J Appl Physiol 62: 1767‐1771, 1987.
 272. Pernoll ML, Metcalfe J, Kovach PA, Wachtel R, Dunham MJ. Ventilation during rest and exercise in pregnancy and postpartum. Respir Physiol 25: 295‐310, 1975.
 273. Phillipson EA, Bowes G, Townsend ER, Duffin J, Cooper JD. Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load. J Appl Physiol 51: 1398‐1403, 1981a.
 274. Phillipson EA, Bowes G, Townsend ER, Duffin J, Cooper JD. Role of metabolic CO2 production in ventilatory response to steady‐state exercise. JClinInvest 68: 768‐774, 1981b.
 275. Phillipson EA, Duffin J, Cooper JD. Critical dependence of respiratory rhythmicity on metabolic CO2 load. J Appl Physiol 50: 45‐54, 1981.
 276. Piccione G, Caola G, Mortola JP. Day/night pattern of arterial blood gases in the cow. Respir Physiol Neurobiol 140: 33‐41, 2004.
 277. Ponte J, Purves MJ. Carbon dioxide and venous return and their interaction as stimuli to ventilation in the cat. J Physiol 274: 455‐475, 1978.
 278. Poon CS. Ventilatory control in hypercapnia and exercise: Optimization hypothesis. J Appl Physiol 62: 2447‐2459, 1987.
 279. Poon CS, Tin C, Yu Y. Homeostasis of exercise hyperpnea and optimal sensorimotor integration: The internal model paradigm. Respir Physiol Neurobiol 159: 1‐13; discussion 14‐20, 2007.
 280. Potts JT, Rybak IA, Paton JF. Respiratory rhythm entrainment by somatic afferent stimulation. J Neurosci 25: 1965‐1978, 2005.
 281. Powers SK, Beadle RE, Thompson D, Lawler J. Ventilatory and blood gas dynamics at onset and offset of exercise in the pony. J Appl Physiol 62: 141‐148, 1987.
 282. Powers SK, Lawler J, Dempsey JA, Dodd S, Landry G. Effects of incomplete pulmonary gas exchange on VO2 max. J Appl Physiol 66: 2491‐2495, 1989.
 283. Ramsay SC, Adams L, Murphy K, Corfield DR, Grootoonk S, Bailey DL, Frackowiak RS, Guz A. Regional cerebral blood flow during volitional expiration in man: A comparison with volitional inspiration. J Physiol 461: 85‐101, 1993.
 284. Reischl P, Gonzalez F Jr, Greco EC Jr, Fordyce WE, Grodins FS. Arterial PCO2 response to intravenous CO2 in awake dogs unencumbered by external breathing apparatus. J Appl Physiol 47: 1099‐1104, 1979.
 285. Rodman JR, Curran AK, Henderson KS, Dempsey JA, Smith CA. Carotid body denervation in dogs: Eupnea and the ventilatory response to hyperoxic hypercapnia. J Appl Physiol 91: 328‐335, 2001.
 286. Rodman JR, Henderson KS, Smith CA, Dempsey JA. Cardiovascular effects of the respiratory muscle metaboreflexes in dogs: Rest and exercise. J Appl Physiol 95: 1159‐1169, 2003.
 287. Rowell LB, Hermansen L, Blackmon JR. Human cardiovascular and respiratory responses to graded muscle ischemia. J Appl Physiol 41: 693‐701, 1976.
 288. Rowell LB, Taylor HL, Wang Y, Carlson WS. Saturation of arterial blood with oxygen during maximal exercise. J Appl Physiol 19: 284‐286, 1964.
 289. Rushmer RF, Smith OA Jr, Lasher EP. Neural mechanisms of cardiac control during exertion. Physiol Rev Suppl 4: 27‐34, 1960.
 290. Sant Ambrogio AG, Sant Ambrogio FB. Reflexes from the airway, lung, chest wall and limbs. In: Crystal RG, Wwst JB, Weibel ER, Barnes PJ, editors. The Lung: Scientfic Foundation Lippicott‐Raven: Philadelphia, New York, 1991, p. 1383‐1395.
 291. Sato Y, Katayama K, Ishida K, Miyamura M. Ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in children. Eur J Appl Physiol 83: 516‐523, 2000.
 292. Savin WM, Haskell WL, Schroeder JS, Stinson EB. Cardiorespiratory responses of cardiac transplant patients to graded, symptom‐limited exercise. Circulation 62: 55‐60, 1980.
 293. Schaefer SL, Mitchell GS. Ventilatory control during exercise with peripheral chemoreceptor stimulation: Hypoxia vs. domperidone. J Appl Physiol 67: 2438‐2446, 1989.
 294. Seifert EL, Mortola JP. Circadian pattern of ventilation during acute and chronic hypercapnia in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 282: R244‐R251, 2002.
 295. Senapati JM. Effect of stimulation of muscle afferents on ventilation of dogs. J Appl Physiol 21: 242‐246, 1966.
 296. Serra A, Brozoski D, Hodges M, Roethle S, Franciosi R, Forster HV. Effects of carotid and aortic chemoreceptor denervation in newborn piglets. J Appl Physiol 92: 893‐900, 2002.
 297. Shea SA, Andres LP, Shannon DC, Banzett RB. Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity. J Physiol 468: 623‐640, 1993.
 298. Sheldon MI, Green JF. Evidence for pulmonary CO2 chemosensitivity: Effects on ventilation. J Appl Physiol 52: 1192‐1197, 1982.
 299. Sherrington C. Co‐ordination in the simple reflex. In: The Interactive Action of the Nervous System. 2nd Ed. New Haven, CT Yale Univ. Press 36‐69, 1947.
 300. Shors E, Huszczuk A, Wasserman K, Whipp B. Effects of spinal cord section and altered CO2 flow on the exercise hyperpnea in the dog. In: Whipp B, Wiberg D, editors.. Modelling and Control of Breathing. New‐York: Elsevier, 1983, p. 274‐281.
 301. Smith CA, Forster HV, Blain GM, Dempsey JA. An interdependent model of central/peripheral chemoreception: Evidence and implications for ventilatory control. Respir Physiol Neurobiol 173: 288‐297, 2010.
 302. Smith CA, Mitchell GS, Jameson LC, Musch TI, Dempsey JA. Ventilatory response of goats to treadmill exercise: Grade effects. Respir Physiol 54: 331‐341, 1983.
 303. Smith JC, Abdala AP, Rybak IA, Paton JF. Structural and functional architecture of respiratory networks in the mammalian brainstem. Philos Trans R Soc Lond B Biol Sci 364: 2577‐2587, 2009.
 304. Smith OA Jr, Jabbur SJ, Rushmer RF, Lasher EP. Role of hypothalamic structures in cardiac control. Physiol Rev Suppl 4: 136‐141, 1960.
 305. Somjen G. The missing error signal–regulation beyond negative feedback. Nrws Physiol Sci 7: 184‐185, 1992.
 306. St Croix CM, Morgan BJ, Wetter TJ, Dempsey JA. Fatiguing inspiratory muscle work causes reflex sympathetic activation in humans. J Physiol 529Pt 2: 493‐504, 2000.
 307. St. Croix CM, Cunningham D, Paterson D, Kowalchuk J. Peripherial chemoreflex drive in moderate intensity exercise. Can J Appl Physiol 21: 285‐300, 1996.
 308. Stacey MJ. Free nerve endings in skeletal muscle of the cat. J Anat 105: 231‐254, 1969.
 309. Stella G. The reflex response of the “apneustic” centre to stimulation of the chemo‐receptors of the carotid sinus. J Physiol 95: 365‐372, 1939.
 310. Stickland MK, Miller JD, Smith CA, Dempsey JA. Carotid chemoreceptor modulation of regional blood flow distribution during exercise in health and chronic heart failure. Circ Res 100: 1371‐1378, 2007.
 311. Stickland MK, Morgan BJ, Dempsey JA. Carotid chemoreceptor modulation of sympathetic vasoconstrictor outflow during exercise in healthy humans. J Physiol 586: 1743‐1754, 2008.
 312. Stornetta RL, Moreira TS, Takakura AC, Kang BJ, Chang DA, West GH, Brunet JF, Mulkey DK, Bayliss DA, Guyenet PG. Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat. J Neurosci 26: 10305‐10314, 2006.
 313. Strange S, Secher NH, Pawelczyk JA, Karpakka J, Christensen NJ, Mitchell JH, Saltin B. Neural control of cardiovascular responses and of ventilation during dynamic exercise in man. J Physiol 470: 693‐704, 1993.
 314. Stremel R, Whipp B, Casaburi R, Huntsman D, Wasserman K. Hypopnea consequent to reduced pulmonary blodd flow in the dog. J Appl Physiol 46: 1171‐1177, 1979.
 315. Stringer W, Casaburi R, Wasserman K. Acid‐base regulation during exercise and recovery in humans. J Appl Physiol 72: 954‐961, 1992.
 316. Sun XG, Hansen JE, Stringer WW, Ting H, Wasserman K. Carbon dioxide pressure‐concentration relationship in arterial and mixed venous blood during exercise. J Appl Physiol 90: 1798‐1810, 2001.
 317. Swanson GD. Overview of ventilatory control during exercise. Med Sci Sports 11: 221‐226, 1979.
 318. Swanson GD. Assembling control models from pulmonary gas exchange dynamics. Med Sci Sports Exerc 22: 80‐87, 1990.
 319. Szal SE, Schoene RB. Ventilatory response to rowing and cycling in elite oarswomen. J Appl Physiol 67: 264‐269, 1989.
 320. Thornton JM, Aziz T, Schlugman D, Paterson DJ. Electrical stimulation of the midbrain increases heart rate and arterial blood pressure in awake humans. J Physiol 539: 615‐621, 2002.
 321. Thornton JM, Guz A, Murphy K, Griffith AR, Pedersen DL, Kardos A, Leff A, Adams L, Casadei B, Paterson DJ. Identification of higher brain centres that may encode the cardiorespiratory response to exercise in humans. J Physiol 533: 823‐836, 2001.
 322. Thorston J, Wassen‐Gustavsson B, Lindholm A, McMicken D, Persson SG, Snow DH, Rose RJ. Effects of training and detraining on oxygen uptake, cardiac output, blood gas tensions, pH, and lactate concentrations during and after exercise in the horse. In: Snow DH, Person SGBH, Rose RJ, editors. Equine Exercise Physiology. Cambridge UK, Granta Editions, 1983, p. 470‐486.
 323. Tibes U, Hemmer B, Boning D. Heart rate and ventilation in relation to venous [K+], osmolality, pH, PCO2, PO2, [orthophosphate], and [lactate] at transition from rest to exercise in athletes and non‐athletes. Eur J Appl Physiol Occup Physiol 36: 127‐140, 1977.
 324. Turner D, Stewart JD. Associative conditioning with leg cycling and inspiratory resistance enhances the early exercise ventilatory response in humans. Eur J Appl Physiol 93: 333‐339, 2004.
 325. Turner DL, Bach KB, Martin PA, Olsen EB, Brownfield M, Foley KT, Mitchell GS. Modulation of ventilatory control during exercise. Respir Physiol 110: 277‐285, 1997.
 326. Uchida Y. Tachypnea after stimulation of afferent cardiac sympathetic nerve fibers. Am J Physiol 230: 1003‐1007, 1976.
 327. Von During M. Andres K. Toppgraphy and ultrastructure of group III and IV nerve terminals of cut gastrocnemius‐soleus muscle. In: Zenker W, Neuhuber W, editors. The primary afferent neuron; A survey of recent morpho‐functional aspects. New York: Plenum Press. 1990, p. 35‐41.
 328. Wagner PD, Gillespie JR, Landgren GL, Fedde MR, Jones BW, DeBowes RM, Pieschl RL, Erickson HH. Mechanism of exercise‐induced hypoxemia in horses. J Appl Physiol 66: 1227‐1233, 1989.
 329. Waldrop TG, Bauer RM, Iwamoto GA. Microinjection of GABA antagonists into the posterior hypothalamus elicits locomotor activity and a cardiorespiratory activation. Brain Res 444: 84‐94, 1988.
 330. Waldrop TG, Eldridge FL, Iwamoto GA, Mitchell JH. Central neural control of respiration and circulation during exercise. In: Rowell LB, Shephard JT, editors. Handbook of Physiology. American Physiologic Society. New York: Oxford. 12: 333‐380, 1996.
 331. Waldrop TG, Mullins DC, Millhorn DE. Control of respiration by the hypothalamus and by feedback from contracting muscles in cats. Respir Physiol 64: 317‐328, 1986.
 332. Ward SA, Blesovsky L, Russak S, Ashjian A, Whipp BJ. Chemoreflex modulation of ventilatory dynamics during exercise in humans. J Appl Physiol 63: 2001‐2007, 1987.
 333. Warner M, Mitchell, G. Ventilatory responses to hyperkalemia and exercise in normoxic and hypoxic goats. Resp Physiol 82: 239‐250, 1990.
 334. Wasserman K. Testing regulation of ventilation with exercise. Chest 70: 173‐178, 1976.
 335. Wasserman K, Whipp BJ, Casaburi R, Golden M, Beaver WL. Ventilatory control during exercise in man. Bull Eur Physiopathol Respir 15: 27‐51, 1979.
 336. Wasserman K, Whipp BJ, Castagna J. Cardiodynamic hyperpnea: Hyperpnea secondary to cardiac output increase. J Appl Physiol 36: 457‐464, 1974.
 337. Wasserman K, Whipp BJ, Koyal SN, Cleary MG. Effect of carotid body resection on ventilatory and acid‐base control during exercise. J Appl Physiol 39: 354‐358, 1975.
 338. Wasserman K, Whipp BJ, Casaburi R, Huntsman D, Castagna J, Lugliani R. Regulation of arterial PCO2 during intrvenous CO2 loading. J Appl Physiol 38: 651‐656, 1975.
 339. Weil JV, Byrne‐Quinn E, Sodal IE, Kline JS, McCullough RE, Filley GF. Augmentation of chemosensitivity during mild exercise in normal man. J Appl Physiol 33: 813‐819, 1972.
 340. Weiler‐Ravell D, Cooper DM, Whipp BJ, Wasserman K. Control of breathing at the start of exercise as influenced by posture. J Appl Physiol 55: 1460‐1466, 1983.
 341. Weissman ML, Whipp BJ, Huntsman DJ, Wasserman K. Role of neural afferents from working limbs in exercise hyperpnea. J Appl Physiol 49: 239‐248, 1980.
 342. Wells GD, Diep T, Duffin J. The ventilatory response to sine wave variation in exercise loads and limb movement frequency. RespirPhysiol Neurobiol 158: 45‐50, 2007.
 343. Whipp B, Ward S, Lamarra N, Davis J, Wasserman K. Parameters of ventilatory and gas exchange dynamics during exercise. J Appl Physiol 52: 1506‐1513, 1982.
 344. Whipp BJ. Peripheral chemoreceptor control of exercise hyperpnea in humans. Med Sci Sports Exerc 26: 337‐347, 1994.
 345. Whipp BJ, Casaburi R. Characterizing O2 uptake response kinetics during exercise. Int J Sports Med 3: 97‐99, 1982.
 346. Whipp BJ. Control of exercise hyperpnea. In: Hornbien TF, editor. Regulation of Breathing. New York: Dekker, 1981, p. 1069‐1140.
 347. Whipp BJ, Lamarra N, Griffiths TL, Wasserman K. Model implications of ventilatory dynamics during exercise. In: Whipp BJ, Weiberg DM, Bellville JW, Ward SA, editors. Modelling and Control of Breathing. New York: Elsevier Biomedical, 1983, p. 229‐236.
 348. Whipp BJ, Ward SA, Lamarra N, Davis JA, Wasserman K. Parameters of ventilatory and gas exchange dynamics during exercise. J Appl Physiol 52: 1506‐1513, 1982.
 349. White MD, Cabanac M. Exercise hyperpnea and hyperthermia in humans. J Appl Physiol 81: 1249‐1254, 1996.
 350. Widdicombe J. Nervous receptors in the respiratory tract and lungs. In: Hornbein TF, editor. Regulation of Breathing. New york: Marcel Dekker. 1981, p. 429‐473.
 351. Williams CA, Roberts JR, Freels DB. Changes in blood pressure during isometric contractions to fatigue in the cat after brain stem lesions: Effects of clonidine. Cardiovasc Res 24: 821‐833, 1990.
 352. Williams JL, Everse SJ, Lutherer LO. Stimulating fastigial nucleus alters central mechanisms regulating phrenic activity. Respir Physiol 76: 215‐227, 1989.
 353. Williamson JW, Fadel PJ, Mitchell JH. New insights into central cardiovascular control during exercise in humans: A central command update. ExpPhysiol 91: 51‐58, 2006.
 354. Williamson JW, McColl R, Mathews D, Mitchell JH, Raven PB, Morgan WP. Brain activation by central command during actual and imagined handgrip under hypnosis. J Appl Physiol 92: 1317‐1324, 2002.
 355. Williamson JW, Raven PB, Foresman BH, Whipp BJ. Evidence for an intramuscular ventilatory stimulus during dynamic exercise in man. Respir Physiol 94: 121‐135, 1993.
 356. Wood HE, Fatemian M, Robbins PA. A learned component of the ventilatory response to exercise in man. J Physiol 553: 967‐974, 2003.
 357. Xu F, Frazier DT. Medullary respiratory neuronal activity modulated by stimulation of the fastigial nucleus of the cerebellum. Brain Res 705: 53‐64, 1995.
 358. Xu F, Frazier DT. Modulation of respiratory motor output by cerebellar deep nuclei in the rat. J Appl Physiol 89: 996‐1004, 2000.
 359. Xu F, Frazier DT. Respiratory‐related neurons of the fastigial nucleus in response to chemical and mechanical challenges. J Appl Physiol 82: 1177‐1184, 1997.
 360. Xu F, Frazier DT. Role of the cerebellar deep nuclei in respiratory modulation. Cerebellum 1: 35‐40, 2002.
 361. Xu F, Owen J, Frazier DT. Hypoxic respiratory responses attenuated by ablation of the cerebellum or fastigial nuclei. J Appl Physiol 79: 1181‐1189, 1995.
 362. Yamamoto WS. Looking at ventilation as a signalling process. In: Dempsey JA, Reid CD, editors. Muscular Exercise and the Lung. Madison: University of Wisconsin Press, 1977, p. 137‐149.
 363. Yamamoto WS, Edwards MW Jr. Homeostasis of carbon dioxide during intravenous infusion of carbon dioxide. J Appl Physiol 15: 807‐818, 1960.
 364. Yamashiro SM, Daubenspeck JA, Lauritsen TN, Grodins FS. Total work rate of breathing optimization in CO2 inhalation and exercise. J Appl Physiol 38: 702‐709, 1975.
 365. Yamashiro SM, Grodins FS. Optimal regulation of respiratory airflow. J Appl Physiol 30: 597‐602, 1971.
 366. Yates BJ, Bronstein AM. The effects of vestibular system lesions on autonomic regulation: Observations, mechanisms, and clinical implications. J Vestib Res 15: 119‐129, 2005.
 367. Young IH, Woolcock AJ. Changes in arterial blood gas tensions during unsteady‐state exercise. J Appl Physiol 44: 93‐96, 1978.
 368. Zuntz N, Geppert J. Ueber die Natur de normalen Atemreize und den Ort ihrer Wikrung. Arch Ges Physiol 38: 337‐338, 1886.

Related Articles:

Top downloaded articles of 2019

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Control of Breathing During Exercise
 

How to Cite

Hubert V. Forster, Philippe Haouzi, Jerome A. Dempsey. Control of Breathing During Exercise. Compr Physiol 2012, 2: 743-777. doi: 10.1002/cphy.c100045