As the above treatise demonstrates, the control of breathing during exercise is dependent on a complex sequence of events, originating in the numerous receptors which provide an input for the control of breathing. It is important to note that different circumstances will result in the stimulation of different receptors. One could hypothesise that, for example, a strong isometric contraction may activate intramuscular receptors and any central command pathways, while the contraction will occlude blood supply to the muscles, so greatly attenuating any signal from receptors sensitive to changes in blood gas composition or muscle metabolites. Conversely, it is possible that electrically stimulated low-intensity leg exercise in paraplegics at altitude would result in a marked hypoxic stimulus, activating the peripheral chemoreceptors, while the muscle afferent and central command inputs would be negligible.
Despite the wide range of hyperpnoeic stimuli which occur during exercise, the rise in ventilation tends to follow a set pattern as described above. There are some exceptions; Cross et al. (1979) reported that prior to carotid bifurcation denervation, the withholding of two breaths in anaesthetised, paralysed and artificially ventilated dogs produced a rise in VE due mostly to a fall in TE, whereas following denervation the rise in VE occurred later and was characterised by a rise in phrenic nerve activity.
In contrast, Gallagher et al. (1987) demonstrated that in man the pattern of breathing at a given level of ventilation was similar regardless of whether it was in response to exercise alone, or a mixture of exercise and hypercapnia. In a similar experiment, Mekjavic et al. (1987) could find no difference in the pattern of breathing elicited by exercise or exercise with hypoxia. This would suggest that there is a convergence of inputs at the level of the respiratory centre, resulting in the production of the ventilatory drive.
Such a statement begs the question as to how the various inputs interact to produce a single drive. Evidence does not favour a simple additive mechanism: studies into the ventilatory
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responses of paraplegics (Adams et al. 1984a,b; Brice et al. 1988a), spinal denervation of dogs (Cross et al. 1982) and individuals with no muscle afferent nerve supply (Duncan et al
1981) could not demonstrate a reduction in exercise hyperpnoea. Similar results have been reported by studies investigating the removal of central command (Adams et al. 1984a, 1987; Brice et al. 1988b; Fernandes 1990) and carotid body resection (Whipp et al. 1980; Wasserman et al. 1975; Honda 1985), although the studies involving carotid body resection did demonstrate a change in the time-course of the ventilatory response, also confirmed by studies investigating the effects of hypoxia and hyperoxia on the kinetics of exercise hyperpnoea (Griffiths et al. 1986; Ward et al. 1987).
These results can, however, be explained by an occlusive control system, in which the level of exercise hyperpnoea is under the control of the strongest signal arising fi-om the various receptors. Under such circumstances, it is possible for there to be no change in ventilation following the attenuation/ablation of an input, if that input is not dominant at that time. Should the input under investigation be dominant, the reduction in ventilation may still only be small if the next input be only slightly less strong than the dominant one. Such a model also provides an explanation for the results of studies which increase the activity of a specific signal, e.g. tendon stretch receptors (Jammes et al. 1981) or central command (Galbo 1987; Eldridge et al. 1985), induces a rise in ventilation. Under such circumstances, the increase in signal strength is sufficient to make it the dominant signal.
There is also evidence of signal interaction at a different level, as evidenced by the increase in gain o f the central chemoreceptors seen during exercise. The increase in gain has been shown to be dependent on the work rate of the exercise (Cummin et al. 1986c), possibly due to modification of the receptor signal strength, by other input(s) to the respiratory centre, or by modification of receptor activity itself; Flenley and Warren (1983) and Weill and Swanson (1990) both report that hypoxic exercise attenuates the response to hypercapnia, Flenley and Warren (1983) suggesting that this is due to an increase in carotid body sensitivity to arterial PCO2 oscillations.
The last level of integration occurs between the respiratory centre and the lung, and is responsible for determining the interaction between rate and depth of breathing by which the rise in ventilation is attained. An important input at this level arises from the lung and airway receptors: Favier et al. (1982) and Clifford et al. (1986) demonstrated that pulmonary denervation in dogs did not affect the ventilatory response to exercise, but did increase VT and decrease^R. Eldridge et al (1985) reported a similar response following vagotomy in the cat, and Flynn et al. (1985) demonstrated a change in breathing pattern in ponies following hilar nerve denervation with no change in Ve.
In conclusion, it is apparent that the control of breathing during exercise in multifactorial in origin, with a number of different levels of signal interaction resulting in a hyperpnoeic stimulus. This stimulus is then modified inputs from the lungs to determine the pattern by which ventilation will be achieved.
Chapter 2