The carotid bodies exercise control over active expiration but not peak performance during high‐intensity treadmill running

During dynamic exercise, substantial cardiorespiratory adjustments are made to meet the increased requirement for oxygen as a substrate for aerobic metabolism, and to maximize clearance of carbon dioxide in defence of acid–base homeostasis. It is generally regarded that the ventilatory response to exercise manifests in response to multiple drivers of pulmonary ventilation, including central command and sensory feedback from various peripheral sites. The carotid bodies are multimodal sensors, pivotal to the control of breathing. The cardiopulmonary response to exercise is usually sufficient to maintain normal arterial oxygen status. However, there are many additional changes in arterial blood chemistry, arising during intense exercise, which provide substrates for enhanced chemoafferent input from the carotid bodies to the brainstem circuits that govern respiratory timing and motor outflow, which are relevant to exercise-induced hyperpnoea. Pulmonary ventilation is facilitated during increased metabolic demand by active expiration. Recruitment of abdominal muscles in the late expiratory phase of the respiratory cycle, arising from disinhibition of the expiratory oscillator (parafacial respiratory group), complements enhanced inspiratory motor drive and serves to accelerate respiratory frequency and increase tidal volume, allowing for impressive gains in the magnitude of pulmonary ventilation. It is established that peripheral chemoreceptor inputs modulate active expiration (Malheiros-Lima, Silva, Souza, Takakura, & Moreira, 2020). In this issue of Experimental Physiology, Spiller, da Silva, Francescato, and Moraes (2020) explore whether the carotid bodies are necessary for the recruitment of active inspiration and expiration during low- and high-intensity exercise in rats. Rats were trained to run on a treadmill and perform low-intensity constant load exercise and progressive incremental high-intensity exercise to volitional exhaustion. Next, the animals were surgically instrumented to record diaphragm (inspiratory) and internal oblique (expiratory) muscle electromyogram activities. Arterial blood samples were obtained before and after exercise bouts. The respiratory electromyogram response to both modes of exercise was determined before and after bilateral removal of the carotid bodies, the efficacy of which was confirmed by the absence of a ventilatory response to cyanide injected intravenously. The principal focus of the study was to quantify the contribution of the carotid bodies to the active inspiratory and expiratory motor response to exercise. Exercise performance during high-intensity exercise was evaluated by means of recording maximum velocities and time to volitional exhaustion. Low-intensity exercise performed at 50% of maximum velocity for 5 min increased respiratory frequency, but had little effect on diaphragm and abdominal electromyogram activities. There were no changes in arterial partial pressure of carbon dioxide, pH, [lactate], [Na+], [K+], osmolality or [glucose]. Bilateral removal of the carotid bodies had largely no effect on baseline parameters, and no effect on the ventilatory and blood chemistry response to low-intensity exercise. High-intensity exercise was characterized by further increases in respiratory frequency and recruitment of diaphragm and abdominal electromyogram activities suggestive of active inspiratory and expiratory contributions to pulmonary ventilation (although the latter was not measured in the study). At end-exercise, arterial partial pressure of carbon dioxide was decreased, pH was decreased, and [lactate], [Na+], [K+], osmolality and [glucose] were all increased compared with pre-exercise baseline values reflecting the high-intensity workload. The major finding of the study was that diaphragm and abdominal electromyogram responses to high-intensity exercise were significantly attenuated following bilateral removal of the carotid bodies, compared with prior trials in the same animals with intact carotid bodies. As such, rats had higher partial pressure of carbon dioxide and lower pH compared with carotid body intact conditions. All other changes in arterial blood chemistry related to high intensity exercise, as well as maximum running velocity and time to exhaustion, were equivalent when compared before and after removal of the carotid bodies. Thus, it is evident that carotid body activation during high-intensity exercise contributes to the recruitment of active expiration, facilitating enhanced pulmonary ventilation. Potassium and lactate are the likely humoral mediators of the carotid body-dependent contribution to high-intensity exercise hyperpnoea. On the face of it, the carotid body contribution to increased ventilatory drive in high-intensity exercise is substantial (∼50%). The pivotal contribution of muscle afferent feedback to cardiorespiratory and central motor control during exercise is well recognized. Recently, hyperadditive effects of muscle afferent and chemoafferent inputs on heart rate and blood pressure responses to exercise were reported in humans (Wan et al., 2020). Synergistic interaction between the muscle metaboreflex and the central chemoreflex has been shown in humans using post-exercise cuff occlusion to activate muscle afferents (Alghaith, Balanos, Eves, & White, 2019). If similar synergistic interaction applies to respiratory motor control during intense whole body exercise, the selective carotid body contribution to exercise hyperpnoea may be less than that evident in the study by Spiller et al. (2020). Nevertheless, whatever the nature of that potential interaction, there is a substantive role for carotid body feedback in the manifestation of the full hyperpnoeic response to exercise, at least in rats. Interestingly, the blunted hyperpnoea during high-intensity exercise following removal of the carotid bodies, resulting in elevated systemic acidosis, did not limit peak exercise performance. This likely relates to the exercise paradigm employed in the study with peak performance (task failure) most strongly related to metabolic factors in the exercising muscles. Systemic acidosis can further limit exercise performance through actions on neuromuscular control. Interestingly, it has been demonstrated that hyperventilation during rest periods between brief repeat sprint trials leads to attenuation of decreased power output in later trials, despite profound metabolic acidosis (Sakomoto, Naito, & Chow, 2014). In this way, reflex or volitional hyperventilation to limit systemic acidosis likely provides important contributions to peak performance in some circumstances, and may be important for recovery of neuromuscular function following intense exercise. On the long-standing issue of the role of the carotid bodies in the ventilatory response to exercise, Spiller et al. (2020) reveal that the principal arterial chemoreceptors are an important component in the integrative feedback system that drives active inspiration and expiration, which appears especially important in the defence of acid–base homeostasis. Removal of the carotid body's contribution to the exercise hyperpnoea results in a greater systemic acidosis during high intensity exercise, with potential implications for muscular performance depending upon the nature of the exercise that is performed. None. Both authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. None.