Muscles bring breathing alive

Abstract

Increases in ventilation, heart rate and systolic blood pressure accompany muscle exercise. Two neural mechanisms contribute to these effects. One of these is centrally mediated motor command, in which there is parallel activation of locomotor and autonomic brain circuits, while the other is feedback from muscle afferent receptors. The relative influence of the latter has been the focus of much attention in recent years.The population of afferent fibres in skeletal muscle is dominated by the small myelinated group III and unmyelinated group IV nerve fibres. Many of these thin fibre muscle afferents are sensitive to metabolites of muscle contraction, and it is well accepted that they play a significant role in the cardiovascular and respiratory response to exercise. Amongst the group III afferents are those that respond to mechanical deformation, and in the last 10 years good evidence has been provided to show that they also play a role in the cardiovascular changes associated with exercise (Hayes & Kaufman, 2001; Gladwell & Coote, 2002). Surprisingly, the role of these thin fibre muscle mechanoreceptors in respiratory control during exercise has been somewhat neglected, although it would be expected that cardiovascular and ventilatory changes are tightly integrated. The paper by Bruce & White (2011) in this issue of Experimental Physiology addresses this issue. In the early 1960s, Kao and colleagues published a series of papers describing cross-perfusion experiments in anaesthetized dogs in order to isolate potential sources of respiratory stimuli. They concluded that ‘It seems necessary to postulate a receptor in skeletal muscle which is responsible for the great intensity of ventilation during muscle exercise’ (see Kao, 1963). In human studies it is less clear, there being evidence for and against an effect of muscle contractions on ventilation. In particular, the close linear relationship between the work of muscles and oxygen consumption argues against a significant role for skeletal muscle mechanoreceptors. This would not be the case for muscle metaboreceptors. In humans, the metaboreceptors can be studied without the presence of command signals, by trapping metabolites produced during contraction with circulatory occlusion of the limb. In the last 10 years, a method has been developed that enables the muscle mechanoreceptor reflex to be studied, also in isolation of central command. This is achieved by passive stretch of a muscle group by dorsiflexion of the foot (Gladwell & Coote, 2002). These techniques are cleverly exploited in the paper by Bruce & White (2011), in which the influence on ventilation, the heart and blood pressure of either metaboreceptors or mechanoreceptors and both together are tested. The ingenious part of the study was to increase the subliminal fringe of the central neuronal circuits by increasing the excitability of central respiratory and other autonomic neurones by raising the inspired carbon dioxide concentration. This enabled the central synaptic effects to summate sufficiently to activate the respiratory and cardiovascular effectors so they could be observed and measured. The experiments controlled for the effects of metabolite sensitization of muscle afferents, hypercapnia-induced elevation of central respiratory drive and central command. The results convincingly show that facilitation of central neurones by hypercapnia results in a significant increase in ventilation when either muscle mechanoreceptors alone or muscle metaboreceptors alone are activated. The cardiovascular responses were also enhanced. This is the first clear indication that, during natural exercise, it is likely that thin fibre mechanoreceptors in skeletal muscles provide a significant signal to central autonomic pools of neurones that act together with the metaboreceptors and central command signals to ensure that the oxygen demands of exercise are precisely met. These results are not only important to the understanding of normal cardiorespiratory control during exercise but may also help to explain the reduced exercise capacity in patients with heart failure, hypertension and chronic obstructive pulmonary disease. In these patients, abnormal cardiorespiratory responses and intolerance of exercise may be linked to inappropriate reflex information generated by the muscle, as recently highlighted by Koba et al. (2009). The paper by Bruce & White (2011) adds weight to the conclusion of the study by Koba et al. (2009) that in these patients, accentuation of muscle mechanoreceptor signals is responsible for the enhanced cardiorespiratory responses in these disease states.