Hide and seek anyone? Exchange of Views rebuttal: reply to Haouzi

We have enjoyed Dr Hauozi's Exchange of Views (Hauozi, 2020) on the topic of thin fibre muscle afferent involvement in the control of breathing in human exercise. The take home message from his article appears to be that this is a difficult area in which to work and the perfect, definitive experiment has yet to be performed. We would agree with that conclusion. The reductionist approach favoured in early experiments provided useful insight into control pathways but perhaps then as now the belief that only one variable was being changed at a time, that is ‘the scientific method’, was incorrect. The great challenge now is to integrate the factors that can influence exercise hyperpnoea into a model capable of explaining all the observed patterns of ventilation seen during all modes of exercise in health and disease. Their synergistic interactions and inbuilt redundancies add a level of complexity that is not surprising in such a fundamental system. In this respect, the approaches that we have discussed, whilst like all others can be criticised, do have merit in our view, despite Dr Haouzi's doubts. Sustained isometric exercise, for example, undoubtedly a natural everyday phenomenon, does restrict or completely occlude muscle blood flow, empty veins and cause muscle temperature to rise, often at quite low percentages of maximum voluntary force, in human muscles (Barcroft & Millen, 1939; Edwards, Hill, & McDonnell, 1972). Continuing this occlusion of circulation after the exercise has ended, by inflation of an upstream occluding cuff, prior to the cessation of exercise will remove the effects of central command and sustain many local factors in the previously exercised muscle, other than predictable time-dependent factors. Furthermore, if the preceding exercise period is modest then the effect of pain, as a confounding factor, can be minimized. Innovative experimental design, including good use of control experiments (e.g. Lam, Greenhough, Nazari, White, & Bruce, 2019), further improves the value of this approach. Methods designed to abolish the influence of thin fibre muscle afferents pharmacologically are very useful but may be of less value when attempting to investigate the effects of an intervention designed to modify the natural level of afferent activation during exercise, e.g. local muscle training. Comparison of ventilatory responses to isometric exercise of a trained muscle group in one limb with its pretraining data, or the contralateral untrained limb or other limbs at a different segmental level, following the training period (AlGhaith & White, 2018) surely negates many of the criticisms listed by Dr Hauozi. Given their limitations, each model on its own provides an interesting, albeit incomplete, glimpse of the mechanisms underlying exercise ventilatory control. However, perhaps problem solving can be benefited by comparing and contrasting data from multiple imperfect models in combination. Indeed, disagreements between models can provide new avenues of enquiry, enhancing understanding of complex integrative physiology (or at least demonstrate an absence of understanding). It would be ideal to only use near-perfect models … but in their continued absence, we strongly support using all the available information to better glimpse the elusive, and interacting, mechanisms of the exercise hyperpnoea. 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.