Reappraisal of systemic venous chemoreceptors: might they explain the matching of breathing to metabolic rate in humans?

New Findings

• What is the topic of this review?

  One of the major unanswered questions in physiology is that of how breathing matches metabolic rate. Venous chemoreceptors seem to have been dismissed since the 1960s.

• What advances does it highlight?

  New evidence shows that their apparent dismissal needs reappraisal.

  • The paper on which this depends has more than one interpretation, and another paper obtained the opposite result.
  • Previous search ignored all locations between skeletal muscle and the right heart.
  • Oxygen sensors other than the arterial chemoreceptors do exist. Heymans and colleagues originally demonstrated some residual breathing response to hypoxia in sino-aortically denervated animals. Similar results occur in humans.

One of the major unanswered questions in physiology is that of how breathing matches metabolic rate. The existence in humans of venous chemoreceptors that might control breathing seems to have been dismissed since the 1960s. New evidence has emerged showing that this apparent dismissal needs reappraisal. Firstly, the paper in humans on which this depends has more than one interpretation. Moreover, a previous paper obtained the opposite result and is not cited. Secondly, previous search for venous chemoreceptors failed to examine all venous locations between skeletal muscle and the right heart and lungs. Thirdly, oxygen sensors other than the arterial chemoreceptors do exist. Heymans himself originally demonstrated some residual breathing response to hypoxia in sino-aortically denervated animals. Others confirm a residual breathing response to hypoxia in mammals, including humans. There is now considerable interest in the importance of afferent feedback in controlling the cardiovascular and respiratory systems. Moreover, it is now clear that arterial, aortic and central chemoreceptors have no role in explaining how breathing matches metabolic rate. These together provide a timely reminder that venous chemoreceptors remain ideal candidates still to be considered as metabolic rate sensors to explain matching in humans. Firstly, this is because venous and values do change appropriately in proportion to metabolic rate, so a metabolic rate signal sufficient to drive breathing might already exist. Secondly, chemoreceptor-like anatomical structures are present in the systemic venous system but remain unexplored. Finally, no extant experimental evidence precludes their existence.

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