On the existence of a central respiratory oxygen sensor

Alexander V. Gourine, Gregory D. Funk
2017 Journal of applied physiology  
Gourine AV, Funk GD. On the existence of a central respiratory oxygen sensor. A commonly held view that dominates both the scientific and educational literature is that in terrestrial mammals the central nervous system lacks a physiological hypoxia sensor capable of triggering increases in lung ventilation in response to decreases in PO 2 of the brain parenchyma. Indeed, a normocapnic hypoxic ventilatory response has never been observed in humans following bilateral resection of the carotid
more » ... of the carotid bodies. In contrast, almost complete or partial recovery of the hypoxic ventilatory response after denervation/removal of the peripheral respiratory oxygen chemoreceptors has been demonstrated in many experimental animals when assessed in an awake state. In this essay we review the experimental evidence obtained using in vitro and in vivo animal models, results of human studies, and discuss potential mechanisms underlying the effects of CNS hypoxia on breathing. We consider experimental limitations and discuss potential reasons why the recovery of the hypoxic ventilatory response has not been observed in humans. We review recent experimental evidence suggesting that the lower brain stem contains functional oxygen sensitive elements capable of stimulating respiratory activity independently of peripheral chemoreceptor input. astrocyte; brain stem; carotid body; chemosensitivity; hypoxia; hypoxic ventilatory response; oxygen THE HIGH METABOLIC RATE of the brain associated with the activities of millions of nerve cells processing information requires constant, optimal nutrient and oxygen supply, as well as effective removal of carbon dioxide and other metabolic waste products. Adequate oxygenation of the arterial blood supplying the brain is monitored by specialized respiratory oxygen sensors located in the carotid bifurcation (carotid bodies) and, in some species, the aortic arch (aortic bodies). These peripheral chemoreceptors detect decreases in the arterial PO 2 and transmit chemosensory information to the brain stem respiratory centers, triggering adaptive changes in breathing (34, 48). This simple "textbook" view on chemosensory control of breathing implies that detection of the arterial partial pressure of O 2 (PO 2 ) at the level of the peripheral chemoreceptor is sufficient to ensure appropriate oxygenation of all regions of the brain. However, significant gradients of brain tissue oxygen levels have been demonstrated at normal arterial PO 2 (15, 31), supporting the contentious idea that many central neurons may operate in a low-oxygen environment (19, 44). Being located "upstream" from the central nervous system, arterial respiratory chemoreceptors are obviously not able to detect and respond to significant regional differences in brain oxygenation or local brain hypoxia. Moreover, all species of terrestrial mammals studied so far survive surgical denervation or removal of the peripheral oxygen chemoreceptors with no major adverse physiological consequences. Although hypoxic stress at sea level is rare, peripherally chemodenervated experimental animals and humans can tolerate hypoxia that might be common during sleep in a host of disparate disease states. A commonly held view that dominates both the scientific and educational literature is that the central nervous system lacks a physiological oxygen sensor capable of stimulating the brain stem respiratory network and lung ventilation in response to decreases in the PO 2 of the brain parenchyma. Indeed, no recovery of the normocapnic hypoxic ventilatory response has ever been reported in humans following bilateral resection of the carotid bodies (63). In contrast, significant evidence from experimental animal studies demonstrates almost complete or partial recovery of the hypoxic ventilatory response after surgical denervation/removal of the peripheral respiratory oxygen chemoreceptors (1, 2, 12-14, 18, 40, 42, 46, 51, 53, 54). In this short review article we discuss the experimental evidence obtained in studies of the hypoxic ventilatory response using animal models (in vitro and in vivo) as well as human subjects with denervated peripheral respiratory oxygen sensors. We consider potential reasons why the recovery of the hypoxic ventilatory response has not been observed in human Address for reprint requests and other correspondence:
doi:10.1152/japplphysiol.00194.2017 pmid:28522760 fatcat:izzgggu4obenrfnhwh5drfm7cq