Is the hypoxic ventilatory response driven by blood oxygen concentration?

Milsom, William K.; Wang, Tobias

doi:10.1242/jeb.151316

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…Notably however, the lack of a ventilatory response to decreases in Ca O 2 is not a universal finding, as others found that decreases in Ca O 2 alone caused similar increase in V E despite no change in Pa O 2 (6). As such, there is still debate in the comparative literature regarding the exact role of Ca O 2 in the acute hypoxic ventilatory response (18). Difficulties with interpreting the above findings are the vastly different species and experimental technical limitations.…”

Section: Discussionmentioning

confidence: 99%

Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

Dominelli

Baker

Wiggins

et al. 2019

Journal of Applied Physiology

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Arterial oxygen tension and oxyhemoglobin saturation ([Formula: see text]) decrease in parallel during hypoxia. Distinguishing between changes in oxygen tension and oxygen content as the relevant physiological stimulus for cardiorespiratory alterations remains challenging. To overcome this, we recruited nine individuals with hemoglobinopathy manifesting as high-affinity hemoglobin [HAH; partial pressure at 50% [Formula: see text] (P50) = 16 ± 0.4 mmHg] causing greater [Formula: see text] at a given oxygen partial pressure compared with control subjects ( n = 12, P50 = 26 ± 0.4 mmHg). We assessed ventilatory and cardiovascular responses to acute isocapnic hypoxia, iso-oxic hypercapnia, and 20 min of isocapnic hypoxia (arterial Po2 = 50 mmHg). Blood gas alterations were achieved with dynamic end-tidal forcing. When expressed as a function of the logarithm of oxygen partial pressure, ventilatory sensitivity to hypoxia was not different between groups. However, there was a significant difference when expressed as a function of [Formula: see text]. Conversely, the rise in heart rate was blunted in HAH subjects when expressed as a function of partial pressure but similar when expressed as a function of [Formula: see text]. Ventilatory sensitivity to hypercapnia was not different between groups. During sustained isocapnic hypoxia, the rise in minute ventilation was similar between groups; however, heart rate was significantly greater in the controls during 3 to 9 min of exposure. Our results support the notion that oxygen tension, not content, alters cellular Po2 in the chemosensors and drives the hypoxic ventilatory response. Our study suggests that in addition to oxygen partial pressure, oxygen content may also influence the heart rate response to hypoxia. NEW & NOTEWORTHY We dissociated the effects of oxygen content and pressure of cardiorespiratory regulation studying individuals with high-affinity hemoglobin (HAH). During hypoxia, the ventilatory response, expressed as a function of oxygen tension, was similar between HAH variants and controls; however, the rise in heart rate was blunted in the variants. Our work supports the notion that the hypoxic ventilatory response is regulated by oxygen tension, whereas cardiovascular regulation may be influenced by arterial oxygen content and tension.

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Section: Discussionmentioning

confidence: 99%

Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

Dominelli

Baker

Wiggins

et al. 2019

Journal of Applied Physiology

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“…This made perfect teleological sense because the ventilatory response matched blood oxygen delivery, and, as pointed out by the authors, raised the interesting question of whether the oxygen-sensitive chemoreceptors in reptiles respond to the partial pressure of oxygen or oxygen concentration. Subsequent studies with Luiz Guilherme Branco and Tobias Wang (both PhD students in Mogens lab in 1991) pointed to partial pressure as the regulated variable ( Wang et al, 1994 ), but the debate continues to this day ( Milsom and Wang, 2017 ). ( Figure 6 )…”

Section: Postdoctoral Studies At Max Planck Institute For Experimentamentioning

confidence: 99%

Mogens Lesner Glass (1946-2018)

Wang

Wood²

2020

Braz J Med Biol Res

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Preto. He provided important contributions to comparative respiratory physiology and trained a number of excellent students in Brazil, many of whom are now leading researchers at various universities in Southeastern Brazil. His role as a mentor and his work has, and will continue to have, a lasting impact on the study of comparative physiology in Brazil. (Figure 1) Childhood and becoming a biologist Mogens was born in Aarhus, the second largest city in Denmark, on March 24, 1946 and attended a private school (Foraeldreskolen) and finished high school nearby, in 1965. In high school (Marselisborg Gymnasium), he followed the linguistic line and therefore received little education in mathematics and physics. Thus, after having spent a year at Askov Højskole, following a centuryold Danish tradition of attending a boarding school for

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“…Air-breathing vertebrates ventilate their lungs to obtain O 2 and to eliminate the CO 2 that is produced by respiration, and lung ventilation is regulated by central chemoreceptors that are sensitive to CO 2 /pH (Branco and Wood, 1993;Santin et al, 2013;Zena et al, 2016b;Milsom et al, 2022). The peripheral chemoreceptors are typically stimulated when arterial partial pressure of O 2 (P O2 ) is below that required for complete saturation of haemoglobin (Milsom and Wang, 2017;Milsom et al, 2022). The ventilatory responses to hypercapnia (high CO 2 ) are very robust in air-breathing vertebrates, while the oxygen shortage typically needs to be rather severe before a ventilatory response is elicited (Dejours, 1988).…”

Section: Introductionmentioning

confidence: 99%

The reduction in arterial pH with increased temperature is not affected by hyperoxia in toads (Rhinella marina) and pythons (Python molurus)

Castro,

Leite,

Wang

2023

Journal of Experimental Biology

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It is well established that arterial pH decreases with increased temperature in amphibians and reptiles through an elevation of arterial PCO2, but the underlying regulation remains controversial. The alphastat hypothesis ascribes the pH fall to a ventilatory regulation of protein ionisation, but the pH reduction with temperature is lower than predicted by the pKa change of the imidazole group on histidine. We hypothesised that arterial pH decreases at high, but not at low, temperatures when toads (Rhinella marina) and snakes (Python molurus) are exposed to hyperoxia. In toads, hyperoxia caused similar elevations of arterial PCO2 at 20 and 30°C, indicative of a temperature-independent oxygen-mediated drive to breathing, whereas PCO2 was unaffected by hyperoxia in snakes at 25 and 35°C. These findings do not support our hypothesis of an increased oxygen-mediated drive to breathing as body temperature increases.

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Is the hypoxic ventilatory response driven by blood oxygen concentration?

Cited by 7 publications

References 9 publications

Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

Mogens Lesner Glass (1946-2018)

The reduction in arterial pH with increased temperature is not affected by hyperoxia in toads (Rhinella marina) and pythons (Python molurus)

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