CrossTalk opposing view: the hypoxic ventilatory response does not include a central, excitatory hypoxia sensing component

Teppema, Luc J.

doi:10.1113/jp275708

Cited by 11 publications

(14 citation statements)

References 29 publications

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“…Our colleague's thesis is that the work from Gourine, Funk and coworkers ‘does not provide conclusive evidence for their hypothesis of an involvement of astrocytes as central O 2 sensors in the ventilatory response to hypoxia (HVR) especially in awake animals and humans’ (Teppema, ). While we agree that unequivocal evidence is not yet available, we emphasize that the converse is also true; there is no conclusive evidence against this hypothesis.…”

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confidence: 99%

“…To begin, many criticisms or alternative interpretations offered by our colleague appear to be based on the invalid assumption that astrocytes and their properties are similar throughout the CNS; e.g. he states ‘… given the CO 2 sensitivity of astrocytes’; ‘that O 2 sensitivity is a general property of astrocytes …’; and ‘… the resulting fall in

P_{aC O_{2}}

would cause vasoconstriction …’ (Teppema, ). The view of astrocytes as a homogeneous cell population is not tenable (Turovsky et al .…”

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confidence: 99%

“…. ' (Teppema, 2018). The view of astrocytes as a homogeneous cell population is not tenable (Turovsky et al 2016;Chai et al 2017).…”

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confidence: 99%

“…Second, CB denervation studies are historically important, but, as discussed at length from both sides (Gourine & Funk, 2017;Funk & Gourine, 2018;Teppema, 2018), unlikely to ever be conclusive. Thus, the focus of our colleague on data from anaesthetized or conscious peripherally chemodenervated animals (Gourine et al 2005;Angelova et al 2015;Rajani et al 2018) is not insightful.…”

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confidence: 99%

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Rebuttal from Gregory D. Funk and Alexander V. Gourine

Funk

Gourine

2018

The Journal of Physiology

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confidence: 99%

P_{aC O_{2}}

would cause vasoconstriction …’ (Teppema, ). The view of astrocytes as a homogeneous cell population is not tenable (Turovsky et al .…”

mentioning

confidence: 99%

“…. ' (Teppema, 2018). The view of astrocytes as a homogeneous cell population is not tenable (Turovsky et al 2016;Chai et al 2017).…”

mentioning

confidence: 99%

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confidence: 99%

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Rebuttal from Gregory D. Funk and Alexander V. Gourine

Funk

Gourine

2018

The Journal of Physiology

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“…It has been further suggested that central hypoxia sensed by brainstem astrocytes regulates brain oxygenation and D O 2 by adjusting pulmonary ventilation and cardiac output (Marina et al 2018). However, in this respect, it should be noted that, although CBF in humans responds to brain hypoxia as a result of anaemia and carbon monoxide (Paulson et al 1973), the ventilatory response is absent (Ren et al 2001) and the physiological significance of these observations of a central hypoxia sensor is disputed (Teppema, 2018).…”

Section: The Cbf Controllermentioning

confidence: 99%

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Duffin

Hare

Fisher

2020

The Journal of Physiology

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Key points The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia. Abstract A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model simulation assesses the physiological plausibility of some currently hypothesized cerebral blood flow control mechanisms in hypoxia and anaemia, and also examines the impact of anaemia and hypoxia on brain hypoxia. In addition, carbon dioxide is examined for its impact on brain hypoxia in the context of concomitant changes associated with anaemia and hypoxia. The model calculations are based on a single compartment of brain tissue with constant metabolism and perfusion pressure, as well as previously developed equations describing oxygen and carbon dioxide carriage in blood. Experimental data are used to develop the control equations for cerebral blood flow regulation. The interactive model illustrates that there are clear interactions of anaemia, hypoxia and carbon dioxide in the determination of cerebral blood flow and brain tissue oxygen tension. In both anaemia and hypoxia, cerebral blood flow increases to maintain oxygen delivery, with brain hypoxia increasing when cerebral blood flow control mechanisms are impaired. Hypocapnia superimposes its effects, increasing brain hypoxia. Hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, and this effect is exacerbated when blood flow regulation is degraded by conditions that negatively impact cerebrovascular control. Differences in brain hypoxia in anaemia and hypoxia suggest that brain oxygen tension is not a plausible sensor for cerebral blood flow control.

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Perinatal Hypoxemia and Oxygen Sensing

Mouradian

Lakshminrusimha

Konduri

2021

Comprehensive Physiology

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The development of the control of breathing begins in utero and continues postnatally. Fetal breathing movements are needed for establishing connectivity between the lungs and central mechanisms controlling breathing. Maturation of the control of breathing, including the increase of hypoxia chemosensitivity, continues postnatally. Insufficient oxygenation, or hypoxia, is a major stressor that can manifest for different reasons in the fetus and neonate. Though the fetus and neonate have different hypoxia sensing mechanisms and respond differently to acute hypoxia, both responses prevent deviations to respiratory and other developmental processes. Intermittent and chronic hypoxia pose much greater threats to the normal developmental respiratory processes. Gestational intermittent hypoxia, due to maternal sleep-disordered breathing and sleep apnea, increases eupneic breathing and decreases the hypoxic ventilatory response associated with impaired gasping and autoresuscitation postnatally. Chronic fetal hypoxia, due to biologic or environmental (i.e. high-altitude) factors, is implicated in fetal growth restriction and preterm birth causing a decrease in the postnatal hypoxic ventilatory responses with increases in irregular eupneic breathing. Mechanisms driving these changes include delayed chemoreceptor development, catecholaminergic activity, abnormal myelination, increased astrocyte proliferation in the dorsal respiratory group, among others. Long-term high-altitude residents demonstrate favorable adaptations to chronic hypoxia as do their offspring. Neonatal intermittent hypoxia is common among preterm infants due to immature respiratory systems and thus, display a reduced drive to breathe and apneas due to insufficient hypoxic sensitivity. However, ongoing intermittent hypoxia can enhance hypoxic sensitivity causing ventilatory overshoots followed by apnea; the number of apneas is positively correlated with degree of hypoxic sensitivity in preterm infants. Chronic neonatal hypoxia may arise from fetal complications like maternal smoking or from postnatal cardiovascular problems, causing blunting of the hypoxic ventilatory responses throughout at least adolescence due to attenuation of carotid body fibers responses to hypoxia with potential roles of brainstem serotonin, microglia, and inflammation, though these effects depend on the age in which chronic hypoxia initiates. Fetal and neonatal intermittent and chronic hypoxia are implicated in preterm birth and complicate the respiratory system through their direct effects on hypoxia sensing mechanisms and interruptions to the normal developmental processes. Thus, precise regulation of oxygen homeostasis is crucial for normal development of the respiratory control network.

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CrossTalk opposing view: the hypoxic ventilatory response does not include a central, excitatory hypoxia sensing component

Cited by 11 publications

References 29 publications

Rebuttal from Gregory D. Funk and Alexander V. Gourine

Rebuttal from Gregory D. Funk and Alexander V. Gourine

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Perinatal Hypoxemia and Oxygen Sensing

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