Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of
            <scp>CO</scp>
            <sub>2</sub>
            and O
            <sub>2</sub>
            and in Arterial pH

Cunningham, D. J.; Robbins, Peter A.; Wolff, Christopher B.

doi:10.1002/cphy.cp030215

Cited by 142 publications

(183 citation statements)

References 316 publications

Supporting

Mentioning

167

Contrasting

Order By: Relevance

“…The magnitude of the AHR can be influenced by many factors such as the background arterial PCO 2 . A rise in Pa CO 2 augments the AHR, and this is known as multiplicative O 2 -CO 2 interaction (6,7,10). This phenomenon is thought to reside in the carotid bodies (15,22,26), but its mechanism at the molecular level in oxygen-sensitive type I cells remains to be elucidated (29).…”

mentioning

confidence: 99%

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Teppema

Dörp

Dahan

2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

ϩ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic Ϫ normoxic) ventilation over (hypoxic Ϫ normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic Ϫ normoxic) ventilation over (logPa O 2 hypoxia Ϫ logPa O 2 normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal PO2 to ϳ50 Torr lasting 5 min each at three different constant end-tidal PCO2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa CO 2 , and a parallel leftward shift of the ventilatory CO 2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O 2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arteriala without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H ϩ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H ϩ ]a response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated. hypoxic sensitivity; O2-CO2 interaction; hydrogen ions; CO2 THE HYPOXIC VENTILATORY RESPONSE in humans is biphasic and consists of an initial rise in ventilation initiated by the carotid bodies followed by a secondary roll-off, usually designated as hypoxic ventilatory decline (HVD) (8,13,16,25). The magnitude of this decline is proportionally related to the initial rise in ventilation in response to acute hypoxia and thus also to the intensity of the hypoxic stimulus (8,18,25). Measurement of the ventilatory response to hypoxia without the "confounding" influence of HVD is possible by exposing subjects to brief step-wise changes in end-tidal PO 2 lasting 3-5 min, a period too short for HVD to develop. Consequently, the ventilatory response to such an acute hypoxic challenge (the acute hypoxic response, AHR) is attributed to the peripheral chemoreceptors in the carotid bodies. The magnitude of the AHR can be influenced by many factors such as the background arterial PCO 2 . A rise in Pa CO 2 augments the AHR, and this is known as multiplicative O 2 -CO 2 interaction (6, 7, 10). This phenomenon is thought to reside in the carotid bodies (15,22,26), but its mechanism at the molecular level in oxygen-sensitive type I cells remains to be elucidated (29). A rise in Pa CO 2 not only leads to extracellular acidosis (acidemia) but also to increases in ...

show abstract

mentioning

confidence: 99%

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Teppema

Dörp

Dahan

2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Hypoxia increases alveolar ventilation, primarily by stimulation of the peripheral chemoreceptors (18), although a central stimulatory effect on ventilation has also been reported (47, 64). Paradoxically, hyperoxia, which decreases peripheral chemoreceptor activity (18), also increases ventilation, thus suggesting that hyperoxia has a central effect (17,32,48).…”

mentioning

confidence: 99%

Hyperbaric oxygen and chemical oxidants stimulate CO₂/H⁺-sensitive neurons in rat brain stem slices

Mulkey

Henderson²,

Putnam³

et al. 2003

Journal of Applied Physiology

153

View full text Add to dashboard Cite

. Hyperbaric oxygen and chemical oxidants stimulate CO2/H ϩ -sensitive neurons in rat brain stem slices. J Appl Physiol 95: 910-921, 2003. First published April 18, 2003 10.1152/japplphysiol.00864. 2002-Hyperoxia, a model of oxidative stress, can disrupt brain stem function, presumably by an increase in O2 free radicals. Breathing hyperbaric oxygen (HBO 2) initially causes hyperoxic hyperventilation, whereas extended exposure to HBO 2 disrupts cardiorespiratory control. Presently, it is unknown how hyperoxia affects brain stem neurons. We have tested the hypothesis that hyperoxia increases excitability of neurons of the solitary complex neurons, which is an important region for cardiorespiratory control and central CO2/H ϩ chemoreception. Intracellular recordings were made in rat medullary slices during exposure to 2-3 atm of HBO 2, HBO 2 plus antioxidant (Trolox C), and chemical oxidants (N-chlorosuccinimide, chloramine-T). HBO 2 increased input resistance and stimulated firing rate in 38% of neurons; both effects of HBO 2 were blocked by antioxidant and mimicked by chemical oxidants. Hypercapnia stimulated 32 of 60 (53%) neurons. Remarkably, these CO 2/H ϩ -chemosensitive neurons were preferentially sensitive to HBO2; 90% of neurons sensitive to HBO2 and/or chemical oxidants were also CO2/H ϩ chemosensitive. Conversely, only 19% of HBO2-insensitive neurons were CO2/H ϩ chemosensitive. We conclude that hyperoxia decreases membrane conductance and stimulates firing of putative central CO2/H ϩ -chemoreceptor neurons by an O2 free radical mechanism. These findings may explain why hyperoxia, paradoxically, stimulates ventilation. central chemoreception; reactive oxygen species; cardiorespiratory control; intracellular recording; hyperoxia THE CENTRAL NERVOUS SYSTEM (CNS) is especially sensitive to oxidative stress. For example, hyperoxia, which is a popular model of oxidative stress, induced by breathing high levels of oxygen at hyperbaric pressure [i.e., hyperbaric oxygen (HBO 2 )], can rapidly disrupt neural function and result in CNS O 2 toxicity (16). Neurological responses to hyperoxia vary, depending on the oxygen tension in the brain and the duration of exposure. For example, the CNS response to hyperoxia can range from moderate, but reversible, changes in neural activity (7,49), to violent and reversible seizures at higher levels of oxygen (16), to irreversible motor deficits and ultimately death at the highest dosages of hyperoxia (16). In each of these instances, the effects of hyperoxia on the CNS are thought to result from increased production and accumulation of O 2 free radicals and subsequent oxidation of cellular components vital to maintaining normal mechanisms of neuronal excitability (16).The cardiorespiratory centers of the brain stem, similarly, are sensitive to a broad range of inspired oxygen. Hypoxia increases alveolar ventilation, primarily by stimulation of the peripheral chemoreceptors (18), although a central stimulatory effect on ventilation has also been reported (47, 64). Paradoxica...

show abstract

“…For the hypothesis to be feasible, at least the following two points sould be satisfied: 1) the carotid body provides a rate sensitivity to Pa~o2 change; and 2) the carotid body responds only to the rate of rise of Pa~o2. The feasibility of these assumptions will be discussed hereinafter (some discussion has already been made by CUNNINGHAM et al, 1986).…”

Section: Resultsmentioning

confidence: 99%

Role of carbon dioxide oscillation in the control of respiration in the anesthetized dog.

Takahashi

Ashe

1989

Jpn.J.Physiol

View full text Add to dashboard Cite

In order to examine the role of respiratory oscillation of Paco2 (CO2 oscillation) in the control of respiration, we performed veno-venous bypass using a membrane lung in 10 anesthetized paralyzed dogs, where the dog was put on fixed mechanical ventilation so that we could keep average Paco2 and Pa02 constant by adjusting FIco2 and Fio2 during CO2 loading/unloading. By venous CO2 loading/unloading we could widely change the CO2 output from the lung (11-440 of the control) resulting in large changes in the arterial CO2 oscillations (50-280% of the control for the maximum rate of rise of Paco2 and 40-350°c of the control for the maximum rate of fall of Paco2), which was measured by a rapidly responding intra-arterial pH electrode. Despite such wide variations in CO2 oscillations we did not find any consistent change in the respiratory center output (minute phrenic activity). This held true after compensating the changes in the minute phrenic activity for the CO2 sensitivity of each individual dog. Thus, the present results may suggest that the CO2 oscillation plays little role in the control of respiration in mild increase in Vco2.

show abstract

Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of CO ₂ and O ₂ and in Arterial pH

Cited by 142 publications

References 316 publications

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Hyperbaric oxygen and chemical oxidants stimulate CO₂/H⁺-sensitive neurons in rat brain stem slices

Role of carbon dioxide oscillation in the control of respiration in the anesthetized dog.

Contact Info

Product

Resources

About

Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of CO 2 and O 2 and in Arterial pH

Cited by 142 publications

References 316 publications

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices

Role of carbon dioxide oscillation in the control of respiration in the anesthetized dog.

Contact Info

Product

Resources

About

Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of CO ₂ and O ₂ and in Arterial pH

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Hyperbaric oxygen and chemical oxidants stimulate CO₂/H⁺-sensitive neurons in rat brain stem slices