Teppema LJ, Dahan A. The Ventilatory Response to Hypoxia in Mammals: Mechanisms, Measurement, and Analysis. Physiol Rev 90: 675-754, 2010; doi:10.1152/physrev.00012.2009.-The respiratory response... Show moreTeppema LJ, Dahan A. The Ventilatory Response to Hypoxia in Mammals: Mechanisms, Measurement, and Analysis. Physiol Rev 90: 675-754, 2010; doi:10.1152/physrev.00012.2009.-The respiratory response to hypoxia in mammals develops from an inhibition of breathing movements in utero into a sustained increase in ventilation in the adult. This ventilatory response to hypoxia (HVR) in mammals is the subject of this review. The period immediately after birth contains a critical time window in which environmental factors can cause long-term changes in the structural and functional properties of the respiratory system, resulting in an altered HVR phenotype. Both neonatal chronic and chronic intermittent hypoxia, but also chronic hyperoxia, can induce such plastic changes, the nature of which depends on the time pattern and duration of the exposure (acute or chronic, episodic or not, etc.). At adult age, exposure to chronic hypoxic paradigms induces adjustments in the HVR that seem reversible when the respiratory system is fully matured. These changes are orchestrated by transcription factors of which hypoxia-inducible factor 1 has been identified as the master regulator. We discuss the mechanisms underlying the HVR and its adaptations to chronic changes in ambient oxygen concentration, with emphasis on the carotid bodies that contain oxygen sensors and initiate the response, and on the contribution of central neurotransmitters and brain stem regions. We also briefly summarize the techniques used in small animals and in humans to measure the HVR and discuss the specific difficulties encountered in its measurement and analysis. Show less
Teppema LJ, van Dorp EL, Dahan A. Arterial [H+]and the ventilatory response to hypoxia in humans: influence of acetazol-amide-induced metabolic acidosis. Am J Physiol Lung Cell Mol Physiol 298: L89... Show moreTeppema LJ, van Dorp EL, Dahan A. Arterial [H+]and the ventilatory response to hypoxia in humans: influence of acetazol-amide-induced metabolic acidosis. Am J Physiol Lung Cell Mol Physiol 298: L89-L95, 2010. First published October 30, 2009; doi:10.1152/ajplung.00255.2009. - In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of ( hypoxic - normoxic) ventilation over ( hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio ( hypoxic - normoxic) ventilation over (logPaO(2) hypoxia - logPaO(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 similar to 50 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-CO2, and a parallel leftward shift of the ventilatory CO2 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 arterial [(+)] ([H+](a)) to higher values of [H+](a) without altering its slope, indicating that it did not affect the O-2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H+ 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+](a) response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated. Show less
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