Teppema LJ, van Dorp EL, Dahan A
Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis. [JOURNAL ARTICLE]
Am J Physiol Lung Cell Mol Physiol 2009 Oct 30.
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 (log PaO2 hypoxia - logPaO2normoxia), 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 ~50 Torr lasting 5 min each at three different constant end-tidal PCO2 levels. Nine subjects ingested 250 mg acetazolamide or placebo every 8 hours for three days in a randomized double blind cross-over design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in PaCO2 and a parallel leftwards shift of the ventilatory CO2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arterial [H(+)] ([H(+)a]) to higher values of [H(+)a] without altering its slope indicating that it did not affect the O2-CO2 interaction. So in contrast to earlier belief CO2 and H(+) have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftwards 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. Key words: hypoxic sensitivity, O2-CO2 interaction, hydrogen ions, CO2.
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