Effect of Central Chemoreceptors on the Peripheral Chemoreflex Response to Hypoxia

In the absence of central chemoreceptor input, the slope of the hypoxic ventilatory response (HVR) to progressive oxyhemoglobin desaturation (L·min-1·mmHg-1·%SaO2-1) – a measure of peripheral chemoreflex sensitivity – increases linearly with carbon dioxide tension (PCO2). We assessed whether this relationship remains linear with increasing central PCO2 in humans. Over four days, 20 participants (10 females; mean±SD age: 24±4 years) completed three repetitions of modified rebreathing with end-tidal PO2 (PETO2) clamped at 150, 70, 60, and 45 mmHg. End-tidal PCO2 (PETCO2), PETO2, ventilation (V̇E), and SaO2 were measured breath-by-breath by dual gas analyser, pneumotach, and pulse oximetry. The V̇E vs PETCO2 relationship in the hyperoxic test gave the central chemoreflex response to PCO2 and the hypoxic tests provided a combined central-peripheral chemoreflex response. The V̇E vs PETCO2 relationship of repeated trials were linear-interpolated, combined, averaged into 1 mmHg bins, and fit with a linear function (V̇ES, L·min-1·mmHg-1) to provide hyperoxic and hypoxic profiles. HVR was computed at 1 mmHg intervals of PETCO2 as follows: the difference in V̇E between the three hypoxic profiles and the hyperoxic profile (ΔV̇E) was calculated; these three ΔV̇E values were plotted against their corresponding SaO2; and linear regression determined HVR (L·min-1·mmHg-1·%SaO2-1). Steps were repeated at each PETCO2 to produce the HVR vs PCO2 relationship. Each participant’s HVR vs PETCO2 relationship was fit with a linear and polynomial function and Akaike Information Criterion identified the best-fit model. One-way repeated measures analysis of variance assessed between-condition differences. V̇ES rose (p<0.001) with isoxic PO2 from 3.7±1.5 L·min-1·mmHg-1 at 150 mmHg to 4.4±1.8, 5.0±1.6, and 6.0±2.2 L·min-1·mmHg-1 at 70, 60, and 45 mmHg, respectively. Mean SaO2 fell progressively (99.3%, 93.7%, 90.4%, and 80.5% for 150, 70, 60, and 45 mmHg, respectively; p<0.001). In all individuals, HVR increased with PETCO2 and this relationship was best described by a linear model in 75% of participants. In most participants, the peripheral chemoreflex-mediated HVR maintained a linear relationship with PETCO2 despite increasing central chemoreflex activation. Data suggest that central chemoreceptors did not alter the peripheral chemoreflex response to low O2. Natural Sciences and Engineering Research Council of Canada This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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