Johnson Nicole A, Strzalkowski Nicholas D J, Russell Monica K, Clermont Christian A, Demarty Jennifer M, Transfiguracion Leo C, Horton John F, Asmussen Michael J, Day Trevor A
Department of Biology, Faculty of Science and Technology, Mount Royal University, Calgary, Alberta, Canada.
Sport Product Testing, Canadian Sport Institute Alberta, Calgary, Alberta, Canada.
J Appl Physiol (1985). 2025 Aug 1;139(2):529-540. doi: 10.1152/japplphysiol.01014.2024. Epub 2025 Jun 17.
During acute exposure to hypoxia, peripheral respiratory chemoreceptors detect decreases in blood oxygenation, eliciting a hypoxic ventilatory response (HVR), which is enhanced with the duration and intensity of exposure (ventilatory acclimatization). The HVR protects oxygenation, but a secondary consequence is the elimination of arterial partial pressure of carbon dioxide ([Formula: see text]), resulting acutely in hypocapnia and respiratory alkalosis. With sustained exposure to hypobaric hypoxic conditions (e.g., high-altitude ascent; HA), the renal tubules reduce [Formula: see text] reabsorption and H excretion, excreting [Formula: see text] and retaining H, returning arterial pHa toward normal values. We aimed to characterize and compare blood oxygenation and acid-base homeostasis between two models of hypoxic exposure with matching inspired partial pressure of oxygen ([Formula: see text]) (∼74-76 mmHg): acute hypoxic exposure eliciting an HVR-mediated hypocapnia over 24 min versus sustained hypoxic-hypocapnia with incremental ascent to HA over 10 days. Using arterial blood draws, we measured arterial partial pressure of oxygen, [Formula: see text], [Formula: see text], [[Formula: see text]]a, and pHa, obtained before and following ) acute stepwise reductions in fraction of inspired oxygen ([Formula: see text]) for ∼24 min, with the last step being an [Formula: see text] of 0.12 ([Formula: see text] ≅ 74 mmHg) and ) sustained exposure to hypoxia during incremental ascent to 5,200 m over 10 days ([Formula: see text] ≅ 76 mmHg). We found that ) acute normobaric hypoxia elicited hypocapnia and respiratory alkalosis, as expected, and ) after sustained exposure to hypobaric hypoxia, there was persistent alkalosis, despite appreciable renal compensation. These findings highlight the time course and magnitude of integrated respiratory responses and subsequent renal compensation mounted by the kidneys, specifically that the hypoxia-mediated hypocapnia and respiratory alkalosis experienced at 5,200 m is likely beyond the threshold for a full renal compensation in healthy lowlanders. No studies have directly compared differences in oxygenation and acid-base balance after differential time courses of exposure to inspired hypoxia. We show that after exposure to the same hypoxic stimulus ([Formula: see text] ∼ 74-76 mmHg) over acute (24 min; [Formula: see text] of 0.12) versus sustained (10 days; 5,200 m) exposures, sustained exposure resulted in a persistent alkalemia, despite appreciable renal compensation. These findings highlight the time course and magnitude of integrated respiratory-renal responses and acid-base compensations in response to hypoxic exposure in healthy individuals.
在急性低氧暴露期间，外周呼吸化学感受器检测到血液氧合降低，引发低氧通气反应（HVR），该反应会随着暴露的持续时间和强度而增强（通气适应）。HVR可保护氧合，但其次要结果是动脉血二氧化碳分压（[公式：见原文]）降低，急性导致低碳酸血症和呼吸性碱中毒。在持续暴露于低压低氧条件下（如高原 ascent；HA），肾小管减少[公式：见原文]重吸收和H排泄，排泄[公式：见原文]并保留H，使动脉血pHa恢复到正常水平。我们旨在表征和比较两种低氧暴露模型之间的血液氧合和酸碱稳态，这两种模型的吸入氧分压（[公式：见原文]）相匹配（约74 - 76 mmHg）：急性低氧暴露在24分钟内引发HVR介导的低碳酸血症，与持续低氧 - 低碳酸血症并在10天内逐步上升至HA。通过采集动脉血，我们测量了动脉血氧分压、[公式：见原文]、[公式：见原文]、[[公式：见原文]]a和pHa，这些指标在以下情况前后获得：）急性逐步降低吸入氧分数（[公式：见原文]）约24分钟，最后一步是[公式：见原文]为0.12（[公式：见原文]≅74 mmHg），以及）在10天内逐步上升至5200米的过程中持续暴露于低氧环境（[公式：见原文]≅76 mmHg）。我们发现，）急性常压低氧如预期引发了低碳酸血症和呼吸性碱中毒，并且）在持续暴露于低压低氧后，尽管有明显的肾脏代偿，仍存在持续性碱中毒。这些发现突出了综合呼吸反应的时间进程和幅度以及随后肾脏进行的代偿，具体而言，在5200米处经历的低氧介导的低碳酸血症和呼吸性碱中毒可能超过了健康低地人完全肾脏代偿的阈值。尚无研究直接比较不同时间进程的吸入性低氧暴露后氧合和酸碱平衡的差异。我们表明，在急性（24分钟；[公式：见原文]为0.12）与持续（10天；5200米）暴露于相同低氧刺激（[公式：见原文]约74 - 76 mmHg）后，持续暴露导致了持续性碱血症，尽管有明显的肾脏代偿。这些发现突出了健康个体对低氧暴露的综合呼吸 - 肾脏反应和酸碱代偿的时间进程和幅度。
