{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:21:57Z","timestamp":1787674917011,"version":"build-2784847793"},"reference-count":44,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100016156","name":"U.S. Army Medical Research and Development Command","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:p> Military and\/or emergency services personnel may be required to perform high-intensity physical activity during exposure to elevated inspired carbon dioxide (CO<jats:sub>2<\/jats:sub>). Although many of the physiological consequences of hypercapnia are well characterized, the effects of graded increases in inspired CO<jats:sub>2<\/jats:sub> on self-paced endurance performance have not been determined. The aim of this study was to compare the effects of 0%, 2%, and 4% inspired CO<jats:sub>2<\/jats:sub> on 2-mile run performance, as well as physiological and perceptual responses during time trial exercise. Twelve physically active volunteers (peak oxygen uptake = 49\u2009\u00b1\u20095 mL\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>; 3 women) performed three experimental trials in a randomized, single-blind, crossover manner, breathing 21% oxygen with either 0%, 2%, or 4% CO<jats:sub>2<\/jats:sub>. During each trial, participants completed 10 min of walking at \u223c40% peak oxygen uptake followed by a self-paced 2-mile treadmill time trial. One participant was unable to complete the 4% CO<jats:sub>2<\/jats:sub> trial due to lightheadedness during the run. Compared with the 0% CO<jats:sub>2<\/jats:sub> trial, run performance was 5\u2009\u00b1\u20093% and 7\u2009\u00b1\u20093% slower in the 2% and 4% CO<jats:sub>2<\/jats:sub> trials, respectively (both P &lt; 0.001). Run performance was significantly slower with 4% versus 2% CO<jats:sub>2<\/jats:sub> ( P = 0.046). The dose-dependent performance impairments were accompanied by stepwise increases in mean ventilation, despite significant reductions in running speed. Dyspnea and headache were significantly elevated during the 4% CO<jats:sub>2<\/jats:sub> trial compared with both the 0% and 2% trials. Overall, our findings show that graded increases in inspired CO<jats:sub>2<\/jats:sub> impair endurance performance in a stepwise manner in healthy humans. <\/jats:p>","DOI":"10.1152\/ajpregu.00132.2022","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T14:56:30Z","timestamp":1662994590000},"page":"R638-R647","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Influence of graded hypercapnia on endurance exercise performance in healthy humans"],"prefix":"10.1152","volume":"323","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-6988","authenticated-orcid":false,"given":"Benjamin J.","family":"Ryan","sequence":"first","affiliation":[{"name":"Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, 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