{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:03:24Z","timestamp":1783933404450,"version":"3.55.0"},"reference-count":48,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:p>We hypothesized that breathing hypoxic, hypercapnic, and CO-containing gases together reduces maximal aerobic capacity (V\u0307o<jats:sub>2max<\/jats:sub>) as the sum of each gas' individual effect on V\u0307o<jats:sub>2max<\/jats:sub>. To test this hypothesis, goats breathed combinations of inspired O<jats:sub>2<\/jats:sub>fraction (Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>) of 0.06\u20130.21 and inspired CO<jats:sub>2<\/jats:sub>fraction of 0.00 or 0.05, with and without inspired CO that elevated carboxyhemoglobin fraction (F<jats:sub>HbCO<\/jats:sub>) to 0.02\u20130.45, while running on a treadmill at speeds eliciting V\u0307o<jats:sub>2max<\/jats:sub>. Individually, hypoxia and elevated F<jats:sub>HbCO<\/jats:sub>decreased fractional V\u0307o<jats:sub>2max<\/jats:sub>(F<jats:sub>V\u0307o<jats:sub>2max<\/jats:sub><\/jats:sub>, fraction of a goat's V\u0307o<jats:sub>2max<\/jats:sub>breathing air) in linear, dose-dependent manners; hypercapnia did not change V\u0307o<jats:sub>2max<\/jats:sub>. Concomitant hypoxia and elevated F<jats:sub>HbCO<\/jats:sub>decreased V\u0307o<jats:sub>2max<\/jats:sub>less than the individual gas effects summed, indicating their combined effects on V\u0307o<jats:sub>2max<\/jats:sub>are attenuated, fitting the following regression: F<jats:sub>V\u0307o<jats:sub>2max<\/jats:sub><\/jats:sub>= 4.24 Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>+ 0.519 F<jats:sub>HbCO<\/jats:sub>\u2212 8.22 (Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>\u00d7 F<jats:sub>HbCO<\/jats:sub>) + 0.117, ( R<jats:sup>2<\/jats:sup>= 0.965, P &lt; 0.001). The F<jats:sub>V\u0307o<jats:sub>2max<\/jats:sub><\/jats:sub>correlated highly with total cardiopulmonary O<jats:sub>2<\/jats:sub>delivery, not peripheral diffusing capacity, and with arterial O<jats:sub>2<\/jats:sub>concentration (Ca<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>), not cardiac output. Hypoxia and elevated F<jats:sub>HbCO<\/jats:sub>decreased Ca<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>by different mechanisms: hypoxia decreased arterial O<jats:sub>2<\/jats:sub>saturation (Sa<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>), whereas elevated F<jats:sub>HbCO<\/jats:sub>decreased O<jats:sub>2<\/jats:sub>capacitance {concentration of hemoglobin (Hb) available to bind O<jats:sub>2<\/jats:sub>([Hb<jats:sub>avail<\/jats:sub>])}. When breathing hypoxic gas (Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>0.12), Ca<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>did not change with increasing F<jats:sub>HbCO<\/jats:sub>up to 0.30 because higher Sa<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>of Hb<jats:sub>avail<\/jats:sub>offset decreased [Hb<jats:sub>avail<\/jats:sub>] due to the following: 1) hyperventilation with hypoxia and\/or elevated F<jats:sub>HbCO<\/jats:sub>; 2) increased Hb affinity for O<jats:sub>2<\/jats:sub>due to both Bohr and direct carboxyhemoglobin effects; and 3) the sigmoid relationship between O<jats:sub>2<\/jats:sub>saturation and partial pressure elevating Sa<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>more with hypoxia than normoxia.<\/jats:p>","DOI":"10.1152\/japplphysiol.01407.2012","type":"journal-article","created":{"date-parts":[[2013,6,29]],"date-time":"2013-06-29T07:26:40Z","timestamp":1372490800000},"page":"643-652","source":"Crossref","is-referenced-by-count":13,"title":["Combined 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