Combined effects of inspired oxygen, carbon dioxide, and carbon monoxide on oxygen transport and aerobic capacity

Crocker GH, Toth B, Jones JH. Combined effects of inspired oxygen, carbon dioxide, and carbon monoxide on oxygen transport and aerobic capacity. J Appl Physiol 115: 643-652, 2013. First published June 27, 2013; doi:10.1152/ japplphysiol.01407.2012.-We hypothesized that breathing hypoxic, hypercapnic, and CO-containing gases together reduces maximal aerobic capacity (VO _2max) as the sum of each gas' individual effect onVO_2max. To test this hypothesis, goats breathed combinations of inspired O2 fraction (FIO2) of 0.06-0.21 and inspired CO2 fraction of 0.00 or 0.05, with and without inspired CO that elevated carboxyhemoglobin fraction (FHbCO) to 0.02- 0.45, while running on a treadmill at speeds eliciting VO_2max. Individually, hypoxia and elevated FHbCO decreased fractional VO_2max (FVO_2max, fraction of a goat's VO_2max breathing air) in linear, dose-dependent manners; hypercapnia did not change VO_2max. Concomitant hypoxia and elevated FHbCO decreased VO_2max less than the individual gas effects summed, indicating their combined effects on VO _2max are attenuated, fitting the following regression: FVO _2max = 4.24 FIO2 + 0.519 FHbCO - 8.22 (FIO2 × FHbCO) + 0.117, (R2 = 0.965, P < 0.001). The FVO_2max correlated highly with total cardiopulmonary O2 delivery, not peripheral diffusing capacity, and with arterial O2 concentration (CaO2), not cardiac output. Hypoxia and elevated FHbCO decreased CaO2 by different mechanisms: hypoxia decreased arterial O2 saturation (SaO2), whereas elevated FHbCO decreased O2 capacitance {concentration of hemoglobin (Hb) available to bind O2 ([Hbavail])}. When breathing hypoxic gas (FIO2 0.12), CaO2 did not change with increasing FHbCO up to 0.30 because higher SaO2 of Hbavail offset decreased [Hbavail] due to the following: 1) hyperventilation with hypoxia and/or elevated FHbCO; 2) increased Hb affinity for O2 due to both Bohr and direct carboxyhemoglobin effects; and 3) the sigmoid relationship between O2 saturation and partial pressure elevating SaO2 more with hypoxia than normoxia.