Purpose: To determine if and how hypoxia combined with elevated carboxyhaemoglobin fraction (F HbCO) affects peripheral diffusing capacity and O2 extraction in animals exercising at their maximal aerobic capacity ([Formula: see text]).
Methods: Six goats ran on a treadmill at speeds eliciting [Formula: see text] while breathing inspired O2 fractions (F IO2) of 0.21 or 0.12 with F HbCO 0.02 or 0.30. We measured O2 consumption and arterial and mixed-venous blood variables to assess how hypoxia and elevated F HbCO individually, and in combination, alter O2 transport and utilisation.
Results: Peripheral diffusing capacity did not differ among the four gas combinations (P = 0.867), whereas O2 extraction fraction increased with hypoxia [0.920 ± 0.018 (SD)] and decreased with elevated F HbCO (0.792 ± 0.038) compared to control (0.897 ± 0.032). Oxygen extraction increases with hypoxia due to the sigmoid relationship between O2 saturation (SO2) and O2 partial pressures (PO2) affecting low (hypoxia) and high (normoxia) PO2 differently. Oxygen extraction decreases with elevated F HbCO because elevated F HbCO increases haemoglobin (Hb) affinity for O2 and raises SO2, especially at very low (mixed-venous) PO2. Pulmonary gas exchange was impaired only with combined hypoxia and elevated F HbCO due to hypoxia decreasing alveolar PO2 and O2 flux coupled with elevated F HbCO increasing Hb affinity for O2 and decreasing the rate of PO2 increase for a given rise in SO2.
Conclusion: This study quantifies the mechanisms by which O2 delivery and peripheral diffusion interact to limit [Formula: see text] when O2 delivery is reduced due to breathing hypoxic gas with elevated F HbCO.