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 ().

Six goats ran on a treadmill at speeds eliciting 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.

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.

This study quantifies the mechanisms by which O₂ delivery and peripheral diffusion interact to limit when O₂ delivery is reduced due to breathing hypoxic gas with elevated F _HbCO.