Ratio of venous-to-arterial PCO2 to arteriovenous oxygen content difference during regional ischemic or hypoxic hypoxia

The purpose of the study was to evaluate the behavior of the venous-to-arterial CO 2 tension difference (ΔPCO 2 ) over the arterial-to-venous oxygen content difference (ΔO 2 ) ratio (ΔPCO 2 /ΔO 2 ) and the difference between venous-to-arterial CO 2 content calculated with the Douglas’ equation (ΔCCO 2D ) over ΔO 2 ratio (ΔCCO 2D /ΔO 2 ) and their abilities to reflect the occurrence of anaerobic metabolism in two experimental models of tissue hypoxia: ischemic hypoxia (IH) and hypoxic hypoxia (HH). We also aimed to assess the influence of metabolic acidosis and Haldane effects on the PCO 2 /CO 2 content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO 2 ) was lowered in a stepwise manner to decrease it beyond critical DO 2 (DO 2crit ) by lowering either arterial PO 2 (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO 2 , oxygen consumption ( V̇O₂ V ˙ O 2 ), ΔPCO 2 /ΔO 2 , and ΔCCO 2D /ΔO 2 were obtained every 15 min. Beyond DO 2crit , V̇O₂ V ˙ O 2 decreased, indicating dysoxia. ΔPCO 2 /ΔO 2 , and ΔCCO 2D /ΔO 2 increased significantly only after reaching DO 2crit in both models. At DO 2crit , ΔPCO 2 /ΔO 2 was significantly higher in the HH-model than in the IH-model (1.82 ± 0.09 vs. 1.39 ± 0.06, p = 0.002). At DO 2crit , ΔCCO 2D /ΔO 2 was not significantly different between the two groups (0.87 ± 0.05 for IH vs. 1.01 ± 0.06 for HH, p = 0.09). Below DO 2crit , we observed a discrepancy between the behavior of the two indices. In both models, ΔPCO 2 /ΔO 2 continued to increase significantly (higher in the HH-model), whereas ΔCCO 2D /ΔO 2 tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO 2 /CO 2 content relationship, but not the Haldane effect. ΔPCO 2 /ΔO 2 was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO 2 values, ΔPCO 2 /ΔO 2 did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO 2 –hemoglobin dissociation curve, and then it should be interpreted with caution.