Ratio of venous-to-arterial PCO(2) 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 ([Formula: see text] ), ΔPCO(2)/ΔO(2), and ΔCCO(2D)/ΔO(2) were obtained every 15 min. Beyond DO(2crit), [Formula: see text] 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.