{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:18:37Z","timestamp":1790486317836,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of the study was to evaluate the behavior of the venous-to-arterial CO<jats:sub>2<\/jats:sub> tension difference (\u0394PCO<jats:sub>2<\/jats:sub>) over the arterial-to-venous oxygen content difference (\u0394O<jats:sub>2<\/jats:sub>) ratio (\u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub>) and the difference between venous-to-arterial CO<jats:sub>2<\/jats:sub> content calculated with the Douglas\u2019 equation (\u0394CCO<jats:sub>2D<\/jats:sub>) over \u0394O<jats:sub>2<\/jats:sub> ratio (\u0394CCO<jats:sub>2D<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub>) 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<jats:sub>2<\/jats:sub>\/CO<jats:sub>2<\/jats:sub> content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO<jats:sub>2<\/jats:sub>) was lowered in a stepwise manner to decrease it beyond critical DO<jats:sub>2<\/jats:sub> (DO<jats:sub>2crit<\/jats:sub>) by lowering either arterial PO<jats:sub>2<\/jats:sub> (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO<jats:sub>2<\/jats:sub>, oxygen consumption (<jats:inline-formula><jats:alternatives><jats:tex-math>$${\\dot{\\text{V}}\\text{O}}_{2}$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:msub>\n                    <mml:mrow>\n                      <mml:mover>\n                        <mml:mtext>V<\/mml:mtext>\n                        <mml:mo>\u02d9<\/mml:mo>\n                      <\/mml:mover>\n                      <mml:mtext>O<\/mml:mtext>\n                    <\/mml:mrow>\n                    <mml:mn>2<\/mml:mn>\n                  <\/mml:msub>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula>), \u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub>, and \u0394CCO<jats:sub>2D<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> were obtained every 15\u00a0min. Beyond DO<jats:sub>2crit<\/jats:sub>, <jats:inline-formula><jats:alternatives><jats:tex-math>$${\\dot{\\text{V}}\\text{O}}_{2}$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:msub>\n                    <mml:mrow>\n                      <mml:mover>\n                        <mml:mtext>V<\/mml:mtext>\n                        <mml:mo>\u02d9<\/mml:mo>\n                      <\/mml:mover>\n                      <mml:mtext>O<\/mml:mtext>\n                    <\/mml:mrow>\n                    <mml:mn>2<\/mml:mn>\n                  <\/mml:msub>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula> decreased, indicating dysoxia. \u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub>, and \u0394CCO<jats:sub>2D<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> increased significantly only after reaching DO<jats:sub>2crit<\/jats:sub> in both models. At DO<jats:sub>2crit<\/jats:sub>, \u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> was significantly higher in the HH-model than in the IH-model (1.82\u2009\u00b1\u20090.09 vs. 1.39\u2009\u00b1\u20090.06, <jats:italic>p<\/jats:italic>\u2009=\u20090.002). At DO<jats:sub>2crit<\/jats:sub>, \u0394CCO<jats:sub>2D<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> was not significantly different between the two groups (0.87\u2009\u00b1\u20090.05 for IH vs. 1.01\u2009\u00b1\u20090.06 for HH, <jats:italic>p<\/jats:italic>\u2009=\u20090.09). Below DO<jats:sub>2crit<\/jats:sub>, we observed a discrepancy between the behavior of the two indices. In both models, \u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> continued to increase significantly (higher in the HH-model), whereas \u0394CCO<jats:sub>2D<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO<jats:sub>2<\/jats:sub>\/CO<jats:sub>2<\/jats:sub> content relationship, but not the Haldane effect. \u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO<jats:sub>2<\/jats:sub> values, \u0394PCO<jats:sub>2<\/jats:sub>\/\u0394O<jats:sub>2<\/jats:sub> did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO<jats:sub>2<\/jats:sub>\u2013hemoglobin dissociation curve, and then it should be interpreted with caution.<\/jats:p>","DOI":"10.1038\/s41598-021-89703-5","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T10:03:16Z","timestamp":1620900196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Ratio of venous-to-arterial PCO2 to arteriovenous oxygen content difference during regional ischemic or hypoxic hypoxia"],"prefix":"10.1038","volume":"11","author":[{"given":"Jihad","family":"Mallat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Vallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"89703_CR1","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1152\/jappl.2000.89.4.1317","volume":"89","author":"B Vallet","year":"2000","unstructured":"Vallet, B., Teboul, J. 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