Intravenous infusion of Tris resulted in a fall in the arterial oxygen tension in 38 anesthetized dogs. Carbon Dioxide tension also fell, while the pH of whole blood, plasma and red blood cells rose. It was demonstrated that the hypoxemia could not be due to (1) an effect of Tris on the PO2 electrode; (2) hypercapnia; (3) increased right-to-left shunt, or (4) increased ventilation-perfusion abnormality. The data are consistent with a combination of: (1) a Tris-induced Bohr effect of alkalosis on the oxygen affinity of hemoglobin, and (2) a slow rate of penetration of Tris into RBC. Experimental results consistent with this hypothesis include the following: (1) infusion of Tris buffered to pH 7.4 was not associated with either a rise in intracellular pH or a significant fall in PaO2; (2) infusion of bicarbonate, which diffuses rapidly into RBC, caused an in-significant decrease in PaO2, probably due entirely to induced hypercapnia; (3) Tris was shown by two techniques to penetrate RBC slowly, taking approximately 20–25 sec, by which time equilibration of blood with alveolar gas had already been completed. Arterial hypoxemia due to Tris infusion, when measured in the conventional manner, appears likely to be more marked than at the tissue level or as measured in this study by a flow-through technique.

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