The influence of a 2,3-diphosphoglycerate (2,3-DPG)-induced displacement of the oxygen dissociation curve (O.D.C.) on the isolated perfused rat liver was studied at different levels of anaemic hypoxia. Rat livers were perfused either with fresh or with 2,3-DPG-depleted human erythrocytes at different haematocrit values (from 30% to 2.5%) at constant Po2 of the inflowing perfusate and at constant blood flow rate. The 2,3-DPG-induced difference in oxygen affinity of the red cells did not cause a significant difference in perfusion pressure during the perfusion experiments. Therefore, there is no evidence that 2,3-DPG did alter the vascular resistance of the liver, since blood flow rate could be adusted at equal values. The decrease in oxygen supply brought about by decrease of haematocrit caused a decrease of O2 consumption, of bile flow rate and of venous Po2 and an increase of lactate/pyruvate (L/P) ratio and of beta-hydroxybutyrate/acetoacetate (betaOH/Acac) ratio. There was no influence of a difference in 2,3-DPG content of the erythrocytes on the above-metioned parameters during severe anaemic hypoxia. At moderate anaemic hypoxia the venous Po2 was higher during perfusion with fresh erythrocytes than during perfusion with 2,3-DPG-depleted erythrocytes. Thus, although 2,3-DPG may play a compensatory role during conditions of mild anaemia, no such effects can be observed during conditions of severe hypoxia.
The influence of the 2,3-diphosphoglycerate (2,3-DPG) induced displacement of the oxygen dissociation curve (O.D.C.) on the isolated perfused rat liver was studied at different levels of stagnant hypoxia (hypoxia induced by decrease of blood flow rate at constant PO2 and at constant haematocrit). Rat livers were perfused with a medium containing either fresh or 2,3-DPG-depleted erythrocytes (2,3-DPG content: 4.3 +/- 0.4 and 0.6 +/- 0.4 mmol/l erythrocytes, respectively). The difference in oxygen affinity of the red cells did not affect the vascular resistance of the perfused liver tissue. The decrease in oxygen supply brought about by a decrease in blood flow rate resulted in a decrease of bile flow rate and of oxygen consumption. The higher 2,3-DPG content of the fresh erythrocytes was reflected in a higher bile flow rate at all blood flow levels, in a higher oxygen consumption at lower blood flow levels, and in a higher venous PO2 at the higher blood flow levels. Venous PO2, lactate/pyruvate (L/P) ratio and beta-hydroxybutyrate/acetoacetate (betaOH/Acac) ratio were relatively insensitive to stagnant hypoxia and to a difference in the 2,3-DPG content of the erythrocytes. The ATP content of the liver tissue was decreased at the lower blood flow levels. However, the ATP content of the livers perfused with fresh erythrocytes did not differ from that of the livers perfused with 2,3-DPG-depleted erythrocytes.
Isolated rat livers were perfused with fresh and 2,3-DPG (2,3-diphosphoglycerate)-depleted human erythrocytes at different levels of hypoxia. The mean P50 values of the measured actual oxygen dissociation curves (O.D.C.) were 24.5 and 18 mm Hg. No changes in flow rate and perfusion pressure occurred under the different experimental conditons. It was shown that an advantage or disadvantage of a shift of the O.D.C. depends on the degree of hypoxia, as reflected in the venous PO2. Perfusions with fresh erythrocytes showed higher venous PO2 values during normoxia or moderate hypoxia and lower venous PO2 values at severe hypoxia. A cross-over point was found at a PO2 in the portal vein of 36 mm Hg. The disadvantage of perfusions with fresh erythrocytes at severre hypoxia was also reflected in higher cytoplasmatic and mitochondrial redox levels. Using bile flow rate as an indirect measure for the rate of hydroxylation-dependent O2 consumption a favourable effect of perfusion with fresh erythrocytes was found at a PO2 in the portal vein of 100 and 40 mm Hg.
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