Synergistic effects of hyperoxic gas breathing and reduced oxygen consumption on tumor oxygenation: A theoretical model

Purpose To simulate effects of reduced oxygen consumption combined with hyperoxic gas breathing on tumor oxygenation, and to test for synergistic effects. Methods and materials Diffusive oxygen transport was simulated for a small region of tumor containing a three-dimensional network of microvessels whose geometry was derived from in vivo observations. Changes in tissue partial pressure of oxygen (PO₂) and hypoxic fraction (PO₂ < 5 mm Hg) resulting from a 30% reduction in oxygen consumption rate or breathing 100% oxygen were estimated. The synergistic effect was defined as the change in PO₂ with the two treatments combined, minus the sum of the changes with the separate treatments. Results Predicted hypoxic fractions were 37% in the control state, 11% with reduced consumption, 23% with oxygen breathing alone, and 0% with the combined treatment. The synergistic effect was about 4 mm Hg at tissue points with very low initial PO₂ levels and decreased as initial PO₂ increased. Conclusions Reduction of oxygen consumption via the Crabtree effect, by administration of glucose, has been proposed as a means to improve tumor oxygenation during radiation treatment. The results support previous experimental studies showing that this approach is more effective when combined with breathing of hyperoxic gases.