Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors.

The extent of hypoxic regions in a tumor tissue depends on the arrangement, blood flow rate and blood oxygen content of microvessels, and on the tissue's oxygen consumption rate. Here, the effects of blood flow rate, blood oxygen content and oxygen consumption on hypoxic fraction are simulated theoretically, for a region whose microvascular geometry was derived from observations of a transplanted mammary andenocarcinoma (R3230AC) in a rat dorsal skin flap preparation. In the control state, arterial PO2 is 100 mmHg, consumption rate is 2.4 cm3 O2/100 g/min, and hypoxic fraction (tissue with PO2 < 3 mmHg) is 30%. Hypoxia is abolished by a reduction in consumption rate of at least 30%, relative to control, or an increase in flow rate by a factor of 4 or more, or an increase in arterial PO2 by a factor of 11 or more. These results suggest that reducing oxygen consumption rate may be more effective than elevating blood flow or oxygen content as a method to reduce tumor hypoxia.