Modulation of spatial O2 tension distribution in experimental tumors by increasing arterial O2 supply

Tumor oxygenation has been measured polarographically in s.c. implanted DS-sarcomas on the dorsum of the hind foot of male Sprague-Dawley rats. pO2 was determined in all 3 spatial dimensions and 3-dimensional pO2 distributions as well as the mean extent of confluent areas with pO2 < 5 mmHg were calculated. Finally, the effect of elevating arterial pO2 (by carbogen breathing) as well as of increasing tumor blood flow (by angiotensin infusion) on the spatial pO2 distribution was analyzed. Depending on the tumor volume, the spatial pO2 distribution is more or less anisotropic. In smaller tumors, areas with physiological pO2 values are found adjacent to large hypoxic areas whereas larger tumors are almost completely hypoxic/anoxic. With carbogen breathing, the mean tissue pO2 is elevated although hypoxia is not eradicated in larger tumors. In small tumors, angiotensin leads to a vasoconstriction of tumor vessels followed by a worsening of tumor oxygenation whereas in large tumors the increased systemic perfusion pressure resulted in an improvement of oxygenation. Thus, carbogen predominantly affects pO2 diffusion by increasing the arterial pO2 whereas angiotensin influences tumor perfusion and leads to an increased oxygen supply to the tumor tissue.