Modulation of Spatial O2 Tension Distribution in Experimental Tumors by Increasing Arterial O2 Supply

Abstract

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 predominately affects pO₂ diffusion by increasing the arterial pO₂ whereas angiotensin influences tumor perfusion and leads to an increased oxygen supply to the tumor tissue.