Concepts of oxygen transport at the microcirculatory level

This article compares and contrasts the classic paradigms underlying the development of chronic and acute hypoxia in tumors. The classic theory of Thomlinson and Gray suggested that chronic hypoxia is the result of large intravascular distances. Newer evidence suggests that a multiplicity of effects contribute to this process, including steep longitudinal gradients of partial pressure of oxygen (Po2) along the vascular tree before arteriolar entry into tumor, rheologic effects on red cell deformability brought on by intravascular hypoxia, uneven distribution of red cell fluxes in microvessels leading to plasma channels, irregular vascular geometry, and oxygen demand that is out of balance with the supply. The most common theories have suggested that vascular stasis is the most common source of acute hypoxia. If this were true, the incidence of this form of hypoxia would be relatively rare because most studies indicate that total stasis probably occurs less than 5% of the time. Studies have suggested, however, that spontaneous fluctuation in tumor blood flow, on the microregional level, can lead to tissue hypoxia, and total vascular stasis is not required. Spontaneous fluctuations in flow and Po2 appear to occur commonly. Thus, the most current evidence suggests that tumor oxygenation is in a continuous state of flux. Collectively, this new information has important implications for therapy resistance and gene expression.