Determinants of tumor blood flow: a review

Blood flow rate in a vascular network is proportional to the pressure difference between the arterial and venous sides and inversely proportional to the viscous and geometric resistances. Despite rapid progress in recent years, there is a paucity of quantitative data on these three determinants of blood flow in tumors and several questions remain unanswered. This paper reviews our current knowledge of these three parameters for normal and neoplastic tissues, the methods of their measurements, and the implications of the results in the growth and metastasis formation as well as in the detection and treatment of tumors. Microvascular pressures in the arterial side are nearly equal in tumor and nontumorous vessels. Pressures in venular vessels, which are numerically dominant in tumors, are significantly lower in a tumor than those in a nontumorous tissue. Decreased intravascular pressure and increased interstitial pressure in tumors are partly responsible for the vessel collapse as well as the flow stasis and reversal in tumors. The apparent viscosity (viscous resistance) of blood is governed by the viscosity of plasma and the number, size, and rigidity of blood cells. Plasma viscosity can be increased by adding certain solutes. The concentration of cells can be increased by adding cells to blood or by reducing plasma volume. The rigidity of RBC, which are numerically dominant in blood, can be increased by lowering pH, elevating temperature, increasing extracellular glucose concentration, or making the suspending medium hypo- or hypertonic. Effective size of blood cells can be increased by forming RBC aggregates (also referred to as rouleaux). RBC aggregation can be facilitated by lowering the shear rate (i.e., decreasing velocity gradients) or by adding macromolecules (e.g., fibrinogen, globulins, dextrans). Since cancer cells and WBC are significantly more rigid than RBC, their presence in a vessel may also increase blood viscosity and may even cause transient stasis. Finally, due to the relatively large diameters of tumor microvessels the Fahraeus effect (i.e., reduction in hematocrit in small vessels) and the Fahraeus-Lindqvist effect (i.e., reduction in blood viscosity in small vessels) may be less pronounced in tumors than in normal tissues. Geometric resistance for a network of vessels is a complex function of the vascular morphology, i.e., the number of vessels of various types, their branching pattern, and their length and diameter. Geometric resistance to flow in a single vessel is proportional to the vessel length and inversely proportional to vessel diameter to the fourth power.(ABSTRACT TRUNCATED AT 400 WORDS)