Blood flow and venous pH of tissue-isolated Walker 256 carcinoma during hyperglycemia

Hemodynamic (blood flow rate, hematocrit, hemoglobin concentration, and blood viscosity) and pH responses to glucose (6 g/kg, i.p.) injections were studied in ten Walker 256 carcinoma tumors (0.5-1.8 g) grown in the "tissue-isolated" tumor preparation. A maximum blood flow reduction of 57 +/- 19% (SD) occurred concurrently with an increase in tumor arterial-venous blood pH difference 20-30 min after glucose administration. Tumor venous blood pH dropped significantly by 0.15 +/- 0.07 pH unit to 7.15 +/- 0.01, while systemic blood pH dropped by 0.06 +/- 0.02 pH unit to 7.38 +/- 0.03. Arteriovenous blood pH differences were found to correlate with blood flow rates; however, both the small magnitude of the pH reduction and the immediate blood flow response argue against the hypothesis of increased resistance to flow caused by low pH-stiffened RBC membranes. Significant increases in systemic and tumor efferent whole blood viscosities at 2.25 and 4.5s-1 occurred after glucose administration, while hemoglobin concentrations of systemic and tumor efferent blood increased by as much as 11 +/- 1 and 16 +/- 2%, respectively. Venous to arterial hematocrit and hemoglobin ratios remained unchanged with glucose administration. These data suggest local tumor blood flow reductions are caused by increased viscous resistance to flow within the tortuous microvasculature of tumor, not as a result of low pH RBC rigidity, but rather from other mechanisms such as glucose-mediated RBC rigidity and systemic hemoconcentration.