Effect of Hemodilution and Resuscitation on Tumor Interstitial Fluid Pressure, Blood Flow, and Oxygenation

Abstract

Hemodilution due to hemorrhage may increase tumor blood flow (TBF) by lowering blood viscosity and decrease tumor interstitial fluid pressure (TIFP) by moving fluid from the interstitium to the vascular compartment and by lowering microvascular pressure (MVP), mainly due to the decrease in systemic pressure. To test this hypothesis, we measured mean arterial blood pressure (MABP), TIFP, hematocrit, relative TBF (RBC flux), and intratumor p O2 during hemorrhage and volume restitution in severe combined immunodeficient mice, bearing LS174T human colon adenocarcinoma xenografts. MABP and TIFP significantly decreased after 0.2 ml of blood (∼12% of blood volume) was withdrawn. MABP decreased from 87.5 ± 3.9 mmHg (mean ± standard error) to 59.8 ± 4.8 mmHg (n = 5, P = 0.01) within 2.5 rain after the withdrawal of blood and then returned to control value within 10 min. TIFP gradually decreased from 18.7 ± 2.3 mmHg to 11.3 ± 0.9 mmHg after 1 hr (n = 8, P = 0.01), while RBC flux increased by a factor of 1.99 ± 0.38 (n = 5, P = 0.02). The systemic hematocrit decreased from 51.2 to 45.9% (n = 7, P = 0.02). Tumor oxygenation did not significantly improve (median pO2 = for control, 28 mmHg, and median p O2 after blood withdrawal, 32 mmHg; P = 0.14). When 0.2 ml blood was withdrawn and replaced (within 2.5 min) with the same volume of normal saline, MABP significantly decreased from 86.4 ± 2.4 mmHg to 65.6 ± 4.6 mmHg (n = 11) at 1 hr post-treatment (P = 0.001). TIFP decreased, but not significantly, from 24.2 ± 2.9 mmHg to 20.4 ± 2.4 mmHg (P = 0.35). Blood withdrawals in excess of 0.3 ml significantly decreased MABP and TIFP without recovery during 1 hr of observation. Volume restitution with hyperoncotic/hyperosmotic 6.0% Dextran 70 and 7.5% saline had effects attributable to a direct transmission of systemic pressure to the tumor microcirculation and to a lowering of tumor venous resistance. These effects appear to be common to saline blood restitution and volume top-load with Dextran 70. In conclusion, mild hemorrhage (withdrawal of ∼12% of blood volume) can significantly lower TIFP without a reduction in TBF and pO2.