Effect of hemodilution and resuscitation on tumor interstitial fluid pressure, blood flow, and oxygenation. 1994

I Lee, and T J Demhartner, and Y Boucher, and R K Jain, and M Intaglietta
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.

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 pO2 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 MABP and TIFP significantly decreased after 0.2 ml of blood (approximately 12% of blood volume) was withdrawn.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 min 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 pO2 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 When 0.2 ml blood was withdrawn and replaced (within 2.5 min) with the same volume of normal saline, MABP significantly decreased from 86.4 +/- 2.4 mmHg to 65.6 +/- 4.6 mmHg (n = 11) at 1 hr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 approximately 12% of blood volume) can significantly lower TIFP without a reduction in TBF and pO2.

UI MeSH Term Description Entries
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D011312 Pressure A type of stress exerted uniformly in all directions. Its measure is the force exerted per unit area. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Pressures
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D005110 Extracellular Space Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall. Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
D005260 Female Females
D006400 Hematocrit The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value. Erythrocyte Volume, Packed,Packed Red-Cell Volume,Erythrocyte Volumes, Packed,Hematocrits,Packed Erythrocyte Volume,Packed Erythrocyte Volumes,Packed Red Cell Volume,Packed Red-Cell Volumes,Red-Cell Volume, Packed,Red-Cell Volumes, Packed,Volume, Packed Erythrocyte,Volume, Packed Red-Cell,Volumes, Packed Erythrocyte,Volumes, Packed Red-Cell
D006438 Hemodilution Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically (1) in states of impaired microcirculation, (2) for replacement of intraoperative blood loss without homologous blood transfusion, and (3) in cardiopulmonary bypass and hypothermia. Hemodilutions

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