The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis.
OBJECTIVE
To examine the hypothesis that elevated interstitial fluid pressure (IFP) is a cause of reduced blood flow in tumors.


METHODS
A physiologic model of tumor blood flow was developed based on a semipermeable, compliant capillary in the center of a spherical tumor. The model incorporates the interaction between the tumor vasculature and the interstitium, as mediated by IFP. It also incorporates the dynamic behavior of the capillary wall in response to changes in transmural pressure, and the effect of viscosity on blood flow.


RESULTS
The model predicted elevated tumor IFP in the range of 0 to 56 mmHg. The capillary diameter in the setting of elevated IFP was greatest at the arterial end, and constricted to between 3.2 and 4.4 microm at the venous end. This corresponded to a 2.4- to 3.5-fold reduction in diameter along the length of the capillary. The IFP exceeded the intravascular pressure distally in the capillary, but vascular collapse did not occur. Capillary diameter constriction resulted in a 2.3- to 9.1-fold steady-state reduction in tumor blood flow relative to a state of near-zero IFP.


CONCLUSIONS
The results suggest that steady-state vascular constriction occurs in the setting of elevated IFP, and leads to reduced tumor blood flow. This may in turn contribute to the development of hypoxia, which is an important cause of radiation treatment failure in many tumors.
Milosevic
M F
MF
Department of Radiation Oncology and Experimental Therapeutics, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada. mike_milosevic@pmh.toronto.on.ca
Fyles
A W
AW
Hill
R P
RP
D001794:Blood Pressure; D001809:Blood Viscosity; D002199:Capillary Permeability / Q000502:physiology*; D005110:Extracellular Space / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply*; D009997:Osmotic Pressure; D011853:Radiobiology; D012039:Regional Blood Flow; D014661:Vasoconstriction