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Viscous Resistance to Blood Flow in Solid Tumors: Effect of Hematocrit on Intratumor Blood Viscosity¹

Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213-3890

Blood flow rate in a vascular network is proportional to the arteriovenous pressure difference and inversely proportional to the geometric and viscous resistances. We have recently shown that the geometric resistance to blood flow increases with increasing tumor size and/or decreasing arterial pressure. In this study, the viscous resistance to blood flow within tumor microvasculature was determined by alternately perfusing mammary adenocarcinoma [R3230AC; N = 12; tumor weight, 2.2 ± 1.6 (SD) g] ex vivo with Krebs-Henseleit solution and with RBC suspensions at hematocrits between 1 and 60%. Our results demonstrate that: (a) intratumor blood viscosity increases with increasing hematocrit; and (b) for fixed hematocrits between 10 and 60%, the intratumor blood viscosity is significantly reduced (P < 0.0001) compared to bulk viscosity measured at shear rates of 460 s^-1 using a cone/plate viscometer. However, this reduction of intratumor blood viscosity is not as pronounced as in a previous study of skeletal muscle. Further comparison shows that as arterial pressure is lowered, intratumor blood viscosity increases at a greater rate and at lower hematocrits than in normal tissues. We attribute the increased viscous resistance in tumor microvasculature to (a) a less pronounced Fahraeus effect (i.e., reduction in hematocrit in small vessels) and a less pronounced Fahraeus-Lindqvist effect (i.e., reduction in blood viscosity in small vessels) in dilated tumor microvessels compared to normal microvessels; (b) low shear rates (i.e., velocity gradients) associated with tumor vessels which may facilitate rouleaux formation at moderate pressures and even at low hematocrits; and (c) vascular fluid losses of 5–14% which may also increase microvessel hematocrit. We also propose that intratumor blood viscosity may be even higher in vivo than ex vivo due to the presence of WBC and cancer cells in vivo; considerably more rigid than RBC, these cells may cause increased viscous resistance and transient vascular stasis in tumors. The implications of these results in tumor blood flow modulation using chemical and physical agents are discussed.

¹ This work is dedicated to Dr. Pietro M. Gullino on his 70th birthday.

Supported by the National Cancer Institute (CA37239). Preliminary reports of this work were presented at the 36th Annual Radiation Research Society Meeting, Philadelphia, PA, April 18–20, 1988; Microcirculation Society Annual Meeting, Las Vegas, NV, April 30–May 1, 1988; and Annual Meeting of Biomedical Engineering Society, Las Vegas, NV, May 2–5, 1988.

² Recipient of NIH Predoctoral Traineeship, 1986–1988.

³ To whom requests for reprints should be addressed.

Received 10/24/88. Revised 3/28/89. Accepted 4/ 3/89.

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