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Microvascular Pressure Is the Principal Driving Force for Interstitial Hypertension in Solid Tumors: Implications for Vascular Collapse¹

Steele Laboratory, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114

The interstitial fluid pressure (IFP) has been found to be as high as 20 to 50 mm Hg in both experimental and human solid tumors. While the IFP is an important determinant of the delivery of therapeutic agents to neoplastic cells in vivo, the mechanisms responsible for interstitial hypertension are not completely understood. The high vascular permeability of tumor blood vessels and the absence of a functional lymphatic circulation suggest that the hydrostatic microvascular pressure (MVP) is the main force governing IFP in tumors. To test this hypothesis, we simultaneously measured IFP and MVP in 13 tissue-isolated R3230AC mammary adenocarcinomas transplanted in rats. The MVP in superficial postcapillary venules of diameters between 25 and 250 µm was measured with the micropuncture technique. MVP was compared to the IFP in the periphery (measured with micropuncture technique) and in the center (measured with wick-in-needle technique). Similar to our previous study, IFP rose rapidly and reached maximum values at a depth of 0.2 to 1.0 mm from the tumor surface. These maximum IFP values [16.5 ± 7.1 mm Hg (SD)] were equal to IFP in the tumor center [18.4 ± 9.3 mm Hg] [R² = 0.86, P > 0.8]. Superficial MVP (17.3 ± 6.1 mm Hg) was equal to both central (P > 0.9) and superficial IFP (P > 0.7). These results demonstrate that the main driving force for IFP in tumors is the MVP. Furthermore, the concept that blood vessel collapse is induced by higher hydrostatic pressures in the tumor interstitium compared to that in the vascular lumen is not supported by the present finding that elevated IFP is accompanied by equally elevated MVP.

¹ This work was supported by grants from the National Cancer Institute (CA-36902, CA-37239, and CA-49792). Preliminary reports of this work were presented at the 40th Annual Meeting of the Radiation Research Society, Salt Lake City, UT, March 14–18, 1992, and at the 39th Annual Meeting of the Microcirculatory Society, Anaheim, CA, April 3–5, 1992.

Received 6/25/92. Accepted 7/31/92.

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