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Differential Response of Normal and Tumor Microcirculation to Hyperthermia¹

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

RBC velocity and vessel lumen diameter were measured in individual microvessels in normal (mature granulation) and neoplastic (VX2 carcinoma) tissues grown in a transparent rabbit ear chamber. Blood flow rates were determined before, during, and after local hyperthermia treatments at 40–52° for 1 hr. Blood flow in normal tissue increased dramatically with temperature, but stasis occurred at higher temperatures and/or longer durations of heating. In tumors, blood flow rate did not increase as much, and stasis occurred at lower levels of hyperthermia.

Both the magnitude and the time of maximum flow appeared to be bimodal functions of temperature. That is, both of these parameters increased with temperature up to a certain critical temperature, and then decreased at higher temperatures. This critical temperature was approximately 45.7° in normal tissue and 43.0° in tumors. Normal tissue required temperatures greater than 47° to bring about vascular stasis in less than 1 hr, while stasis occurred in tumors in the same time frame at temperatures greater than 41°. Normal tissue could increase its maximum flow capacity up to 6 times its preheating value, while neoplastic tissue could only double its maximum flow capacity. This differential flow response in individual microvessels was used to develop a theoretical framework relating various mechanisms of blood flow modifications due to hyperthermia.

¹ Financial assistance was furnished by grants from the American Cancer Society, the National Science Foundation, and the R. K. Mellon Foundation; a Research Career Development Award from the National Cancer Institute; and a Guggenheim Fellowship to R. K. Jain. A preliminary report of this work has been presented at the 74th Annual Meeting of the American Institute of Chemical Engineers, November 1982, Los Angeles, and at the 31st Annual Meeting of the Radiation Research Society, February to March 1983, San Antonio, TX.

² Present address: Travenol Laboratories, Inc., P. O. Box 490, Round Lake, IL 60073.

³ To whom requests for reprints should be addressed.

Received 7/ 5/83. Accepted 11/ 8/83.

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