Differential response of normal and tumor microcirculation to hyperthermia

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 degrees 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 degrees in normal tissue and 43.0 degrees in tumors. Normal tissue required temperatures greater than 47 degrees 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 degrees. 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.