Circulatory and metabolic responses of malignant tumors during localized hyperthermia

Abstract

The effect of localized hyperthermia on the circulatory responses and on the oxygen and glucose supply has been evaluated in tissue-isolated rat tumors utilizing an in situ perfusion system. On the average, localized hyperthermia caused a significant increase in total tumor blood flow after raising of the mean tumor temperature from 37 degrees C to 39.5 degrees C. At higher temperatures (42 degrees C) total tumor blood flow decreased to a level somewhat below the flow during normothermia. However, there were great interindividual differences in the response of blood flow to temperature. The changes in blood flow were paralleled by variations of the O2-consumption and of the glucose uptake of the tumor tissue. The alteration of the oxygen and glucose supply seem to be predominantly mediated through changes of tumor blood flow with temperature. Tumor microcirculation appears to be improved at moderate hyperthermic temperatures (39 degrees C -40 degrees C) and deteriorated at higher temperatures. Whereas a vasodilation of tumor vessels seems to be a paramount factor for flow improvements, a reduction of red blood cell flexibility due to severe tissue acidosis, multiple microthromboses as well as occlusions of microvessels should be taken into consideration as factors for flow impairments at higher tumor temperatures.

Oxygenation of malignant tumors after localized microwave hyperthermia

“…This dilatation is consistent with the observed "revival" of tumor blood flow [34]. No vessel damage is detectable at this hyperthermia level [6,8].…”

“…It is largely determined by the efficiency of nutritive blood flow through tumors. Some recent experimental evidence suggests that hyperthermia has profound effects on tumor blood flow, including tumor microcirculation [3,5,7,9,18,30,34,39]. Histopathological studies of hyperthermic effects on the tumor microvasculature reveal patterns of gradual changes which likely cause these variations in tumor blood flow [6,8,40].…”

“…When tissue temperatures exceeded this "temperature optimum", a distinct decline of the mean tissue PO2 values became obvious, both in small rodent tumors [39] and in human tumors [3]. These temperature-mediated changes of the 0 2 supply to the tumor tissue (during a 30 min-hyperthermia) were found in several tumor models, applying various heating techniques and using different tumor cell lines [2,3,34,39].…”

“…150 ~tl). In the blood samples taken sequentially, all relevant respiratory gas parameters were determined, e.g., 02 and CO2 partial pressures, pH, oxyhemoglobin saturation, 02 content, hematocrit, hemoglobin concentration (for details see [34]). …”

Longitudinal optical imaging of tumor metabolism and hemodynamics

“…Previous methods for measuring oxygen demand in tumors include pO 2 microelectrode measurements coupled with theoretical simulations of oxygen diffusion, 16 an isolated tumor perfusion system combined with Fick's principle calculations, 17 and cryospectrophotometric microtechniques.…”