Die mikrovascul�re Perfusion maligner Tumoren ?eine therapeutische Gr��e zur Steigerung des Hyperthermieeffektes?

Abstract

Hypoxic regions of malignant tumors are poorly vascularized; they appear to be more susceptible to hyperthermia in vivo than tumor cells in vitro after an exposure to heat. In an attempt to explain this discrepancy, changes of microcirculatory flow in the tumor have been proposed as key mechanism for destroying adjacent tumor cells in particular. This study was conducted to define the impact of the microcirculation on tumor destruction after local hyperthermia. A transparent chamber was implanted in the dorsal skin fold and two permanent indwelling catheters placed in carotid artery and jugular vein of 45 Syrian golden hamsters. 48 h later, 4 X 10(4) cells of the amelanotic melanoma A-Mel-3 were implanted into the s.c. tissue covered by the chamber. 5 days later, at a tumor diameter of 3 mm, the microcirculation of this tumor was studied using intravital microscopy, a platinum multiwire electrode, television as well as micropuncture techniques for the determination of local PO2, microcirculatory blood flow and microvascular pressure. Measurements were taken at 30 degrees C and 15 min after reaching a tumor temperature of 35 degrees and 42.5 degrees C. When heating up the melanoma to 35 degrees C, an increase in capillary perfusion by 35% was noted. With an apparent maximum of capillary perfusion, there was no change in arteriolar pressure but a significant drop in venular pressure from 11.0 +/- 1.1 to 7.4 +/- 0.6 mmHg resulting in an increase of the arteriolo-venular pressure gradient while the systemic pressures were unchanged. At a tumor temperature of 42.5 degrees C, prestasis and stasis became apparent in capillaries and collecting venules. This was accompanied by a rise in capillary and venular pressure by 5 mmHg. At the same time, pronounced tissue hypoxia was present in the tumor with more than 50% of the values within the hypoxic range between 0 and 5 mmHg. Despite tissue hypoxia, the constriction of all tumor arterioles became evident 15-30 min after reaching a tumor temperature of 42.5 degrees C. The deterioration of tumor oxygenation was associated with damage of tumor cells such as swelling and destruction of mitochondria which was seen under the electron microscope. After 40 min at 42.5 degrees C, the attenuation of the endothelial lining around the entire vascular perimeter was seen in tumor capillaries.(ABSTRACT TRUNCATED AT 400 WORDS)