PubMed1982
The present study was based upon the assumption that the efficacy of tumor treatment depends not only on the response of malignant cells to a given drug but on local oxygen tension as well as on number and alignment of capillaries. Transparent chambers were implanted in the dorsal skin flap of 32 Syrian (Gold) hamsters. Permanent indwelling catheters in carotid artery and jugular vein served for measuring the systemic pressures and heart rate; 48 hours later, 4 X 10(4) cells of the amelanotic melanoma A-Mel-3 were transplanted (16 animals) s.c. in the area exposed for daily intravital microscopy. A platinum multiwire electrode and quantitative video techniques were utilized for measurements of local PO2 and capillary blood flow. Capillary density, capillary diameter and surface area were analyzed throughout the vascularized melanoma during the first 12 days of growth. When compared to controls (16 animals) and tissue in the immediate neighborhood of the tumor, mean local PO2 on the tumor's surface decreased with tumor size. Capillary density of the melanoma was elevated 4 days after tumor inoculation but decreased significantly until day 12. As a result of enhanced capillary diameters, capillary surface area increased eight-fold during earliest growth of the melanoma. Of hemodynamic significance were huge platelet conglomerates consistently noted in short, dilated capillaries at the melanoma edge. As a consequence, the number of erythrocyte perfused capillaries decreased with tumor growth and 38% and 50% of the arterial inflow was bypassing the capillary network 8 and 12 days after tumor inoculation. These data indicate that due to rarefication of capillaries, the full impact of tumor treatment is diminished by an elevated microvascular resistance which could significantly affect the therapy of the melanoma. On the basis of these studies it is concluded that improvement of the blood's fluidity might result in a better response to adjuvant chemotherapy of the melanoma.