Influence of vascular thermotolerance on the heat-induced changes in blood flow, pO2, and cell survival in tumors.

Vascular thermotolerance in SCK tumors of A/J mice was studied by comparing the changes in blood flow, as measured by the 86Rb uptake method, from a single heating with those from two heatings. The heat-induced decline in 86Rb uptake in tumors could be substantially inhibited when the tumors were preheated, indicating the development of vascular thermotolerance. In SCK tumors, the vascular thermotolerance peaked 5 or 18 h after the tumors were heated for 1 h at 41.5 degrees C or 42.5 degrees C, respectively. Consequently, the tumor blood flow decreased by 50% in 81 min when the tumors were heated at 43.5 degrees C without preheating, whereas the tumor blood flow decreased by 50% in 195 min at 43.5 degrees C when the tumors were preheated 18 h earlier at 42.5 degrees C for 1 h. The influence of vascular thermotolerance on the heat-induced changes in intratumor pO2 was also investigated. The average intratumor pO2 was 8.9 mm Hg before heating. Heating at 43.5 degrees C or 44.5 degrees C for 1 h dramatically decreased the intratumor pO2 to 3.0 or 1.2 mm Hg, respectively. However, the intratumor pO2 decreased to 6.6 or 3.8 mm Hg when the tumors were heated at 43.5 degrees C or 44.5 degrees C, respectively, 18 h after preheating at 42.5 degrees C for 1 h. Heating the tumors when tumor vasculatures were at peak thermotolerance was relatively ineffective in suppressing tumor growth. The data demonstrate that vascular thermotolerance in tumors may exert profound effects on tumor response to multiple heatings in clinical hyperthermia.