USE OF THE VASODILATOR SODIUM-NITROPRUSSIDE DURING LOCAL HYPERTHERMIA- EFFECTS ON TUMOR TEMPERATURE AND TUMOR RESPONSE IN A RAT-TUMOR MODEL

Purpose: The effect of a decrease in the mean arterial blood pressure (MAP) induced by sodium nitroprusside (SNP) on the tumor temperature d uring hyperthermia (HT), and on the cytotoxic effect of HT, was studie d in the BT(4)An tumor transplanted to the hind limb of BD IX rats. Ex periments with two different anesthetics, pentobarbital and the midazo lam/fentanyl/fluanisone combination (MFF), were performed to secure re liable conclusions. Methods and Materials: In the tumor response exper iments local waterbath HT at 44.0 degrees C was given for 60 min. Sodi um nitroprusside was administered as a continuous intravenous infusion to lower the MAP to 60 or 80 mmHg during HT. In two other experiments the temperature at the base of the tumor during HT was measured befor e and during SNP infusion. In animals without tumor the temperature wa s measured subcutaneously on the foot during HT with or without SNP-in duced hypotension. Results: When SNP was given to lower the MAP to 60 mmHg during HT in MFF anesthetized animals, the median tumor growth ti me (TGT) was 70 days, compared to 14.5 days in the HT alone group. The corresponding figures were 127 and 12.1 days with pentobarbital anest hesia. In the HT + SNP group, more than 40% cure was observed in both experiments. No cures were seen in any of the other groups. Hypertherm ia alone prolonged the TGT slightly, whereas SNP given alone had no ef fect, compared to controls. When the MAP was lowered to 80 mmHg by SNP infusion during HT (MFF anesthesia), the median TGT was 19.9 days, wh ich was significantly longer than that in the HT alone group (10.9 day s). In the MAP range from 60 to 120 mmHg, a nearly linear relationship between the MAP and the tumor temperature was found during HT in MFF anesthetized animals. With both anesthetics, the median temperature at the base of the tumor was about 0.8 degrees C higher during HT when t he MAP was lowered to 60 mmHg by SNP. In animals without tumors, the t emperature subcutaneously on the foot was 0.3 and 0.4 degrees C higher during SNP infusion in the MFF and pentobarbital group, respectively. Conclusion: We have developed a small animal model in inbred rats fea sible for exploring the influence of a stable blood pressure reduction induced by SNP, on the effect of HT given alone or in combination wit h other treatment modalities to a transplantable tumor. The greatly in creased cytotoxic effect of local waterbath HT in the present tumor re sponse experiments is probably a consequence of increased tumor temper ature during SNP infusion.