INTRAVENOUS-INFUSION OF GLUCOSE AND THE VASODILATOR SODIUM-NITROPRUSSIDE IN COMBINATION WITH LOCAL HYPERTHERMIA - EFFECTS ON TUMOR PH AND TUMOR RESPONSE IN THE BT(4)AN RAT-TUMOR MODEL

The influence of sodium nitroprusside (SNP) induced hypotension on the extracellular tumour pH during local hyperthermia (HT), and on the cy totoxic effect of HT, was studied in the BT(4)An tumour transplanted t o the hind limb of ED IX rats. Experiments with intravenous infusion o f glucose before the HT/SNP combination were also performed. Local wat erbath HT was given at 44 degrees C. Sodium nitroprusside was administ ered as a continuous i.v. infusion to lower the mean arterial blood pr essure to 60 mmHg. Glucose was given as an i.v. infusion at a dosage o f 4.8 g/kg body weight in 60 min before HT. Extracellular tumour pH wa s measured by a needle type glass electrode. The tumour pH fell from 7 .19 to 6.81, on average, after 60 min HT. Sodium nitroprusside induced hypotension during HT did not increase the pH fall after Ih HT, but t he pH 60 min after discontinuation of HT was lower in this group than in the HT alone group. Pretreatment with glucose before HT gave simila r results as the HT/SNP combination. When glucose was given before HT/ SNP a highly relevant decline in tumour pH during HT from 7.22 to 5.95 was observed. In a separate tumour response experiment adding SNP to HT was found to prolong the tumour growth time. Pre-treatment with glu cose before the HT/SNP combination prolonged the tumour growth time sl ightly. The applicability of this treatment protocol in the clinical t reatment of patients is discussed.