Intravenous infusion of glucose and the vasodilator sodium nitroprusside in combination with local hyperthermia: Effects on tumour pH and tumour response in the BT₄An rat tumour model

Abstract

The influence of sodium nitroprusside (SNP) induced hypotension on the extracellular tumour pH during local hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT₄ An tumour transplanted to the hind limb of BD IX rats. Experiments with intravenous infusion of glucose before the HT/SNP combination were also performed. Local waterbath HT was given at 44d`C. Sodium nitroprusside was administered as a continuous i.v. infusion to lower the mean arterial blood pressure to 60 mm Hg. Glucose was given as an i.v. infusion at a dosage of 4.8g/kg body weight in 60 min before HT. Extracellular tumour pH was 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 1 h HT, but the pH 60 min after discontinuation of HT was lower in this group than in the HT alone group. Pre-treatment with glucose before HT gave similar 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 glucose before the HT/SNP combination prolonged the tumour growth time slightly. The applicability of this treatment protocol in the clinical treatment of patients is discussed.

Key Words:

• BT₄An
• glioma
• hyperthermia
• nitroprusside
• pH