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 extra-cellular tumour pH during local hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT4An 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 44 degrees C. Sodium nitroprusside was administered as a continuous i.v. infusion to lower the mean arterial blood pressure to 60 mmHg. Glucose was given as an i.v. infusion at a dosage of 4.8 g/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. Pretreatment 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.

The Dynamic in vivo Distribution of Bone Marrow-Derived Mesenchymal Stem Cells after Infusion

“…When sodium nitroprusside was used, as reported here, the radioactivity in the lungs was decreased by 15% and that in the liver, kidneys and bone increased by 10-50%. Sodium nitroprusside is a strong vasodilator and also is an inhibitor of aggregation and adhesion of platelets [Tinker and Michenfelder, 1976;Krossnes et al, 1996Krossnes et al, , 1998]. Therefore, the administration of sodium nitroprusside may have influenced the distribution of infused MSCs by enlarging the diameter of the pulmonary capillaries and preventing cell adhesion and aggregation.…”

Effect of calcitonin gene related peptide vs sodium nitroprusside to increase temperature in spontaneous canine tumours during local hyperthermia

“…Vasoactive drugs have been studied extensively in pre-clinical models as a means to sensitize tumours to hyperthermia by either increasing temperatures during heating or by creating acute changes in the microenvironment that result in lowering of pH to increase thermal sensitivity of tumour cells [2][3][4][6][7][8][9][11][12][13][14]17 . Krossnes and Hornsleth 14 showed favourable increases in temperature in a rodent tumour model treated with SNP.…”

“…This strategy has been tested by Krossnes et al 8,9,13,14 , who found that temperatures were significantly increased during hyperthermia in the presence of nitroprusside in a murine model. Prescott et al 15 demonstrated a significant increase in canine tumour temperature distributions during hyperthermia when nitroprusside was used to decrease blood pressure by 40%.…”