ACUTE CHANGES OF SYSTEMIC PARAMETERS IN TUMOR-BEARING RATS, AND OF TUMOR GLUCOSE, LACTATE, AND ATP LEVELS UPON LOCAL HYPERTHERMIA AND OR HYPERGLYCEMIA

Arterial blood pressure and relevant parameters of the arterial blood (O2 and CO2 tensions, pH, haematocrit, serum electrolytes and osmolality) were determined in tumour-bearing rats upon local hyperthermia (HT) and/or hyperglycaemia (HG). Tumour heating was performed in a saline bath (44-degrees-C) for 120 min; hyperglycaemia was induced by i. v. infusion of 40% glucose solution for 150 min [blood glucose levels: 35-40 mM during heating; total amount of glucose: 1.19 g/100 g body wt.; infusion rates: 0.31 ml (100 g body wt.)-1 min-1 for 2 min, 0.02 ml (100 g body wt.)-1 min-1 for 88 min, and 0.01 ml (100 g body wt.)-1 min-1 for 60 min]. Immediately after treatment, glucose, lactate and ATP levels were determined in tumour and muscle specimens and compared to these values under normothermic (NT) and/or normoglycaemic (NG) conditions. In all groups (NT/NG, NT/HG, HT/NG, HT/HG) there were only minor but characteristic changes in blood parameters, which were mainly due to the volume and type of the infused fluids (glucose solution, saline). During hyperglycaemia, tumour glucose levels rose 13- to 17-fold, whereas muscle glucose concentrations exhibited only a 3- to 5-fold increase; lactate levels were 1.9-2.5 times higher in tumours than in muscle, indicating an increase in the metabolic differences between normal and malignant tissues. Despite an increased glucose availability, tumours did not show an improved energy status and, thus, would not be expected to develop a decrease in thermal sensitivity or stimulation in growth rate. The good systemic tolerability of the combined treatment (HT/HG) and the differential changes in malignant and normal tissue occurring under these conditions, support further attempts to manipulate tumour metabolic environment by glucose in order to achieve better therapeutic results.