Abstract
The effect of localized hypothermia on microcirculatory and metabolic parameters in s.c. DS sarcomas on the hind foot dorsum of Sprague-Dawley rats was investigated. Tumours were cooled by superfusion of the tumour surface with cooled saline solution to 25 degrees C or 15 degrees C. Control tumours remained at 35 degrees C. These temperatures were maintained for 30 min. In tumour oxygenation measurements, hypothermia at 25 degrees C and 15 degrees C caused progressive decreases in the size of the fraction of pO2 measurements between 0 and 2.5 mmHg together with a reduction in pO2 variability. No significant changes in median or mean pO2 or in the fraction of pO2 measurements between 0 and 5 mmHg, and 0 and 10 mmHg were observed. Using laser Doppler flowmetry, red blood cell flux was found to decrease significantly upon 25 degrees C or 15 degrees C hypothermia treatment to 67% and 37% of starting values respectively, whereas no significant changes were seen in control tumours over the whole observation period. Viscosity was measured in blood and plasma samples over a range of temperatures and was found to increase with decreasing temperature. Assessment of tumour glucose levels showed an increased concentration of glucose following 15 degrees C hypothermia, an observation consistent with a 'slowing down' of glycolysis. No changes in lactate or adenylate phosphate levels were observed. As a way of improving tumour oxygenation, localized hypothermia may therefore be a useful means of radiosensitization.
Highlights
The aim of this study was. . to identify changes occurrinc in tumour oxygenation in superficial rat tumours during localized hypothermia at either 25°C or 15°C which might be relevant for the outcome of oxygen-dependent therapy modalities. and to characterize accompanying changes in microcirculatory and metabolic parameters which might be responsible for these changes in oxygenation
a significant decrease of 53% in the fraction of pO, measurements between 0 and 2.5 mmHg was seen at 15°C hypothermia (P < 0.05)
Hypothermia treatment resulted in a reduction in the fraction of pO, measurements between 0 and 2.5 mmHg, an effect which may prove to be radiotherapeutically exploitable as tumour oxygenation is a parameter known to influence the outcome of standard radiotherapy
Summary
Hypothermia at 25cC and 15°C caused progressive decreases in the size of the fraction of P02 measurements between 0 and 2.5 mmHg together with a reduction in P02 variability. No significant changes in median or mean P02 or in the fraction of P02 measurements between 0 and 5 mmHg, and 0 and 10 mmHg were observed. Using laser Doppler flowmetry, red blood cell flux was found to decrease significantly upon 25°C or 15°C hypothermia treatment to 67% and 370/o of starting values respectively, whereas no significant changes were seen in control tumours over the whole observation period. Assessment of tumour glucose levels showed an increased concentration of glucose following 150C hypothermia, an observation consistent with a 'slowing down' of glycotysis. As a way of improving tumour oxygenation, localized hypothermia may be a useful means of radiosensitization
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