This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation,
vascular endothelial growth factor (
VEGF) expression and vascularisation) to chronic
hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-
sarcomas in rats. In order to induce more pronounced tumour
hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic
hypoxia). A second group was acutely exposed to inspiratory
hypoxia for only 20 min prior to the measurements (acute
hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute
hypoxia reduced the median
oxygen partial pressure (pO(2)) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO(2) was significantly improved (median pO(2)=4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory
hypoxia, the number of perfused vessels increased (compared to acute
hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in
VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic
hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion.