FLUCTUATIONS IN RED-CELL FLUX IN TUMOR MICROVESSELS CAN LEAD TO TRANSIENT HYPOXIA AND REOXYGENATION IN TUMOR PARENCHYMA

Hypoxia occurs in tao forms in tumors. Chronic or diffusion-limited hy poxia is relatively well characterized. In contrast, intermittent or p erfusion-limited hypoxia is not well characterized, and it is not know n how common it is in tumors. The purpose of this study was to determi ne whether spontaneous fluctuations in tumor microvessel flow rate can modify vessel oxygen tension (pO2) sufficiently to cause intermittent hypoxia (PI; tissue pO2 < 3 mmHg) in the tumor parenchyma supplied by such vessels.,Microvessel red cell flux (RCF) and perivascular pO2 we re measured simultaneously and continuously in dorsal flap window cham bers of Fischer-344 rats with implanted R3230Ac tumors. In all vessels , RCF was unstable, with apex/nadir ratios ranging from 1.5 to 10. RCF and pO2 were temporally coordinated, and there were linear relationsh ips between the two parameters. Vascular pO2 was less sensitive to cha nges in RCF in well-vascularized tumor regions compared with poorly va scularized regions. Simulations of oxygen transport in a well-vascular ized region of a tumor demonstrated that two-fold variations in RCF ca n produce IH in 30% of the tissue in that region. In poorly vasculariz ed regions, such fluctuations would lead to an even greater percentage of tissue involved in transient hypoxia. These results suggest that I II is a relatively common phenomenon. It could affect binding of hypox ic cytotoxins to tumor cells, in addition to being an important source of treatment resistance. Intermittent hypoxia also could contribute t o tumor progression by providing repeated exposure of tumor cells to h ypoxia-reoxygenation injury.