Dynamic Response of Breast Tumor Oxygenation to Hyperoxic Respiratory Challenge Monitored with Three Oxygen-Sensitive Parameters

The simultaneous measurement of three oxygen-sensitive parameters [arterial hemoglobin oxygen saturation (SaO2 ), tumor vascular-oxygenated hemoglobin concentration ( [HbO2 ), and tumor oxygen tension (pO]2 ) in response to hyperoxic respiratory challenge is demonstrated in rat breast tumors. The effects of two hyperoxic gases ] [oxygen and carbogen (5% CO2 and 95% O2 ) were compared, by use of two groups of Fisher rats with subcutaneous 13762NF breast tumors implanted in pedicles on the foreback. Two different gas-inhalation sequences were compared, i.e., air-carbogen-air-oxygenair and air-oxygen-air-carbogen-air. The results demonstrate that both of the inhaled, hyperoxic gases significantly improved the tumor oxygen status. All three parameters displayed similar dynamic response to hyperoxic gas interventions, but with different response times: the fastest for arterial SaO]2 , followed by biphasic changes in tumor vascular [HbO2 , and then delayed responses for pO]2 . Both of the gases induced similar changes in vascular oxygenation and regional tissue pO2 in the rat tumors, and changes in [HbO2 and mean pO]2 showed a linear correlation with large standard deviations, which presumably results from global versus local measurements. Indeed, the pO2 data revealed heterogeneous regional response to hyperoxic interventions. Although preliminary near-infrared measurements had been demonstrated previously in this model, the addition of the pO2 optical fiber probes provides a link between the noninvasive relative measurements of vascular phenomena based on endogenous reporter molecules, with the quantitative, albeit, invasive pO2 determinations.