Oxygen Pressures in the Interstitial Space of Skeletal Muscle and Tumors in vivo

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Abstract
A new Oxyphor (Oxyphor G3) has been used to selectively determine the oxygen pressure in interstitial (pericellular) spaces. Oxyphor G3 is a Pd-tetrabenzoporphyrin, encapsulated inside generation 2 poly-arylglycine (AG) dendrimer, and therefore is a true near infrared oxygen sensor, having a strong absorption band at 636nm and emission near 800nm. The periphery of the dendrimer is modified with oligoethylene glycol residues (Av. MW 350) to make the probe water soluble and biologically inert. Oxyphor G3 was injected along ’tracks’ in the tissue using a small needle (30gage or less) and remained in the pericellular space, allowing oxygen measurements for several hours with a single injection. The oxygen pressure distributions (histograms) were compared with those for Oxyphor G2 in the intravascular (blood plasma) space. In normal muscle, in the lower oxygen pressure region of the histograms (capillary bed) the oxygen pressure difference was small. At higher oxygen pressures in the histograms there were differences consistent with the presence of high flow vessels with oxygen pressures substantially above those of the surrounding interstitial space. In tumors, the oxygen pressures in the two spaces were similar but with large differences among tumors. In mice, anesthesia with ketamine plus xylazine markedly decreased oxygen pressures in the interstitial and intravascular spaces compared to awake or isoflurane anesthetized mice.