A method for the assessment of hypoxia in the arterial wall, with potential application in vivo

According to the anoxemia theory of atherosclerosis, an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerotic lesions. Direct in vitro and in situ measurements have shown that Po-2 is decreased in the inner part of the media, but the degree of hypoxia in vivo or the distribution of hypoxia along the arterial tree is not known. We applied a hypoxia marker, 7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline (NITP), to develop a method for the detection of hypoxia in the arterial wall. Immunoperoxidase and immunofluorescence were used to detect the marker, and a clearly Po-2 dependent staining was observed in the media of rabbit and swine aorta in vitro. The cutoff Po-2 level was probably around 2 to 3 mm Hg. In experimental atherosclerotic lesions in the rabbit the marker seemed to bind to foam cells that were already at a higher surrounding Po-2, which might reflect a higher local oxygen consumption. The binding of the marker to endothelial cells was not Po-2 dependent. One explanation for this finding could be that the marker was metabolized via a non-oxygen-dependent pathway in these cells. We propose that this method may be used to assess arterial wall hypoxia in vivo. Furthermore, the spatial resolution allows the detection of local variations within the arterial tree.