Evidence of hypoxic areas within the arterial wall in vivo

The anoxemia theory of atherosclerosis states that an imbalance between the demand and supply of oxygen in the arterial wall is a key factor for the d evelopment of atherosclerotic lesions. Direct in vitro and in situ measurem ents have shown that Po, is decreased in the more deeply situated parts of the media, but the degree of hypoxia in vivo or the distribution of hypoxia along the arterial tree is not known. For this reason, we have developed a method for the detection of hypoxia in the arterial wall in vivo by using a hypoxia marker, 7-(4'-(2-nitroimidazol-1-yl)-butyl)theophylline, that may be visualized by immunofluorescence. In the present study, we have used th is method in rabbits with experimentally induced atherosclerosis. Our resul ts indicate that zones of hypoxia occur at depth in the atherosclerotic pla que. The mechanism was probably an impaired oxygen diffusion capacity due t o the thickness of the lesion, together with high oxygen consumption by the foam cells. Thus, we have for the first time demonstrated that hypoxia act ually does exist in the arterial wall in vivo, lending support to the anoxe mia theory of atherosclerosis.