Summary:Vascular endothelial growth factor (VEGF) induces increased vessel permeability and formation of abnormal vessels. To investigate cerebral blood flow (CBF) during local overexpression of VEGF recombinant adenoviruses carrying the human VEGF165 complementary DNA (2.3 to 23 · 10 8 pfu/mL) were injected stereotactically into the caudate nucleus of anesthetized rats. Saline and adenoviruses carrying the -galactosidase gene served as controls. Eleven days later (1) size and density of vessels were assessed in hematoxylin-eosinstained sections, (2) vascular permeability was measured by intravenous Evans blue injections, and (3) local CBF (lCBF) was quantified using the iodo-[ 14 C]antipyrine technique. Dosedependent increases were found in (1) vessel density and size (only vessels >43 m could be quantified morphologically), (2) Evans blue extravasation and brain edema formation, and (3) lCBF (up to eightfold). At medium doses, hyperemic areas and smaller areas of decreased lCBF were found. In low flow areas, vascular cross-sectional areas were increased 223-fold and vessel density up to 10-fold. In high flow areas, these parameters were increased 32-fold and up to 15-fold, respectively. Adenovirus mediated VEGF overexpression results in (1) increased vessel size and density, (2) areas of increased and of decreased flow, and (3) more and smaller vessels in high flow than in low flow areas. These results indicate a diverging flow pattern of newly formed vessels.
In sheep, incidence of histological and clinical ischemic injury of the spinal cord following endografting was very low. Complete thoracic aortic stent-grafting was feasible without permanent neurologic deficit. Following endovascular coverage or clipping of their origins, there is retrograde filling of the intercostal arteries which remain patent.
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