Hemodynamically “insignificant” stenoses stimulate neointimal thickening in experimental vein grafts

Abstract

Vein graft stenoses <50% are believed to be clinically “insignificant” because they cause little decrement in blood flow. However, the possible deleterious effects of minor flow disturbances on long-term cellular proliferation are unknown. The purpose of this study was to evaluate the effect of artificially created 50% stenoses on neointimal thickening in experimental vein grafts. Fifteen male New Zealand White rabbits underwent carotid interposition bypass grafting using the external jugular vein. Mid-graft 50% stenoses were created in eight grafts by the application of a two-millimeter internal diameter stainless steel clip. After four weeks, the grafts were perfusion-fixed, excised, and histologic sections were examined for neointimal thickening. Application of the clip caused a 50% reduction in external diameter (3.9 ± 0.4 mm to 2.0 mm), causing only slight perturbations in pressure gradient (Δp = 2.1 ± 1.1 to 2.3 ± 1.5 mmHg) and mean blood flow (flow 16 ± 3.0 to 14 ± 4.4 ml/min). After four weeks, four grafts had occluded (two from each group) and one clip had become dislodged, leaving ten grafts for analysis. Neointimal thickness was minimal in control grafts (88 ± 12 μm), but was significantly increased in stenotic grafts both immediately proximal (200 ± 39 μm; p = 0.03) and immediately distal to the stenosis (230 ± 50 μm; p = 0.02). Hemodynamically “insignificant” stenoses stimulate vein graft neointimal thickening. These results support the continued use of graft surveillance and an aggressive approach to the treatment of “minimal” vein graft lesions.