Prostacyclin production in regions of arterial stenosis

The effect of abnormal flow dynamics on prostacyclin (PGI2) production by intact endothelium is unknown. To investigate this we studied the effects of graded stenoses on vessel wall PGI2 production in dogs (n = 8) whose femoral and carotid arteries (n = 32) were narrowed by machine-milled clips, producing 1.0 cm segmental stenoses of 25%, 50%, 75%, and 90% diameter reduction. Three dogs were injected with Indium 111-labeled platelets and 12 vessels were scanned for platelet deposition. All stenotic vessels were excised at 6 weeks for histologic study (hematoxylin-eosin section and immunohistochemistry for factor VIII) and PGI2 radioimmunoassay (as the metabolite 6-keto PGF1 alpha). All vessels remained patent with no thrombus formation in any segment. Vessel imaging in platelet-labeled animals showed no significant deposition. Histologic analysis demonstrated an intact endothelial surface in the stenotic segments, confirmed by the demonstration of factor VIII production by these cells. PGI2 production (per unit surface area) by the arterial segments with greater than or equal to 50% stenosis markedly exceeded the PGI2 production by the normal proximal and distal segments (p less than 0.0002) and showed further significantly increased production with increasing degrees of stenosis (p less than 0.00001). The data indicate increased PGI2 production by normal endothelium in regions of arterial stenosis. The mechanism of this increase is unknown, but this endothelial "turn on" effect may serve to inhibit deposition of platelets and thrombus formation in the presence of disordered flow patterns.