ENDOTHELIAL-CELL ADAPTATION TO CHRONIC THROMBOSIS

BACKGROUND: The autogenous vein graft has proven to be the most durabl e conduit in lower extremity vascular bypass grafts. Failures due to t hrombosis, intimal hyperplasia, and progression of atherosclerotic dis ease commonly plague the vascular surgeon. Part of the ability of vein grafts to provide a nonthrombogenic surface relies on the capability of the endothelial cell to produce prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. Once a graft fails and thrombos es, little is known as to the effects of the thrombus on the function and morphology of endothelial cells. Earlier studies by this laborator y demonstrated the ability of arterialized canine vein grafts to recov er function after 5 days of exposure to thrombus. This investigation s ought to explore the limits of endothelial cell viability and recovery to extended periods of thrombosis. METHODS: Using a canine model of a rterialized vein grafts, prostacyclin production (measured as 6-keto-P GF(1a)) was assessed in an ex vivo perfusion system from grafts expose d to thrombus for 10 days (group I) and 20 days (group II). Both group s underwent thrombectomy and a recovery period of 30 days. The grafts were perfused with Hanks' balanced salt solution and samples were obta ined at 5 and 30 minutes to determine prostacyclin levels. Arachidonic acid was then added to a new perfusate of Hanks' solution and samples were again obtained at 5 and 30 minutes. Results were expressed as PG F/graft area (cm(2)/min). Representative samples of each graft underwe nt scanning electron microscopy. RESULTS: Without arachidonic acid, pr ostacyclin production of group 11 (20 day) grafts was greater than gro up I (10 day) grafts at 5 minutes of perfusion (4.31 versus 2.42, P = 0.08) and at 30 minutes (1.88 versus 0.95, P = 0.02). In response to t he addition of arachidonic acid both groups increased prostacyclin pro duction (group I, P = 0.004; group II, P = 0.12). A comparison was mad e between prostacyclin production at baseline and after addition of ar achidonic acid. Group I grafts demonstrated a greater percent increase in prostacyclin production compared to group II (385% versus 229%, P = 0.01). Scanning electron microscopy showed no differences in endothe lial coverage between the study groups, CONCLUSIONS: these results dem onstrate that although endothelial cells are able to recover a basal l evel of prostacyclin production, the response to substrate stimulation diminishes with increased exposure time to thrombus. This diminished response may be important in understanding the ability of vein grafts to survive after a period of thrombosis. (C) 1997 by Excerpta Medica, Inc.