Endothelial cell adaptation to chronic thrombosis

The autogenous vein graft has proven to be the most durable conduit in lower extremity vascular bypass grafts. Failures due to thrombosis, intimal hyperplasia, and progression of atherosclerotic disease 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 thromboses, little is known as to the effects of the thrombus on the function and morphology of endothelial cells. Earlier studies by this laboratory demonstrated the ability of arterialized canine vein grafts to recover function after 5 days of exposure to thrombus. This investigation sought to explore the limits of endothelial cell viability and recovery to extended periods of thrombosis.

Using a canine model of arterialized vein grafts, prostacyclin production (measured as 6-keto-PGF1a) was assessed in an ex vivo perfusion system from grafts exposed to thrombus for 10 days (group I) and 20 days (group II). Both groups underwent thrombectomy and a recovery period of 30 days. The grafts were perfused with Hanks' balanced salt solution and samples were obtained 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 PGF/graft area (cm2/min). Representative samples of each graft underwent scanning electron microscopy.

Without arachidonic acid, prostacyclin production of group II (20 day) grafts was greater than group I (10 day) grafts at 5 minutes of perfusion (4.31 versus 2.42, P = 0.08) and at 30 minutes (1.86 versus 0.95, P = 0.02). In response to the addition of arachidonic acid both groups increased prostacyclin production (group I, P = 0.004; group II, P = 0.12). A comparison was made between prostacyclin production at baseline and after addition of arachidonic 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 endothelial coverage between the study groups.

These results demonstrate that although endothelial cells are able to recover a basal level 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.