Heparin fails to suppress intimal proliferation in experimental vein grafts

Heparin has been shown to suppress both vascular smooth muscle cell proliferation in vitro and intimal hyperplasia in animal models of arterial injury. We investigated the effect of heparin on early postoperative smooth muscle cell proliferation and intimal thickening in vein grafts placed in the rat infrarenal aorta. Experimental animals (n = 6) received subcutaneous heparin (800 units/kg with levels monitored by activated factor X assay) every 12 hours for 3 days after surgery to coincide with the known period of maximal vascular wall DNA synthesis after injury. Control animals (n = 7) received identical vein grafts but no heparin. Grafts were harvested with perfusion fixation 14 days after insertion. Tritiated thymidine autoradiography was used to derive a mitotic index in regions of interest along the grafts, and computerized planimetric measurements of intimal and medial thickness were made in the same regions. Evans blue lumenal staining at harvesting revealed confluent endothelial coverage of both experimental and control grafts. The mitotic index of the vein graft's midsection and perianastomotic regions was significantly higher (p less than 0.005) than that of the native aorta in all animals, indicating cellular proliferation within all grafts, with no differences noted between heparinized and control animals. Similarly, both groups exhibited vein graft intimal and medial thickening at the anastomoses relative to the midsection of the vein graft (p less than 0.001). Heparin, administered in the equivalent of pharmacologic clinical doses, failed to suppress cellular proliferation and intimal hyperplasia in this model of vein grafting.