Saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion, decreases platelet aggregation and intimal hyperplasia in a rat carotid endarterectomy model

Purpose: Post-carotid endarterectomy, thrombosis, and intimal hyperplasia m ay be decreased by the inhibition of platelet adhesion and activation. In t his study, a novel agent, saratin, was used to inhibit platelet-to-collagen adhesion in a rat carotid endarterectomy model. Saratin is a recombinant p rotein isolated from the saliva of the medicinal leech Hirudo medicinalis, which is thought to act by binding to collagen, and inhibits von Willebrand factor-collagen interaction under conditions of increased shear and theref ore, the adherence and activation of platelets at the vessel wall. Saratin has the advantage of being a nonsystemic, site-specific topical application . Methods. A rat carotid endarterectomy model was used in which an open techn ique with arteriotomy and intimectomy was used. Saratin was applied to the endarterectomized surface of the carotid artery before arterial closure. En d point measurements included platelet adhesion, thrombosis rate, intimal h yperplasia development, bleeding times, and platelet counts. Electron micro graphs of carotid arteries were used for quantitative analysis of platelet aggregation and platelet counts. Intimal hyperplasia and thrombosis were as sessed with computer-assisted morphometric analysis of elastin-stained caro tid artery sections with direct measurement of the intimal hyperplasia area . Results. The topical application of saratin significantly decreased platele t adhesion compared with controls at 3 hours after carotid endarterectomy ( 64 +/- 17 vs 155 +/- 33 platelets per grid, P=.05),and 24 hours after carot id endarterectomy (35 +/- 11 vs 149 +/- 37 platelets per grid, P=.0110), re spectively. A percent luminal stenosis, as a measure of intimal hyperplasia , was significantly decreased with saratin application compared with contro ls (10.9%+/-1.8% vs 29.8%+/-6.8%, P=.0042). This decrease in intimal hyperp lasia formation correlated with the inhibition of platelet adhesion. Thirty -three percent of control arteries were found to be thrombosed 2 weeks afte r carotid endarterectomy compared with a 0% thrombosis rate in the saratin- treated group (P=.0156). No increased bleeding was encountered along the ar terial suture line in the saratin group. Bleeding times and systemic platel et counts were not found to change significantly in the saratin-treated rat s compared with control rats at 3 and 24 hours after endarterectomy. Conclusion: Saratin significantly decreased platelet adhesion, intimal hype rplasia, luminal stenosis, and thrombosis after carotid endarterectomy in r ats. Saratin did not increase suture line bleeding or bleeding times, and d id not decrease platelet counts. Saratin may serve as a topical agent to be used for the site-specific inhibition of thrombosis and intimal hyperplasi a after vascular manipulation.