Saratin (an inhibitor of platelet-collagen interaction) decreases platelet aggregation and homocysteine-mediated postcarotid endarterectomy intimal hyperplasia in a dose-dependent manner

Background: This study investigated Saratin's (Merck KGaA, Darmstadt, Germany) prevention of platelet adhesion and intimal hyperplasia at different doses and in the hyperhomocystinemia rat carotid endarterectomy (CEA) model. Methods: Rats were divided into two groups: (1) platelet adhesion or (2) luminal stenosis because of intimal hyperplasia. At CEA, rats received 0, 0.5, 5.0, 10.0, or 20.0 mug Saratin on the artery. Post-CEA platelet aggregation was evaluated by standard error of the mean. Intimal hyperplasia group received either (1) control or (2) 4.5 g/kg DL-homocystine diets for two weeks followed by CEA and treated with diluent or 5.0 mug Saratin. Endpoints included platelet adhesion, intimal hyperplasia, plasma homocysteine (HCys), and its metabolic enzymes cystathionine beta-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR). Results: Platelet adhesion: post-CEA, platelet adhesion was reduced by 63%, 67%, and 67% in Saratin doses greater than or equal to5.0 mug. Intimal hyperplasia: 5.0 mug Saratin in the HCys group decreased intimal hyperplasia by 45% compared with the non-Saratin-treated HCys group. Plasma HCys levels were not altered with Saratin treatment in the HCys groups nor were CBS or MTHFR. Conclusions: Saratin significantly inhibited platelet adhesion at greater than or equal to5.0 mug, and Saratin at 5.0 Ag attenuated luminal stenosis in a hyperhomocysteinemic rat CEA model. (C) 2004 Excerpta Medica Inc. All rights reserved.