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 microg 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 microg 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 > or =5.0 microg. Intimal hyperplasia: 5.0 microg 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 > or =5.0 microg, and Saratin at 5.0 microg attenuated luminal stenosis in a hyperhomocysteinemic rat CEA model.
Davis
Joseph A
JA
University of Arkansas for Medical Sciences, Central Arkansas Veterans HealthCare System, Vascular Service, 112/PV, Little Rock, AR 72205, USA.
Brown
Aliza T
AT
Alshafie
Tarek
T
Poirier
Lionel A
LA
Cruz
Carlos P
CP
Wang
Yunfang
Y
Eidt
John F
JF
Moursi
Mohammed M
MM
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D016893:Carotid Stenosis / Q000473:pathology* / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016894:Endarterectomy, Carotid / Q000379:methods*; D006711:Homocystine / Q000008:administration & dosage; D007150:Immunohistochemistry; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D010975:Platelet Aggregation Inhibitors; D012471:Salivary Proteins and Peptides; C440095:saratin; D006711:Homocystine