Studies of Suloctidil in Experimental Thrombosis in Baboons

Abstract

SummarySuloctidil has been evaluated in the baboon for its antithrombotic efficacy using models of both acute and chronic arterial thrombogenesis. Acute thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous shunts. 111In-platelet deposition was measured by scintillation camera imaging for one hour. The results after oral administration of suloctidil (100 mg/kg/d in two divided doses) were not different from control studies. Moreover, concurrent heparin anticoagulation did not affect 111In-platelet deposition compared with control data. In contrast, ticlopidine (20 mg/ kg/d) significantly decreased platelet deposition that was reduced further by the addition of heparin.Chronic arterial-thromboembolism was initiated by segments of polyurethane (Biomer) cannula introduced into chronic arteriovenous shunts. Thrombus formation by the polyurethane cannula was measured as 111In-platelet turnover (corrected for removal of senescent platelets). Cannula platelet consumption was unaffected by suloctidil (20 mg/kg/d given in two divided doses for two days preceding and throughout the period of platelet survival measurement). In contrast, dipyridamole (10 mg/ kg/d) and sulfinpyrazone (100 mg/kg/d) completely interrupted cannula platelet consumption.We conclude that suloctidil probably has little or no effect on platelet-dependent thrombus formation.

Safety and Antithrombotic Efficacy of Moderate Platelet Count Reduction by Thrombopoietin Inhibition in Primates

“…In untreated animals, platelet deposition onto the grafts after 60 min of blood exposure showed a positive linear correlation with platelet count (Fig. 2A) (R 2 = 0.91, P < 0.0001), consistent with the premise that platelet concentrations within the normal range do not saturate arterial-type thrombogenesis in large vessels, and with earlier observations that normal platelet count variations predict arterial-type thrombus propagation rate in primates (36). In animals given control pre-immune serum, thrombosis experiments also showed a correlation between platelet count and deposition (Fig.…”

Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis.

“…25 24 Hirudin, the most specific known inhibitor of thrombin was, however, shown to be a potent antithrombotic agent in the same model.22 Therefore, we think that the antifibrin and antiplatelet effects of APC are related to its inhibition of thrombin generation and that platelet deposition in this model of arterial thrombosis is a thrombin-dependent process.…”

Interruption of acute platelet-dependent thrombosis by the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone.

“…1B). Neither aspirin (32.5 mg/kg per day given orally 2 hr prior to graft placement) nor aspirin combined with heparin (100 units/kg) affected vascular graft 'In-platelet deposition (27,31,32 By all measures, FPRCH2CI effectively interrupted graft thrombus formation. The platelet count was somewhat decreased in the animals before treatment due to formation of vascular graft thrombus.…”