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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effect of argatroban, a selective thrombin inhibitor, on animal models of cerebral thrombosis.

Argatroban, (2R,4R)-4-methyl-1-(N2 [(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)-sulfonyl]-L-arginyl)-2-pi peridinecarboxylic acid, a selective and competitive thrombin inhibitor, was examined for effectiveness in three different experimental models of cerebral thrombosis in rats, namely, the four-vessel occlusion model, the middle cerebral artery occlusion model, and the distal middle cerebral artery occlusion model. Argatroban was demonstrated to be effective in these experimental models of thrombosis. Among these models, the distal middle cerebral artery occlusion model was the most similar to clinical cerebral thrombosis with respect to restriction of the infarction to the cerebral cortex and the accompanying stable neurologic deficits. In this model, the thrombus was generated at the Y-shaped bifurcation of the middle cerebral artery by green light irradiation through a cranial window after administration of rose bengal. Argatroban given after thrombus formation by intraperitoneal implantation of an osmotic pressure pump was shown to reduce infarct size and neurologic deficits on day 3 and microthrombi generation on day 1, and to raise the regional cerebral blood flow on day 1, at a plasma level of 0.2 to 0.6 microM supporting its clinical usefulness in the treatment of acute-phase cerebral thrombosis. Argatroban was considered to exert its effects by salvaging neuronal cells in the ischemic penumbra and suppressing extension of the infarction into the penumbra by keeping blood vessels patent, mainly through the inhibition of microthrombogenesis.[1]

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