title: Hirudin and s18886 maintain luminal patency after thrombolysis with alfimeprase.
abstract: BACKGROUND
  An optimal strategy to improve reperfusion in patients with arterial occlusions is a recognized clinical need. We hypothesized that hirudin (thrombin inhibitor) and S18886 [S18, thromboxane A(2) receptor (TP) antagonist] would improve blood flow and reperfusion rates after thrombolysis with the direct-acting fibrinolytic enzyme alfimeprase.
  
  
  METHODS
  In anesthetized beagles, carotid artery thrombosis was induced by electrolytic endothelial injury. After 30 minutes of occlusion, animals were administered vehicle, hirudin, and/or S18. Carotid artery blood flow was monitored for 90 minutes after the infusion of alfimeprase or recombinant tissue plasminogen activator (rt-PA).
  
  
  RESULTS
  The onset to reperfusion was more rapid in animals treated with alfimeprase than in those treated with rt-PA. All the animals treated with hirudin + S18 + alfimeprase maintained vessel patency, and all vehicle-treated animals reoccluded. In animals treated with hirudin + S18 + alfimeprase, time to reocclusion and total reflow time after thrombolysis were longer compared with vehicle-treated animals. The quality and quantity of blood flow were most improved in animals treated with hirudin + S18 + alfimeprase. There were no significant differences in time to reocclusion, total reflow time, and quality and quantity of blood flow between vehicle + rt-PA-treated animals and hirudin + S18 + rt-PA-treated animals.
  
  
  CONCLUSIONS
  Dual antithrombotic therapy with hirudin and S18 improves reperfusion after thrombolysis with alfimeprase but not rt-PA.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-5632, USA. jullial@umich.edu
authors.forename: Jullia Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Francis S
authors.initials: FS
authors.lastname: Markland
authors.forename: Benedict R
authors.initials: BR
authors.lastname: Lucchesi
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D002341:Carotid Artery Thrombosis / Q000188:drug therapy; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D008297:Male; D008666:Metalloendopeptidases / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D015424:Reperfusion / Q000379:methods; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D009281:Naphthalenes; D011422:Propionates; D017482:Receptors, Thromboxane; C501362:terutroban; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; C436755:alfimeprase