title: The free-radical scavenger edaravone accelerates thrombolysis with alteplase in an experimental thrombosis model.
abstract: OBJECTIVE
  Reperfusion injury after thrombolytic therapy can have adverse neurologic effects. The free-radical scavenger edaravone is used in combination with the recombinant tissue plasminogen activator alteplase to treat acute ischemic stroke. However, basic investigations of this combination use remain inadequate. Here, we used an in vivo model to investigate the effects of edaravone on alteplase-induced thrombolysis.
  
  
  METHODS
  Thrombolysis was evaluated by using a He-Ne-laser-induced thrombosis model in rat mesenteric microvessels. Changes in thrombus volume were analyzed with the image analysis software Image-Pro Plus (Media Cybernetics, USA). There were three experimental groups (placebo, alteplase 0.6 mg/kg, alteplase 0.6 mg/kg + edaravone 10.5 mg/kg). Sequential changes (0 to 60 min) in thrombus volume were compared by using a relative optical density method that we had used previously.
  
  
  RESULTS
  In the placebo group, the thrombus volume at 60 min, reflecting the extent of thrombolysis, was 97.2% ± 5.7% of the initial value. In the alteplase group, thrombus volume decreased to 70.7% ± 4.1% (P<0.01) after 20 min and 14.2% ± 6.6% after 60 min. In the alteplase+edaravone group, thrombus volume decreased to 66.9% ± 7.2% (P<0.001) after 10 min and 10.9% ± 2.3% after 60 min.
  
  
  CONCLUSIONS
  These results support the hypothesis that edaravone accelerates thrombolysis by alteplase.
authors.affiliation: Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan. Electronic address: tsutomu@nutr.kobegakuin.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D000077553:Edaravone; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000737:chemistry*; D008297:Male; D008833:Microcirculation; D010919:Placebos; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D020521:Stroke / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D010919:Placebos; D010959:Tissue Plasminogen Activator; D000077553:Edaravone; D000983:Antipyrine
keywords: Alteplase; Edaravone; Stroke; Thrombolysis; Tissue plasminogen activator