Dose-response of rt-PA and its combination with aspirin in a rat embolic stroke model.
The efficacy and safety of thrombolysis with different dose regimens of recombinant tissue plasminogen activator (rt-PA) and its combination with aspirin was tested in an embolic stroke model. In rats the carotid territory was embolized with a single clot formed in a polyethylene tube and washed with saline. Fifteen minutes after embolization 10 animals were treated with rt-PA 10 mg kg-1; 11 with 15 mg kg-1; 12 with 20 mg kg-1 and 9 with 10 mg kg-1 + 20 mg kg-1 aspirin and 34 animals with saline. Rt-PA 10 mg kg-1 reduced median infarct volume (in percent of the ipsilateral hemisphere volume) from 19.5 to 4.8; rt-PA 15 mg kg-1 to 2.0; rt-PA 20 mg kg-1 to 0.0, while rt-PA 10 mg kg-1 + aspirin resulted in a median infarct volume of 9.5%. Thrombolytic therapy significantly and dose dependently (p = 0.001) reduced the infarct volume, improved the presacrifice clinical score and increased (p = 0.02) angiographically verified reperfusion. There was no additional benefit of coadministration of aspirin.
Overgaard
K
K
Department of Neurology, University Hospital of Copenhagen, Rigshospitalet, Denmark.
Sereghy
T
T
Pedersen
H
H
Boysen
G
G
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000188:drug therapy; D002533:Cerebral Angiography; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D001241:Aspirin