title: Delayed treatment with a t-PA analogue and streptokinase in a rabbit embolic stroke model.
abstract: Fibrinolytic therapy may be effective in the treatment of ischemic stroke, and clinical trials are under way. We evaluated two fibrinolytic agents, an analogue of tissue plasminogen activator (Fb-Fb-CF, the catalytic fragment of the tissue plasminogen activator molecule with a prolonged serum half-life, n = 10) and streptokinase (n = 7), in a rabbit model of embolic stroke. Both agents were given 3 hours after stroke onset, a time relevant to the clinical setting. Fb-Fb-CF was significantly better (p less than 0.04) than saline (n = 7) in restoring blood flow to previously occluded intracranial arteries, but streptokinase was ineffective. Neither fibrinolytic agent was associated with a substantial risk for intracerebral hemorrhagic side effects. Our study demonstrates that Fb-Fb-CF can safely and effectively reperfuse rabbit intracranial arteries 3 hours after occlusion, while streptokinase does not.
authors.affiliation: Department of Radiology, University of Massachusetts Medical School, Worcester.
authors.forename: D A
authors.initials: DA
authors.lastname: Phillips
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: M A
authors.initials: MA
authors.lastname: Davis
authors.forename: T W
authors.initials: TW
authors.lastname: Smith
authors.forename: R H
authors.initials: RH
authors.lastname: Pang
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002533:Cerebral Angiography; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000000981:diagnostic imaging; D002544:Cerebral Infarction / Q000000981:diagnostic imaging; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D011817:Rabbits; D013205:Staphylococcal Protein A / Q000009:adverse effects / Q000627:therapeutic use*; D013300:Streptokinase / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D010446:Peptide Fragments; D013205:Staphylococcal Protein A; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; C059835:tissue plasminogen activator-(staphylococcal A, B fragment) dimer