Delayed treatment with a t-PA analogue and streptokinase in a rabbit embolic stroke model.
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.
Phillips
D A
DA
Department of Radiology, University of Massachusetts Medical School, Worcester.
Fisher
M
M
Davis
M A
MA
Smith
T W
TW
Pang
R H
RH
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*
D010446:Peptide Fragments; D013205:Staphylococcal Protein A; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; C059835:tissue plasminogen activator-(staphylococcal A, B fragment) dimer