Comparison of intrathecally administered urokinase, tissue-type plasminogen activator, and combination of urokinase and lysine-plasminogen for clot lysis after experimental subarachnoid hemorrhage in dogs.
OBJECTIVE
The purpose of this study was to compare the fibrinolytic effect of urokinase (UK) with that of tissue plasminogen activator (tPA) on subarachnoid clots and to investigate the effect of lysine-plasminogen (Lys-plg) on fibrinolytic therapy.


METHODS
We measured subarachnoid clot lysis rate chronologically for 24 hours during continuous intrathecal irrigation with tPA or UK alone in a canine subarachnoid hemorrhage model. Also, we measured the clot lysis rate for 24 hours during continuous irrigation with UK and Lys-plg or with UK after preadministration of Lys-plg in the same model.


RESULTS
The rate of clot lysis caused by UK and tPA dose-dependently increased up to 3,000 IU/ml and 125,000 IU/ml, respectively. With the same molar concentrations, the lytic effect of tPA was significantly higher than that of UK. The slope of the dose-response curve, however, was almost the same with both agents, and the slope of the dose-response curve of UK and tPA for a 24-hour irrigation was 25 and 23% per log 10 concentration, respectively. On the other hand, clot lysis with the combined use of UK and Lys-plg was higher than that with the single use of UK. Particularly, the preadministration of Lys-plg markedly enhanced clot lysis by UK at the early stage of irrigation.


CONCLUSIONS
Subarachnoid clot lysis can be accelerated by administration of Lys-plg before UK administration and by use of high concentrations of UK or tPA.
Kajimoto
Y
Y
Department of Neurosurgery, Osaka Medical College, Takatsuki, Japan.
Ohta
T
T
Kuroiwa
T
T
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D007278:Injections, Spinal; D002542:Intracranial Embolism and Thrombosis / Q000097:blood* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010958:Plasminogen / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000473:pathology; D013346:Subarachnoid Space / Q000473:pathology; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C018998:lysyl-plasminogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator