TISSUE-PLASMINOGEN ACTIVATOR - COMPARISON OF DOSE AND ROUTE OF ADMINISTRATION IN A RABBIT MODEL OF THROMBOEMBOLIC STROKE

The thrombolytic activity of tissue plasminogen activator was evaluate d in a rabbit model of thromboembolic stroke using both various concen trations (3, 5, and 10 mg/kg; 20% bolus with the remaining 80% given o ver 30 min.) and routes of administration (intravenous versus regional intra-arterial). An autologous tin-tagged clot was embolized to the b rain via the carotid artery. Tissue plasminogen activator was then giv en at the doses and routes noted (n = 3 in all groups). Thrombolytic a ctivity was followed by serial x-rays of the tin-laden clot over a fou r-hour period. The brains were then removed and subjected to gross ins pection. Only the intravenous dose of 5 mg/kg tissue plasminogen activ ator produced greater than 50% clot lysis in all animals. Doses of t-P A higher (10 mg/kg) or lower (3 mg/kg) than this were less effective i n producing thrombolysis, demonstrating greater than 50% clot lysis in only one animal of each group. We conclude that in this mode/ of thro mboembolic stroke the intravenous administration of tissue plasminogen activator is more effective than intra-arterial, and that the optimal dose is in the range of 5 mg/kg.