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 evaluated in a rabbit model of thromboembolic stroke using both various concentrations (3, 5, and 10 mg/kg; 20% bolus with the remaining 80% given over 30 min.) and routes of administration (intravenous versus regional intra-arterial). An autologous tin-tagged clot was embolized to the brain via the carotid artery. Tissue plasminogen activator was then given at the doses and routes noted (n = 3 in all groups). Thrombolytic activity was followed by serial x-rays of the tin-laden clot over a four-hour period. The brains were then removed and subjected to gross inspection. Only the intravenous dose of 5 mg/kg tissue plasminogen activator produced greater than 50% clot lysis in all animals. Doses of t-PA higher (10 mg/kg) or lower (3 mg/kg) than this were less effective in producing thrombolysis, demonstrating greater than 50% clot lysis in only one animal of each group. We conclude that in this model of thromboembolic 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.
Bednar
M M
MM
Division of Neurosurgery, University of Vermont, Burlington 05405.
Raymond
S J
SJ
Gross
C E
CE
D000818:Animals; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D011817:Rabbits; D013923:Thromboembolism / Q000150:complications / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
D010959:Tissue Plasminogen Activator