Delayed tissue-plasminogen activator therapy in a rabbit model of thromboembolic stroke.
This study investigated the efficacy and safety of delayed therapy with tissue-plasminogen activator (t-PA) in a rabbit model of thromboembolic stroke. The t-PA therapy was started 3, 4, or 5 hours after autologous clot embolization. New Zealand rabbits were randomized to receive a 2-hour intravenous infusion of either t-PA (6.3 mg/kg) or a saline solution (0.9% saline) after an autologous clot had embolized the anterior cerebral circulation. Regional cerebral blood flow (rCBF), intracranial pressure (ICP), and infarct size were measured to determine the effects of the delayed administration of the t-PA after intracranial embolization. Additionally, the following physiological parameters were monitored throughout the protocol: mean arterial pressure, hematocrit, arterial blood gases, glucose, and core and brain temperatures. All animals were studied for 4 hours after the administration of the t-PA or control solution; thus, the duration of each experiment was 7, 8, or 9 hours after autologous clot embolization. In control animals, brain infarct size and final ICP values were directly related to the length of time studied after clot embolization; among control animals, the largest infarct size and greatest rise in ICP were seen 9 hours after embolization.(ABSTRACT TRUNCATED AT 250 WORDS)
Gross
C E
CE
Division of Neurosurgery, Vermont Center for Vascular Research, Burlington, USA.
Raymond
S J
SJ
Howard
D B
DB
Bednar
M M
MM
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D005260:Female; D007262:Infusions, Intravenous; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use* / Q000633:toxicity
D010959:Tissue Plasminogen Activator