Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke.
Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.
Bednar
M M
MM
Division of Neurosurgery, University of Vermont, Burlington.
McAuliffe
T
T
Raymond
S
S
Gross
C E
CE
D000818:Animals; D001158:Arteries; D001921:Brain / Q000473:pathology*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D002542:Intracranial Embolism and Thrombosis / Q000150:complications*; D007427:Intracranial Pressure; D008297:Male; D010100:Oxygen / Q000097:blood; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D002245:Carbon Dioxide; D010959:Tissue Plasminogen Activator; D010100:Oxygen