Tissue plasminogen activator-mediated thrombolysis of cerebral emboli and its effect on hemorrhagic infarction in rabbits.
Tissue plasminogen activator (tPA) dissolves intravascular thrombus and restores blood flow after thromboembolic vascular occlusion. The utility of this agent for treatment of stroke in humans may be limited by post-reperfusion hemorrhagic complications. We studied tPA-mediated thrombolysis in an animal model of cerebrovascular occlusion in order to determine what factors, if any, predispose tPA-treated animals to suffer hemorrhage. Small blood clot emboli were injected into the internal carotid arteries of rabbits. Angiograms confirmed occlusion of the middle cerebral artery or internal carotid artery in 100% of subjects. tPA or saline was administered as a 30-minute infusion at various times after embolization. Hemorrhage rates were similar in all groups regardless of treatment. tPA increased the prothrombin time and the thrombin time but not the partial thromboplastin time. There was no correlation between these changes in blood coagulation and the finding of cerebral hemorrhage. We observed a significant association between stroke severity and cerebral hemorrhage. We conclude that tPA treatment successfully causes thrombolysis of cerebral emboli without causing an increase in the incidence of cerebral hemorrhage in rabbits.
Lyden
P D
PD
Department of Neurology, Veterans Administration Medical Center, San Diego, CA 92093.
Zivin
J A
JA
Clark
W A
WA
Madden
K
K
Sasse
K C
KC
Mazzarella
V A
VA
Terry
R D
RD
Press
G A
GA
D000818:Animals; D001780:Blood Coagulation Tests; D002533:Cerebral Angiography; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology* / Q000473:pathology; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002542:Intracranial Embolism and Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator