INFLUENCE OF TISSUE PLASMINOGEN-ACTIVATOR AND HEPARIN ON CEREBRAL-ISCHEMIA IN A RABBIT MODEL

Background and Purpose: The aims of this study were to verify that tissue-type plasminogen activator given either 1 or 2 hours after experimental embolic stroke in rabbits diminishes the volume of resulting ischemic brain and to ascertain the effect of the simultaneous administration of heparin. Methods: We embolized the middle cerebral artery of rabbits by injecting preformed autologous arterial ("white") thrombus into one internal carotid artery. Treatment with 2 mg/kg tissue-type plasminogen activator, alone or in combination with heparin, was commenced either 1 or 2 hours after embolization. The animals were killed 5 hours after treatment commenced, and their brains were examined for evidence of ischemia and hemorrhage. Results: Administration of tissue-type plasminogen activator significantly diminished the size of the resulting brain ischemia. Administration of heparin, with or instead of tissue-type plasminogen activator, did not result in a significant decrease in the volume of cerebral ischemia, but it also did not lead to hemorrhagic transformation of the stroke. Conclusions: In the rabbit model, administration of tissue-type plasminogen activator within 2 hours diminished the volume of brain rendered acutely ischemic by embolic stroke. Since the simultaneous administration of heparin during this same period did not result in any instances of hemorrhagic transformation, tissue-type plasminogen activator may have some place for use in such circumstances to mitigate a tendency to further embolic or thrombotic events.