Hemorrhagic transformation after fibrinolytic therapy with tissue plasminogen activator in a rat thromboembolic model of stroke.

In this study, the effects of early vs. delayed tPA treatment on the development of hemorrhagic transformation was compared in a rat thromboembolic model of stroke. Fibrinolysis was performed by administering tPA intravenously at 2 or 6 h after ischemic onset. Twenty-four hours later, confluent hemorrhagic infarction was observed only in rats treated with tPA at 6 h at the rate of 50%. In this delayed treatment group, significantly increased numbers of polymorphonuclear leukocytes (PMNL) were observed to accumulate inside microvessels within the ischemic core. PMNL accumulation may be related to the induction of hemorrhagic infarction after delayed tPA treatment.