A long-half-life and fibrin-specific form of tissue plasminogen activator in rabbit models of embolic stroke and peripheral bleeding. Stroke 25: 2072–2078, discussion 2078–2079

Background and Purpose We compared the activity of a new long-half-life, fibrin-specific tissue-type plasminogen ac-tivator (TPA) variant with that of wild-type TPA in rabbit models of embolic stroke and peripheral bleeding. Methods In the embolic stroke model, TPA-induced clot lysis is followed by continuous monitoring of a radiolabeled clot lodged in the middle cerebral artery. Twenty-four hours after embolization and treatment with either thrombolytic agent or excipient, the brains are removed, fixed, and evalu-ated for cerebral hemorrhage. In a parallel template bleeding time experiment, the effects of equipotent doses of the two TPA molecules were measured. Results Infusion of wild-type TPA or bolus administration of the TPA variant resulted in dose-dependent clot lysis. The TPA variant was found to be an order of magnitude mor