Thrombolytic effect of a plasminogen‐plasminogen activator chimera in a photochemically induced thrombosis (PIT) model

Abstract

The thrombolytic effects of the plasminogen/plasminogen activator chimera (SUN9216), comprising the fibrin‐binding kringle 1 domain of plasminogen and two kringle and the serine protease domain of the wild‐type tissue plasminogen activator (t‐PA) including a modification of the mannose glycosylation on the kringle 1 of t‐PA (PK1ΔFE1X), was compared with that of t‐PA by use of a photochemically induced thrombus (PIT) in the rat femoral artery. When SUN9216 was administered either as an i.v. infusion (1.0 mg kg−1) or as a single bolus i.v. injection (1.0 mg kg−1), all parameters were markedly improved compared to t‐PA administered as an i.v. infusion (3.0 mg kg−1). A higher concentration of plasminogen activator (PA) activity in plasma was observed after administration of SUN9216 which persisted for longer than that after t‐PA. It is concluded that the thrombolytic effect of SUN9216 is markedly greater than that of t‐PA. 1993 British Pharmacological Society