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(Circulation. 1996;93:857-865.)
© 1996 American Heart Association, Inc.

Articles

Fibrin-Selective Thrombolytic Therapy for Acute Myocardial Infarction

D. Collen, MD, PhD

From the Center for Molecular and Vascular Biology, University of Leuven, and Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute of Biotechnology, Campus Gasthuisberg KU Leuven, Belgium.

Correspondence to D. Collen, MD, PhD, Center for Molecular and Vascular Biology, Campus Gasthuisberg, O & N, Herestr 49, B-3000 Leuven, Belgium. E-mail desire.collen@med.kuleuven.ac.be.

Key Words: Bench to Bedside • fibrin • myocardial infarction • thrombolysis

	Introduction

 
Thrombolytic therapy of acute myocardial infarction is based on the premise that coronary artery thrombosis is its proximate cause. Rupture of atheromatous plaque leads to occlusive thrombosis that produces myocardial ischemia and cell necrosis, leading to loss of ventricular function and possibly death.^{1 2} One approach to the treatment of established thrombosis consists of pharmacological dissolution of the blood clot by intravenous infusion of plasminogen activators that activate the fibrinolytic system (Fig 1). The fibrinolytic system includes a proenzyme, plasminogen, which is converted by plasminogen activators to the active enzyme plasmin, which in turn digests fibrin to soluble degradation products. Inhibition of the fibrinolytic system takes place at the level of both the plasminogen activators (mainly by plasminogen activator inhibitor-1) and plasmin (mainly by ₂-antiplasmin).³ Thrombolytic agents that are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction include streptokinase, recombinant tissue-type plasminogen activator (rTPA, prepared either as alteplase or as duteplase), rTPA derivatives such as reteplase and TNK-rTPA, anisoylated plasminogen streptokinase activator complex, two-chain urokinase-type plasminogen activator (UPA), recombinant single-chain UPA (prourokinase), and more recently, recombinant staphylokinase and derivatives. The hypothesis underlying thrombolytic therapy in acute myocardial infarction is that early and sustained recanalization prevents cell death, reduces infarct size, preserves myocardial function, and reduces early and late mortality.

View larger version (22K): [in this window] [in a new window]   Figure 1. Schematic representation of the fibrinolytic system. The proenzyme plasminogen is activated to the active enzyme plasmin by plasminogen activators. Plasmin degrades fibrin into soluble fibrin degradation products. Inhibition of the fibrinolytic system . . . [Full Text of this Article]

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