Fibrin-selective thrombolytic therapy for acute myocardial infarction.

Abstract

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 α2-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. 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 may occur at the level of the plasminogen activators by plasminogen activator inhibitors (PAI) or at the level of plasmin, mainly by α2-antiplasmin. SK indicates streptokinase. The beneficial effects of thrombolytic therapy in acute myocardial infarction are now well established, and it has become routine …