Plasminogen Activator Inhibitor Type-1 (Part Two): Role for Failure of Thrombolytic Therapy. PAI-1 Resistance as a Potential Benefit for New Fibrinolytic Agents

Rapid and sustained reperfusion of an occluded coronary artery is the goal of thrombolytic therapy in acute myocardial infarction. However, the clot-dissolving efficacy of fibrinolytic agents such as tissue-type plasminogen activator (t-PA) is limited, in vivo, in part by the action of plasminogen activator inhibitor type-1 (PAI-1). A new generation of fibrinolytic agents has been genetically engineered to have greater resistance to PAI-1 inhibition. This article␣reviews the pathophysiologic role of PAI-1 in failure␣of thrombolytic therapy and describes the advantages that PAI-1-resistance may confer upon␣fibrinolytic agents such as TNK-t-PA, the new fibrinolytic agent with the most powerful PAI-1 resistance.