Research of prevention and mechanisms for coronary reocclusion after coronary thrombolytic therapy

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Reocclusion of recanalized coronary arteries often limits the efficacy of coronary thrombolytic therapy in patients with acute myocardial infarction. The fibrinolytic system is impaired in patients with acute myocardial infarction. The primary regulatory element of fibrinolytic activity is plasminogen activator inhibitor (PAI). We measured the serial changes of PAI activity and tissue plasminogen activator (t-PA) antigen after recombinant t-PA (rt-PA) therapy. Plasma PAI activity levels were increased on admission and further increased within 24 hours in patients treated with rt-PA.There were two peaks in plasma PAI activity levels (IU/ml) at 4 hours (27.0<plus-minus>2.9) and at 16 hours (25.6<plus-minus>2.5) after the initiation of rt-PA infusion. The early increase of PAI activity may diminish the efficiency of reperfusion of rtActivated protein C (APC) is an important regulatory enzyme in hemostasis. After activation by thrombin-thrombomodulin complex on the endothelial cells, APC i … More nactivated factors VIIIa and Va and leads to inhibition of thrombin formation. APC also has been shown to enhance clot lysis by inhibiting the activity of PAI in endothelial cell cultures and in clot lysis assays. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the effect of APC on thrombolysis with rt-PA was studied in a canine model of coronary artery thrombosis. The dogs were randomly assigned to receive one of the following intravenous adjunctive hterapies : (1) control group ; (2) APC group : APC (0.6mg/kg) at a rate of 0.83mL/min ; (3) heparin group : heparin (200U/kg) at a rate of 0.83mL/min. In a 120-min observation after the termination of rt-PA,reocclusion developed in all the dogs in the control and heparin groups but in only 3 of the 10 dogs in the APC group. Time from recanalization to reocclusion was prolonged in the APC group as compared with the control and heparin groups. Bleeding time was prolonged in only the heparin group after the treatment. It is concluded that APC prevents coronary artery reocclusion after recanalization with rt-PA in a canine model of coronary artery thrombosis. Less