Effect of intravenous administration of tissue-type plasminogen activator (AK-124) in acute myocardial infarction and changes in blood coagulation and fibrinolytic activity by the drug

We administered tissue-type plasminogen activator (t-PA) intravenously to 10 patients with acute myocardial infarction (AMI) within 6 hours after onset of symptoms, and then examined the state of reperfusion by coronary arteriography (CAG) and observed changes in blood coagulation and fibrinolytic activity to evaluate their effects. AK-124 (by Asahi Chemical Industry and Kowa Co., Ltd. in collaboration), a t-PA produced by tissue culture of normal human lung cells, was given in dosage of 48, 000-576, 000 A. K. units by intravenous infusion over 30-45 minutes. In 7 patients who received t-PA reflow or improved flow was detected on CAG. In t-PA treated patients, euglobulin lysis activity clearly increased, euglobulin lysis time clearly shortened, and D-dimer increased. Levels of circulating fibrinogen and α2-plasmin inhibitor decreased after treatment with t-PA by an average of 12%, 14% of baseline values respectively, but plasminogen showed no detectable change. A hematoma at the site of the catheter insertion was observed in one patient. These observations suggest that t-PA has a higher specificity for fibrin bound plasminogen than for plasminogen and prduces coronary thrombolysis without causing systemic fibrinolysis at least with the present dosage.