EFFECTS OF INTRAVENOUS ADMINISTRATIONOF A TISSUE-TYPE PLASMINOGEN ACTIVATOR (AK-124) IN ACUTE MYOCARDIAL INFARCTION, INCLUDING CHANGES IN BLOOD COAGULATION AND FIBRINOLYTIC ACTIVITY.- PRELIMINARY REPORT

We administered a tissue-type plasminogen activator (t-PA) intravenously to 10 patients with acute myocardial infarction (AMI), within 6 hours after the onset of symptoms, and then examined the state of reperfusion by coronary arterio graphy (CAG), and observed changes in blood coagulation and fibrinolytic activity to evaluate the drug effects. AK-124 (produced by Asahi Chemical Industry and Kowa Co., Ltd.in collaboration), a t-PA produced the by tissue cultureof normal human lung cells, was given in a dosage of48,000_576,000 A.K. units by intravenous infusionover 30_45 minutes. In 7 patients who received t-PA, areflow or improved flow was detected on CAG. In t-PAtreated patients, euglobulin lysis activity clearly increased, euglobulin lysis time clearly shortened, and D-dimer increased. After t-PA treatment, the levels of circulating fibrinogen and a2-plasmin inhibitor decreased by an average of 12%, and 14% of base-line 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 plasma plasminogen, and produces coronary thrombolysis without causing systemic fibrinolysis, at least with the above dosage.