taprostene and Myocardial-Infarction

Taprostene is a prostacyclin analogue that inhibits platelet aggregation and thus might be a useful adjuvant to thrombolytic agents in acute myocardial infarction. In a placebo-controlled dose rising study, taprostene or placebo was intravenously infused in 80 patients treated with the thrombolytic agent saruplase (rscu-PA) for acute myocardial infarction. Three doses of taprostene were used: 6.25; 12.5; or 25.0 ng.kg-1 x min-1. Taprostene or placebo was infused for 48 h, followed by a 24 h tapering period. All 80 patients had short symptom-to-treatment delay and marked ST segment elevation. Patency at 90 min was documented in 58/78 patients (two patients had no angiography). Success rate varied from 67-82% in the four treatment arms (P = 0.33). Patency after rescue PTCA was seen in 10 out of 13 patients. Of the 58 patients having a patent artery at 90 min, none of the 43 taprostene patients and one of the 15 placebo patients had a re-occluded artery at the second angiography at 32-48 h (5/58 patients had no recatheterization). Conversely, of nine patients who had successful rescue PTCA, three of four placebo patients had a re-occluded artery at the second angiography compared to one of five taprostene patients (one placebo patient had no recatheterization) (P = 0.33). Safety evaluation revealed no major difference between the placebo plus saruplase and the taprostene plus saruplase groups. Taprostene was well tolerated up to 25 ng.kg-1 x min-1. Although taprostene did not affect 90 min patency, there was a trend to better maintenance of patency after rescue PTCA.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Double-Blind Method; Drug Therapy, Combination; Epoprostenol; Hemodynamics; Humans; Infusions, Intravenous; Myocardial Infarction; Pilot Projects; Recombinant Proteins; Survival Rate; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator

In open chest dogs myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX). Reperfusion of the LCX was achieved by infusion of the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA). The myocardial salvage by r-scu-PA alone and in combination with the epoprostenol (prostacyclin) analog taprostene (CG 4203) was compared. There were four experimental groups: group 1 (n = 4) did not receive any treatment after LCX thrombosis; in group 2 (n = 9) at 100 min after LCX thrombosis r-scu-PA (20 micrograms.kg-1.min-1 i.v. for 30 min) was infused; in groups 3 and 4 treatment with taprostene started concomitantly with r-scu-PA infusion. The taprostene infusions lasted for 120 min and the doses were 0.1 microgram.kg-1.min-1 in group 3 (n = 6) and 0.215 microgram.kg-1.min-1 in group 4 (n = 6). Time to r-scu-PA-induced recanalisation ranged from 18-22 min with no significant difference between groups 2-4. Percent of left ventricle at risk did not differ between the groups. Infarct size as percent of the risk zone was 48.3 +/- 7.7 in group 1, 25.3 +/- 3.7 in group 2, 21.3 +/- 6.5 in group 3 and 17.1 +/- 3.5 in group 4 (p less than 0.05 groups 2-4 vs group 1). Incidence of ectopic beats increased after r-scu-PA-induced reperfusion in groups 2-4, but was significantly reduced by taprostene.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Coronary Thrombosis; Creatine Kinase; Dogs; Epoprostenol; Female; Hemodynamics; Male; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Plasminogen Activators; Recombinant Proteins; Urokinase-Type Plasminogen Activator