Acylated Streptokinase – Plasminogen Complex in Patients with Acute Myocardial Infarction

Abstract

SummaryBRL 26921 is the p-anisoyl derivative of the primary streptokinase-human plasminogen complex in which the acyl group is specifically located at the catalytic centre of the enzyme. Doses of BRL 26921 ranging from 5 mg to 25 mg were given intravenously or into a coronary artery to 12 patients with acute myocardial infarction. The complex was well tolerated and produced no serious bleeding. Coronary artery reperfusion was demonstrated angiographically in three patients.In most patients, fibrinogen, plasminogen, α2 antiplasmin and a2 macroglobulin levels fell and the level of fibrinogen degradation products increased acutely post treatment indicating systemic fibrinolytic activation. The degree of this activation was variable but was profound in some. It appeared to be dose related and modified by the presence of streptokinase antibodies. BRL 26921 appears less “selectively” thrombolytic in patients than had been expected from animal models.

Coronary Thrombolysis in the Treatment of Women with Acute Myocardial Infarction

“…Indeed, the available evidence, although sparse, shows that previous studies identifying a more dramatic fibrinolytic response among women were likely the result of excessive dosing (per kilogram body weight) [5,8,9]. Observed differences may also be influenced by race [10], as blacks have been shown to express a more profound response following tPA administration.…”

Molecular Mechanisms of Thrombolytic Therapy

“…The affinity of plasminogen for fibrin, although specific, is however believed to be relatively low [39], Binding of the acylated complexes to fi brin, followed by deacylation, is expected to result in the generation of fibrin-associated plasmin and thus in a more fibrin-specific thrombolytic effect as compared to streptoki nase. The potential value of these complexes as thrombolytic agents is presently being in vestigated in animal models [37,40] and in humans [41],…”

The Acyl-Enzymes and Pro-Urokinase: Promising New Thrombolytic Agents

“…Even after an injection of 12 mg of BRL 26921 no change in fibrinogen level was observed [19]. How ever, therapeutic doses (loading dose of 10 mg. followed by injections of 5-10 mg ev ery 8 h during 3-5 days), as employed in the treatment of deep vein thrombosis, or 30 mg, as used in myocardial infarction [2,25], pro duced a defibrination syndrome as observed during SK therapy.…”

“…In acute myocardial infarction reperfusion occurred in 70-75% of patients after intra coronary administration of 5-30 mg of BRL 26921, and in 60-65 % of patients after intra venous administration of 30 mg of BRL 26921 [1,2,17,25],…”