Tissue-type plasminogen activator (t-PA) is a pivotal enzyme in the mammalian fibrinolytic system. It exerts its action by converting the zymogen plasminogen into the proteolytically active serine protease plasmin, which, in turn, degrades fibrin clots. Because of its affinity for fibrin, t-PA is the prototypic fibrin-specific plasminogen activator (1). This specificity and its lack of antigeni...

BACKGROUND AND PURPOSE The aims of this study were to verify that tissue-type plasminogen activator given either 1 or 2 hours after experimental embolic stroke in rabbits diminishes the volume of resulting ischemic brain and to ascertain the effect of the simultaneous administration of heparin. METHODS We embolized the middle cerebral artery of rabbits by injecting performed autologous arteri...

BACKGROUND AND PURPOSE The capacity of an intravenous infusion of double-stranded tissue-type plasminogen activator to salvage neurological functions in a rat model of thromboembolic stroke was studied. METHODS The model of thromboembolic stroke was induced by the intracarotid injection of 2-hour-old homologous blood clots to rats. Neurological functions were scored on a 5-point scale 48 hour...

An overview of eight randomized controlled trials of tissue-type plasminogen activator (Alteplase or Duteplase) and 10 of anisoylated plasminogen streptokinase activator complex (Anistreplase) showed that the odds of early death were reduced by 29% by tissue-type plasminogen activator and 46% by anisoylated plasminogen streptokinase activator complex, with overlapping 95% confidence intervals. ...

Recent experiments in vitro have shown that inhibition of human ci2-antiplasmin by a monoclonal antibody (MAb RWR) markedly enhances clot lysis by plasminogen activators. To extend these studies in vivo, we tested whether inhibition of clot or fibrin-bound o2-antiplasmin by MAb RWR could enhance the lysis of a human clot by tissue-type plasminogen activator (t-PA) in a rabbit jugular vein throm...

We review laboratory tests that evaluate thrombogenesis during acute coronary syndromes. These tests have been found to be valuable research tools in more clearly understanding the pathophysiology of acute coronary syndromes. In particular, we describe tissue factor, tissue factor pathway inhibitor, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrinopeptide A, tissue plasminogen ac...

To test the hypothesis that NO contributes to effects of angiotensin-converting enzyme inhibitors on fibrinolysis, fibrinolytic balance was assessed in 17 normal subjects during placebo and after randomized, double-blind 4-week treatment with the NO precursor L-arginine (3 g TID), ramipril (10 mg QD), or L-arginine+ramipril. Neither L-arginine nor ramipril alone affected basal plasminogen activ...

The discovery that tissue plasminogen activator can promote neuronal degeneration has uncovered a novel pathway leading to neuronal cell death and raises important issues concerning the use of tissue plasminogen activator as a thrombolytic therapy for stroke.

Previous studies have shown that angiotensin II stimulates the synthesis of plasminogen activator inhibitor-1 in cultured vascular cells, which suggests that activation of the renin-angiotensin system may impair fibrinolysis. We have investigated the effects of angiotensin II and of valsartan, a recently developed angiotensin II antagonist that is highly specific and selective for the angiotens...