Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion.
نویسندگان
چکیده
BACKGROUND Optimal coronary thrombolysis should be prompt and persistent. Although activation of platelets and increased thrombin activity have been associated with clinical thrombolysis, the role of each in delaying thrombolysis or inducing early coronary reocclusion has been difficult to define. METHODS AND RESULTS In conscious dogs with coronary thrombosis induced by electrical current, we assessed the impact on the rapidity of thrombolysis and the incidence of reocclusion of two types of adjunctive treatment given concomitantly with intravenous tissue-type plasminogen activator (t-PA): 1) inhibition of platelet function with a peptide mimetic antagonist of platelet glycoprotein IIb/IIIa receptors or with lysine acetylsalicylic acid (ASA) and 2) inhibition of thrombin activity with recombinant hirudin or with heparin. ASA but not the receptor antagonist shortened the time to thrombolysis with t-PA (20 +/- 13 [mean +/- SD] minutes with ASA, 36 +/- 15 minutes with receptor antagonist, and 43 +/- 16 minutes with the saline control). Reocclusion occurred promptly after completion of the infusion of t-PA in all seven dogs given saline. Reocclusion was delayed and prevented in some dogs within 90 minutes after the end of the infusion of t-PA by both antiplatelet agents but still occurred in 42% despite continued inhibition of platelet function (i.e., three of six dogs given ASA and two of six given receptor antagonist). In contrast, inhibition of thrombin activity with recombinant hirudin in a dose that prolonged the partial thromboplastin time modestly (1.5-2-fold) resulted in accelerated lysis (19 +/- 10 minutes) and prevention of reocclusion in each of six dogs. Heparin given in doses that elicited similar prolongation of the partial thromboplastin time did not accelerate lysis nor prevent reocclusion, which occurred in five of six dogs. CONCLUSIONS Inhibition of thrombin by recombinant hirudin facilitates thrombolysis and maintains patency of coronary arteries recanalized with t-PA particularly effectively. The benefit conferred may reflect direct anticoagulant effects plus diminished activation of platelets secondary to decreased thrombin activity.
منابع مشابه
Reduced tissue factor pathway inhibitor-1 after pharmacological thrombolysis: an epiphenomenon or potential culprit in rethrombosis?
Thrombosis following plaque rupture is the proximate trigger for abrupt coronary artery occlusion and acute coronary syndromes.1,2 Coronary thrombolysis was reintroduced in the early eighties as a means of recanalizing acutely occluded coronary arteries in evolving myocardial infarction, limiting myocardial damage, preserving ventricular function, and improving clinical outcomes.3–5 However, it...
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Since the introduction of thrombolytic therapy for acute myocardial infarction, the incidence of coronary artery reocclusion has been intensively studied. Also, the prediction and diagnosis of reocclusion by angiographic and clinical variables, as well its invasive and pharmacologic prevention, have gained much attention. By angiographic definition, reocclusion requires three angiographic obser...
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The composition of an evolving arterial thrombus may be a determinant of how effectively pharmacologic agents prevent reocclusion after initially successful thrombolysis. In this study, reoccluding plateletor fibrin-rich thrombi as delineated by scanning electron microscopy were produced selectively in the femoral arteries of dogs with the use of electrically induced vascular injury or implanta...
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The composition of an evolving arterial thrombus may be a determinant of how effectively pharmacologic agents prevent reocclusion after initially successful thrombolysis. In this study, reoccluding platelet- or fibrin-rich thrombi as delineated by scanning electron microscopy were produced selectively in the femoral arteries of dogs with the use of electrically induced vascular injury or implan...
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عنوان ژورنال:
- Circulation
دوره 83 3 شماره
صفحات -
تاریخ انتشار 1991