title: Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator.
abstract: Platelet activation may limit the response to tissue-type plasminogen activator (t-PA) during coronary thrombolysis in humans. As an index of platelet activation, we assessed thromboxane A2 biosynthesis during coronary thrombolysis with intravenous t-PA in patients with acute myocardial infarction. Urinary 2,3-dinor-thromboxane B2, a metabolite of thromboxane A2, was increased to a peak of 3,327 +/- 511 pg/mg creatinine (n = 12) following administration of intravenous t-PA and remained elevated for 48 hours. This increase was abolished by pretreatment with aspirin 325 mg orally (n = 6), indicating de novo biosynthesis of thromboxane A2 rather than washout of preformed metabolites during reperfusion. Prostacyclin (PGI2) biosynthesis, determined by excretion of 2,3-dinor-6-keto-PGF1 alpha, also increased after t-PA administration. However, this increase was less pronounced in patients who reperfused (28 +/- 3.3 ng.hr/mg creatinine) than in patients who failed to reperfuse (118 +/- 30 ng.hr/mg creatinine, p less than 0.05). These data provide evidence of platelet activation during coronary thrombolysis with t-PA. In patients who reperfuse, the reduction in PGI2 biosynthesis may be a marker of reperfusion injury to the vasculature and may further amplify platelet activation.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.
authors.forename: D M
authors.initials: DM
authors.lastname: Kerins
authors.forename: L
authors.initials: L
authors.lastname: Roy
authors.forename: G A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: D J
authors.initials: DJ
authors.lastname: Fitzgerald
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D015425:Myocardial Reperfusion / Q000379:methods; D015539:Platelet Activation / Q000187:drug effects*; D015912:Thrombolytic Therapy; D013928:Thromboxane A2 / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D013928:Thromboxane A2; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D001241:Aspirin