title: Thrombolytic therapy with urokinase reduces increased circulating endothelial adhesion molecules in acute myocardial infarction.
abstract: The aim was to investigate circulating E-selectin and Intercellular Adhesion Molecule-1 (ICAM-1) in acute myocardial infarction. Our study was carried out in 80 patients, 40 hospitalized for acute myocardial infarction (AMI), 20 suffering from chronic stable angina and 20 healthy control subjects. Samples of venous blood were taken from all patients at the moment of hospitalization and after 2, 4, 6, 8, 10, 12 and 24 hours from the thrombolytic treatment (AMI + urokinase) or conventional therapy (AMI + nitroglycerin), for the dosage of creatinine kinase (CK) and adhesion molecules. The CK was determined by means of a Hitachi 901 automatic analyser using an enzymatic method (reagents Boheringer-Biochemia, Germany). Soluble E-selectin (sE-selectin) and soluble ICAM-1 (sICAM-1) were measured in the serum using a specific immunoassay (British Biotechnology Products). The serum levels of Tumor Necrosis Factor (TNF-alpha) were evaluated using an immunoenzymatic assay to quantitate the serum levels of the cytokine (British Biotechnology Products). Patients with acute myocardial infarction (AMI) had increased serum levels of soluble E-selectin (sE-selectin; AMI + urokinase = 312 +/- 20 ng/ml; AMI + nitroglycerin = 334 +/- 15 ng/ml) and soluble ICAM-1 (sICAM-1; AMI + urokinase = 629 +/- 30 ng/ml; AMI + nitroglycerin = 655 +/- 25 ng/ml) compared to both patients with chronic angina (sE-selectin = 67 +/- 10 ng/ml; sICAM-1 = 230 +/- 20 ng/ml) and healthy control subjects (sE-selectin = 53 +/- 15 ng/ml; sICAM-1 200 +/- 16 ng/ml). Furthermore patients with acute myocardial infarction also had increased serum levels of Tumor Necrosis Factor (TNF-alpha = 309 +/- 10 pg/ml; control subjects = 13 +/- 5 pg/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus for 5 minutes, followed by an infusion of an additional 1,000,000 IU for the following two hours) succeeded in producing reperfusion and reduced the serum levels of sE-selectin (52 +/- 13 ng/ml) and sICAM-1 (202 +/- 31 ng/ml). In contrast patients not eligible for thrombolytic therapy and therefore treated with conventional therapy (a continuous i.v. infusion of nitroglycerin at the dose of 50 mg/die) did not show any significant reduction in both sE-selectin and sICAM-1 throughout the study. Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.
authors.affiliation: Institute of Pharmacology, University of Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Squadrito
authors.forename: A
authors.initials: A
authors.lastname: Saitta
authors.forename: D
authors.initials: D
authors.lastname: Altavilla
authors.forename: M
authors.initials: M
authors.lastname: Ioculano
authors.forename: P
authors.initials: P
authors.lastname: Canale
authors.forename: G M
authors.initials: GM
authors.lastname: Campo
authors.forename: G
authors.initials: G
authors.lastname: Squadrito
authors.forename: G
authors.initials: G
authors.lastname: Di Tano
authors.forename: A
authors.initials: A
authors.lastname: Mazzu
authors.forename: A P
authors.initials: AP
authors.lastname: Caputi
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D003402:Creatine Kinase / Q000097:blood; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D019040:E-Selectin; D007527:Isoenzymes; D018799:Intercellular Adhesion Molecule-1; D006493:Heparin; D003402:Creatine Kinase; D014568:Urokinase-Type Plasminogen Activator; D001241:Aspirin