THROMBOLYTIC THERAPY WITH UROKINASE REDUCES INCREASED CIRCULATING ENDOTHELIAL ADHESION MOLECULES IN ACUTE MYOCARDIAL-INFARCTION

The aim was to investigate circulating E-selectin and Intercellular Ad hesion Molecule-1 (ICAM-1) in acute myocardial infarction. Our study w as carried out in 80 patients, 40 hospitalized for acute myocardial in farction (AMI), 20 suffering from chronic stable angina and 20 healthy control subjects. Samples of venous blood were taken from all patient s at the moment of hospitalization and after 2, 4, 6, 8, 10, 12 and 24 hours from the thrombolytic treatment (AMI + urokinase) or convention al therapy (AMI + nitroglycerin), for the dosage of creatinine kinase (CK) and adhesion molecules. The CK was determined by means of a Hitac hi 901 automatic analyser using an enzymatic method (reagents Bohering er-Biochemia, Germany). Soluble E-selectin (sE-selectin) and soluble I CAM-1 (sICAM-1) were measured in the serum using a specific immunoassa y (British Biotechnology Products). The serum levels of Tumor Necrosis Factor (TNF-alpha) were evaluated using an immunoenzymatic assay to q uantitate the serum levels of the cytokine (British Biotechnology Prod ucts). Patients with acute myocardial infarction (AMI) had increased s erum 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-s electin = 67 +/- 10 ng/ml; sICAM-1 = 230 +/- 20 ng/ml) and healthy con trol subjects (sE-selectin = 53 +/- 15 ng/ml; sICAM-1 200 +/- 16 ng/ml ). Furthermore patients with acute myocardial infarction also had incr eased serum levels of Tumor Necrosis Factor (TNF-alpha = 309 +/- 10 pg /ml; control subjects = 13 +/- 5 pg/ml). Thrombolytic therapy with uro kinase (1,000,000 IU as an intravenous bolus for 5 minutes, followed b y an infusion of an additional 1,000,000 IU for the following two hour s) succeeded in producing reperfusion and reduced the serum levels of sE-selectin (52 +/- 13 ng/ml) and sICAM-1 (202 +/- 31 ng/ml). In contr ast patients not eligible for thrombolytic therapy and therefore treat ed with conventional therapy (a continuous i.v. infusion of nitroglyce rin at the dose of 50 mg/die) did not show any significant reduction i n both sE-selectin and sICAM-1 throughout the study. Our results confi rm previous experimental data and indicate that adhesion mechanisms su pporting leukocyte-endothelium interaction may also be operative in hu man acute myocardial infarction.