Abstract

The aim of this randomised, double-blind, placebo controlled, parallel group study was to assess the effect of trimetazidine (TMZ), a potent antiischaemic drug, on plasma C-reactive protein (C-RP), cytokine and adhesion molecule levels. The study population consists of 18 patients (16 males, 2 females, average age 56.45 +/- 10.97 years) with acute myocardial infarction admitted within 6 hours after onset of symptoms and treated with streptokinase. Blood samples were taken at 3-hour intervals during the time of treatment. All patients were randomised blindly using a centralised randomisation process, between trimetazidine (40 mg bolus i.v. then 60 mg per day for 48 hours intravenously in glucose infusion) or placebo group. Plasma C-RP level was significantly lower in TMZ group (39.5 mg/ml +/- 9.7 mg/ml) as compared to placebo (75.7 +/- 29.4 mg/ml, p < or = 0.001) and peaked 28 hours later in TMZ group. Plasma interleukin 6 (IL 6) level showed a sharp peak 9 hours after the onset of the symptoms in TMZ group (116.9 +/- 180.2 pg/ml vs. 45.4 +/- 37.9 pg/ml) and was increased up to 30 hours after the onset of the symptoms. Plasma interleukin 1 beta (IL 1 beta) was also higher in TMZ group notably 21 hours after the onset of symptoms (26.4 +/- 9.3 pg/ml vs. 16.2 +/- 2.4 pg/ml). TMZ group showed lower plasma E-selectin levels. Plasma IL 8, TNF alpha and ICAM 1 levels were without statistical significant differences. The present study demonstrates a significant reduction of plasma C-reactive protein level in the course of acute myocardial infarction treated with streptokinase and intravenous trimetazidine infusion compared with the group of patients without trimetazidine treatment.

Highlights

  • The association of inflammation with acute myocardial infarction (AMI) has been known for over a half of the century

  • During ischaemia-reperfusion, such as in acute myocardial infarction, the tissue damage may result from direct anoxic and hypoxic injury and from other deleterious events occurring after the blood flow reestablishment to the occluded vascular bed

  • Animal studies have shown that trimetazidine protects the myocardium from ischaemia and reperfusion during experimental myocardial infarction

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Summary

Introduction

The association of inflammation with acute myocardial infarction (AMI) has been known for over a half of the century. Inflammatory lesions seen in tissue specimens many hours to days after the onset of infarction reflect, in part, a healing process. In recent years many investigators have studied the potential pathogenic role of inflammation in the myocardial ischaemia-reperfusion (MI/R) process [11]. Inappropriate inflammatory response can cause severe tissue destruction. During ischaemia-reperfusion, such as in acute myocardial infarction, the tissue damage may result from direct anoxic and hypoxic injury and from other deleterious events occurring after the blood flow reestablishment to the occluded vascular bed. Reperfusion injury is partly caused by oxygen radicals, proteolytic enzymes and cytokines released by adhered and activated leucocytes that infiltrate into the affected area, because neutrophil depletion or prevention of neutrophil accumulation significantly diminishes tissue damage and enhances the recovery of cardiac function [5]

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