Influence of thrombolytic therapy on the condition of matrix metalloproteinase and their inhibitors system in patients with Q-wave myocardial infarction

Abstract

Myocardial infarction (MI) is one of the most important problems of modern cardiology all over the world and, particularly, in Ukraine. Implementation of thrombolysis into the treatment leads to significant reduction of mortality from MI. Nowadays the most progressive treatment method is percutaneous coronary intervention. It was proved in several randomized controlled clinical trials (DANAMI-2, PRAGUE-2, SIAM-III). But in our country not all centers for treatment of MI are equipped by catheterization laboratory. That is why thrombolytic therapy (TLT) remains actual till today. In any type of treatment tactic in postinfarction heart would be seen remodeling processes with involvement to the pathological process of extracellular morphologic substrate. Pathological changes of extracellular matrix lead to increases of myocardium stiffness and reconstruction of heart chambers geometry. It leads to transformation of spatial organization of heart chambers, violation of blood filling and ejection and formation of systolic and diastolic dysfunction. The synthesis and degradation of extracellular substance is controlled by systems MMP/TIMP, the ratio of which influence on the character of extracellular matrix of myocardium restructuring. Till today influence of TLT on the state of MMP/TIMP system and postinfarction remodeling formation still is not clarified.The purpose of the study - to investigate the influence of thrombolytic therapy on condition of system of matrix metalloproteinase (MMP-9) and its inhibitors (TIMP-1), the status of intracardiac hemodynamics, frequency of acute postinfarction left ventricular aneurysm development in patients with Q-wave myocardial infarction.Patients and methods. 116 patients with a diagnosis of acute Q-wave MI of anterior wall of the left ventricle (LV) were examined. Patients, admitted before 12 hours from the beginning of MI and who had no contraindications, received TLT using streptokinase and basic therapy. Patients, admitted later than 12 hours from the beginning of MI or who had contraindications, received basic therapy only, which included statins, anticoagulants, antiplatelet agents, beta-blockers, ACE inhibitors, nitrates by demand. Depending on the implementation of TLT all patients were divided into next groups: the 1st – 74 patients who received TLT, the 2nd - 42 patients, who were treated without TLT. All patients were examined by clinical, laboratory and EchoCG methods on the fifth day. Serum levels of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were determined.Results and discussion. Analysis of indicators which characterize the MMP/TIMP system showed the lower level of MMP-9 in patients of the first group. Serum level of TIMP-1 in the first group was higher in comparison with patients of the second group.During EchoCG in patients of the second group higher than in the first group indexes of end-diastolic diameter of LV, end-systolic diameter of LV, LV myocardial mass index, stroke volume, stroke index, cardiac output, velocity of early diastolic filling of LV, the ratio of the velocity of early diastolic filling and late diastolic filling of LV, average pressure in pulmonic artery, the frequency of left ventricular aneurysm detection and the phenomenon of spontaneous ventricular contrasting were found. Such indexes as ejection fraction, atrial systole flow velocity, deceleration time of early diastolic filling flow and isovolumic relaxation time of LV were lower than in the first group.ConclusionsExcessive activation of proteolysis system on the background of relative deficit of TIMP-1was revealed in patients with Q-wave MI, who were treated without TLT.Treatment of patients with Q-wave MI with basic therapy only, lead to the LV remodeling, to dilation way predominantly.Violation of diastolic function of LV was typical for all patients with Q-wave MI, but absence of TLT changes it from impaired relaxation to the restrictive type.In patients with Q-wave MI without usage of TLT more frequently aneurysm of LV and the phenomenon of spontaneous ventricular contrast were revealed, that confirms the high thrombogenic potential.Correlation analysis demonstrated close relationship between main regulators of extracellular matrix condition and indicators of postinfarction remodeling process.