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The paper gives data on the proven efficiency of myocardial cytoprotection with the pFOX inhibitors trimetazidine and meldonium for coronary heart disease. However, no algorithm has been defined for their differentiated use at different ischemic remodeling stages in these patients in terms of the mechanism of metabolic effects. Sequential use of meldonium and trimetazidine in different periods of acute and chronic myocardial ischemia may become one of the possible ways to increase the efficacy of the pFOX inhibitors.

Introduction of trimetazidine to 10-month-aged rats with experimental ischemic heart disease leads to an increase in carbohydrate utilization with energy purposes in myocardium, which is manifested by increasing activity of glycolysis enzymes with decreasing lactate level in myocardium, increasing activity of pyruvate dehydrogenase and citrate synthase in mitochondrial cardiomyocytes, and increasing ATP content in myocardium. This is accompanied by signs of stabilization of cardiomyocyte membranes and reduction in the degree of tissue hypoxia. The efficiency of trimetazidine decreases with increasing age: in 24-month-aged rats, the direction of changes is retained, but they are less pronounced.

We present data of the study of effect of trimetazidine MB on the state of cellular membranes assessed on lymphocytes as highly sensitive model of hypoxia and endothelial dysfunction. Detection of external cytoplasmatic membrane blebbing and registration of quantity of membrane released microparticles by the method of phase-contrast microscopy were carried out in groups of patients with hypertensive disease without and with ischemic heart disease (IHD). It was found that number of cells in the state of terminal blebbing statistically significantly decreased and number of cells with intact cytoplasmic membrane increased at the background of intake of trimetazidine in all groups of patients. With correlation coefficient 0.76 (p<0.05) between content of membrane microparticles and terminal blebbing lowering of content of membrane released microparticles was noted in peripheral blood of patients of all studied groups. The investigation conducted allows to make conclusion that stabilization of cellular membranes is one of spectra of trimetazidine actions underlying improvement of self feeling of patients with vascular pathology.

By changing the principal energy substrate, trimetasidine has reduced severity of ischemic myocardial damage as shown by greater integrity of membrane structures, improvement of contractile and rhythmic functions, central hemodynamics and lethality early after experimental myocardial contusion.

The aim of the study was to estimate the efficiency of combination therapy with Preductal and Prestarium after MI. We investigated 152 patients with acute MI of anterior wall (Q wave) and Heart Failure (II-III class by NYHA). I group included 92 p, which were treated by Preductal (60 mg daily) on the background of the standard therapy. II group (60 p) treated by standard therapy. (ACE inhibitor, diuretic, beta-blocks). We divided the patients in 2 subgroups, with EF>45% and EF<45%. Echo investigation was performed after 1,3,6.12 months from the beginning of MI. We estimated LV EDV and ESV, EF, FS, SV and diastolic function. 12 month after myocardial infarction decreases of average heart failure and angina classes. After 6,12 months was noted decreased EDV and ESV, increased EF, FS,SV in both groups confidence, but spatially in the I gr. Patients, who had EF<45% and were treated with Preductal improved EF with 30,1%(p<0,05) confidence, which was 1,5 times more then in the control gr, also increased FS and SV by 32,7%, 13,6% p<0,05. At the same time was observed diastolic function improvement, particular decreased Ve, Ve/Va, and increased Va specially in the Preductal group more intensive and confidence. The treatment with Preductal during 12 months indicates his positive influence on the LV systolic and diastolic function, which is most significant in the patients with low EF.

Coronary bypass grafting with the use of cardiopulmonary bypass was performed in 119 patients (age 41-75 years) with stable angina. In addition to standard therapy in pre and post operative periods patients of group 1 (n=40) received mildronate (750 mg/day for 3 days then 750 mg twice weekly), patients of group 2 (n=41) received trimetazidine (70 mg/day). Patients of group 3 (n=38) received no "metabolic" drugs. The use of cardioprotectors mildronate and trimetazidine facilitated improvement of total and local myocardial contractility both before and after surgery, and caused limitation of development of myocardial stunning, associated with derangement of local contractility in post operative period.

Trimetazidine is a new metabolic antiischemic agent, which increases the tolerance of cardiomyocytes to ischemia. The aim of the study was to evaluate the effect of additional trimatazidine therapy in patients with ischemic cardiomyopathy (ICMP) in comparison with standard therapy of cardiac insufficiency. According to the results of the study, trimetazidine improves the clinical status, functional class of cardiac insufficiency, left ventricular ejection fraction, in ICMP patients. Trimetazidine increases physical exercise tolerance according to the results of six-minute walking test. Thus, the optimization of myocardial energetic metabolism may be a promising perspective in the treatment of coronary heart disease with systolic dysfunction.

The study was undertaken to evaluate the effects of long-term (6-month) therapy with the selective beta-blocker bisoprolol, the cytoprotector trimetazidine and their combination on the clinical course of disease, the morphofunctional parameters of the left ventricle (LV) and life quality in 71 patients with coronary heart disease (CHD) concurrent with functional classes (FC) III-IV chronic heart failure (CHF) (ejection fraction (EF) < 35%, as evidenced by echoCG). In Groups 1, 2, and 3, basic therapy was supplemented by bisoprolol, trimetazidine, and bisoprolol plus trimetazidine, respectively. The initial dose of bisoprolol was 1.25 mg with its subsequent titration to an individually tolerable. Trimetazidine was given in a dose of 20 mg thrice daily. The patients' clinical status and echoCG were monthly assessed. There was a decrease in FC of CHD in all the groups, a reduction in LV end diastolic and systolic volumes, and an increase in shortening faction, LV EF, and an improvement of LV diastolic function. There was evidence that it should be expedient and safe to use the cytoprotector trimetazidine in the treatment of CHF in patients with CHD. In patients with CHD concurrent with CHF, therapy using a combination of bisoprolol and trimerazidine was found to have the most pronounced impact, which yielded the maximum clinical and hemodynamic effect (LV EF increased by 42.6% of the baseline values, the rate of early and late ventricular diastolic filling decreased by 59% of the baseline values). The revealed regularities of the positive effect on the clinical and hemodynamic parameters of long-use of bisoprolol, trimetazidine, and their combination in patients with CHD concurrent with FC III-IV CHF show it expedient to include these drugs and their combination into therapy for CHF that develops in the presence of CHD.

Aim: To assess effect of trimetazidine on clinical course of postinfarction period and restoration of left ventricular myocardium., Material and Methods: 1.5-2.0 months after acute myocardial infarctions 123 patients receiving conventional therapy (aspirin, beta-blockers, angiotensin converting enzyme inhibitors, nitrates) were divided into 2 groups. Patients of group 1 (n=62) were given 60 mg/day of trimetazidine and patients of group 2 (n=61) were not. All patients were followed up for 12 months after onset of myocardial infarction., Results: 12 months after myocardial infarction decreases of average heart failure and angina classes, increase of left ventricular ejection fraction, reduction of left ventricular end systolic and end diastolic volumes and left atrial dimensions occurred in group 1. Ejection fraction in this group became significantly higher while left ventricular end systolic and end diastolic volumes and left atrial dimensions significantly lower than in group 2. Index of diastolic function V(e)/V(a)ased in trimetazidine treated patients with normal and hypertrophic types of transmitral diastolic blood flow and became higher than in group 2., Conclusion: Trimetazidine facilitates restoration of systolic and diastolic left ventricular function after myocardial infarction.

Aim: To assess effect of trimetazidine on global and regional systolic and diastolic left ventricular function in patients with combined postinfarction ischemic syndrome., Material: Patients (n=32) with healed myocardial infarction and signs of global systolic (ejection fraction 38,5+/-2,7%) and diastolic (EIA=0,88+/-0,03) left ventricular dysfunction confirmed by Doppler echocardiography., Methods: Regional systolic and diastolic function was assessed by dobutamine stress echocardiography with Doppler tissue imaging before and after 3 months during which the patients received 60 mg/day of trimetazidine., Results: The segments with hibernating myocardium were found in every patient. These segments along with segments with scars displayed greatest degree of local systolic and diastolic dysfunction and because of their prevalence made significant contribution to the setting of global diastolic dysfunction. Improvement of global diastolic function at rest after trimetazidine was associated with decrease of total number of ischemic segments (from 80 to 67%) especially of those with hibernation (from 61 to 46%)., Conclusion: The hibernating myocardium was most sensitive to metabolic intervention and its presence after myocardial infarction predicted improvement after drug treatment of not only systolic but also diastolic left ventricle dysfunction. Restoration of function of hibernating myocardium turned out to be possible not only after myocardial revascularization but also after medical therapy.

32 circulatory bands of coronary arteries of 5 pigs were studied. It has been revealed that the bands develop long-term tonic contraction activity in Krebs's solution (30 mM of KCl). In this case adrenalin in concentration of 10(-7) g/ml causes mild relaxation. In concentration of 10(-6) g/ml, it causes obvious relaxation. Trimetazidin and mildronat do not affect tonic contraction of the bands. They can quickly and reversibly increase relaxation effects of adrenaline. The preparations can increase ten-fold beta-adrenoreactivity of smooth muscles. This shows an important role of endogenic sensibilizers of beta-adrenoreceptors in regulation of coronary blood flow in humans.

Effects of amino acid composition MP-33 in combination with trimetazidine were studied in metabolic therapy of elderly patients (age 63.3 +/- 1.7 years) with ischemic heart disease (angina pectoris functional class II-III). MP-33 (100 mg 3 times a day subling.), trimetazidine (20 mg 3 times a day per os), trimetazidine + amino acid composition MP-33 in the above doses in addition to basic therapy were given to 30, 15 and 15 patients, respectively. Combined therapy with trimetazidine and MP-33 significantly activated antioxidant enzymes and depressed lipid peroxidation due to GSH-dependent regulation of cellular redox status by MP-33.

In the paper, results are reflected of a swimming test in 78 laboratory rats. ATF-LONG has been shown to be capable of augmenting the animals' powers of endurance during loading tests. The established dose-dependent actoprotective activity of ATF-LONG is superior to that of adenosine triphosphate, trimetasidine (preductal), and mildronate. Possible pharmacological mechanisms of its actoprotective activity are discussed. The authors come to the conclusion that performance capability gets improved under exposure to purine nucleotides.

Fluctuations of the thiol disulfide system were shown to be interrelated with changes in the ECG indices. Trimetazidine since it has antioxidant properties was found to be effective in patients with low thiol disulfide ratios. A single dose of 0.8 mg/kg of the body mass was shown to inhibit the appearance of stress-dependent ischemic symptoms during surgical procedures.