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Aim: To study efficacy of the myocardial cytoprotector trimethasidine MB and metabolic drug 3-(2,2,2-trimethylhydrasine) propionate dihydrate (3-TMHP) in the treatment of chronic cardiac failure (CCF)., Material and Methods: Sixty-five patients with CCF after myocardial infarction (> 6 months) with left ventricular ejection fraction (LV EF) <40% were randomized into 3 groups: group 1 (n=28) received basic therapy plus trimethasidine in a daily dose 70 mg; group 2 (n=25)--basic therapy plus 3-TMHP in a daily dose 1000 mg; control group (n=12) received basic therapy with ACE inhibitors, beta-blockers and diuretics. Before and after 6-month treatment all the patients have undergone stress echocardiography with dobutamine. Perfusion and myocardial metabolism were determined in 34 patients with single photon emission computed tomography of the myocardium (SPECT) with 99m-Tc-technetril and positron-emission tomography of the myocardium (PET) with F-18-fluorodesoxyglucose., Results: Groups 1 and 2 significantly reduced functional class of CCF and prolonged the distance of a 6-min walk. Significant improvement of life quality was observed only in the treatment with trimethasidine. According to PET, treatment with trimethasidine MB and 3-TMHP has an anti-ischemic action manifesting with a significant attenuation of glucose hypermetabolism in the ischemic segment to normal values. However, significant improvement of systolic thickening in hybernated segments by SPECT as well as a significant rise of LV EF were recorded only in the treatment with trimethasidine MB. Stress echocardiography with dobutamine had high specificity (85.7%) but low sensitivity (50.4%) in detection of hybernated myocardium., Conclusion: Trimethasidine MB (preductal MB) has advantages over 3-TMHP, so it is preferable in ischemic CHF.

The aim of the work was to study the effect of metabolic triad with different mechanisms of acting--high-dose Glucose-Insulin-Potassium--25% polarizing solution (25% glucose, 50 IU soluble insulin and 4% 144 ml KCL-GIK), mildronat, preductal MR on the functional condition of heart during the acute myocardial infarction. 20 patients from the main group and 20 from the control one have been under the study. Patients with diabetes and heavy forms of heart failure (killip class>2) were not included in the study. Evaluation of the functional condition of heart was based on ECG and echocardiography data received before and after the treatment. It was determined that the frequency of the rhythm disorder decreases in the conditions of metabolic triad as well as during the thrombolitic reperfusion. Average period of time for normalization of S-T segment elevation made up 5.4+/-1.8 days and 7.3+/-1.2 days in case of the control group. The received data make it relevant to include the complex metabolic triad for preventive purpose during the complications followed after the acute myocardial infarction.

Background: Partial fatty acid oxidation inhibitors have raised great interest since they are expected to counteract a dysregulated gene expression of hypertrophied cardiocytes. Some of these compounds have been developed for treating non-insulin-dependent diabetes mellitus and stable angina pectoris. A shift from fatty acid oxidation to glucose oxidation leads to a reduced gluconeogenesis and improved economy of cardiac work. An increased glucose oxidation can be achieved with the following enzyme inhibitors: etomoxir, oxfenicine, methyl palmoxirate, S-15176, metoprolol, amiodarone, perhexiline (carnitine palmitoyltransferase-1); aminocarnitine, perhexiline (carnitine palmitoyltransferase-2); hydrazonopropionic acid (carnitine-acylcarnitine translocase); MET-88 (gamma-butyrobetaine hydroxylase); 4-bromocrotonic acid, trimetazidine, possibly ranolazine (thiolases); hypoglycin (butyryl-CoA dehydrogenase); dichloroacetate (pyruvate dehydrogenase kinase). CLINICAL TRIALS with trimetazidine and ranolazine showed that this shift in substrate oxidation has an antianginal action. Etomoxir and MET-88 improved the function of overloaded hearts by increasing the density of the Ca(2+) pump of sarcoplasmic reticulum (SERCA2). The promoters of SERCA2 and alpha-myosin heavy-chain exhibit sequences which are expected to respond to transcription factors responsive to glucose metabolites and/or peroxisome proliferator-responsive element (PPAR) agonists. Further progress in elucidating novel compounds which upregulate SERCA2 expression is closely linked to the characterization of regulatory sequences of the SERCA2 promoter.

Overall ninety patients with chronic obstructive bronchitis presenting with signs of pulmonary-cardiac insufficiency (CPI) were studied by static radionuclide ventriculography with pertechnetate and rotation viscosimetry before and after a 14-day course of treatment. All the patients received basic treatment with cardiac glycosides on a differential basis depending upon CPI severity. Those patients having been prescribed mildronate additionally in a daily dose of 10 mg/kg body mass demonstrated improvement in left ventricular performance: the total and regional ejection fractions got increased, with the end-diastolic and end-systolic volumes having gotten reduced. Those patients receiving mildronate combined with thrental at a daily dose of 7-8 mg/kg body mass showed improvement in rheologic properties of blood as well as in intracardiac haemodynamics. At the same time, the right and left ventricles of the heart improved their performance, with their dysfunction having been lessened: the total and regional ejection fractions appeared to be increased, the end-diastolic and end-systolic volumes reduced, the amplitude-time characteristics of the processes of ejection and filling of the ventricles of the heart were found out to get better.

In experiments on dogs, application of the cross-over circulation method revealed that mildronate increased coronary blood flow due to active coronary dilation. In experiments on cats, a cardioprotective effect of mildronate was found, which prevented the development of acute ischemic heart failure by stabilizing the major hemodynamic parameters. Clinical studies of patients with Functional Classes I-III angina provided evidence for positive effects of mildronate on coronary blood flow.