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Background: Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown., Methods: A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium's neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen-glucose deprivation reperfusion was used to study meldonium's protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker ® probes, mitochondrial stress, real-time ATP rate and western blotting., Results: Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia-reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3β signaling pathway to inhibit mitochondria-dependent neuronal apoptosis., Conclusion: Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis., (© 2024. The Author(s).)

Purpose: Temozolomide (TMZ), a cytotoxic DNA alkylating agent, is the main chemotherapy used for the treatment of high grade astrocytomas. The active alkylator, methylhydrazine, is not recovered in urine and thus renal function is not expected to affect clearance. Prescribing information for TMZ states pharmacokinetics have not been studied in adults with poor renal function, eGFR < 36 mL/min/1.73 m 2 . We reviewed our clinical experience with TMZ in patients with impaired renal function to evaluate safety of administering full dose TMZ., Methods: The primary endpoint was to characterize the incidence and severity of thrombocytopenia in patients with eGFR < 60 mL/min/1.73 m 2 who received TMZ for treatment of high grade gliomas (HGG) or primary CNS lymphoma (PCNSL). Secondary endpoints included incidence and severity of neutropenia, lymphopenia hepatotoxicity, and number of TMZ cycles administered. Medical records of patients with HGG or PCNSL treated with TMZ from October 1, 2016-September 30, 2019 were accessed to identify cases for this study., Results: Thirty-two patients were eligible for this study. Of the seven patients with eGFR < 36 mL/min/1.73m 2 , 38/39 cycles (97%) were completed without grade 3-4 thrombocytopenia. No patients experienced grade 3-4 neutropenia, and grade 3-4 lymphopenia occurred in 5 cycles (15%). One patient discontinued TMZ 7 days prior to completion of radiation due to thrombocytopenia., Conclusion: Hematologic toxicity in patients with severe renal dysfunction, eGFR < 36 mL/min/1.73m 2 , is similar to that of patients with normal renal function. Severe renal impairment does not preclude use of temozolomide, but cautious monitoring of blood counts is warranted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.

The diabetic heart has a decreased ability to metabolize glucose. The anti-ischemic drug meldonium may provide a route to counteract this by reducing l-carnitine levels, resulting in improved cardiac glucose utilization. Therefore, the aim of this study was to use the novel technique of hyperpolarized magnetic resonance to investigate the in vivo effects of treatment with meldonium on cardiac metabolism and function in control and diabetic rats. Thirty-six male Wistar rats were injected either with vehicle, or with streptozotocin (55 mg/kg) to induce a model of type 1 diabetes. Daily treatment with either saline or meldonium (100 mg/kg/day) was undertaken for three weeks. in vivo cardiac function and metabolism were assessed with CINE MRI and hyperpolarized magnetic resonance respectively. Isolated perfused hearts were challenged with low-flow ischemia/reperfusion to assess the impact of meldonium on post-ischemic recovery. Meldonium had no significant effect on blood glucose concentrations or on baseline cardiac function. However, hyperpolarized magnetic resonance revealed that meldonium treatment elevated pyruvate dehydrogenase flux by 3.1-fold and 1.2-fold in diabetic and control animals, respectively, suggesting an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that meldonium reduced the normalized acetylcarnitine signal by 2.1-fold in both diabetic and control animals. The increase in pyruvate dehydrogenase flux in vivo was accompanied by an improvement in post-ischemic function ex vivo, as meldonium elevated the rate pressure product by 1.3-fold and 1.5-fold in the control and diabetic animals, respectively. In conclusion, meldonium improves in vivo pyruvate dehydrogenase flux in the diabetic heart, contributing to improved cardiac recovery after ischemia., (© 2021 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy. Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our results showed that meldonium decreased animal body mass gain, food and water intake, and carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1, causing manganese superoxide dismutase expression and activity to increase, as well as lipid peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex changes in renal lipidomics. Taken together, our results have confirmed that meldonium pre-treatment protects against I/R-induced oxidative stress and apoptosis/necrosis., Competing Interests: The authors declare no conflict of interest.

The purpose of this study is to scrutiny the Dynamics of heart rate variability (HRV) in patients with PICS with 2nd type DM against the background of Taurine (TN) and meldonium (ME). The results of the investigations prove the decrease of the oxidative stress, which is basis of DACN, under the influence of sulfur-containing amino acid taurine (TN), and meldonium (ME) - a competitive inhibitor of gamma-butyrobetaine hydroxylase. Biochemical mechanisms of synergistic action of ME and TN are also described. The results of the studies of 98 patients with PICS and concomitant 2nd type diabetes mellitus were analyzed. They were distributed by simple randomization method into two groups, comparable according to age and sex: the main group (MG) (n = 68): and group of comparison (GoC) (n = 30). HRV was evaluated twice daily at the Cardiosense HMEGG system: at baseline and after 12 weeks of treatment. For the assessment of HRV the frequency and spectral parameters were used. While evaluating the different methods of treatment, their influence on the range of spectral and time indices of HRV was determined (p = 0.001 by the criterion of Kruskall-Wallis). It was learned that the combined application of ME and TN gives a statistically significant (p <0.01) increase of SDNN, HF at night, pNN - on 50% by day (p <0.01, p <0.001 and p <0.01 respectively), and statistically significant decrease in LF at night, compared to GHG., (©Carol Davila University Press.)

Mitochondrial dysfunction seems to play a fundamental role in the pathogenesis of neurodegeneration in Huntington's disease (HD). We assessed possible neuroprotective actions of meldonium, a small molecule affecting mitochondrial fuel metabolism, in in vitro and in vivo HD models. We found that meldonium was able to prevent cytotoxicity induced by serum deprivation, to reduce the accumulation of mutated huntingtin (mHtt) aggregates, and to upregulate the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in mHTT-expressing cells. The PGC-1α increase was accompanied by the increment of mitochondrial mass and by the rebalancing of mitochondrial dynamics with a promotion of the mitochondrial fusion. Meldonium-induced PGC-1α significantly alleviated motor dysfunction and prolonged the survival of a transgenic HD Drosophila model in which mHtt expression in the nervous system led to progressive motor performance deficits. Our study strongly suggests that PGC-1α, as a master coregulator of mitochondrial biogenesis, energy homeostasis, and antioxidant defense, is a potential therapeutic target in HD., (© 2018 Wiley Periodicals, Inc.)

The article presents a theoretical generalization of the results of the clinical efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis (NASH) in comorbidity with obesity and chronic kidney disease (CKD) of the 1st-2nd stages. The objective of the article was to determine the likely effect of S-adenosylmethionine and Meldonium on the clinical course of non-alcoholic steatohepatitis (NASH) and chronic kidney disease (CKD) of the I-II stages. We examined 75 patients with NASH with comorbid obesity I degree and CKD I and II dgrees. To determine the efficacy of the treatment, 3 groups of patients were randomized according to age, sex, degree of obesity, activity of the cytolytic syndrome of NASH and the stage of the CKD. SAM possesses powerful membrane-stabilizing properties, stably eliminates the manifestations of cytolysis, cholestasis, mesenchymal-inflammatory syndrome, increases the albumin-synthesizing function of the liver in patients with NASH and prevents the loss of albumins in the conditions of CKD І-ІІ st. At the same time, complex therapy of SAM and vazonate is superior to the effectiveness of correction of these syndromes due to the implementation of powerful metabolic, antioxidant, antihypoxant, energy-specific properties of Meldonium and may be recommended for the introduction into the practice of internal medicine and gastroenterology for treatment NASH on the background of obesity and CKD I and II stages. The established nephroprotective properties of SAM that are potentiated by Meldonium are probably due to the ability of these drugs to eliminate endothelial dysfunction, improve microcirculation, and prevent the progression of kidney fibrosis. S-adenosylmethionine (ahepta) in a dose of 600 mg sublingually in patients with non-alcoholic steatohepatitis on the background of obesity and chronic kidney disease of the 1st and 2nd st. produces powerful membrane-stabilizing effects on the affected hepatocytes, stably eliminates the clinical manifestations of the disease, the intensity of cytolysis, cholestasis, mesenchymal-inflammatory syndrome, inhibits the progression of hepatic and renal dysfunction (increases the albumin-synthesizing function of the liver, the velocity of glomerular filtration) by optimizing the control of fibrosis of the liver and kidneys. Complex therapy with S-adenosylmethionine (ahape) and Meldonium (500 mg /day)(vasonate) is superior to the correction of these syndromes NASH and CKD, since the vasonate potentially potentiates the action of S-adenosylmethionine in acute and distant observation periods.

Purpose: to assess efficacy and endotheliotropic properties of short-term addition of meldonium to basic therapy of patients with chronic ischemic heart failure and type 2 diabetes., Results and Conclusion: The study demonstrated the ability of meldonium to significantly improve endothelial function and the state of microcirculatory vascular bed, as well as to influence beneficially heart rate variability.

Meldonium (mildronate; 3-(2,2,2-trimethylhydrazinium)propionate; THP; MET-88) is a clinically used cardioprotective drug, which mechanism of action is based on the regulation of energy metabolism pathways through l-carnitine lowering effect. l-Carnitine biosynthesis enzyme γ-butyrobetaine hydroxylase and carnitine/organic cation transporter type 2 (OCTN2) are the main known drug targets of meldonium, and through inhibition of these activities meldonium induces adaptive changes in the cellular energy homeostasis. Since l-carnitine is involved in the metabolism of fatty acids, the decline in its levels stimulates glucose metabolism and decreases concentrations of l-carnitine related metabolites, such as long-chain acylcarnitines and trimethylamine-N-oxide. Here, we briefly reviewed the pharmacological effects and mechanisms of meldonium in treatment of heart failure, myocardial infarction, arrhythmia, atherosclerosis and diabetes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Kirov State Medical Academy, Kirov The results of the 20-years studies of the presence in blood serum and other body fluids of endogenous modulators of adrenergic and M-cholinergic impact a A COMPONENT of humoral element of autonomic nervous system. The article is devoted to the endogenous sensitizer of beta-adrenergic receptor (ESBAR) - water-soluble low molecular weight substances, analogues of which are histidine, tryptophan, tyrosine, mildronat and preduktal. It is shown, that separate dilutions of human serum and animal (as a source of ESBAR) and ESBAR - analogues ways to enhance the effectiveness of activation of beta-adrenoceptors (AR) of smooth muscle (uterus, coronary and renal arteries, trachea, stomach), myocardium and erythrocytes and platelets (respectively influenced of histidine and tryptophan). It is reported? that content of ESBAR in human serum (according to the titers of its dilution) depends on the sex and the presence of somatic diseases, and at women are also on the stage of reproduction and obstetric complications It is discussed hossible mechanisms of ESBAR action, its physiological role, including as a component of beta-adrenoreceptor myometrium inhibitory mechanism, as well as the prospect of the use of analogues ESBAR, including for the prevention of preterm labor, and for the treatment of bronchial asthma, coronary heart disease, hypertension and heart failure.

Purpose: to analyze clinical and economical effectiveness of meldonium as component of integrated program of cardio-rehabilitation in patients with ischemic heart disease (IHD) in the early period after percutaneous coronary intervention (PCI) with incomplete revascularization., Material and Methods: A program of controlled physical training (CPT) was carried out in patients with stable IHD and positive post PCI exercise test (n=48, age less or equal 65 years) starting 8-10 days after PCI. CRT program consisted of 2 phases - inhospital (exercise on treadmill with max heart rate [HR] 80% of that achieved in initial test, 10 times during 2 weeks) and home (exercise on treadmill with max HR 60% of HR achieved in initial test, 3 times a week for 2 months). Before initiation of CRT patients were distributed into 2 groups: CRT without (n=23; 56.7+/-7.1 years) and with (n=25; 54.6+/-6.8 years) administration of meldonium (1000 mg/day intravenously). Control group (n=24; 50+/-8.4 years) consisted of patients who were under outpatient observation, received similar drug therapy, but were not subjected to CRT. After completion of CRT (in 2.5 months) all patients underwent clinical-instrumental examination with determination of exercise tolerance., Results: Exercise duration and metabolic equivalent (MET) increased by 43.9, 36.6, 4.1% and 42.1, 34.8, 3.4% in CRT+ meldonium, CRT only, and control groups, respectively., Conclusion: In patients with documented ischemia after PCI inclusion of meldonium in the scheme of rehabilitation was associated with improved physical performance and optimal cost-effectiviness.

The authors performed the clinical study of efficiency of Vasonat usage in complex treatment of chronic toxic hepatitis. Under observation there were 122 patients with chronic toxic hepatitis (37--with chronic medicament hepatitis and 85--with chronic alcohol hepatitis). During treatment with Vasonat the severity of clinical signs decreased to 0-1 points, GGTP level decreased in 2,2 times that showed the better efficiency of Vasonat usage compare with basis treatment. Thus Vasonat in dosage 500 mg per day may be recommend to inclusion on complex treatment of patients with chronic toxic hepatitis.

Mildronate, a carnitine congener drug, previously has been shown to provide neuroprotection in an azidothymidine-induced mouse model of neurotoxicity and in a Parkinson's disease rat model. The aim of this study was to investigate the effects of mildronate treatment on cognition and pathology in Alzheimer's disease (AD) model mice (APP(SweDI)). Mildronate was administered i.p. daily at 50 or 100 mg/kg for 28 days. At the end of treatment, the animals were behaviorally and cognitively tested, and brains were assessed for AD-related pathology, inflammation, synaptic markers, and acetylcholinesterase (AChE). The data show that mildronate treatment significantly improved animal performance in water maze and social recognition tests, lowered amyloid-β deposition in the hippocampus, increased expression of the microglia marker Iba-1, and decreased AChE staining, although it did not alter expression of proteins involved in synaptic plasticity (GAP-43, synaptophysin, and GAD67). Taken together, these findings indicate mildronate's ability to improve cognition and reduce amyloid-β pathology in a mouse model of AD and its possible therapeutic utility as a disease-modifying drug in AD patients., (Copyright © 2013 Wiley Periodicals, Inc.)

To study the effect of sanatorium treatment (ST) using sodium chloride baths and metabolic drug mildronat on the dynamics of the ambulatory blood pressure monitoring (ABPM), markers of endothelial function in children with primary arterial hypertension (PAH). ABPM and held defined level of asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1) and nitric oxide (NO) in the serum of 114 children with PAH aged 12-17. The positive dynamics of ABPM in all groups, but significantly (P < 0.05) decrease in mean BP was noted in the group with combined ST using sodium chloride baths. When analyzing the level of NO a positive trend (P < 0.01) in the group was using metabolic therapy, but significantly (P < 0.001) pronounced effect was observed when it is combined balneotherapy and metabolic therapy. Analysis of ET-1 and ADMA at ST in conjunction with therapy and metabolic rate of sodium chloride baths there was a significant (P < 0.01) decrease in these parameters in comparison with those before treatment. In children with PAH have been identified violations of the functional activity of the endothelium, which is reflected in increased levels of ET-1, ADMA and reducing NO. Conducting rehabilitation inclusion complex balneotherapy and metabolic therapy helps to reduce average daily blood pressure, normalization of functional activity of the endothelium as a normalization of the synthesis of NO (P < 0.,001), a significant decrease of ET-1 (P < 0.01) and ADMA (P < 0.01).

Aim: To evaluate the impact of 10-14-day intravenous administration of meldonium as part of combination therapy in patients with chronic heart failure in the early post-infarction period on the recovery period, structural and functional parameters, and heart rate variability (HRV)., Subjects and Methods: The investigation enrolled 60 patients (men and women) aged 45 to 75 years at weeks 3-4 after post-myocardial infarction with symptoms of Functional Class II-III heart failure. All the patients underwent 24-hour electrochocardiography monitoring, cardiac echocardiography, and HRV study. After dividing the patients into 2 groups, Group 1 (a study group) (n = 30) was given intravenous meldonium (idrinol) 1000 mg/day in addition to the basic therapy of coronary heart disease. The patients in the study and control (Group 2; n = 30) groups were at baseline matched for age, gender, disease severity, and basic therapy pattern., Results: Following 10-14 days of treatment, both groups showed clinical improvement and the favorable changes in cardiac structural and functional parameters and HRV values, which were more pronounced in the patients receiving meldonium., Conclusion: The patients with CHF using meldonium as part of combination therapy in the early post-infarction period were observed to have clinical improvement, a significant reduction in the rate of angina attacks and in the need for nitrates, a decrease in the number of arrhythmic and ischemic episodes, and favorable changes in cardiac structural and functional parameters and HRV values.

Was examined 92 patients with congestive heart failure III-IV FC with fraction of emission left ventricle < 45% against coronary artery disease. Patients of control group received basic therapy (according to recommendations of the Ukrainian society of cardiology), the 1 group--in addition received a preparation of Vazonat within 15 days intravenously in a dose of 1000 mg a day further are out-patient within 1 month on 250 mg 3 times per os; the 2 group--under the same scheme a preparation of Vazonat and a day tranquilizer of Adapto in a dose of 500 mg twice a day throughout all term of supervision. It is established that addition of Vazonat to basic treatment leads to additional effect concerning improvement of indicators cardio-hemodynamic, to improvement congestive functions. Joint appointment of preparations of Vazonat and Adaptol against basic treatment leads to more expressed improvement congestive functions, to progressive reduction of degree of trouble, depression.

Aim: To evaluate the anti-ischemic and anti-anginal efficacy of meldonium (Idrinol) in its short-term use as part of combination therapy in patients with chronic heart failure in the early post-infarction period., Subjects and Methods: The investigation enrolled 60 patients (men and women) aged 45 to 75 years at weeks 3-4 after postmyocardial infarction with symptoms of Functional Class II-III heart failure. All the patients underwent physical examination, 24-hour ECG monitoring, heart rate variability (HRV) study, and quality of life assessment using the Seattle questionnaire. After randomization of the patients into 2 groups, Group 1 (a study group) (n = 30) was given intravenous Idrinol 1000 mg/day in addition to the basic therapy of coronary heart disease. The study and control (Group 2; n = 30) groups were matched for age, gender, disease severity, and basic therapy pattern., Results: Following 10-14 days of treatment, both groups showed clinical improvement and the autonomically normalizing effect of meldonium (Idrinol), which were more pronounced in Group 1 patients., Conclusion: Meldonium (Idrinol) was effective when parenterally administered in a dose of 1000 mg/day for 10-14 days as part of combination therapy in the early post-infarction period, which showed up as clinical improvement, a significant reduction in the frequency of angina attacks and in the need to use nitroglycerin, a decrease in the number of arrhythmia episodes, and its normalizing effect of HRV.

Background and Objective: Mildronate, an inhibitor of carnitine-dependent metabolism, is considered to be an anti-ischemic drug. This study is designed to evaluate the efficacy and safety of mildronate injection in treating acute ischemic stroke., Methods: We performed a randomized, double-blind, multicenter clinical study of mildronate injection for treating acute cerebral infarction. 113 patients in the experimental group received mildronate injection, and 114 patients in the active-control group received cinepazide injection. In addition, both groups were given aspirin as a basic treatment. Modified Rankin Scale (mRS) score was performed at 2 weeks and 3 months after treatment. National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score were performed at 2 weeks after treatment, and then vital signs and adverse events were evaluated., Results: A total of 227 patients were randomized to treatment (n = 113, mildronate; n = 114, active-control). After 3 months, there was no significant difference for the primary endpoint between groups categorized in terms of mRS scores of 0-1 and 0-2 (p = 0.52 and p = 0.07, respectively). There were also no significant differences for the secondary endpoint between groups categorized in terms of NIHSS scores of >5 and >8 (p = 0.98 and p = 0.97, respectively) or BI scores of >75 and >95 (p = 0.49 and p = 0.47, respectively) at 15 days. The incidence of serious adverse events was similar between the two groups., Conclusion: Mildronate injection is as effective and safe as cinepazide injection in treating acute cerebral infarction.

Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.

An aim of the present study was to evaluate the treatment efficacy of the antioxidant mildronate in patients with transitory ischemic attacks. We studied the dynamics of clinical status, psychometric data and indices of free-radical lipid oxidation in 40 patients. The improvement in the subjective state, memory and attention was seen in 24 patients.

Detailed clinical data about patients who used emergency services during 2011 are presented. The main attention is focused on the state of patients with acute and chronic brain ischemia before and after treatment with mildronate. Mean age of patients with ischemic stroke and chronic brain ischemia was 63.4 and 57.7 years, respectively. Mildronate was injected slowly intravenously in one dose 1000 mg (10 ml of 10% solution). The results obtained in the study allow to recommend mildronate for such patients and provide the useful information to physicians and medical attendants about current methods of diagnosis and treatment of patients with acute and chronic brain ischemia in out- and inpatient health services.

Background and Objective: Ischemic stroke may initiate a reperfusion injury leading to brain damage cascades where inflammatory mechanisms play a major role. Therefore, the necessity for the novel stroke-protecting agents whose the mechanism of action is focused on their anti-inflammatory potency is still on the agenda for drug designers. Our previous studies demonstrated that cerebrocrast (a 1,4-dihydropyridine derivative) and mildronate (a representative of the aza-butyrobetaine class) possessed considerable anti-inflammatory and neuroprotective properties in different in vitro and in vivo model systems. The present study investigated their stroke-protecting ability in an endothelin-1 (ET-1)-induced ischemic stroke model in rats., Material and Methods: Male Wistar rats were pretreated (for 7 days, per os) with cerebrocrast (0.1 mg/kg), mildronate (100 mg/kg), or their combination, followed by the intracerebral injection of ET-1. Functional and behavioral tests were carried out up to 14 days after the ET-1 injection. Ex vivo, the number of degenerated neurons and the infarction size in the cerebral cortical tissue were assessed histologically., Results: Cerebrocrast and mildronate effectively normalized ET-1-induced disturbances in neurological status, improved the muscle tone, and decreased the number of degenerated cortical cells. Both drugs also reduced the infarction size, and cerebrocrast showed at least a 2-fold higher activity than mildronate. The combination of both drugs did not cause a more pronounced effect in comparison with the action of drugs administered separately., Conclusions: The 1,4-dihydropyridine and aza-butyrobetaine structures may serve for the design of novel stroke-protecting agents to prevent severe neurological poststroke consequences.

Cerebrovascular pathology has long moved from the category of a single medical problem in the social problem. Progression of vascular lesions of the brain results in significant disability, and in the later stages interfere with the ability to self-service and significantly reduces the quality of life. The key link is ischemic brain damage, or glutamate cascade, which many researchers believe trigger excitotoxic damage and a major cause of neuronal death. One important component of effective control of the effects of ischemic disorders is complex neuro-cytoprotective therapy. To correct for the effects of both acute and chronic ischemia of the brain need to effectively act in several directions simultaneously, normalizing metabolic changes, eliminating the cytokine imbalance transcription violations, reducing the severity of oxidative stress and excitotoxicity.

Mildronate (3-(2,2,2-trimethylhydrazinium) propionate) is an inhibitor of l-carnitine biosynthesis and an anti-ischemic drug. In the present study, we investigated the effects of mildronate in rats following focal cerebral ischemia. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90min, followed by the intraperitoneal administration of mildronate at doses of 100 and 200mg/kg 2h after reperfusion and then daily for an additional 14days. The beam-walking, rota-rod and cylinder tests were used to assess sensorimotor function, and vibrissae-evoked forelimb-placing and limb-placing tests examined responses to tactile and proprioceptive stimulation. Following behavioural testing, the infarct volume was measured. The cerebellar concentrations of l-carnitine, γ-butyrobetaine (GBB) and mildronate were also measured. The results showed that saline-treated MCAO rats had minor or no spontaneous recovery in sensorimotor and proprioceptive function up to 14days post-stroke. Treatment with mildronate at a dose of 200mg/kg was found to accelerate recovery of motor and proprioceptive deficits in limb-placing, cylinder and beam-walking tests. Analysis of rat cerebellar tissue extracts revealed that l-carnitine and GBB concentrations changed with mildronate treatment; the concentration of l-carnitine was significantly decreased by mildronate treatment, whereas the concentration of GBB was significantly increased. Cerebellar concentrations of mildronate also increased in a dose-dependent manner following systemic administration. Infarct size did not differ among the experimental groups on post-stroke day 14. The present study suggests that mildronate treatment improves the functional outcome in MCAO rats without influencing infarct size., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Streptozotocin (STZ) was used to induce the diabetic rat model. STZ rats were treated with mildronate (100 mg/kg daily, per os or intraperitoneally for 6 weeks). Body weight, blood glucose, triglyceride, ketone body concentrations, glycated hemoglobin percent (HbA1c%), glucose tolerance, and the development of neuropathic pain were monitored throughout the experiment. In the STZ + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose (on week 4) and triglyceride concentrations (on weeks 3-6), significantly slowed the increase in HbA1c% (on week 6) and improved glucose tolerance 120 minutes after glucose ingestion during oral glucose tolerance test versus the STZ group. Mildronate completely protected development of STZ-induced neuropathic pain from the first administration week up to end of the experiment. The obtained data indicate clinical usefulness of the drug for the treatment of diabetes mellitus and its complications.

Mildronate is a cardioprotective drug, the mechanism of action of which is based on the regulation of l-carnitine concentration. We studied the metabolic effects of treatment with mildronate, metformin and a combination of the two in the Zucker rat model of obesity and impaired glucose tolerance. Zucker rats were p.o. treated daily with mildronate (200mg/kg), metformin (300 mg/kg), and a combination of both drugs for 4 weeks. Weight gain and plasma metabolites reflecting glucose metabolism were measured. The expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ and target genes was measured in rat heart and liver tissues. Each treatment decreased the blood glucose concentration during the fed and fasted states by 1 to 2 mmol/l. Treatment with mildronate and metformin decreased the plasma insulin concentration by 31 and 29%, respectively, while the combination of both drugs significantly reduced fed insulin concentration by about 47%. Mildronate treatment increased the expression of PPAR-α in the heart tissue and PPAR-γ in the heart and liver tissues. In addition, treatment increased the expression of PPAR target genes in the heart, but not in the liver tissue. In contrast to monotherapy, treatment with the combination of mildronate and metformin significantly decreased weight gain by 19% and did not affect food intake. In conclusion, our results demonstrate that mildronate, an inhibitor of l-carnitine biosynthesis, improves adaptation to hyperglycemia- and hyperlipidemia-induced metabolic disturbances and increases PPAR-α activity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Research of efficiency and safety of Vasonat has been carried out. 31 patients aged 46-75 years who had had hemispheric athero- thrombotic or hemodynamic schemic stroke with moderate severity and being treated in 2-5-month of early rehabilitation period have been observed. The control group of patients received placebo. Results of the study, 4 weeks treatment using Vasonat in the dosage of 500 mg/day have shown positive effect on common signs of the disease by decreasing headache intensity, dizziness, a nausea, and on focal neurological symptoms by decreasing hemiparesis degree; psychoemotional and mnestic activity (main memory and attention) improved as well. It was more distinct in patients with localization of the stroke in the right hemisphere of the brain. It was also noted more rapid improvement of motion function and quality of life of patients.

In paper influence of a cytoprotective drug "Mildrocard" on morfo-functional condition of cardiorespiratory system at patients with chronic heart failure with concomitant chronic obstructive pulmonary disease is estimated. It is established, that joining "Mildrocard" to complex therapy associated to pathology promotes reduction clinical display of heart failure, shows cardioprotective and pulmoprotective effects.

Anti-ischaemic drug mildronate suppresses fatty acid metabolism and increases glucose utilization in myocardium. It was proposed that it could produce a favourable effect on metabolic parameters and glucose transport in diabetic animals. Rats with streptozotocin diabetes mellitus were treated with mildronate (100 mg/kg daily, per os, 6 weeks). Therapeutic effect of mildronate was monitored by measuring animal weight, concentrations of blood glucose, insulin, blood triglycerides, free fatty acids, blood ketone bodies and cholesterol, glycated haemoglobin per cent (HbA1c%) and glucose tolerance. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of real time RT-PCR and immunohistochemistry correspondingly. In the streptozotocin + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose, cholesterol, free fatty acid and HbA1c concentrations and improved glucose tolerance. Induction of streptozotocin diabetes mellitus provoked increase of both GLUT1 gene and protein expression in kidneys, heart and muscle, mildronate treatment produced normalization of the GLUT1 expression levels. In the liver a similar effect was observed for GLUT1 protein expression, while GLUT1 gene expression was increased by mildronate. Mildronate produces therapeutic effect in streptozotocin diabetes model. Mildronate normalizes the GLUT1 expression up-regulated by streptozotocin diabetes mellitus in kidneys, heart, muscle and liver. Copyright © 2011 John Wiley & Sons, Ltd., (Copyright © 2011 John Wiley & Sons, Ltd.)

Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson's disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.

Modern view on pathogenesis and clinics of one of the most important forms of chronic cerebrovascular insufficiency--discirculatory encephalopathy has been presented in this article. The author has analyzed requirements to optimal treatment choice of this pathology. Action mechanisms and peculiarities of clinical use of Vasonat medication were detailed. This medication with good clinical and pharmacological properties allows to realize the strategy of pathogenetically proved neuromethabolical pharmacotherapy in angioneurology. Clinical advantage of Vasonat, its safety characteristics, and recommendations of practical use have been detailed.

In the course of observation over 40 patients after an old myocarditis against general systemic diseases of connective tissue who had been given a pharmacotherapy regarding main disease and a chronic heart failure, additionally Vazonat (campaign of "Olajnfarm", Latvia), preparation of the myocardial cytoprotection was prescribed in a therapeutic dose of 500 mg per day. Vazonat inclusion in basic therapy during 1 month was accompanied by improvement of a clinical condition of the patients, reduction of heart failure signs, and improvement of life quality.

Nowadays particular interest of clinicians is attracted by metabolic therapy of patients with chronic heart failure (CHF). The objective of this study was to investigate the influence of complex therapy with addition of Vasonat on the dynamics of remodeling indexes of left ventricle and functional class of CHF on classification of NYHA. It has been shown that application of metabolic modulator Vasonat in addition to conventional therapy of CHF facilitated the clinical improvement and significant decline of functional class. Vasonat use resulted in the meaningful improvement of the contractive function of myocardium and increase of tolerance to the physical exercise. Moreover, high efficiency of Vasonat has been demonstrated in the control of the syndrome of oxidizing stress, by decrease in intensity of free-radical processes and activation of the antioxidant defense system.

Background and Purpose: Mildronate [3-(2,2,2-trimethylhydrazinium) propionate] is an anti-ischaemic drug whose mechanism of action is based on its inhibition of L-carnitine biosynthesis and uptake. As L-carnitine plays a pivotal role in the balanced metabolism of fatty acids and carbohydrates, this study was carried out to investigate whether long-term mildronate treatment could influence glucose levels and prevent diabetic complications in an experimental model of type 2 diabetes in Goto-Kakizaki (GK) rats., Experimental Approach: GK rats were treated orally with mildronate at doses of 100 and 200 mg.kg(-1) daily for 8 weeks. Plasma metabolites reflecting glucose and lipids, as well as fructosamine and beta-hydroxybutyrate, were assessed. L-carnitine concentrations were measured by ultra performance liquid chromatography with tandem mass spectrometry. An isolated rat heart ischaemia-reperfusion model was used to investigate possible cardioprotective effects. Pain sensitivity was measured with a tail-flick latency test., Key Results: Mildronate treatment significantly decreased L-carnitine concentrations in rat plasma and gradually decreased both the fed- and fasted-state blood glucose. Mildronate strongly inhibited fructosamine accumulation and loss of pain sensitivity and also ameliorated the enhanced contractile responsiveness of GK rat aortic rings to phenylephrine. In addition, in mildronate-treated hearts, the necrosis zone following coronary occlusion was significantly decreased by 30%., Conclusions and Implications: These results demonstrate for the first time that in GK rats, an experimental model of type 2 diabetes, mildronate decreased L-carnitine contents and exhibited cardioprotective effects, decreased blood glucose concentrations and prevented the loss of pain sensitivity. These findings indicate that mildronate treatment could be beneficial in diabetes patients with cardiovascular problems.

The aim of the study was to examine effect of cardioversion (CV) on the subjective and objective status of patients with persistent atrial fibrillation (AF) receiving different therapy. The study included 4 groups of patients (n = 85). Group 1 (n = 30) were given standard treatment. In group 2 (n = 25), standard therapy was supplemented by i.v. injections of emoxipin (200 mg/day). Treatment of group 3 (n = 10) included mildronat (50 mg/day, i.v.), patients of group 4 (n = 20) were given riboxin (200 mg/day, i.v.). It was shown that the recovery of sinus rhythm improved the quality of life and parameters of cardiovascular function in all the treated patients.

Aim: To study fractional composition of red cell membrane (RCM) lipids in patients with severe iron-deficiency anemia (IDA) complicated by myocardiodystrophy prior to treatment and after 1-month combined treatment with sorbifer and mildronate., Material and Methods: Fatty acid composition of RCM lipids was studied in 12 patients with severe chronic posthemorrhagic IDA complicated by myocardiodystrophy and in 15 healthy subjects. Extraction of lipids from blood red cells and methylation of fatty acids were performed according to K.M. Sinyak et al. (1976). Relative content of fatty acids was determined at chromatography., Results: The study detected increased content of saturated fatty acids, especially palmitic and decreased content of unsaturated fatty acids especially fraction of omega6-polyunsaturated fatty acids: arachidonic and gamma-linolenic., Conclusion: Sorbifer in combination with mildronate improved fatty acid composition of blood red cells in patients with iron-deficiency anemia.

Aim: To clarify mildronate effects on oxidant stress and tissue oxygen in combined treatment of peripheral (sensomotor) neuropathy in patients with type 2 diabetes mellitus (DM)., Material and Methods: An open randomized trial investigated 70 matched patients with type 2 DM and sensomotor neuropathy. They were randomized into two groups. The study group received basic anti-diabetic treatment, alpha-lipoic acid and mildronate for 3 months. Patients of the control group received the same treatment but mildronate., Results: Mildronate administration improved clinical condition of the study group patients vs controls by neuropathy and symptoms count scales, electrophysiological properties of the nerve fibers, optimization of oxygen tissue balance, reduced production of lipid peroxidation products and activated enzymes of antioxidant defense., Conclusion: It is recommended to add 1 g/day mildronate to standard schemes of treatment for diabetes and sensomotor neuropathy.

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.

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.

The aim of this open randomized study was to compare the clinical efficacy of mildronate in complex therapy of chronic heart failure (CHF) and basic therapy in patients with CHF and type 2 diabetes mellitus (DM2) during the postinfarction period. The subjects were 60 II to III NYHA CHF patients aged 43 to 70 yo also suffering from DM2; the patients were observed during the early postinfarction period (weeks 3 to 4 from the onset of myocardial infarction). The patients were randomized into two groups: the 30 patients of the main group received basic therapy plus mildronate in a dose of 1 g a day, while the 30 patients of the control group received basic therapy only. The observation lasted 16 weeks. The following parameters were measured dynamically: NYHA functional class (FC), 6-min walking test results, left ventricular ejection fraction (LVEF), LV isovolumic relaxation time, microalbuminuria, glomerular filtration speed (GFS), functional renal reserve (FRR), carbohydrate and lipid exchange, cardiac rhythm variability parameters, and the quality of life. The use of mildronate in addition to basic therapy was associated with a more evident decrease in CHF FC, (by 19% vs. 14%), increase in 6-min walking test distance (25.5% vs. 18%), as well as a tendency to normalization of diastolic heart function and an increase in LVEF (by 12% vs. 7%). By comparison with basic therapy, the patients in the mildronate group displayed a statistically significant improvement in renal functioning: GFS increased by 20% vs. 2% (p < 0.05), the proportion of patients with an exhausted FRR decreased (p < 0.05), the average level of MAU decreased significantly (24% vs. 9%, p < 0.05). In the main group, a significant decrease in blood triglyceride level (by 33%, p < 0.05) and total cholesterol level (by 28%, p < 0.1) was noted. A hypoglycemizing ability of mildronate was noted. The use of mildronate in the basic therapy favors the normalization of vegetative homeostasis and improves the quality of life.

Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is a commonly used antiretroviral drug in AIDS treatment, however its use is limited by severe toxic side effects due to its influence on mitochondria that result in myopathy, particularly affecting the cardiac muscle. We suggest that effective protection of azidothymidine-induced cardiopathology can be expected from drugs that are capable of targeting mitochondria. Therefore the present study in mice was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine class, which previously has been shown to act as a highly potent protector of mitochondrial processes. In our study, saline (control), azidothymidine (50 mg/kg), mildronate (50, 100 and 200 mg/kg), and azidothymidine + mildronate (at the doses mentioned) were injected intraperitoneally daily in separate groups of mice for two weeks. At the termination of the experiment, mice were sacrificed, the hearts were removed and cardiac tissue was examined morphologically and immunohistochemically. It was found that azidothymidine, compared to control and mildronate groups, induced major morphologic changes in cardiac tissue, which were manifestated as degeneration and inflammation. These changes were prevented when mildronate was co-administered with azidothymidine. Mildronate also reduced the azidothymidine-induced expression of nuclear factor kappaBp65 (NF-kappaBp65). The obtained data demonstrate a high ability of mildronate of preventing azidothymidine-induced cardiopathologic changes, and suggest mildronate's indirect action on azidothymidine-caused oxidative stress reactions leading to mitochondrial dysfunction. This offers a rational combination of mildronate with azidothymidine or other anti-HIV drugs for beneficial application in AIDS therapy.

Alcoholic cardiomyopathy is specific cardial pathology characteristic for chronic consumption of alcohol. Endothelin-1 is an endothelium-derived potent vasoconstrictor peptide, which level directly influence the severity of this condition. Mildronate is an antiischemic drug. It inhibits carnitine biosynthesis (suppress beta-oxidation of the fatty acids) and increases the production of nitric oxide in the vascular endothelium. The aim of the study was to establish how Mildronate influences concentration of ET-1 in blood of rats on a background of chronic consumption of alcohol and at abstinence. White rats (n=28) instead of drinking water were taking 15% ethanol with the following regimens: A) three-week alcohol consumption, B) after 3 weeks of alcohol consumption on a background of alcohol they took mildronate, C) four-week alcohol consumption; D) after 4 weeks alcohol consumption they took only mildronate. Concentration of ET-1 in the group A was 6,00 +/- 0,35 fmol/ml, in the group B - 4,82 +/- 0,31 fmol/ml, in the group C - 13,25 +/- 0,49 fmol/ml and in the group D - 9,17 +/- 0,17 fmol/ml. Consumption of alcohol concentration ET-1 in blood high, for this purpose it is enough also 3-week alcohol consumption; the concentration of ET-1 progressively elevates with increase of duration of alcohol consumption; mildronate lowers concentration of ET-1 both on the background of alcohol consumption and on the background of acceptance of alcohol; under influence of mildronate the condition is improved in parallel the with complete alcohol consumption and acceptance of alcohol.

Mildronate is a fatty acid oxidation inhibitor approved as an antianginal drug in parts of Europe. We carried out the first study to determine whether a 10-day course of mildronate could reduce myocardial infarct size (IS) during acute myocardial ischemia. Sprague Dawley rats received 200 mg/kg/d of mildronate (treated group, n = 16) or sterile water (control group, n = 14) subcutaneously for 10 days before ischemia-reperfusion. Rats were then subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. The 2 groups had identical areas at risk: treated 38 +/- 3%; controls 38 +/- 2%. The amount of necrosis was smaller in the mildronate group at 16 +/- 2% of the left ventricle versus controls, 22 +/- 2% (P = 0.05); and for any amount of risk >25%, necrosis was smaller in the treated group (P = 0.0035). Myocardial IS (% of risk zone) was 43+/-3% in the mildronate-treated rats, and 57+/-4% in controls (P = 0.004). During occlusion, there were no differences between the 2 groups in heart rate (216 +/- 12 bpm, mildronate and 210 +/- 9 bpm, control), in mean arterial pressure (60 +/- 2 mm Hg, mildronate and 64 +/- 3 mm Hg, control) or in the frequency of arrhythmias. Our study for the first time demonstrated that a 10-day treatment with mildronate reduced myocardial IS in an experimental model of acute myocardial ischemia, without any effect on hemodynamics.

We used antiischemic cardiovascular preparation mildronat as neuroprotective and cytoprotective therapy to treat and prevent glaucomatous optic neuropathy. Prescription of mildronat was given to 35 patients. From 35 patients 20 were women and 15 men, at the age 40-75, visual acuity 0.1-1.0, Pt=18-24, treatment course 2,5-3 months. Before and after treatment patients were observed with routine methods (visometry, tonometry, determinig visual field on goldman spheroperymeter) and besides that on automated static perimetry Humphrey (30-2; 24-2; Armally) and Medmont studio (Glaucoma test; Full test). Also we used method of biomicroophtalmoscopy by positive lens +83 dptr on slit lamp and described optic nerve head with our scheme. According to the subjective and objective data positive dynamics were signed in 34 patients (63 eyes), negative dynamics in 1 patient (2 eyes). Glaucoma is medical and social problem in many countries. With the difference of expensive methods in prevention and treatment of glaucomatous optic neuropathy, using a mildronat as neuroprotective and cytoprotective drug is available for the majority of glaucoma patients. We recommend using mildronat in patients with primary open angle glaucoma with normolised intraocular pressure and in patients with normal tension glaucoma.

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.

Aim: To study efficacy of mildronate in the treatment of elderly patients with cardiac failure (CF)., Material and Methods: A total of 91 patients with chronic CF (NYHA FC I-III) entered the study. The study group of 63 patients received standard therapy for a month and mildronate in a dose 750 mg/day. The control group of 28 patients was treated conventionally. Subjective and objective assessment of the patients' condition, quality of life questionnaire, ECG, 6-min walk test were used for evaluation of the treatment efficacy., Results: In the study group daily frequency of anginal attacks reduced from 1.6 to 0.7 (in the control group from 1.46 to 1.25, p > 0.05), intensity of the attacks--from 1.4 to 0.7 points by 7-score scale (p < 0.05). Crepitation disappeared in 8 (12.8%) patients, edema of the legs--in 3 (4.8%) patients. Systolic blood pressure went down by 8 mmHg, diastolic one--by 4 mmHg. In the control group clinical changes were insignificant., Conclusion: Elderly patients tolerated mildronate well. It was a safe drug attenuating CF symptoms, increasing exercise tolerance and improving quality of life.