Mildronate belongs to the representatives of a new group of medication - partial inhibitors of fatty acids (partial fatty and oxidation inhibitors - pFOX-inhibitor) , which reduces the intensity of beta-oxidation of free fatty acids, limiting the transport through the mitochondrial membranes of long-chain fatty acids, preventing the accumulation of deficient fatty acids in mitochondria. The drug belongs to the cytoprotectors-antihypoxants, provides protection and energy supply to various cells of the body in conditions of ischemia and increased physical activity. Mildronate is a reversible inhibitor of gamma-butyrobetaine, which catalyzes the conversion of gamma-butirobetaina in carnitine, thus reducing the carnitine dependent transport of fatty acids into the mitochondria of muscle tissue .
Due to the limited transport and oxidation of fatty acids in the mitochondria, their concentration in the cytoplasm increases, as a result, the alternative way of energy production aerobic glycolysis increases.
Mildronate increases the sensitivity of insulin receptors to insulin and stimulates insulin-controlled glucose uptake, which promotes the availability of glucose for incorporation into the processes of energy production. At the same time, Mildronate activates and induces the synthesis of the two most important enzymes of aerobic glycolysis - hexokinase and pyruvate dehydrogenase, which involve pyruvate formed from glucose in the Krebs cycle, preventing the formation of lactate .
In experimental and clinical studies have shown anti-ischemic efficacy of Mildronate for angina (research MILSS, MILSs I, MILSS II), myocardial infarction, coronary artery bypass grafting. Mildronate, used with standard therapy at a dose of 1.0 g / d (1-2 times a day in the morning) during 1,5-3-6 during months, reduces the frequency of angina attacks, reduces the consumption of nitrates, increases exercise tolerance, increases the time before the occurrence of ST segment depression improves the quality of life .
The positive effect of Mildronate on endothelial function was noted. The drug stimulates endothelial NO-synthase, thereby increasing the production of nitric oxide, affecting the smooth muscles of blood vessels, causing vasodilation. Vazodilatiruushimi effect of Mildronate due to its azetilholinovogo action.
Vascular effects of Mildronate - reduced peripheral resistance, reduction of vasospastic reaction, inhibition of platelet aggregation and improved energy metabolism in the myocardium-led to its use in chronic heart failure .
Currently, the regimens recommended for the treatment of patients with HHST include Mildronate as a drug that optimizes energy metabolism, reducing the need for tissues in oxygen, regardless of its type and location .
Nechaeva G. I. to assess the effectiveness of Mildronate in rehabilitation treatment in DST, 240 patients (mean age 24.41±7.62 years) were examined. Mildronate was used in all patients by 5 ml 10% intravenously for 10 days, then-inside 250 mg 2 times a day for 4 months. The author noted the improvement in the quality of life of patients: reducing the frequency of complaints of fatigue, fatigue, muscle weakness; reducing the proportion of patients with ECG signs of violation of repolarization (p<0.05); increase in the final diastolic volume, left ventricular ejection fraction according to the results of echocardiography. After treatment when you run the test with the physical loading, the authors observed increase of tolerance to physical activity and the prevalence of normotimicescoe reaction. When using the drug, good tolerability, no adverse reactions were noted .
Kadurina T. I. recommends in the treatment of patients with NNST the developed method of correction of biochemical disorders by individually selected and pathogenetically justified schemes of systematic treatment, including Mildronate. Against the background of the therapy, a significant improvement in clinical and biochemical parameters, the condition of children with DST is noted, which, according to the authors, contributes to the slowdown in the progression of the disease .
Zemtsovsky E. V. considering the problems of diagnosis and place among other diseases of mitral valve prolapse, functional disorders of the cardiovascular system caused by changes in intracardiac hemodynamics, disorders of the structure of the extracellular matrix and dysfunction of the autonomic nervous system, justifies the feasibility of complex treatment, including Mildronate, in the case of systemic involvement of connective tissue and the detection of NNST .
Neurological aspects of DST are investigated Botulinum E. G. patients (over 500 people) young working age. Depending on the severity of DST, vascular disorders, vegetative disorders, asthenic, vertebro-gene syndromes, pyramid disorders without motor dysfunction, vestibular dysfunction, neuropathy were observed. The authors recommended a comprehensive approach to the treatment of patients with NNST, including non-drug treatment using many physical therapy methods and physical therapy, as well as drug treatment according to the schemes of the Russian recommendations on NNST, including Mildronate .
Indeed, Mildronate for patients with NNST is a universal drug, its effective action is observed in different tissues in pathological conditions. Mildronate increases the resistance of brain cells to hypoxia in ischemia, converting the oxidation of free fatty acids to a more economical way in pathological conditions. Mildronate, restoring the balance between delivery and consumption of oxygen, as effective in brain ischemia, as in myocardial ischemia. It is important to note that the use of Mildronate is indicated for neuropathies of different Genesis and vegetative disorders .
The properties of Mildronate as a cytopro-Tector and replenishing the energy deficit of the drug served as the basis for its inclusion in the treatment regimens of the NSDC in the published recommendations of the Russian society of cardiology (2009, 2012), as well as in the draft recommendations of the Russian national society of therapists and pediatricians, the recommendations of the Belarusian scientific society of cardiologists.
Over the years since the beginning of the XXI century, the interest of different specialists in the NNST has increased significantly. The variety of syndromes and difficulties in their differential diagnosis of systemic manifestations, the recognition of which presupposes knowledge of the signs of dysmorphogenesis; the relationship and interdependence of external and visceral signs, the abundance of complaints, often associated with dysfunction of the autonomic nervous system, and due to frequent visits of the doctor and the long search for a heavy somatic diseases; identifying anomalies, treatment and prognosis for which is unclear are few of the problems that arise when meeting a patient with an NNST. The difficulties continue at the stage of selection and justification of therapy, as the evidence base for the use of non-drug and medical products is often based on the results of short-term observations of individual researchers. Individual works highlight the impact of the NTST on the clinical manifestations of the most common cardiovascular diseases.
At the same time, changes in the structure and metabolism of connective tissue have a significant negative impact on myocardial remodeling, contribute to the appearance of life-threatening arrhythmias, the development of fibrosis. Correction of disorders of energy supply of cardiomyocytes, endothelial dysfunction, vasospasm, arising at a young age in patients with NNST can be considered as a primary prevention of coronary artery disease and heart failure.