The aim of the study: to investigate the involvement of distinct parasympathetic and sympathetic beta-adrenergic mechanisms in infarct-limiting effect of remote ischemic conditioning. Materials and methods. Experiments have been conducted on white male rats. Remote ischemic conditioning was performed as 15-min bilateral femoral arteries occlusion before the onset of myocardial ischemia (RIPC, n=8), on the 10-th minute of ischemia (RIPerC, n=8) or on the 10-th minute of reperfusion (RIPostC10', n=8). To study the role of vagal nerves in the development of remote ischemic conditioning femoral arteries occlusion was performed in conditions of bilateral vagotomy (Vagotomy+RIPC, n=8; Vagotomy+RIPerC, n=7; Vagotomy+RIPostC10', n=8). M-cholinoreceptors were blocked by atropine (groups Atropine+RIPC, n=10; and Atropine+RIPostC10', n=6). Beta-adrenoreceptors blockade was induced by injection of metoprolol or atenolol on the 1-st minute of reperfusion to animals with intact vagal nerves (groups MetR+RIPostC10', n=10; and AtenR+RIPostC10', n=10) or after bilateral vagotomy (groups Vagotomy+MetR+RIPostC10', n=10; Vagotomy+AtenR+RIPostC10', n=10). Results. RIPC, RIPerC и RIPostC10' limited infarct size by 56%, 58% and 49% respectively (all p<0,001 vs Control). Bilateral vagotomy, performed before the onset of myocardial ischaemia, abolished infarct-limiting effect of RIPC and RIPerC, but had no effect on cardioprotection induced by RIPostC10'. Atropine administration abolished cardioprotective effect of both RIPC and RIPostC10'. I.v. infusion of metoprolol or atenolol to the animals with intact vagal nerves had no effect on cardioprotection induced by RIPostC10', but administration of these agents in combination with vagotomy abolished this phenomenon (p>0,05 vs Control, p<0,001% vs RIPostC10'). Conclusions. Cardioprotective effect of RIPC and RIPerC is mediated mainly by vagal control of heart, whereas in RIPostC10' beta-adrenoreceptors are also important. Meanwhile, М-cholynoreceptors stimulation is a key point in the development of both RIPC, as well as RIPostC10'.

The aim of the study. Comparative analysis of the risk assessment of thromboembolism by CHADS2 and CHA2DS2-VASc scores, and to study the preventive effectiveness of different antithrombotic agents in patients with long-lasting аtrial fibrillation (AF) at 1 year follow-up. Materials and methods. The study included 108 patients aged 38 to 78 years old (mean age 62,6±8,4 years) with persistent or permanent AF. In 93.5% of patients revealed coronary artery disease and / or arterial hypertension, in 6.5% - non-coronary heart diseases. The risk of tromboembolism assessed by CHADS2 and CHA2DS2-VASc scores. Results. Patients at low risk of tromboembolism, according to CHADS2 score was 2.8%, in their absence, on a CHA2DS2-VASc score. Patients with moderate risk of tromboembolism, in these scores were 63.9% and 7,4% (χ2=72.653; p=0.000) respectively, and a high risk of tromboembolism - 33,3% and 92,6% (χ2=78,796, p=0.000) respectively. Depending on the ways to prevent tromboembolism, patients were divided into 2 groups. 1st group included patients treated with warfarin (n=90), and the endpoints were observed in 5.6% of patients. 2nd group included patients (n=18) treated with acetylsalicylic acid (ASA) and the end point was observed in 27.8% of patients. Conclusion. The introduction of a new CHA2DS2-VASc score led to an increase number of patients, who need mandatory anticoagulant therapy by 2.8 times. In the group of patients with atrial fibrillation treated with warfarin compared with a group of patients treated with aspirin, where cases of ischemic stroke have developed less often, and their clinical manifestation are less pronounced and are characterized by a benign course.

The optimization of the drug therapy for pulmonary arterial hypertension (PAH) associated with the introduction into clinical practice of highly effective drugs of pathogenetic action affecting the main targets of disease - activating the endothelin (ET-1) system, deficiency of endogenous prostacyclin and nitric oxide. The role of ET-1 in the pathogenesis of PAH due to powerful vasoconstrictive action, the ability to induce cell proliferation and differentiation, production of growth factors, cytokines, biologically active substances. Endothelin receptor antagonists (ERAs) - is the most important class of PAH- specific therapies, including two drugs - nonselective ERA bosentan and selective ERA - ambrisentan. The evidence base related to the application ambrisentan in PAH includes three key studies: testing of different dose regimes of the drug; 2 randomized, placebo-controlled, double-blind clinical studies and the study with replacement of ERAs on ambrisentan in patients intolerant other ERAs . In the study on ambrisentan dosage regimes testing increase of the distance in 6 - minute walk distance (6-MWT) was dose-dependent. Using the drug in doses ranging from 1mg to 10 mg to 12 wks. there achieved a significant increase in 6-MWT distance of 33.9 m with 1mg dose (p=0.003) to 38.1m with 5mg (p=0.001). In two 12wk randomized, placebo-controlled studies ARIES- 1 and ARIES- 2 (Ambrisentan in PAH-a phase III, Randomized, Double-blind, placebo-controlled, multicenter, Efficacy Study of ambrisentan on Subjects with pulmonary arterial hypertension) the treatment with ambrisentan resulted to the significant increase of exercise tolerance according to 6-MWT from 22 m to 59 m when using the dose of 2.5mg (p = 0.022) and 10mg (p < 0.001), respectively. Ambrisentan treatment helped to reduce the need for lung transplantation, atrial septostomy, hospitalization for PAH progression. Achieved improvement was maintained for 2-year treatment with ambrisentan. Ambrisentan therapy was well tolerated. By 12 weeks the frequency of transaminases and bilirubin elevations was significantly lower with ambrisentan than for placebo group (0.8% versus 2.3%, respectively). Long-term follow up in the open study in 383 patients treated with ambrisentan, 95% of patients were alive at 1 year and 94 % of patients continued the treatment. Patients with adverse events when receiving bosentan or sitaksentan after translation to ambrisentan had no increase of liver transaminases. Thus, treatment with ambrisentan in PAH pts. resulted in the improvement of clinical symptoms and hemodynamic parameters, the increase in exercise tolerance and the prolongation of the time to the development of clinical deterioration. Favorable effects of long-term therapy with ambrisentan are shown for at least 2 years. In 2012 ambrisentan was approved by the Russian National Pharmacological Committee for the treatment of patients with PAH (Functional Classes II-III) at the dose of 5 mg and 10 mg PO.

Objective. Studying of a possible role of interstitial fibrosis in remodeling of myocardium. Material and methods. For the purpose of estimation of fibrosis, depending on degree of dilatation of the left ventricle there has been carried out examination of 42 patients with inflammatory cardiomyopathy, (middle age 35,01±1,0). Patients have been divided into 2 groups. The first group was made of 23 patients with EDS <5,8 cm, and the second - 19 patients with EDS >5,8 cm. To all patients has been carried out ECG and EchoCG research. Results. At the patients of the 1st group CFV has made -9,1±2,2%, while in the 2nd group - 13,3±2,4%. By comparison of two groups of the patients substantial growth of collagen fraction volume at the patients with expressed dilatation of cavities of the left ventricles and its prevalence at the patients with heavy С is revealed more. At the patients with inflammatory cardiomyopathy thus the average index of distribution of collagen faction volume has made 11,1±3,1 % with fluctuations from 6 to 16 %. It is necessary to notice that in process of increase of signs of cardiac insufficiency CFV increases. So, at the patients with I-II CI FC CFV has made 9,8±3,0 % (CI 7,9-11,6), and at III - IV CI FC this indicator has increased already to 12,7±2,5 % (CI 11,0-14,4). The data obtained by us testifies that myocardium fibrosis at the patients with expressed cardiac insufficiency with dilatation of LV cavities much more, than at the patients with moderated СН. Conclusion. Thus, correlation between IMMLV and LVBW, which specifies dependence of structural changes on degree of fibrosis, and also the factors, promoting development of fibrosis at the patients with inflammatory cardiomyopathy is revealed.

CTEPH is the only type of surgically curable pulmonary arterial hypertension. In spite that, up to 50% of all CTEPH patients are rejected of surgical treatment because of distal lesions of pulmonary arteries or because of other contraindications. Medical treatment was proven to be one of the options to support this cohort of patients. Recent clinical studies addressed some medication regimens for treatment of CTEPH patients and showed distinct changes of different PH-variables with time. We discuss the main principles of drug therapy for inoperable CTEPH as well as for patients awaiting surgery, during and after pulmonary thrombo-endarterectomy.