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Aim: To analyze the relationship between metabolic disorders and obesity with hemodynamic parameters and the severity of the condition of patients with chronic thromboembolic pulmonary hypertension (CTEPH) based on the POLET register., Materials and Methods: The study included patients with CTEPH from the POLET register. Data from medical history, lipid profile, glycemia, uric acid level, weight, height, functional class (FC), distance in the 6-minute walk test (6MWT), echocardiography, and right heart catheterization were used for analysis., Results: The study included 84 patients 60±14 years old, including 45 men. The majority of patients had FC III - 51 (65%), which corresponded to 6MWT - 338±113 m. Nineteen (23%) people had experience in taking PAH specific therapy, 37 (46%) had cardiovascular comorbidity. In the general group, the body mass index (BMI) was 25.7±4.5 kg/m 2 , and normal glycemia, lipid profile, and uric acid levels were also determined. mPAP was 51±12 mmHg, RA area was 25.5 (20; 30) cm 2 . Correlations were identified between: RA area and the level of total cholesterol (r=0.60; p <0.01), triglycerides (r=-0.24; p <0.001), LDL cholesterol (r=0.75; p = 0.04), uric acid (r=0.75; p =0.03); total cholesterol and 6MWT (r=0.44; p =0.04). Analysis of metabolic disorders, FC and comorbidity revealed differences between FC III and IV groups in the level of HDL cholesterol ( p =0.02) and triglycerides ( p <0.01)., Conclusion: The POLET registry includes mainly older patients. Severe FC (87% - III and IV) may be a result of the older age and the presence of concomitant pathology in almost half of the patients. The discovered relationships between the area of RA and FC with lipid and purine metabolism were discovered for the first time, however, they correspond to the direction of the world scientific researches, are important due to the use of these indicators in the scale for calculating the risk of death in patients with PAH and require further development.

The article reviews current approaches to diagnosing and treating chronic thromboembolic pulmonary hypertension (CTEPH). The definition of the CTEPH is given, and its main risk factors are described. It is shown that the modern algorithm of diagnostic search includes four stages; the examination methods used at each stage are characterized. The most rational approach to CTEPH therapy is provided; the possibilities and limitations of pulmonary endarterectomy, transluminal balloon angioplasty of the pulmonary arteries, and specific therapy of pulmonary hypertension in such patients are described. The clinical presentation and treatment of CTEPH according to the Russian Pulmonary Hypertension Registry are reviewed.

On December 13, 2021, an expert council was held to determine the position of experts of different specialties regarding the reasons for the low level of diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in real clinical practice in a pandemic of a new coronavirus infection and possible ways to improve detection in patients with pulmonary embolism (PE) ) in history. The reasons for the low level of diagnosis of CTEPH are the insufficient level of knowledge of specialists, especially primary care physicians; lack of clear regulatory documents and expert centers for the management of this category of patients. Primary diagnosis of CTEPH in a pandemic can be strengthened through the widespread use of telemedicine for consultations of primary care physicians with specialists from expert centers; to maximize the role of echocardiography and computed tomography (CT) as differential diagnostic tools for dyspnea, in particular in patients with COVID-19. To increase the detection rate of CTEPH, diagnostic vigilance is required in patients with risk factors and episodes of venous thromboembolism. To improve the screening of CTEPH, it is necessary to create an algorithm for monitoring patients who have had PE; provide educational activities, including through the media; create materials for patients with accessible information. The regulatory documents should designate the circle of responsible specialists who will be engaged in long-term monitoring of patients with PE. Educational programs are needed for primary care physicians, cardiologists, and other physicians who come into the field of view of patients with CTEPH; introduction of a program to create expert centers for monitoring and managing patients with the possibility of performing ventilation-perfusion lung scintigraphy, cardiopulmonary stress test, CT, right heart catheterization. It seems important to build cooperation with the Ministry of Health of Russia in order to create special protocols, procedures for managing patients with PE and CTEPH.

For patients with pulmonary hypertension (PH) there have been no recommendations for physical rehabilitation for a long time, and in fact physical activity was discouraged. Nowadays, the position regarding exercise in patients with PH has changed studies have shown the safety and effectiveness of exercise in these patients. Most of the studies published to date on rehabilitation in patients with PH have assessed its effect on exercise tolerance. This review provides an overview of published studies and their conclusions on the effectiveness of rehabilitation in patients with chronic thromboembolic hypertension being as a complex therapy using medical and surgical methods of treatment and rehabilitation. The inclusion of rehabilitation in complex treatment allows to achieve patients highest possible tolerance to physical activity, increase in the functional class, quality of life and restore working capacity.

Pulmonary hypertension (PH) is a severe and often rapidly progressive disease with fatal outcome. Endothelial dysfunction in PH is associated with decreased nitric oxide production. After reviewing the mechanisms of action and the evidence base for specific therapy with phosphodiesterase 5 inhibitors (PDE-5) and soluble guanylate cyclase stimulators, a reseach review on switching from PDE-5 to riociguat is conducted. A potential advantage of riociguat is its independence from endogenous nitric oxide and from the other (besides PDE-5) isoenzymes of phosphodiesterases. The favorable efficacy profile of sildenafil has been proven for the main forms of pulmonary arterial hypertension, of riociguat for the main forms of pulmonary arterial hypertension and chronic thromboembolic PH. The clinical efficacy of replacing PDE-5 with riociguat has been demonstrated in uncontrolled trials and in the randomized controlled study REPLACE. The possibility of therapy optimization by switching from IFDE-5 to riociguat is fixed in the Russian (class and level of evidence B-3) and Eurasian (class and level of evidence IIb-B) clinical guidelines, as well as in the materials of the Cologne Expert Consensus. An additional argument for switching is the lower cost as compared to combination therapy in the Russian Federation. According to the Russian and Eurasian guidelines for PH and the Russian instructions for the use of riociguat, the drug should be taken at least 24 hours after sildenafil discontinuation.

The paper summarizes the most important aspects of modern treatment of patients with pulmonary arterial hypertension (PAH): the goals of therapy are indicated, the issues of risk stratification of PAH progression/mortality, the place of combination specific therapy and switching strategies are considered, as well as new promising approaches to therapy; features of the course of the new coronavirus infection COVID-19 in this category of patients are discussed.

Aim: To assess demographic and clinical characteristics, to describe of the functional and hemodynamic status, profile of concomitant pathology, data of instrumental examination in chronic thromboembolic pulmonary hypertension (CTEPH) patients; to study the features of specific and supportive therapy according to the data of the Russian national registry., Materials and Methods: From 2012 till 2020 a multicenter, prospective study in 15 regional expert centers of the Russian Federation (www.medibase.pro) included 404 newly diagnosed CTEPH patients over the age of 18 years in the Russian registry of patients with pulmonary arterial hypertension and CTEPH (NCT03707561). The diagnosis was established by European and Russian clinical guidelines for the diagnosis and management of pulmonary hypertension. 154 inoperable CTEPH patients an additional analysis of specific and supportive therapy was performed., Results: The study included 404 patients (55.6% women and 44.3% men) at the age of 58.6 [48.6; 69.3] years. Median time from symptom onset to the diagnosis verification waswas 2.4 years (from 0.1 to 2.9 years). 79.1% of patients were in the III and IV functional class (World Health Organization) at the time of diagnosis and in 44.1% with RHF (right heart failure). In assessing the profile of concomitant pathology, it was noted that CTEPH patients were more often with arterial hypertension (39.1%), erosive-ulcerative lesions of the stomach/duodenum (16.1%), atrial fibrillation (13.8%), obesity (13.1%). Distance in 6MWD (6-min walk distance) was 337.2 [250; 422] m, Borg dyspnea index scale 4.1 [3.0; 5.0] points. Hemodynamic parameters according to right heart catheterization were: Mean PAP (pulmonary arterial pressure) (51.114.04) mmHg, CO (cardiac output) (3.50.98) l/min, CI (cardiac index) (2.00.48) l/min/m2, PVR (2008528) dyns/cm5., Conclusion: According to the Russian registry, inoperable CTEPH patients had precapillary PH (pulmonary hypertension) with severe functional status, in combination with frequent concomitant pathology (arterial hypertension, erosive-ulcerative lesions of the stomach/duodenum, atrial fibrillation, obesity, right heart failure). 66% of inoperable CTEPH patients received specific drug therapy.

Aim: to perform the complex analysis of clinical, functional, hemodynamics profile in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) compared to the idiopathic pulmonary arterial hypertension (IPAH) group at the time of diagnosis verification according to the Russian registry, and to evaluate the features of medical therapy and it's influence on prognosis in these patients., Materials and Methods: In the retrospective study 193 patients with IPAH and 130 patients with inoperable CTEPH older than 18 years were included. All included patients were the participants of Russian registry (www.medibase.pro) in 15 Russian expert centers during the period from 01.01.2012 to 31.12.2018 year. The diagnosis was verified according to the algorithm, reflected in the Russian guidelines on diagnosis and treatment of PH and CTEPH (2016 year). The comparison analysis of clinical, functional, hemodynamics parameters in patients with IPAH and inoperable CTEPH was made., Results: The status of 193 patients with IPAH (32 male and 162 female) and 130 patients with inoperable CTEPH - (40 male and 90 female) was analyzed during the study. The CTEPH patients were older compared to the IPAH patients: 52.2 [41.1; 60.6] and 36.5 [26.8; 36.5] years, respectively. The median period since symptom occurrence till CTEPH verification was 1.08 [0.2; 3.1] years, in IPAH patients - 2.01 [0.6; 4.2] years. More than 80% of inoperable CTEPH patients had III and IV functional class (FC) according to the World Health Organization classification at the time of diagnosis verification versus 61% of IPAH patients. According to echocardiography the level of mean pulmonary arterial pressure was comparable in two groups of PH patients. However in inoperable CTEPH patients the right atrial area was larger. The significantly higher value of mean pulmonary arterial pressure and lower value oxygen saturation of arterial blood according to the right heart catheterization were revealed. The 5-year survival in CTEPH patients, receiving initial dual combination therapy in 75% cases (in 40% - combination of riociguat and iloprost ) was 93% versus 86.5% in patients with IPAH., Conclusion: It was revealed, that inoperable CTEPH patients were significantly older with severe functional and hemodynamics status at the time of diagnosis verification, although with higher level of 5-year survival compared to the IPAH patients according to the Russian registry.

Aim: To evaluate the effectiveness of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH)., Materials and Methods: Forty patients with inoperable CTEPH were enrolled in this study. The indications were determined by multidisciplinary team. The average age of patients was 53.5 [43; 63] years. In 65% of cases patients had functional class III (according to WHO); the distance in the 6-minute walk test (6MWD) was 327 [280; 400] m; catheterization of the right heart revealed systolic pulmonary artery pressure (SPAP) 82 [64; 100] mm Hg, mean pulmonary artery (mPAP) 48.5 [38; 56] mm Hg, pulmonary vascular resistance (PVR) 784 [525; 1257] dyn·s/cm-5. Each patient underwent 6 BPA., Results: The effectiveness of BPA was assessed 2 months after the last session. According to the data of right heart catheterization SPAP decreased by 27.3%, mPAP by 26%, PVR by 34.5% from baseline. After all series of BPA echocardiography and magnetic resonance imaging demonstrated reverse remodeling of the right heart. Also significant decrease in the level of BNP by 62%, increasing in 6MWD distance by 39% and improvement of the functional class up to I in 60% cases and up to II in 40% cases were noted., Conclusion: The results of the present study demonstrated a high efficacy of BPA allowing to normalize hemodynamic and clinical parameters, increasing the physical activity. Balloon pulmonary angioplasty is a new highly effective, safe method for treating patients with inoperable CTEPH.

Aim: Assess the prevalence, clinical course, current therapy, and mortality in patients with pulmonary arterial hypertension (PAH) in the National Registry., Materials and Methods: In the prospective study we included patients over 18 years of age with diagnosed PAH [idiopathic PAH (IPAH); Drug- and Toxin-Induced Pulmonary Hypertension; inherited PAH; PAH associated with congenital heart disease (PAH-CHD); PAH associated with systemic connective tissue disease (PAH-CTD); PAH associated with HIV infection (PAH-HIV); with portal pulmonary hypertension (portoPAH)]. The observation was carried out in 15 expert centers of Russia from 01.01.2012 to 31.12.2017., Results: Our registry included 470 patients with PAH: IPAH - 41.5%, PAH-CHD - 36%, PAH-CTD - 19.5%, inherited PAH - 0.4%, portoPAH - 1.9%, PAH-HIV - 0.4%, Drug- and Toxin-Induced PAH - 0.4%. The prevalence among women was 84%. The mean age at the time of patient enrollment in the registry for the overall group of PAH was 42.7±15.3 years. The distance in the 6-minute walking test was 361.3±129.3 m. Among all patients with PAH, 65% had functional class (FC) III/IV at the time of diagnosis, among IPAH - 62%. 69.9% received PAH-specific therapy, of which 62.1% - monotherapy, 32.7% - dual combination therapy, and 5.2% triple therapy. Sildenafil is the most commonly prescribed drug in the regimen of monotherapy. 31.6% of patients were treated with bosentan, 6.4% - riociguat, 3.4% - ambrisentan, 2.1% - macitentan and 2.0% iloprost. Survival of patients with PAH was 98.9% at 1 year of follow-up, 94.1% at 3 years and 86.0% at 5 years., Conclusion: The registry data indirectly indicates the need to increase efforts aimed at improving the diagnosis of systemic connective tissue diseases in adults, as well as congenital heart defects in children for timely surgical treatment. In recent years, PAH-specific drugs of the new generation have been introduced into clinical practice, but currently in Russia there are no parenteral prostanoids, which are recommended for the most severe patients.

Aim: The aim of current study was to estimate the economic burden of the chronic thromboembolic pulmonary hypertension (CTEPH) in Russia based on patient registry., Materials and Methods: Cost of illness study was based on data derived from CTEPH patient registry that was developed at the Division of hypertension of FSBI "National Medical Research Center of Cardiology". Demographic and clinical patient characteristics were analyzed with descriptive statistic methods. Cost of illness study was performed from the state perspective and with bottom-up approach. Bootstrapping was used for calculation of average costs per patient/year. Within the study direct costs (medical costs: outpatient, inpatient, emergency, PAH-specific therapy, concomitant therapy; non-medical costs: pension due to disability status, payments for patients on sick-leave) and indirect costs (loss in GDP) were estimated., Results: Overall, 113 CTEPH patients (67 women and 46 men) from 33 Russian regions were included, mean age of patients with CTEPH was 54.6±13.95 years. Most of the patients (55%) were in able-bodied age. It was found that about half of patients with diagnosed CTEPH had a disability. Average duration of disease at the time of analysis was 6.88±11.41 years. Period from the first occurrence of symptoms to the confirmation of diagnosis of CTEPH was 2.58±5.21 years on average. More than 70% of patients had III and IV FC (WHO) at the time of diagnosis. Mean number of outpatient visits was 1.97±1.65 per patient/year, and inpatient visits were reported for 59% of patients. About 54% of patients used PAH-specific therapy, moreover 46% patients had interruptions of PAH-specific therapy (58.4±66.3 days). The total costs of CTEPH per patient/year were calculated as 805,901 RUB. The overall burden of CTEPH in Russia for total CTEPH population (470 patients) was 379 million RUB per year., Conclusion: CTEPH is the rare disease that is characterized with later diagnosis due to absence of disease-specific symptoms. Therefore economic burden of the CTEPH is significantly low in comparison to widespread cardiovascular diseases. Development of network of expert PH-centers and increase of the access for PAH-specific therapy will help to increase the quality of health care for patients with CTEPH.

Aim: to assess the state of vascular bed, parenchyma, and perfusion of lungs in patients with chronic thromboembolic pulmonary hypertension (CTEPH) using the method of subtraction computed tomography (CT)., Methods: CT pulmonary angiography (CTPA) was performed in 45 patients with verified CTEPH (18 men, 27 women, age 26-79 years) by CT scanner using the "Lung subtraction" standard protocol. Parameters analyzed were characteristics of the state of main pulmonary artery (MPA) and the right ventricle (RV), and calculated CT angiographic (CTA) obstruction and perfusion defect scores., Results: Significant correlation was found between CTA obstruction score and perfusion defect score (r=0.34, p=0.02). Mean pulmonary arterial pressure (mPAP) correlated with MPA diameter (r=0.4, p=0.02), RV wall thickness (r=0.6, p=0.0003) and the ratio of MPA diameter to ascending aortic diameter (r=0.5, p=0.002). Significant correlation was also found between RV wall thickness and pulmonary vascular resistance (PVR) (r=0.4, p=0.04). Neither CTA obstruction score nor perfusion defect score correlated with PVR and mPAP. The data of CT did not correlate with results of 6-minute walk test., Conclusion: In patients with CTEPH subtraction CTPA allows carrying out complex diagnostics of the state of vascular bed, parenchyma and perfusion of the lungs.

Aim: To evaluate the vascular bed and lung perfusion in patients with chronic thromboembolic pulmonary hypertension (CTEPH) by computed tomography (CT) and to compare the severity of pulmonary arterial (PA) thrombotic lesions concurrent with parenchymal perfusion disorders with angiopulmonographic findings and clinical and hemodynamic characteristics., Subjects and Methods: In the period from November 2015 to May 2016, 22 patients (7 men, 15 women) aged 27 to 67 years with a verified diagnosis of CTEPH were examined using an Aquilion ONE VISION Edition 640 (Toshiba Medical Systems, Japan) CT scanner with a 320-row detector. Perfusion defect in this study was evaluated with the new software allowing one to combine contrast and contrast-free images by a subtraction method. CT data analysis included visual assessment of the vascular bed and lung parenchyma and quantitative assessment with perfusion map construction and semi-automatic determination of the obstruction index (OI) and perfusion defect index (PDI). OI was compared with PDI and mean LA pressure according to the data of right heart catheterization and 6-minute walk test., Results: A statistically significant correlation was found between OI and PDI in patients with CTEPH (Pearson r=0.56; p=0.0065). There were no relationships between mean LA pressure and vascular perfusion indices (OI and PDI) or between vascular perfusion parameters and 6-minute walk test results., Conclusion: CT angiopulmonography in conjunction with pulmonary perfusion assessment (within one study) allows evaluation of the severity of vascular lesions and perfusion disorders and determination of the efficiency of treatment in patients with CTEPH.

The results of evaluating the efficacy and safety of bosentan in patients with pulmonary arterial hypertension (PAH), as shown by the data of foreign randomized controlled trials and the authors' own experience, convincingly demonstrate that the introduction of the drug into clinical practice has led to a significant improvement of the possibilities of drug therapy in patients with this serious illness. Bosentan substantially improves physical activity in patients, reduces the severity of clinical symptoms, slows down the rates of disease progression, and prolongs survival in patients with different forms of PAH.

The paper gives current approaches to treating chronic thromboembolic pulmonary hypertension (CTEPH) from the document «Federal Guidelines for the Diagnosis and Treatment of CTEPH» approved at the Third Russian Congress on Pulmonary Hypertension on December 11, 2015. The guidelines had been elaborated to optimize the treatment of patients with CTEPH on the basis of an analysis of the data of the present-day registries and multicenter randomized clinical trials, national and international guidelines and consensus documents, and documents published in recent years. CTEPH is a unique form of pulmonary hypertension since it is potentially curable by surgical treatment. The paper presents indications for and contraindications to pulmonary thromboendartectomy; preparation for surgery; operating room facilities; the specific features of postoperative management and possible complications; and long-term RESULTS: In terms of therapy, in addition to non-pharmacological measures, the authors discuss maintenance and specific treatment options for CTEPH, balloon pulmonary angioplasty, and lung/heart-lung transplantation. In conclusion they propose a management algorithm in patients with CTEPH and requirements for its problem to the center of experts.

Chronic thromboembolic pulmonary hypertension (CTEPH) is precapillary pulmonary hypertension, in which chronic obstruction of large and middle branches of pulmonary arteries (PAs) and secondary changes in the lung microcirculatory bed result in a progressive increase in pulmonary vascular resistance and PA pressure with the development of severe right cardiac dysfunction and heart failure. CTEPH is a unique form of pulmonary hypertension since it is potentially curable by surgical treatment. The diagnostic criteria for CTEPH are a mean PA pressure of ≥25 mm Hg, as evidenced by right heart catheterization; a PA wedge pressure of ≤15 mm Hg; a pulmonary vascular resistance of >2 Wood units; the presence of chronic/organized thrombi/emboli in the elastic PAs (pulmonary trunk, lobular, segmental, subsegmental PAs); effective anticoagulant therapy at therapeutic dosages over at least 3 months. Up to now, our country has had no guidelines for the diagnosis and treatment of this rare severe disease that, when appropriately untreated, has an extremely poor prognosis. The main task in the preparation of this document was to generalize and analyze the data of current registries, multicenter randomized clinical trials, national and international guidelines, and consensus documents recently published on this problem in order to optimize a diagnostic process and treatment in this category of patients. Part 1 gives a definition of CTEPH, its place in the clinical classification, epidemiology and prognosis, risk factors, pathogenesis and morphology, diagnostic approaches and determination of operability in patients, and specific features of differential diagnosis.

Pulmonary hypertension (PH) is a group of diseases characterized by progressive increases in pulmonary vascular resistance and pulmonary artery pressure, which results in right ventricular heart failure and sudden death. Based on the current version of the guidelines for PH diagnosis and treatment, adopted by the experts of the European Society of Cardiology and the European Respiratory Society in 2009, and on the data of Russian and foreign clinical trials, the Russian experts elaborated clinical guidelines for PH in 2013. The latter consider the current classifications of PH, the specific features of its pathogenesis, and its diagnostic algorithm. The section dealing with drugs for maintenance therapy discusses data on the use of oral anticoagulants, diuretics, cardiac glycosides, and oxygen therapy. PH-specific therapy includes calcium antagonists, prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Surgical procedures for PH involve atrial septostomy, thromboendartectomy, and lung or heart-lung transplantation. A treatment algorithm is proposed for PH patients. The current medicinal approaches using specific therapy agents and their combinations offer new promises for the effective treatment of patients with PH and improve its prognosis.

Aim: To investigate the demographic and clinical characteristics of patients with pulmonary hypertension (PH) and chronic thromboembolic pulmonary hypertension (CTEPH), regions of their residence, the specific features of diagnosis and drug therapy, and the patients' survival within the framework of a multicenter open-label prospective study., Subjects and Methods: The study enrolled patients over 18 years of age with PH classified as Group 1 (PH) and Group 4 (CTEPH). The follow-up was made in 9 expert centers of Russia on January 1 to February 28, 2014. The data of patients with PH and CTEPH were electronically entered at the register website: www.pul-hyp.medibase.ru., Results: The study included 242 patients (183 women and 59 men) from 44 regions of the Russian Federation. PH of different etiologies was present in 79.3%, including 43.8% with idiopathic PH, 28.5% with congenital heart disease-associated PH, 6.2% with diffuse connective tissue-associated PH, 0.8% with hereditary PH; 20.7% were diagnosed with CTEPH. The patients' mean age at the inclusion in the register was 43.2 ± 15.8 years; the median PH duration was 4.4 years (1.4 to 10.6%). The distance covered during a 6-minute walk test was 395.2?111.1 m; the Borg dyspnea index was 3.4 ± 1.4 scores and the functional class was 2.5 ± 0.8. After right cardiac catheterization, the mean pulmonary artery pressure was 53.1 ± 19.5 mm Hg; cardiac output, 3.8 ± 1.2 l/ min; cardiac index, 2.1 ± 0.6 l/min/m2; pulmonary vascular resistance, 1105 ± 677.6 dyn·sec/cm5. A positive acute pharmacological test was seen in 16.3% of the patients. The most common comorbidity was erosive ulcerative lesion of the gastrointestinal tract (23.5%), hypertension (16.9%), and obesity (16.5%). 66% of the patients received PH-specific therapy: sildenafil (51.6%), bosentan (20.9%), or iloprost (7%); 7.4% of the patients were observed within the framework of clinical trials, 17.7% received combined therapy for PH: 16.3 and 1.4% had dual- or triple-component therapy, respectively; 55.8% of the patients took calcium antagonists, 61.4% had diuretics, 85.6% had antithrombotic drugs. The survival rates were 98% in the first year of the follow-up and 90.1% by the end of 2013., Conclusion: The formation of a national register of patients with PH and CTEPH makes it possible to introduce current approaches to diagnosing and treating the patients of this category and to evaluate the efficiency and quality of rendered medical care and will contribute to the estimation of required health care volumes and the expenditure of public health resources.

Aim: To study the effect of bosentan on the clinical status and cellular immunity of patients with idiopathic pulmonary hypertension (IPH)., Subjects and Methods: The study enrolled 35 patients with Functional Class (FC) II and IV IPH who had received conventional therapy for 3 months. All the patients took bosentan 125 mg/day for 4 weeks. Then they were randomized to have bosentan 125 or 250 mg/day (Groups 1 and 2). FC was assessed and 6-minute walk test (6MWT), transthoracic echocardiography (EchoCG), and right heart catheterization (RHC) were performed at baseline and after 12 weeks. Peripheral blood lymphocytes were immunophenotyped and the functional activity of neutrophils was determined by their ability to absorb latex particles at baseline and following 3 and 12 weeks., Results: After 12 weeks of treatment, both groups showed a statistically significant increase in the distance covered during the 6MWT. The Borg index and FC also decreased statistically significantly. EchoCG demonstrated a statistically significant reduction in systolic pulmonary artery pressure (SPAP) in Group 1; and in Group 2, SPAP was lower at baseline and remained substantially unchanged (it statistically significantly decreased as evidenced by RHC). Bosentan statistically significantly diminished pulmonary vascular resistance in both groups. No adverse reactions were noted. At baseline, the patients showed a statistically significant elevation in NKT-like lymphocytes up to 10.79 +/- 6.2%. The other indicators of peripheral blood lymphocyte phenotyping did not exceed the normal range. The count of NKT-like lymphocytes remained significantly above the normal levels throughout the follow-up in both groups and slightly dropped in Group 1 patients only after 12 weeks of treatment. In Group 2, the level of CD3+CD25+ lymphocytes rose as compared to the normal levels at 3 and 12 weeks of treatment. At 3 weeks of treatment, there was a statistically significant difference between the groups in phagocytic number., Conclusion: Bosentan treatment statistically significantly improves the clinical status of patients with IPH and it is characterized by good tolerability. Bosentan does not exceed the normal count of peripheral blood NKT-like lymphocytes, but it has a direct or indirect positive effect on the B-lymphocytic component of the immune system in patients with IPH.

Aim: To evaluate the efficiency and safety of intravenous infusion of levosimendan in patients with idiopathic pulmonary hypertension (IPH) and its clinical, hemodynamic, and neurohumoral effects., Subjects and Methods: The study included 9 patients (mean age 31.8 +/- 8.7 years) with Functional Class III and IV IPH and severe right ventricular failure (RVF). Levosimendan was administered as dropwise intravenous infusion. The patients' general condition, blood pressure, heart rate, and 6-minute walk test results were assessed at baseline and 24 hours after levosimendan infusion, and then following 12 weeks. The time course of changes in blood neurohumoral mediators was determined and transthoracic echocardiography performed., Results: At 24 hours after initiation of levosimendan infusion, there were substantial reductions in pulmonary artery systolic pressure, mean pulmonary artery pressure, mean right atrial pressure, and pulmonary vascular resistance. There was a significant increase in exercise tolerance. The blood exhibited lower norepinephrine and NT-proBNP and higher epinephrine concentrations. At 12 weeks after termination of levosimendan infusion, the improved functional status was preserved in the patients with IPH. There were no noticeable changes in the achieved key hemodynamic parameters. Only one patient needed re-administration of the drug 12 weeks later. The achieved changes in vasoactive mediators were retained 12 weeks following levosimendan infusion. Levosimendan treatment was not followed by clinically relevant adverse reactions requiring infusion termination and therapy discontinuation., Conclusion: 24-hour intravenous levosimendan infusion in patents with FC III-IV IPH and severe RVF causes positive changes in the key hemodynamic parameters and neurohumoral status of the patients and promotes stabilization in those with IPH at 12-week follow-up.

Aim: To study the impact of 24-week therapy with nebivolol in a dose of 5 mg/day on the clinical and functional status of patients with idiopathic pulmonary hypertension (IPH), echocardiographic parameters, and blood levels of vasoactive mediators and nitric oxide (NO) metabolite., Subjects and Methods: During continuous standard therapy comprising dihydropyridine calcium antagonists, warfarin, and diuretics, 12 patients with IPH and functional class (FC) II-III received nebivolol in a dose of 5 mg/day for 24 weeks. According to the data of right heart catheterization, all the patients had a positive acute pharmacological test with a vasodilator (NO). Six-minute walk test (6'WT), estimation of the Borg dyspnea index (BDI) and FC, transthoracic echocardiography (EchoCG), and measurements of the levels of NO metabolites, endothelin-1, (ET-1), thromboxane B2 (TxB2), and 6-keto-prostaglandin F1alpha (6-ketoPG F1alpha) were done at baseline and after 12 and 24 weeks of the therapy., Results: Following 24-week nebivolol treatment, there was a statistically significant increase in 6'WT distance (from 473 +/- 47.6 to 516.7 +/- 58.4 m; p < 0.0001) and a drop in BDI (from 3.4 +/- 2.2 to 1.1 +/- 0.7; p < 0.05) and FC (from 2.9 +/- 0.4 to 1.7 +/- 0.2; p < 0.05). Doppler EchoCG showed that pulmonary artery systolic pressure statistically significantly decreased (91.6 +/- 30 to 78.3 +/- 39 mm Hg; p = 0.05) at 12 weeks and slightly increased up to 83.2 +/- 32.4 mm Hg at 24 weeks. After 24-week treatment, the anteroposterior dimensions of the right ventricle (RV) statistically significantly reduced (from 4.4 +/- 0.6 to 3.8 +/- 1.2 cm; p < 0.05). The other EchoCG parameters remained substantially unchanged. There was a statistically reduction in the level of ET-1 (from 2.99 +/- 1.1 to 2.17 +/- 0.8 micromol/l; p < 0.05). The concentrations of 6-ketoPG Fla, TxB2, and NO metabolite remained substantially unchanged at 24 weeks of treatment with nebivolol. There were no adverse reactions requiring that the dose of the drug be discontinued or reduced. Heart rate tended to be lower at a 24-week follow-up. All the patients continued taking nebivolol after completion of the study., Conclusion: Therapy with nebivolol in a dose of 5 mg/day for 24 weeks led to a significant functional improvement in the patients with IPH and reductions in RV dimensions and blood ET-1 levels. The therapy did not cause adverse reactions.

Aim: To study structural and functional changes of the right ventricle (RV) in patients with pulmonary hypertension (PH) of various etiologies and to assess an association of these changes with the levels of natriuretic peptides (NP)., Subjects and Methods: The study enrolled 102 patients with PH (29 with idiopathic PH (IPH), 15 with PH in the presence of chronic pulmonary thromboembolism (PTE), 18 with HP associated with scleroderma systematica (SS), 13 with PH in the presence of chronic obstructive pulmonary disease (COPD), 15 with PH associated with congenital heart disease, 12 with residual PH and a control group of 21 healthy volunteers. Conventional echocardiography (EchoCG) and tissue myocardial Doppler (TMD) EchoCG were performed. The plasma levels of brain NP (BNP) and atrial NP were measured., Results: Conventional EchoCG revealed the most significant remodeling of the heart and pulmonary artery in patients IPH and the least one in those with COPD. TMD findings suggest that RV diastolic function was most and less significantly impaired in patients with IPH and in those with COPD, respectively, and corresponded to the level of NT-proBNP in patients with PH. In patients with PTE with SS, RV diastolic dysfunction (DD) dominated over systolic ones, the functional class and the level of NT-proBNP being comparable with those in patients with ILH. TMD could reveal RV DD in a larger proportion of patients with PH (in all groups) than could Doppler EchoCG. The ratio of the maximum RV early filling velocity to RV tricuspid valve (TV) ring peak movement rate in early diastole (TV E/EM) corresponded to the levels of NP and the magnitude of cardiac remodeling in patients with PH. ROC analysis revealed the intrinsic separating values of TV E/Em from the mitral ring (MR E/Em) which allowed the patients with higher NT-proBNP levels to be identified with a high sensitivity and a high specificity. An aggregate of factors, such as age, right atrial volume, and PA systolic pressure as shown by conventional EchCG and TMD readings, identified patients with PH and elevated NT-proBNP with 73.3% sensitivity and 90.7% specificity., Conclusion: TMD has advantages over conventional EchoCG in the detection of RV DD associated with elevated NP levels in patients with PH.

Aim: To study the condition of the sympathico-adrenal system (SAS), synthesis of cAMP dependent on beta2-adrenoreceptors and parameters of free radical oxidation in patients with primary pulmonary hypertension (PPH); to examine efficacy of non-selective beta- and alpha1-adrenoblocker carvedilol in PPH patients., Material and Methods: Twenty patients with PPH had 6-minute walk test, ECG monitoring with assessment of heart rhythm variability (HRV). Tests for noradrenalin and adrenalin concentration in blood plasma, cAMP synthesis by blood lymphocytes in basal conditions and under stimulation with isoproterenol and forskolin, free radical oxidation were made initially, 1 and 6 months later. Ten patients received carvedilol in addition to standard therapy, 10 patients served control., Results: PPH patients had higher NA in the blood, low cAMP synthesis, high malonic aldehyde, low activity of glutathionperoxidase, increased activity of superoxidedismutase and catalase of erythrocytes. The most pronounced changes in the above parameters were observed in patients with PPH FC III-IV. HRV declined in progression of cardiac failure. 6-months of combined treatment with carvedilol increased the distance of 6-min walk. Carvedilol had no effect on HRV, it reduced NA, stimulated cAMP synthesis, demonstrated no antioxidant activity., Conclusion: In PPH there is activation of SAS and desensitization of beta2-AR cells, oxidative stress develops. Addition of carvedilol to standard therapy with PPH improves clinical condition due to adrenoblocking properties of the drug.

Aim: To design a mathematical express model of expected lifespan of patients with primary pulmonary hypertension (PPH)., Material and Methods: A retrospective analysis of 418 case histories of 132 PPH patients (81 females, 51 males, age 16-57 years). Ninety one of them were hospitalized at least twice. The following characteristics of the patients were registered: a PPH form, age at onset, gender, morphological structure of the lung, date of the first visit to doctor. Relationship of these factors with lifespan was analysed and the express formula of expected lifespan was calculated using the multifactorial analysis of variance with standard computer statistical programs., Results: Lifespan was studied for dependence on static factors free of therapy effects (gender, age, form of PPH). The presence of a factor named "duration of the disease development" (DDD) is suggested. A correlation was found between DDD and lifespan in PPH patients explaining survival by 84.5%. The formula of the prognosis was derived for patients with known morphological structure of the lung in whom the above dependence explains survival by 93.5%., Conclusion: Among effect modifiers, of significance for survival are age, PPH form, morphological structure of the lung. An artificial index DDD was used for deriving a formula for prognosis of survival for a newly hospitalized PPH patient.

We studied the role of oxidative stress in the pathogenesis of primary pulmonary hypertension. In patients with primary pulmonary hypertension the content of malonic dialdehyde in the plasma was higher than in healthy volunteers (5.18 0.46 and 2.95 0.14 nmol/liter, respectively, p<0.01). However, glutathione peroxidase activity in the plasma decreased in these patients (0.50 0.17 vs. 1.19 0.14 U/ml in the control, p<0.05). By contrast, glutathione peroxidase activity in erythrocytes from patients surpassed the control (6.13 0.39 and 4.63 0.45 U/h hemoglobin). The increase in malonic dialdehyde content in the plasma and glutathione peroxidase activity in erythrocytes and the decrease in glutathione peroxidase activity in the plasma were most pronounced in patients with severe cardiac insufficiency and pulmonary hypertension. Our results indicate that antioxidant preparations improve the prognosis in patients with primary pulmonary hypertension.

Aim: To evaluate carvedilol effect on clinical state, norepinephrine (NE) and epinephrine (E) plasma concentration and lymphocyte beta 2-adrenoreceptor dependent cAMP synthesis in patients with primary pulmonary hypertension (PPH)., Material and Methods: 14 patients with PPH were included in the study; 9 patients were treated by carvedilol; 5 patients were in the control group. The primary efficiency parameters were submaximal exercise measured by 60 min walk test, systolic pulmonary artery pressure (SPAP) measured by Doppler echocardiography, heart rate (HR) measured by 24-hour ECG-monitoring., Results: One month carvedilol treatment of PPH patients resulted in a significant HR reduction. There was a tendency to SPAP decrease, the 6-minute walk test results improved in IIINYHA patients., Conclusion: Carvedilol therapy improves clinical state and evoked lymphocyte beta 2-adrenoceptor resensitization in PPH patients.

Aim: To evaluate norepinephrine (NE) and epinephrine (E) plasma concentration and lymphocyte beta-2-adrenoceptor dependent cAMP synthesis in primary pulmonary hypertension (PPH) patients in comparison with healthy controls., Material and Methods: Seven volunteers and fifteen patients with PPH were included in the study. NE and E plasma levels were measured by high performance liquid chromatography. Basal and stimulated (isoproterenol and forskolin) adenylyl cyclase activity in lymphocytes was measured by cAMP production using an enzyme immunoassay (Biotrak, Amersham UK)., Results: There was a 110% (p = 0.001) NE level increase in PPH patients. In systolic pulmonary artery pressure (SPAP) > 95 mm Hg lymphocyte cAMP production associated with adenylyl cyclase catalytic subunit was decreased by 170% and 70% vs PPH patients with SPAP < 95 mm Hg and healthy controls, respectively (p < 0.05). A significant negative correlation between forskolin cAMP production by lymphocytes and SPAP level was observed in PPH patients (k = -0.810, p = 0.011 by Kendell; k = -0.893, p = 0.007 by Spirman). Heart failure progressing from I-II to III NYHA functional classes was accompanied by plasma NE enhance and lymphocyte beta-2-adrenoreceptor-activated cAMP production decrease., Conclusion: The data demonstrate sympathoadrenal system activation and lymphocyte beta-2-adrenoceptor desensitization in PPH patients.

Pulmonary artery pressure (PAP) was monitored for 24-48 hours in 10 and 8 patients with primary and secondary pulmonary hypertension, respectively. The data obtained were compared with results of prolonged PAP monitoring in 2 healthy volunteers. Variability of mean PAP was 7.43-/+3.1, 5.78-/+1.64, and 3.4-/+0.63 mm Hg, coefficient of variability - 10.39-/+3.68, 13.04-/+6.01 and 22.73-/+8.03% in patients with primary and secondary pulmonary hypertension and healthy subjects, respectively. After surgery in patients with secondary pulmonary hypertension coefficient of variability rose from 13.04-/+6.01 to 16.7-/+12.8%, while variability decreased from 5.78-/+1.64 to 4.3-/+1.65 mm Hg. Level of spontaneous fluctuations of PAP was the highest in healthy subjects (71.4%) and the lowest - in patients with primary pulmonary hypertension (34.9%). Thus PAP variability is a widespread phenomenon which should be taken into consideration during right heart catheterization and acute pharmacological tests.

Aim: A comparative analysis of the content of the soluble form of cell adhesion protein P-selectin in the blood plasma of patients with acute myocardial infarction (AMI), massive atherosclerosis (MA) and primary pulmonary hypertension (PPH), investigation of the relationship between plasma content of P-selectin and known markers of platelets and endothelial cells activation, preliminary assessment of the prognostic value of P-selectin determination., Materials and Methods: This study included 16 patients with AMI, 20 patients with MA, 21 patients with PPH and 18 healthy donors. The follow-up was 1-5 years. End-points in the group of patients with AMI were recurrent acute coronary syndrome and coronary artery by-pass operation, in the group with MA--thrombotic complications (acute coronary syndrome, ischemic stroke) and in the group with PPH--death. P-selectin was measured by ELISA and platelet factor 4 (PF4), thromboxane B2 (TXB2), endothelin-I and stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by means of commercial ELISA kits., Results: Mean level of P-selectin in blood plasma of patients with AMI (1 day) (361 +/- 18 ng/ml), MA (410 +/- 31 ng/ml) and PPH (627 +/- 83 ng/ml) was increased in comparison with the group of healthy donors (269 +/- 12 ng/ml) (everywhere p < 0.001). In AMI, P-selectin was increased on day 1 only, on days 2, 3 and 10-14 of the disease the level of P-selectin was significantly lower than on day 1 and did not differ from the control level in the group of donors. In patients with MA a significant correlation was detected between plasma content of P-selectin and platelet activation marker PF4 (r = 0.606, P = 0.007) and in patients with PPH between the content of P-selectin and another platelet activation marker TXB2 (r = 0.622, p = 0.013). However, no correlation was found in PPH patients between the content of P-selectin and markers of endothelial activation and/or damage (endothelin-1 and 6-keto-PGF1 alpha). Difference in the concentration of P-selectin in patients with or without end-points during the follow-up period was detected in patients with AMI (353 +/- 14 ng/ml and 451 +/- 24 ng/ml, p = 0.009) and PPH (477 +/- 58 ng/ml and 927 +/- 184 ng/ml, p = 0.017) but not with MA (426 +/- 37 ng/ml and 361 +/- 24 ng/ml, p = 0.295)., Conclusion: The level of P-selectin in plasma was increased in patients with acute thrombosis (AMI, 1 day) as well as in patients without clinical signs of thrombosis but with a massive injury of the vasculature (MA and PPH). The increase of P-selectin was, presumably, caused by its secretion from activated platelets since its concentration in plasma correlated with platelet concentration but not endothelial activation markers. Preliminary data indicate that blood plasma soluble P-selectin may be considered as a potential prognostic marker in AMI and PPH.

The respiratory section of lung biopsies from patients with primary pulmonary hypertension (PPH) was studied by electron transmission microscopy. The alterations found allow to suggest the presence of apoptotic degeneration of cells of the capillary endothelium and lung epithelium, this being confirmed also by an alveolar macrophages increase. The role of apoptosis in the PPH pathogenesis is discussed.

Aim: To investigate aspirin efficacy in patients with primary pulmonary hypertension (PPH) after a course of prostaglandin E-1 (PE) treatment., Materials and Methods: 12 PPH patients (mean age 35.7 +/- 2.5 years) having the disease for 6.7 +/- 1.1 years were assigned to a 6-month course of aspirin treatment in a dose 100 mg/day in combination with calcium antagonist isradipin. All the patients have previously undergone 21-day PE treatment (vasaprostan). Before and after the treatment, the patients were examined clinically and biochemically., Results: As shown by ECG, chest x-ray, bicycle exercise, aspirin used in combination with isradipin led to stabilization of the disease. Platelet aggregation also remained stable, thromboxan B2 and endothelin-1 levels went down. Low doses of aspirin allowed to avoid side effects typical for this drug., Conclusion: Use of aspirin in a dose 100 mg/day in combination with calcium antagonists to treat primary pulmonary hypertension is justified.

Aim: Assessment of RAAS and vasopressin in patients with primary pulmonary hypertension (PPH)., Materials and Methods: Activity of plasma renin (APR), angiotensin-converting enzyme (ACE), plasma levels of angiotensin II (AII) and vasopressin (VP), serum concentration of aldosteron (AS) were measured by radioimmunoassay and enzyme immunoassay in 21 PPH patients with circulatory failure (age 34.7 +/- 2.1 years), 11 patients with NYHA functional class II-III, 10 with class IV, and 10 control subjects (age 29.8 +/- 1.5 years)., Results: Compared to controls, 21 PPH patients had elevated RAAS parameters: APR up to 3.52 ng/ml/h (p < 0.05), activity of ACE up to 43.13 units, AII level up to 33.93 ng/ml (p < 0.01), AS up to 468.86 ng/ml (p < 0.01), VP up to 5.26 ng/ml (p < 0.001). Circulatory failure progression resulted in activation of all the RAAS components. This and VP activation was the greatest in PPH patients with ACE > 5 ng/ml/h. PPH patients with mean pressure in the pulmonary artery higher than 60 mm Hg demonstrated higher ARP, AS, VP, AII, ACE than those who had this pressure under 60 mm Hg., Conclusion: PPH patients display a noticeable activation of RAAS and VP. This activation seems to be secondary as the changes increase with elevation of the pressure in the pulmonary artery and aggravation of circulatory insufficiency. Plasma renin activity determines the degree of RAAS activation as a whole. The discovered activation of RAAS in PPH gives grounds for doubts in the validity of using ACE inhibitors in the treatment of PPH.

The aim of the study was elucidation of hemostatic effects of low-molecular heparin Flaxiparin in patients with primary pulmonary hypertension (PPH). 10 PPH patients (mean age 39.0 (+)- 3.2 years, mean history of the disease 5.1 (+)- 0.9 years) were treated up to 6 months. For the first month Flaxiparin was injected in therapeutic doses 15,000 AXa ICU, twice a day. The next 5 months prophylactic doses were administered twice a day (7,500 AXa ICU). D-dimer, fragment 1 + 2, complex thrombin-antithrombin, beta-thromboglobulin, protein C, antithrombin III, antigen of tissue plasminogen activator and inhibitor of tissue plasminogen activator of type I, activity of the latter were measured before the treatment, after the therapeutic and prophylactic courses, 6 months after the treatment. Initially, the patients had procoagulative hemostatic disorders. i.e. activation of blood coagulation; fibrinolytic system was also affected. In the course of Flaxiparin therapy blood coagulation and fibrinolysis improved significantly. However, the effect was not persistent after the drug discontinuation. Flaxiparin can be recommended for treatment of PPH.

Techniques for noninvasive observation of heart states play an important part in experimental and therapeutic cardiology. The objective of this work is to describe a new method for intelligible pictorial representation of data acquired by an orthogonal electrocardiographic lead system and demonstration of possibilities of this method in estimating the results of longterm treatment for a cardiac disease. The method used, dipole electrocardiotopography (DECARTO), provides a set of maps (decartograms) that depict in an explicit form the instantaneous, as well as integral electrophysiological properties of the heart during the excitation cycle. The observed group of patients contained 10 females and 2 males with primary pulmonary hypertension. It was found that in all but one cases tested, the features of the maps strongly correlated with the results of the other diagnostical methods and clinical findings. The trends to improvement (6 cases), stabilization (4 cases), or deterioration (1 case) of the heart state were clearly indicated. In one case, however, the interpretation of the decartograms was ambiguous. The advantage of the DECARTO technique lays in clearness of data representation for visual analysis and facilitation of electrophysiological and anatomical interpretation of the data. (Fig. 6, Ref. 2)

VCG data (McFee--Parungao system) were obtained from 12 patients with primary pulmonary hypertension (PPH). During 2 years, VCG investigations were repeated from 2 to 5 times. Various VCG-parameters were analyzed. Space and horizontal QRS areas, projection of integra QRS vector to axis y and the sum of Rx and Sx were diagnostically most significant. Their values proved abnormal at the beginning of survey. In the course of observation, states of the right heart chambers together with VCG-parameter dynamics were investigated in every patient. States of the right cardiac chambers improved in 4 patients. In all of them the parameter turned to normal values. In two patients, during the monitoring time monotonous increase of parameters was observed, with the state of the right heart chambers declining. In 6 patients, state of right heart chambers appeared relatively stable. In these patients, values of all the parameters were either stable or insignificantly changeable around some mean values. Thus, the dynamics of VCG-parameters makes it possible to estimate adequately the states of the right cardiac chambers in PPH patients. (Tab. 1, Fig. 4, Ref. 4)

To evaluate the condition of left and right ventricular functions in patients with primary pulmonary hypertension (PPH) 21 patients (13 females and 8 males, mean age 35.4 +/- 10.0) were examined. The patients were ill for 5.7 +/- 3.5 years. Ventricular filling was characterized basing on computer data of transmitral and transtricuspid diastolic flow obtained at doppler echocardiography. Right ventricular function proved impaired in all the examinees: early in the disease the speed of early filling (Ve) was inhibited, while late filling was enhanced (Va). At terminal stages of the disease Ve increased, but Va reduced. Left ventricular function was also involved in all the patients: low Ve with the disease progression became more and more evident.

Potentialities of magnetic resonance imaging (MRI) have been studied for evaluation of patients with pulmonary hypertension. For this purpose 54 patients with primary and secondary pulmonary hypertension have been studied using resistive and superconductive MRI systems. MRI proved useful for determination of the cause of pulmonary hypertension (primary, secondary), assessment of the right heart chambers. The cine-MRI enabled detection of tricuspid and pulmonary regurgitation, paradoxical movement of the interventricular septum, thrombi in the pulmonary artery. There were some correlations between MRI parameters and indexes of pulmonary hemodynamics. As a non-invasive imaging modality MRI has a great diagnostic value in characterization of the heart and great vessels in patients with pulmonary hypertension.

Spirometry and bicycle ergometry were performed before and 3 weeks, 6 months after lomir treatment (mean dose 10.62 +/- 2.59 mg/day) of 8 patients with primary pulmonary hypertension. It was found that 3 weeks of the treatment produced a significant increase in the maximum power working capacity and performance, in 6 months of the treatment there were positive trends in gas exchange: anaerobic threshold became higher and maximum oxygen consumption rose. Thus, lomir is recommended for management of primary pulmonary hypertension as it improves exercise tolerance and gas exchange measured by means of spirometry and bicycle ergometry useful both for evaluating functional condition of the patients and the disease advance as well as its response to the therapy conducted.

Cardiolipin antibodies (CAb) were measured in 14 patients with primary pulmonary hypertension (PPH). These included 9 females and 5 males (mean age 36.8 +/- 9.6 years) with duration of PPH 4.9 +/- 4.1 years. No rise in CAb IgG was noted, whereas CAb IgM arose to 13.0-42.5 MPI in 3 patients. 2 lethal outcomes were registered in the group of patients with normal CAb levels and 2 in the group with elevated CAb (20% against 66.7%, respectively). The deaths were caused by progressive circulatory failure and venous occlusion, pulmonary artery embolism, respectively. It is suggested that IgM CAb increase may indicate involvement of immune disorders in PPH onset and the same nature of the mechanisms underlying some PPH subtypes and autoimmune rheumatic affections.

To ascertain the role of invasive investigations in the diagnosis of primary pulmonary hypertension (PPH), 12 PPH patients underwent catheterization of the left and right heart compartments, contrast right and left ventriculography and oximetry. Compared to control values, the patients had high pressure in the pulmonary artery and right ventricle. Some of them exhibited elevated pressure in the right atrium. Pulmonary artery wedge pressure, left ventricular end-diastolic and systolic, diastolic pressure in the aorta did not differ significantly from those in the controls. Right and left ventriculography revealed an increase in the end-systolic and end-diastolic volumes of the right ventricle which diminished its stroke index and ejection fraction. The latter two were reduced in the left ventricle also. Because the procedure was well tolerated by the patients, it is recommended for PPH diagnosis and follow-up.

Morphological investigation of 12 cases of primary pulmonary hypertension (PPH) (4 males and 8 females, from 20 to 48 years old, duration of the disease from 1 to 10 years) is performed. Heart weight increase (from 390 to 640 g) and thickening of the right ventricle wall were observed. 3 groups were distinguished on the basis of histology: 1) plexigenic pulmonary arteriopathy (PPA)-2 cases, 2) recurrent pulmonary thromboembolism (RPT)-5 cases, 3) vein-occlusive disease (VOD-5 cases. The third group was divided into two subgroups: vascular-occlusive disease (VOD) with thrombotic lesions of arteries and veins and vein-occlusive disease proper (VOD-p) with thrombosis of pulmonary veins only. Morphometrically, thickening of arterial intima and media was found in PPA and RPT and in some cases of VOD-p. The thickening of the above layers in veins found in some cases of PPA and RPT was obviously secondary and indicated the development of mixed pre- and postcapillary pulmonary hypertension.

A physical and X-ray examination and echo-, electro- and phonocardiographies were performed in 29 patients with primary pulmonary hypertension. Their central hemodynamics was also conducted by introducing a Swan-Ganz flowing balloon catheter into the right cardiac cavities. With evolving chronic circulatory insufficiency, the patients showed profound hemodynamic changes both in the right (end-diastolic pressure in the right ventricle and atrium rose and ventricular stroke index dropped) and left (heart rate increased, cardiac and stroke indices decreased in the ventricle) ventricles. There were slight changes in peripheral hemodynamics. Pulmonary pressure became lower, but this fact cannot be considered to be positive as this led to significantly lower right ventricular stroke index that indicates the critical diminution in right ventricular performance, unlike cases successfully treated with peripheral vasodilators.

The authors relate the results of a clinical and post mortem examination of 12 patients who died for primary pulmonary hypertension (PPH). The clinical, x-ray, echocardiography and electrocardiography data were of the same type in all the patients. Macroscopic studies of the heart also demonstrated similar changes: the heart mass was increased because of hypertrophy of its right parts. At the same time the microscopic picture of small vessels of the lungs turned out fairly diverse. Based on these differences all the cases were divided into 3 groups: veno-occlusive disease, recurrent pulmonary thromboembolism, plexogenic pulmonary arteriopathy. However, certain differences were noted inside the groups either. It is therefore assumed that PPH is a collective notion, uniting different alterations in small pulmonary vessels, that lead to a considerable rise of pressure in the pulmonary artery.

The paper is concerned with 18 patients suffering from primary vascular pulmonary hypertension. Of these, 7 patients had the thromboembolic pattern of primary vascular pulmonary hypertension and 11 primary pulmonary hypertension. All the patients underwent comprehensive examinations including routine clinical examinations, x-raying of the chest organs, ECG, ultrasound cardiography, measurement of the pressure in the pulmonary artery by invasive and non-invasive methods. The patients were also subjected to radionuclide studies using radionuclide scintigraphy of the lungs by means of 99mTc microspheres and radionuclide phlebography. Analysis of the clinical picture and of the findings obtained with the majority of instrumental methods including radionuclide scintigraphy did not reveal any appreciable differences between the patients with the thromboembolic pattern of primary vascular pulmonary hypertension and those suffering from primary pulmonary hypertension. Radionuclide phlebography has demonstrated that the patients with the thromboembolic pattern showed the changes in the phlebogram significantly more often than those with primary pulmonary hypertension. It is advisable that radionuclide phlebography should be included into the schedule for examining patients with primary vascular pulmonary hypertension.