Understanding mechanisms of chemotherapy cardiotoxicity is an important problem due to the lack of clear understanding of its occurrence. Development of endothelial dysfunction is considered to be one of possible ways in implementation of these side effects. The analysis of endothelin-1 and e-selectin levels in 26  patients with lymphoproliferative diseases before and after the completion of the treatment program was been performed. The results of the study showed normal values of E-selectin level and increased level of endothelin-1 in the whole group of patients before treatment. After completion of chemotherapy program, in the whole group, there was a decrease of these two markers. However, values of level of endothelin-1 with vasoconstrictor effect remained high even after the end of therapy. It is imp ortant that at detailed analysis the dynamics of investigated markers in patients of older age group (median age 64 years) was associated with worsening of endothelial dysfunction.

Aim      To evaluate the dynamics of indexes of oxidative stress and markers of myocardial injury and dysfunction in patients with aggressive type lymphomas during the antitumor therapy.Material and methods  This study included 75 patients with lymphoproliferative diseases of aggressive type. The main group consisted of 53 patients who received one course of antitumor therapy during the study. The comparison group consisted of 22 patients who have not received any specific treatment so far. Troponin I (TnI), high-sensitivity troponin (hsTnI), heart-type fatty acid binding protein (Н-FAВР), N-terminal pro-brain natriuretic peptide (NT-prоBNP), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in patients of both groups at baseline, and in the main group, they were measured at 4 hours after administration of antitumor agents and on completion of the course. Functional status of the cardiovascular system was evaluated by electrocardiography in all patients at baseline and after the course of antitumor treatment and by echocardiography.Results The chemotherapy was associated with increased levels of NT-prоBNP, SOD, and MPO (30.670±15.367 vs. 52.309±25.718 pmo l/l; 1.61±0.135 vs. 1.74±0.193 U/ml; and 507.54±91.51 vs. 742.3±49.01 ng/ml, respectively). The study results indicated activation of oxidative stress on the background of the administered antitumor therapy, progressive myocardial dysfunction, and increased frequency of arrhythmic episodes.Conclusion      The study results allowed identifying NT-prоBNP, MPO, and SOD as important indexes for determining a patient group at high risk of cardiotoxicity during the antitumor treatment.

Aim      To evaluate in a pilot study time-related changes in the clinical state, indexes of the acute phase of inflammation, parameters of blood lipid profile, intracardiac hemodynamics, and disorders of cardiac rhythm/conduction in patients who are not candidates for autologous hemopoietic stem cell transplantation, during three bortezomib-containing chemotherapy courses (VCD) followed by a correlation analysis.Material and methods  This pilot study included 20 patients diagnosed with myeloma, who were not candidates for autologous hemopoietic stem cell transplantation and who had undergone three courses of VCD chemotherapy (bortezomib, cyclophosphamide and dexamethasone). In addition to mandatory examinations, measurement of blood lipid profile, transthoracic echocardiography (EchoCG), and 24-h Holter electrocardiogram (ECG) monitoring were performed for all participants before and after a specific therapy.Results Following three bortezomib-containing courses of chemotherapy, patients of the study group had significant increases in the neutrophil-lymphocyte ratio (NLR) (1.6±0.2 and 2.5±0.4; р=0.05), cholesterol concentration (4.8±1.1 and 5.6±1.1 mmol/l, р=0.05), and low-density lipoprotein concentration (2.8±0.4 and 3.5±0.8 mmol/l, р=0.02). In comparing the changes in parameters of intracardiac hemodynamics, criteria for genuine cardiotoxicity were not met, however, a tendency to emergence/progression of myocardial diastolic dysfunction was noted. No clinically significant disorders of cardiac rhythm/conduction were observed. The correlation analysis performed prior to the start of chemotherapy, showed significant strong, direct correlations between the C-protein concentration and left atrial (LA) volume (r=0.793; p=0.006), right atrial (RA) volume (r=0.857; p=0.002), left ventricular (LV) end-diastolic dimension (EDD) (r=0.589; p=0.043), and LV end-diastolic volume (EDV) (r=0.726; p=0.017). Following the specific treatment, significant, medium-power and strong correlations were found between NLR and EDV (r= –0.673; p=0.033), NLR and end systolic volume (ESV) (r= –0.710; p=0.021), respectively. Significant direct correlations were found between the bortezomib dose per one injection and the serum concentration of triglycerides following the treatment (r=0.78; p=0.05); a single bortezomib dose and parameters of intracardiac hemodynamics: LA (r=0.71; p=0.026), RA (r=0.74; p=0.014), EDD (r=0.837; p=0.003), EDV (r=0.749; p=0.013), ESV (r=0.553; p=0.049).Conclusion      For the first time, a comprehensive evaluation was performed in patients with multiple myeloma, including the dynamics of blood lipid profile, intracardiac hemodynamics and disorders of cardiac rhythm/conduction during bortezomib-containing antitumor therapy, with an analysis of correlation with levels of acute inflammation phase markers. Although in the observation window for genuine cardiotoxicity, clinically significant cardiovascular complications were not detected, the found correlations may evidence a potential role of systemic inflammation activity in myocardial remodeling in the studied patient cohort.

Inhibitory coagulopathy is a rare variant of hemorrhagic syndrome. Acquired hemophilia A is caused by the formation of inhibitors (antibodies) to Factor VIII of the blood coagulation system leading to impaired activation of the key stage of blood clotting (factor X) and development of hemorrhagic syndrome of different severity. Acquired hemophilia A is a rare disease with an incidence of 1.38-1.48 per 1 million population per year. We report a case off severe idiopathic acquired hemophilia A in a 53 year-old woman manifest as skin hemorrhages, subcutaneous and intramuscular hematomas. Hemostatic therapy described in the article resulted in the elimination of hemorrhagic syndrome and complete remission. This case represents a rare disease the knowledge of which can be useful for preventing the development of debilitating complications, and sometimes saving the patient’s life.

Оценка роли показателей окислительного стресса и ранних маркеров повреждения и дисфункции миокарда у больных лимфопролиферативными заболеваниями Ключевые слова: окислительный стресс, кардиотоксичность, лимфома, хемилюминесценция лейкоцитов, малоновый диальдегид.