Введение. Поиск новых неинвазивных маркеров прогнозирования развития антрациклин-опосредованной кардиотоксичности (КТ) является одной из самых важных задач при лечении пациентов со злокачественными новообразованиями молочной железы. Цель. Изучить уровень классических сердечных биомаркеров и металлопротеиназ (ММР-2, ММР-3) в плазме крови пациентов с первичным раком молочной железы (РМЖ), а также определить их взаимосвязь с показателями фракции выброса левого желудочка (ФВЛЖ), глобальной продольной деформации миокарда (Global Longitudinal Strain, GLS) и кумулятивной дозой доксорубицина. Материалы и методы. В исследование включено 100 пациентов с подтвержденным диагнозом РМЖ, проходивших лечение на базе учреждения здравоохранения «Гродненская университетская клиника» (Гродно, Беларусь). Результаты. У пациентов после окончания химиотерапии (ХТ) отмечается статистически значимое повышение медиан сTnI и сTnТ, NT-proBNP и ММР-3, а после разделения пациентов на подгруппы с наличием кардиотоксического эффекта (КТ+) и его отсутствием (КТ–) зафиксирован статистически незначимый рост и ММР-2. В подгруппе КТ+ установлена взаимосвязь между показателями GLS и ММР-2 (ρ Спирмена 0,472, р<0,05). В подгруппе с суммарной дозой доксорубицина 360 мг/м2 выявлена тенденция к более высокой частоте развития КТ-эффекта – 27,7%, по сравнению с подгруппой, получавшей суммарную дозу доксорубицина 240 мг/м2, – 18,3% соответственно. Полученные данные позволяют полагать, что в подгруппе КТ+ при суммарной дозе 240 мг/м2 увеличение уровня сердечных биомаркеров и ММР-3 на 30% и более, ММР-2 на 7% и более может выступать в качестве раннего маркера развития КТ-эффекта. В то же время единственным показателем, обладающим высоким потенциалом в качестве раннего маркера КТ-эффекта при суммарной дозе 360 мг/м2, является ММР-3 и его прирост после окончания химиотерапии на 30 и более процентов. Заключение. Полученные данные служат основанием полагать, что отмеченная незначительная динамика уровня cTnI, cTnT, NT-proBNP и металлопротеиназ (ММР-2 и ММР-3) в плазме крови обладает потенциалом раннего маркера КТ на этапе отсутствия изменений при ЭхоКГ непосредственно после окончания ХТ антрациклинами. Выявлена слабая корреляция (0,3–0,5) между уровнем исследуемых биохимических показателей крови (cTnI, cTnT, NT-proBNP, ММР-2 и ММР-3) и показателями GLS, ФВЛЖ. Это может быть объяснено тем, что регистрируемые методом ЭхоКГ и лабораторными методами изменения относятся к разным этапам развития КТ. Выявлена связь между суммарной дозой доксорубицина и динамикой уровней cTnI, cTnT, NT-proBNP, ММР-2 и ММР-3 в группах КТ+ и КТ–. Introduction. The search for new non-invasive markers for predicting the development of anthracycline-mediated cardiotoxicity (CT) is one of the most important tasks in the treatment of patients with malignant neoplasms of the breast. Purpose. To study classical cardiac biomarkers and metalloproteinases (MMP-2, MMP-3) plasma levels in patients with primary breast cancer (BC) and to determine their correlation with left ventricular ejection fraction (LVEF) values, global myocardial longitudinal strain (Global Longitudinal Strain, GLS) and doxorubicin cumulative dose. Materials and methods. The study included 100 patients with confirmed diagnosis of breast cancer who underwent treatment at the health care institution "Grodno University Clinic" (Grodno, Belarus). Results. In patients after chemotherapy (CT) completion, a statistically significant increase in cTnI and cTnT, NT-proBNP and MMP-3 medians was observed; and after patients’ distribution into subgroups with cardiotoxic effect (CT+) or without it (CT–), also a statistically insignificant increase in MMP-2 was registered. In CT+ subgroup, a correlation was established between GLS and MMP-2 indicators (Spearman’s ρ 0.472, p<0.05). In CT– subgroup with the total doxorubicin dose of 360 mg/m2 a trend towards a higher incidence of CT effect was revealed in 27.7%, compared to the subgroup receiving the total doxorubicin dose of 240 mg/m2 with 18.3%, respectively. The obtained data allow suggesting that in CT+ subgroup at the total dose of 240 mg/m2 the increase in cardiac biomarkers and MMP-3 levels by 30% or more, MMP-2 by 7% or more may be considered as an early marker of CT effect. At the same time, the only indicator with high potential as an early marker of CT effect at the total dose of 360 mg/m2 is MMP-3 and its increase after chemotherapy completion by 30% or more. Conclusion. The data obtained provide grounds for suggesting that the observed slight increase in cTnI, cTnT, NT-proBNP and metalloproteinases (MMP-2 and MMP-3) plasma level possesses the potential of an early CT marker at the stage of no changes in echocardiography immediately after chemotherapy with anthracyclines. A weak correlation (0.3–0.5) was revealed between the studied blood biochemical parameters (cTnI, cTnT, NT-proBNP, MMP-2 and MMP-3) levels and GLS and LVEF indicators. This can be explained by the fact that the changes registered by echocardiography and laboratory methods refer to different CT stages. A correlation between the total doxorubicin dose and cTnI, cTnT, NT-proBNP, MMP-2 and MMP-3 levels changes in CT+ and CT– groups was revealed.

Aim. To study the association of rs2232228 (HAS3 gene), rs2229774 (RARG gene), rs1056892 (CBR3 gene), rs1786814 (CELF4 gene), rs1695 (GSTP1 gene), rs8187710 (ABCC2 gene), rs7853758 (SLC28A3 gene), rs243865 (MMP­2 gene), rs243866 (MMP­2 gene), rs35068180 (MMP­3 gene), rs522616 (MMP­3 gene), rs679620 (MMP­3 gene), rs17576 (MMP­9 gene), rs3918242 (MMP­9 gene) with the probability of early doxorubicin cardiotoxicity signs in patients with breast cancer of moderate and low HFA-ICOS risk groups.Material and methods. The study included 100 patients (women, over 18 years old) diagnosed with breast cancer who received chemotherapy using doxorubicin.To identify early cardiotoxicity signs, echocardiography was performed before, immediately after and 12 months after the end of chemotherapy. The status of polymorphic variants of the studied genes was determined by real-time polymerase chain reaction.Results. Based on the decrease in global longitudinal myocardial strain (>12%) immediately after and 12 months after the end of chemotherapy, the patients were divided into two following groups: A — early signs of myocardial dysfunction can be diagnosed after the end of chemotherapy (19%); B — early signs of myocardial dysfunction are detected for the first time only 12 months after the chemotherapy end (17%). In patients from category A, a number of allelic variants and genotypes with potential as independent factors for predicting the early signs of myocardial dysfunction were identified, with an emphasis on targets involved in metabolism and detoxification of doxorubicin and its derivatives. In category B, the greatest differences in the frequencies of allelic variants and genotypes were found among target genes encoding matrix metalloproteinases involved in the processes of response to the intensification of oxidative stress caused by doxorubicin and its derivatives.Conclusion. In total, patients in the low- and moderate-risk groups can be divided into at least 2 categories based on molecular genetic testing. For these categories, the development of early signs of doxorubicin-related myocardial dysfunction before the start of chemotherapy can be predicted.

Цель. Изучить изменения электрокардиографических показателей миокарда у пациентов с верифицированным раком молочной железы (РМЖ) после окончания химиотерапии (ХТ) доксорубицином. Материал и методы. В исследование включены 100 пациентов с подтвержденным диагнозом – РМЖ, проходивших лечение на базе учреждения здравоохранения «Гродненская университетская клиника» (Гродно, Беларусь). Участникам до и после ХТ измерили ряд электрокардиографических показателей миокарда методом электрокардиографии и 24-часового холтеровского мониторирования. На основании данных ЭхоКГ и выбранного порогового значения относительного снижения GLS (более 12%) обследуемые были разделены на подгруппы с наличием кардиотоксичности – КТ+ (n=19) и без таковой – КТ- (n=81). Результаты. Выявлено увеличение электрокардиографических параметров деполяризации и реполяризации (P, P-Q, QRSс, J-Tc, Tpic-Tendс, Q-Tc, Q-Tdc – р<0,001; р<0,001; р=0,005; р=0,023; р=0,009; р<0,001; р=0,006, соответственно), количества наджелудочковых экстрасистол (р<0,001) в общей группе до/после ХТ. Показатели интервала J-Tc, Q-Tc (продолжительнее в подгруппе КТ- по сравнению с подгруппой КТ+: р=0,033 и р=0,037, соответственно), количество и общее время эпизодов синусовой тахикардии (р=0,011 и р=0,010, соответственно) после ХТ статистически значимо различались в подгруппах по кардиотоксичности ХТ. Выводы. При проведении ХТ доксорубицином наблюдалось увеличение продолжительности интервалов J-Tc, Q-Tc, увеличилось количество и время эпизодов синусовой тахикардии. Оценка динамики данных показателей на этапах до/после ХТ может предоставить дополнительную информацию о состоянии миокарда еще до выявления функциональных нарушений методом эхокардиографии.

Aim. To evaluate the relationship of polymorphic variants rs2232228 of the HAS3 gene, rs8187710 of the ABCC2 gene, rs35068180 of the MMP-3 gene with cardiotoxicity after the end of adjuvant chemotherapy in patients with breast cancer.Material and methods. The study included 100 patients (women, mean age 52,5±9,4 years) diagnosed with breast cancer who received anthracycline antibiotics (doxorubicin, total dose 240 mg/m2 or 360 mg/m2). Echocardiography was performed before and after the end of chemotherapy. Polymorphic status of selected targets was determined using the real-time polymerase chain reaction.Results. After the end of chemotherapy, based on the changes of left ventricular ejection fraction and global longitudinal strain, cardiotoxicity (CT) was detected in 20 patients. There were following significant differences between subgroups: rs8187710 of the ABCC2 gene — not identified; rs2232228 of the HAS3 gene — genotype AA, odds ratio (OR) 3,37 (95% confidence interval (CI) 1,14; 9,97) and allelic variant A, OR 2,17 (95% CI 0,98; 4,80) are significantly more common (p<0,05) in the cardiotoxicity+ subgroup; rs35068180 of the MMP-3 gene — genotype 6A/6A, OR 2,53 (95% CI 0,93; 6,88) and allelic variant 6A, OR 2,19 (95% CI 1,08; 4,44) are significantly more often (p<0,05) in the cardiotoxicity+ subgroup.Conclusion. Genotype 6A/6A, allelic variant 6A rs35068180 of the MMP-3 gene, genotype AA and allelic variant A rs2232228 of the HAS3 gene can be considered as predictors of early cardiotoxicity after the end of chemotherapy in patients with breast cancer receiving doxorubicin.

Сreating new methods of surgical treatment of diseases is always of great interest to the anatomy of the organs affected. The rapid development of cardiac surgery causes more attentively to the questions about the structure of the heart and its structures. Objective: study the structural features of intraventricular cardiac structures and their correlation relationship. Subjects: 115 preparations of the human heart. Methods: dissection, morphometry, statistical analysis. Results: examined variable anatomy of elements cardiac valvular apparatus and studied their correlation relationship. Conclusions: The findings significantly deepen and complement the picture of the human heart structure and will contribute to the study of the diagnosis, treatment and prevention of heart disease.

Background. One of the most actual problems of applied morphology is the problem of demonstrativeness. In the educational process it is important to demonstrate the organs taken from the human body with all features of their structure preserved. The basic method of normal anatomy is a dissection of cadaveric material. It gives anatomical preparations demonstrating the structure of the human body. But classical dissection has certain difficulties: the complexity of layer-by-layer tissue separation and extraction of important anatomical structures. Currently for the manufacture of anatomical preparations a number of other methods are used: method of corrosion and polymeric embalming. However these techniques are time consuming, expensive, and also can cause damage to the structures of the heart during their extraction out of adipose tissue. Objective. To create a new method for the dissection of the human heart, allowing to reduce the time and to improve the quality of the preparations. Methods. We have prepared two solutions with different freezing temperature. Tissue which needed to be preserved (myocardium) was impregnated with solution №1. Tissue that need to be deleted (adipose tissue), impregnated with solution №2. After freezing the heart myocardium frizzes, but unfrozen adipose tissue could be easily separated. We examined 30 human hearts: 15 preparations by the classical dissection, 15 preparations with the help of cryodissection. Results. Preparation of hearts by the classical method took about 180 minutes, with the help of cryodissection – 30 minutes. Visualization of the coronary arteries and their branches after our method is better, myocardium is smooth, also preserve the natural color of the drug. Additionally, there is no contact of the researcher with harmful conservatives (for example formaldehyde). Conclusion. We have developed a method for dissection of cadaveric material, which improves the quality of anatomical preparations and reduces the time of their creation.