Cardioprotective Strategies for Doxorubicin-induced Cardiotoxicity: Present and Future

The improvement of drugs and protocols of chemotherapeutic treatment has led to improved outcomes and survival in patients with cancer. But along with this, at first glance a positive point, there was another interdisciplinary problem, which is the need for early detection and treatment of developing cardiotoxicity when taking chemotherapy drugs. The study of cardioprotective strategies has recently become increasingly relevant, due to the fact that many patients who have successfully undergone treatment for cancer have a high risk of developing or are at high risk of death from cardiovascular diseases. One of the main drugs for the treatment of a number of oncological diseases is an anthracycline – type antibiotic-doxorubicin. This review briefly examines the risk factors and pathophysiological mechanisms underlying anthracycline cardiotoxicity. The current possibilities of cardioprotection of anthracycline cardiotoxicity are considered in detail, and some promising targets and drugs for improving cardioprotective strategies are discussed

Statins and highly sensitive cardiac troponins: cardiotoxicity or cross-reactivity?

To date, hypolipidemic drugs of the statin group are among the most popular therapeutic agents used for the prevention and treatment of the most common worldwide atherosclerotic cardiovascular diseases (CVD). Therefore, considerable attention of researchers is focused on statins to study the additional effects of these drugs, which is accompanied by the discovery of new mechanisms of action and properties that should be taken into account to optimize the tactics of managing patients with CVD. In addition to the key lipid-lowering effect of statins associated with the inhibition of the ratelimiting enzyme (3-hydroxy-3-methylglutaryl-coenzyme A reductase), researchers report a variety of other properties of these drugs. Important circumstances contributing to the disclosure of new effects of statins are: improvement of research methods, and first of all, their sensitivity and specificity; the discovery of new molecules and molecular pathways that may be affected by statins. In general, the currently established numerous non-lipid effects of statin drugs can be divided into two groups: favorable and side effects, which must be taken into account when managing patients with CVD and comorbid diseases. Thanks to recent studies using modern clinical diagnostic cardiomarkers (highly sensitive cardiac troponins (CT)), molecular genetic and morphological methods, potential cardiotoxic properties of statin group drugs have been identified. Of particular concern are the data on a statininduced increase in the concentration of highly sensitive CT, which are a key and generally recognized criterion for myocardial damage. In this article we discuss possible mechanisms of increasing the concentration of CT and cardiotoxic effects when using statins

МикроРНК: роль в патофизиологии фибрилляции предсердий и возможности использования в качестве биомаркера

The aim of the study was to analyze medical literature on the role of microRNA in the pathophysiology of atrial fibrillation and the possibilities of using microRNAs as biomarkers.The analysis of modern medical literature was carried out using the PubMed – NCBI database.Atrial fibrillation (AF) is a common and serious cardiovascular disease. The pathophysiological mechanisms underlying the development of atrial fibrillation are not entirely clear. In addition, there are no optimal biomarkers for early detection and assessment of the prognosis for patients with atrial fibrillation. Recently, the attention of researchers has been directed to the molecules of microRNA. There is a lot of evidence that they are involved in the pathogenesis of neurological, oncological, and cardiovascular diseases. This review examines the role of microRNAs in the pathophysiology of atrial fibrillation. The possibility of using microRNA as a biomarker for the diagnosis and prediction of atrial fibrillation is also discussed.MicroRNAs play a crucial role in the pathophysiology of atrial fibrillation, regulating the mechanisms of atrial remodeling, such as electrical remodeling, structural remodeling, remodeling of the autonomic nervous system, and impaired regulation of calcium levels. The stability of microRNAs and the possibility to study them in various biological fluids and tissues, including blood, make these molecules a promising diagnostic biomarker for various cardiovascular diseases. The presented data clearly indicate that AF is associated with changes in the expression level of various microRNAs, which can be quantified using a polymerase chain reaction. Further research is required to assess the role of microRNAs as biomarkers for atrial fibrillation, in particular to establish precise reference limits.Проведен анализ современной медицинской литературы по базе данных PubMed – NCBI. Фибрилляция предсердий является широко распространенным и серьезным сердечно-сосудистым заболеванием. Патофизиологические механизмы, лежащие в основе развития фибрилляции предсердий, не совсем ясны. Кроме того, отсутствуют оптимальные биомаркеры для раннего выявления и оценки прогноза пациентов с фибрилляцией предсердий.В последнее время внимание исследователей привлекли молекулы микрорибонуклеиновой кислоты (микроРНК). Накоплено немало данных, согласно которым они участвует в патогенезе неврологических, онкологических и сердечно-сосудистых заболеваний. Рассмотрена роль микроРНК в патофизиологии фибрилляции предсердий. Также обсуждается возможность использования микроРНК в качестве биомаркеров для диагностики и прогнозирования фибрилляции предсердий

Comboridity of chronic obstructive pulmonary disease and cardiovascular diseases: general factors, pathophysiological mechanisms and clinical significance

Currently, the comorbidity (combination) of chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) is an important problem for the health care. This is due to the high prevalence and continuing growth of these pathologies. CVD and COPD have common risk factors and mechanisms underlying their development and progression: smoking, inflammation, sedentary lifestyle, aging, oxidative stress, air pollution, and hypoxia. In this review, we summarize the current knowledge related to the prevalence and frequency of cardiovascular diseases in people with COPD and the mechanisms that underly their coexistence. The implications for clinical practice, in particular the main problems of diagnosis and treatment of COPD/CVD comorbidity, are also discussed

Аритмогенные эффекты доксорубицина

The article discusses the adverse arrhythmogenic effects of an antitumor drug – doxorubicin.Doxorubicin has a significant effect on the action potentials and ion currents of cardiomyocytes, the dynamics of intracellular calcium concentration.Oncological diseases are the leading causes of death and disability of the population, causing extremely high socio-economic damage. Among the many currently available drugs for the treatment of cancer, an important place is taken by the anthracycline antibiotic – doxorubicin. However, adverse concomitant effects on several organs and systems of the human body, in particular on the cardiovascular system, do not allow the full use of the high potential of doxorubicin`s antitumor effectiveness. Cardiotoxicity of doxorubicin is manifested in the form of electrocardiographic abnormalities and arrhythmias, degenerative cardiomyopathy and chronic heart failure. The authors consider the following arrhythmogenic effects of doxorubicin: the mechanisms of influence of doxorubicin on electrocardiographic parameters, the action potential of cardiomyocytes, cardiac ion currents and the dynamics of intracellular calcium concentration. The study and assessment of specific pathophysiological mechanisms of arrhythmogenic effects of doxorubicin is necessary for the development and justified use of cardioprotective measures.В статье обсуждаются неблагоприятные аритмогенные эффекты противоопухолевого препарата – доксорубицина. Доксорубицин оказывает значимое влияние на потенциал действия и ионные токи кардиомиоцитов, динамику внутриклеточной концентрации кальция.Онкологические заболевания – одна из ведущих причин смертности и инвалидизации населения. Среди множества доступных на сегодняшний день методов лечения онкопатологий важное место занимает антибиотик антрациклинового ряда – доксорубицин. Однако неблагоприятное сопутствующее воздействие на организм человека, в частности сердечно-сосудистую систему, не позволяет в полной мере использовать противоопухолевые свойства доксорубицина. Кардиотоксичность доксорубицина проявляется в виде электрокардиографических нарушений и аритмий, дегенеративной кардиомиопатии, хронической сердечной недостаточности. В обзоре рассмотрены аритмогенные эффекты доксорубицина: влияние на электрокардиографические показатели, потенциал действия кардиомиоцитов, сердечные ионные токи, динамику внутриклеточной концентрации кальция. Изучение и установление конкретных патофизиологических механизмов аритмогенного действия доксорубицина необходимы для разработки и обоснованного применения кардиопротекторных мероприятий

Experimental models of pulmonary embolism

Pulmonary embolism (PE) ranks third in the structure of acute cardiovascular diseases. Every year there is a rapid increase in morbidity and mortality from PE. Laboratory biomarkers for PE diagnosis do not have the necessary specificity, and therefore are ineffective. PE requires timely active treatment, in particular for the prevention of serious complications. In this regard, further research is needed to study and search for novel promising biomarkers for the early detection of PE, pathophysiological mechanisms and targets for therapeutic effects. To a large extent, novel data on the pathophysiology of cardiovascular diseases, including PE, scientists receive from experimental studies using animal models. In this review, we summarize the main existing experimental models of PE, describe the principles and methods for modeling this disease. There are following models of PE: intravenous thrombin infusion, adenosine diphosphate-induced PE, PE induction by thromboplastin, recombinant human tissue factor or high molecular weight polyphosphates, collagen/adrenaline-induced PE, ex vivo thrombus intravenous administration, surgical model. This publication also presents our own experience in creating an artificial model of PE in animals using an intravenous thrombus. In our model, confirmation of PE was obtained during pathological examination and an increase in the level of following biomarkers: troponin, N-terminal pro-brain natriuretic peptide, and D-dimer. In this pilot study, a PE model was created to study the pathogenesis and novel treatment options for this disease. To confirm the effectiveness of the model, future studies are required

Особенности метаболизма сердечных тропонинов (обзор литературы)

The review summarizes all recent data on the metabolism of cardiac troponin isoforms. The main mechanisms of troponin release from intact myocardium are described. These mechanisms ensure its baseline levels (less than the 99th percentile) in all healthy individuals. There are various fragments of troponin that circulate in the blood flow as a heterogeneous pool. Their circulation is related to various intracellular and extracellular proteases. In-depth understanding ofthese mechanisms is required to improve the diagnostic process. The article provides new insights into the evaluation of cardiac troponins in other human biological fluids: pericardial, cerebrospinal, amniotic, urine, and oral fluid. The measurements of saliva and urine levels of troponins seem to be promising alternative for non-invasive diagnosis. Recent circadian patterns of high-sensitive cardiac troponin T alterations are reported. These patterns should be taken into account while practicing fast diagnostic algorithms. В обзоре литературы суммированы сведения об особенностях метаболизма сердечных изоформ тропонинов. Описаны основные механизмы высвобождения тропонинов из интактного миокарда, которые обеспечивают базовые концентрации (менее 99-го перцентиля) у всех здоровых индивидуумов. Тропонины циркулируют в кровотоке в виде гетерогенного пула, в основном в виде фрагментов, что обеспечивается различными внутри- и внеклеточными протеазами. Уточнение данных механизмов необходимо для улучшения диагностики. В статье также сообщается о возможности исследования сердечных тропонинов в других биологических жидкостях человека: перикардиальной, спинномозговой, амниотической, моче и ротовой жидкости. Определение тропонинов в слюне и моче является перспективным направлением неинвазивной диагностики. Сообщается о недавно обнаруженных циркадных особенностях колебаний концентрации кардиального высокочувствительного тропонина Т, которые, вероятно, должны учитываться в современных быстрых алгоритмах диагностики инфаркта миокарда

Increased natriuretic peptides not associated with heart failure

Natriuretic peptides (NPs) are key diagnostic and prognostic biomarkers for patients with heart failure (HF). The main mechanism for increasing serum NP levels, which is characteristic of heart failure, is secretion in response to myocardial wall distention. At the same time, according to Russian and foreign literature, an increase in NPs is reported in a number of many other conditions that are not associated with HF. The study of these causes and mechanisms is necessary to improve the differential diagnosis of HF.This article discusses the mechanisms of increasing NPs and their diagnostic value in heart failure, as well as a number of other conditions, such as acute coronary syndrome and coronary artery disease, atrial fibrillation, exercise, kidney failure, taking cardiotoxic drugs (chemotherapy) and sacubitril/valsartan. The article also provides data on identifying NPs in non-invasively obtained biological fluids (urine and oral fluid)

Circadian rhythms of cardiac troponins: mechanisms and clinical significance

Modern laboratory methods for determining biomarkers of cardiovascular diseases are highly sensitive and can detect almost single molecules in human biological fluids, significantly speeding up and improving the diagnosis of cardiovascular diseases. However, in this case, there is a decrease in specificity and it is necessary to take into account a number of additional factors that may affect the result of the study. Recent studies have shown that circadian rhythms (CR) are among these factors. This review article is devoted to the discussion of recently discovered CR of cardiac troponins (CT). A number of articles reported that, both in healthy people and in patients with a number of chronic diseases, CT concentrations change during the day. Given that modern algorithms for diagnosing myocardial infarction (MI) are based on serial studies (0-1 h and 0-3 h) of blood serum, and the values of CT in the blood serum for the diagnosis of myocardial infarction (MI) for this period of time are only a few ng/l, the CT CR can to some extent affect the accuracy of MI diagnosis. Thus, natural physiological changes in the concentration of CT during the day can be mistakenly interpreted as diagnostically significant deviations and lead to an erroneous interpretation of laboratory test results

Diagnostic significance of complete blood count in cardiovascular patients; Samara State Medical University

This article discusses the relationship between parameters of complete blood count (CBC) and cardiovascular diseases (CVD). The main advantages of CBC over other methods of CVD diagnostics are low cost and wide availability. At the same time, the low specificity of CBC is an important disadvantage, limiting its diagnostic value.After analyzing the results of numerous clinical studies, we concluded that the most important CBC are red cell distribution width, mean platelet volume, total leukocyte count, neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte to high-density lipoprotein ratio. We discuss the diagnostic value of each of the above indicators in CVD. Careful attention to these parameters by clinicians can, to a certain extent, improve the therapeutic and diagnostic process in patients with CVD