Cardiotoxic effect of bleomycin with a single administration in the experiment

The aim of the study was to evaluate the effect of a single injection of bleomycin on the heart Material and methods. The study was conducted in the Research Institute of Transport Medicine during 2016-2021. The experimental model of the cardiotoxic effect of the bleomycin was performed using the medication "Bleocin" manufactured by Nippon Kayaku Co., Ltd. (Japan). According to the task, the study was performed on 10 mature rats of both sexes of the Wistar line with a body weight of 237 ± 20 g. Rats were housed in standard vivarium conditions of Odessa National Medical University. Animals were divided into 2 groups: experimental group (n = 5) and control (n = 5). Bleomycin animals of the experimental group were obtained intraperitoneally at a dose of 0.5 IU / kg once. Withdrawal of animals from the experiment was performed on the 5th day of the experiment, followed by morphological and morphometric examination. Statistical processing of the obtained data was performed by methods of variance, correlation and regression analysis using Statistica 14.0 software (TIBCO, USA) Results. Single administration os bleomycin causes changes in macroscopic parameters (myocardial weight, visual changes) are minimal. The main changes at the microscopic level are represented by contractural degeneration with segmental and / or partial-lateral lysis, ie there is not total but partial myocardial damage. Conclusion. A single injection of bleomycin can cause inflammatory-dystrophic changes of the myocardium.

Genetic basis of anthracyclines cardiotoxicity: Literature review

The purpose of this review was to systematize data on molecular genetic markers of increased risk of cardiotoxic effects, as well as to search for risk and protective variants of candidate genes. Today, the therapy of malignant neoplasms is based on the use of anthracyclines – drugs of the cytostatic mechanism of action. Along with their effectiveness, these drugs can have a cardiotoxic effect on cardiomyocytes by increasing the amount of reactive oxygen species and disrupting mitochondrial biogenesis. Pathological disorders lead to an increased risk of myocardial dysfunction and a number of other cardiovascular pathologies in patients receiving chemotherapy using anthracyclines. The cardiotoxic effect of anthracyclines leads to cardiomyopathy, heart failure, myocardial infarction, and thrombosis. Early detection of cardiotoxic damage leads to reducing the negative effects of these drugs due to changes in chemotherapy tactics. It is known that the risk of cardiotoxic myocardial damage is genetically determined and controlled by more than 80 genes. In this review, the description of basic molecules such as ATP-binding cassette transporters and solute carrier family (SLC transporters), carbonyl reductase, molecules of antioxidant defense, xenobiotic and iron metabolism was performed. In addition, a special attention is paid to the study of epigenetic and post-translational regulation. The available data are characterized by some inconsistency that may be explained by the ethnic differences of the studied populations. Thus, a more detailed research of various ethnic groups, gene-gene interactions between potential candidate genes and epigenetic regulation is necessary. Thus, understanding the contribution of genetic polymorphism to the development of cardiotoxicity will help to assess the individual risks of cardiovascular pathology in patients with various types of cancer, as well as reduce the risk of myocardial damage by developing individual preventive measures and correcting chemotherapy.

Successful treatment of severe calcium channel blocker poisoning: a clinical case

The article describes the successful experience of treating a female patient with severe poisoning by a mixture of drugs with a predominant cardiotoxic effect. The number of drugs taken was many times higher than the potentially lethal dose. Hemodynamics has been supported by vasopressors and inotropic drugs for a long time, antidotes, sorbents, detoxification agents were used. Due to inadequate spontaneous ventilation, the patient was on artificial lung ventilation for 24 days. After 26 days in the intensive care unit, she was transferred to the therapeutic department in a stable state and without neurological deficit. We believe that this material will be useful for intensive care physicians when providing emergency care to patients in such situations.

Mortality among involuntary inpatients of psychiatric hospital

Background Mortality is often used as an indicator of public health efforts. Even if mortality in psychiatric hospitals decreased since the introduction of modern treatment, the death toll is still high. The authors have analyzed the forensic autopsy data and the medical documentation regarding 115 death cases from psychiatric hospitals in south-eastern Romania during the period of 2000–2020. Results The average annual mortality rate was 5.13‰, the necropsy data corroborated with those from the medical documentary material indicates acute myocardial infarction as the dominant cause, with 65 (56.5%) cases, followed by upper respiratory tract occlusion with 23 cases (20%) and pulmonary thromboembolism in 4 cases (12.2%). Furthermore, in 6 cases (5.2%) the cause of death was traumatic: 4 cases of cranio-cerebral trauma and 2 cases of hanging. Conclusions In the mortality structure of psychiatric patients, cardiac death predominated, being influenced by the cardiotoxic effect of medication administered for the specific pathology; hence, an early involvement of cardiologists in the follow-up of patients and the finding of treatment schemes with a reduced cardiotoxic effect are required.

Cumulative cardiotoxic effect of bleomycin in experiment

The aim of the study was to evaluate the cumulative toxic effect of bleomycin under experimental conditions Material and Methods. The study was conducted in the Research Institute of Transport Medicine during 2016-2021. The experimental model of the cardiotoxic effect of the bleomycin was performed using the medication "Bleocin" manufactured by Nippon Kayaku Co., Ltd. (Japan). According to the task, the study was performed on 10 mature rats of both sexes of the Wistar line with a body weight of 237 ± 20 g. Rats were housed in standard vivarium conditions of Odessa National Medical University. Animals were divided into 2 groups: experimental group (n = 5) and control (n = 5). Bleomycin animals of the experimental group were obtained intraperitoneally at a dose of 0.5 IU / kg on 1st and 8th days. Withdrawal of animals from the experiment was performed on the 5th, 14th and 28th day of the experiment, followed by morphological and morphometric examination. The material after weighing and morphometry was fixed with a neutral 10% formalin solution and poured into paraffin. Histological sections were stained with hematoxylin-eosin, MSB, Van Gizon. Performed light microscopy. After two weeks there was a decrease in myocardial weight by 7-10% from baseline, there were pronounced dystrophic changes in the myocardium. Repeated administration of bleomycin has a cumulative cardiotoxic effect leading to irreversible changes in the myocardium and endothelial dysfunction clinically manifested by heart attack, vascular pathology at significant cumulative doses of bleomycin. Morphofunctional changes of the right ventricle are prominent and considered to be pathognomic for bleomycin toxicity. Conclusions: 1. Bleomycin has a cumulative toxic effect on the myocardium of mammals 2. The severity of the cardiotoxic effect of bleomycin is proportional to the tissue concentration of the drug, which is proportional to the duration of exposure

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

Along with a pronounced antitumor effect, Doxorubicin causes systemic effects with damage to vital organs, including the heart. It prompts the search for ways to prevent the cardiotoxic effect of the drug, one of which could be its intravesical administration. The aim of the study was to develop a method of serial intravesical administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received intravesical chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysium). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During intravesical chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data partially indicate the development of dilated cardiomyopathy in experimental animals. However, these changes were less pronounced than the previously described changes that occur after systemic administration of the drug. Additional studies of the electrophysiological activity of the heart and biochemical markers will make it possible to fully assess the degree of cardiotoxicity of Doxorubicin after its intravesical administration. Thus, serial intravesical administration of Doxorubicin in moderate therapeutic doses according to the proposed method causes changes in the myocardium of experimental animals, which are partially similar to the changes in the heart of people receiving chemotherapy with this drug.

CURRENT VIEWS ON PREDICTORS AND BIOMARKERS OF EARLY DIAGNOSIS OF ANTHRACYCLINE-MEDIATED CARDIOTOXICITY IN PATIENTS WITH BREAST CANCER (REVIEW OF LITERATURE)

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.

Arrhythmogenic left ventricular cardiomyopathy

Arrhythmogenic ventricular cardiomyopathy (AVC) is a heritable heart muscle disorder characterized by fibrofatty infiltration of the myocardium. Intramyocardial fat deposition is considered arrhythmogenic and predisposes patients to life-threatening arrhythmias and sudden cardiac death. The classic subtype of AVC is characterized by fibrofatty replacement of the right ventricular myocardium (i.e. arrhythmogenic right ventricular cardiomyopathy). In advanced cases of arrhythmogenic right ventricular cardiomyopathy, the left ventricle may be involved as well. Predominantly left ventricular involvement by AVC is exceedingly rare and lack of specific diagnostic criteria as well as its potential cardiotoxic effect make its diagnosis challenging and of high importance.