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1.
J Muscle Res Cell Motil ; 44(4): 299-309, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37249732

RESUMO

Pulmonary arterial hypertension (PAH) leads to changes in the pump function of the heart and causes right-sided myocardial hypertrophy and heart failure. This study was the first to compare the contractile characteristics of the multicellular myocardial preparations of the right atrium (RA) and right ventricle (RV) of male rats from the control group (CON) and the group with monocrotaline (MCT)-induced hypertrophy at the molecular and multicellular levels. In both RA and RV in MCT-treated rats, the fraction of motile filaments and the maximum sliding velocity of actin and reconstituted thin filaments over myosin decreased, and the ratio of α-/ß-myosin heavy chains (MHC) shifted towards ß-MHC. In the RA strips and RV trabeculae, the maximum shortening velocity, the extent of muscle shortening, the amplitude of isometric stress, the amount of work decreased. PAH leads to a greater drop in right atrial contractility than that of the ventricle.


Assuntos
Fibrilação Atrial , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Ratos , Masculino , Animais , Hipertensão Arterial Pulmonar/complicações , Ventrículos do Coração , Monocrotalina/toxicidade , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/complicações , Fibrilação Atrial/complicações , Hipertrofia Ventricular Direita/induzido quimicamente , Átrios do Coração , Modelos Animais de Doenças
2.
Int J Mol Sci ; 23(8)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35457235

RESUMO

Exposure to lead is associated with an increased risk of cardiovascular diseases. Outbred white male rats were injected with lead acetate intraperitoneally three times a week and/or were forced to run at a speed of 25 m/min for 10 min 5 days a week. We performed noninvasive recording of arterial pressure, electrocardiogram and breathing parameters, and assessed some biochemical characteristics. Electrophoresis in polyacrylamide gel was used to determine the ratio of myosin heavy chains. An in vitro motility assay was employed to measure the sliding velocity of regulated thin filaments on myosin. Isolated multicellular preparations of the right ventricle myocardium were used to study contractility in isometric and physiological modes of contraction. Exercise under lead intoxication normalized the level of calcium and activity of the angiotensin-converting enzyme in the blood serum, normalized the isoelectric line voltage and T-wave amplitude on the electrocardiogram, increased the level of creatine kinase-MB and reduced the inspiratory rate. Additionally, the maximum sliding velocity and the myosin heavy chain ratio were partly normalized. The effect of exercise under lead intoxication on myocardial contractility was found to be variable. In toto, muscular loading was found to attenuate the effects of lead intoxication, as judged by the indicators of the cardiovascular system.


Assuntos
Chumbo , Miocárdio , Animais , Cardiotoxicidade , Chumbo/toxicidade , Masculino , Contração Miocárdica , Cadeias Pesadas de Miosina , Miosinas , Ratos
3.
Int J Mol Sci ; 22(7)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801669

RESUMO

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO-NP and PbO-NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling ß-MHC. The type of CdO-NP + PbO-NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb-NP and CdO-NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.


Assuntos
Compostos de Cádmio/toxicidade , Coração/efeitos dos fármacos , Chumbo/toxicidade , Nanopartículas Metálicas/toxicidade , Nanotecnologia/métodos , Óxidos/toxicidade , Músculos Papilares/efeitos dos fármacos , Animais , Cardiotoxicidade , Fragmentação do DNA , Injeções Intraperitoneais , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Cadeias Pesadas de Miosina , Miosinas/química , Isoformas de Proteínas , Ratos , Testes de Toxicidade Subcrônica
4.
Cardiovasc Toxicol ; 24(1): 49-61, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38108959

RESUMO

Lead compounds are one of the most common pollutants of the workplace air and the environment. In the occupational setting, the sources of their emission, including in nanoscale form, are various technological processes associated with lead smelting and handling of non-ferrous metals and their alloys, the production of copper and batteries. Both lead poisoning and lead exposure without obvious signs of poisoning have a detrimental effect on the cardiovascular system. The purpose of this research was to investigate the mechanisms of the cardiotoxic effect of lead oxide nanoparticles (PbO NPs). The toxicological experiment involved male albino rats subchronically exposed to PbO NPs (49.6 ± 16.0 nm in size) instilled intraperitoneally in a suspension. We then assessed post-exposure hematological and biochemical parameters of blood and urine, histological and ultrastructural changes in cardiomyocytes, and non-invasively recorded electrocardiograms and blood pressure parameters in the rodents. Myocardial contractility was studied on isolated preparations of cardiac muscles. We established that PbO NPs induced oxidative stress and damage to the ultrastructure of cardiomyocytes, and decreased efficiency of the contractile function of the myocardium and blood pressure parameters. We also revealed such specific changes in the organism of the exposed rats as anemia, hypoxia, and hypocalcemia.


Assuntos
Chumbo , Nanopartículas , Ratos , Masculino , Animais , Nanopartículas/toxicidade , Óxidos/toxicidade , Óxidos/química , Estresse Oxidativo
5.
Food Chem Toxicol ; 144: 111641, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32758638

RESUMO

This investigation continues our study of the effects of Pb-Cd poisoning on the heart, extending the enquiry from isometric to auxotonic contractions, thereby examining the effect on the ability of myocardial tissues to perform mechanical work. Different shifts were revealed in myocardial force-velocity relations following subchronic exposure of rats to lead acetate and cadmium chloride acting separately, in combination, or in combination with a bioprotective complex (BPC). The experiments were conducted on isolated preparations of trabecules and papillary muscles of the right ventricle in physiological loading conditions and on isolated heart muscle contractile proteins examined by the in vitro motility assay. The results of the latter correlate with the shifts in the ratio of cardiac myosin isoforms. The amount of work performed by the myocardium was calculated on the basis of the tension-shortening loop area and was found to be similar in the preparations from all experimental groups. This fact presumably reflects adaptive capacity of the myocardial function even when contractility is damaged due to the metallic intoxication of a moderate severity. Some characteristics of rat myocardium altered by the impact of lead-cadmium intoxication became fully or partly normalized if intoxication developed against background administration of a bioprotective complex (BPC). Together with previously reported results obtained in the isometric mode of contractility, all these results strengthen the scientific foundations of risk assessment and risk management projects in the occupational and environmental conditions characterized by human exposure to lead and/or cadmium.


Assuntos
Cádmio/toxicidade , Coração/efeitos dos fármacos , Chumbo/toxicidade , Animais , Cádmio/administração & dosagem , Técnicas In Vitro , Chumbo/administração & dosagem , Masculino , Ratos , Testes de Toxicidade Subcrônica
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