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 β–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.
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.
Effect of different Ca concentrations in the bathing solution [Ca] on the parameters of single isometric contraction and slow force response to stretching was studied in isolated preparations of healthy and hypertrophied myocardium of male and female Wistar rats. In all groups of experimental animals, the increase in calcium concentration was followed by a decrease in the myocardium slow response intensity. We revealed a complementary relationship between the current and medium-term systems of myocardial contractility regulation by the length of the myocardium aimed at the maintenance of the constant level during adaptation to the load. Slow responses of the hypertrophied rat heart myocardium were suppressed in comparison with those in the healthy myocardium and their intensity did not depend on animal sex.
Sex differences in the morphogenesis and adaptation of the mechanisms controlling myocardium contractility during physiological and pathological hypertrophy of the right ventricle were demonstrated in mature rats. The study revealed sex-dependent effects of physiological and pathological cardiac hypertrophy on the coefficient of variation of the cardiomyocyte diameter, length-dependent control of the contractile force, and the maximum velocity of isotonic shortening.
Pulmonary arterial hypertension (PAH) leads to changes in the pump function of the heart and causes right-sided hypertrophy and heart failure. The study of the mechanical function of multicellular myocardial preparations was performed on isolated strips of the right atrium (RA) and trabeculae of the right ventricle (RV) of control (CONT) and monocrotaline-treated (MCT) male rats. The mechanical characteristics of the actin-myosin interaction were studied in the right-sided heart chambers from the CONT and MCT groups. For the first time, a comparative study of the contractile characteristics of myocardial preparations of both RA and RV in MCT-induced PAH at the molecular and multicellular levels was performed. For both RA and RV of MCT-treated rats, it was shown a decrease in the fraction of motile filaments and the maximum sliding velocity of actin and reconstituted thin filaments over myosin accompanied by a shift in α-/β-myosin heavy chains (MHC) ratio towards β-MHC. In the RA strips and RV trabeculae, a decrease in the maximum shortening velocity, the amplitude of isometric tension, the amount of work, and an increase in the end-systolic length were found. PAH leads to a greater drop in right atrial contractility than that of the ventricle.
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