Cardiac Myosin and Thin Filament as Targets for Lead and Cadmium Divalent Cations.

Lead and cadmium are heavy metals widely distributed in the environment and contribute significantly to cardiovascular morbidity and mortality. Using Leadmium Green dye, we have shown that lead and cadmium enter cardiomyocytes, distributing throughout the cell. Using an motility assay, we have shown that sliding velocity of actin and native thin filaments over myosin decreases with increasing concentrations of Pb and Cd.

Direct Effects of Toxic Divalent Cations on Contractile Proteins with Implications for the Heart: Unraveling Mechanisms of Dysfunction.

The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. In this article, we summarized the impact of these cations on myosin ATPase activity and EF-hand proteins, with special attention given to toxic cations.

Characteristics of the right atrial and right ventricular contractility in a model of monocrotaline-induced pulmonary arterial hypertension.

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-/β-myosin heavy chains (MHC) shifted towards β-MHC.

Molecular mechanisms of mechanical function changes of the rat myocardium under subchronic lead exposure.

A moderate degree of lead intoxication was observed in male rats after repeated intraperitoneal injections with two doses of lead acetate three times a week during 5 (12.5 mg of Pb per kg body mass) and 6 (6.01 mg of Pb per kg body mass) weeks.

Changes in the Cardiotoxic Effects of Lead Intoxication in Rats Induced by Muscular Exercise.

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.

Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles.

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.

Force-velocity characteristics of isolated myocardium preparations from rats exposed to subchronic intoxication with lead and cadmium acting separately or in combination.

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.

Changes in rat myocardium contractility under subchronic intoxication with lead and cadmium salts administered alone or in combination.

Subchronic intoxications induced in male rats by repeated intraperitoneal injections of lead acetate and cadmium chloride, administered either alone or in combination, are shown to affect the biochemical, cytological and morphometric parameters of blood, liver, heart and kidneys. The single twitch parameters of myocardial trabecular and papillary muscle preparations were measured in the isometric regime to identify changes in the heterometric (length-force) and chronoinotropic (frequency-force) contractility regulation systems. Differences in the responses of these systems in trabecules and papillary muscles to the above intoxications are shown.

Further analysis of rat myocardium contractility changes associated with a subchronic lead intoxication.

A moderate subchronic lead intoxication was observed in male rats after repeated intraperitoneal injections of lead acetate. Right ventricular trabeculae and papillary muscles were isolated for in vitro studying of the contraction-relaxation cycle under isotonic and physiological loading. The contractile function of the myocardium was also assessed by measuring the velocity of thin filament movement over myosin.

Effects of subchronic lead intoxication of rats on the myocardium contractility.

Outbred male rats were repeatedly injected IP with sub-lethal doses of lead acetate 3 times a week during 5 weeks. They developed an explicit, even if moderate, lead intoxication characterized by typical hematological and some other features. The next day after the last injection the heart of each animal was excised, and the trabecules and papillary muscles from the right ventricle were used for modeling in vitro isometric (with varying starting length of the preparation) regimes of the contraction-relaxation cycle with different preloads.