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

Protsenko, Yuri; Katsnelson, Boris A.; Klinova, Svetlana V.; Lookin, Oleg; Балакин, А. А.; Никитина, Л. В.; Gerzen, Oksana P.; Nabiev, Salavat R.; Minigalieva, Ilzira A.; Privalova, Larisa I.; Gurvich, Vladimir B.; Sutunkova, Marina P.; Katsnelson, Leonid B.

doi:10.1016/j.fct.2018.12.054

Cited by 13 publications

(5 citation statements)

References 57 publications

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“…Not all of them had systematically studied the length effect on inotropic and lusitropic characteristics of the human myocardium. Nevertheless, they provide the experimentally observed ranges of TTP, t 70 and t 50 values which we used for verification of the parameters of the TP+M model responsible for its mechanical behavior. Thus, our simulations are within the ranges of these mechanical characteristics obtained in the referenced above experiments.…”

Section: Figmentioning

confidence: 99%

“…6a,b): isometric contraction at a fixed initial length until muscle force approaches an imposed afterload level (reflects the phase of isovolumetric ventricular contraction); isotonic shortening down to an end-systolic length (ejection); isometric relaxation at the fixed end-systolic length (volumetric relaxation); and final stretch back to the initial length (filling). Similarly to the PV-loop, the "Length -Force" (LF) loop during the physiological contraction cycle is also used to evaluate muscle contractility, and the area of the LF-loop is used to calculate work and power of the muscle [68][69][70].…”

Section: Figmentioning

confidence: 99%

“…From top to bottom in both (a) and (b): force, sample length, intracellular Ca 2+ transient ([Ca 2+ ]i) and membrane potential changes. c-dThe value tCa70 is time from peak of Ca 2+ transient to 70% decay. APD 90 is action potential duration at 90% of repolarization…”

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confidence: 99%

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Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

Balakina-Vikulova

Panfilov

Solovyova

et al. 2019

Preprint

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Experiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g. load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the ‘ten Tusscher – Panfilov’ electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the ‘Ekaterinburg – Oxford’ model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

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Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

Balakina-Vikulova

Panfilov

Solovyova

et al. 2019

Preprint

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“…Chronic exposure to cadmium [ 44 , 45 ], lead [ 46 , 47 , 48 ], and mercury [ 49 ] has been associated with multiple cardiovascular diseases. Cardiotoxicity after chronic and acute exposure was experimentally confirmed in the animal models for cadmium [ 16 , 50 , 51 , 52 , 53 , 54 ], lead [ 19 , 35 , 55 , 56 , 57 ], and mercury [ 16 ]. For each of viz.…”

Section: Accumulation Competition and Toxicity Of Divalent Cationsmentioning

confidence: 99%

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

Gerzen,

Votinova,

Potoskueva

et al. 2023

IJMS

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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. Optimal binding to EF-hand proteins occurs at an ionic radius close to that of Mg2+ and Ca2+. In skeletal Troponin C, Cd2+, Sr2+, Pb2+, Mn2+, Co2+, Ni2+, Ba2+, Mg2+, Zn2+, and trivalent lanthanides can substitute for Ca2+. As myosin ATPase is not a specific MgATPase, Ca2+, Fe2+, Mn2+, Ni2+, and Sr2+ could support myosin ATPase activity. On the other hand, Zn2+ and Cu2 significantly inhibit ATPase activity. The affinity to various divalent cations depends on certain proteins or their isoforms and can alter with amino acid substitution and post-translational modification. Cardiac EF-hand proteins and the myosin ATP-binding pocket are potential molecular targets for toxic cations, which could significantly alter the mechanical characteristics of the heart muscle at the molecular level.

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“…It has been proposed from the experiments in rats that even low levels of Pb 2+ interfere with the contractile proteins of the heart and their contraction cycle (Katsnelson et al, 2020;Silva et al, 2015). More recent reports also found a negative inotropic of the Pb 2+ exposome (Klinova et al, 2020;Protsenko et al, 2018Protsenko et al, , 2019. However, some reports maintain that Pb 2+ has a positive inotropic effect in rats (Fioresi et al, 2014).…”

Section: Cardiac Effects Of the Lead Exposomementioning

confidence: 99%

Functional consequences of lead and mercury exposomes in the heart

Ferreira

Santander

Chavarría

et al. 2022

Molecular Aspects of Medicine

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

Cited by 13 publications

References 57 publications

Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

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

Functional consequences of lead and mercury exposomes in the heart

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