Physiological simulation of atrial-ventricular mechanical interaction in male rats during the cardiac cycle.

Adequate assessment of the contribution of the different phases of atrial mechanical activity to the value of ejection volume and pressure developed by the ventricle is a complex and important experimental and clinical problem. A new method and an effective algorithm for controlling the interaction of isolated rat right atrial and right ventricular strips during the cardiac cycle were developed and tested in a physiological experiment. The presented functional model is flexible and has the ability to change many parameters (temperature, pacing rate, excitation delay, pre- and afterload levels, transfer length, and force scaling coefficients) to simulate different types of cardiac pathologies.

On the Mechanisms of the Cardiotoxic Effect of Lead Oxide Nanoparticles.

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.

Differences in Mechanical, Electrical and Calcium Transient Performance of the Isolated Right Atrial and Ventricular Myocardium of Guinea Pigs at Different Preloads (Lengths).

There are only a few studies devoted to the comparative and simultaneous study of the mechanisms of the length-dependent regulation of atrial and ventricular contractility. Therefore, an isometric force-length protocol was applied to isolated guinea pig right atrial (RA) strips and ventricular (RV) trabeculae, with a simultaneous measurement of force (Frank-Starling mechanism) and Ca transients (CaT) or transmembrane action potentials (AP). Over the entire length-range studied, the duration of isometric contraction, CaT and AP, were shorter in the RA myocardium than in the RV myocardium.

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.

Differences in Effects of Length-Dependent Regulation of Force and Ca Transient in the Myocardial Trabeculae of the Rat Right Atrium and Ventricle.

The comparative differences in the fundamental mechanisms of contractility regulation and calcium handling of atrial and ventricular myocardium remain poorly studied. An isometric force-length protocol was performed for the entire range of preloads in isolated rat right atrial (RA) and ventricular (RV) trabeculae with simultaneous measurements of force (Frank-Starling mechanism) and Ca transients (CaT). Differences were found between length-dependent effects in RA and RV muscles: (a) the RA muscles were stiffer, faster, and presented with weaker active force than the RV muscles throughout the preload range; (b) the active/passive force-length relationships were almost linear for the RA and RV muscles; (c) the value of the relative length-dependent growth of passive/active mechanical tension did not differ between the RA and RV muscles; (d) the time-to-peak and amplitude of CaT did not differ between the RA and RV muscles; (e) the CaT decay phase was essentially monotonic and almost independent of preload in the RA muscles, but not in the RV muscles.

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.

Contractile Behavior of Right Atrial Myocardium of Healthy Rats and Rats with the Experimental Model of Pulmonary Hypertension.

There is a lack of data about the contractile behavior of the right atrial myocardium in chronic pulmonary heart disease. We thoroughly characterized the contractility and Ca transient of isolated right atrial strips of healthy rats (CONT) and rats with the experimental model of monocrotaline-induced pulmonary hypertension (MCT) in steady state at different preloads (isometric force-length), during slow force response to stretch (SFR), and during post-rest potentiation after a period of absence of electrical stimulation (PRP). The preload-dependent changes in the isometric twitch and Ca transient did not differ between CONT and MCT rats while the kinetics of the twitch and Ca transient were noticeably slowed down in the MCT rats.

Omecamtiv mecarbil attenuates length-tension relationship in healthy rat myocardium and preserves it in monocrotaline-induced pulmonary heart failure.

The cardiac-specific myosin activator, omecamtiv mecarbil (OM), is an effective inotrope for treating heart failure but its effects on active force and Ca kinetics in healthy and diseased myocardium remain poorly studied. We tested the effect of two concentrations of OM (0.2 and 1 µmol/L in saline) on isometric contraction and Ca-transient (CaT) in right ventricular trabeculae of healthy rats (CONT, n = 8) and rats with monocrotaline-induced pulmonary heart failure (MCT, n = 8).

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.

The role of pacing rate in the modulation of mechano-induced immediate and delayed changes in the force and Ca-transient of cardiac muscle.

Myocardial function is tuned by dynamic changes in length and load via mechano-calcium feedback. This regulation may be significantly affected by heart rhythm. We evaluated the mechano-induced modulation of contractility and Ca-transient (CaT) in the rat myocardium subjected to twitch-by-twitch shortening-re-lengthening (↓-↑) trains of different lengths (N = 1 … 720 cycles) at low (1 Hz) and near-physiological (3.

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.

Length-Dependent Activation of Contractility and Ca-Transient Kinetics in Auxotonically Contracting Isolated Rat Ventricular Cardiomyocytes.

Length-dependent activation (LDA) of contraction is an important mechanism of proper myocardial function that is often blunted in diseases accompanied by deficient contractility and impaired calcium homeostasis. We evaluated how the extent of LDA is related to the decreased force in healthy rat myocardium under negative inotropic conditions that affect the calcium cycle. The length-dependent effects on auxotonic twitch and Ca-transient were compared in isolated rat ventricular cardiomyocytes at room temperature ("25C") and near-physiological temperature ("35C") in normal Tyrode and at 25°C with thapsigargin-depleted sarcoplasmic reticulum ("25C + Thap").

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.

The lack of slow force response in failing rat myocardium: role of stretch-induced modulation of Ca-TnC kinetics.

The slow force response (SFR) to stretch is an important adaptive mechanism of the heart. The SFR may result in ~ 20-30% extra force but it is substantially attenuated in heart failure. We investigated the relation of SFR magnitude with Ca transient decay in healthy (CONT) and monocrotaline-treated rats with heart failure (MCT).

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.

Inhibition of AT1 receptors by losartan affects myocardial slow force response in healthy but not in monocrotaline-treated young rats.

The slow force response (SFR) of a cardiac muscle to a sudden stretch is thought to be important in the regulatory adaptation of myocardial contraction. Autocrine-paracrine regulation pathways which involve angiotensin II are participating in this mechanism. On the other hand, renin-angiotensin-aldosterone system (RAS) is altered in hypertrophic or failing myocardium.

Experimental study and modelling the evolution of viscoelastic hysteresis loop at different frequencies in myocardial tissue.

Our work involved experimental study of the influence of actomyosin complexes and the main structural components of the myocardial tissue - connective tissue collagen framework and cardiomyocytes - on the characteristics of viscoelastic hysteresis at different frequencies. In this paper a new method was introduced for the analysis of the viscoelastic characteristics of the force hysteresis in the isolated myocardial preparation for the assessment of mechanical energy expenditure in the tension-compression cycle. We established that basic myocardial structures have an impact on the to the characteristics of the viscoelastic hysteresis in many ways.

The phenomena of mechanical interaction of segments of hypertrophied myocardium.

The main aims of adaptation mechanisms of heart contractility are to regulate the stroke volume and optimize the global heart function. These mechanisms manifest themselves in hearts of healthy animals and in hearts with severe hypertrophy in different ways. Severe right ventricle hypertrophy was induced by single treatment with monocrotaline.

The length-dependent activation of contraction is equally impaired in impuberal male and female rats in monocrotaline-induced right ventricular failure.

The length-dependent activation of contraction is attenuated in the failing myocardium of adult male rats. This pathological change is not seen in adult female rats, possibly because of a protective effect of sex hormones. The present study evaluated length-dependent changes in isometric twitch, Ca(2+) transient (CaT) and action potential (AP) in the right ventricular myocardium of impuberal healthy male and female rats (control) and in rats treated with a single injection of 50 mg/kg monocrotaline (MCT).

Sex differences in stretch-dependent effects on tension and Ca(2+) transient of rat trabeculae in monocrotaline pulmonary hypertension.

We aim to compare the effects of stretch on isometric tension/Ca(2+) transient in the right ventricular trabeculae of control (CONT) and hypertensive (MCT, monocrotaline application) adult male and female rats. The treatment with MCT resulted in RV hypertrophy in males only. Blunted active force-length relation and substantially prolonged twitch were found in MCT-males but not MCT-females (vs same-sex CONT).

Viscoelastic properties of the papillary muscle: experimental and theoretical study.

It is well known that the structure of biological tissue is closely related to tissue functions and defines its viscoelastic properties. It is necessary to create a model combining structural organization of myocardium and its viscoelastic properties to develop a model of cardiac wall of intact or deceased heart. This paper is devoted to experimental and theoretical study of viscoelastic behavior of isolated myocardial samples.

Slow force response and auto-regulation of contractility in heterogeneous myocardium.

Classically, the slow force response (SFR) of myocardium refers to slowly developing changes in cardiac muscle contractility induced by external mechanical stimuli, e.g. sustained stretch.

Contribution of mechanical factors to arrhythmogenesis in calcium overloaded cardiomyocytes: model predictions and experiments.

It is well-known that Ca²⁺ overload in cardiomyocytes may underlie arrhythmias. However, the possible contribution of mechanical factors to rhythm disturbances in Ca²⁺ overloaded myocytes has not been sufficiently investigated. We used a mathematical model of the electrical and mechanical activity of cardiomyocytes to reveal an essential role of the mechanisms of cardiac mechano-electric feedback in arrhythmogenesis in Ca²⁺ overloaded myocardium.

Hybrid duplex: a novel method to study the contractile function of heterogeneous myocardium.

In an earlier study, we experimentally mimicked the effects of mechanical interaction between different regions of the ventricular wall by allowing pairs of independently maintained cardiac muscle fibers to interact mechanically in series or in parallel. This simple physiological model of heterogeneous myocardium, which has been termed "duplex," has provided new insight into basic effects of cardiac electromechanical heterogeneity. Here, we present a novel "hybrid duplex," where one of the elements is an isolated cardiac muscle and the other a "virtual cardiac muscle.