Activity Of Cardiac Muscle Research Articles

CHANGES IN THE CONTENT AND ACTIVITY OF MUSCLE PROTEINS AS A MARKER IN THE CASE OF EXPOSURE TO IONIZING RADIATION IN ANIMALS

Objective. To find out the specifics of muscle tissue contraction under the conditions of exposure to low doses of ionizing radiation in parents and their irradiated offspring by evaluating changes in the content of contractile proteins and ATPase activity of skeletal and cardiac muscles. Methods. Experimental studies were conducted on 50 rats. Animals were randomized as follows: group 1 — intact sexually mature rats; 2 — sexually mature animals irradiated with a dose of 1.0 Gy; group 3 — monthold rats obtained from intact individuals; group 4 — month-old rat pups obtained from parents irradiated with a dose of 1.0 Gy; group 5 — month-old rats obtained from animals irradiated with a dose of 1.0 Gy, which were irradiated at the same dose. The results. Muscle dysfunction in irradiated offspring and parents is manifested by a decrease in the content of contractile proteins, functional dysfunction of the actomyosin bridge, and a decrease in the ATPase activity of contractile proteins. Marked muscle dysfunctions during the post-radiation time period may be the reason for the formation of orthopedic pathology in a significant contingent of irradiated persons. Conclusions. The expression of muscle dysfunction in the offspring of irradiated animals, which were also exposed to ionizing radiation, is greater than the corresponding processes in their irradiated parents, which indicates the mediation of muscle dysfunction in the second generation of irradiated animals by epigenetic mechanisms. Marked muscle dysfunctions during the post-radiation time period may be the reason for the formation of orthopedic pathology in a significant contingent of irradiated persons

Have a Little Heart (or Not): Highly Minimized Skeletal Muscle Regulatory Cassettes with Low or No Activity in the Heart.

Adeno-associated virus-mediated gene therapies for certain muscle disorders require regulatory cassettes that provide high-level, striated muscle-specific activity. However, cardiotoxicity has emerged as a serious concern in clinical trials for Duchenne muscular dystrophy and X-linked myotubular myopathy. While this may be caused by systemic inflammatory effects of the treatment, high transgene expression in the heart may also play a role. Thus, certain muscle disorders may require a modulated level of therapeutic expression in the heart, while others may not require any cardiac expression at all. Additionally, the size of some cargos requires regulatory cassettes to be small enough that large cDNAs and other therapeutic payloads can be accommodated. Thus, we have performed enhancer/promoter optimization to develop highly minimized regulatory cassettes that are active in skeletal muscles, with either low or no detectable activity in cardiac muscle. Our No-heart (NH) cassette is active in most skeletal muscles, but exhibits only very low activity in extensor digitorum longus (EDL), soleus, and diaphragm, and no activity in the heart. By contrast, our Have a Little Heart (HLH) cassette displays high activity in most skeletal muscles, comparable to the ∼800-bp CK8 cassette, with increased activity in EDL, soleus, and diaphragm, and low activity in the heart. Due to their small size, these cassettes can be used in therapeutic strategies with both flexible (e.g., antisense) and stringent (e.g., CRISPR/Cas or bicistronic) size limitations. Thus, our new cassettes may be useful for gene therapies of muscle disorders in which the need for low or almost no expression in cardiac muscle would outweigh the need for high levels of therapeutic product in certain skeletal muscles.

Super-relaxed or super-stressed: Modeling length-dependent activation in cardiac muscle

Super-relaxed or super-stressed: Modeling length-dependent activation in cardiac muscle

Differences in thick filament activation in fast rodent skeletal muscle and slow porcine cardiac muscle.

There is a growing appreciation that regulation of muscle contraction requires both thin filament and thick filament activation in order to fully activate the sarcomere. The prevailing mechano-sensing model for thick filament activation was derived from experiments on fast-twitch muscle. We address the question whether, or to what extent, this mechanism can be extrapolated to the slow muscle in the hearts of large mammals, including humans. We investigated the similarities and differences in structural signatures of thick filament activation in porcine myocardium as compared to fast rat extensor digitorum longus (EDL) skeletal muscle under relaxed conditions and sub-maximal contraction using small angle X-ray diffraction. Thick and thin filaments were found to adopt different structural configurations under relaxing conditions, and myosin heads showed different changes in configuration upon sub-maximal activation, when comparing the two muscle types. Titin was found to have an X-ray diffraction signature distinct from those of the overall thick filament backbone, and its spacing change appeared to be positively correlated to the force exerted on the thick filament. Structural changes in fast EDL muscle were found to be consistent with the mechano-sensing model. In porcine myocardium, however, the structural basis of mechano-sensing is blunted suggesting the need for additional activation mechanism(s) in slow cardiac muscle. These differences in thick filament regulation can be related to their different physiological roles where fast muscle is optimized for rapid, burst-like, contractions, and the slow cardiac muscle in large mammalian hearts adopts a more finely tuned, graded response to allow for their substantial functional reserve. KEY POINTS: Both thin filament and thick filament activation are required to fully activate the sarcomere. Thick and thin filaments adopt different structural configurations under relaxing conditions, and myosin heads show different changes in configuration upon sub-maximal activation in fast extensor digitorum longus muscle and slow porcine cardiac muscle. Titin has an X-ray diffraction signature distinct from those of the overall thick filament backbone and this titin reflection spacing change appeared to be directly proportional to the force exerted on the thick filament. Mechano-sensing is blunted in porcine myocardium suggesting the need for additional activation mechanism(s) in slow cardiac muscle. Fast skeletal muscle is optimized for rapid, burst-like contractions, and the slow cardiac muscle in large mammalian hearts adopts a more finely tuned graded response to allow for their substantial functional reserve.

Analysis of QRS complex morphology in children and adolescents with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) leads to many cardiovascular, neurologic, metabolic, and neurocognitive consequences. Conduction deficits, deviations in electrical axis, and changes in QRS morphology reflect the impairments in cardiac muscle activity and underlie the cardiovascular complications of OSAS. Here we aimed to determine the relationship between OSAS and changes in the cardiac conduction system in children and adolescents. During the 6-month duration of the study, all children having the diagnosis of OSAS in Sleep and Disorders Unit following a full-night polysomnography (PSG) were consecutively evaluated. ECGs were performed and analyzed in the Division of Pediatric Cardiology, Department of Pediatrics. The maximum spatial vector size (QRSmax), QRS electrical axis (EA), left and right ventricular hypertrophy, and the presence of fragmented QRS (fQRS) or prolonged R or S wave were examined in detail. A total of 17 boys with OSAS and 13 healthy boys participated in the study. The mean QRSmax and the QRSmax on V5 derivative were significantly lower in the patient group compared to those in the control group (p = 0.011 and p = 0.017, respectively). EA was similar between the two groups. While none of the patients with OSAS nor the control group had left ventricular hypertrophy, only one boy with OSAS had right ventricular hypertrophy according to ECG-derived analysis. The percentage of fQRS or notched R or S waves was significantly higher in patients with OSAS compared to healthy controls (p = 0.035), especially in children below the age of 5years (p = 0.036). Conclusion: This study demonstrated that male children and adolescents with OSAS have a combination of QRS complex changes characterized by low QRS voltages, and increased frequency of fragmented QRS. These findings reflect that the electrical remodeling and structural remodeling of the myocardium are considerably affected by OSAS in children and adolescents, leading to ventricular changes and intraventricular conduction problems. What is Known: • Pediatric obstructive sleep apnea syndrome (OSAS) characterized by recurrent intermittent hypoxemia, hypercapnia, and sleep fragmentation results in sympathetic nervous system activation, increased inflammation, and hypoxic endothelial dysfunction. When left untreated, OSAS leads to many cardiovascular, neurologic, metabolic and neurocognitive consequences, and also to sudden infant death syndrome in young children, probably due to the involvement of the cardiac conduction system. What is New: • This study demonstrated that mean QRSmax was significantly lower in male children and adolescents with OSAS, reflecting the structural and electrical remodeling of the myocardium, and one boy with OSAS had RVH according to ECG-derived analysis. The percentage of fQRS or notched R or S waves was much higher in boys with OSAS, especially in children below the age of five years. These finding showed that myocardium was considerably affected to impair the intraventricular conduction in younger children with OSAS.

Regulating Striated Muscle Contraction: Through Thick and Thin.

Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin motors for the interaction with actin. This review summarizes the mechanisms of thin and thick filament activation that regulate the contractility of skeletal and cardiac muscle. A novel dual-filament paradigm of muscle regulation is emerging, in which the dynamics of force generation depends on the coordinated activation of thin and thick filaments. We highlight the interfilament signaling pathways based on titin and myosin-binding protein-C that couple thin and thick filament regulatory mechanisms. This dual-filament regulation mediates the length-dependent activation of cardiac muscle that underlies the control of the cardiac output in each heartbeat.

A CNN based multifaceted signal processing framework for heart rate proctoring using Millimeter wave radar ballistocardiography

The recent pandemic has refocused the medical world’s attention on the diagnostic techniques associated with cardiovascular disease. Heart rate provides a real-time snapshot of cardiovascular health. A more precise heart rate reading enables a better understanding of cardiac muscle activity. Although many existing diagnostic techniques are approaching the limits of perfection, there remains potential for further development. In this paper, we propose MIBINET, a novel multifaceted approach for real-time proctoring of heart rate from Millimeter wave (mm-wave) radar ballistocardiography signals via inter-beat-interval (IBI) using a convolutional neural NETwork (CNN). The central theme of our approach is to synergize the feature extraction capabilities of CNN with novel signal processing techniques, resulting in enhanced estimation accuracy while simultaneously reducing computational complexity. This proposed network can be used in hospitals, homes, and passenger vehicles due to its lightweight and contactless properties. It employs classical signal processing prior to fitting the data into the network. Although MIBINET is primarily designed to work on mm-wave signals, it is found equally effective on signals of various modalities such as PCG, ECG, and PPG. Our approach outperforms state-of-the-art techniques by more than 5% in inter-beat-interval (IBI) estimation accuracy. The architecture achieves a 98.73% correlation coefficient and a 20.69 ms Root-Mean-Square Error (RMSE) over 11 different test subjects. The paper contributes by being the first to apply CNN-based feature extraction in concert with unique signal processing strategies to mm-wave radar data for heart rate monitoring. Our methodology also introduces a synthetic IBI augmentation technique, custom loss function, and novel post-processing methods, all contributing to the robust performance of the model in various settings and modalities.

ATPase activity of actomyosin and myosin in different types of muscles of intact and irradiated animals

The large-scale use of sources of ionizing radiation and related accidents caused a fundamentally new problem. The body's resistance to the influence of adverse environmental factors and the probability of pathological disorders are significantly determined by the state of adaptive systems. One of the general manifestations of adaptation is a change in motor activity, which is associated, in particular, with changes in the content of contractile proteins, muscle function, and muscle contraction. It is crucial to understand the detailed mechanisms of muscle tissue functioning in the body of intact animals and animals exposed to different doses of radiation because, in this case, preventive and curative/rehabilitative medical measures should be milder for muscle dysfunctions caused by ionizing radiation The purpose of the work is to investigate the effect of different doses of radiation on Mg2+, Ca2+-ATPase and K+-ATPase activity of actomyosin and myosin in the mechanisms of intact and irradiated in different doses of sexually mature animals in order to find out the mechanisms of adaptation of the organism to the influence of stress factor by studying changes in the activity of Mg2+, Ca2+-ATPase and K+-ATPase in the muscle system. The data obtained showed that irradiation at a dose of 0.5 Gy affects Mg2+,Ca2+-ATPase and K+-ATPase activity, however, these changes occur differently. K+-ATPase actomyosin activity in cardiac and skeletal muscles decreased starting from the 1st day of the experiment. Its gradual increase was observed only on the 30th day but still, it was smaller when compared with such an indicator in intact animals. It was proved that the Mg2+, Ca2+-ATPase actomyosin activity in sexually mature animals irradiated at a dose of 1.0 Gy increased 1 day after irradiation in skeletal muscle. In сardiac muscle an acute increase in Mg2+, Ca2+-ATPase actomyosin activity was observed on the 1st day and its decrease - by the 30th day. The conclusion was made that irradiation at a dose of 1.0 Gy is accompanied by skeletal muscle damage, as well as modification of the actomyosin protein complex, which is the major unit of muscle contraction. This leads to changes in its functional activity and is expressed in an increase in K+-ATPase actomyosin activity of muscles sensitive to irradiation. We assume such a mechanism of the effect of ionizing radiation on the actomyosin complex. The authors sure that a decrease in Mg2+, Ca2+-ATP-ase myosin activity as a result of exposure to ionizing radiation at a dose of 1.0 Gy can be caused by a violation of the structure of its active center since the ATPase center of pure myosin is free from interaction with actin, and that is why myosin appears more sensitive to the action of ionizing radiation.

Complementary in vitro functional studies and in silico alchemical free energy simulations of the sarco-endoplasmic reticulum calcium pump (SERCA) and phospholamban (PLN) complex.

SERCA is ubiquitously expressed in all eukaryotic cells and is responsible for actively transporting calcium ions from the cytoplasm into the SR/ER lumen. PLN is a small transmembrane peptide that regulates SERCA's calcium transport activity in cardiac muscle. Human genetic variants of PLN have been implicated in cardiomyopathies. PLN is a 52 amino acid peptide with an N-terminal cytoplasmic helix (residues 1-17), a short linker region (residues 18-27) and a C-terminal transmembrane helix (residues 28-52). Previous structural studies have identified the binding groove for PLN formed by transmembrane segments M2, M6, and M9 of SERCA (PDB: 4KYT). The structure of the SERCA-PLN complex consists of SERCA in a calcium-free, E1-like state and includes the linker region and transmembrane helix of PLN (residues 20-52). Here, we carry out in vitro functional studies and in silico free energy calculations to examine the effects of alanine scanning mutations in PLN (residues 20-52) on SERCA regulation. From the functional studies, changes in kinetics parameters such as calcium affinity (KCa) and maximal activity (VMax) of SERCA are determined for each of the alanine substitutions. From the in silico alchemical free energy simulations (using Compute Canada supercomputing resources), each of the residues in PLN are alchemically transformed to alanine to determine the change in Gibbs free energy (Δ;Δ;G) relative to the wild-type SERCA-PLN complex. Together, the complementary in vitro and in silico mutational studies provide novel insights into a membrane protein-peptide complex. The PLN variants are quantified in terms of their physiological significance – gain-of-function, loss-of-function, or neutral – and the molecular determinants that control binding specificity.

213: ONE SHOCK TREATED WITH ANOTHER: NEW-ONSET ATRIAL FIBRILLATION AFTER HIGH-VOLTAGE ELECTRICAL INJURY

Introduction: Development of atrial fibrillation following electrical injury has been rarely reported in literature. This can place medical providers in a situation where they are uncertain on how to manage such event. We present a case of high voltage electrical injury (7200V) resulting in new onset atrial fibrillation. Description: A 38-year-old electric line worker with no previous medical history came in with complaint of new onset palpitations and lightheadedness that started an hour prior to arrival. Patient stated he was standing on a boom lift, pressure-washing a church’s tower when his lance touched an electrical wire overhead. The lines were coming from a main electric pole estimated to be 7200V that connected to the transformer. Patient felt a shock pass through his right hand down to the rest of his body for a few seconds, and then he fell. He was not wearing any gloves. He denied any loss of consciousness, alcohol use, chest pain or any previous heart condition. In the ED, he was found to be in atrial fibrillation with heart rate ranging from 110-150. His CPK was 295 units/L and troponin was < 6 ng/L. Patient received IV diltiazem 15mg and IV amiodarone 150mg. He was started on amiodarone drip, admitted to ICU for monitoring and transitioned to Metoprolol 25mg BID and Xarelto 15mg daily the next day before discharge. Three weeks later, he underwent transesophageal echocardiogram (TEE) guided electrical cardioversion for persistent atrial fibrillation. Discussion: Electrical injury can induce cardiac arrhythmias via different mechanisms. The sheer energy of the electric current could directly stimulate the myocytes. It could also impair the sodium-potassium adenosine triphosphatase transporter which plays a major role in electrical-mechanical activity of cardiac muscle. Myocardial necrosis can also lead to production of new arrhythmogenic foci. Troponin and CPK are not always strong indicators of myocardial injury, however, high CK levels >400 units/L may be associated with longer hospitalization, and a greater risk of skin grafting or amputation. Atrial fibrillation in setting of electrical injury is managed with the use of beta blockers, anti-arrhythmics and in some cases, electrical cardioversion.

Ventriculography for the study of TAKO-TSUBO Syndrome

Tako-Tsubo Cardiomyopathy (TTC) is an acute syndrome, identified in the early 1990s by Japanese researchers, which mimics an acute myocardial infarction. Cardiomyopathy is transient and begins with a clinical picture similar to that of an acute myocardial infarction. This pathology seems to be related to intense psychological and physical stress with a prevalence in the female sex (95%) in post-menopause. The term Tako-Tsubo means ‘octopus trap’ in Japanese: the left ventricle takes on a peculiar appearance in systole, similar to a narrow-necked amphora, morphologically identical to the vessel (tsubo) that Japanese fishermen use to catch octopuses (tako). The appearance of the left ventricle (tako-tsubo shape) is due to a ‘complete’ depletion of cardiac muscle activity (myocardial stunning), a kind of ‘stunning’ or paralysis of the middle and apical portions of the heart. Coronarography and ventriculography are an essential step in the diagnosis of TTC. The mere demonstration of a coronary tree free of angiographically significant stenosis is not sufficient for the diagnosis of TTC. The other key diagnostic element is, in fact, the demonstration of left ventricular hypokinesia or akinesia. Since left ventricular wall motility disorders change rapidly, ventriculography performed immediately after coronary examination is the gold standard examination to allow the characteristic appearance of the syndrome to be verified and, consequently, to distinguish it from an acute coronary syndrome with uninjured coronary arteries, thus avoiding a diagnostic error.

Ventriculography for the study of TAKO-TSUBO Syndrome

Tako-Tsubo Cardiomyopathy (TTC) is an acute syndrome, identified in the early 1990s by Japanese researchers, which mimics an acute myocardial infarction. Cardiomyopathy is transient and begins with a clinical picture similar to that of an acute myocardial infarction. This pathology seems to be related to intense psychological and physical stress with a prevalence in the female sex (95%) in post-menopause. The term Tako-Tsubo means 'octopus trap' in Japanese: the left ventricle takes on a peculiar appearance in systole, similar to a narrow-necked amphora, morphologically identical to the vessel (tsubo) that Japanese fishermen use to catch octopuses (tako). The appearance of the left ventricle (tako-tsubo shape) is due to a 'complete' depletion of cardiac muscle activity (myocardial stunning), a kind of 'stunning' or paralysis of the middle and apical portions of the heart. Coronarography and ventriculography are an essential step in the diagnosis of TTC. The mere demonstration of a coronary tree free of angiographically significant stenosis is not sufficient for the diagnosis of TTC. The other key diagnostic element is, in fact, the demonstration of left ventricular hypokinesia or akinesia. Since left ventricular wall motility disorders change rapidly, ventriculography performed immediately after coronary examination is the gold standard examination to allow the characteristic appearance of the syndrome to be verified and, consequently, to distinguish it from an acute coronary syndrome with uninjured coronary arteries, thus avoiding a diagnostic error.

Targeting the sarcomere in inherited cardiomyopathies.

Variants in >12 genes encoding sarcomeric proteins can cause various cardiomyopathies. The two most common are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Current therapeutics do not target the root causes of these diseases, but attempt to prevent disease progression and/or to manage symptoms. Accordingly, novel approaches are being developed to treat the cardiac muscle dysfunction directly. Challenges to developing therapeutics for these diseases include the diverse mechanisms of pathogenesis, some of which are still being debated and defined. Four small molecules that modulate the myosin motor protein in the cardiac sarcomere have shown great promise in the settings of HCM and DCM, regardless of the underlying genetic pathogenesis, and similar approaches are being developed to target other components of the sarcomere. In the setting of HCM, mavacamten and aficamten bind to the myosin motor and decrease the ATPase activity of myosin. In the setting of DCM, omecamtiv mecarbil and danicamtiv increase myosin activity in cardiac muscle (but omecamtiv mecarbil decreases myosin activity in vitro). In this Review, we discuss the therapeutic strategies to alter sarcomere contractile activity and summarize the data indicating that targeting one protein in the sarcomere can be effective in treating patients with genetic variants in other sarcomeric proteins, as well as in patients with non-sarcomere-based disease.

Facile synthesis of bromelain copper nanoparticles to improve the primordial therapeutic potential of copper against acute myocardial infarction in diabetic rats.

Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) - induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.

Structural Changes in the Myosin Motors Induced by Stretch and Phosphorylation of the Myosin Regulatory Light Chain in Rat Cardiac Trabeculae

The contractility of cardiac muscle is potentiated by phosphorylation of the myosin regulatory light chain (RLC) and by length-dependent activation, but the molecular pathways mediating these effects remain unclear. Here we studied the role of structural changes in the thick filament in the activation of cardiac muscle by stretch and RLC phosphorylation. We used fluorescence polarization from bifunctional sulphorhodamine probes on the N- and C-lobes of the myosin RLC to monitor changes in the orientation of the myosin motors induced by increasing the sarcomere length in the range 2.0-2.3 µm in relaxed and partially calcium-activated demembranated cardiac trabeculae, at different levels of RLC phosphorylation. We show that under relaxing or diastolic conditions at near physiological temperature and lattice spacing the RLC lobe orientations are consistent with about one third of the myosin motors being folded onto the filament surface in the interacting-heads motif seen in isolated filaments. This folded conformation is disrupted by cooling relaxed trabecula, but not by RLC phosphorylation or stretch at diastolic [Ca2+]. These results indicate that in near-physiological conditions the myosin filament is not switched on by RLC phosphorylation or by the titin-based passive tension at longer sarcomere lengths in diastole, as suggested previously. However, stretching cardiac trabecula at near-systolic [Ca2+] triggers a stress-dependent activation of the thick filament and a delayed increase in active force. Physiological levels of RLC phosphorylation potentiate both the stress-dependent release of myosin motors from the folded state and the stretch-activated force. We conclude that the increase in heart contractility induced by RLC phosphorylation and stretch can be explained by an inter-filament signaling pathway involving both thin filament sensitization and thick filament mechano-sensing (Supported by Wellcome Trust, BHF, UK).

Natural shear wave imaging using vocal tract vibrations: Introducing vocal passive elastography (V-PE) to thyroid elasticity mapping

We present a shear wave elastography (SWE) approach for thyroid characterization that is inspired by passive elastography, which extracts elasticity from the natural vibrations in living tissues that are caused by cardiac motion, blood pulsatility, and muscle activity. On thyroid, this physiological noise is mainly due to the carotid pulsation, which is in the 1–10 Hz bandwidth and is located right next to the gland. In order to decrease the shear wavelength and increase the signal to noise ratio, we propose to create in the thyroid a complex shear wave field by using natural vocal tract vibrations. The nature of the sound can be easily modified to be narrow or broad band, with small or large amplitude. Using correlation-based algorithm and a sound sustained at 150 Hz, we have developed an innovative technique using ultrasound, allowing us to compute a 2D shear wave velocity map, superposed onto a B-mode ultrasound image of a volunteer's thyroid. Using our vocal passive elastography method, shear wave velocity was measured at every point within a mask surrounding the thyroid with a pixel resolution of 150 × 150 μm2. The mean shear wave speed value measured is 3.2 m/s, taking its value from 0.7 m/s to 8.8 m/s. The values obtained were in good agreement with comparative shear wave elastography (SWE) measurements.

Effects of guanidinoacetic acid supplementation on zootechnical performance and some biometric indices in broilers challenged with T3-Hormone

The objective was to elucidate the effects of dietary guanidinoacetic acid (GAA) supplementation on broiler performance, serum enzymes, oxidative biomarkers, mitochondrial activities, carcase traits, gross lesion of cardiac muscle and liver histopathology in broilers challenged with T3-hormone. A total-of-192 one-day-old mixed sexed broilers were randomly assigned in a two factorial design, including two dietary treatments; control diet supplemented with or without T3-hormone (1.5 ppm) and GAA diet (0.06%) supplemented with or without T3-hormone (1.5 ppm). Each group was subdivided into eight replicates. Results showed interactions between GAAxT3-hormone. GAA diet significantly mitigated the negative effect of T3-hormone on serum total creatine kinase (CK), cardiac muscle (CK-MB), liver malondialdehyde (MDA) and superoxide dismutase (SOD), mitochondrial activities of cardiac muscle and liver histopathological lesion. In conclusion, GAA at a rate of 0.06% may have the potential to mitigate the negative effect of dietary T3-hormone but could not reduce the ascites mortality at such inclusion rate. HIGHLIGHTS GAA protected heart muscle. GAA mitigated the oxidative radicals in T3-hormone challenged birds. GAA modulated the mitochondrial activities in T3-hormone challenged birds.

Myorelaxation, respiratory depression and electrocardiographic changes caused by the administration of extract of açai (Euterpe oleracea Mart.) stone in rats.

The biological and pharmacological properties of natural polyphenols of the extract of Euterpe oleracea stone (EEOS) are associated with the central nervous system (CNS). To investigate the sedative and myorelaxant activity of EEOS in vivo, this study aimed to present the myorelaxant and sedative effects of EEOS in Wistar rats using spontaneous locomotor activity and motor electrophysiology. A total of 108 animals were used in the following experiments: a) behavioral tests (n = 27); b) electromyographic recordings of skeletal muscle (n = 27); c) respiratory muscle activity recordings (n = 27); d) cardiac muscle activity recordings (n = 27). The behavioral characteristics were measured according to the latency time of onset, the transient loss of posture reflex and maximum muscle relaxation. Electrodes were implanted in the gastrocnemius muscle and in the tenth intercostal space for electromyographic (EMG) signal capture to record muscle contraction, and in the D2 lead for electrocardiogram acquisition. After using the 300 mg/kg dose of EEOS intraperitoneally, a myorelaxant activity exhibited a lower frequency of contractility with an amplitude pattern of low and short duration at gastrocnemius muscle and intercostal muscle, which clearly describes a myorelaxant activity and changes in cardiac activity. The present report is so far the first study to demonstrate the myorelaxant activity of this extract, indicating an alternative route for açai stone valorization and its application in pharmaceutical fields.

Cardiac muscle activation; the role of length dependent activation and the novel myosin activator danicamtiv

Abstract B: Alterations in the length dependent activation (LDA) of left ventricular (LV) muscle fibres, the mechanistic driver of the Frank-Starling Law of the heart, are thought to mediate impaired LV function in heart failure (HF). However, little is known about LDA's role in the left atria (LA). Given the concomitant presence of LA dysfunction in HF, the purpose of this study was to compare/assess LDA on LA and LV muscle, as well to evaluate the effects of a novel small-molecule acto-myosin activator, danicamtiv (formerly known as MYK-491). M: LA and LV myofibrils from healthy Yucatan mini-pigs were used to determine biomechanical function with ATPase assays, with and without danicamtiv. Skinned LA and LV muscle fibres from these same animals were prepared to study contractile force, Ca2+ sensitivity, active/passive stiffness, and responsiveness to increasing sarcomere length (2.0 and 2.3). These parameters were also evaluated in the presence of danicamtiv. R: LA myofibrils had significantly faster ATPase and Pi release rates compared to LV, consistent with their respective alpha/beta myosin-isoform content. Despite increased metabolic rate, LA fibres generated less maximum isometric tension (12.3±1.96 vs 35.2±3.07 mN/mm2) and had a lower pCa50 than LV fibres (5.66±0.02 vs 5.82±0.02), demonstrating reduced force-generating capability and Ca2+ sensitivity. Stretch of LV fibres resulted in a gain in tension over a range of pCas (pCa6.4, 6.2, 6.0, and 5.8, all p&amp;lt;0.05). However, in LA, LDA-induced gain was not significant at submaximal pCas (pCa6.4, 6.2, 6.0, all p&amp;gt;0.05). Stretch had no effect on active stiffness, but increased passive stiffness in both muscle types. Stretched LA fibres showed grater passive stiffness compared to LV (196.7±21.5 vs. 138.5±22.3 kN/m3). A stiffer myofilament would in part explain the blunted ability of the LA to generate force in response to stretch. Danicamtiv activated both LA and LV myofibrils, increasing ATPase and Pi release rates, and increased Ca2+ sensitivity in fibres (ΔpCa; LV, 0.320±0.032; LA, 0.149±0.028, p&amp;lt;0.01). Unlike with stretch, danicamtiv had no effect on passive stiffness, yet altered the active stiffness/tension (S/T) relationship in both fiber types, but, differentially. In LV, danicamtiv increased the number of available heads (Y0; 129.9±26.3 vs 10.1±4.2 kN/m3, p&amp;lt;0.001) with no significant effect on slope. In the LA, Y0 was largely unchanged with a significant increase in the slope of the S/T relationship (slope: 34.0±2.9 vs. 20.0±1.9 au, p&amp;lt;0.01). Together, these data suggest an increased number of force producing cross-bridges, without altering passive stiffness. C: These data confirm the functional differences between LA and LV muscle fibres and demonstrate a blunted ability of LA tissue to recruit force when stretched. The acto-myosin activator danicamtiv increased biochemical activity, Ca2+ sensitivity, and the active S/T relationship in LA and LV fibres without altering passive strain. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): MyoKardia Inc.

A miniaturized endocardial electromagnetic energy harvester for leadless cardiac pacemakers.

Life expectancy of contemporary cardiac pacemakers is limited due to the use of an internal primary battery. Repeated device replacement interventions are necessary, which leads to an elevated risk for patients and an increase of health care costs. The aim of our study is to investigate the feasibility of powering an endocardial pacemaker by converting a minimal amount of the heart’s kinetic energy into electric energy. The intrinsic cardiac muscle activity makes it an ideal candidate as continuous source of energy for endocardial pacemakers. For this reason, we developed a prototype able to generate enough power to supply a pacing circuit at different heart rates. The prototype consists of a mass imbalance that drives an electromagnetic generator while oscillating. We developed a mathematical model to estimate the amount of energy harvested from the right ventricle. Finally, the implemented prototype was successfully tested during in-vitro and in-vivo experiments.