Force Of Contraction Research Articles

Glucagon Can Increase Force of Contraction via Glucagon Receptors in the Isolated Human Atrium

Glucagon can increase the force of contraction (FOC) in, for example, canine hearts. Currently, whether glucagon can also increase the FOC via cAMP-increasing receptors in the human atrium is controversial discussed. Glucagon alone did not (up to 1 µM) raise the FOC in human right atrial preparations (HAP). Only in the additional presence of the phosphodiesterase (PDE) 3 inhibitor cilostamide (1 µM) or 1 nM isoprenaline did glucagon raise the FOC, starting at 1 µM. The positive inotropic effects of glucagon in HAP were attenuated by a glucagon receptor antagonist (1 µM SC203972), but not by 100 nM exendin(9-39), a glucagon-like peptide-1 receptor (GLP-1R) antagonist. Glucagon (in the presence of cilostamide) demonstrated a reduced efficacy in elevating the FOC in HAP when compared with isoprenaline. In contrast to glucagon, exenatide alone, a GLP-1R agonist, starting at 1 nM, increased the FOC and was more potent and effective than glucagon in raising the FOC in HAP. The effects of exenatide on the FOC were attenuated by exendin(9-39). Hence, glucagon and GLP-1R agonists act functionally via different receptors in the human right atrium. Clinically, these data suggest that endogenous or exogenous glucagon can stimulate glucagon receptors in the human atrium, but only in the presence of PDE inhibitors.

Negligible contribution of body density to in-water vertical jump performance in elite male water polo players.

The aim of this study was to investigate the associations among in-water vertical jump and various dry-land physical measures by taking the law of Archimedes into consideration, and by normalizing the dry-land measures both to body density and body mass. Seventeen elite water polo players from Hungarian first league were tested for dry-land counter movement and squat jump mechanical impulse, isometric squat force, and in-water vertical jump height. Body density was estimated by anthropometric measurements. Body density alone did not influence in-water vertical jump height. Both the impulse of counter movement jump normalized to body mass (9.42±0.86 N·s/kg) and impulse of counter movement jump normalized to body density (773.92±109.68 N·s/kg/g/cm3) correlated with the in water vertical jump height (69.37±6.12 cm) (p≤0.05), but the magnitudes of the correlation coefficients 0.49 vs. 0.50 were not statistically different (p = 0.480, z = 0.04). Neither the impulse of squat jump normalized to body mass (7.07±0.59 N·s/kg) nor impulse of squat jump normalized to body density (577.87±89.16 N·s/kg/g/cm3) correlated with the in water vertical jump height (both p>0.05). The correlation between the force of the maximum voluntary isometric contraction normalized to body density (1052.13±244.65 N/kg/g/cm3) and the in water vertical jump height only approached the level of significance (p = 0.077). We concluded that dry-land reactive strength determines the ability to jump out of water, but players' body density does not seem to contribute to jump height.

Using Transcranial Magnetic Nerve Stimulation to Differentiate Motor and Sensory Fascicles in a Mixed Nerve: Experimental Rat Study.

Accurately matching the correct fascicles in a ruptured mixed nerve is critical for functional recovery. This study investigates the use of transcranial magnetic stimulation (TMS) to differentiate motor and sensory fascicles in a mixed nerve. In all 40 rats, the median nerve in the left upper arm was evenly split into three segments. The rats were separated into two groups. In Group A (20 rats), the segment with the highest amplitude during TMS was selected as the motor neurotizer and transferred to the musculocutaneous nerve. In Group B (20 rats), only the medial one-third segment was selected and transferred without using TMS. The results were compared using grooming tests, nerve electrophysiological studies, muscle tetanus contraction force measurements, muscle weight, and axon counts at 16 weeks. The grooming test showed that Group A performed significantly better than Group B at 12 and 16 weeks postoperatively. Tetanic muscle contraction force measurements also revealed that Group A had significantly better outcomes than Group B. However, electrophysiological testing, muscle weight, and axon counts showed no significant differences between the two groups. This study suggests that TMS can be used to distinguish motor fascicles from sensory fascicles in a mixed nerve. It is desirable to apply this technique intraoperatively to differentiate motor and sensory fascicles for appropriate nerve matching and to select the motor fascicles as a motor neurotizer for functioning free muscle innervation in human mixed nerve injury.

Microstring-engineered tension tissues: a novel platform for replicating tissue mechanics and advancing mechanobiology.

Replicating the mechanical tension of natural tissues is essential for maintaining organ function and stability, posing a central challenge in tissue engineering and regenerative medicine. Existing methods for constructing tension tissues often encounter limitations in flexibility, scalability, or cost-effectiveness. This study introduces a novel approach to fabricating soft microstring chips using a sacrificial template method, which is easy to operate, offers controlled preparation, and is cost-effective. Through experimental testing and finite element simulations, we validated and characterized the relationship between microstring deformation, tissue width, and the reaction force exerted by the microstrings, enabling precise measurement of tissue contraction force. We successfully constructed microstring-engineered tension tissues (METTs) and demonstrated that they exhibit a significant mechanical response to profibrotic factors. Additionally, we conceptually demonstrated the application of microstring chips in constructing METTs with asymmetric, biomimetic constraints. The results indicate effective construction and regulation of METTs, providing a robust platform for mechanobiology and biomedical research.

High-Density Surface Electromyography Feedback Enhances Fibularis Longus Recruitment in Chronic Ankle Instability.

This study aimed to determine whether individuals with chronic ankle instability (CAI) can activate the fibularis longus compartments with high-density surface electromyography (HD-sEMG) biofeedback to the same extent as those without CAI, and to analyze the effect of ankle position on compartment activation in individuals with CAI using HD-sEMG feedback. There were 16 volunteers per group (CAI and No-CAI). The sEMG amplitude at each compartment (anterior and posterior) and the barycenter of the spatial sEMG amplitude distribution of the fibularis longus were recorded during eversion in neutral and plantar flexion positions at 30% and 70% of maximum voluntary contraction force, both with and without visual feedback on the spatial sEMG amplitude distribution. sEMG amplitude of the posterior compartment of the fibularis longus in the CAI group trained with HD-sEMG feedback during eversion at 70% maximum voluntary contraction (in plantar flexion) was significantly higher than without HD-sEMG feedback (95% CI = 3.75-34.50% root mean square) and was similar to the activation of the No-CAI group (95% CI = -14.34% to 34.20% root mean square). Furthermore, individuals with CAI who underwent training with HD-sEMG feedback in plantar flexion exhibited a posterior displacement of the barycenter (95% CI = 0.56-2.84 mm). Utilizing HD-sEMG feedback during eversion in plantar flexion position increases activation of the fibularis longus posterior compartment in individuals with CAI to the same extent as healthy people. HD-sEMG-based topographic maps can serve as effective feedback training to restore motor control of the ankle. Long-term efficacy for improving motor function requires investigation through longitudinal studies.

Stimulation of histamine H1-receptors produces a positive inotropic effect in the human atrium.

There is a controversy whether histamine H1-receptor activation raises or lowers or does not affect contractility in the human heart. Therefore, we studied stimulation of H1-receptors in isolated electrically stimulated (one beat per second) human atrial preparations (HAP). For comparison, we measured force of contraction in left atrial preparations (LA) from mice with overexpression of the histamine H1-receptor in the heart (H1-TG). We detected the messenger ribonucleic acid (mRNA) expression of human histamine H1-receptors in HAP. In LA from H1-TG, each cumulatively applied concentration of histamine and a dual H1/H2-agonist called 2-(2-thiazolyl)-ethylamine (ThEA) caused a time-dependent initial negative inotropic effect followed over time by a lasting positive inotropic effect. Both effects were concentration-dependent in LA from H1-TG. After 100 µM cimetidine, 10 µM histamine exercised a positive inotropic effect in HAP that was diminished by 10 µM mepyramine, an H1-receptor antagonist. The concentrations of mepyramine and cimetidine used here are based on the work of others and our own work (e.g., Guo et al.J Cardiovasc Pharmacol. 6:1210-5 1984, Rayo Abella et al. J Pharmacol Exp Ther. 389:174-185 2024). Similarly, we observed that ThEA (10 µM, 30 µM, 100 µM cumulatively applied) induced a concentration- and time-dependent positive inotropic effect in HAP. In HAP, we detected never negative inotropic effects to either histamine or ThEA. The positive inotropic effects to ThEA in HAP were reduced by mepyramine. The positive inotropic effects of ThEA in LA from H1-TG and in HAP were not accompanied by reductions in the time of tension relaxation. We conclude that stimulation of histamine H1-receptors only increases and does not decrease force of contraction in the HAP in our patients.

Energy‐based characterization of polymer/particle interphase region as piled‐up equilibrated molecular layers: The impact of different distribution patterns of adsorption energy

AbstractIn this study, a novel energy‐based strategy was developed, based on equilibrating the adsorption and resistive energies, to investigate the physical/mechanical features of the polymer/particle interphase region. To this end, the interphase region was assumed to consist of a specific number of layers, with constant initial thickness, subjected to contraction force by the adsorbent. The distribution of the distance‐dependent adsorption energy inside the interphase was modeled according to linear, oval, exponential, and scaling‐based patterns. On the other hand, the values of resistive energies acting on each layer, including bulk and tensile energies, were estimated considering the equilibrated thickness of the bottom layers. The incorporation of the molecular features of the adsorbed polymer chains into the characterizing pattern of the adsorbing energy proved to considerably increase the related prediction accuracy. The validation process was performed by combining the devised strategy with a particularly developed mechanical model based on the concepts of Kolarik's approach and involving the impact of aggregation/agglomeration phenomenon. Comparing the analytical data with those elicited from the literature revealed that the exponential and scaling‐based patterns could provide reliable results (error <6%); however, oval and linear patterns considerably alleviated the accuracy of the mechanical model (error <17%).Highlights Characterizing the interphase based on energy equilibrium in the region. Representing different patterns of adsorption energy distribution in the interphase. Involving molecular characteristics of the adsorbed polymer chains on nanoparticles. High prediction accuracy while applying exponential and scaling‐based patterns. Designing a novel mechanical model to predict the tensile modulus of nanocomposite.

Regional differences in three-dimensional fiber organization, smooth muscle cell phenotype, and contractility in the pregnant mouse cervix.

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous contractions, distension had a minimal effect on contractility, and the upper cervix had forceful contractions in response to labor-inducing agents (oxytocin and prostaglandin E2). These findings identify regional differences in cervix contractility related to contractile SMC content and fiber organization, which could be targeted with diagnostic technologies and for therapeutic intervention.

Local Myoelectric Sensing During Human Colonic Tissue Perfusion.

Objectives: Anastomotic leakage (AL) is one of the most devastating complications after colorectal surgery. The verification of the adequate perfusion of the anastomosis is essential to ensuring anastomosis integrity following colonic resections. This study aimed to evaluate the efficacy of measuring the electrical activity of the colonic muscularis externa at an anastomosis site for perfusion analysis following colorectal surgery. Methods: Strips of human isolated colon were maintained in a horizontal tissue bath to record spontaneous contractions and myoelectric activity and spike potentials (using a bipolar electrode array for the wireless transmission of myoelectric data-the xBar system) from the circular muscle. Intraoperative myoelectric signal assessment was performed by placing the electrode array on the colon prior to and following mesenteric artery ligation, just prior to colonic resection. Results: In human isolated colon, the amplitude, duration, and frequency of contractions were inhibited during hypoxia by >80% for each measurement, compared to control values and time-matched oxygenated muscle. Intraoperative (N = 5; mean age, 64.8 years; range, 54-74 years; 60% females) myoelectric signal assessment revealed a decline in spike rate following arterial ligation, with a mean reduction of 112.64 to 51.13 spikes/min (p < 0.0008). No adverse events were observed during the study, and the device did not substantially alter the surgical procedure. Conclusions: The electrical and contraction force of the human colon was reduced by ischemia, both in vitro and in vivo. These preliminary findings also suggest the potential of the xBar system to measure such changes during intraoperative and possibly postoperative periods to predict the risk of anastomotic viability as a surrogate of evolving dehiscence.

Comparing the Effects of Collagen Hydrolysate and Dairy Protein on Recovery from Eccentric Exercise: A Double Blind, Placebo-Controlled Study.

Consuming collagen hydrolysate (CH) may improve symptoms of exercise-induced muscle damage (EIMD); however, its acute effects have not been compared to dairy protein (DP), the most commonly consumed form of protein supplement. Therefore, this study compared the effects of CH and DP on recovery from EIMD. Thirty-three males consumed either CH (n = 11) or DP (n = 11), containing 25 g of protein, or an isoenergetic placebo (n = 11) immediately post-exercise and once daily for three days. Indices of EIMD were measured before and 30 min and 24, 48, and 72 h after 30 min of downhill running on a -15% slope at 80% of VO2max speed. Downhill running induced significant EIMD, with time effects (all p < 0.001) for the delayed onset of muscle soreness (visual analogue scale), countermovement jump height, isometric midthigh pull force, maximal voluntary isometric contraction force, running economy, and biomarkers of muscle damage (creatine kinase) and inflammation (interleukin-6, high-sensitivity C-reactive protein). However, no group or interaction effects (all p > 0.05) were observed for any of the outcome measures. These findings suggest that the post-exercise consumption of CH or DP does not improve indices of EIMD during the acute recovery period in recreationally active males.

The effect of lysophosphatidic acid on myometrial contractility and the mRNA transcription of its receptors in the myometrium at different stages of endometrosis in mares

BackgroundEndometrosis (chronic degenerative endometritis) results in morphological changes in the equine endometrium and impairs its secretory function. However, the effect of this condition on the myometrium remains unclear. Lysophosphatidic acid (LPA) may affect female reproductive function and embryo transport by influencing uterine contractility through its receptors (LPARs). The objective of this study was to determine myometrial LPAR1–6 mRNA transcription, and the effects of LPA on myometrial contractions in mares with endometrosis during the mid-luteal and follicular phases of the estrous cycle.ResultsA reduction in myometrial LPAR1 mRNA transcription was observed in mares with endometrosis during the mid-luteal phase, in comparison to those with category I endometria (P < 0.05). While, upregulation of myometrial LPAR3 or LPAR6 mRNA transcription was observed in mares with category III or IIB endometria; respectively (P < 0.05). An increase in myometrial LPAR1, LPAR3 and LPAR5 mRNA transcription was observed during the follicular phase in mares with category IIA endometrium in comparison to their expression in category I endometrium (P < 0.05). During endometrosis progression LPA reduced the force of myometrial contractions in both phases of the estrous cycle (P < 0.05). However, in mares with category IIA endometrium during the follicular phase, LPA was found to increase the force of contraction of myometrial strips in comparison to mares with category I endometrium (P < 0.01).ConclusionIn the course of endometrosis in mares, a disruption in the myometrial mRNA transcription of LPARs has been observed. This is the first study to examine the impact of LPA on myometrial contractility at diffrent stage of endometrosis. However, it is essential to consider that multiple factors may contribute to this process. Alternations in contractile activity and changes in myometrial LPARs mRNA transcription may indicate impaired LPA-signaling mechanisms in equine myometrium during endometrosis.

Control of Tissue Strain Is Essential for Enhanced Dermal Innervation in the Three-Dimensional Skin Engineering.

Engineered skin models with sensory innervation are a growing and challenging field of research aimed at applications in regenerative medicine, biosensing, and drug screening. Researchers are attempting to fabricate innervated skin tissues using collagen sponges, cell culture inserts, and microfluidic devices to partially mimic the layered structure of the skin. However, innervation of the full-thickness skin model has not yet been achieved. Here, using the anchoring culture device we previously reported, which is a powerful tool to construct a full-thickness three-dimensional (3D) skin model with balanced tissue contraction forces, we drastically improved dermal layer innervation using a composite hydrogel of collagen and Matrigel (Coll:MG). To determine the preferable hydrogel matrix for neurite extension in the 3D skin construct, DRG neural spheroids were placed at the bottom of the dermal layer composed of various hydrogel scaffold, including type I collagen from different origins (dermis or tendon) and Coll:MG composite hydrogel with different compositions. We showed that the Coll:MG (2:1) composite hydrogel significantly increased vertical neurite extension in the dermal layer, concomitant with the reduced tissue shrinkage during the culture. In contrast, in the collagen-only hydrogel, neurite extension occurred mostly in the horizontal direction, and tissues sometimes detached from the anchors due to significant shrinkage, indicating that tissue shrinkage may affect the direction of neurite extension. To exemplify this idea, 3D skin constructed in the device was partially detached from the anchors to comply with the cell-induced tissue shrinkage and reduce the strain on the tissue. The data showed that the partial allowance of in-plane tissue strain remarkably increased vertical neurite extension compared to the control cultures. Collectively, our results strongly suggest that neurite extension angles can be modulated by adjusting the tissue strain during the culture. Our findings highlight the importance of controlling tissue strain for the advancement of an innervated skin model.

The N-Terminal Mutations of cMyBP-C Affect Calcium Regulation, Kinetics, and Force of Muscle Contraction.

The cardiac myosin binding protein-C (cMyBP-C) regulates cross-bridge formation and controls the duration of systole and diastole at the whole heart level. As known, mutations in cMyBP-C increase the cross-bridge number and rate of their cycling, hypercontractility, and myocardial hypertrophy. We investigated the effects of the mutations D75N and P161S of cMyBP-C related to hypertrophic cardiomyopathy on the mechanism of force generation in isolated slow skeletal muscle fibers. The mutation D75N slowed the kinetics of force development but did not affect the relaxation rate. The mutation P161S slowed both the relaxation and force development. The mutation D75N increased the calcium sensitivity of force, and the mutation P161S decreased it. The mutation D75N decreased the maximal isometric tension and increased the tension and stiffness at low calcium. Both mutations studied disrupt the calcium regulation of contractile force and affect the kinetics of its development and thus may impair cardiac diastolic function and cause myocardial hypertrophy.

Clozapine is a functional antagonist at cardiac human H2-histamine receptors.

Clozapine is an atypical antipsychotic (neuroleptic) drug. Clozapine binds to H2-histamine receptors in vitro. We wanted to test the hypothesis that clozapine might be a functional antagonist at human cardiac H2-histamine receptors. To that end, we studied isolated electrically stimulated left atrial preparations and spontaneously beating right atrial preparations from transgenic mice with cardiomyocyte-specific overexpression of the human H2-histamine receptor (H2-TG). For comparison, we used wild-type littermate mice (WT). Finally, we measured isometric force of contraction in isolated electrically stimulated muscle strips from the human right atrium (HAP) obtained from patients during bypass surgery. After pre-stimulation with histamine, clozapine (up to 10 µM) concentration and time dependently decreased beating rate in right atrial preparations from H2-TG. Clozapine concentration dependently 1, 3, and 10 µM decreased histamine-stimulated force of contraction in HAP. Clozapine (10 µM) decreased also the isoprenaline-stimulated force of contraction in HAP. In summary, clozapine can antagonize the function of H2-histamine and β-receptors in the human heart.

The effect of fatiguing muscle contractions on kicking performance in experienced soccer players

ABSTRACT The objective of this study was to clarify the effects of fatiguing muscle contractions of the m. quadriceps femoris on kicking abilities of experienced soccer players. 16 male professional (n = 5) and amateur players (n = 11) performed kicking tests in two conditions (fatigue and control) on separate days in a randomised crossover design. The fatiguing protocol performed with the kicking leg consisted of 5 sets of 10 maximal voluntary concentric and eccentric knee extensions. Maximal voluntary isometric contraction force (MVIC), 15 hz/50 hz stimulation force ratio (force ratio), and kicking abilities were assessed before and after completion of the fatiguing protocol or rest (control). The fatiguing protocol successfully induced fatigue of 14.0 ± 2.7% (mean ± SE) reduced MVIC and 14.0 ± 3.7% reduced force ratio while no reductions occurred in the control condition. Between group difference showed ball speed declined 2.1 ± 0.95% more following the fatigue protocol compared to control condition. On the control day shooting accuracy improved by 13.3 ± 5.6% and was numerically impaired on the intervention day by 1.0 ± 9.2%. Despite this, no significant between group difference was observed in shooting accuracy (p = 0.18). The study demonstrated that fatigue induced by prior muscle contractions impairs maximal shooting speed, but we observed no significant impairment of shooting accuracy.

Prostaglandin pathways in equine myometrium regulations: endometrosis progression.

Prostaglandins (PG) are important regulators of the myometrial contractility in mammals. Endometrosis, a condition characterized by morphological changes in the equine endometrium, also affects endometrial secretory function. However, it remains unclear whether and how endometrosis affects myometrial function. This study investigated: (i) mRNA transcription of genes encoding specific enzymes responsible for PG synthesis, such as prostaglandin-endoperoxide synthase (PTGS2), PGE2 synthase (PTGES), PGF2α synthase (PTGFS) and PG receptors: PGE2 receptors (PTGER1- 4), and PGF2α receptor (PTGFS) in equine myometrium and, (ii) the effects of PGE2 and PGF2α on myometrial contractile activity, during endometrosis in mares. The myometria used in experiments 1 and 2 were collected from mares in the mid-luteal (n = 23) and follicular (n = 20) phases of the estrous cycle, according to the histological classification of the endometrium (Kenney and Doig categories I, IIA, IIB, and III). In experiment 1, changes in mRNA transcription of PG synthase or PG receptors in the myometrium during the course of endometrosis were determined using qPCR. During the mid-luteal phase, myometrial mRNA transcription of PTGES increased in mares with endometrial category IIB compared to category I. However, myometrial mRNA transcription of PTGER1 decreased during the progression of endometrosis compared to category I. During the follicular phase, mRNA transcription of PTGER1 and PTGER2 increased in mares with endometrial categories III or IIA, respectively. In addition, mRNA transcription of PTGFS increased in mares with endometrium category IIA compared to category I. In experiment 2, the force of myometrial contractions was measured using an isometric concentration transducer. In the follicular phase, PGE2 decreased the force of contractions in mares with endometrial categories IIA, IIB, and III compared to the respective control groups. Prostaglandin F2α increased the force of myometrial contractions in mares with category IIA endometrium, whereas it decreased in category IIB compared to the respective control groups. We concluded that in the progression of endometrosis there are changes in the myometrial transcription of mRNA encoding PG synthases and receptors, particularly PTGER1 and PTGER2. Mares with endometrosis had abnormal myometrial contractile responses to PG. These findings suggest that myometrial function may be compromised during the progression of endometrosis.

The ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status.

Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle fiber size, contraction force, and exercise capacity, along with defects in calcium handling within fast-twitch muscle fibers. However, the role of the ARK2N gene in human muscle physiology, and particularly in athletic populations, remains poorly understood. The aim of this study was threefold: (a) to compare ARK2N gene expression between power and endurance athletes; (b) to analyze the relationship between ARK2N gene expression and muscle fiber composition; and (c) to investigate the association between the functional variant of the ARK2N gene, muscle fiber size, and sport-related phenotypes. We found that ARK2N gene expression was significantly higher in power athletes compared to endurance athletes (p = 0.042) and was positively associated with the proportion of oxidative fast-twitch (type IIA) muscle fibers in untrained subjects (p = 0.017, adjusted for age and sex). Additionally, we observed that the ARK2N rs6507691 T allele, which predicts high ARK2N gene expression (p = 3.8 × 10-12), was associated with a greater cross-sectional area of fast-twitch muscle fibers in strength athletes (p = 0.015) and was over-represented in world-class strength athletes (38.6%; OR = 2.2, p = 0.023) and wrestlers (33.8%; OR = 1.8, p = 0.044) compared to controls (22.0%). In conclusion, ARK2N appears to be a gene specific to oxidative fast-twitch myofibers, with its functional variant being associated with muscle fiber size and strength-athlete status.

The Heart is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect.

The Frank-Starling law and Anrep effect describe two intrinsic mechanisms that regulate contraction force in the heart. Based on recent advancements and the historical literature, we propose new perspectives and address several critical issues in this review. (a) The Frank-Starling mechanism and Anrep effect are dynamically linked and act synergistically. (b) An open question is how cardiomyocytes sense mechanical load and transduce to biochemical signals (called mechano-chemo-transduction or MCT) to regulate contraction in response to load changes. (c) One research focus is to identify various mechanosensors and decipher their downstream MCT pathways. (d) Innovative experimental techniques engage different mechanosensors that detect different local strain and stress in the cell architecture. (e) Closed-loop MCT feedback in the dynamic excitation-Ca2+ signaling-contraction system enables autoregulation of contraction in response to physiological load changes. ( f ) However, pathological overload such as volume and pressure overload lead to excessive MCT-Ca2+ gain, cardiac remodeling, and heart diseases.

C60 fullerene helps restore muscle soleus contraction dynamics after achillotomy-induced atrophy

Background. The search for new means that would effectively influence the pathological consequences of muscle immobilization is an urgent priority request of modern biomedicine. Previously, the positive effect of water-soluble C60 fullerenes, as strong antioxidants, was established on the background of muscle ischemia, mechanical muscle injury, and other muscle dysfunctions. These carbon nanoparticles have been shown to reliably protect muscle tissue from damage caused by oxidative stress. Materials and Methods. The biomechanical parameters of muscle soleus contraction of rats were studied by simulating non-functioning hind limbs using a clinical model – a rupture of the Achilles tendon (achillotomy). Muscle contraction parameters, namely the maximum contraction force and muscle force impulse, were determined on the 15th, 30th, and 45th days after initiation of atrophy using tensometry. As a therapeutic nanoagent, daily oral administration of C60 fullerene aqueous solution at a dose of 1 mg/kg was used throughout the experiment. Results. Previous registration of muscle soleus contraction force when applying 1 Hz stimulation lasting 1800 s with three pools revealed a decrease in maximal force responses after 15, 30, and 45 days of atrophy. The 45th day after atrophy is considered to be the limit for the fastest recovery of the muscle after immobilization, the further process takes place over several months. In all the tests performed, the therapeutic admini­stration of water-soluble C60 fullerenes (dose 1 mg/kg) an increase in biomechanical parameters was recorded (maximum force of contraction – the change in the form of the “stimulation – force contraction” dependence is a consequence of the development of the pathological process in muscle and the muscle force impulse, which allows assessing the performance of the muscular system after a long-term immobilization), by approximately 29–49±2 % for the maximum contraction force and by 21–37±2 % for the muscle force impulse compared to the atrophy group for 15, 30 and 45 days. Conclusions. The obtained results indicate the prospects of using water-soluble C60 fullerenes, which can alleviate pathological conditions in the muscular system that arise from skeletal muscle atrophy due to immobilization.

The effects of inorganic nitrate supplementation on muscular power and endurance across the menstrual cycle.

Oral inorganic nitrate ([Formula: see text]) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power in males and females, although data in females are limited. Estrogen increases NO bioavailability and fluctuates throughout the menstrual cycle, with low levels in the early follicular (EF) phase and peaking during the late follicular (LF) phase. The purpose of the present study was to examine the effects of [Formula: see text] supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance, and recovery from fatigue in healthy young females during the EF and LF phases of the menstrual cycle. Ten eumenorrheic females were tested in a double-blinded, randomized, placebo-controlled design. Participants consumed ∼13 mmol [Formula: see text], in the form of 140 mL beetroot juice (BRJ), or an identical [Formula: see text]-depleted placebo (PL), for ∼5 days prior to visits and 2 h prior to testing. Plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition (P < 0.05). Although isokinetic peak power was unchanged, calculated maximal power (Pmax) and maximal velocity (Vmax) were significantly worsened in the BRJ treatment independent of the menstrual cycle phase (P = 0.02 and 0.03, respectively). Muscular endurance, MVIC, and fatigue recovery were unaltered by BRJ or the menstrual cycle. These data indicate that [Formula: see text] supplementation decreased maximal power and velocity in females and suggest that the benefits of [Formula: see text] supplementation previously found in males may not extend to young females.NEW & NOTEWORTHY Recent data have suggested that inorganic nitrate ([Formula: see text]) supplementation may benefit males, however, females may experience worsened endurance capacity independent of menstrual cycle phase. This study revealed neither [Formula: see text] supplementation nor the follicular phase of the menstrual cycle influenced maximal isometric voluntary contraction or endurance capacity in healthy, young, naturally menstruating females, whereas [Formula: see text] supplementation significantly worsened estimated peak power (Pmax) and velocity (Vmax) independent of the menstrual cycle phase.