Shortening Velocity Research Articles

Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction

Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/− recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/− mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/− mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/− mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.

A comparison of thermal sensitivities of wing muscle contractile properties from a temperate and tropical bat species.

Endotherms experience temperature variation among body regions, or regional heterothermy, despite maintaining high core body temperatures. Bat forelimbs are elongated to function as wings, which makes them vulnerable to heat loss and exaggerates regional heterothermy. A tropical bat species, Carollia perspicillata, flies with distal wing muscles that are substantially (>10°C) cooler than proximal wing muscles and significantly less temperature sensitive. We hypothesized that the difference between proximal and distal wing muscles would be even more extreme in a temperate bat species that is capable of flight at variable environmental temperatures. We measured the contractile properties of the proximal pectoralis muscle and distal extensor carpi radialis muscle at a range of temperatures in the big brown bat, Eptesicus fuscus, and compared their thermal dependence with that of the same muscles in C. perspicillata. We found that, overall, temperature sensitivities between species were remarkably similar. The sole exception was the shortening velocity of the pectoralis muscle in E. fuscus, which was less temperature sensitive than in C. perspicillata. This decreased temperature sensitivity in a proximal muscle runs counter to our prediction. We suggest that the relative lability of body temperature in E. fuscus may make better pectoralis function at low temperatures advantageous.

The influence of longitudinal muscle fascicle growth on mechanical function.

Skeletal muscle has the remarkable ability to remodel and adapt, such as the increase in serial sarcomere number (SSN) or fascicle length (FL) observed after overstretching a muscle. This type of remodeling is termed longitudinal muscle fascicle growth, and its impact on biomechanical function has been of interest since the 1960s due to its clinical applications in muscle strain injury, muscle spasticity, and sarcopenia. Despite simplified hypotheses on how longitudinal muscle fascicle growth might influence mechanical function, existing literature presents conflicting results partly due to a breadth of methodologies. The purpose of this review is to outline what is currently known about the influence of longitudinal muscle fascicle growth on mechanical function and suggest future directions to address current knowledge gaps and methodological limitations. Various interventions indicate longitudinal muscle fascicle growth can increase the optimal muscle length for active force, but whether the whole force-length relationship widens has been less investigated. Future research should also explore the ability for longitudinal fascicle growth to broaden the torque-angle relationship's plateau region, and the relation to increased force during shortening. Without a concurrent increase in intramuscular collagen, longitudinal muscle fascicle growth also reduces passive tension at long muscle lengths; further research is required to understand whether this translates to increased joint range of motion. Finally, some evidence suggests longitudinal fascicle growth can increase maximum shortening velocity and peak isotonic power; however, there has yet to be direct assessment of these measures in a neurologically intact model of longitudinal muscle fascicle growth.

Force and Shortening Velocity are Reduced in 24‐month Fischer 344 Rats

The diaphragm muscle (DIAm) shortens and produces force to generate negative intra‐thoracic pressure for airflow into the lungs and positive intra‐abdominal pressure for airway clearance and expulsive behaviors. Breathing is a low force repetitive behavior that requires recruitment of fatigue resistant type I and IIa DIAm fibers. In contrast, short duration airway clearance behaviors are infrequent and associated with greater DIAm force that require the additional recruitment of more fatigable type IIx/IIb fibers. Aging is characterized by selective atrophy of type IIx/IIb DIAm fibers and decreased specific force, i.e., sarcopenia. Older individuals are able to breathe without difficulty but have trouble with some higher force airway clearance behaviors of the DIAm such as coughing and sneezing. In 6‐ and 24‐month Fischer 344 rats (n=6 per group), DIAm strips were dissected from the mid‐costal region, mounted in a tissue chamber filled with Rees‐Simpson solution, and stimulated directly to measure maximum isometric specific force (Po) and maximum shortening velocity (Vmax) using a Cambridge dual‐mode length‐force servo controller (model 300B). In addition, power fatigue was assessed during repetitive isovelocity (30%Vmax) contractions evoked by 75 Hz in 400‐ms‐duration stimulus trains repeated for a 2‐min period. Additional muscle segments were rapidly frozen at optimal sarcomere length in melting isopentane, and transverse muscle fiber sections were cut at 10 µm thickness for determination of muscle fiber type (based on myosin heavy chain immunoreactivity) and fiber cross‐sectional areas. The relationship between force (load) and shortening velocity was determined using the Hill equation. Aging significantly reduced maximum isometric force, maximum shortening velocity, and maximum power output of the DIAm in older rats. The reduction in power during repetitive isovelocity shortening was reduced in older rats, but the residual power output after 2 min stimulation was comparable between young and old rats. These changes in mechanical and fatigue properties were consistent with the selective atrophy of type IIx/IIb DIAm fibers and reflected the sustained output of type I and IIa DIAm fibers, which are recruited for essential breathing behaviors.

Cumulative effects of H+ and Pi on peak power of skeletal muscle fibers from young and older adults

The cellular mechanisms for the age‐related loss in muscle power output and increased fatigability during dynamic contractions remain unresolved. We recently observed that the depressive effects of fatiguing levels of acidosis (H+: pH 6.2) and inorganic phosphate (Pi: 30 mM) did not differ in muscle fibers from young compared with old men. However, the effects of these metabolites may have been saturated in the severe fatigue‐mimicking condition, potentially masking any age differences in the sensitivity of the cross‐bridge to these metabolites. Therefore, in this study we compared the contractile mechanics of myofibers (n = 327) from the vastus lateralis of 13 young (20‐32 years, 7 women) and 12 older adults (70‐90 years, 6 women) in conditions mimicking quiescent muscle and a range of fatiguing levels of acidosis (pH 6.8, 6.6, 6.2) and Pi(12, 20, 30 mM). The knee extensors of the older adults demonstrated hallmark signs of aging muscle including 19% lower thigh lean mass, 60% lower absolute power output, and ~1.8‐fold greater fatigability compared with young. Single fiber force, shortening velocity, and power decreased progressively with increasing concentrations of H+ and Pi; however, there were no age or sex differences in the depressive effects of these metabolites in any of the fatigue‐mimicking conditions. The cross‐sectional area of the fast fibers was 41% smaller in older compared with young adults, which corresponded with lower absolute fiber power. In contrast, there were no differences in fast fiber size‐specific power, indicating the age‐related decline in absolute fiber power was explained entirely by the differences in fiber size. Estimates of the amount of fast muscle in the thigh were associated with age‐related differences in whole‐muscle power output (r=0.78). These data suggest that the age‐related loss in whole‐muscle power output is primarily determined by the atrophy of fast fibers for both men and women, but that the age‐related increase in fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi.

RPI‐194 is a Novel Troponin Activator that Increases the Calcium Sensitivity of Striated Muscle Contraction

IntroductionSystolic heart failure is a cardiac disease in which the contractile function of heart muscle becomes weakened and unable to pump blood with adequate force. As of yet, no existing positive inotrope is able to lower the mortality rate in systolic heart failure. Cardiac troponin complex (cTn) is a trimeric complex consisting of troponin C (cTnC), troponin I (cTnI) and troponin T (cTnT). cTnC regulates blood supply to the heart by turning muscle contraction on and off in a calcium‐dependent manner. More precisely, the regulatory N‐domain of cTnC (cNTnC) binds the switch region of cTnI to activate contraction. Drug‐like molecules need to bind to this cNTnC‐cTnI switch region interface and modulate the pumping activity of the heart. Our objective was to identify a small molecule that has the ability to stabilize the activated conformation of cTn by binding to this interface and thereby enhance cardiac muscle contraction.HypothesisA cardiac troponin activator could potentially compensate the impaired contractile function of the heart in the treatment of systolic heart failureMethodsA total of 47 new compounds were designed using existing knowledge of calcium sensitizers. The compounds were screened against a recombinantly purified cNTnC‐cTnI chimeric construct, named gChimera, using nuclear magnetic resonance and fluorescence spectroscopy. We identified a novel small molecule cardiac troponin activator, RPI‐194, and measured its binding affinity to recombinantly purified cNTnC and gChimera. We also investigated the activity of RPI‐194 in rat skinned cardiac muscle trabeculae, isolated mouse cardiomyocytes, and isolated working mouse hearts. RPI‐194 activity was also tested in skinned skeletal muscle fibers from rats as both cardiac and slow skeletal muscle share the same isoform of cTnC.ResultsWe demonstrated that a small molecule troponin activator RPI‐194 binds to gChimera with a KD of 12‐24 µM and is able to stabilize activated cTn. It also slowed down the rate of calcium release from reconstituted cTn. RPI‐194 showed increasing calcium sensitivity of isometric contraction in skinned cardiac muscle trabeculae, as well as in slow and fast skeletal muscle fibers, suggesting it to be a calcium sensitizer, with cross‐reactivity within striated muscle. Contrarily, RPI‐194 was unable to slow down calcium release from isolated cNTnC. It also reduced the velocity of unloaded shortening in skeletal muscle fibers, suggesting that it slows the rate of actin‐myosin cross‐bridging, although no effect on myosin ATPase activity was found. RPI‐194 decreased the velocity and amplitude of contractions in isolated cardiomyocytes but contractility was preserved in isolated working hearts.ConclusionsRPI‐194 is a small molecule troponin activator that acts as a calcium sensitizer in striated muscle. Because of the isoform sharing of cTnC in cardiac and slow skeletal muscle, it is nearly impossible to develop a cardiac‐specific troponin activator. Whole animal model studies are needed to determine the impact of RPI‐194 on the different striated muscle types and whether this would be acceptable for therapeutic intervention.

Exercise Preconditioning Alters Markers of Cellular Senescence and Prevents DOX‐Induced Cardiorespiratory Dysfunction

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however its clinical use is limited due to cardiorespiratory complications, including the development of dyspnea, exercise intolerance, and cardiomyopathy. While the mechanisms responsible for DOX‐induced cardiorespiratory dysfunction remain unclear, evidence indicates that DOX administration causes DNA damage and promotes oxidative stress‐induced cellular senescence. Factors shown to contribute to DOX‐induced cellular senescence include cell cycle arrest, driven by signaling through the p16INK4a/Rb and p21/p53 pathways, impaired mitochondrial function, upregulation of pro‐survival pathways, increased lysosomal mass, and expression of the proinflammatory senescence‐associated secretory phenotype (SASP). In contrast, exercise has been shown to prevent cellular senescence in several tissues, leading to the hypothesis that endurance exercise preconditioning is sufficient to prevent senescence induced in the heart and diaphragm muscle following DOX chemotherapy treatment. To determine the relationship between DOX‐induced cardiorespiratory impairment, exercise preconditioning and the impact of accelerated cellular senescence, female Sprague‐Dawley rats underwent two weeks of endurance exercise training (treadmill running, 5 days/week, 60 min/day, 30m/min, 0% grade) before receiving a bolus dose of DOX (20mg/kg IP) or saline treatment. Functional measures were evaluated 48 hours after DOX or saline administration, followed by tissue collection for subsequent analysis of cellular senescence markers. Our results revealed that exercise preconditioning prior to DOX administration prevented diastolic and systolic dysfunction in the heart, with marked improvements in fractional shortening, myocardial performance index, and posterior wall shortening velocity compared to sedentary DOX‐treated animals. DOX‐induced weight loss, reduction in grip strength, and diaphragm weakness were partially rescued with exercise as well, with diaphragm specific force production preserved at frequencies of 60‐160Hz. Finally, both exercise and DOX appear to alter expression of proteins associated with the senescent phenotype in the heart and diaphragm. Therefore, the protective effects of exercise against DOX cardiorespiratory dysfunction may be related to changes in muscle cellular senescence.

The Relationships Between 25-Hydroxyvitamin D and Echocardiographic Parameters in Female Basketball Players.

This study was undertaken to (1) describe the cardiac structure and function and (2) to quantify the relationships between 25-hydroxyvitamin D [25(OH)D] and echocardiographic parameters in female basketball players. A cross-sectional experimental design. Controlled laboratory setting. Professional, female basketball players (n = 18). 25(OH)D and echocardiographic screening at the midpoint of the in-season phase, over a 2-week period in late Fall. 25(OH)D and echocardiographic parameters. A high prevalence of vitamin D insufficiency was observed in the female players examined (77.8%), with most also displaying eccentric cardiac hypertrophy (77.8%). Nonsignificant, moderate correlations were found between 25(OH)D and structural echocardiographic parameters, including left atrium diameter (r = 0.34, P = 0.16), left ventricular (LV) end-systolic diameter (r = -0.46, P = 0.06), posterior wall thickness (r = 0.36, P = 0.14), LV mass (r = 0.30, P = 0.23), and LV index (r = 0.33, P = 0.18). Significant, large correlations were found between 25(OH)D and echocardiographic parameters indicative of systolic function, including LV ejection fraction (r = 0.59, P = 0.01), fractional shortening (r = 0.59, P = 0.01), and peak systolic mitral tissue velocity (r = 0.51, P = 0.003). Similarly, a significant, large correlation was found between 25(OH)D and diastolic function as indicated by mitral valve inflow deceleration time (r = 0.51, P = 0.03). Our findings suggest the importance of female basketball players maintaining 25(OH)D concentration, given its possible physiological benefits on cardiac structure and function.

Live-Cell Imaging of the Contractile Velocity and Transient Intracellular Ca2+ Fluctuations in Human Stem Cell-Derived Cardiomyocytes.

Live-cell imaging techniques are essential for acquiring vital physiological and pathophysiological knowledge to understand and treat heart disease. For live-cell imaging of transient alterations of [Ca2+]i in human cardiomyocytes, we engineered human-induced pluripotent stem cells carrying a genetically-encoded Ca2+-indicator (GECI). To monitor sarcomere shortening and relaxation in cardiomyocytes in real-time, we generated a α-cardiac actinin (ACTN2)-copepod (cop) green fluorescent protein (GFP+)-human-induced pluripotent stem cell line by using the CRISPR-Cas9 and a homology directed recombination approach. The engineered human-induced pluripotent stem cells were differentiated in transgenic GECI-enhanced GFP+-cardiomyocytes and ACTN2-copGFP+-cardiomyocytes, allowing real-time imaging of [Ca2+]i transients and live recordings of the sarcomere shortening velocity of ACTN2-copGFP+-cardiomyocytes. We developed a video analysis software tool to quantify various parameters of sarcoplasmic Ca2+ fluctuations recorded during contraction of cardiomyocytes and to calculate the contraction velocity of cardiomyocytes in the presence and absence of different drugs affecting cardiac function. Our cellular and software tool not only proved the positive and negative inotropic and lusitropic effects of the tested cardioactive drugs but also quantified the expected effects precisely. Our platform will offer a human-relevant in vitro alternative for high-throughput drug screenings, as well as a model to explore the underlying mechanisms of cardiac diseases.

Ventilation asymmetry, diaphragmatic mobility and exercise capacity in men with traumatic brachial plexus injury

ObjectiveTo investigate the repercussions of traumatic brachial plexus injury (TBPI) on diaphragmatic mobility and exercise capacity, compartmental volume changes, as well as volume contribution of each hemithorax and ventilation asymmetry during different respiratory maneuvers, and compare with healthy individuals. The velocity of shortening of the diaphragm, inspiratory, and expiratory muscles were also assessed. ParticipantsThe cross-sectional study was conducted with 40 male individuals (20 with TBPI who have not undergone nerve transfer surgery [mean age 30.1 ± 5.3] and 20 healthy paired by age and body mass index). Only patients with C8-T1 root avulsion were studied. Main outcomeCompartmental and hemithoracic volumes, as well as asymmetry between the affected and unaffected sides were assessed using optoelectronic plethysmography. The 6 minute walking test was performed to evaluate exercise capacity, while diaphragm mobility was assessed during quiet breathing (QB) using an ultrasound device. ResultsTBPI patients with mean lesion time of 174 ± 45.24 days showed a decreased pulmonary function, respiratory muscle strength, exercise capacity, and diaphragm mobility (all p < .001) compared with healthy. The pulmonary ribcage compartment of the affected side was the main contributor to the reduction in volume during inspiratory capacity, vital capacity, and inspiratory load imposition (all p < .05). This compartment also exhibited a higher ventilation asymmetry with reduced shortening velocity of the inspiratory ribcage muscles. ConclusionCompared with healthy, TBPI patients who have not undergone nerve transfer surgery present low exercise capacity and diaphragmatic mobility, as well as reduced volume of the upper ribcage compartment on the affected side that leads to reduced shortening velocity and ventilation asymmetry.

A high-whey-protein diet does not enhance mechanical and structural remodeling of cardiac muscle in response to aerobic exercise in rats.

[Purpose]Aerobic exercise training results in distinct structural and mechanical myocardial adaptations. In skeletal muscle, whey protein supplementation is effective in enhancing muscle adaptation following resistance exercise. However, it is unclear whether cardiac adaptation to aerobic exercise can be enhanced by systematic protein supplementation.[Methods]Twelve-week-old rats were assigned to 12 weeks of either sedentary or aerobic exercise with either a standard (Sed+Standard, Ex+Standard) or high-protein (Sed+Pro, Ex+Pro) diet. Echocardiography was used to measure cardiac structural remodeling and performance. Skinned cardiac fiber bundles were used to determine the active and passive stress properties, maximum shortening velocity, and calcium sensitivity.[Results]Aerobic training was characterized structurally by increases in ventricle volume (Ex+Standard, 19%; Ex+Pro, 29%) and myocardial thickness (Ex+Standard, 26%; Ex+-Pro, 12%) compared to that of baseline. Skinned trabecula r fiber bundles also had a greater unloaded shortening velocity (Sed+Standard, 1.04±0.05; Sed+Pro, 1.07±0.03; Ex-+Standard, 1.16±0.04; Ex+Pro, 1.18±0.05 FL/s) and calcium sensitivity (pCa50: Sed+Standard, 6.04±0.17; Sed+Pro, 6.08±0.19; Ex+Standard, 6.30±0.09; Ex+Pro, 6.36±0.12) in trained hearts compared to that of hearts from sedentary animals. However, the addition of a high-protein diet did not provide additional benefits to either the structural or mechanical adaptations of the myocardium.[Conclusion]Therefore, it seems that a high-whey-protein diet does not significantly enhance adaptations of the heart to aerobic exercise in comparison to that of a standard diet.

Bridging the muscle genome to phenome across multiple biological scales.

Muscle is highly hierarchically organized, with functions shaped by genetically controlled expression of protein ensembles with different isoform profiles at the sarcomere scale. However, it remains unclear how isoform profiles shape whole-muscle performance. We compared two mouse hindlimb muscles, the slow, relatively parallel-fibered soleus and the faster, more pennate-fibered tibialis anterior (TA), across scales: from gene regulation, isoform expression and translation speed, to force-length-velocity-power for intact muscles. Expression of myosin heavy-chain (MHC) isoforms directly corresponded with contraction velocity. The fast-twitch TA with fast MHC isoforms had faster unloaded velocities (actin sliding velocity, Vactin; peak fiber velocity, Vmax) than the slow-twitch soleus. For the soleus, Vactin was biased towards Vactin for purely slow MHC I, despite this muscle's even fast and slow MHC isoform composition. Our multi-scale results clearly identified a consistent and significant dampening in fiber shortening velocities for both muscles, underscoring an indirect correlation between Vactin and fiber Vmax that may be influenced by differences in fiber architecture, along with internal loading due to both passive and active effects. These influences correlate with the increased peak force and power in the slightly more pennate TA, leading to a broader length range of near-optimal force production. Conversely, a greater force-velocity curvature in the near-parallel fibered soleus highlights the fine-tuning by molecular-scale influences including myosin heavy and light chain expression along with whole-muscle characteristics. Our results demonstrate that the individual gene, protein and whole-fiber characteristics do not directly reflect overall muscle performance but that intricate fine-tuning across scales shapes specialized muscle function.

Altered Gastrocnemius Contractile Behavior in Former Achilles Tendon Rupture Patients During Walking.

Achilles tendon rupture (ATR) remains associated with functional limitations years after injury. Architectural remodeling of the gastrocnemius medialis (GM) muscle is typically observed in the affected leg and may compensate force deficits caused by a longer tendon. Yet patients seem to retain functional limitations during—low-force—walking gait. To explore the potential limits imposed by the remodeled GM muscle-tendon unit (MTU) on walking gait, we examined the contractile behavior of muscle fascicles during the stance phase. In a cross-sectional design, we studied nine former patients (males; age: 45 ± 9 years; height: 180 ± 7 cm; weight: 83 ± 6 kg) with a history of complete unilateral ATR, approximately 4 years post-surgery. Using ultrasonography, GM tendon morphology, muscle architecture at rest, and fascicular behavior were assessed during walking at 1.5 m⋅s–1 on a treadmill. Walking patterns were recorded with a motion capture system. The unaffected leg served as control. Lower limbs kinematics were largely similar between legs during walking. Typical features of ATR-related MTU remodeling were observed during the stance sub-phases corresponding to series elastic element (SEE) lengthening (energy storage) and SEE shortening (energy release), with shorter GM fascicles (36 and 36%, respectively) and greater pennation angles (8° and 12°, respectively). However, relative to the optimal fascicle length for force production, fascicles operated at comparable length in both legs. Similarly, when expressed relative to optimal fascicle length, fascicle contraction velocity was not different between sides, except at the time-point of peak series elastic element (SEE) length, where it was 39 ± 49% lower in the affected leg. Concomitantly, fascicles rotation during contraction was greater in the affected leg during the whole stance-phase, and architectural gear ratios (AGR) was larger during SEE lengthening. Under the present testing conditions, former ATR patients had recovered a relatively symmetrical walking gait pattern. Differences in seen AGR seem to accommodate the profound changes in MTU architecture, limiting the required fascicle shortening velocity. Overall, the contractile behavior of the GM fascicles does not restrict length- or velocity-dependent force potentials during this locomotor task.

The legacy of A. V. Hill's Nobel Prize winning work on muscle energetics.

A. V. Hill was awarded the 1922 Nobel Prize, jointly with Otto Meyerhof, for Physiology or Medicine for his work on energetic aspects of muscle contraction. Hill used his considerable mathematical and experimental skills to investigate the relationships among muscle mechanics, biochemistry and heat production. The main ideas of the work for which the Nobel Prize was awarded were superseded within a decade, and the legacy of Hill and Meyerhof's Nobel work was not a set of persistent, influential ideas but rather a prolonged period of extraordinary activity that advanced the understanding of how muscles work far beyond the concepts that led to the Nobel Prize. Hill pioneered the integration of mathematics into the study of physiology and pharmacology. Particular aspects of Hill's own work that remain in common use in muscle physiology include mathematical descriptions of the relationships between muscle force output and shortening velocity and between force output and calcium concentration, and the model of muscle as a contractile element in series with an elastic element. We describe some of the characteristics of Hill's broader scientific activities and then outline how Hill's work on muscle energetics was extended after 1922, as a result of Hill's own work and that of others, to the present day.

Scale-Invariant Feature Transform (SIFT) Algorithm-Based Detection of Cardiac Insufficiency in Sepsis Patients with Echocardiography

This research aimed to explore the application of cardiac ultrasound imaging (CUI) in the examination and diagnosis of sepsis patients with cardiac insufficiency under a speckle tracking algorithm (STA). Scale-invariant feature transform (SIFT) algorithm was introduced to process images of CUI through STA under feature points of cardiac ultrasonic images. 90 patients with sepsis who were admitted to the hospital were selected and randomly divided into a sound cardiac function group (n = 62) (group A) and a cardiac insufficient group (n = 28) (group B) under whether they had cardiac insufficiency, and 20 healthy people were selected as a control group. Sepsis patients were examined on the seventh day after diagnosis including laboratory-related indicators, echocardiography, and echocardiographic data. The results showed that there were differences in cardiac ultrasound, cardiac marker, and laboratory examinations of subjects in the three groups ( P &lt; 0.05). Creatine kinase isoenzyme-MB (CK-MB), glycogen phosphorylase isoenzyme BB (GPBB), and heart-type fatty acid-binding protein (H-FABP) of subjects in the three groups showed statistically marked differences ( P &lt; 0.05). The other results indicated tricuspid late diastolic blood flow velocity (A′) value was greater than stroke volume (SV) and isovolumetric relaxation time (IVRT) value, followed by left ventricular ejection fraction (EF) and cardiac output per minute output (CO), and EF and CO values were over peak velocity of right ventricular free wall tricuspid valve systolic movement (SM) and left ventricular fractional shortening (FS) value, and left ventricular end-diastolic volume (EDV) value came next. The analysis of CUI based on STA could help doctors to judge sepsis patients with cardiac function. In addition, sepsis patients with sound cardiac function and sepsis patients with cardiac insufficiency could be distinguished by CUI, which had certain guiding significance for clinical diagnosis.

The effect of small changes in rate of force development on muscle fascicle velocity and motor unit discharge behaviour

When rate of force development is increased, neural drive increases. There is presently no accepted explanation for this effect. We propose and experimentally test the theory that a small increase in rate of force development increases medial gastrocnemius fascicle shortening velocity, reducing the muscle’s force-generating capacity, leading to active motor units being recruited at lower forces and with increased discharge frequencies. Participants produced plantar flexion torques at three different rates of force development (slow: 2% MVC/s, medium: 10% MVC/s, fast: 20% MVC/s). Ultrasound imaging showed that increased rate of force development was related to higher fascicle shortening velocity (0.4 ± 0.2 mm/s, 2.0 ± 0.9 mm/s, 4.1 ± 1.9 mm/s in slow, medium, fast, respectively). In separate experiments, medial gastrocnemius motor unit recruitment thresholds and discharge frequencies were measured using fine-wire electromyography (EMG), together with surface EMG. Recruitment thresholds were lower in the fast (12.8 ± 9.2% MVC) and medium (14.5 ± 9.9% MVC) conditions compared to the slow (18.2 ± 8.9% MVC) condition. The initial discharge frequency was lower in the slow (5.8 ± 3.1 Hz) than the fast (6.7 ± 1.4 Hz), but not than the medium (6.4 ± 2.4 Hz) condition. The surface EMG was greater in the fast (mean RMS: 0.029 ± 0.017 mV) compared to the slow condition (0.019 ± 0.013 mV). We propose that the increase in muscle fascicle shortening velocity reduces the force-generating capacity of the muscle, therefore requiring greater neural drive to generate the same forces.

Essential myosin light chain MLC-1sa decelerates actin and thin filament gliding on beta-myosin molecules

The β-myosin heavy chain expressed in ventricular myocardium and the myosin heavy chain (MyHC) in type-I fibers of slow-twitch skeletal musculus soleus are both encoded by MYH7. Thus, these myosin molecules are deemed equivalent. However, some reports suggested variations in the myosin light chain composition between soleus muscle and ventricular myosin, which could influence functional parameters such as maximum velocity of shortening. To test for functional differences of the actin gliding velocity on immobilized myosin molecules we made use of the in vitro motility assay.

Investigating the active contractile function of the rat paraspinal muscles reveals unique cross-bridge kinetics in the multifidus

Various aspects of paraspinal muscle anatomy, biology, and histology have been studied; however, information on paraspinal muscle contractile function is almost nonexistent, thus hindering functional interpretation of these muscles in healthy individuals and those with low back disorders. The aim of this study was to measure and compare the contractile function and force-sarcomere length properties of muscle fibers from the multifidus (MULT) and erector spinae (ES) as well as a commonly studied lower limb muscle (Extensor digitorum longus (EDL)) in the rat. Single muscle fibers (n = 77 total from 6 animals) were isolated from each of the muscles and tested to determine their active contractile function; all fibers used in the analyses were type IIB. There were no significant differences between muscles for specific force (sFo) (p = 0.11), active modulus (p = 0.63), average optimal sarcomere length (p = 0.27) or unloaded shortening velocity (Vo) (p = 0.69). However, there was a significant difference in the rate of force redevelopment (ktr) between muscles (p = < 0.0001), with MULT being significantly faster than both the EDL (p = < 0.0001) and ES (p = 0.0001) and no difference between the EDL and ES (p = 0.41). This finding suggests that multifidus has faster cross-bridge turnover kinetics when compared to other muscles (ES and EDL) when matched for fiber type. Whether the faster cross-bridge kinetics translate to a functionally significant difference in whole muscle performance needs to be studied further.

Аналіз застосування Мексикору у хворих із гострим коронарним синдромом

Матеріали та методи. Під спостереженням знаходилися дві групи хворих із гострим коронарним синдромом. Перша група включала 48 хворих із нестабільною стенокардією (НС) віком 58,5 ± 3,8 року. Діагноз НС верифікований на підставі скарг хворих і змін на електрокардіограмі — підйому або депресії інтервалу на 1 мм тривалістю не більше 3 діб, відсутності зон гіпокінезії при УЗД серця, негативного тропонінового тесту. Другу групу становили 45 хворих із гострим інфарктом міокарда. Діагноз верифіковано за допомогою тропонінового тесту і змін на ЕКГ. У цю групу включалися хворі з Q-позитивним гострим інфарктом міокарда (ГІМ). Чоловіки — 83,2 %, жінки — 16,8 %. Середній вік хворих становив 60,3 ± 1,2 року. Задньобазальна локалізація виявлена у 40,2 %, передня — у 59,8 %. В анамнезі у 70 % хворих гіпертонічна хвороба ІІ ст. «Стаж» ішемічної хвороби серця становив у середньому 10,8 ± 4,5 року. 80 % хворих цієї групи неодноразово лікувалися в кардіологічних стаціонарах із приводу загострень ішемічної хвороби серця. У 38,5 % хворих на момент надходження відзначені надшлуночкові і шлуночкові (екстрасистолія) порушення ритму. Результати. Застосування Мексикору у хворих із ГІМ значно покращувало систолічну функцію серця, що проявлялося у вірогідній різниці основних показників, що її відображають (фракція викиду, швидкість циркуляторного скорочення волокон, серцевого викиду), і відповідних показників у хворих контрольної групи. Подібні сприятливі зміни були виявлені і при вивченні в динаміці показників діастолічної функції серця, що визначаються за швидкістю трансмітрального потоку. Обговорення. Зазначені зміни ми пов’язуємо з відновленням або поліпшенням скоротливості ішемізованого міокарда та функціонального стану так званих інтактних відділів серця, що компенсують своєю діяльністю втрату скоротливості некротизованих ділянок. Це підтверджується динамікою стану зон акінезії і дискінезії у хворих на ІМ, де відстежується відновлення скоротливості окремих ділянок серця на фоні застосування Мексикору (перехід граничних із зонами інфаркту сегментів зі стану акінезії в гіпокінез, гіпокинезу — в нормокінез), і практично зворотною динамікою у хворих контрольної групи. Мексикор сприяв поліпшенню клінічного перебігу ІМ, що проявлялося в обмеженні величини вогнища некрозу і стимуляції репаративних процесів, поліпшенні скорочувальної функції серця і газообміну, зменшенні частоти пролонгованого і рецидивного перебігу, ймовірності розвитку аневризми серця і випадків серцевої недостатності, порушень ритму і провідності, недостатності кровообігу і в кінцевому підсумку летальності. За результатами холтерівського моніторування у хворих на НС Мексикор прискорював стабілізацію стенокардії і зменшував, порівняно з контрольною групою, добову частоту і тривалість періодів ішемії міокарда, епізодів порушень ритму, сприятливо впливав на зміну інтеграла зміщення ST і співвідношення больових/безбольових періодів ішемії. Висновки. Включення Мексикору в традиційну терапію гострого коронарного синдрому вже на догоспітальному етапі дозволяє істотно зменшити прояви окислювального стресу, сприяє нормалізації діяльності серцево-судинної системи і покращує клінічний перебіг захворювань.

СОВРЕМЕННЫЕ ПОДХОДЫ К МЕДИЦИНСКОЙ ПРОФИЛАКТИКЕ КАРДИОТОКСИЧЕСКИХ ЭФФЕКТОВ КОМПЛЕКСНОГО ЛЕЧЕНИЯ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

Objectives. To study the effect of complex treatment of breast cancer (BC) on the parameters of the structural and functional state of the cardiovascular system. To develop a model for predicting the ejection fraction (EF) of the left ventricle (LV) measured by the Simpson method after the end of antitumor therapy on the basis of initial laboratory and instrumental data. Methods. The cardiovascular system was examined in 100 women who received complex treatment of BC. The groups were formed depending on the presence of arterial hypertension (AH) and on the cardiotropic therapy (CT) received: the BC group, the BC+ CT group, the BC+ AH+CT group. Results. The research showed a decrease in LVEF measured by the Simpson method from 66,0 (62,0; 71,0)% to 60,0 (57,0-66,0)%, an increase in LV end systolic diameter from 27,0 (24,0–29,0) mm to 27,0 (25,0–31,0) mm, LV end systolic volume from 27,0 (22,0; 32,0) ml to 28,0 (24,0; 37,0) ml; a decrease in the mitral ratio of peaks early to late diastolic filling velocity from 1,4 (1,1; 1,8) to 1,2 (1,1; 1,5), in the ratio of early to late diastolic mitral annular velocity from 1,4 (1,2; 1,7) to 1,2 (1,0; 1,6); in the of early to late diastolic tricuspid annular velocity from 1,4 (1,2; 1,7) to 1,0 (0,8; 1,1), reduction of the increase in the diameter (d) of the brachial artery (BA) after performing a post-occlusion test from 12,5 (11,0; 16,0)% to 9,0 (6,0; 12,0)%, the reduction of heart rate variability: standard deviation of NN intervals from 57,7 (44,9; 72,9) ms to 54,1 (44,0; 63,3) ms, root mean square of successive RR interval differences from 29,6 (17,5; 43,3) ms to 20,0 (15,2; 28,0) ms, total power of the spectrum from 1326,3 (996,4; 2061,7) to 1132,4 (824,3; 1649,8) ms2/ Hz; power of the high-frequency (HF) from 647,3 (416,8; 921,4) to 443,7 (315,9; 669,0) ms2/ Hz; an increase in ratio of low-frequency to HF from 0,8 (0,7; 1,0) to 1,05 (0,8; 1,2). A Simpson-based EF prognostic model after the end of BC treatment has been developed. It includes the total dose of doxorubicin calculated for the body surface area, the peak early diastolic filling velocity of transtricuspid flow, the diameter of the pulmonary artery, the velocity of circumferential fiber shortening, the intima-medial thickness of the left common carotid artery, HF, % increase of the d of the BA. The developed model has a high prognostic ability. Conclusions. Breast cancer treatment negatively affects the structural and functional state of the cardiovascular system. The administration of a combination of valsartan and carvedilol prevents the development of adverse changes. The developed EF prognostic model allows to identify patients for the preventive administration of cardiotropic therapy.