Maximum Contraction Velocity Research Articles

The influence of Sex on the Effects of Inorganic Nitrate Supplementation on Muscular Power and Endurance.

Inorganic nitrate (NO3-) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power and endurance, although most studies are in males. Therefore, the present double-blind, randomized, placebo-controlled study examined the effects of NO3- supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance (time-to-task failure; TTF), and recovery from fatigue in young females (n=12) and males (n=14). Participants consumed ~13mmol NO3- (BRJ), or an identical NO3--depleted beverage (PL), for ~3 days and 2 hours before testing visits. Plasma nitrate and nitrite were elevated in the BRJ condition (p ≤ 0.05). Peak power (W·kg-1) showed a sex effect (p ≤ 0.05) at all angular velocities and a sex-by-treatment effect at 270 and 360°/sec (p ≤ 0.05). Post hoc analysis revealed no significant differences between treatments (p > 0.05). Estimated maximal knee extension power (Pmax) and maximal knee extension velocity (Vmax) demonstrated no sex, treatment, or sex-by-treatment effect (p > 0.05). There were no significant effects for TTF (F: PL; 269±161 vs BRJ; 277±158s and M: PL; 228±171 vs BRJ; 194±100s; p > 0.05). Cohen's d effect sizes for peak power showed moderate to large effect sizes at 270 (d=0.92) and 360 deg/sec (d=0.81), showing a possible differentiated effect of dietary nitrate in females and males. The present data indicate that NO3- supplementation does not significantly affect knee extensor maximal power, maximal contraction velocity, and muscular endurance in either sex. The sex-dependent response to dietary nitrate supplementation requires further investigation as data on females is scarce.

Acute Responses to Traditional and Cluster-Set Squat Training With and Without Blood Flow Restriction.

Cornejo-Daza, PJ, Sánchez-Valdepeñas, J, Páez-Maldonado, J, Rodiles-Guerrero, L, Boullosa, D, León-Prados, JA, Wernbom, M, and Pareja-Blanco, F. Acute responses to traditional and cluster-set squat training with and without blood flow restriction. J Strength Cond Res 38(8): 1401-1412, 2024-To compare the acute responses to different set configurations (cluster [CLU] vs. traditional [TRA]) under distinct blood flow conditions (free vs. restricted) in full-squat (SQ). Twenty resistance-trained males performed 4 protocols that differed in the set configuration (TRA: continuous repetitions; vs. CLU: 30 seconds of rest every 2 repetitions) and in the blood flow condition (FF: free-flow; vs. blood flow restriction [BFR]: 50% of arterial occlusion pressure). The relative intensity (60% 1RM), volume (3 sets of 8 repetitions), and resting time (2 minutes) were equated. Mean propulsive force (MPF), velocity (MPV) and power (MPP), and electromyography (EMG) parameters were recorded during each repetition. Tensiomyography (TMG), blood lactate, countermovement jump (CMJ) height, maximal voluntary isometric contraction, in SQ, and movement velocity against the load that elicited a 1 m·s -1 velocity at baseline (V1-load) in SQ were assessed at pre- and post-exercise. The CLU protocols allowed a better maintenance of MPF, MPV, MPP, and EMG median frequency during the exercise compared to TRA (clu-time interaction, p < 0.05). The TRA protocols experienced greater impairments post-exercise in TMG- and EMG-derived variables (clu-time interaction, p < 0.05) and SQ and CMJ performance (clu-time interaction, p = 0.08 and p < 0.05, respectively), as well as higher blood lactate concentrations (clu-time interaction, p < 0.001) than CLU. Moreover, BFR displayed decreases in TMG variables (bfr-time interaction, p < 0.01), but BFR-CLU resulted in the greatest reduction in twitch contraction time ( p < 0.001). Cluster sets reduced fatigue during and after the training session and BFR exacerbated impairments in muscle mechanical properties; however, the combination of both could improve contraction speed after exercise.

The effect of low-frequency fatigue on the torque-velocity relationship in human quadriceps.

Low-frequency fatigue (LFF) is usually defined as the decline in low:high-frequency force of electrically evoked isometric muscle contractions. The influence of LFF on dynamic muscle function is not well studied. Our aim was to assess the effect of LFF on the electrically evoked torque-velocity relationship in humans. Sixteen participants underwent a series of electrically evoked knee extensions in an isokinetic dynamometer to establish torque-velocity relationships at 15 and 50 Hz using isokinetic contractions. Hereafter, fatigue was induced by five sets of 10 repetitions of maximal voluntary dynamic knee extensions. After 30 min of rest, torque-velocity tests were repeated. Maximal torque (Fmax) was measured, whereas maximal contraction velocity (Vmax) and maximal power (Pmax) were estimated using Hill's force-velocity equation, 15:50 Hz ratios were calculated for Fmax, Vmax, and Pmax as markers of LFF. Fmax decreased by 40% at 15 Hz (P = 0.001) and by 15% at 50 Hz (P = 0.001) in the fatigued state. No significant change was detected for Vmax at 15 Hz [-2%, (P = 0.349)] or 50 Hz [+3% (P = 0.763)], whereas 15 and 50 Hz Pmax decreased by 30% (P = 0.004) and 10% (P = 0.008), respectively. Following the fatigue protocol, the 15:50 Hz Fmax ratio decreased by 31% (P < 0.001), indicating LFF. The 15:50 Hz Pmax ratio also decreased by 23% (P = 0.002), whereas the 15:50 Hz Vmax ratio was unchanged (P = 0.313). In conclusion, fatiguing contractions decreased Fmax and Pmax at both high and low stimulation frequencies, whereas Vmax appeared unaffected. Nevertheless, LFF influences power production during human dynamic contractions at a range of submaximal velocities.NEW & NOTEWORTHY Force-velocity relationships were established using either low- or high-frequency electrical stimulation before and after fatiguing voluntary eccentric/concentric contractions of the knee extensors. Low-frequency fatigue was assessed by the relative decrease in low- and high-frequency maximal torque, maximal shortening velocity, and maximal power estimated by the force-velocity relationship. Low-frequency fatigue manifests itself as a large decrease in low-frequency maximal force and power with a modest decrease in high-frequency maximal force and power. Contraction velocity does not seem to decrease in the same manner.

Thapsigargin-resistant thiacalix[4]arene C-1087-sensitive component of the contractile activity in rat myometrium reflects the functioning of plasma membrane calcium pump

Background. According to existing knowledge, thiacalix[4]arene С-1087 is highly capable of inhibiting Са2+-pump (Са2+, Mg2+-АТРase) of the plasma membrane; at the same time it inhibits the functioning of Са2+-pump of the sarcoplasmic reticulum of uterine smooth muscles to some degree. The aim of this research was to study the effects of С-1087 on the concentration of Ca2+ ions and contractile activity of the rat myometrium cells using an inhibitor of Са2+-pump of the sarcoplasmic reticulum – thapsigargin. Materials and Methods. The experiments were conducted using outbred white non-pregnant rats. The contractile activity in the preparations of longitudinal SM of uterine horns with preserved endothelium was registered in the isometric mode. To determine the changes in [Ca2+]i level, myocytes were treated with probes Hoechst 33342 (to test the nucleus of the cell) and fluo-4 AM (to test the change in Са2+-concentration in the cell). Results. The tenzometric studies with the subsequent mechanokinetic analysis demonstrated that under the action of thapsigargin (0.5 µM), thiacalix[4]arene C-1087 (10 µM) caused considerable changes in the kinetics of the spontaneous contractile activity processes in the myometrium of rats, including the decrease in the maximal contraction velocity and the increase in the maximal relaxation velocity. By means of confocal microscopy with Ca2+-sensitive fluorescent probe fluo-4, it was demonstrated that the application of thiacalix[4]arene С-1087 to immobilized myocytes of the uterus against the background of thapsigargin caused a transient spike of Са2+-signal with the subsequent turn of the intracellular concentration of Ca ions to the stable increased level. The effects of С-1087 under the action of thapsigargin regarding the relaxation phase in the spontaneous myometrium contractions were removed after the preliminary blocking of nitric oxide synthases L-NAME (100 µM). Under the action of L-NAME, thiacalix[4]arene С-1087 (10 µM) caused complete inhibition of the relaxation process in the contraction of myometrium preparations, induced by high-potassium solution (80 mM). Conclusions. The primary reason for changes in the contractile activity and Ca2+-signal in uterine myocytes under the effect of thiacalix[4]arene С-1087 is its ability to inhibit Са2+-pump of the plasma membrane; further С-1087-induced changes in the smooth muscle tissues may be caused by the increased level of Са2+ concentration in myocytes. The obtained results demonstrate thiacalix[4]arene С-1087 is a promising compound for the elaboration of pharmacological preparations for modulating the contractile activity in smooth muscles, including myometrium.

Chromatic pupillometry isolation and evaluation of intrinsically photosensitive retinal ganglion cell-driven pupillary light response in patients with retinitis pigmentosa.

The pupil light response (PLR) is driven by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to isolate ipRGC-driven pupil responses using chromatic pupillometry and to determine the effect of advanced retinitis pigmentosa (RP) on ipRGC function. A total of 100 eyes from 67 patients with advanced RP and 18 healthy controls (HCs) were included. Patients were divided into groups according to severity of visual impairment: no light perception (NLP, 9 eyes), light perception (LP, 19 eyes), faint form perception (FFP, 34 eyes), or form perception (FP, 38 eyes). Pupil responses to rod-weighted (487 nm, -1 log cd/m2, 1 s), cone-weighted (630 nm, 2 log cd/m2, 1 s), and ipRGC-weighted (487 nm, 2 log cd/m2, 1 s) stimuli were recorded. ipRGC function was evaluated by the postillumination pupil response (PIPR) and three metrics of pupil kinetics: maximal contraction velocity (MCV), contraction duration, and maximum dilation velocity (MDV). We found a slow, sustained PLR response to the ipRGC-weighted stimulus in most patients with NLP (8/9), but these patients had no detectable rod- or cone-driven PLR. The ipRGC-driven PLR had an MCV of 0.269 ± 0.150%/s and contraction duration of 2.562 ± 0.902 s, both of which were significantly lower than those of the rod and cone responses. The PIPRs of the RP groups did not decrease compared with those of the HCs group and were even enhanced in the LP group. At advanced stages, ipRGC responses gradually became the main component of the PLR. Chromatic pupillometry successfully isolated an ipRGC-driven PLR in patients with advanced RP. This PLR remained stable and gradually became the main driver of pupil contraction in more advanced cases of RP. Here, we present baseline data on ipRGC function; we expect these findings to contribute to evaluating and screening candidates for novel therapies.

Electropharmacological Characterization of Licorice Using the Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Sheets and the Chronic Atrioventricular Block Dogs.

Licorice has been traditionally prescribed for palpitation, whereas its overdose has caused lethal arrhythmias including torsade de pointes. Licorice contains glycyrrhizic acid of ≥ 2% (w/w), which is hydrolyzed to glycyrrhetinic acid (GRA) in the intestine. Since their cardiac electropharmacological properties are not fully understood, we assessed them to ask mechanism of licorice-induced torsade de pointes. GRA at 0.1, 1 and 10μg/mL was cumulatively applied to the human induced pluripotent stem cell-derived cardiomyocytes sheets (n = 6). GRA shortened spontaneous activation interval and repolarization period, and decreased maximum contraction velocity, indicating Ca2+ channel blockade. It prolonged effective refractory period and post-repolarization refractoriness with a steep frequency-dependency, whereas it delayed conduction with a modest use-dependency, resembling lidocaine in the mode of Na+ channel-blocking action. Meanwhile, Kanzoto containing a decoction of licorice alone in a dose of 2 or 6g/body/day was orally administered to the conscious chronic atrioventricular block dogs for 3days (n = 4). Kanzoto prolonged QT interval with increasing its temporal dispersion, suggesting K+ channel suppression, and slightly decreased the plasma K+ concentration without inducing torsade de pointes. Moreover, it significantly suppressed atrial and idioventricular rates, leading to sinus arrest along with the onset of ventricular fibrillation in one animal, possibly due to Na+ channel blockade. These results indicate that electropharmacological profile of licorice can be explained by Na+, Ca2+ and K+ channels blockade, which may be associated with low torsadogenic risk, but might contribute to the onset of other types of lethal ventricular arrhythmias.

Effects of motor imagery training on skeletal muscle contractile properties in sports science students.

Studies on motor imagery (MI) practice based on different designs and training protocols have reported changes in maximal voluntary contraction (MVC) strength. However, to date, there is a lack of information on the effects of MI training on contractile properties of the trained muscle. Forty-five physically active sport science students (21 female) were investigated who trained three times per week over a 4-week period in one of three groups: An MI group conducted MI practice of maximal isometric contraction of the biceps brachii; a physical exercise (PE) group physically practiced maximal isometric contractions of the biceps brachii in a biceps curling machine; and a visual imagery (VI) group performed VI training of a landscape. A MVC test of the arm flexors was performed in a biceps curling machine before and after 4 weeks of training. The muscular properties of the biceps brachii were also tested with tensiomyography measurements (TMG). Results showed an interaction effect between time and group for MVC (p=0.027, η 2 = 0.17), with a higher MVC value in the PE group (Δ5.9%) compared to the VI group (Δ-1.3%) (p=0.013). MVC did not change significantly in the MI group (Δ2.1%). Analysis of muscle contractility via TMG did not show any interaction effects neither for maximal radial displacement (p=0.394, η 2 = 0.05), delay time (p=0.79, η 2 = 0.01) nor contraction velocity (p=0.71, η 2 = 0.02). In spite of MVC-related changes in the PE group due to the interventions, TMG measurements were not sensitive enough to detect concomitant neuronal changes related to contractile properties.

Abstract P1145: Hydrogel Matrix Support Of Suspension-differentiated Hipscs Impacts Resulting In Vitro Cardiac Tissue Functionality

Functional in vitro cardiac tissues are needed to provide insight into the cellular level of disease. Previously, we demonstrated hydrogel-encapsulated hiPSCs undergo cardiac differentiation and achieve cardiomyocyte (CM) maturation including T-tubule formation. To investigate the effect of encapsulation on differentiation and cardiac tissue functionality, here we compared PEG-fibrinogen (PF) microsphere (MS)-supported differentiation approach to self-aggregated embryoid body (EB) differentiation. Briefly, hiPSCs were encapsulated or formed into EBs; cardiac differentiation was initiated by Wnt activation and subsequent inhibition. CM content, contractile functionality, drug response, and electrophysiological properties were determined by flow cytometry, microscopy, and optical mapping, respectively.Initial diameter was 673±22 μm (coefficient of variance, COV=0.03) for MS and145±34 μm (COV=0.24) for EBs. The number of CMs produced (differentiation day 10) per initial hiPSC was significantly higher for MS (2.8 ± 1.8) than EBs (0.6±0.12). MS also yielded a higher percentage of CMs; MS-encapsulated hiPSC differentiation resulted in 74.7±13.8% CMs while for EBs it was 56±16.1 % (cTnT+, MF20+, n=14 and 5 batches, respectively, p&lt;0.05). Myocardial contractility was also enhanced in cardiac MS as compared to EBs (similar CM content, day 10); maximum contraction velocity was four times higher for MS than EBs (139±17.5 μm/s versus 33.4±5.1 μm/s) and maximum relaxation velocity was fourteen times higher (97±7.2 μm/s versus 7.4±0.4 μm/s).Furthermore, cardiac MS responded more vigorously to isoproterenol (IP) and propranolol (P) (frequency +124% (IP), - 61% (P), versus +49% (IP) and -27%(P) for EB), suggesting that MS-CM β-adrenergic signaling may be more mature. Calcium transient propagation was more uniform in MS-CMs compared to EB-CMs; calcium transient duration (CTD) at 50% and 80% repolarization and calcium transient velocity were similar. In conclusion, MS supported cardiac differentiation supported higher CM content, faster contractility, and improved drug response in comparison to similarly differentiated EBs, demonstrating the potential of encapsulation to enhance cardiac tissue functionality for disease modeling.

Functional Evaluation of Human Bioengineered Cardiac Tissue Using iPS Cells Derived from a Patient with Lamin Variant Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is caused by various gene variants and characterized by systolic dysfunction. Lamin variants have been reported to have a poor prognosis. Medical and device therapies are not sufficient to improve the prognosis of DCM with the lamin variants. Recently, induced pluripotent stem (iPS) cells have been used for research on genetic disorders. However, few studies have evaluated the contractile function of cardiac tissue with lamin variants. The aim of this study was to elucidate the function of cardiac cell sheet tissue derived from patients with lamin variant DCM. iPS cells were generated from a patient with lamin A/C (LMNA) -mutant DCM (LMNA p.R225X mutation). After cardiac differentiation and purification, cardiac cell sheets that were fabricated through cultivation on a temperature-responsive culture dish were transferred to the surface of the fibrin gel, and the contractile force was measured. The contractile force and maximum contraction velocity, but not the maximum relaxation velocity, were significantly decreased in cardiac cell sheet tissue with the lamin variant. A qRT-PCR analysis revealed that mRNA expression of some contractile proteins, cardiac transcription factors, Ca2+-handling genes, and ion channels were downregulated in cardiac tissue with the lamin variant.Human iPS-derived bioengineered cardiac tissue with the LMNA p.R225X mutation has the functional properties of systolic dysfunction and may be a promising tissue model for understanding the underlying mechanisms of DCM.

Effects of Kinesio Taping on Muscle Contractile Properties: Assessment Using Tensiomyography.

Although functional effects of kinesio taping (KT) have been widely studied, its effects on contractile properties of the target muscle remain unclear. Tensiomyography is suitable for quantifying muscle stiffness and rate of force development upon imposed twitch contraction. To test the hypothesis that KT has effects on contractile properties of targeted muscle using tensiomyography. Prospective cohort study. Performance laboratory of a sports rehabilitation center. A total of 11 healthy volunteers. Tensiomyography measurements before KT facilitation technique applied (pre-KT), 45minutes, and 24hours after KT (post-KT1 and post-KT2, respectively) without removing the tape. Maximal radial displacement, contraction time, delay time, sustain time, relaxation time, and velocity of contraction. Significant effects were shown for maximal radial displacement (P = .004), contraction time (P = .013), relaxation time (P = .035), and velocity of contraction (P = .0033), but not for delay time (P = .060) and sustain time (P = .078). Post hoc testing indicated a significant decrease in maximal radial displacement for post-KT1 only (from 6.33 [1.46] to 4.87 [2.14] mm), and a significant increase in contraction time for both post-KT1 and post-KT2 (from 30.87 [11.39] to 39.71 [13.49] ms, and 37.41 [14.73] ms, respectively). Post hoc testing also showed a significant decrease in relaxation time for post-KT2 (from 65.97 [53.43] to 47.45 [38.12] ms), and a significant decrease in velocity of contraction for both post-KT1 and post-KT2 (from 0.22 [0.08] to 0.15 [0.09] mm/s, and 0.16 [0.07] mm/s), respectively. The findings indicate that KT leads to an increased muscle stiffness and a reduced muscle rate of force production despite the facilitation technique applied.

Motor imagery and the muscle system

Many studies have investigated the activation of cortical areas and corticospinal excitability during motor imagery (MI) in relation to motor execution. Similar activation of cortical areas during imagined and executed bodily movements and increased corticospinal excitability while imagining movements has been demonstrated. Despite these similarities on the central nervous system level, there is no overt movement during MI. This suggests that centrally generated signals must be inhibited at some level. Second, even in the absence of movement, some studies find behavioral effects of MI interventions. Most of the studies have investigated the role of MI on the cortical or spinal level, but less is known about the peripheral level, such as the muscle system. Testing muscular excitability during MI will give further hints whether and how low-threshold motor commands during MI reach the muscular system. Furthermore, the extent of the shown effects during imagery depends considerably on type of imagery, available proprioceptive information, and imagery ability. Therefore, this study investigates muscular excitability of the biceps brachii muscle manipulating imagery mode (MI vs. visual imagery) and proprioceptive information (with or without muscle effort). 40 participants were included in the analysis. The mechanical response of the muscle after a single electrical stimulus was assessed via tensiomyography. The corresponding variables maximal displacement, delay time, and contraction velocity were used to calculate 2 × 2 ANOVAs with repeated measurements. The absence of interaction effects shows that possible imagery effects on the muscle system are not increased by effort. MI altered time to contraction with lower delay time compared to control condition. Velocity and maximal displacement of the muscle belly during contraction did not differ between imagery conditions. This indicates that MI might impact on the initiation of muscle contraction but does not change the contraction itself. Thus, neuronal factors are moving further into focus in the context of MI research.

Targeting IRE1α-JNK-c-Jun/AP-1-sEH Signaling Pathway Improves Myocardial and Coronary Endothelial Function Following Global Myocardial Ischemia/Reperfusion.

Objectives: Endoplasmic reticulum (ER) stress and soluble epoxide hydrolase (sEH) upregulation/activation have been implicated in myocardial ischemia/reperfusion (I/R) injury. We previously reported that ER stress mediates angiotensin II-induced sEH upregulation in coronary endothelium, whether and how ER stress regulates sEH expression to affect postischemic cardiac function remain unexplored. This study aimed to unravel the signaling linkage between ER stress and sEH in an ex vivo model of myocardial I/R injury.Methods: Hearts from male Wistar-Kyoto rats were mounted on a Langendorff apparatus and randomly allocated to 7 groups, including control, I/R (30-min ischemia and 60-min reperfusion), and I/R groups pretreated with one of the following inhibitors: 4-PBA (targeting: ER stress), GSK2850163 (IRE1α), SP600125 (JNK), SR11302 (AP-1), and DCU (sEH). The inhibitor was administered for 15 min before ischemia with a peristaltic pump. Hemodynamic parameters including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal velocity of contraction (+dp/dtmax) and relaxation (-dp/dtmax) of the left ventricle were continuously recorded using an intraventricular balloon. Endothelial dilator function of the left anterior descending artery was studied in a wire myograph upon completion of reperfusion. The expression of ER stress molecules, JNK, c-Jun, and sEH was determined by western-blot.Results: I/R decreased LVSP (105.5±6.4 vs. 146.9±13.4 mmHg), and increased LVEDP (71.4±3.0 vs. 6.0±2.7 mmHg), with a resultant decreased LVDP (34.1±9.2 vs. 140.9±13.1 mmHg). I/R attenuated +dp/dtmax (651.7±142.1 vs. 2806.6±480.6 mmHg/s) and -dp/dtmax (-580.0±109.6 vs. -2118.0±244.9 mmHg/s) (all ps<0.001). The I/R-induced cardiac dysfunction could be alleviated by 4-PBA (LVSP 119.5±15.6 mmHg, p<0.01; LVEDP 21.2±4.2 mmHg, LVDP 98.3±12.0 mmHg, +dp/dtmax 2166.7±208.4 mmHg/s, and -dp/dtmax -1350.9±99.8 mmHg/s, all ps<0.001), GSK2850163 (LVSP 113.4±10.9 mmHg, p<0.01; LVEDP 37.1±3.1 mmHg, LVDP 76.3±13.9 mmHg, +dp/dtmax 1586.5±263.3 mmHg/s, -dp/dtmax -1127.7±159.9 mmHg/s, all ps<0.001), SP600125 (LVSP 113.9±5.6 mmHg, LVDP 40.5±3.3 mmHg, +dp/dtmax 970.1±89.8 mmHg/s, all ps<0.01), SR11302 (LVSP 97.9±7.5 mmHg, p<0.01; LVEDP 52.7±8.6mmHg, p<0.001; LVDP 45.2±9.8mmHg, p<0.05; +dp/dtmax 1231.5±196.6 mmHg/s, p<0.01; -dp/dtmax -658.3±68.9 mmHg/s, p<0.05), or DCU (LVSP 109.9±4.1 mmHg, p<0.01; LVEDP 11.7±1.8 mmHg, LVDP 98.2±4.9 mmHg, +dp/dtmax 1869.8±121.9 mmHg/s, and -dp/dtmax -1492.3±30.8 mmHg/s, all ps<0.001). The relaxant response of the coronary artery to acetylcholine was decreased after I/R in terms of both magnitude and sensitivity (p<0.001). All inhibitors improved acetylcholine-induced relaxation. Global I/R increased sEH expression and induced ER stress in both myocardium and coronary artery. Inhibition of ER stress or IRE1α downregulated I/R-induced sEH expression and inhibited JNK and c-Jun phosphorylation. Both JNK and AP-1 inhibitors lowered sEH level in myocardium and coronary artery in I/R-injured hearts.Conclusions: This study deciphered the molecular linkage between ER stress and sEH regulation in global I/R insult by uncovering a novel signaling axis of IRE1α-JNK-c-Jun/AP-1-sEH, which provided basis for future research on the therapeutic potential of targeting the IRE1α-JNK-c-Jun/AP-1-sEH axis for ischemic myocardial injury.

Rules of nature’s Formula Run: Muscle mechanics during late stance is the key to explaining maximum running speed

The maximum running speed of legged animals is one evident factor for evolutionary selection—for predators and prey. Therefore, it has been studied across the entire size range of animals, from the smallest mites to the largest elephants, and even beyond to extinct dinosaurs. A recent analysis of the relation between animal mass (size) and maximum running speed showed that there seems to be an optimal range of body masses in which the highest terrestrial running speeds occur. However, the conclusion drawn from that analysis—namely, that maximum speed is limited by the fatigue of white muscle fibres in the acceleration of the body mass to some theoretically possible maximum speed—was based on coarse reasoning on metabolic grounds, which neglected important biomechanical factors and basic muscle-metabolic parameters. Here, we propose a generic biomechanical model to investigate the allometry of the maximum speed of legged running. The model incorporates biomechanically important concepts: the ground reaction force being counteracted by air drag, the leg with its gearing of both a muscle into a leg length change and the muscle into the ground reaction force, as well as the maximum muscle contraction velocity, which includes muscle–tendon dynamics, and the muscle inertia—with all of them scaling with body mass. Put together, these concepts’ characteristics and their interactions provide a mechanistic explanation for the allometry of maximum legged running speed. This accompanies the offering of an explanation for the empirically found, overall maximum in speed: In animals bigger than a cheetah or pronghorn, the time that any leg-extending muscle needs to settle, starting from being isometric at about midstance, at the concentric contraction speed required for running at highest speeds becomes too long to be attainable within the time period of a leg moving from midstance to lift-off. Based on our biomechanical model, we, thus, suggest considering the overall speed maximum to indicate muscle inertia being functionally significant in animal locomotion. Furthermore, the model renders possible insights into biological design principles such as differences in the leg concept between cats and spiders, and the relevance of multi-leg (mammals: four, insects: six, spiders: eight) body designs and emerging gaits. Moreover, we expose a completely new consideration regarding the muscles’ metabolic energy consumption, both during acceleration to maximum speed and in steady-state locomotion.

Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure.

IntroductionMyocardial recovery is one of the targets for heart failure treatment. A non-negligible number of heart failure with reduced ejection fraction (EF) patients experience myocardial recovery through treatment. Although myocardial hypoxia has been reported to contribute to the progression of heart failure even in non-ischemic cardiomyopathy, the relationship between contractile recovery and re-oxygenation and its underlying mechanisms remain unclear. The present study investigated the effects of hypoxia/re-oxygenation on bioengineered cardiac cell sheets-tissue function and the underlying mechanisms.MethodsBioengineered cardiac cell sheets-tissue was fabricated with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) using temperature-responsive culture dishes. Cardiac tissue functions in the following conditions were evaluated with a contractile force measurement system: continuous normoxia (20% O2) for 12 days; hypoxia (1% O2) for 4 days followed by normoxia (20% O2) for 8 days; or continuous hypoxia (1% O2) for 8 days. Cell number, sarcomere structure, ATP levels, mRNA expressions and Ca2+ transients of hiPSC-CM in those conditions were also assessed.ResultsHypoxia (4 days) elicited progressive decreases in contractile force, maximum contraction velocity, maximum relaxation velocity, Ca2+ transient amplitude and ATP level, but sarcomere structure and cell number were not affected. Re-oxygenation (8 days) after hypoxia (4 days) was associated with progressive increases in contractile force, maximum contraction velocity and relaxation time to the similar extent levels of continuous normoxia group, while maximum relaxation velocity was still significantly low even after re-oxygenation. Ca2+ transient magnitude, cell number, sarcomere structure and ATP level after re-oxygenation were similar to those in the continuous normoxia group. Hypoxia/re-oxygenation up-regulated mRNA expression of PLN.ConclusionsHypoxia and re-oxygenation condition directly affected human bioengineered cardiac tissue function. Further understanding the molecular mechanisms of functional recovery of cardiac tissue after re-oxygenation might provide us the new insight on heart failure with recovered ejection fraction and preserved ejection fraction.

Power Amplification Increases With Contraction Velocity During Stretch-Shortening Cycles of Skinned Muscle Fibers.

Muscle force, work, and power output during concentric contractions (active muscle shortening) are increased immediately following an eccentric contraction (active muscle lengthening). This increase in performance is known as the stretch-shortening cycle (SSC)-effect. Recent findings demonstrate that the SSC-effect is present in the sarcomere itself. More recently, it has been suggested that cross-bridge (XB) kinetics and non-cross-bridge (non-XB) structures (e.g., titin and nebulin) contribute to the SSC-effect. As XBs and non-XB structures are characterized by a velocity dependence, we investigated the impact of stretch-shortening velocity on the SSC-effect. Accordingly, we performed in vitro isovelocity ramp experiments with varying ramp velocities (30, 60, and 85% of maximum contraction velocity for both stretch and shortening) and constant stretch-shortening magnitudes (17% of the optimum sarcomere length) using single skinned fibers of rat soleus muscles. The different contributions of XB and non-XB structures to force production were identified using the XB-inhibitor Blebbistatin. We show that (i) the SSC-effect is velocity-dependent—since the power output increases with increasing SSC-velocity. (ii) The energy recovery (ratio of elastic energy storage and release in the SSC) is higher in the Blebbistatin condition compared with the control condition. The stored and released energy in the Blebbistatin condition can be explained by the viscoelastic properties of the non-XB structure titin. Consequently, our experimental findings suggest that the energy stored in titin during the eccentric phase contributes to the SSC-effect in a velocity-dependent manner.

SENSITIVITY OF MODEL-PREDICTED MUSCLE FORCES OF PATIENTS WITH CEREBRAL PALSY TO VARIATIONS IN MUSCLE-TENDON PARAMETERS

Computational musculoskeletal modeling and simulation platforms are efficient tools to gain insight into the muscular coordination of patients with motor disabilities such as cerebral palsy (CP). Muscle force predictions from simulation programs are influenced by the architectural and contractile properties of muscle-tendon units. In this study, we aimed to evaluate the sensitivity of major lower limb muscle forces in patients with CP to changes in muscle-tendon parameters. Open-access datasets of children with CP ([Formula: see text]) and healthy children ([Formula: see text]) were considered. Monte Carlo analysis was executed to specify how sensitive the muscle forces to perturbations between [Formula: see text]% and [Formula: see text]% of the nominal value of the maximum isometric muscle force, optimal muscle fiber length, muscle pennation angle, tendon slack length, and maximum contraction velocity of muscle. The sensitivity analysis revealed that muscle forces of CP patients and healthy individuals were most sensitive to perturbations in the tendon slack length ([Formula: see text]), while forces of CP patients were more sensitive to tendon slack length when compared to the healthy group ([Formula: see text]). Muscle forces of patients and healthy individuals were insensitive to the other four parameters ([Formula: see text]), except for the gracilis and sartorius muscles in which the proportion of optimal muscle fiber length to tendon slack length is higher than 1; forces of these two muscles were also sensitive to the optimal muscle fiber length. The results of this study are expected to contribute to our understanding of which parameters should be personalized when conducting musculoskeletal modeling and simulation of patients with CP.

M-Mode Ultrasound Examination of Soleus Muscle in Healthy Subjects: Intra- and Inter-Rater Reliability Study.

Objective: M-mode ultrasound imaging (US) reflects the motion of connective tissue within muscles. The objectives of this study were to evaluate inter-rater and intra-rater reliability of soleus muscle measurements between examiners with different levels of US experience in asymptomatic subjects and to investigate the level of soleus muscle isometric activity in two positions (knee extended and knee flexed at 30°). Methods: Thirty volunteers without a history of ankle pain were evaluated with US examinations of the soleus muscle. Each muscle was scanned independently by two evaluators. Muscle at rest thickness, maximal isometric contraction thickness, time and velocity measures were detailed and blinded to the other examiner. Results: Intra- and inter-rater reliability at rest, in maximal isometric contraction thickness, contraction time and contraction velocity measures for both positions (extended and flexed knee) were reported from good to excellent for all outcome measurements. The position with the knee extended reported a statistically significant increase in thickness after motion showing 1.33 ± 0.27 mm for measurements at rest thickness with knee extended versus 1.50 ± 0.29 mm for measurements at end thickness with the knee in flexed position (p = 0.001), as well as 1.31 ± 0.23 mm for rest thickness with the knee in flexed position measurements with respect to 1.34 ± 0.24 mm for maximal isometric contraction thickness with extended knee measurements (p = 0.058). Conclusions: This study found that intra- and inter-examiner reliability of M-mode ultrasound imaging of the soleus muscle was excellent in asymptomatic subjects and the soleus muscle activity was different between the position with the knee extended and the position with the knee flexed.

Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle.

In non-diabetic patients with severe disease, such as acute myocardial infarction or acute heart failure, admission blood glucose level is associated with their short-term and long-term mortality. We examined whether transient elevation of glucose affects contractile properties in non-diabetic hearts. Force, intracellular Ca2+ ([Ca2+]i), and sarcomere length were measured in trabeculae from rat hearts. To assess contractile properties, maximum velocity of contraction (Max dF/dt) and minimum velocity of relaxation (Min dF/dt) were calculated. The ratio of phosphorylated troponin I (P-TnI) to troponin I (TnI) was measured. One hour after elevation of glucose from 150 to 400mg/dL, developed force, Max dF/dt, and Min dF/dt were reduced without changes in [Ca2+]i transients at 2.5Hz stimulation and 2.0mM [Ca2+]o,while developed force and [Ca2+]i transients showed no changes at 0.5Hz stimulation and 0.7mM [Ca2+]o. In the presence of 1μM KN-93, a Ca2+/calmodulin-dependent protein kinaseII (CaMKII) inhibitor, or 50μM diazo-5-oxonorleucine, a L-glutamine-D-fructose-6-phosphate amidotransferase inhibitor, the reduction of contractile properties after elevation of glucose was suppressed. Furthermore, 1 h after elevation of glucose to 400mg/dL at 2.0mM [Ca2+]o, the ratio of P-TnI to TnI was increased. These results suggest that in non-diabetic hearts under higher Ca2+-load, transient elevation of glucose for 1 h reduces contractile properties probably by activating CaMKII through O-GlcNAcylation. Thus, in the patients with severe disease, transient elevation of blood glucose, such as due to stress, may worsen cardiac function and thereby affect their mortality without known diabetes.

Chromatic Pupilloperimetry Measures Correlate With Visual Acuity and Visual Field Defects in Retinitis Pigmentosa Patients

PurposeTo evaluate the ability of chromatic pupilloperimetry to identify visual field (VF) defects in patients with retinitis pigmentosa (RP) and to test the correlation between pupilloperimetry impairment and retinal structural and functional measures.MethodsThe pupil responses of 10 patients with RP (mean age, 41.3 ± 16.2 years) and 32 healthy age-similar controls (mean age, 50.7 ± 15.5 years) for 54 focal blue and red stimuli presented in a 24-2 VF were recorded. The pupilloperimetry measures were correlated with Humphrey VF mean deviation, best-corrected visual acuity, and ellipsoid zone area.ResultsSubstantially lower percentage of pupil contraction and maximal pupil contraction velocity (MCV) were recorded in patients with RP throughout the VF in response to blue and red stimuli. The mean absolute deviation (MADEV) in the latency of MCV (LMCV) was significantly larger in patients compared with controls for blue and red stimuli (P = 1.0 × 10−7 and P = 1.0 × 10−6, respectively). The LMCV MADEV differentiated between patients and controls with high specificity and sensitivity (area under the receiver operating characteristic curve, 0.987 and 0.973 for blue and red, respectively). The MADEV of LMCV for blue stimuli correlated with best-corrected visual acuity (ρ = 0.938, P = 5.9 × 10−5) and ellipsoid zone area (ρ = −0.857; P = 0.002). The MADEV of LMCV for red stimuli correlated with Humphrey VF mean deviation (ρ = −0.709; P = 0.022). Minimizing the test to 15 targets maintained a diagnosis of retinal damage in patients with RP with high sensitivity and specificity (area under the receiver operating characteristic curve, 0.927).ConclusionsThe chromatic pupilloperimetry measures significantly correlated with retinal function and structure in patients with RP at various disease stages.Translational RelevanceChromatic pupilloperimetry may enable objective assessment of visual field defects and visual acuity in RP.

Ultrasound Measurement of Skeletal Muscle Contractile Parameters Using Flexible and Wearable Single-Element Ultrasonic Sensor.

Skeletal muscle is considered as a near-constant volume system, and the contractions of the muscle are related to the changes in tissue thickness. Assessment of the skeletal muscle contractile parameters such as maximum contraction thickness (), contraction time (), contraction velocity (), sustain time (), and half-relaxation () provides valuable information for various medical applications. This paper presents a single-element wearable ultrasonic sensor (WUS) and a method to measure the skeletal muscle contractile parameters in A-mode ultrasonic data acquisition. The developed WUS was made of double-layer polyvinylidene fluoride (PVDF) piezoelectric polymer films with a simple and low-cost fabrication process. A flexible, lightweight, thin, and small size WUS would provide a secure attachment to the skin surface without affecting the muscle contraction dynamics of interest. The developed WUS was employed to monitor the contractions of gastrocnemius (GC) muscle of a human subject. The GC muscle contractions were evoked by the electrical muscle stimulation (EMS) at varying EMS frequencies from 2 Hz up to 30 Hz. The tissue thickness changes due to the muscle contractions were measured by utilizing a time-of-flight method in the ultrasonic through-transmission mode. The developed WUS demonstrated the capability to monitor the tissue thickness changes during the unfused and fused tetanic contractions. The tetanic progression level was quantitatively assessed using the parameter of the fusion index (FI) obtained. In addition, the contractile parameters (, , , , and ) were successfully extracted from the measured tissue thickness changes. In addition, the unfused and fused tetanus frequencies were estimated from the obtained FI-EMS frequency curve. The WUS and ultrasonic method proposed in this study could be a valuable tool for inexpensive, non-invasive, and continuous monitoring of the skeletal muscle contractile properties.