Work Loop Research Articles

Fusion of Wearable Kinetic and Kinematic Sensors to Estimate Triceps Surae Work during Outdoor Locomotion on Slopes.

Muscle–tendon power output is commonly assessed in the laboratory through the work loop, a paired analysis of muscle force and length during a cyclic task. Work-loop analysis of muscle–tendon function in out-of-lab conditions has been elusive due to methodological limitations. In this work, we combined kinetic and kinematic measures from shear wave tensiometry and inertial measurement units, respectively, to establish a wearable system for estimating work and power output from the soleus and gastrocnemius muscles during outdoor locomotion. Across 11 healthy young adults, we amassed 4777 strides of walking on slopes from −10° to +10°. Results showed that soleus work scales with incline, while gastrocnemius work is relatively insensitive to incline. These findings agree with previous results from laboratory-based studies while expanding technological capabilities by enabling wearable analysis of muscle–tendon kinetics. Applying this system in additional settings and activities could improve biomechanical knowledge and evaluation of protocols in scenarios such as rehabilitation, device design, athletics, and military training.

Shortening the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating sarcomere length range

Titin's C-zone is an inextensible segment in titin, comprised of 11 super-repeats and located in the cMyBP-C-containing region of the thick filament. Previously we showed that deletion of titin's super-repeats C1 and C2 (TtnΔC1–2 model) results in shorter thick filaments and contractile dysfunction of the left ventricular (LV) chamber but that unexpectedly LV diastolic stiffness is normal. Here we studied the contraction-relaxation kinetics from the time-varying elastance of the LV and intact cardiomyocyte, cellular work loops of intact cardiomyocytes, Ca2+ transients, cross-bridge kinetics, and myofilament Ca2+ sensitivity. Intact cardiomyocytes of TtnΔC1–2 mice exhibit systolic dysfunction and impaired relaxation. The time-varying elastance at both LV and single-cell levels showed that activation kinetics are normal in TtnΔC1–2 mice, but that relaxation is slower. The slowed relaxation is, in part, attributable to an increased myofilament Ca2+ sensitivity and slower early Ca2+ reuptake. Cross-bridge dynamics showed that cross-bridge kinetics are normal but that the number of force-generating cross-bridges is reduced. In vivo sarcomere length (SL) measurements revealed that in TtnΔC1–2 mice the operating SL range of the LV is shifted towards shorter lengths. This normalizes the apparent cell and LV diastolic stiffness but further reduces systolic force as systole occurs further down on the ascending limb of the force-SL relation. We propose that the reduced working SLs reflect titin's role in regulating diastolic stiffness by altering the number of sarcomeres in series. Overall, our study reveals that thick filament length regulation by titin's C-zone is critical for normal cardiac function.

Abstract P315: Shortening The Thick Filament By Partial Deletion Of Titin’S C-zone Alters Cardiac Function By Reducing The Operating Sarcomere Length Range Of The Heart.

Titin’s C-zone is the inextensible part of titin that binds along the thick filament at its cMyBP-C -containing region. Previously it was shown that deletion of titin’s super-repeats C1 and C2 ( Ttn ΔC1-2 mouse model) results in shorter thick filaments and contractile dysfunction, but LV chamber stiffness is normal. Here we studied the contraction-relaxation kinetics from the time-varying elastance of the left ventricle (LV) and from cellular work loops of intact loaded cardiac myocytes. Ca 2+ transients were also measured as well as crossbridge cycling kinetics and Ca 2+ sensitivity of force. It was found that intact cardiomyocytes of Ttn ΔC1-2 mice exhibit systolic dysfunction and impaired relaxation. The time-varying elastance of the LV chamber showed that the kinetics of LV activation are normal but that relaxation is slower in Ttn ΔC1-2 mice. The slowed relaxation was, in part, attributable to an increased myofilament Ca 2+ sensitivity and slower early Ca 2+ reuptake. Dynamic stiffness at the myofilament level showed that cross-bridge kinetics are normal, but that the number of force-generating cross-bridges is reduced. In vivo sarcomere length (SL) measurements in the mid-wall region of the LV revealed that the operating SL range is shifted in Ttn ΔC1-2 mice towards shorter lengths. This normalizes the apparent cell and LV chamber stiffness but reduces the number of force generating cross-bridges due to suboptimal thin and thick filament overlap. Thus the contractile dysfunction in Ttn ΔC1-2 mice is not only due to shorter thick filaments but also to a reduced operating sarcomere length range. Overall these results reveal that for normal cardiac function, thick filament length regulation by titin’s C-zone is critical.

Mavacamten preserves length-dependent contractility and improves diastolic function in human engineered heart tissue.

Comprehensive functional characterization of cardiac tissue includes investigation of length and load dependence. Such measurements have been slow to develop in engineered heart tissues (EHTs), whose mechanical characterizations have been limited primarily to isometric and near-isometric behaviors. A more realistic assessment of myocardial function would include force-velocity curves to characterize power output and force-length loops mimicking the cardiac cycle to characterize work output. We developed a system that produces force-velocity curves and work loops in human EHTs using an adaptive iterative control scheme. We used human EHTs in this system to perform a detailed characterization of the cardiac β-myosin specific inhibitor, mavacamten. Consistent with the clinically proposed application of this drug to treat hypertrophic cardiomyopathy, our data support the premise that mavacamten improves diastolic function through reduction of diastolic stiffness and isometric relaxation time. Meanwhile, the effects of mavacamten on length- and load-dependent muscle performance were mixed. The drug attenuated the length-dependent response at small stretch values but showed normal length dependency at longer lengths. Peak power output of mavacamten-treated EHTs showed reduced power output as expected but also shifted peak power output to a lower load. Here, we demonstrate a robust method for the generation of isotonic contraction series and work loops in engineered heart tissues using an adaptive-iterative method. This approach reveals new features of mavacamten pharmacology, including previously unappreciated effects on intrinsic myosin dynamics and preservation of Frank-Starling behavior at longer muscle lengths.NEW & NOTEWORTHY We applied innovative methods to comprehensively characterize the length and load-dependent behaviors of engineered human cardiac muscle when treated with the cardiac β-myosin specific inhibitor mavacamten, a drug on the verge of clinical implementation for hypertrophic cardiomyopathy. We find mechanistic support for the role of mavacamten in improving diastolic function of cardiac tissue and note novel effects on work and power.

Test-Driven Requirements Engineering

Requirements and testing belong together. Historically, testers have often seen the requirements only after the system has already been partially implemented. This had two serious disadvantages. On the one hand, insufficient requirements quality came far too late to the table. On the other hand, it was quite a lot of extra work without deriving suitable test cases in the context of the requirements definition. A lot of additional work and long correction loops were the result.

Oxygen transport kinetics underpin rapid and robust diaphragm recovery following chronic spinal cord injury.

Key points Spinal treatment can restore diaphragm function in all animals 1 month following C2 hemisection induced paralysis. Greater recovery occurs the longer after injury the treatment is applied.Through advanced assessment of muscle mechanics, innovative histology and oxygen tension modelling, we have comprehensively characterized in vivo diaphragm function and phenotype.Muscle work loops reveal a significant deficit in diaphragm functional properties following chronic injury and paralysis, which are normalized following restored muscle activity caused by plasticity‐induced spinal reconnection.Injury causes global and local alterations in diaphragm muscle vascular supply, limiting oxygen diffusion and disturbing function. Restoration of muscle activity reverses these alterations, restoring oxygen supply to the tissue and enabling recovery of muscle functional properties.There remain metabolic deficits following restoration of diaphragm activity, probably explaining only partial functional recovery. We hypothesize that these deficits need to be resolved to restore complete respiratory motor function. Months after spinal cord injury (SCI), respiratory deficits remain the primary cause of morbidity and mortality for patients. It is possible to induce partial respiratory motor functional recovery in chronic SCI following 2 weeks of spinal neuroplasticity. However, the peripheral mechanisms underpinning this recovery are largely unknown, limiting development of new clinical treatments with potential for complete functional restoration. Utilizing a rat hemisection model, diaphragm function and paralysis was assessed and recovered at chronic time points following trauma through chondroitinase ABC induced neuroplasticity. We simulated the diaphragm's in vivo cyclical length change and activity patterns using the work loop technique at the same time as assessing global and local measures of the muscles histology to quantify changes in muscle phenotype, microvascular composition, and oxidative capacity following injury and recovery. These data were fed into a physiologically informed model of tissue oxygen transport. We demonstrate that hemidiaphragm paralysis causes muscle fibre hypertrophy, maintaining global oxygen supply, although it alters isolated muscle kinetics, limiting respiratory function. Treatment induced recovery of respiratory activity normalized these effects, increasing oxygen supply, restoring optimal diaphragm functional properties. However, metabolic demands of the diaphragm were significantly reduced following both injury and recovery, potentially limiting restoration of normal muscle performance. The mechanism of rapid respiratory muscle recovery following spinal trauma occurs through oxygen transport, metabolic demand and functional dynamics of striated muscle. Overall, these data support a systems‐wide approach to the treatment of SCI, and identify new targets to mediate complete respiratory recovery.

Human-prosthesis coordination: A preliminary study exploring coordination with a powered ankle-foot prosthesis

BackgroundPowered ankle-foot prostheses were developed to replicate the mechanics of the biological ankle by providing positive work during the push-off phase of gait. However, the benefits of powered prostheses on improving overall human gait efficiency (usually quantified by metabolic cost) have not been consistently shown. Here, we have focused on the mechanical work produced at the prosthetic ankle and its interaction with the amputee's movement. MethodsFive unilateral transtibial amputees walked on a treadmill using 1) a powered ankle-foot prosthesis and 2) their daily passive device. We determined the net ankle work and ankle work loops on the prosthesis-side to quantify the efficiency of the human-prosthesis physical interaction. We further studied peak propulsion timing and the posture of the amputee's lower limb and prosthesis as indicators of the human-prosthesis coordination. Comparisons were made between the passive and powered prosthesis conditions for each participant. FindingsThe powered prosthesis did not consistently increase net ankle work compared to each participant's passive device. For participants that lacked efficiency in interacting with the powered prosthesis, we observed 1) early prosthesis-side peak propulsion timing (≥ 4% earlier) and 2) a more vertical residual shank at the time of peak propulsion (> 2° more vertical) indicating that the human's limb movement and the prosthesis control during push-off were not well coordinated. InterpretationResults from this preliminary study highlight the need for future work to systematically quantify the coordination between the human and powered prosthesis and understand how such coordination at the joint level influences overall gait efficiency.

An in vitro platform using the human and rat primary cardiomyocyte work loop assay to screen for drug-induced effects on cardiac contractility

An in vitro platform using the human and rat primary cardiomyocyte work loop assay to screen for drug-induced effects on cardiac contractility

Mechanical Characteristics of Ultrafast Zebrafish Larval Swimming Muscles

Zebrafish (Danio rerio) swim within days of fertilization, powered by muscles of the axial myotomes. Forces generated by these muscles can be measured rapidly in whole, intact larval tails by adapting protocols developed for ex vivo muscle mechanics. But it is not known how well these measurements reflect the function of the underlying muscle fibers and sarcomeres. Here, we consider the anatomy of the 5-day-old, wild-type larval tail, and implement technical modifications to measuring muscle physiology in intact tails. Specifically, we quantify fundamental relationships between force, length, and shortening velocity, and capture the extreme contractile speeds required to swim with tail-beat frequencies of 80–100 Hz. Therefore, we analyze 1000 frames/s videos to track the movement of structures, visible in the transparent tail, which correlate with sarcomere length. We also characterize the passive viscoelastic properties of the preparation to isolate forces contributed by nonmuscle structures within the tail. Myotomal muscles generate more than 95% of their maximal isometric stress (76 ± 3 mN/mm2) over the range of muscle lengths used in vivo. They have rapid twitch kinetics (full width at half-maximal stress: 11 ± 1 ms) and a high twitch/tetanus ratio (0.91 ± 0.05), indicating adaptations for fast excitation-contraction coupling. Although contractile stress is relatively low, myotomal muscles develop high net power (134 ± 20 W/kg at 80 Hz) in cyclical work loop experiments designed to simulate the in vivo dynamics of muscle fibers during swimming. When shortening at a constant speed of 7 ± 1 muscle lengths/s, muscles develop 86 ± 2% of isometric stress, whereas peak instantaneous power during 100 Hz work loops occurs at 18 ± 2 muscle lengths/s. These approaches can improve the usefulness of zebrafish as a model system for muscle research by providing a rapid and sensitive functional readout for experimental interventions.

Shear Wave Tensiometry Reveals an Age-Related Deficit in Triceps Surae Work at Slow and Fast Walking Speeds.

Prior studies have observed an age-related decline in net ankle power and work at faster walking speeds. However, the underlying changes in muscle-tendon behavior are not well-understood, and are challenging to infer from joint level analyses. This study used shear wave tensiometry to investigate the modulation of force and work done by the triceps surae across walking speeds. Fourteen healthy young (7F/7M, 26 ± 5 years) and older (7F/7M, 67 ± 5 years) adults were tested. Subjects walked on an instrumented treadmill at four walking speeds (0.75, 1.00, 1.25, and 1.50 m/s) while lower extremity kinematics and Achilles tendon shear wave speeds were collected. Subject-specific calibrations were used to compute Achilles tendon force from wave speed. Excursions of the soleus and gastrocnemius muscle-tendon units were computed from the kinematic data and subject-specific measures of the Achilles tendon moment arm. Work loop plots were then used to assess effective muscle-tendon stiffness during lengthening, and positive, negative, and net work production during stance. Two-way mixed ANOVAs were used to evaluate the effects of age group and walking speed on each outcome measure. Tendon loading during muscle-tendon lengthening (effective stiffness) did not differ between age groups, but did vary with speed. The soleus became effectively stiffer with increasing speed while the gastrocnemius became effectively more compliant. There was a marked age-related deficit in net soleus (−66% on average) and gastrocnemius (−36%) work across all walking speeds. We did not observe an age-speed interaction effect on net work production. These results suggest the age-related deficit in triceps surae output in walking is pervasive across speed, and hence seemingly not linked to absolute mechanical demands of the task.

Contractile work directly modulates mitochondrial protein levels in human engineered heart tissues.

Engineered heart tissues (EHTs) have emerged as a robust in vitro model to study cardiac physiology. Although biomimetic culture environments have been developed to better approximate in vivo conditions, currently available methods do not permit full recapitulation of the four phases of the cardiac cycle. We have developed a bioreactor which allows EHTs to undergo cyclic loading sequences that mimic in vivo work loops. EHTs cultured under these working conditions exhibited enhanced concentric contractions but similar isometric contractions compared with EHTs cultured isometrically. EHTs that were allowed to shorten cyclically in culture had increased capacity for contractile work when tested acutely. Increased work production was correlated with higher levels of mitochondrial proteins and mitochondrial biogenesis; this effect was eliminated when tissues were cyclically shortened in the presence of a myosin ATPase inhibitor. Leveraging our novel in vitro method to precisely apply mechanical loads in culture, we grew EHTs under two loading regimes prescribing the same work output but with different associated afterloads. These groups showed no difference in mitochondrial protein expression. In loading regimes with the same afterload but different work output, tissues subjected to higher work demand exhibited elevated levels of mitochondrial protein. Our findings suggest that regulation of mitochondrial mass in cultured human EHTs is potently modulated by the mechanical work the tissue is permitted to perform in culture, presumably communicated through ATP demand. Precise application of mechanical loads to engineered heart tissues in culture represents a novel in vitro method for studying physiological and pathological cardiac adaptation.NEW & NOTEWORTHY In this work, we present a novel bioreactor that allows for active length control of engineered heart tissues during extended tissue culture. Specific length transients were designed so that engineered heart tissues generated complete cardiac work loops. Chronic culture with various work loops suggests that mitochondrial mass and biogenesis are directly regulated by work output.

The cardiac work-loop technique: An in vitro model for identifying and profiling drug-induced changes in inotropy using rat papillary muscles

The cardiac work-loop technique closely mimics the intrinsic in vivo movement and characteristics of cardiac muscle function. In this study, six known inotropes were profiled using the work-loop technique to evaluate the potential of this method to predict inotropy. Papillary muscles from male Sprague-Dawley rats were mounted onto an organ bath perfused with Krebs-Henseleit buffer. Following optimisation, work-loop contractions were performed that included an initial stabilisation period followed by vehicle control or drug administration. Six known inotropes were tested: digoxin, dobutamine, isoprenaline, flecainide, verapamil and atenolol. Muscle performance was evaluated by calculating power output during work-loop contraction. Digoxin, dobutamine and isoprenaline caused a significant increase in power output of muscles when compared to vehicle control. Flecainide, verapamil and atenolol significantly reduced power output of muscles. These changes in power output were reflected in alterations in work loop shapes. This is the first study in which changes in work-loop shape detailing for example the activation, shortening or passive re-lengthening have been linked to the mechanism of action of a compound. This study has demonstrated that the work-loop technique can provide an important novel method with which to assess detailed mechanisms of drug-induced effects on cardiac muscle contractility.

Flight muscle power increases with strain amplitude and decreases with cycle frequency in zebra finches (Taeniopygia guttata).

Birds that use high flapping frequencies can modulate aerodynamic force by varying wing velocity, which is primarily a function of stroke amplitude and wingbeat frequency. Previous measurements from zebra finches (Taeniopygia guttata) flying across a range of speeds in a wind tunnel demonstrate that although the birds modulated both wingbeat kinematic parameters, they exhibited greater changes in stroke amplitude. These two kinematic parameters contribute equally to aerodynamic force, so the preference for modulating amplitude over frequency may instead derive from limitations of muscle physiology at high frequency. We tested this hypothesis by developing a novel in situ work loop approach to measure muscle force and power output from the whole pectoralis major of zebra finches. This method allowed for multiple measurements over several hours without significant degradation in muscle power. We explored the parameter space of stimulus, strain amplitude and cycle frequencies measured previously from zebra finches, which revealed overall high net power output of the muscle, despite substantial levels of counter-productive power during muscle lengthening. We directly compared how changes to muscle shortening velocity via strain amplitude and cycle frequency affected muscle power. Increases in strain amplitude led to increased power output during shortening with little to no change in power output during lengthening. In contrast, increases in cycle frequency did not lead to increased power during shortening but instead increased counter-productive power during lengthening. These results demonstrate why at high wingbeat frequency, increasing wing stroke amplitude could be a more effective mechanism to cope with increased aerodynamic demands.

WorkloopR: Analysis of work loops and other data from muscle physiology experiments in R

workloopR: Analysis of work loops and other data from muscle physiology experiments in R

Abstract 336: The Effect Of Phosphodiesterase 9a Inhibition In 2 Mouse Models Of Diastolic Dysfunction

Low myocardial cGMP-PKG activity is associated with increased cardiomyocyte stiffness in HFpEF. cGMP is mainly hydrolyzed by PDE (phosphodiesterases)5a and PDE9a. Importantly, PDE9a protein expression was reported to be upregulated in human HFpEF myocardium and chronic administration of PDE9a inhibitor reversed pre-established cardiac hypertrophy and systolic dysfunction in mice subjected to TAC (Transverse Aortic Constriction). We evaluated whether PDE9a inhibition had a beneficial effect on diastolic dysfunction (DD). We investigated two mouse models of DD: 1) TAC-DOCA (TAC with deoxycorticosterone acetate (DOCA) supplementation) and 2) LepR db/db , a metabolically induced DD models. Mice were subjected to subcutaneous implantation with osmotic minipumps containing either PD9a inhibitor (PF-4449613) or vehicle for 4 wks. PDE9a transcript was not upregulated in myocardium of either TAC-DOCA or LepR db/db mice. PV analysis revealed that in TAC-DOCA mice, inhibition of PDE9a resulted in reduced LV diastolic stiffness, but impairment of systolic function observed as ventricular-vascular decoupling. In LepR db/db mice, cardiomyocyte stiffness was slightly but significantly reduced in PDE9a inhibitor treated animals. No differences in myocardial fibrosis or cardiac morphometry were observed. The effect of acute PDE9a inhibition was investigated in intact cardiomyocytes isolated from LVs of TAC-DOCA mice. Cellular work loop force measurement was conducted before and after administration of PDE9a inhibitor combined with ANP (Atrial Natriuretic Peptide) for 15 mins. Cardiomyocytes from TAC-DOCA had high diastolic stiffness compared to sham hearts, however, no stiffness reduction was observed after acute inhibitor treatment. Conclusion: Chronic inhibition of PDE9a ameliorates LV diastolic stiffness, but suppresses systolic function in TAC-DOCA induced DD mice. The LV stiffness reduction is in part due to cardiomyocyte stiffness reduction. The advantage of PDE9a inhibition on diastolic function might be more evident, with less systolic suppression, in hearts with PDE9a upregulation.

End-diastolic force pre-activates cardiomyocytes and determines contractile force: role of titin and calcium.

Titin functions as a molecular spring, and cardiomyocytes are able, through splicing, to control the length of titin. We hypothesized that together with diastolic [Ca2+], titin‐based stretch pre‐activates cardiomyocytes during diastole and is a major determinant of force production in the subsequent contraction. Through this mechanism titin would play an important role in active force development and length‐dependent activation. Mutations in the splicing factor RNA binding motif protein 20 (RBM20) result in expression of large, highly compliant titin isoforms. We measured single cardiomyocyte work loops that mimic the cardiac cycle in wild‐type (WT) and heterozygous (HET) RBM20‐deficient rats. In addition, we studied the role of diastolic [Ca2+] in membrane‐permeabilized WT and HET cardiomyocytes. Intact cardiomyocytes isolated from HET left ventricles were unable to produce normal levels of work (55% of WT) at low pacing frequencies, but this difference disappeared at high pacing frequencies. Length‐dependent activation (force–sarcomere length relationship) was blunted in HET cardiomyocytes, but the force–end‐diastolic force relationship was not different between HET and WT cardiomyocytes. To delineate the effects of diastolic [Ca2+] and titin pre‐activation on force generation, measurements were performed in detergent‐permeabilized cardiomyocytes. Cardiac twitches were simulated by transiently exposing permeabilized cardiomyocytes to 2 µm Ca2+. Increasing diastolic [Ca2+] from 1 to 80 nm increased force development twofold in WT. Higher diastolic [Ca2+] was needed in HET. These findings are consistent with our hypothesis that pre‐activation increases active force development. Highly compliant titin allows cells to function at higher diastolic [Ca2+].

Does Dietary-Induced Obesity in Old Age Impair the Contractile Performance of Isolated Mouse Soleus, Extensor Digitorum Longus and Diaphragm Skeletal Muscles?

Ageing and obesity independently have been shown to significantly impair isolated muscle contractile properties, though their synergistic effects are poorly understood. We uniquely examined the effects of 9 weeks of a high-fat diet (HFD) on isometric force, work loop power output (PO) across a range of contractile velocities, and fatigability of 79-week-old soleus, extensor digitorum longus (EDL) and diaphragm compared with age-matched lean controls. The dietary intervention resulted in a significant increase in body mass and gonadal fat pad mass compared to the control group. Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater. Obesity did not cause an alteration in the contractile velocity that elicited maximal PO. In the obese group, normalised diaphragm PO was significantly reduced, with a tendency for reduced isometric stress and fatigability was unchanged. HFD soleus isolated from larger animals produced lower maximal PO which may relate to impaired balance in older, larger adults. The increase in absolute PO is smaller than the magnitude of weight gain, meaning in vivo locomotor function is likely to be impaired in old obese adults, with an association between greater body mass and poorer normalised power output for the soleus. An obesity-induced reduction in diaphragm contractility will likely impair in vivo respiratory function and consequently contribute further to the negative cycle of obesity.

Work loop dynamics of the pigeon (Columba livia) humerotriceps demonstrate potentially diverse roles for active wing morphing.

Control of wing shape is believed to be a key feature that allows most birds to produce aerodynamically efficient flight behaviors and high maneuverability. Anatomical organization of intrinsic wing muscles suggests specific roles for the different motor elements in wing shape modulation, but testing these hypothesized functions requires challenging measurements of muscle activation and strain patterns, and force dynamics. The wing muscles that have been best characterized during flight are the elbow muscles of the pigeon (Columba livia). In vivo studies during different flight modes revealed variation in strain profile, activation timing and duration, and contractile cycle frequency of the humerotriceps, suggesting that this muscle may alter wing shape in diverse ways. To examine the multifunction potential of the humerotriceps, we developed an in situ work loop approach to measure how activation duration and contractile cycle frequency affected muscle work and power across the full range of activation onset times. The humerotriceps produced predominantly net negative power, likely due to relatively long stimulus durations, indicating that it absorbs work, but the work loop shapes also suggest varying degrees of elastic energy storage and release. The humerotriceps consistently exhibited positive and negative instantaneous power within a single contractile cycle, across all treatments. When combined with previous in vivo studies, our results indicate that both within and across contractile cycles, the humerotriceps can dynamically shift among roles of actuator, brake, and stiff or compliant spring, based on activation properties that vary with flight mode.

An exercise-induced improvement in isolated skeletal muscle contractility does not affect the performance-enhancing benefit of 70 µmol l-1 caffeine treatment.

This study aimed to examine the effects of exercise-induced increases in skeletal muscle contractile performance on isolated skeletal muscle caffeine sensitivity in mice. CD1 mice (n=28; 30 weeks old) either served as controls or underwent 8 weeks of voluntary wheel running. Following the treatment intervention, whole soleus (SOL) or a section of the costal diaphragm (DIA) was isolated from each mouse and tested to determine the effect of 70 µmol l-1 caffeine on work loop power output. Although caffeine elicited a significant increase in power of both the SOL and the DIA relative to levels in a non-caffeine-treated control, the effect was not different between the experimental groups, despite the muscles of the trained group producing significantly greater muscle power. There was no significant relationship between training volume or baseline work loop power and the caffeine response. These results indicate that an exercise-induced increase in muscle performance did not influence the performance-enhancing effects of caffeine.

Investigating a dose-response relationship between high-fat diet consumption and the contractile performance of isolated mouse soleus, EDL and diaphragm muscles.

Recent evidence has demonstrated an obesity-induced, skeletal muscle-specific reduction in contractile performance. The extent and magnitude of these changes in relation to total dose of high-fat diet consumption remains unclear. This study aimed to examine the dose-response relationship between a high-fat diet and isolated skeletal muscle contractility. 120 female CD1 mice were randomly assigned to either control group or groups receiving 2, 4, 8 or 12 weeks of a high-calorie diet (N = 24). At 20weeks, soleus, EDL or diaphragm muscle was isolated (n = 8 in each case) and isometric force, work loop power output and fatigue resistance were measured. When analysed with respect to feeding duration, there was no effect of diet on the measured parameters prior to 8weeks of feeding. Compared to controls, 8-week feeding caused a reduction in normalised power of the soleus, and 8- and 12-week feeding caused reduced normalised isometric force, power and fatigue resistance of the EDL. Diaphragm from the 12-week group produced lower normalised power, whereas 8- and 12-week groups produced significantly lower normalised isometric force. Correlation statistics indicated that body fat accumulation and decline in contractility will be specific to the individual and independent of the feeding duration. The data indicate that a high-fat diet causes a decline in muscle quality with specific contractile parameters being affected in each muscle. We also uniquely demonstrate that the amount of fat gain, irrespective of feeding duration, may be the main factor in reducing contractile performance.