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NASA NTRS1993

Development and evaluation of a musculoskeletal model of the elbow joint complex

This paper describes the development and evaluation of a musculoskeletal model that represents human elbow flexion-extension and forearm pronation-supination. The length, velocity, and moment arm for each of the eight musculotendon actuators were based on skeletal anatomy and position. Musculotendon parameters were determined for each actuator and verified by comparing analytical torque-angle curves with experimental joint torque data. The parameters and skeletal geometry were also utilized in the musculoskeletal model for the analysis of ballistic elbow joint complex movements. The key objective was to develop a computational model, guided by parameterized optimal control, to investigate the relationship among patterns of muscle excitation, individual muscle forces, and movement kinematics. The model was verified using experimental kinematic, torque, and electromyographic data from volunteer subjects performing ballistic elbow joint complex movements.

Gonzalez, Roger V.↗

NASA NTRS2001

ISS Flight 2A.2B (STS-106): Commercial Generic Bioprocessing Apparatus (CGBA) Payload BioServe Space Technologies

The two experiments housed in the Commercial Generic Bioprocessing Apparatus (CGBA) during STS-106 were designed to explore how biological processes are affected by microgravity. The first was a developmental study into the effects of microgravity on motor-neuronal growth in the fruit fly species Drosophila melanogaster and the second study was designed to characterize changes in kidney cell gene expression. The objective of the primary experiment, called NIH-B1, was to determine how gravity affects neuronal development of the D. melanogaster embryo and larvae in microgravity, specifically observing the neural connections to muscle fibers.

Stodieck, Louis↗

NASA NTRS2001

Stimulated single fiber electromyography in the mouse: techniques and normative data

As the number of new transgenic mouse models of human neuromuscular disease continues to increase, the development of sophisticated electrophysiologic techniques for assessing the peripheral nervous system in these models has become important. Neuromuscular junction (NMJ) dysfunction, in particular, is often not detectable by morphologic or other techniques. To enable sensitive testing of murine NMJ function, we developed and tested a method for stimulated single fiber electromyography (S-SFEMG) in the gastrocnemius muscles of anesthetized mice. Jitter was assessed by measuring the mean consecutive latency difference (MCD) of single fiber responses to sciatic nerve stimulation at 2 HZ. Mean MCD values in normothermic mice were in the range of 6-8 micros for different strains, with no MCD values exceeding 25 micros. Reduced core temperature (to 29 degrees--30 degrees C) resulted in increased jitter, whereas intubation and mechanical ventilation of mice did not alter these values. Intraperitoneal and intravenous injection of vecuronium, however, resulted in progressively increased jitter followed by blocking in continuously monitored fibers. These observations validate the utility of S-SFEMG in mice as an index of NMJ function under a variety of physiologic conditions, and suggest that a high safety factor for neuromuscular transmission exists at mouse NMJs. Copyright 2001 John Wiley & Sons, Inc.

Non-NASA Center↗

NASA NTRS2012

International Space Station as Analog of Interplanetary Transit Vehicle For Biomedical Research

Astronaut missions lasting up to six months aboard the International Space Station (ISS) have much in common with interplanetary flights, especially the outbound, Earth-to-Mars transit portion of a Mars mission. Utilization of ISS and other appropriate platforms to prepare for crewed expeditions to planetary destinations including Mars has been the work of NASA's Human Research Program (HRP) since 2005. HRP is charged specifically to understand and reduced the risks to astronaut health and performance in space exploration missions: everything HRP does and has done is directly related to that responsibility. Two major categories of human research have capitalized on ISS capabilities. The first category centers on the biomedical aspects of long-duration exposure to spaceflight factors, including prolonged weightlessness, radiation exposure, isolation and confinement, and actual risk to life and limb. These studies contribute to astronaut safety, health and efficiency on any long-duration missions, whether in low Earth orbit (LEO) or beyond. Qualitatively, weightlessness is weightlessness, whether in LEO or en route to Mars. The HRP sponsors investigations into losses in muscle and bone integrity, cardiovascular function, sensory-motor capability, immune capacity and psychosocial health, and development and demonstration of appropriate treatments and preventative measures. The second category includes studies that are focused on planetary expeditions beyond LEO. For these, ISS offers a high fidelity analog to investigate the combined effects of spaceflight factors (described above) plus the isolation and autonomy associated with simulated increasing distance from Earth. Investigations address crew cohesion, performance and workload, and mission control performance. The behavioral health and performance and space human factors aspects of planetary missions dominate this category. Work has already begun on a new investigation in this category which will examine the effects of a simulated lag in communications (mimicking that expected in transit to Mars) on astronaut performance aboard ISS. Extension of the current ISS increment duration from six months to nine or even twelve months would provide opportunities for expanded research relevant to long duration missions, albeit at the cost of fewer astronauts as subjects for those investigations. Given the possible limited access to ISS after 2020, if ISS is intended to facilitate future exploration missions, then the in-flight human investigations should focus on those that clearly enable future exploration missions.

Charles, John B.↗

NASA NTRS2014

Verification, Validation and Credibility Assessment of a Computational Model of the Advanced Resistive Exercise Device (ARED)

The Advanced Resistive Exercise Device (ARED) is the resistive exercise device used by astronauts on the International Space Station (ISS) to mitigate bone loss and muscle atrophy due to extended exposure to microgravity (micro g). The Digital Astronaut Project (DAP) has developed a multi-body dynamics model of biomechanics models for use in spaceflight exercise physiology research and operations. In an effort to advance model maturity and credibility of the ARED model, the DAP performed verification, validation and credibility (VV and C) assessment of the analyses of the model in accordance to NASA-STD-7009 'Standards for Models and Simulations'.

Werner, C. R.↗

NASA NTRS1997

Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope

BACKGROUND: Autonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope. METHODS AND RESULTS: We studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening. CONCLUSIONS: Patients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.

Non-NASA Center↗

NASA NTRS2017

Perfluorinated Alkyl Acids and Fecundity Assessment in Striped Mullet (Mugil Cephalus) at Merritt Island National Wildlife Refuge

This study investigated wild caught Striped mullet (Mugil cephalus) at Merritt Island National Wildlife Refuge (MINWR) for levels of 15 perfluoroalkyl acids (PFAAs) in tandem with fecundity measurements (n 42) and oocyte developmental stages (n 128). PFAAs measurements were undertaken for liver (n 128), muscle (n 49), and gonad (n 10). No significant negative impacts of liver PFAA burden on wild-caught, mullet fecundity endpoints are observed in this study; however, changes in PFAAs are seen in the liver as mullet progress through different sub-stages of oocyte development. Of the PFAAs with significant changes by sub-stage of oocyte development, the carboxylic acids (perfluorooctanoic acid, perfluorononanoic acid, and perfluorotridecanoic acid) increase in the liver with increasing sub-stage while the sulfonic acid and its precursor (perfluorooctanesulfonic acid (PFOS) and perfluorooctanesulfonamide, respectively) decrease in the liver with increasing stage of oocyte development. This is a unique find and suggests PFAAs change location of compartmentalization as mullet progress towards spawning. Investigations also revealed higher than expected median muscle and gonad levels of PFOS in Striped mullet collected at MINWR (9.01 ngg and 80.2 ngg, respectively).

Jacqueline T Bangma↗

NASA NTRS2006

Biomimetic actuators using electroactive polymers (EAP) as artificial muscles

Evolution has resolved many of nature's challenges leading to lasting solutions with maximal performance and effective use of resources. Nature's inventions have always inspired human achievements leading to effective materials, structures, tools, mechanisms, processes, algorithms, methods, systems and many other benefits. The field of mimicking nature is known as Biomimetics and one of its topics includes electroactive polymers that gain the moniker artificial muscles. Integrating EAP with embedded sensors, self-repair and many other capabilities that are used in composite materials can add greatly to the capability of smart biomimetic systems. Such development would enable fascinating possibilities potentially turning science fiction ideas into engineering reality.

Electroactive Polymers (EAP)↗

NASA NTRS2011

Muscle Adaptations Following Short-Duration Bed Rest with Integrated Resistance, Interval, and Aerobic Exercise

Unloading of the musculoskeletal system during space flight results in deconditioning that may impair mission-related task performance in astronauts. Exercise countermeasures have been frequently tested during bed rest (BR) and limb suspension; however, high-intensity, short-duration exercise prescriptions have not been fully explored. PURPOSE: To determine if a high intensity resistance, interval, and aerobic exercise program could protect against muscle atrophy and dysfunction when performed during short duration BR. METHODS: Nine subjects (1 female, 8 male) performed a combination of supine exercises during 2 weeks of horizontal BR. Resistance exercise (3 d / wk) consisted of squat, leg press, hamstring curl, and heel raise exercises (3 sets, 12 repetitions). Aerobic (6 d / wk) sessions alternated continuous (75% VO2 peak) and interval exercise (30 s, 2 min, and 4 min) and were completed on a supine cycle ergometer and vertical treadmill, respectively. Muscle volumes of the upper leg were calculated pre, mid, and post-BR using magnetic resonance imaging. Maximal isometric force (MIF), rate of force development (RFD), and peak power of the lower body extensors were measured twice before BR (averaged to represent pre) and once post BR. ANOVA with repeated measures and a priori planned contrasts were used to test for differences. RESULTS: There were no changes to quadriceps, hamstring, and adductor muscle volumes at mid and post BR time points compared to pre BR (Table 1). Peak power increased significantly from 1614 +/- 372 W to 1739 +/- 359 W post BR (+7.7%, p = 0.035). Neither MIF (pre: 1676 +/- 320 N vs. post: 1711 +/- 250 N, +2.1%, p = 0.333) nor RFD (pre: 7534 +/- 1265 N/ms vs. post: 6951 +/- 1241 N/ms, -7.7%, p = 0.136) were significantly impaired post BR.

Hackney, Kyle J.↗

NASA NTRS2018

Design and Development of Modules to Support Live Microscopic Imaging on Ground-Based Microgravity Simulators

In space, astronauts are exposed to environmental stressors that often result in physiological changes. One prominent stressor in spaceflight is microgravity, and research has shown that long term microgravity exposure causes muscle atrophy, bone loss, cardiovascular concerns, and vision impairment. It is critical to understand how altered gravity affects physiology on the cellular, molecular, and gene level in order to accurately assess health risks and to develop effective countermeasures. Ground-based microgravity simulators such as random positioning machines (RPMs) are used to produce some of the biological effects of altered gravity on different cell types and organisms. Real-time imaging during simulations are of particular interest as we can study how basic cell functions such as cell division, cell migration, and proliferation progress under microgravity conditions. However, design limitations of present microgravity simulators such as susceptibility to parasitic vibration and displacement of the sample from the center of rotation challenge the accuracy of experiment results and live images. We have developed a cell culture sample holder module suitable for live microscopic imaging on an RPM. CAD modeling and 3D printing technology were used to implement modifications to the sample holder and to install a digital microscope to perform live bright-field and fluorescent imaging. Vibration damping materials were also investigated to allow for stable imaging while the microgravity simulator was within a cell culture incubator. Novel methods and hardware modifications for improving live cell imaging on ground-based microgravity simulators were proposed and discussed.

3D printing↗

NASA NTRS2015

The Hopper: A Wearable Robotic Device Testbed for Micro-Gravity Bone-Loading Proof-of-Concept

Wearable robotic systems are showing increased potential for addressing crew countermeasures needs. Wearable robots offer a compactness, programmability, and eccentric loading capability not present in more conventional exercise equipment. Correspondingly, advancements in the man to machine interface has progressed, allowing for higher loads to be applied directly to the person in new and novel ways. Recently, the X1 exoskeleton, a lower extremity wearable robot originally designed for mobility assistance and rehabilitation, underwent human subject testing to assess its potential as a knee dynamometer. This was of interest to NASA physiologists because currently strength is not assessed in flight due to hardware limitations, and thus there is a poor understanding of the time course of in-flight changes to muscle strength. The study concluded that the X1 compared well with the Biodex, the "gold standard" in terrestrial dynamometry, with coefficients of variation less than 6.0%. In a following study, the X1 powered ankle was evaluated for its efficacy in exercising calf muscles. Current on-orbit countermeasures equipment does not adequately protect the calf from atrophy. The results of this study were also positive (targeted muscle activity demonstrated via comparing pre- and post-exercise magnetic resonance imaging T2 measurements), again showing the efficacy of wearable robotic devices for addressing the countermeasure needs of our astronauts. Based on these successes and lessons learned, the Grasshopper was co-developed between IHMC (Florida Institute for Human and Machine Cognition) and NASA. The Grasshopper, or the Hopper for short, is a wearable robotic device designed to address muscle and bone density loss for astronauts spending extended periods of time in micro-gravity. The Grasshopper connects to the user's torso like a hiking backpack, over the shoulders and around the waist. At the feet are footplates that strap to the user. There are two actuators, one at each "knee" joint, which are capable of high fidelity torque control. Because the Hopper uses motors instead of gravity to create the load on the user, the device is suited for use on space missions. Exercise in zero-gravity conditions is critical to maintain muscle strength and bone mass. In operation, the actuators try to fold up, or collapse, the device, putting a compressive load between the user's feet and torso. This force is similar to carrying a heavy backpack. The user then bends and extends his or her knees, replicating a weightlifting squat exercise. The applied load is precisely controlled by a computer, and can be programmed to simulate gravitation loads or any desired load prescription, such as free-weight squat exercise. It is even possible to perform eccentric exercises, or negatives, without the need for a spotter. Because the hip joints, as well as the spine and long leg bones, are in the applied load path, there is the potential to stimulate bone growth, countering the typical bone loss when astronauts return from extended duration space travel.

Beck, C. E.↗

NASA NTRS2002

Mechanical stimulation improves tissue-engineered human skeletal muscle

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

Non-NASA Center↗

NASA NTRS1996

A double fluorescence staining protocol to determine the cross-sectional area of myofibers using image analysis

A double fluorescence staining protocol was developed to facilitate computer based image analysis. Myofibers from experimentally treated (irradiated) and control growing turkey skeletal muscle were labeled with the anti-myosin antibody MF-20 and detected using fluorescein-5-isothiocyanate (FITC). Extracellular material was stained with concanavalin A (ConA)-Texas red. The cross-sectional area of the myofibers was determined by calculating the number of pixels (0.83 mu m(2)) overlying each myofiber after subtracting the ConA-Texas red image from the MF-20-FITC image for each region of interest. As expected, myofibers in the irradiated muscle were smaller (P < 0.05) than those in the non-irradiated muscle. This double fluorescence staining protocol combined with image analysis is accurate and less labor-intensive than classical procedures for determining the cross-sectional area of myofibers.

Non-NASA Center↗

NASA NTRS1995

Human-like Compliance for Dexterous Robot Hands

This paper describes the Active Electromechanical Compliance (AEC) system that was developed for the Jau-JPL anthropomorphic robot. The AEC system imitates the functionality of the human muscle's secondary function, which is to control the joint's stiffness: AEC is implemented through servo controlling the joint drive train's stiffness. The control strategy, controlling compliant joints in teleoperation, is described. It enables automatic hybrid position and force control through utilizing sensory feedback from joint and compliance sensors. This compliant control strategy is adaptable for autonomous robot control as well. Active compliance enables dual arm manipulations, human-like soft grasping by the robot hand, and opens the way to many new robotics applications.

Compliant Control↗

NASA NTRS2007

Locomotor Dysfunction after Spaceflight: Characterization and Countermeasure Development

Astronauts returning from space flight show disturbances in locomotor control manifested by changes in various sub-systems including head-trunk coordination, dynamic visual acuity, lower limb muscle activation patterning and kinematics (Glasauer, et al., 1995; Bloomberg, et al., 1997; McDonald, et al., 1996; 1997; Layne, et al., 1997; 1998, 2001, 2004; Newman, et al., 1997; Bloomberg and Mulavara, 2003). These post flight changes in locomotor performance, due to neural adaptation to the microgravity conditions of space flight, affect the ability of crewmembers especially after a long duration mission to egress their vehicle and perform extravehicular activities soon after landing on Earth or following a landing on the surface of the Moon or Mars. At present, no operational training intervention is available pre- or in- flight to mitigate post flight locomotor disturbances. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially "learns to learn" and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to "normal". Rather the training regimen should facilitate the reorganization of available sensorimotor sub-systems to achieve safe and effective locomotion as soon as possible after space flight. We have previously confirmed that subjects participating in adaptive generalization training programs, using a variety of visuomotor distortions and different motor tasks from throwing to negotiating an obstacle course as the dependent measure, can learn to enhance their ability to adapt to a novel sensorimotor environment (Roller et al., 2001; Cohen et al. 2005). Importantly, this increased adaptability is retained even one month after completion of the training period. Our laboratory is currently developing adaptive generalization training procedures and the associated flight hardware to implement such a training program, using variations of visual flow, subject loading, and treadmill speed; during regular in-flight treadmill operations.

Mulavara, A. P.↗

NASA NTRS2007

An Implanted, Stimulated Muscle Powered Piezoelectric Generator

A totally implantable piezoelectric generator system able to harness power from electrically activated muscle could be used to augment the power systems of implanted medical devices, such as neural prostheses, by reducing the number of battery replacement surgeries or by allowing periods of untethered functionality. The features of our generator design are no moving parts and the use of a portion of the generated power for system operation and regulation. A software model of the system has been developed and simulations have been performed to predict the output power as the system parameters were varied within their constraints. Mechanical forces that mimic muscle forces have been experimentally applied to a piezoelectric generator to verify the accuracy of the simulations and to explore losses due to mechanical coupling. Depending on the selection of system parameters, software simulations predict that this generator concept can generate up to approximately 700 W of power, which is greater than the power necessary to drive the generator, conservatively estimated to be 50 W. These results suggest that this concept has the potential to be an implantable, self-replenishing power source and further investigation is underway.

Lewandowski, Beth↗

NASA NTRS1992

The role of pyridoxine as a countermeasure for in-flight loss of lean body mass

Ground based and in flight research has shown that humans, under conditions of microgravity, sustain a loss of lean body tissue (protein) and changes in several biological processes including, reductions in red blood cell mass, and neurotransmitters. The maintenance of muscle mass, the major component of lean body mass, is required to meet the needs of space station EVAs. Central to the biosynthesis of amino acids, the building blocks of protein, is pyridoxine (vitamin B-6). Muscle mass integrity requires the availability of vitamin B-6 for protein metabolism and neurotransmitter synthesis. Furthermore, the formation of red blood cells require pyridoxine as a cofactor in the biosynthesis of hemoglobin, a protein that carries oxygen to tissues. In its active form, pyridoxal-5'-phosphate (PLP), vitamin B-6 serves as a link between amino acid and carbohydrate metabolism through intermediates of glycolysis and the tricarboxylic acid cycle. In addition to its role in energy metabolism, PLP is involved in the biosynthesis of hemoglobin and neurotransmitter which are necessary for neurological functions. Alterations in pyridoxine metabolism may affect countermeasures designed to overcome some of these biochemical changes. The focus of this research is to determine the effects of microgravity on the metabolic utilization of vitamin B-6, integrating nutrition as an integral component of the countermeasure (exercise) to maintain lean body mass and muscle strength. The objectives are: 1) to determine whether microgravity effects the metabolic utilization of pyridoxine and 2) to quantitate changes in B-6 vitamer distribution in tissue and excreta relative to loss of lean body tissue. The rationale for this study encompasses the unique challenge to control biochemical mechanisms effected during space travel and the significance of pyridoxine to maintain and counter muscle integrity for EVA activities. This experiment will begin to elucidate the importance of biochemical interactions between micronutrients and the homeostasis condition of biological processes in the space environment. To address this research topic a simulated microgravity model has been developed. The experiment uses radioisotopically labelled pyridoxine administered as an oral dose to rats which are maintained by tail suspension to simulate a microgravity environment. At the termination of the study, liver, muscle, blood and urine are collected and analyzed by reverse phase high pressure liquid chromatography to determine the quantity and distribution of the B-6 vitamers in tissue and excreta relative to lean body tissue loss. Earlier studies, published by this investigator, have shown that differences in vitamer distribution among samples from experimental versus control subjects indicate changes in metabolic utilization and storage of vitamin B-6.

Gilbert, Joyce A.↗

NASA NTRS1976

Mineral and nitrogen metabolic studies on Skylab flights and comparison with effects of earth long-term recumbency

A metabolic study of the effects of space flight on various chemical elements, particularly those with special relevance to the musculo-skeletal system, was carried out on the nine astronauts who participated in the three Skylab flights of 28, 59 and 84 days in 1973-1974. The study required of the cooperating crewmen constant dietary intake, continuous 24-hour urine collections and total fecal collections for 21-31 days before each flight, throughout each flight and for 17-18 days post-flight. Increases in urinary calcium and negative calcium balances during space flight were generally similar to those found in previous immobilization and bedrest studies. The persistence of these alterations in calcium metabolism throughout the flights suggested that calcium losses would continue in weightlessness for a very long time. Significant losses of nitrogen and phosphorus occurred, associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite rigorous exercise regimens in flight. It was concluded that unless protective measures can be developed, capable musculo-skeletal function is likely to be impaired in space flights, ultimately to be conducted to Mars, of 1-1/2 to 3 years duration.

Whedon, G. D.↗