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At least 19 records

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

Tsika, R. W.↗

Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

Non-NASA Center↗

Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.

Non-NASA Center↗

ANG II is required for optimal overload-induced skeletal muscle hypertrophy

ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

NASA Discipline Musculoskeletal↗

Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

Myocardial hypertrophy is one of the basic mechanisms by which the heart compensates for hemodynamic overload. The mechanisms by which hemodynamic overload is transduced by the cardiac muscle cell and translated into cardiac hypertrophy are not completely understood. Candidates include activation of the renin-angiotensin system (RAS) and angiotensin II receptor (AT1) stimulation. In this study, we tested the hypothesis that load, independent of the RAS, is sufficient to stimulate cardiac growth. Four groups of cats were studied: 14 normal controls, 20 pulmonary artery-banded (PAB) cats, 7 PAB cats in whom the AT1 was concomitantly and continuously blocked with losartan, and 8 PAB cats in whom the angiotensin-converting enzyme (ACE) was concomitantly and continuously blocked with captopril. Losartan cats had at least a one-log order increase in the ED50 of the blood pressure response to angiotensin II infusion. Right ventricular (RV) hypertrophy was assessed using the RV mass-to-body weight ratio and ventricular cardiocyte size. RV hemodynamic overload was assessed by measuring RV systolic and diastolic pressures. Neither the extent of RV pressure overload nor RV hypertrophy that resulted from PAB was affected by AT1 blockade with losartan or ACE inhibition with captopril. RV systolic pressure was increased from 21 +/- 3 mmHg in normals to 68 +/- 4 mmHg in PAB, 65 +/- 5 mmHg in PAB plus losartan and 62 +/- 3 mmHg in PAB plus captopril. RV-to-body weight ratio increased from 0.52 +/- 0.04 g/kg in normals to 1.11 +/- 0.06 g/kg in PAB, 1.06 +/- 0.06 g/kg in PAB plus losartan and 1.06 +/- 0.06 g/kg in PAB plus captopril. Thus 1) pharmacological modulation of the RAS with losartan and captopril did not change the extent of the hemodynamic overload or the hypertrophic response induced by PAB; 2) neither RAS activation nor angiotensin II receptor stimulation is an obligatory and necessary component of the signaling pathway that acts as an intermediary coupling load to the hypertrophic response; and 3) load, independent of the RAS, is capable of stimulating cardiac growth.

Non-NASA Center↗

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Non-NASA Center↗

Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload

Sleep loss, circadian desynchronization, and work overload occur to some extent for ground and flight crews, prior to and during spaceflight missions. Ground evidence indicates that such risk factors may lead to performance decrements and adverse health outcomes, which could potentially compromise mission objectives. Efforts are needed to identify the environmental and mission conditions that interfere with sleep and circadian alignment, as well as individual differences in vulnerability and resiliency to sleep loss and circadian desynchronization. Specifically, this report highlights a collection of new evidence to better characterize the risk and reveals new gaps in this risk as follows: Sleep loss is apparent during spaceflight. Astronauts consistently average less sleep during spaceflight relative to on the ground. The causes of this sleep loss remain unknown, however ground-based evidence suggests that the sleep duration of astronauts is likely to lead to performance impairment and short and long-term health consequences. Further research is needed in this area in order to develop screening tools to assess individual astronaut sleep need in order to quantify the magnitude of sleep loss during spaceflight; current and planned efforts in BHP's research portfolio address this need. In addition, it is still unclear whether the conditions of spaceflight environment lead to sleep loss or whether other factors, such as work overload lead to the reduced sleep duration. Future data mining efforts and continued data collection on the ISS will help to further characterize factors contributing to sleep loss. Sleep inertia has not been evaluated during spaceflight. Ground-based studies confirm that it takes two to four hours to achieve optimal performance after waking from a sleep episode. Sleep inertia has been associated with increased accidents and reduced performance in operational environments. Sleep inertia poses considerable risk during spaceflight when emergency situations necessitate that crewmembers wake from sleep and make quick decisions. A recently completed BHP investigation assesses the effects of sleep inertia upon abrupt awakening, with and without hypnotics currently used in spaceflight; results from this investigation will help to inform strategies relative to sleep inertia effects on performance. Circadian desynchrony has been observed during spaceflight. Circadian desynchrony during spaceflight develops due to schedule constraints requiring non-24 operations or 'slam-shifts' and due to insufficient or mis-timed light exposure. In addition, circadian misalignment has been associated with reduced sleep duration and increased medication use. In ground-based studies, circadian desynchrony has been associated with significant performance impairment and increased risk of accidents when operations coincide with the circadian nadir. There is a great deal of information available on how to manage circadian misalignment, however, there are currently no easily collected biomarkers that can be used during spaceflight to determine circadian phase. Current research efforts are addressing this gap. Work overload has been documented during current spaceflight operations. NASA has established work hour guidelines that limit shift duration, however, schedule creep, where duty requirements necessitate working beyond scheduled work hours, has been reported. This observation warrants the documentation of actual work hours in order to improve planning and in order to ensure that astronauts receive adequate down time. In addition to concerns about work overload, ground based evidence suggests that work underload may be a concern during deep space missions, where torpor may develop and physically demanding workload will be exchanged for monitoring of autonomous systems. Given that increased automation is anticipated for exploration vehicles, fatigue effects in the context of such systems needs to be further understood. Performance metrics are needed to evaluate fitness-for-duty during spaceflight. Although ground-based evidence supports the notion that sleep loss, circadian desynchronization and work overload lead to performance impairment, inconsistency in the measures used to evaluate performance during spaceflight make it difficult to evaluate the magnitude of performance impairment during spaceflight. Work is underway to standardize measures of performance evaluation during spaceflight. Once established, such performance indicators need to be correlated with operational performance. Individual differences in sleep need and circadian preference, phase shifting ability and period have been documented in ground-based studies. Individual differences in response to sleep loss and circadian misalignment have also been documented and are presumed to be associated with genetic polymorphisms. No studies have systematically reported individual differences in sleep or circadian-related outcomes during spaceflight. More work is needed in this area in order to identify genetic or phenotypic biomarkers that predict resilience or vulnerability to sleep loss in order to personalize countermeasure strategies and mitigate performance impairment during spaceflight. Two laboratory and field investigations specific to this topic are currently ongoing; additional efforts, including an effort to mine existing biological data from spaceflight relative to sleep and circadian outcomes, are planned. Sex differences in sleep need and circadian period and phase have been reported in ground-based studies. The impact of these sex differences on performance is unclear. Sex differences in sleep need and circadian rhythms have not been systematically studied during spaceflight, presumably due to the small number of women that have flown in space. More research is needed in this area to evaluate whether any of the observed sex differences in physiology lead to altered performance in spaceflight and on the ground.

Flynn-Evans, Erin↗

Overload protection system for power inverter

An overload protection system for a power inverter utilized a first circuit for monitoring current to the load from the power inverter to detect an overload and a control circuit to shut off the power inverter, when an overload condition was detected. At the same time, a monitoring current inverter was turned on to deliver current to the load at a very low power level. A second circuit monitored current to the load, from the monitoring current inverter, to hold the power inverter off through the control circuit, until the overload condition was cleared so that the control circuit may be deactivated in order for the power inverter to be restored after the monitoring current inverter is turned off completely.

Nagano, S.↗

Prostaglandin E2 Restores Cancellous Bone to Immobilized Limb and Adds Bone to Overloaded Limb in Right Hindlimb Immobilization Rats

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127 to +188 percent) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels. Our findings indicate that daily 3 or 6 mg PGE2/kg/d treatment restores and maintains PTM cancellous bone mass in continuously immobilized (right) tibiae, and adds and maintains extra bone to slightly overloaded PTM cancellous bone in female rats.

Li, M.↗

Orion Capsule Parachute Assembly System (CPAS) Overload Testing Approach and Results

The qualification of the Orion Capsule Parachute Assembly System (CPAS) system includes exposure to loads and dynamic pressures above the required values as validation of the parachutes' structural integrity. As outlined in the certification plan, each of the four parachutes of the system are to be subjected to 110% of their respective maximum dynamic pressure requirements. The Main and Drogue parachutes have satisfied this overload condition in drop testing and due to cost and schedule constraints, the Forward Bay Cover Parachute (FBCP) and Pilot parachute were subjected to the overload condition in the ground testing described in this document. The test objectives and pass/fail criteria were established and require the parachutes to achieve and maintain a target riser load (associated with a minimum of 110% dynamic pressure overload) for a minimum of three seconds while sustaining no failures of any structural members (vent hoop, radials, suspension line) or any damage which propagates into catastrophic failure of the canopy. Considering the assumptions and limitations associated with the ground testing (primarily non-uniform flow field of the ground test system and variations in parachute manufacturing), a method of establishing the desired overload condition was determined by the technical community and covers the 2-sigma bounds of the drag area distribution derived from drop testing. On June 27, 2017 the testing was executed at the High Velocity Airflow System (HiVAS) facility located at the Weapon Survivability Laboratory (WSL) at the Naval Air Warfare Center, Weapons Division (NAWCWD) China Lake. Engineering Development Unit (EDU) parachutes were used as pathfinders to gain experience with achieving the test conditions. Additional runs were executed to measure the airflow at the same location as the canopy skirt, although this data is not required to satisfy the test objectives and parachute pass/fail criteria. The qualification parachutes were successfully exposed to the target conditions and sustained only minor damage.

Daum, Jared S.↗

Modelling and measurement of crack closure and crack growth following overloads and underloads

Ignoring crack growth retardation following overloads can result in overly conservative life predictions in structures subjected to variable amplitude fatigue loading. Crack closure is believed to contribute to the crack growth retardation, although the specific closure mechanism is dabatable. The delay period and corresponding crack growth rate transients following overload and overload/underload cycles were systematically measured as a function of load ratio and overload magnitude. These responses are correlated in terms of the local 'driving force' for crack growth, i.e. the effective stress intensity factor range. Experimental results are compared with the predictions of a Dugdale-type (1960) crack closure model, and improvements in the model are suggested.

Dexter, R. J.↗

Mechanisms of fatigue crack retardation following single tensile overloads in powder metallurgy aluminum alloys

In ingot metallurgy (IM) alloys, the number of delay cycles following a single tensile overload typically increases from a minimum at an intermediate baseline stress intensity range, Delta-K(B), with decreasing Delta-K(B) approaching threshold and increasing Delta-K(B) approaching unstable fracture to produce a characteristic 'U' shaped curve. Two models have been proposed to explain this behavior. One model is based on the interaction between roughness and plasticity-induced closure, while the other model only utilizes plasticity-induced closure. This article examines these models, using experimental results from constant amplitude and single overload fatigue tests performed on two powder metallurgy (PM) aluminum alloys, AL-905XL and AA 8009. The results indicate that the 'U'-shaped curve is primarily due to plasticity-induced closure, and that the plasticity-induced retardation effect is through-thickness in nature, occurring in both the surface and interior regions. However, the retardation effect is greater at the surface, because the increase in plastic strain at the crack tip and overload plastic zone size are larger in the plane-stress surface regions than in the plane-strain interior regions. These results are not entirely consistent with either of the proposed models.

Bray, G. H.↗

Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

Non-NASA Center↗

Fuse protects circuit from voltage and current overloads

Low-melting resistor connected in series with the load protects the circuit against current overloads. It protects test subjects and patients being monitored by electronic instrumentation from inadvertant overloads of current, and sensitive electronic equipment against high-voltage damage.

Casey, L. O.↗

Overload protection for switching regulators

Circuit protects all output lines of switching regulator against overloads without requiring current sensors on every line. If overload is sensed, device short circuits bias on switching transistor so that power is rapidly cut off from loads. Circuit also includes delay network to inhibit erroneous operation during startup.

Lachochi, E.↗

Aviation noise overload in the immediate proximity of the Warsaw-Okecie airport

The results are presented for investigations on noise overload around the Warszawa-Okecie airport on persons inhabiting the area where it exceeds 100 dB for a single aircraft flight. Of 256 subjects, 91.1 percent complained about aircraft noise overload. In the population studied considerable differences were noted respecting the subjective sensitivity scale. Statistical analysis showed numerous correlations between the individual noise sensitivity threshold and the subject's state of health, age, sex, type of work, etc. At the same time investigations demonstrated various forms and levels of disturbance in the organism for individual subjects and groups. The most frequent complaint was chronic fatigue (68.1 percent), followed by nervousness (36.6 percent), frequent headaches (36.2 percent), hearing disturbances (30.0 percent) and sleep disorders (23.9 percent).

Koszarny, Z.↗

Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

Max, S. R.↗

Fatigue crack growth with single overload - Measurement and modeling

This paper compares experiments with an analytical model of fatigue crack growth under variable amplitude. The stereoimaging technique was used to measure displacements near the tips of fatigue cracks undergoing simple variations in load amplitude-single overloads and overload/underload combinations. Measured displacements were used to compute strains, and stresses were determined from the strains. Local values of crack driving force (Delta-K effective) were determined using both locally measured opening loads and crack tip opening displacements. Experimental results were compared with simulations made for the same load variation conditions using Newman's FAST-2 model. Residual stresses caused by overloads, crack opening loads, and growth retardation periods were compared.

Davidson, D. L.↗