bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of interstitial fluid volume in superficial tissues detected by a miniature ultrasound device
Authors: Eichler Wolfgang , Eisenbeiss Christine , Schumacher Jan , Klaus Stefan , Vogel Rolf , Klotz Karl Friedrich
Published: December 2017

We evaluated the changes of tissue layer thickness in circumscribed superficial tissue areas with a 10-MHz A-mode and a 20-MHz B-mode ultrasound device under alterations in body posture and plasma volume to detect fluid shifts between the different compartments. In 20 male volunteers, we measured tissue thickness by A mode and corium and subcutis thickness by B mode at the forehead before and 30 min after three procedures: change from upright to supine position (P1); change from upright to 30° head-down-tilt position (P2); infusion of 10 ml/kg body wt of Ringer solution (P3). We found a significant correlation between baseline tissue thickness and the sum of corium and subcutis thicknesses ( r = 0.75, P < 0.01). The changes of body posture and plasma volume resulted in significant increases of tissue thickness (P1, 2.9%; P2, 11.6%; P3, 5.8%) and corium thickness (P1, 4.7%; P2, 8.1%; P3, 9.1%) but not of the sum of chorium and subcutis thicknesses. We conclude that fluid shifts from the intravascular to the extravascular compartment are detectible by evaluating corium thickness with a B-mode, or more easily tissue thickness with an A-mode, ultrasound device.
Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr
Authors: Janssen Ian , Heymsfield Steven B. , Wang ZiMian , Ross Robert
Published: December 2017

We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly ( P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body ( P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained ∼50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.
Estimation of skeletal muscle mass by bioelectrical impedance analysis
Authors: Janssen Ian , Heymsfield Steven B. , Baumgartner Richard N. , Ross Robert
Published: December 2017

The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared with BIA measurements in a multiethnic sample of 388 men and women, aged 18–86 yr, at two different laboratories. Within each laboratory, equations for predicting SM mass from BIA measurements were derived using the data of the Caucasian subjects. These equations were then applied to the Caucasian subjects from the other laboratory to cross-validate the BIA method. Because the equations cross-validated (i.e., were not different), the data from both laboratories were pooled to generate the final regression equation[Formula: see text] [Formula: see text] where Ht is height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women = 0; and age is in years. The r 2 and SE of estimate of the regression equation were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was applicable to Hispanics and African-Americans, but it underestimated SM mass in Asians. These results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.
Role of KATP + channels and adenosine in the control of coronary blood flow during exercise
Authors: Richmond Keith Neu , Tune Johnathan D. , Gorman Mark W. , Feigl Eric O.
Published: December 2017

The present study was designed to examine the role of ATP-sensitive potassium (KATP +) channels during exercise and to test the hypothesis that adenosine increases to compensate for the loss of KATP + channel function and adenosine inhibition produced by glibenclamide. Graded treadmill exercise was used to increase myocardial O2 consumption in dogs before and during KATP + channel blockade with glibenclamide (1 mg/kg iv), which also blocks adenosine mediated coronary vasodilation. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous values by using a previously tested mathematical model (Kroll K and Stepp DW. Am J Physiol Heart Circ Physiol 270: H1469–H1483, 1996). Coronary venous O2 tension was used as an index of the balance between O2 delivery and myocardial O2consumption. During control exercise, myocardial O2consumption increased ∼4-fold, and coronary venous O2tension fell from 19 to 14 Torr. After KATP +channel blockade, coronary venous O2 tension was decreased below control vehicle values at rest and during exercise. However, during exercise with glibenclamide, the slope of the line of coronary venous O2 tension vs. myocardial O2 consumption was the same as during control exercise. Estimated interstitial adenosine concentration with glibenclamide was not different from control vehicle and was well below the level necessary to overcome the 10-fold shift in the adenosine dose-response curve due to glibenclamide. In conclusion, KATP + channel blockade decreases the balance between resting coronary O2 delivery and myocardial O2 consumption, but KATP +channels are not required for the increase in coronary blood flow during exercise. Furthermore, interstitial adenosine concentration does not increase to compensate for the loss of KATP +channel function.
Strength loss after eccentric contractions is unaffected by creatine supplementation
Authors: Warren Gordon L. , Fennessy John M. , Millard-Stafford Melinda L.
Published: December 2017

This study's objective was to determine whether 14 days of dietary creatine supplementation preceding an injurious bout of eccentric contractions affect the in vivo strength loss of mouse anterior crural muscles. Three groups of nine mice each were fed a meal diet for 14 days, one group at each of three levels of creatine supplementation (i.e., 0, 0.5, and 1% creatine). Electrically stimulated concentric, isometric, and eccentric contraction torques produced about the ankle were measured both before and after a bout of 150 eccentric contractions. Tibialis anterior muscle creatine concentration was significantly increased by the supplementation, being 12% higher in the mice fed the 1% creatine diet compared with control mice. After the bout of eccentric contractions, the reductions in torque (i.e., 46–58%) were similar for the isometric contraction, all eccentric contractions, and the slow (i.e., ≤200o/s) concentric contractions; above 200o/s, the percent reduction in concentric torque increased progressively to 85–88% at 1,000–1,200o/s. However, there was no effect of creatine supplementation on the isometric torque loss or on the torque loss at any eccentric or concentric angular velocity ( P ≥ 0.62). In conclusion, a moderate increase in muscle creatine concentration induced by dietary supplementation in mice does not affect the strength loss after eccentric contractions.
Racial differences in visceral adipose tissue but not anthropometric markers of health-related variables
Authors: Perry Arlette C. , Applegate E. Brooks , Jackson M. Loreto , Deprima Steven , Goldberg Ronald B. , Ross Robert , Kempner Lani , Feldman Brandon B.
Published: December 2017

This study sought to determine whether visceral adipose tissue (VAT) and/or its anthropometric surrogates could significantly predict health-related variables (HRV) in overweight Caucasian (CC) ( n = 36) and African-American (AA) ( n = 30) women. With the use of magnetic resonance imaging, findings showed significantly higher volume and area of VAT ( P < 0.0001 for both) as well as higher triacylglycerol ( P = 0.009) in CC compared with AA women. Furthermore, VAT volume, race, and VAT volume × race interaction could significantly predict triacylglycerol ( P = 0.0094), high-density lipoprotein cholesterol ( P = 0.0057), insulin ( P = 0.0002), and insulin resistance ( P < 0.0001). Additionally, the VAT volume × race interaction for insulin ( P = 0.040) and insulin resistance ( P = 0.003) was significant. In a separate analysis, waist circumference and race predicted the identical variables. Our results support the use of volume or area of VAT in predicting HRV in CC women; however, its use in AA women appears limited. In contrast, waist circumference can provide a suitable VAT alternative for both CC and AA women; however, VAT clearly represents the more powerful predictor.
Supine lower body negative pressure exercise simulates metabolic and kinetic features of upright exercise
Authors: Boda Wanda L. , Watenpaugh Donald E. , Ballard Richard E. , Hargens Alan R.
Published: December 2017

Exercise within an artificial gravity environment may help prevent microgravity-induced deconditioning. We hypothesized that supine lower body negative pressure (LBNP) exercise simulates physiological and biomechanical features of upright exercise. Walking (4.5 ± 0.3 km/h) and running (8.0 ± 1.0 km/h) while supine within a LBNP exerciser were compared with walking and running while upright. Eight healthy subjects exercised for 5 min at each of the four posture/gait conditions. LBNP of 52 ± 4 mmHg generated one body weight of supine ground reaction force (GRF). Gait parameters and GRFs were measured during the third minute of exercise, and heart rate and oxygen consumption were measured during the fifth minute. Oxygen consumption during supine LBNP treadmill exercise [walking: 14.6 ± 0.9; running: 32.2 ± 1.6 (SE) ml · min−1 · kg−1] was similar to that during upright treadmill exercise (walking: 15.1 ± 0.9; running: 34.0 ± 1.9 ml · min−1 · kg−1). Heart rate for supine LBNP exercise (grand mean: 133 ± 11 beats/min) was also similar to that for upright exercise (136 ± 11 beats/min). Footward forces integrated over each stride (330.5 ± 34.4 vs. 319.1 ± 29.6 N · s) and rate of force generation (26,483 ± 4,310 vs. 25,634 ± 4,434 N/s) were similar for upright and LBNP exercise, respectively. Our collective results indicate that supine exercise within LBNP can simulate the physiological stress and GRFs that are generated during upright gait.
Effects of exercise training and ACE inhibition on insulin action in rat skeletal muscle
Authors: Foianini Kara R. , Steen Michelle S. , Kinnick Tyson R. , Schmit Melanie B. , Youngblood Erik B. , Henriksen Erik J.
Published: December 2017

Our laboratory has demonstrated (Steen MS, Foianini KR, Youngblood EB, Kinnick TR, Jacob S, and Henriksen EJ, J Appl Physiol 86: 2044–2051, 1999) that exercise training and treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril interact to improve insulin action in insulin-resistant obese Zucker rats. The present study was undertaken to determine whether a similar interactive effect of these interventions is manifest in an animal model of normal insulin sensitivity. Lean Zucker ( Fa/−) rats were assigned to either a sedentary, trandolapril-treated (1 mg · kg−1· day−1for 6 wk), exercise-trained (treadmill running for 6 wk), or combined trandolapril-treated and exercise-trained group. Exercise training alone or in combination with trandolapril significantly ( P < 0.05) increased peak oxygen consumption by 26–32%. Compared with sedentary controls, exercise training alone or in combination with ACE inhibitor caused smaller areas under the curve for glucose (27–37%) and insulin (41–44%) responses during an oral glucose tolerance test. Exercise training alone or in combination with trandolapril also improved insulin-stimulated glucose transport in isolated epitrochlearis (33–50%) and soleus (58–66%) muscles. The increases due to exercise training alone or in combination with trandolapril were associated with enhanced muscle GLUT-4 protein levels and total hexokinase activities. However, there was no interactive effect of exercise training and ACE inhibition observed on insulin action. These results indicate that, in rats with normal insulin sensitivity, exercise training improves oral glucose tolerance and insulin-stimulated muscle glucose transport, whereas ACE inhibition has no effect. Moreover, the beneficial interactive effects of exercise training and ACE inhibition on these parameters are not apparent in lean Zucker rats and, therefore, are restricted to conditions of insulin resistance.
Potent bronchoprotective effect of deep inspiration and its absence in asthma
Authors: Kapsali Trisevgeni , Permutt Solbert , Laube Beth , Scichilone Nicola , Togias Alkis
Published: December 2017

In the absence of deep inspirations, healthy individuals develop bronchoconstriction with methacholine inhalation. One hypothesis is that deep inspiration results in bronchodilation. In this study, we tested an alternative hypothesis, that deep inspiration acts as a bronchoprotector. Single-dose methacholine bronchoprovocations were performed after 20 min of deep breath inhibition, in nine healthy subjects and in eight asthmatics, to establish the dose that reduces forced expiratory volume in 1 s by >15%. The provocation was repeated with two and five deep inspirations preceding methacholine. Additional studies were carried out to assess optimization and reproducibility of the protocol and to rule out the possibility that bronchoprotection may result from changes in airway geometry or from differential spasmogen deposition. In healthy subjects, five deep inspirations conferred 85% bronchoprotection. The bronchoprotective effect was reproducible and was not attributable to increased airway caliber or to differential deposition of methacholine. Deep inspirations did not protect the bronchi of asthmatics. We demonstrated that bronchoprotection is a potent physiologic function of lung inflation and established its absence, even in mild asthma. This observation deepens our understanding of airway dysfunction in asthma.
In situ localization of cholesterol in skeletal muscle by use of a monoclonal antibody
Authors: Clarke Mark S. F. , Vanderburg Charles R. , Bamman Marcas M. , Caldwell Robert W. , Feeback Daniel L.
Published: December 2017

A common perception is that cholesterol, the major structural lipid found in mammalian membranes, is localized nearly exclusively to the plasma membrane of living cells and that it is found in much smaller quantities in internal membranes. This perception is based almost exclusively on cell fractionation studies, in which density gradient centrifugation is used for purification of discrete subcellular membrane fractions. Here we describe a monoclonal antibody, MAb 2C5-6, previously reported to detect purified cholesterol in synthetic membranes (Swartz GM Jr, Gentry MK, Amende LM, Blanchette-Mackie EJ, and Alving CR. Proc Natl Acad Sci USA85: 1902–1906, 1988), that is capable of detecting cholesterol in situ in the membranes of skeletal muscle sections. Localization of cholesterol, the dihydropyridine receptor of the T tubule, and the Ca2+-ATPase of the sarcoplasmic reticulum (SERCA2) by means of double and triple immunostaining protocols clearly demonstrates that cholesterol is primarily localized to the sarcoplasmic reticulum membranes of skeletal muscle rather than the sarcolemmal or T tubule membranes. The availability of this reagent and its ability to spatially localize cholesterol in situ may provide a greater understanding of the relationship between membrane cholesterol content and transmembrane signaling in skeletal muscle.
Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans
Authors: Simon Peggy M. , Habel Alfred M. , Daubenspeck J. Andrew , Leiter J. C.
Published: December 2017

We studied the capacity of four “normal” and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within ±3–5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.
Preservation of neural function in the perinate by high PGE2levels acting via EP2receptors
Authors: Najarian Taline , Hardy Pierre , Hou Xin , Lachapelle Julie , Doke Anjali , Gobeil Fernand , Roy Marie-Sylvie , Lachapelle Pierre , Varma Daya R. , Chemtob Sylvain
Published: December 2017

Despite increasingly frequent and longer lasting hypoxic episodes during progressive labor, the neonate is alert and vigorous at birth. We investigated whether high levels of PGs during the perinatal period assist in preserving neural function after such “stressful” hypoxic events. Visual evoked potentials (VEPs) and electroretinograms (ERGs) were recorded before and 45 min after mild moderate asphyxic hypoxia (two 4-min asphyxic-hypoxic periods induced by interrupting ventilation at 8-min intervals) in newborn piglets <12 h old treated or not treated with inhibitors of PG synthase (ibuprofen or diclofenac) with or without PG analogs. At 45 min after the hypoxic episode, P2 and b-wave amplitudes were slightly decreased and latencies were delayed. These changes in the VEP and ERG returned to near normal by 120 min. Ibuprofen and diclofenac decreased brain and retinal PG levels and markedly intensified 45 min after hypoxia-induced changes in VEP and ERG, but cerebral and retinal blood flows improved. Combined treatment with PG synthase inhibitor in combination with 16,16-dimethyl-PGE2(a PGE2analog), but not with PGI2and PGF2αanalogs, and in combination with the EP2receptor agonist butaprost (but not EP1or EP3agonists), prevented ibuprofen- and diclofenac-aggravated postasphyxia electrophysiological changes. In conclusion, high levels of PGE2in nervous tissue, via actions on EP2receptors, seem to contribute to preservation of neural function in the perinate subjected to frequent hypoxic events.
Volume-timing relationships during cough and resistive loading in the cat
Authors: Bolser Donald C. , Davenport Paul W.
Published: December 2017

The relationship between pulmonary volume-related feedback and inspiratory (CTi) and expiratory (CTe) phase durations during cough was determined. Cough was produced in anesthetized cats by mechanical stimulation of the intrathoracic tracheal lumen. During eupnea, the animals were exposed to single-breath inspiratory and expiratory resistive loads. Cough was associated with large increases in inspiratory volume (Vi) and expiratory volume (Ve) but no change in phase durations compared with eupnea. There was no relationship between Viand CTi during coughing. A linear relationship with a negative slope existed between Vi and eupneic inspiratory time during control and inspiratory resistive loading trials. There was no relationship between Ve and CTe during all coughs. However, when the first cough in a series or a single cough was analyzed, the Ve/CTe relationship had a positive slope. A linear relationship with a negative slope existed between Ve and eupneic expiratory time during control and expiratory resistive loading trials. These results support separate ventilatory pattern regulation during cough that does not include modulation of phase durations by pulmonary volume-related feedback.
Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle
Authors: Fitts Robert H. , Riley Danny R. , Widrick Jeffrey J.
Published: December 2017

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.
Constraints on cardiac hypertrophy imposed by myocardial viscosity
Authors: Denslow Stewart
Published: December 2017

Laplace's law constrains how thin the ventricular wall may be without experiencing excessive stress. The present study investigated constraints, imposed by myocardial viscosity (resistance to internal rearrangement), on how thick the wall may be. The ventricle was modeled as a contracting, spherical shell. The analysis demonstrated that viscosity generates stress and energy dissipation with inverse fourth- and eighth-power dependence, respectively, on distance from the cavity center. This result derives from the combination of squared dependence of viscous forces on shearing velocity gradients and the greater shear rearrangement required for inner layers of a contracting sphere. These predictions are based solely on geometry and fundamentals of viscosity and are independent of material properties, cytoskeletal structure, and internal structural forces. Calculated values of energy and force required to overcome viscosity were clearly large enough to affect the extent of thickening of the left ventricle. It is concluded that load-independent viscous resistance to contraction is an important factor in cardiac mechanics, especially of the thickened ventricles of concentric hypertrophy.
Endurance training does not alter the level of neuronal nitric oxide synthase in human skeletal muscle
Authors: Frandsen U. , Höffner L. , Betak A. , Saltin B. , Bangsbo J. , Hellsten Y.
Published: December 2017

The effect of endurance training on neuronal nitric oxide synthase (nNOS) content and distribution in muscle was investigated. Seven male subjects performed 6 wk of one-legged knee-extensor endurance training ( protocol A). Muscle biopsies, obtained from vastus lateralis muscle in the untrained and the trained leg, were analyzed for nNOS protein and activity as well as immunohistochemical distribution of nNOS and endothelial nitric oxide synthase (eNOS). Muscle biopsies were also obtained from another seven male subjects before and after 6 wk of training by endurance running (p rotocol B) and analyzed for nNOS protein. No difference was found in the amount of nNOS protein in the untrained and the trained muscle either with protocol Aor protocol B ( P > 0.05). In protocol A, the activity of nNOS was 4.76 ± 0.56 pmol · mg protein−1 · min−1 in the control leg, and the level was not different in the trained leg ( P> 0.05). nNOS was present in the sarcolemma and cytosol of type I and type II muscle fibers, and the qualitative distribution was similar in untrained and trained muscle. The number of eNOS immunoreactive structures and the number of capillaries per muscle fiber were higher ( P < 0.05) after training than before. The present findings demonstrate that, in contrast to findings on animals, nNOS levels remain unaltered with endurance training in humans. Evidence is also provided that endurance training may increase the amount of eNOS, in parallel with an increase in capillaries in human muscle.
Nine months in space: effects on human autonomic cardiovascular regulation
Authors: Cooke William H. , Ames James E. , Crossman Alexandra A. , Cox James F. , Kuusela Tom A. , Tahvanainen Kari U. O. , Moon L. Boyce , Drescher Jürgen , Baisch Friedhelm J. , Mano Tadaaki , Levine Benjamin D. , Blomqvist C. Gunnar , Eckberg Dwain L.
Published: December 2017

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.
Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling
Authors: Colleran Patrick N. , Wilkerson M. Keith , Bloomfield Susan A. , Suva Larry J. , Turner Russell T. , Delp Michael D.
Published: December 2017

Bone loss occurs as a consequence of exposure to microgravity. Using the hindlimb-unloaded rat to model spaceflight, this study had as its purpose to determine whether skeletal unloading and cephalic fluid shifts alter bone blood flow. We hypothesized that perfusion would be diminished in the hindlimb bones and increased in skeletal structures of the forelimbs and head. Using radiolabeled microspheres, we measured skeletal perfusion during control standing and after 10 min, 7 days, and 28 days of hindlimb unloading (HU). Femoral and tibial perfusion were reduced with 10 min of HU, and blood flow to the femoral shaft and marrow were further diminished with 28 days of HU. Correspondingly, the mass of femora (−11%, P < 0.05) and tibiae (−6%, P < 0.1) was lowered with 28 days of HU. In contrast, blood flow to the skull, mandible, clavicle, and humerus was increased with 10 min HU but returned to control levels with 7 days HU. Mandibular (+10%, P < 0.05), clavicular (+18%, P < 0.05), and humeral (+8%, P < 0.1) mass was increased with chronic HU. The data demonstrate that simulated microgravity alters bone perfusion and that such alterations correspond to unloading-induced changes in bone mass. These results support the hypothesis that alterations in bone blood flow provide a stimulus for bone remodeling during periods of microgravity.
β-Adrenergic blockade augments glucose utilization in horses during graded exercise
Authors: Geor Raymond J. , Hinchcliff Kenneth W. , Sams Richard A.
Published: December 2017

To examine the role of β-adrenergic mechanisms in the regulation of endogenous glucose (Glu) production [rate of appearance (Ra)] and utilization [rate of disappearance (Rd)] and carbohydrate (CHO) metabolism, six horses completed consecutive 30-min bouts of exercise at ∼30% (Lo) and ∼60% (Hi) of estimated maximum O2uptake with (P) and without (C) prior administration of the β-blocker propranolol (0.22 mg/kg iv). All horses completed exercise in C; exercise duration in P was 49.9 ± 1.2 (SE) min. Plasma Glu was unchanged in C during Lo but increased progressively in Hi. In P, plasma Glu rose steadily during Lo and Hi and was higher ( P < 0.05) than in C throughout exercise. Plasma insulin declined during exercise in P but not in C; β-blockade attenuated ( P < 0.05) the rise in plasma glucagon and free fatty acids and exaggerated the increases in epinephrine and norepinephrine. Glu Rawas 8.1 ± 0.8 and 8.4 ± 1.0 μmol · kg−1· min−1at rest and 30.5 ± 3.6 and 42.8 ± 4.1 μmol · kg−1· min−1at the end of Lo in C and P, respectively. During Hi, Glu Raincreased to 54.4 ± 4.4 and 73.8 ± 4.7 μmol · kg−1· min−1in C and P, respectively. Similarly, Glu Rdwas ∼40% higher in P than in C during Lo (27.3 ± 2.0 and 39.5 ± 3.3 μmol · kg−1· min−1in C and P, respectively) and Hi (37.4 ± 2.6 and 61.5 ± 5.3 μmol · kg−1· min−1in C and P, respectively). β-Blockade augmented CHO oxidation (CHOox) with a concomitant reduction in fat oxidation. Inasmuch as estimated muscle glycogen utilization was similar between trials, the increase in CHOoxin P was due to increased use of plasma Glu. We conclude that β-blockade increases Glu Raand Rdand CHOoxin horses during exercise. The increase in Glu Rdunder β-blockade suggests that β-adrenergic mechanisms restrain Glu Rdduring exercise.
Role of neuronal nitric oxide synthase in hypoxia-induced anapyrexia in rats
Authors: Steiner Alexandre A. , Carnio Evelin C. , Branco Luiz G. S.
Published: December 2017

Anapyrexia (a regulated decrease in body temperature) is a response to hypoxia that occurs in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Recently, it has been shown that the NO pathway plays a major role in hypoxia-induced anapyrexia. However, very little is known about which of the three different nitric oxide synthase isoforms (neuronal, endothelial, or inducible) is involved. The present study was designed to test the hypothesis that neuronal nitric oxide synthase (nNOS) plays a role in hypoxia-induced anapyrexia. Body core temperature (Tc) of awake, unrestrained rats was measured continuously using biotelemetry. Rats were submitted to hypoxia, 7-nitroindazole (7-NI; a selective nNOS inhibitor) injection, or both treatments together. Control animals received vehicle injections of the same volume. We observed a significant ( P < 0.05) reduction in Tc of ∼2.8°C after hypoxia (7% inspired O2), whereas intraperitoneal injection of 7-NI at 25 mg/kg caused no significant change in Tc. 7-NI at 30 mg/kg elicited a reduction in Tc and was abandoned in further experiments. When the two treatments were combined (25 mg/kg of 7-NI and 7% inspired O2), we observed a significant attenuation of hypoxia-induced anapyrexia. The data indicate that nNOS plays a role in hypoxia-induced anapyrexia.
Series-to-parallel transition in the filament lattice of airway smooth muscle
Authors: Seow Chun Y. , Pratusevich Victor R. , Ford Lincoln E.
Published: December 2017

Force-velocity curves measured at different times during tetani of sheep trachealis muscle were analyzed to assess whether velocity slowing could be explained by thick-filament lengthening. Such lengthening increases force by placing more cross bridges in parallel on longer filaments and decreases velocity by reducing the number of filaments spanning muscle length. From 2 s after the onset of stimulation, when force had achieved 42% of it final value, to 28 s, when force had been at its tetanic plateau for ∼15 s, velocity decreases were exactly matched by force increases when force was adjusted for changes in activation, as assessed from the maximum power value in the force-velocity curves. A twofold change in velocity could be quantitatively explained by a series-to-parallel change in the filament lattice without any need to postulate a change in cross-bridge cycling rate.
Postprandial increases in serum antioxidant capacity in older women
Authors: Cao Guohua , Prior Ronald L.
Published: December 2017

Eight women were recruited for studying the effects of a meal on overall antioxidant status. Subjects resided in a metabolic research unit for two 36-h periods. During period A, subjects fasted overnight (12 h) and were then given a breakfast, a lunch, a snack, and a dinner. During period B, subjects fasted for 23 h and were then given a dinner. These meals were designed to contain negligible antioxidants. Blood samples were collected for analyzing total antioxidant capacity (TAC) and individual antioxidants. The results showed that serum TAC significantly increased by up to 23% after the consumption of the lunch and dinner during period A. Serum TAC did not increase until after the consumption of the dinner during period B. Among the antioxidants (vitamin C, α-tocopherol, bilirubin, and uric acid) examined, serum uric acid was the only one that showed a significant postprandial increase, which was also parallel to the postprandial response in serum TAC. These results indicate that food intake, even if low in antioxidants, can increase the serum total antioxidant activity.
Effect of budesonide and salbutamol on surfactant properties
Authors: Palmer D. , Schürch S. , Belik J.
Published: December 2017

The objective of this study was to evaluate the in vitro effect of budesonide and salbutamol on the surfactant biophysical properties. The surface-tension properties of two bovine lipid extracts [bovine lipid extract surfactant (BLES) and Survanta] and a rat lung lavage natural surfactant were evaluated in vitro by the captive bubble surfactometer. Measurements were obtained before and after the addition of a low and high concentration of budesonide and salbutamol. Whereas salbutamol had no significant effect, budesonide markedly reduced the surface-tension-lowering properties of all surfactant preparations. Surfactant adsorption (decrease in surface tension vs. time) was significantly reduced ( P < 0.01) at a high budesonide concentration with BLES, both concentrations with Survanta, and a low concentration with natural surfactant. At both concentrations, budesonide reduced ( P < 0.01) Survanta film stability (minimal surface vs. time at minimum bubble volume), whereas no changes were seen with BLES. The minimal surface tension obtained for all surfactant preparations was significantly higher ( P < 0.01), and the percentage of film area compression required to reach minimum surface tension was significantly lower after the addition of budesonide. In conclusion, budesonide, at concentrations used therapeutically, adversely affects the surface-tension-lowering properties of surfactant. We speculate that it may have the same adverse effect on the human surfactant.
Comparative respiratory system mechanics in rodents
Authors: Gomes R. F. M. , Shen X. , Ramchandani R. , Tepper R. S. , Bates J. H. T.
Published: December 2017

Because of the wide utilization of rodents as animal models in respiratory research and the limited data on measurements of respiratory input impedance (Zrs) in small animals, we measured Zrs between 0.25 and 9.125 Hz at different levels (0–7 hPa) of positive end-expiratory pressure (PEEP) in mice, rats, guinea pigs, and rabbits using a computer-controlled small-animal ventilator (Schuessler TF and Bates JHT, IEEE Trans Biomed Eng 42: 860–866, 1995). Zrs was fitted with a model, including a Newtonian resistance (R) and inertance in series with a constant-phase tissue compartment characterized by tissue damping (Gti) and elastance (Hti) parameters. Inertance was negligible in all cases. R, Gti, and Hti were normalized to body weight, yielding normalized R, Gti, and Hti (NHti), respectively. Normalized R tended to decrease slightly with PEEP and increased with animal size. Normalized Gti had a minimal dependence on PEEP. NHti decreased with increasing PEEP, reaching a minimum at ∼5 hPa in all species except mice. NHti was also higher in mice and rabbits compared with guinea pigs and rats at low PEEPs, which we conclude is probably due to a relatively smaller air space volume in mice and rabbits. Our data also suggest that smaller rodents have proportionately wider airways than do larger animals. We conclude that a detailed, comparative study of respiratory system mechanics shows some evidence of structural differences among the lungs of various species but that, in general, rodent lungs obey scaling laws similar to those described in other species.
Airway closure with high PEEP in vivo
Authors: Brown Robert H. , Mitzner Wayne
Published: December 2017

When airway smooth muscle is contracted in vitro, the airway lumen continues to narrow with increasing concentrations of agonist until complete airway closure occurs. Although there remains some controversy regarding whether airways can close in vivo, recent work has clearly demonstrated that, if the airway is sufficiently stimulated with contractile agonists, complete closure of even large cartilaginous conducting airways can readily occur with the lung at functional residual capacity (Brown RH and Mitzner W. J Appl Physiol 85: 2012–2017, 1998). This result suggests that the tethering of airways in situ by parenchymal attachments is small at functional residual capacity. However, at lung volumes above functional residual capacity, the outward tethering of airways should increase, because both the parenchymal shear modulus and tethering forces increase in proportion to the transpulmonary pressure. In the present study, we tested whether we could prevent airway closure in vivo by increasing lung volume with positive end-expiratory pressure (PEEP). Airway smooth muscle was stimulated with increasing methacholine doses delivered directly to airway smooth muscle at three levels of PEEP (0, 6, and 10 cmH2O). Our results show that increased lung volume shifted the airway methacholine dose-response curve to the right, but, in many airways in most animals, airway closure still occurred even at the highest levels of PEEP.
Changes in intra-abdominal pressure during postural and respiratory activation of the human diaphragm
Authors: Hodges Paul W. , Gandevia Simon C.
Published: December 2017

In humans, when the stability of the trunk is challenged in a controlled manner by repetitive movement of a limb, activity of the diaphragm becomes tonic but is also modulated at the frequency of limb movement. In addition, the tonic activity is modulated by respiration. This study investigated the mechanical output of these components of diaphragm activity. Recordings were made of costal diaphragm, abdominal, and erector spinae muscle electromyographic activity; intra-abdominal, intrathoracic, and transdiaphragmatic pressures; and motion of the rib cage, abdomen, and arm. During limb movement the diaphragm and transversus abdominis were tonically active with added phasic modulation at the frequencies of both respiration and limb movement. Activity of the other trunk muscles was not modulated by respiration. Intra-abdominal pressure was increased during the period of limb movement in proportion to the reactive forces from the movement. These results show that coactivation of the diaphragm and abdominal muscles causes a sustained increase in intra-abdominal pressure, whereas inspiration and expiration are controlled by opposing activity of the diaphragm and abdominal muscles to vary the shape of the pressurized abdominal cavity.
Altered airway surfactant phospholipid composition and reduced lung function in asthma
Authors: Wright Sarah M. , Hockey Peter M. , Enhorning Goran , Strong Peter , Reid Kenneth B. M. , Holgate Stephen T. , Djukanovic Ratko , Postle Anthony D.
Published: December 2017

Pulmonary surfactant in bronchoalveolar lavage fluid (BALF) and induced sputum from adults with stable asthma ( n = 36) and healthy controls ( n = 12) was analyzed for phospholipid and protein compositions and function. Asthmatic subjects were graded as mild, moderate, or severe. Phospholipid compositions of BALF and sputum from control subjects were similar and characteristic of surfactant. For asthmatic subjects, the proportion of dipalmitoyl phosphatidylcholine (16:0/16:0PC), the major phospholipid in surfactant, decreased in sputum ( P < 0.05) but not in BALF. 1 In BALF, mole percent 16:0/16:0PC correlated with surfactant function measured in a capillary surfactometer, and sputum mole percent 16:0/16:0PC correlated with lung function (forced expiratory volume in 1 s). Neither surfactant protein A nor total protein concentration in either BALF or sputum was altered in asthma. These results suggest altered phospholipid composition and function of airway (sputum) but not alveolar (BALF) surfactant in stable asthma. Such underlying surfactant dysfunction may predispose asthmatic subjects to further surfactant inhibition by proteins or aeroallergens in acute asthma episodes and contribute to airway closure in asthma. Consequently, administration of an appropriate therapeutic surfactant could provide clinical benefit in asthma.
A predictive model of fatigue in human skeletal muscles
Authors: Ding Jun , Wexler Anthony S. , Binder-Macleod Stuart A.
Published: December 2017

Fatigue is a major limitation to the clinical application of functional electrical stimulation. The activation pattern used during electrical stimulation affects force and fatigue. Identifying the activation pattern that produces the greatest force and least fatigue for each patient is, therefore, of great importance. Mathematical models that predict muscle forces and fatigue produced by a wide range of stimulation patterns would facilitate the search for optimal patterns. Previously, we developed a mathematical isometric force model that successfully identified the stimulation patterns that produced the greatest forces from healthy subjects under nonfatigue and fatigue conditions. The present study introduces a four-parameter fatigue model, coupled with the force model that predicts the fatigue induced by different stimulation patterns on different days during isometric contractions. This fatigue model accounted for 90% of the variability in forces produced by different fatigue tests. The predicted forces at the end of fatigue testing differed from those observed by only 9%. This model demonstrates the potential for predicting muscle fatigue in response to a wide range of stimulation patterns.
Neurocirculatory consequences of intermittent asphyxia in humans
Authors: Xie Ailiang , Skatrud James B. , Crabtree David C. , Puleo Dominic S. , Goodman Brian M. , Morgan Barbara J.
Published: December 2017

We examined the neurocirculatory and ventilatory responses to intermittent asphyxia (arterial O2 saturation = 79–85%, end-tidal Pco 2 =3–5 Torr above eupnea) in seven healthy humans during wakefulness. The intermittent asphyxia intervention consisted of 20-s asphyxic exposures alternating with 40-s periods of room-air breathing for a total of 20 min. Minute ventilation increased during the intermittent asphyxia period (14.2 ± 2.0 l/min in the final 5 min of asphyxia vs. 7.5 ± 0.4 l/min in baseline) but returned to the baseline level within 2 min after completion of the series of asphyxic exposures. Muscle sympathetic nerve activity increased progressively, reaching 175 ± 12% of baseline in the final 5 min of the intervention. Unlike ventilation, sympathetic activity remained elevated for at least 20 min after removal of the chemical stimuli (150 ± 10% of baseline in the last 5 min of the recovery period). Intermittent asphyxia caused a small, but statistically significant, increase in heart rate (64 ± 4 beats/min in the final 5 min of asphyxia vs. 61 ± 4 beats/min in baseline); however, this increase was not sustained after the return to room-air breathing. These data demonstrate that relatively short-term exposure to intermittent asphyxia causes sympathetic activation that persists after removal of the chemical stimuli. This carryover effect provides a potential mechanism whereby intermittent asphyxia during sleep could lead to chronic sympathetic activation in patients with sleep apnea syndrome.
Effects of β-hydroxy-β-methylbutyrate on muscle damage after a prolonged run
Authors: Knitter A. E. , Panton L. , Rathmacher J. A. , Petersen A. , Sharp R.
Published: December 2017

This study examined the effects of supplemental β-hydroxy-β-methylbutyrate (HMB) on muscle damage as a result of intense endurance exercise. Subjects ( n = 13) were paired according to their 2-mile run times and past running experience. Each pair was randomly assigned a treatment of either HMB (3 g/day) or a placebo. After 6 wk of daily training and supplementation, all subjects participated in a prolonged run (20-km course). Creatine phosphokinase and lactate dehydrogenase (LDH) activities were measured before and after a prolonged run to assess muscle damage. The placebo-supplemented group exhibited a significantly greater (treatment main effect, P = 0.05) increase in creatine phosphokinase activity after a prolonged run than did the HMB-supplemented group. In addition, LDH activity was significantly lower (treatment main effect, P = 0.003) with HMB supplementation compared with the placebo-supplemented group. In conclusion, supplementation with 3.0 g of HMB results in a decreased creatine phosphokinase and LDH response after a prolonged run. These findings support the hypothesis that HMB supplementation helps prevent exercise-induced muscle damage.
Dynamic viscoelastic behavior of lower extremity tendons during simulated running
Authors: De Zee M. , Bojsen-Møller F. , Voigt M.
Published: December 2017

The aim of this project was to see whether the tendon would show creep during long-term dynamic loading (here referred to as dynamic creep). Pig tendons were loaded by a material-testing machine with a human Achilles tendon force profile (1.37 Hz, 3% strain, 1,600 cycles), which was obtained in an earlier in vivo experiment during running. All the pig tendons showed some dynamic creep during cyclic loading (between 0.23 ± 0.15 and 0.42 ± 0.21%, means ± SD). The pig tendon data were used as an input of a model to predict dynamic creep in the human Achilles tendon during running of a marathon and to evaluate whether there might consequently be an influence on group Ia afferent-mediated length and velocity feedback from muscle spindles. The predicted dynamic creep in the Achilles tendon was considered to be too small to have a significant influence on the length and velocity feedback from soleus during running. In spite of the characteristic nonlinear viscoelastic behavior of tendons, our results demonstrate that these properties have a minor effect on the ability of tendons to act as predictable, stable, and elastic force transmitters during long-term cyclic loading.