bluuebunny/crossref_metadata_2025 huggingface dataset:
Forebrain and brain stem neural circuits contribute to altered sympathetic responses to heating in senescent rats
Authors: Kenney Michael J. , Fels Richard J.
Published: March 2015

Acute heating in young rats increases visceral sympathetic nerve discharge (SND); however, renal and splanchnic SND responses to hyperthermia are attenuated in senescent compared with young Fischer 344 (F344) rats (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520, 2002). Central mechanisms by which aging alters visceral SND responses to heating are unknown. We tested the hypothesis that forebrain neural circuits are involved in suppressing sympathoexcitatory responses to heating in chloralose-anesthetized, senescent F344 rats. Renal and splanchnic SND responses to increased (38°C-41°C) internal temperature were determined in midbrain-transected (MT) and sham-MT young (3-mo-old), mature (12-mo-old), and senescent (24-mo-old) F344 rats and in cervical-transected (CT) and sham-CT senescent rats. Renal SND remained unchanged during heating in MT and sham-MT senescent rats but was increased in CT senescent rats. Splanchnic SND responses to heating were higher in MT vs. sham-MT senescent rats and in CT vs. MT senescent rats. SND responses to heating were similar in MT and sham-MT young and mature rats. Mean arterial pressure (MAP) was increased during heating in MT but not in sham-MT senescent rats, whereas heating-induced increases in MAP were higher in sham-MT vs. MT young rats. These data suggest that in senescent rats suppression of splanchnic SND to heating involves forebrain and brain stem neural circuits, whereas renal suppression is mediated solely by brain stem neural circuits. These results support the concept that aging alters the functional organization of pathways regulating SND and arterial blood pressure responses to acute heating.
Regional measurement of canine skeletal muscle blood flow by positron emission tomography with H2 15O
Authors: Fischman Alan J. , Hsu Hongbing , Carter Edward A. , Yu Yong M. , Tompkins Ronald G. , Guerrero J. Luis , Young Vernon R. , Alpert Nathaniel M.
Published: March 2015

Positron emission tomography (PET) with H2 15O was used as an in vivo, relatively noninvasive, quantitative method for measuring regional blood flow to hindlimb skeletal muscle of anesthetized dogs. A hydrooccluder positioned on the femoral artery was used to reduce flow, and high-flow states were produced by local infusion of adenosine. Three to four measurements were made in each animal. Approximately 40 mCi of H2 15O were injected intravenously, and serial images and arterial blood samples were acquired over 2.5 min. Data analysis was performed by fitting tissue and arterial blood time-activity curves to a modified, single-compartment Kety model. The model equation was also solved on a pixel-by-pixel basis to yield maps of regional skeletal muscle blood flow. After each PET determination, flow was measured with radioactive microspheres. Results of the PET measurements demonstrated that basal flow to hindlimb skeletal muscle was 3.83 ± 0.36 ml · min−1 · 100 g−1(mean ± SE). This value was in excellent agreement with the microsphere data, 3.73 ± 0.32 ml · min−1 · 100 g−1( P = 0.69, not significant). Adenosine infusion resulted in flows as high as 30 ml · min−1 · 100 g−1, and the PET and microsphere data were highly correlated over the entire range of flows ( r 2 = 0.98, P < 0.0001). We conclude that muscle blood flow can be accurately measured in vivo by PET with H2 15O and that this approach offers promise for application in human studies of muscle metabolism under varying pathophysiological states.
Selected Contribution: Long-livedDrosophila melanogasterlines exhibit normal metabolic rates
Authors: Van Voorhies Wayne A. , Khazaeli Aziz A. , Curtsinger James W.
Published: March 2015

The use of model organisms, such as Drosophila melanogaster, provides a powerful method for studying mechanisms of aging. Here we report on a large set of recombinant inbred (RI) D. melanogaster lines that exhibit approximately a fivefold range of average adult longevities. Understanding the factors responsible for the differences in longevity, particularly the characteristics of the longest-lived lines, can provide fundamental insights into the mechanistic correlates of aging. In ectothermic organisms, longevity is often inversely correlated with metabolic rate, suggesting the a priori hypothesis that long-lived lines will have low resting metabolic rates. We conducted ∼6,000 measurements of CO2production in individual male flies aged 5, 16, 29, and 47 days postemergence and simultaneously measured the weight of individual flies and life spans in populations of each line. Even though there was a wide range of longevities, there was no evidence of an inverse relationship between the variables. The increased longevity of long-lived lines is not mediated through reduction of metabolic activity. In Drosophila, it is possible to both maintain a normal metabolic rate and achieve long life. These results are evaluated in the context of 100 years of research on the relationship between metabolic rate and life span.
Effect of gender on bone turnover in adult rats during simulated weightlessness
Authors: Hefferan T. E. , Evans G. L. , Lotinun S. , Zhang M. , Morey-Holton E. , Turner R. T.
Published: March 2015

Prologned spaceflight results in bone loss in astronauts, but there is considerable individual variation. The goal of this rat study was to determine whether gender influences bone loss during simulated weightlessness. Six-month-old Fisher 344 rats were hindlimb unweighted for 2 wk, after which the proximal tibiae were evaluated by histomorphometry. There were gender differences in tibia length, bone area, cancellous bone architecture, and bone formation. Compared with female rats, male rats had an 11.6% longer tibiae, a 27.8% greater cortical bone area, and a 37.6% greater trabecular separation. Conversely, female rats had greater cortical (316%) and cancellous (145%) bone formation rates, 28.6% more cancellous bone, and 30% greater trabecular number. Hindlimb unweighting resulted in large reductions in periosteal bone formation and mineral apposition rate in both genders. Unweighting also caused cancellous bone loss in both genders; trabecular number was decreased, and trabecular separation was increased. There was, however, no change in trabecular thickness in either gender. These architectural changes in cancellous bone were associated with decreases in bone formation and steady-state mRNA levels for bone matrix proteins and cancellous bone resorption. In conclusion, there are major gender-related differences in bone mass and turnover; however, the bone loss in hindlimb unweighted adult male and female rats appears to be due to similar mechanisms.
Effect of ischemia and reperfusion without airway occlusion on vascular barrier function in the in vivo mouse lung
Authors: Dodd-o Jeffrey M. , Hristopoulos Maria L. , Faraday Nauder , Pearse David B.
Published: March 2015

Ischemia-reperfusion (I/R) lung injury causes increased vascular permeability and edema. We developed an in vivo murine model of I/R allowing measurement of pulmonary vascular barrier function without airway occlusion. The left pulmonary artery (PA) was occluded with an exteriorized, slipknotted suture in anesthetized C57BL/6J mice. The effect of ischemic time was determined by subjecting mice to 5, 10, or 30 min of left lung ischemia followed by 150 min of reperfusion. The effect of reperfusion time was determined by subjecting mice to 30 min of left lung ischemia followed by 30 or 150 min of reperfusion. Changes in pulmonary vascular barrier function were measured with the Evans blue dye (EBD) technique, dual-isotope radiolabeled albumin (RA), bronchoalveolar lavage (BAL) protein concentration, and wet weight-to-dry weight ratio (WW/DW). Increasing left lung ischemia with constant reperfusion time or increasing left lung reperfusion time after constant ischemic time resulted in significant increases in left lung EBD content at all times compared with both right lung values and sham surgery mice. The effects of left lung ischemia on lung EBD were corroborated by RA but the effects of increasing reperfusion time differed, suggesting binding of EBD to lung tissue. An increase in WW/DW was only detected after 30 min of reperfusion, suggesting edema clearance. BAL protein concentrations were unaffected. We conclude that short periods of I/R, without airway occlusion, increase pulmonary vascular permeability in the in vivo mouse, providing a useful model to study molecular mechanisms of I/R lung injury.
Differential metabolic capacity of mice selected for magnitude of swim stress-induced analgesia
Authors: Łapo Iwona B. , Konarzewski Marek , Sadowski Bogdan
Published: March 2015

Maximum oxygen consumption (V˙o2) elicited by swimming in 20°C water or by exposure to −2.5°C in helium-oxygen (Helox) atmosphere is higher in mice selected for low (LA) than for high (HA) stress-induced analgesia (SIA) produced by swimming. However, this line difference is greater with respect to swim- than to cold-elicited V˙o2. To study the relationship between the analgesic and thermogenic mechanisms, we acclimated HA and LA mice to 5°C or to daily swimming at 20 or 32°C. Next, the acclimated mice were exposed to a Helox test at −2.5°C and to a swim test at 20°C to compareV˙o2and hypothermia (ΔT). Cold acclimation raised V˙o2and decreased ΔT. These effects were similar in both lines in the Helox test but were smaller in the HA than in the LA line in the swim test. HA and LA mice acclimated to 20 or 32°C swims increasedV˙o2and decreased ΔT elicited by swimming, but only HA mice acclimated to 20°C swims increasedV˙o2and decreased ΔT in the Helox test. We conclude that the between-line difference in swimV˙o2results from a stronger modulation of thermogenic capacities of HA mice by a swim stress-related mechanism, resulting in SIA. We suggest that the predisposition to SIA observed in laboratory as well as wild animals may significantly affect both the results of laboratory measurements ofV˙o2and the interpretation of its intra- and interspecific variation.
Influence of clenbuterol on bone metabolism in exercised or sedentary rats
Authors: Cavalié H. , Lac G. , Lebecque P. , Chanteranne B. , Davicco M.-J. , Barlet J.-P.
Published: March 2015

This paper reports that the selective β2-adrenergic receptor agonist clenbuterol affects bone metabolism in growing 3-mo-old male Wistar rats treated over 8 wk. Thirty-two 3-mo-old growing Wistar rats weighing 234 ± 2 g were assigned to a progressive isometric force, strength-training exercise program plus oral clenbuterol (2 mg · kg body wt−1 · day−1) for 5 days each week, exercise program without clenbuterol 5 days each week, no exercise program plus oral clenbuterol (2 mg · kg−1 · day−1) for 5 days each week, or no exercise without clenbuterol 5 days each week. At the end of 8 wk, lean mass, fat mass, and right total femoral, distal metaphyseal femoral, and diaphyseal femoral bone mineral density were measured by Hologic QDR 4500 dual X-ray absorptiometry (DEXA) technique. Left femoral bones were harvested after death on day 58, and femoral resistance was determined by three-point bending testing. We found that fat mass was decreased in rats given strength training exercise and decreased further in rats treated with clenbuterol. Lean mass was increased in clenbuterol-treated animals. Strength-training exercise appeared to have no effect on bone mineral density, serum osteocalcin, or urinary deoxypyridinoline. However, clenbuterol treatment decreased femoral length, diameter, bone mineral density, and mechanical resistance. Clenbuterol had no effect on osteocalcin but increased urinary deoxypyridinoline. We concluded that clenbuterol treatment decreased bone mineral density and increased bone resorption independent of the level of exercise rats were given.
Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome
Authors: Kirkness Jason P. , Madronio Melanie , Stavrinou Rosie , Wheatley John R. , Amis Terence C.
Published: March 2015

Lowering surface tension (γ) of upper airway lining liquid (UAL) reduces upper airway opening (anesthetized humans) and closing (anesthetized rabbits) pressures. We now hypothesize that in sleeping obstructive sleep apnea hypopnea syndrome (OSAHS) patients lowering γ of UAL will enhance upper airway stability and decrease the severity of sleep-disordered breathing. Nine OSAHS patients [respiratory disturbance index (RDI): 49 ± 8 (SE) events/h, diagnostic night] participated in a two-part, one-night, polysomnography study. In the first part, upper airway closing pressures (during non-rapid eye movement sleep, Pcrit) were measured and samples of UAL (awake) were obtained before and after 2.5 ml of surfactant (Exosurf, Glaxo Smith Kline) was instilled into the posterior pharynx. The γ of UAL was determined with the use of the “pull-off” force technique. In the second part, subjects received a second application of 2.5 ml of surfactant and then slept the remainder of the night (205 ± 30 min). Instillation of surfactant decreased the γ of UAL from 60.9 ± 3.1 mN/m (control) to 45.2 ± 2.5 mN/m (surfactant group) ( n = 9, P < 0.001). Pcrit decreased from 1.19 ± 1.14 cmH2O (control) to -0.56 ± 1.15 cmH2O (surfactant group) ( n = 7, P < 0.02). Compared with the second half of diagnostic night, surfactant decreased RDI from 51 ± 8 to 35 ± 8 events/h ( n = 9, P < 0.03). The fall in RDI (ΔRDI) correlated with the fall in γ of UAL (Δγ) (ΔRDI = 1.8 × Δγ, r = 0.68, P = 0.04). Hypopneas decreased ∼50% from 42 ± 8 to 20 ± 5 events/h ( n = 9, P < 0.03, paired t-test). The γ of UAL measured the next morning remained low at 49.5 ± 2.7 mN/m ( n = 9, P < 0.001, ANOVA, compared with control). In conclusion, instillation of surfactant reduced the γ of UAL in OSAHS patients and decreased Pcrit and the occurrence of hypopneas. Therapeutic manipulation of γ of UAL may be beneficial in reducing the severity of sleep-disordered breathing in OSAHS patients.
Does age, sex, or ACE genotype affect glucose and insulin responses to strength training?
Authors: Hurlbut D. E. , Lott M. E. , Ryan A. S. , Ferrell R. E. , Roth S. M. , Ivey F. M. , Martel G. F. , Lemmer J. T. , Fleg J. L. , Hurley B. F.
Published: March 2015

The purpose of the present study was to determine whether age, sex, or angiotensin I-converting enzyme (ACE) genotype influences the effects of strength training (ST) on glucose homeostasis. Nineteen sedentary young (age = 20–30 yr) men ( n = 10) and women ( n = 9) were studied and compared with 21 sedentary older (age = 65–75 yr) men ( n = 12) and women ( n = 9) before and after a 6-mo total body ST program. Fasting insulin concentrations were reduced in young men and in older men with ST ( P< 0.05 in both). In addition, total insulin area under the curve decreased by 21% in young men ( P < 0.05), and there was a trend for a decrease (11%) in older men ( P = 0.06). No improvements in insulin responses were observed in young or older women. The ACE deletion/deletion genotype group had the lowest fasting insulin and insulin areas under the oral glucose tolerance test (OGTT) curve before training (all P < 0.05), but those with at least one insertion allele had a trend for a greater reduction in total insulin area than deletion homozygotes ( P = 0.07). These results indicate that ST has a more favorable effect on insulin response to an OGTT in men than in women and offer some support for the hypothesis that ACE genotype may influence insulin responses to ST.
Speech movements do not scale by orofacial structure size
Authors: Riely Rachel R. , Smith Anne
Published: March 2015

The potential role of a size-scaling principle in orofacial movements for speech was examined by using between-group (adults vs. 5-yr-old children) as well as within-group correlational analyses. Movements of the lower lip and jaw were recorded during speech production, and anthropometric measures of orofacial structures were made. Adult women produced speech movements of equal amplitude and velocity to those of adult men. The children produced speech movement amplitudes equal to those of adults, but they had significantly lower peak velocities of orofacial movement. Thus we found no evidence supporting a size-scaling principle for orofacial speech movements. Young children have a relatively large-amplitude, low-velocity movement strategy for speech production compared with young adults. This strategy may reflect the need for more time to plan speech movement sequences and an increased reliance on sensory feedback as young children develop speech motor control processes.
Role of airway endogenous nitric oxide on lung function during and after exercise in mild asthma
Authors: Suman Oscar E. , Beck Kenneth C.
Published: March 2015

We hypothesized that nitric oxide (NO), a known mild bronchodilator that can be released by several cell types within pulmonary airways, might protect airways during exercise in asthmatic subjects. We studied 17 individuals with documented exercise-induced asthma (screening exercise evaluation) on 2 study days: after treatment with inhaled NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA; 2 ml of 25 mg/ml mist) and after treatment with saline vehicle. Pulmonary resistance (Rl, esophageal manometry) rose and forced expiratory volume in 1 s fell more after l-NMMA compared with saline treatment, suggesting a bronchoprotective role for NO at baseline. The rise in Rlseen after l-NMMA treatment was nearly completely reversed early in exercise, suggesting a non-NO-mediated bronchodilation. A slow rise in Rl during constant-load exercise and dramatic increase in Rl after exercise were the same on the 2 treatment days, indicating little role for NO in regulating airway function during and after exercise. We conclude that endogenous NO plays little role in regulating airway function during and after exercise in subjects with mild asthma.
Effects of thyroid state on AMP-activated protein kinase and acetyl-CoA carboxylase expression in muscle
Authors: Park S. H. , Paulsen S. R. , Gammon S. R. , Mustard K. J. , Hardie D. G. , Winder W. W.
Published: March 2015

AMP-activated protein kinase (AMPK) consists of three subunits: α, β, and γ. Two isoforms exist for the α-subunit (α1and α2), two for the β-subunit (β1and β2), and three for the γ-subunit (γ1, γ2, and γ3). Although the specific roles of the β- and γ-subunits are not well understood, the α-subunit isoforms contain the catalytic site and also the phosphorylation/activation site for the upstream kinase. This study was designed to determine the role of thyroid hormones in controlling expression levels of these AMPK subunits and of one downstream target, acetyl-CoA carboxylase (ACC), in muscle. AMPK subunit and ACC levels were determined by Western blots in control rats, in rats given 0.01% propylthiouracil (PTU) in drinking water for 3 wk, and in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 1 or 3 wk. In gastrocnemius muscle, all isoforms of AMPK subunits were significantly increased in rats given thyroid hormones for 3 wk vs. those treated with PTU. Similar patterns were seen in individual muscle types. Expression of muscle ACC was also significantly increased in response to 3 wk of treatment with excess thyroid hormones. Muscle content of malonyl-CoA was elevated in PTU-treated rats and depressed in thyroid hormone-treated rats. These data provide evidence that skeletal muscle AMPK subunit and ACC expression is partially under the control of thyroid hormones.
Corticosteroids and skeletal muscle function in cystic fibrosis
Authors: Barry Sinead C. , Gallagher Charles G.
Published: March 2015

Patients with cystic fibrosis (CF) have reduced peripheral muscle strength. We tested the hypothesis that steroid treatment contributes to muscle weakness in adults with CF. Twenty-three stable CF patients were studied. Measurements included knee extensor (KE), knee flexor (KF), elbow flexor (EF), handgrip (HG), expiratory (Pemax), and inspiratory (Pimax) muscle strengths. Spirometry, body mass index (BMI), and days spent in hospital over the preceding 12 mo (DH) were also measured. Average daily dose of prednisolone over the preceding 12 mo (ADD) was 5.1 mg/day. Pearson's correlation analysis revealed that ADD correlated significantly with skeletal muscle strengths (KF%, r = -0.63, P < 0.01) with the exception of HG%. These findings are independent of age, BMI, pulmonary function, and DH. Multiple-regression analysis revealed that ADD was the most significant predictor of all measures of skeletal muscle function except HG%. It was independently responsible for 54% of the variance in Pimax%, for 46% of the variance in Pemax%, for 45% of the variance in KE%, for 39% of the variance in KF%, and for 41% of the variance in EF%. Concomitant medications (e.g., theophylline) were shown to have no causative effect. Corticosteroids contribute to the skeletal muscle weakness seen in CF patients. The correlation of proximal muscle strength, but not HG strength, with steroid dosage further supports a cause-effect relationship.
Relation of heart rate to percentV˙o 2 peak during submaximal exercise in the heat
Authors: Arngrímsson Sigurbjörn Á. , Stewart Darby J. , Borrani Fabio , Skinner Kristie A. , Cureton Kirk J.
Published: March 2015

We tested the hypothesis that elevation in heart rate (HR) during submaximal exercise in the heat is related, in part, to increased percentage of maximal O2 uptake (%V˙o 2 max) utilized due to reduced maximal O2 uptake (V˙o 2 max) measured after exercise under the same thermal conditions. Peak O2 uptake (V˙o 2 peak), O2 uptake, and HR during submaximal exercise were measured in 22 male and female runners under four environmental conditions designed to manipulate HR during submaximal exercise and V˙o 2 peak. The conditions involved walking for 20 min at ∼33% of controlV˙o 2 max in 25, 35, 40, and 45°C followed immediately by measurement ofV˙o 2 peak in the same thermal environment. V˙o 2 peak decreased progressively (3.77 ± 0.19, 3.61 ± 0.18, 3.44 ± 0.17, and 3.13 ± 0.16 l/min) and HR at the end of the submaximal exercise increased progressively (107 ± 2, 112 ± 2, 120 ± 2, and 137 ± 2 beats/min) with increasing ambient temperature (Ta). HR and %V˙o 2 peak increased in an identical fashion with increasing Ta. We conclude that elevation in HR during submaximal exercise in the heat is related, in part, to the increase in %V˙o 2 peak utilized, which is caused by reduced V˙o 2 peak measured during exercise in the heat. At high Ta, the dissociation of HR from %V˙o 2 peak measured after sustained submaximal exercise is less than ifV˙o 2 max is assumed to be unchanged during exercise in the heat.
In vivo rabbit hindquarter model for assessment of regional burn hypermetabolism
Authors: Xu Ji , Fei Zhewei , Yu Yong-Ming , Xu Wenyin , Rhodes Andrew , Tompkins Ronald G. , Schulz John T.
Published: March 2015

Severe burn injury evokes hypermetabolism and muscle wasting, despite nominally adequate nutrition. Although there is much information on whole organism and isolated tissue metabolism after burn injury, data examining regional burn hypermetabolism in vivo are lacking. Using surgically implanted (general anesthesia) regional vascular catheters and primed constant infusion of l-[1-13C]phenylalanine tracer, we have determined in vivo burn-induced alterations in rabbit hindquarter protein and energy metabolism. Burn injury evokes increased whole body resting energy expenditure and phenylalanine turnover, accompanied by significantly increased hindquarter proteolysis, creating a negative protein balance in burned rabbit hindquarter. Hindquarter oxygen consumption showed an increase after burn injury, but it did not reach statistical significance. Burn-induced changes in hindquarter protein turnover account for approximately one-third of the whole animal hypermetabolism. This model offers a system for regional manipulation of postburn hypermetabolism.
Local particle deposition patterns may play a key role in the development of lung cancer
Authors: Balásházy Imre , Hofmann Werner , Heistracher Thomas
Published: March 2015

The apparent discrepancy between the reported preferential occurrence of bronchial carcinomas in central bronchial airways and current dose estimates for inhaled particles suggests that experimentally observed local accumulations of particles within bronchial airway bifurcations may play a crucial role in lung cancer induction. Here, we computed three-dimensional particle deposition patterns in lobar-segmental airway bifurcations and quantified the resulting inhomogeneous deposition patterns in terms of deposition enhancement factors, which are defined as the ratio of local to average deposition densities. Our results revealed that a small fraction of epithelial cells located at carinal ridges can receive massive doses that may be even a few hundred times higher than the average dose for the whole airway. This lends further credence to the hypothesis that the apparent site selectivity of neoplastic lesions may indeed be caused by the enhanced deposition of toxic particulate matter at bronchial airway bifurcations.
Oxygen uptake kinetics during two bouts of heavy cycling separated by fatiguing sprint exercise in humans
Authors: Tordi N. , Perrey S. , Harvey A. , Hughson R. L.
Published: March 2015

We tested the hypothesis that O2 uptake (V˙o 2) kinetics at the onset of heavy exercise would be altered in a state of muscle fatigue and prior metabolic acidosis. Eight well-trained cyclists completed two identical bouts of 6-min cycling exercise at >85% of peak V˙o 2 separated by three successive bouts of 30 s of sprint cycling. Not only was baselineV˙o 2 elevated after prior sprint exercises but also the time constant of phase IIV˙o 2 kinetics was faster (28.9 ± 2.4 vs. 22.2 ± 1.7 s; P < 0.05). CO2 output (V˙co 2) was significantly reduced throughout the second exercise bout. SubsequentlyV˙o 2 was greater at 3 min and increased less after this after prior sprint exercise. Cardiac output, estimated by impedance cardiography, was significantly higher in the first 2 min of the second heavy exercise bout. Normalized integrated surface electromyography of four leg muscles and normalized mean power frequency were not different between exercise bouts.V˙o 2 andV˙co 2 kinetic responses to heavy exercise were markedly altered by prior multiple sprint exercises.
Increased serum nIgM in voluntarily physically active rats: a potential role for B-1 cells
Authors: Elphick Gwendolyn F. , Greenwood Benjamin N. , Campisi Jay , Fleshner Monika
Published: March 2015

Moderate, habitual physical activity improves health, possibly because of beneficial changes in immune function. For example, physical activity can increase natural killer cell cytotoxicity, T cell proliferation, and macrophage function but has minimal impact on antigen-driven B-2-mediated immunoglobulin (Ig) responses. The following studies tested whether physical activity selectively impacts nonantigen-driven B-1-natural IgM (nIgM) but not antigen-driven B-2 Ig. Adult male, pathogen-free Sprague-Dawley rats in a barrier facility voluntarily ran in wheels from 7 to 56 days or were housed in an enriched environment for 56 days. Rats received either no antigen or keyhole limpet hemocyanin (KLH) to assess the B-2 response. Blood samples assessed serum nIgM, total IgG, total serum protein, anti-KLH IgM, and anti-KLH IgG. Physically active rats had higher serum nIgM after 7 days of running, and nIgM remained elevated over 56 days of running. In contrast, free-wheel running produced no changes in total IgG, total serum protein, anti-KLH IgM, and anti-KLH IgG. Environmental enrichment did not alter immune measures from controls. These results suggest that B-1, not B-2, cell responses are selectively impacted by physical activity. Because nIgM is important in multiple aspects of the immune response, an elevation in this innate humoral component could contribute to improved immunity in physically active organisms.
Role of the autonomic nervous system in push-pull gravitational stress in anesthetized rats
Authors: Hakeman Amy L. , Sheriff Don D.
Published: March 2015

Tolerance to +Gzstress is reduced by preceding exposure to −Gz (push-pull effect). The mechanism(s) responsible for this effect are not fully understood, although the arterial baroreceptor reflexes have been implicated. We investigated the integrative response of the autonomic nervous system by studying responses to gravitational stress before and after autonomic function was inhibited by hexamethonium in 10 isoflurane-anesthetized male and female Sprague-Dawley rats. Animals were restrained supine and subjected to two rotations imposed about the x-axis: 1) a control G profile consisting of rotation from 0 Gz (+1 Gy) to 90° head-up tilt (+1 Gz) for 10 s and 2) a push-pull G profile consisting of rotation from 0 Gz to 90° head-down tilt (−1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. Eight G profiles consisting of equal numbers of control and push-pull trials were imposed by using a counterbalanced design. We found that hexamethonium lowered baseline arterial pressure and abolished the push-pull effect. The lack of a push-pull effect after autonomic blockade persisted when arterial pressure was restored to baseline levels by phenylephrine infusion. Lowering baseline arterial pressure by sodium nitroprusside infusion or by hemorrhage when autonomic function was intact also abolished the push-pull effect. We conclude that intact autonomic function and a normal baseline arterial pressure are needed for expression of the push-pull effect in anesthetized rats subjected to tilting.
Selected Contribution: Skeletal muscle capillarity and enzyme activity in rats selectively bred for running endurance
Authors: Howlett Richard A. , Gonzalez Norberto C. , Wagner Harrieth E. , Fu Zhenxing , Britton Steven L. , Koch Lauren G. , Wagner Peter D.
Published: March 2015

To attempt to explain the difference in intrinsic (untrained) endurance running capacity in rats selectively bred over seven generations for either low (LCR) or high running capacity (HCR), the relationship among skeletal muscle capillarity, fiber composition, enzyme activity, and O2transport was studied. Ten females from each group [body wt: 228 g (HCR), 247 g (LCR); P= 0.03] were studied at 25 wk of age. Peak normoxic maximum O2consumption and muscle O2conductance were previously reported to be 12 and 33% higher, respectively, in HCR, despite similar ventilation, arterial O2saturation, and a cardiac output that was <10% greater in HCR compared with LCR. Total capillary and fiber number in the medial gastrocnemius were similar in HCR and LCR, but, because fiber area was 37% lower in HCR, the number of capillaries per unit area (or mass) of muscle was higher in HCR by 32% ( P < 0.001). A positive correlation ( r = 0.92) was seen between capillary density and muscle O2conductance. Skeletal muscle enzymes citrate synthase and β-hydroxyacyl-CoA dehydrogenase were both ∼40% higher ( P < 0.001) in HCR (12.4 ± 0.7 vs. 8.7 ± 0.4 and 3.4 ± 0.2 vs. 2.4 ± 0.2 mmol · kg−1· min−1, respectively), whereas phosphofructokinase was significantly ( P = 0.02) lower in HCR (27.8 ± 1.2 vs. 35.2 ± 2.5 mmol · kg−1· min−1) and hexokinase was the same (0.65 ± 0.04 vs. 0.65 ± 0.03 mmol · kg−1· min−1). Resting muscle ATP, phosphocreatine, and glycogen contents were not different between groups. Taken together, these data suggest that, in rats selectively bred for high-endurance exercise capacity, most of the adaptations for improved O2utilization occur peripherally in the skeletal muscles and not in differences at the level of the heart or lung.
Gender-specific K+-channel contribution to adenosine-induced relaxation in coronary arterioles
Authors: Heaps Cristine L. , Bowles Douglas K.
Published: March 2015

We examined the contribution of K+-channel activity on basal tone and adenosine-mediated relaxation of coronary arterioles isolated from sexually mature male and female miniature swine. Arterioles (∼100–200 μm ID) isolated from the apical region of the heart were cannulated and studied using videodimensional analysis under constant intraluminal pressure. Coronary arterioles from male and female pigs demonstrated similar levels of basal tone and reductions in basal diameter in response to the K+-channel blockers 4-aminopyridine (4-AP; 1 mM), tetraethylammonium (1 mM), and glibenclamide (Glib; 10 μM), with 4-AP producing significantly greater constriction than tetraethylammonium or Glib. After endothelin-induced preconstriction, relaxation responses to adenosine were not significantly different between coronary arterioles of male and female pigs. Inhibition of 4-AP-sensitive channels significantly impaired adenosine-mediated relaxation in arterioles from male but not female pigs. However, inhibition of K+ channels with iberiotoxin (100 nM) or Glib had no effect on adenosine-induced relaxation in either sex. Results obtained in the presence of nitric oxide synthase inhibition suggest a potential interaction of 4-AP-sensitive channels and nitric oxide at low adenosine concentrations. In conclusion, our data indicate that 4-AP-sensitive channels 1) contribute significantly to basal tone in coronary arterioles of both male and female pigs, 2) contribute to adenosine-mediated relaxation in male but not female pigs, and 3) can contribute to adenosine-induced relaxation independent of nitric oxide production in male pigs. These data are consistent with a significant role for voltage-dependent K+channels in adenosine-mediated relaxation of coronary arterioles from males.
Transpulmonary speed of sound input into the supraclavicular space
Authors: Paciej R. , Vyshedskiy A. , Shane J. , Murphy R.
Published: March 2015

The transpulmonary speed of sound input at the mouth has been shown to vary with lung volume. To avoid the disadvantages that exist in certain clinical situations in inputting sound at the mouth, we input sound in the supraclavicular space of 21 healthy volunteers to determine whether similar information on the relationship of sound speed to lung volume could be obtained. We measured the transit time at multiple microphones placed over the chest wall using a 16-channel lung sound analyzer (Stethographics). There was a tight distribution of transit times in this population of subjects. At functional residual capacity, it was 9 ± 1 (SD) ms at the apical sites and 13 ± 1 ms at the lung bases. The sound speed at total lung capacity was 24 ± 2 m/s and was 22 ± 2 m/s at residual volume ( P < 0.001). In all subjects, the speed of sound was faster at higher lung volume. This improved method of studying the mechanism of sound transmission in the lung may help in the development of noninvasive tools for diagnosis and monitoring of lung diseases.
Impedance, gas mixing, and bimodal ventilation in constricted lungs
Authors: Anafi Ron C. , Beck Kenneth C. , Wilson Theodore A.
Published: March 2015

To evaluate the effect of increasing smooth muscle activation on the distribution of ventilation, lung impedance and expired gas concentrations were measured during a 16-breath He-washin maneuver in five nonasthmatic subjects at baseline and after each of three doses of aerosolized methacholine. Values of dynamic lung elastance (El,dyn), the curvature of washin plots, and the normalized slope of phase III ( S N) were obtained. At the highest dose, El,dyn was 2.6 times the control value and S N for the 16th breath was 0.65 liter−1. A previously described model of a constricted terminal airway was extended to include variable muscle activation, and the extended model was tested against these data. The model predicts that the constricted airway has two stable states. The impedances of the two stable states are independent of smooth muscle activation, but driving pressure and the number of airways in the high-resistance state increase with increasing muscle activation. Model predictions and experimental data agree well. We conclude that, as a result of the bistability of the terminal airways, the ventilation distribution in the constricted lung is bimodal.
Gender-related differences in elite gymnasts: the female athlete triad
Authors: Weimann Edda
Published: March 2015

High-intensity training can alter the normal pattern of pubertal development in elite gymnasts. We investigated sex hormones, the obgene product leptin, body composition, nutrition, and eating habits in female and male elite gymnasts from national cadres to elucidate gender-related differences. Serum leptin levels were decreased, particularly in pubertal girls, and did not show the normal developmental pattern. After leptin levels were transformed into standard deviation scores, mainly pubertal female gymnasts had significantly lower values than normal controls of the same gender, pubertal stage, and body mass index. The percentage of body fat was reduced compared with a normal age-matched population in both genders but to a higher degree in female gymnasts. When leptin standard deviation scores were based on percent body fat instead of body mass index, mean values were still significantly decreased compared with those of normal controls: −1.05 in girls ( P < 0.001) and −0.60 in boys ( P = 0.025). In both genders, total energy consumption and nutritional intake were insufficient, although to a lesser extent in male gymnasts. Pubertal development is influenced to a different degree in female and male elite gymnasts. In contrast to their male counterparts, high-intensity training takes place during the sensitive phase of pubertal maturation in female gymnasts. Whereas the girls displayed low estrogen levels, hypoleptinemia, reduced body fat mass, insufficient caloric intake, and retarded menarche, the pubertal development of male gymnasts remained almost unaltered.
Validation of surface recordings of the diaphragm response to transcranial magnetic stimulation in humans
Authors: Demoule Alexandre , Verin Eric , Locher Chrystèle , Derenne Jean-Philippe , Similowski Thomas
Published: March 2015

The integrity of the central efferent motor pathways to the diaphragm can be assessed by using transcranial magnetic stimulation to measure the latency of the corresponding motor evoked potentials with surface electrodes. Because transcranial magnetic stimulation does not activate the diaphragm alone, signal contamination is a potential problem. To evaluate this issue, surface diaphragmatic motor-evoked potential latencies were compared with latencies recorded from diaphragm needle in 9 healthy volunteers. Surface latencies of muscles likely to contaminate the diaphragm signals (serratus anterior, pectoralis major, and tranversus abdominis) were also recorded. The latencies in response to nonfocal transcranial stimulation from surface electrodes were not significantly different from the needle ones (17 ± 1.3 vs. 17.2 ± 1.1 ms, respectively) but were significantly different from the latencies of the other muscles. In two cases, signal contamination appeared likely (serratus anterior in 1 case, abdominal muscles in 1 case). It is possible to reliably measure the latency of the diaphragm response to transcranial magnetic stimulation with adequately positioned surface electrodes.
Quantification of subcellular glycogen in resting human muscle: granule size, number, and location
Authors: Marchand I. , Chorneyko K. , Tarnopolsky M. , Hamilton S. , Shearer J. , Potvin J. , Graham T. E.
Published: March 2015

A few qualitative investigations suggested that location of muscle glycogen (G) granules in specific sites may be associated with distinct metabolic roles. Similarly, it has been suggested that the acid-soluble and -insoluble G fractions (macro- and proglycogen, respectively) are different metabolic pools and also could exist as separate entities. We employed a transmission electron microscopic technique to quantify subcellular G particle size, number, and location in human vastus lateralis biopsies of 11 resting men. The intra- and interobserver variability for the various measures was generally <4%. Granule size and number were quantified in subcellular compartments (subsarcolemmal, intra- and intermyofibrillar). Subcellular location was critical: G was more densely concentrated in the subsarcolemmal than in the myofibrillar space, whereas the single-particle volume was greater in the latter. Single-particle diameter ranged from 10 to 44 ηm and followed a continuous, normal distribution. This implies that proglycogen is not a distinct entity, but rather that pro- and macroglycogen are divisions of smaller and larger molecules. These results demonstrate a compartmentalized pattern of subcellular G deposition in human skeletal muscle for both the size and density of granules.
A new surface electromyography analysis method to determine spread of muscle fiber conduction velocities
Authors: Lange Fiete , Van Weerden Tiemen W. , Van Der Hoeven Johannes H.
Published: March 2015

Muscle fiber conduction velocity (MFCV) estimation from surface signals is widely used to study muscle function, e.g., in neuromuscular disease and in fatigue studies. However, most analysis methods do not yield information about the velocity distribution of the various motor unit action potentials. We have developed a new method–the interpeak latency method (IPL)–to calculate both the mean MFCV and the spread of conduction velocities in vivo, from bipolar surface electromyogram (sEMG) during isometric contractions. sEMG was analyzed in the biceps brachii muscle in 15 young male volunteers. The motor unit action potential peaks are automatically detected with a computer program. Associated peaks are used to calculate a mean MFCV and the SD. The SD is taken as a measure of the MFCV spread. The main finding is that the IPL method can derive a measure of MFCV spread at different contraction levels. In conclusion, the IPL method provides accurate values for the MFCV and additionally gives information about the scatter of conduction velocities.
Gender-specific effects of thyroid hormones on cardiopulmonary function in SHHF rats
Authors: Schlenker E. H. , Tamura T. , Gerdes A. M.
Published: March 2015

Spontaneously hypertensive heart failure (SHHF) rats develop hypertension and heart failure. We hypothesized that induction of hyperthyroidism should accelerate development of heart failure in male SHHF rats. Male and female SHHF rats received diets containing desiccated thyroid glands (DTG) or a control diet for 8 wk. Male and female Wistar-Kyoto rats were used as normotensive controls. DTG treatment reduced body weight in male, but not female, SHHF rats but increased body temperature and heart weight-to-body weight ratio in both genders. In DTG-treated male SHHF rats, serum triiodothyronine levels doubled relative to SHHF controls, whereas O2 consumption increased in DTG-treated SHHF rats. Frequency of breathing in air increased in DTG-treated female rats, and ventilation increased in DTG-treated male rats. Ventilatory equivalents exhibited gender differences in SHHF rats, were decreased in both genders by DTG treatment, and reached levels similar to those of Wistar-Kyoto rats. DTG increased heart rate, right ventricular pressure, and contractility in both genders and increased left ventricular pressure in SHHF male rats. These results refute our hypothesis and suggest that cardiopulmonary function of SHHF male rats may be improved by DTG treatment.
Invited Review: Aging and the cardiovascular system
Authors: Ferrari Alberto U. , Radaelli Alberto , Centola Marco
Published: March 2015

Aging is associated with complex and diversified changes of cardiovascular structure and function. The heart becomes slightly hypertrophic and hyporesponsive to sympathetic (but not parasympathetic) stimuli, so that the exercise-induced increases in heart rate and myocardial contractility are blunted in older hearts. The aorta and major elastic arteries become elongated and stiffer, with increased pulse wave velocity, evidence of endothelial dysfunction, and biochemical patterns resembling early atherosclerosis. The arterial baroreflex is sizably altered in aging, but different components are differentially affected: there is a definite impairment of arterial baroreceptor control of the heart but much better preserved baroreceptor control of peripheral vascular resistance. Alterations at the afferent, central neural, efferent, and effector organ portions of the reflex arch have been claimed to account for age-related baroreflex changes, but no conclusive evidence is available on this mechanistic aspect. Reflexes arising from cardiopulmonary vagal afferents are also blunted in aged individuals. The cardiovascular and reflex changes brought about by aging may have significant implications for circulatory homeostasis in health and disease.
Skeletal muscle adaptations to microgravity exposure in the mouse
Authors: Harrison B. C. , Allen D. L. , Girten B. , Stodieck L. S. , Kostenuik P. J. , Bateman T. A. , Morony S. , Lacey D. , Leinwand L. A.
Published: March 2015

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to ∼11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced ( P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb ( P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.
Differential CO2-induced c-fosgene expression in the nucleus tractus solitarii of inbred mouse strains
Authors: Tankersley Clarke G. , Haxhiu Musa A. , Gauda Estelle B.
Published: March 2015

Genetic determinants confer variation between inbred mouse strains with respect to the magnitude and pattern of ventilation during hypercapnic challenge. Specifically, inheritance patterns derived from low-responsive C3H/HeJ (C3) and high-responsive C57BL/6J (B6) mouse strains suggest that differential hypercapnic ventilatory sensitivity (HCVS) is controlled by two independent genes. The present study also tests whether differential neuronal activity in respiratory control regions of the brain is positively associated with strain variation in HCVS. With the use of whole body plethysmography, ventilation was assessed in C3 and B6 strains at baseline and during 30 min of hypercapnia (inspired CO2fraction = 0.15, inspired O2fraction = 0.21 in N2). Subsequently, in situ hybridization histochemistry was performed to determine changes in c- fos gene expression in the commissural subnucleus of the nucleus tractus solitarius (NTS). During hypercapnia, breathing frequency and tidal volume were significantly ( P < 0.01) different between strains: C3 mice showed a slow, deep-breathing pattern relative to a rapid, shallow phenotype of B6 mice. CO2-induced increase in c- fos gene expression was significantly ( P < 0.01) greater in NTS regions of B6 compared with C3 mice. In this genetic model of differential HCVS, the results suggest that a genomic basis for varied hypercapnic chemoreception or transduction confers greater afferent neuronal activity in the caudal NTS for high-responsive B6 mice compared with low-responsive C3 mice.