bluuebunny/crossref_metadata_2025 huggingface dataset:
Training induces nonuniform increases in eNOS content along the coronary arterial tree
Authors: Laughlin M. H. , Pollock J. S. , Amann J. F. , Hollis M. L. , Woodman C. R. , Price E. M.
Published: December 2017

Exercise training produces enhanced nitric oxide (NO)-dependent, endothelium-mediated vasodilator responses of porcine coronary arterioles but not conduit coronary arteries. The purpose of this study was to test the hypothesis that exercise training increases the amount of endothelial NO synthase (eNOS) in the coronary arterial microcirculation but not in the conduit coronary arteries. Miniature swine were either exercise trained or remained sedentary for 16–20 wk. Exercise-trained pigs exhibited increased skeletal muscle oxidative capacity, exercise tolerance, and heart weight-to-body weight ratios. Content of eNOS protein was determined with immunoblot analysis in conduit coronary arteries (2- to 3-mm ID), small arteries (301- to 1,000-μm ID), resistance arteries (151- to 300-μm ID), and three sizes of coronary arterioles [large (101- to 150-μm ID), intermediate (51- to 100-μm ID), and small (<50-μm ID)]. Immunoblots revealed increased eNOS protein in some sizes of coronary arteries and arterioles but not in others. Content of eNOS was increased by 60–80% in small and large arterioles, resistance arteries, and small arteries; was increased by 10–20% in intermediate-sized arterioles; and was not changed or decreased in conduit arteries. Immunohistochemistry revealed that eNOS was located in the endothelial cells in all sizes of coronary artery. We conclude that exercise training increases eNOS protein expression in a nonuniform manner throughout the coronary arterial tree. Regional differences in shear stress and intraluminal pressures during exercise training bouts may be responsible for the distribution of increased eNOS protein content in the coronary arterial tree.
Influence of static stretching on viscoelastic properties of human tendon structures in vivo
Authors: Kubo Keitaro , Kanehisa Hiroaki , Kawakami Yasuo , Fukunaga Tetsuo
Published: December 2017

The purpose of this study was to investigate the influences of static stretching on the viscoelastic properties of human tendon structures in vivo. Seven male subjects performed static stretching in which the ankle was passively flexed to 35° of dorsiflexion and remained stationary for 10 min. Before and after the stretching, the elongation of the tendon and aponeurosis of medial gastrocnemius muscle (MG) was directly measured by ultrasonography while the subjects performed ramp isometric plantar flexion up to the maximum voluntary contraction (MVC), followed by a ramp relaxation. The relationship between the estimated muscle force (Fm) of MG and tendon elongation ( L) during the ascending phase was fitted to a linear regression, the slope of which was defined as stiffness of the tendon structures. The percentage of the area within the Fm- L loop to the area beneath the curve during the ascending phase was calculated as an index representing hysteresis. Stretching produced no significant change in MVC but significantly decreased stiffness and hysteresis from 22.9 ± 5.8 to 20.6 ± 4.6 N/mm and from 20.6 ± 8.8 to 13.5 ± 7.6%, respectively. The present results suggest that stretching decreased the viscosity of tendon structures but increased the elasticity.
Enhanced synthesis of albumin and fibrinogen at high altitude
Authors: Imoberdorf Reinhard , Garlick Peter J. , McNurlan Margaret A. , Casella George A. , Peheim Edgar , Turgay Meral , Bärtsch Peter , Ballmer Peter E.
Published: December 2017

The acute effects of active and passive ascent to high altitude on plasma volume (PV) and rates of synthesis of albumin and fibrinogen have been examined. Measurements were made in two groups of healthy volunteers, initially at low altitude (550 m) and again on the day after ascent to high altitude (4,559 m). One group ascended by helicopter (air group, n = 8), whereas the other group climbed (foot group, n = 9), so that the separate contribution of physical exertion to the response could be delineated. PV was measured by dilution of125I-labeled albumin, whereas synthesis rates of albumin and fibrinogen were determined from the incorporation of isotope into protein after injection of [ ring-2H5]phenylalanine. In the air group, there was no change in PV at high altitude, whereas, in the foot group, there was a 10% increase in PV ( P < 0.01). Albumin synthesis (mg · kg−1· day−1) increased by 13% in the air group ( P = 0.058) and by 32% in the foot group ( P < 0.001). Fibrinogen synthesis (mg · kg−1· day−1) increased by 40% in the air group ( P = 0.068) and by 100% in the foot group ( P < 0.001). Hypoxia and alkalosis at high altitude did not differ between the groups. Plasma interleukin-6 was increased modestly in both groups but C-reactive protein was not changed in either group. It is concluded that increases in PV and plasma protein synthesis at high altitude result mainly from the physical exercise associated with climbing. However, a small stimulation of albumin and fibrinogen synthesis may be attributable to hypobaric hypoxia alone.
Computational modeling of RBC and neutrophil transit through the pulmonary capillaries
Authors: Huang Yaqi , Doerschuk Claire M. , Kamm Roger D.
Published: December 2017

A computational model of the pulmonary microcirculation is developed and used to examine blood flow from arteriole to venule through a realistically complex alveolar capillary bed. Distributions of flow, hematocrit, and pressure are presented, showing the existence of preferential pathways through the system and of large segment-to-segment differences in all parameters, confirming and extending previous work. Red blood cell (RBC) and neutrophil transit are also analyzed, the latter drawing from previous studies of leukocyte aspiration into micropipettes. Transit time distributions are in good agreement with in vivo experiments, in particular showing that neutrophils are dramatically slowed relative to the flow of RBCs because of the need to contract and elongate to fit through narrower capillaries. Predicted neutrophil transit times depend on how the effective capillary diameter is defined. Transient blockage by a neutrophil can increase the local pressure drop across a segment by 100–300%, leading to temporal variations in flow and pressure as seen by videomicroscopy. All of these effects are modulated by changes in transpulmonary pressure and arteriolar pressure, although RBCs, neutrophils, and rigid microspheres all behave differently.
Role of nitric oxide in the airway response to exercise in healthy and asthmatic subjects
Authors: De Gouw H. W. F. M. , Marshall-Partridge S. J. , Van der Veen H. , Van den Aardweg J. G. , Hiemstra P. S. , Sterk P. J.
Published: December 2017

A role of nitric oxide (NO) has been suggested in the airway response to exercise. However, it is unclear whether NO may act as a protective or a stimulatory factor. Therefore, we examined the role of NO in the airway response to exercise by using N-monomethyl-l-arginine (l-NMMA, an NO synthase inhibitor), l-arginine (the NO synthase substrate), or placebo as pretreatment to exercise challenge in 12 healthy nonsmoking, nonatopic subjects and 12 nonsmoking, atopic asthmatic patients in a double-blind, crossover study. Fifteen minutes after inhalation of l-NMMA (10 mg),l-arginine (375 mg), or placebo, standardized bicycle ergometry was performed for 6 min using dry air, while ventilation was kept constant. The forced expiratory volume in 1-s response was expressed as area under the time-response curve (AUC) over 30 min. In healthy subjects, there was no significant change in AUC betweenl-NMMA and placebo treatment [28.6 ± 17.0 and 1.3 ± 20.4 (SE) for placebo and l-NMMA, respectively, P = 0.2]. In the asthmatic group, l-NMMA and l-arginine induced significant changes in exhaled NO ( P < 0.01) but had no significant effect on AUC compared with placebo (geometric mean ± SE: −204.3 ± 1.5, −186.9 ± 1.4, and −318.1 ± 1.2% · h for placebo,l-NMMA, and l-arginine, respectively, P > 0.2). However, there was a borderline significant difference in AUC between l-NMMA and l-arginine treatment ( P = 0.052). We conclude that modulation of NO synthesis has no effect on the airway response to exercise in healthy subjects but that NO synthesis inhibition slightly attenuates exercise-induced bronchoconstriction compared with NO synthase substrate supplementation in asthma. These data suggest that the net effect of endogenous NO is not inhibitory during exercise-induced bronchoconstriction in asthma.
Fiber type and metabolic dependence of T2 increases in stimulated rat muscles
Authors: Prior Barry M. , Ploutz-Snyder Lori L. , Cooper Thomas G. , Meyer Ronald A.
Published: December 2017

This study examined the relationships between muscle fiber type, metabolism, and blood flow vs. the increase in skeletal muscle 1H-NMR transverse relaxation time (T2) after stimulation. Triceps surae muscles of anesthetized rats were stimulated in situ at 1–10 Hz for 6 min, and T2 was calculated from1H-NMR images acquired at 4.7 T immediately after stimulation. At low-to-intermediate frequencies (1–5 Hz), the stimulation-induced T2 increase was greater in the superficial, fast-twitch white portion of the gastrocnemius muscle compared with the deeper, more aerobic muscles of the triceps surae group. Although whole triceps muscle area changed in parallel with T2 after stimulation when blood flow was intact, clamping of the femoral artery during stimulation prevented an increase in muscle area but not an increase in T2. Partial inhibition of lactic acid production with iodoacetate diminished intracellular acidification (measured by 31P-NMR spectroscopy) during brief (1.5 min) stimulation but had no significant effect either on estimated osmolite accumulation or on muscle T2 after stimulation. Depletion of muscle phosphocreatine content by feeding rats β-guanidinopropionate decreased both estimated osmolite accumulation and T2 after 1.5-min stimulation. The results are consistent with the hypothesis that the T2 increase in stimulated muscle is related to osmotically driven shifts of fluid into an intracellular compartment.
Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans
Authors: Doerzbacher Kelly J. , Ray Chester A.
Published: December 2017

Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B2in the drug group (from 36 ± 6 to 22 ± 3 pg/ml, P < 0.04), whereas thromboxane B2in the placebo group increased from 40 ± 5 to 61 ± 9 pg/ml from trial 1 to trial 2 ( P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B2concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.
Validity of two-component models for estimating body fat of black men
Authors: Wagner Dale R. , Heyward Vivian H.
Published: December 2017

Commonly used two-component model conversion formulas that estimate relative body fat (%BF) from body density (Db) were cross-validated on a heterogeneous sample of black men ( n = 30; age = 19–45 yr). A four-component model was used to obtain criterion measures of %BF, and linear regression and analysis of individual residual scores were conducted to assess the predictive accuracy of the formulas under investigation. The two-component formula commonly used to estimate %BF of black men (Schutte JE, Townsend EJ, Hugg J, Shoup RF, Malina RM, and Blomqvist CG. J Appl Physiol 56: 1647–1649, 1984) significantly ( P ≤ 0.01) and systematically (87% of sample) overestimated %BF (−1.28%); thus we developed the following two-component Db conversion formula: %BF = [(4.858/Db) − 4.394] × 100. Because our formula was derived from a four-component model and a larger, more heterogeneous sample than the commonly used two-component formula, we recommend using it to convert Db to %BF for black men. Additionally, there was good agreement between dual-energy X-ray absorptiometry and the four-component model, making this a suitable alternative for estimating the %BF of black men.
Training affects muscle phospholipid fatty acid composition in humans
Authors: Helge Jørn W. , Wu Ben J. , Willer Mette , Daugaard Jens R. , Storlien Leonard H. , Kiens Bente
Published: December 2017

Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 ± 0.5% and 3.2 ± 0.4% of total fatty acids, respectively) than the untrained leg (8.8 ± 0.5% and 2.6 ± 0.4%, P < 0.05). The ratio between n-6 and n-3 fatty acids was significantly lower in the trained (11.1 ± 0.9) than the untrained leg (13.1 ± 1.2, P < 0.05). In contrast, training did not affect muscle triacylglycerol fatty acid composition. Citrate synthase activity was increased by 17% in the trained compared with the untrained leg ( P < 0.05). In this model, diet plays a minimal role, as the influence of dietary intake is similar on both legs. Regular exercise training per se influences the phospholipid fatty acid composition of muscle membranes but has no effect on the composition of fatty acids stored in triacylglycerols within the muscle.
Airway responses to chronic ozone exposure are partially mediated through mast cells
Authors: Kleeberger Steven R. , Ohtsuka Yoshinori , Zhang Liu-Yi , Longphre Malinda
Published: December 2017

Airways inflammation and epithelial injury induced by chronic ozone (O3) in genetically mast cell-deficient mice (KitW/KitW-v) were compared with those in mast cell-sufficient mice (+/+) and KitW/KitW-v mice repleted of mast cells (KitW/KitW-v-BMT). Mice were exposed to 0.26 ppm O3 8 h/day, 5 days/wk, for 1–90 days. Background was 0.06 ppm O3. Age-matched mice were exposed to filtered air for O3 controls. Reversibility of lesions was evaluated 35 days after exposure. Compared with KitW/KitW-v, O3 caused greater increases in lavageable macrophages, epithelial cells, and polymorphonuclear leukocytes in +/+ and KitW/KitW-v-BMT mice. O3 also caused lung hyperpermeability, but the genotypic groups were not different. Cells and permeability returned to air control levels after O3. O3 induced lung cell proliferation only in +/+ and KitW/KitW-v-BMT mice; proliferation remained elevated or increased in +/+ and KitW/KitW-v-BMT mice after O3. Greater O3-induced cell proliferation was found in nasal epithelium of +/+ and KitW/KitW-v-BMT mice compared with KitW/KitW-v mice. Results are consistent with the hypothesis that mast cells affect airway responses induced by chronic O3 exposure.
Invited Review: Redox modulation of skeletal muscle contraction: what we know and what we don't
Authors: Reid Michael B.
Published: December 2017

Over the past decade, reactive oxygen species (ROS) and nitric oxide (NO) derivatives have been established as physiological modulators of skeletal muscle function. This mini-review addresses the roles of these molecules as endogenous regulators of muscle contraction. The article is organized in two parts. First, established concepts are briefly outlined. This section provides an overview of ROS production by muscle, antioxidant buffers that oppose ROS effects, enzymatic synthesis of NO in muscle, the effects of endogenous ROS on contractile function, and NO as a contractile modulator. Second, a selected group of unresolved topics are highlighted. These more controversial issues include putative source(s) of regulatory ROS, the relative importance of the two NO synthase isoforms constitutively coexpressed by muscle fibers, molecular mechanisms of ROS and NO action, and the physiological relevance of redox regulation. By discussing current questions, as well as the established paradigm, this article is intended to further debate and stimulate research in this area.
Limitation of lower limbV˙o2during cycling exercise in COPD patients
Authors: Simon Mathieu , LeBlanc Pierre , Jobin Jean , Desmeules Marc , Sullivan Martin J. , Maltais François
Published: December 2017

Patients with chronic obstructive pulmonary disease (COPD) usually stop exercise before reaching physiological limits in terms of O2delivery and extraction. A plateau in lower limb O2uptake (V˙o2) and blood flow occurs despite progression of the imposed workload during cycling in some patients with COPD, suggesting that maximal capacity to transport O2had been reached and that it had been extracted in the peripheral exercising muscles. This study addresses this observation. Symptom-limited incremental cycle exercise was performed by 14 men [62 ± 11 (SD) yr] with severe COPD (forced expiratory volume in 1 s = 35 ± 7% of predicted value). Leg blood flow was measured at each exercise step with a thermodilution catheter inserted in the femoral vein. This value was multiplied by two to account for both working legs (Q˙LEGS). Arterial and femoral venous blood was sampled at each exercise step to measure blood gases. Leg O2consumption (V˙o2LEGS) was calculated according to the Fick equation. Total bodyV˙o2(V˙o2TOT) was measured from expired gas analysis, and tidal volume (Vt) and minute ventilation (V˙e) were derived from the flow signal. In eight patients, V˙o2LEGSkept increasing in parallel withV˙o2TOTas external work rate was increasing. In six subjects, a plateau inV˙o2LEGSandQ˙LEGSoccurred during exercise (increment of <3% between 2 consecutive increasing workloads) despite the increase in workload and V˙o2TOT[corresponding mean was 110 ± 38 ml (11 ± 4%)]. These six patients also exhibited a plateau in O2extraction during exercise. Peak exercise work rate was higher in the eight patients without a plateau than in the six with a plateau (51 ± 10 vs. 40 ± 13 W, P = 0.043). Vt,V˙e, and dyspnea were significantly greater at submaximal exercise in patients of the plateau group compared with those of the nonplateau group. These results show that, in some patients with COPD, blood flow directed to peripheral muscles and O2extraction during exercise may be limited. We speculate that redistribution of cardiac output and O2from the lower limb exercising muscles to the ventilatory muscles is a possible mechanism.
Catecholamines increase lung edema clearance in rats with increased left atrial pressure
Authors: Azzam Zaher S. , Saldias Fernando J. , Comellas Alejandro , Ridge Karen M. , Rutschman David H. , Sznajder Jacob I.
Published: December 2017

During hydrostatic pulmonary edema, active Na+transport and alveolar fluid reabsorption are decreased. Dopamine (DA) and isoproterenol (ISO) have been shown to increase active Na+transport in rat lungs by upregulating Na+-K+-ATPase in the alveolar epithelium. We studied the effects of DA and ISO in isolated rat lungs with increased left atrial pressure (Pla = 15 cmH2O) compared with control rats with normal Pla (Pla = 0). Alveolar fluid reabsorption decreased from control value of 0.51 ± 0.02 to 0.27 ± 0.02 ml/h when Pla was increased to 15 cmH2O ( P < 0.001). DA and ISO increased the alveolar fluid reabsorption back to control levels. Treatment with the D1antagonist SCH-23390 inhibited the stimulatory effects of DA (0.30 ± 0.02 ml/h), whereas fenoldopam, a specific D1-receptor agonist, increased alveolar fluid reabsorption in rats exposed to Pla of 15 cmH2O (0.47 ± 0.04 ml/h). Propranolol, a β-adrenergic-receptor antagonist, blocked the stimulatory effects of ISO; however, it did not affect alveolar fluid reabsorption in control or DA-treated rats. Amiloride (a Na+channel blocker) and ouabain (a Na+-K+-ATPase inhibitor), either alone or together, inhibited the stimulatory effects of DA. Colchicine, which disrupts the cellular microtubular transport of ion-transporting proteins to the plasma membrane, inhibited the stimulatory effects of DA, whereas the isomer β-lumicolchicine did not block the stimulatory effects of DA. These data suggest that DA and ISO increase alveolar fluid reabsorption in a model of increased Pla by regulating active Na+transport in rat alveolar epithelium. The effects of DA and ISO are mediated by the activation of dopaminergic D1receptors and the β-adrenergic receptors, respectively.
Expression and functional behavior of troponin C in soleus muscle fibers of rat after hindlimb unloading
Authors: Kischel P. , Bastide B. , Stevens L. , Mounier Y.
Published: December 2017

Troponin C (TnC) plays a key role in the regulation of muscle contraction, thereby modulating the Ca2+-activation characteristics of skinned muscle fibers. This study was performed to assess the effects of a 15-day hindlimb unloading (HU) period on TnC expression and its functional behavior in the slow postural muscles of the rat. We investigated the TnC isoform expression in whole soleus muscles and in single fibers. The latter were also checked for their Ca2+activation characteristics and sensitivity to bepridil, a Ca2+sensitizer molecule. This drug has been described as exerting a differential effect on slow and fast fibers, depending on the TnC isoform. With regard to TnC expression, three populations were found in control muscle fibers: slow, hybrid slow, and hybrid fast fibers, with the TnC fast being always coexpressed with TnC slow. In the whole muscle, TnC fast expression increased after HU because of the increase in the proportion of hybrid fast fibers. The HU hybrid fast fibers had properties similar to those of control hybrid fast fibers. The fibers that remained slow after HU exhibited similar bepridil and Sr2+properties as control slow fibers. Therefore, in these fibers, the changes could not be related to the TnC molecule.
Historical Perspectives: Plasticity of mammalian skeletal muscle
Authors: Pette Dirk
Published: December 2017

More than 40 years ago, the nerve cross-union experiment of Buller, Eccles, and Eccles provided compelling evidence for the essential role of innervation in determining the properties of mammalian skeletal muscle fibers. Moreover, this experiment revealed that terminally differentiated muscle fibers are not inalterable but are highly versatile entities capable of changing their phenotype from fast to slow or slow to fast. With the use of various experimental models, numerous studies have since confirmed and extended the notion of muscle plasticity. Together, these studies demonstrated that motoneuron-specific impulse patterns, neuromuscular activity, and mechanical loading play important roles in both the maintenance and transition of muscle fiber phenotypes. Depending on the type, intensity, and duration of changes in any of these factors, muscle fibers adjust their phenotype to meet the altered functional demands. Fiber-type transitions resulting from multiple qualitative and quantitative changes in gene expression occur sequentially in a regular order within a spectrum of pure and hybrid fiber types.
Invited Review: Pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation
Authors: Hernandez Olga M. , Housmans Philippe R. , Potter James D.
Published: December 2017

Cardiac muscle contraction depends on the tightly regulated interactions of thin and thick filament proteins of the contractile apparatus. Mutations of thin filament proteins (actin, tropomyosin, and troponin), causing familial hypertrophic cardiomyopathy (FHC), occur predominantly in evolutionarily conserved regions and induce various functional defects that impair the normal contractile mechanism. Dysfunctional properties observed with the FHC mutants include altered Ca2+sensitivity, changes in ATPase activity, changes in the force and velocity of contraction, and destabilization of the contractile complex. One apparent tendency observed in these thin filament mutations is an increase in the Ca2+sensitivity of force development. This trend in Ca2+sensitivity is probably induced by altering the cross-bridge kinetics and the Ca2+affinity of troponin C. These in vitro defects lead to a wide variety of in vivo cardiac abnormalities and phenotypes, some more severe than others and some resulting in sudden cardiac death.
Invited Review: Plasticity and energetic demands of contraction in skeletal and cardiac muscle
Authors: Sieck Gary C. , Regnier Michael
Published: December 2017

Numerous studies have explored the energetic properties of skeletal and cardiac muscle fibers. In this mini-review, we specifically explore the interactions between actin and myosin during cross-bridge cycling and provide a conceptual framework for the chemomechanical transduction that drives muscle fiber energetic demands. Because the myosin heavy chain (MHC) is the site of ATP hydrolysis and actin binding, we focus on the mechanical and energetic properties of different MHC isoforms. Based on the conceptual framework that is provided, we discuss possible sites where muscle remodeling may impact the energetic demands of contraction in skeletal and cardiac muscle.
Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent
Authors: Gordon Scott E. , Flück Martin , Booth Frank W.
Published: December 2017

This investigation examined the effect of mechanical loading state on focal adhesion kinase (FAK), paxillin, and serum response factor (SRF) in rat skeletal muscle. We found that FAK concentration and tyrosine phosphorylation, paxillin concentration, and SRF concentration are all lower in the lesser load-bearing fast-twitch plantaris and gastrocnemius muscles compared with the greater load-bearing slow-twitch soleus muscle. Of these three muscles, 7 days of mechanical unloading via tail suspension elicited a decrease in FAK tyrosine phosphorylation only in the soleus muscle and decreases in FAK and paxillin concentrations only in the plantaris and gastrocnemius muscles. Unloading decreased SRF concentration in all three muscles. Mechanical overloading (via bilateral gastrocnemius ablation) for 1 or 8 days increased FAK and paxillin concentrations in the soleus and plantaris muscles. Additionally, whereas FAK tyrosine phosphorylation and SRF concentration were increased by ≤1 day of overloading in the soleus muscle, these increases did not occur until somewhere between 1 and 8 days of overloading in the plantaris muscle. These data indicate that, in the skeletal muscles of rats, the focal adhesion complex proteins FAK and paxillin and the transcription factor SRF are generally modulated in association with the mechanical loading state of the muscle. However, the somewhat different patterns of adaptation of these proteins to altered loading in slow- vs. fast-twitch skeletal muscles indicate that the mechanisms and time course of adaptation may partly depend on the prior loading state of the muscle.
Exogenous testosterone treatment decreases diaphragm neuromuscular transmission failure in male rats
Authors: Blanco Cesar E. , Zhan Wen-Zhi , Fang Yun-Hua , Sieck Gary C.
Published: December 2017

The effect of chronic exogenous testosterone (T) treatment on neuromuscular transmission in the diaphragm (Dia) muscle of adult male rats was determined. The contribution of neuromuscular transmission failure (NTF) to Dia fatigue was evaluated by superimposing intermittent direct muscle stimulation on repetitive nerve stimulation of isometric contraction in vitro. T treatment significantly reduced the contribution of NTF to Dia fatigue by ∼20% ( P < 0.001). Fiber type-specific effects on NTF were determined by measuring Dia fiber glycogen levels subsequent to repetitive nerve or muscle stimulation. T treatment had no effect on glycogen depletion in Dia type I and IIa fibers regardless of stimulation route. In the control group, type IIx fibers demonstrated significantly less glycogen depletion after nerve stimulation compared with direct muscle stimulation ( P < 0.05), suggesting the presence of NTF. In contrast, T treatment increased glycogen depletion of type IIx fibers during nerve stimulation to levels similar to those after direct muscle stimulation. These data indicate that testosterone treatment substantially improves neuromuscular transmission in the Dia.
In vivo specific tension of human skeletal muscle
Authors: Maganaris Constantinos N. , Baltzopoulos Vasilios , Ball D. , Sargeant Anthony J.
Published: December 2017

In this study, we estimated the specific tensions of soleus (Sol) and tibialis anterior (TA) muscles in six men. Joint moments were measured during maximum voluntary contraction (MVC) and during electrical stimulation. Moment arm lengths and muscle volumes were measured using magnetic resonance imaging, and pennation angles and fascicular lengths were measured using ultrasonography. Tendon and muscle forces were modeled. Two approaches were followed to estimate specific tension. First, muscle moments during electrical stimulation and moment arm lengths, fascicular lengths, and pennation angles during MVC were used ( data set A). Then, MVC moments, moment arm lengths at rest, and cadaveric fascicular lengths and pennation angles were used ( data set B). The use of data set B yielded the unrealistic specific tension estimates of 104 kN/m2in Sol and 658 kN/m2in TA. The use of data set A, however, yielded values of 150 and 155 kN/m2in Sol and TA, respectively, which agree with in vitro results from fiber type I-predominant muscles. In fact, both Sol and TA are such muscles. Our study demonstrates the feasibility of accurate in vivo estimates of human muscle intrinsic strength.
Effect of aerobic capacity on the T2 increase in exercised skeletal muscle
Authors: Reid Robert W. , Foley Jeanne M. , Jayaraman R. C. , Prior Barry M. , Meyer Ronald A.
Published: December 2017

The increase in nuclear magnetic resonance transverse relaxation time (T2) of muscle water measured by magnetic resonance imaging after exercise has been correlated with work rate in human subjects. This study compared the T2 increase in thigh muscles of trained (cyclingV˙o 2 max = 54.4 ± 2.7 ml O2 · kg−1 · min−1, mean ± SE, n = 8, 4 female) vs. sedentary (31.7 ± 0.9 ml O2 · kg−1 · min−1, n = 8, 4 female) subjects after cycling exercise for 6 min at 50 and 90% of the subjects' individually determinedV˙o 2 max. There was no significant difference between groups in the T2 increase measured in quadriceps muscles within 3 min after the exercises, despite the fact that the absolute work rates were 60% higher in the trained group (253 ± 15 vs. 159 ± 21 W for the 90% exercise). In both groups, the increase in T2 of vastus muscles was twofold greater after the 90% exercise than after the 50% exercise. The recovery of T2 after the 90% exercise was significantly faster in vastus muscles of the trained compared with the sedentary group (mean recovery half-time 11.9 ± 1.2 vs. 23.3 ± 3.7 min). The results show that the increase in muscle T2varies with work rate relative to muscle maximum aerobic power, not with absolute work rate.
Substrate utilization during exercise with glucose and glucose plus fructose ingestion in boys ages 10–14 yr
Authors: Riddell M. C. , Bar-Or O. , Wilk B. , Parolin M. L. , Heigenhauser G. J. F.
Published: December 2017

We measured substrate utilization during exercise performed with water (W), exogenous glucose (G), and exogenous fructose plus glucose (FG) ingestion in boys age 10–14 yr. Subjects ( n = 12) cycled for 90 min at 55% maximal O2uptake while ingesting either W (25 ml/kg), 6% G (1.5 g/kg), or 3% F plus 3% G (1.5 g/kg). Fat oxidation increased during exercise in all trials but was higher in the W (0.28 ± 0.023 g/min) than in the G (0.24 ± 0.023 g/min) and FG (0.25 ± 0.029 g/min) trials ( P = 0.04). Conversely, total carbohydrate (CHO) oxidation decreased in all trials and was lower in the W (0.63 ± 0.05 g/min) than in the G (0.78 ± 0.051 g/min) and FG (0.74 ± 0.056 g/min) trials ( P = 0.009). Exogenous CHO oxidation, as determined by expired13CO2, reached a maximum of 0.36 ± 0.032 and 0.31 ± 0.030 g/min at 90 min in G and FG, respectively ( P = 0.04). Plasma insulin levels decrease during exercise in all trials but were twofold higher in G than in W and FG ( P < 0.001). Plasma glucose levels decreased transiently after the onset of exercise in all trials and then returned to preexercise values in the W and FG (∼4.5 mmol/l) trials but were elevated by ∼1.0 mmol/l in the G trial ( P < 0.001). Plasma lactate concentrations decreased after the onset of exercise in all trials but were lower by ∼0.5 mmol/l in W than in G and FG ( P = 0.02). Thus, in boys exercising at a moderate intensity, the oxidation rate of G plus F is slightly less than G alone, but both spare endogenous CHO and fat to a similar extent. In addition, compared with flavored W, the ingestion of G alone and of G plus F delays exhaustion at 90% peak power by ∼25 and 40%, respectively, after 90 min of moderate-intensity exercise.
Dorsal horn administration of muscimol abolishes the muscle pressor reflex
Authors: Wilson L. Britt
Published: December 2017

The purpose of this study was to determine the effect of blocking synaptic transmission in the dorsal horn on the cardiovascular responses produced by activation of muscle afferent neurons. Synaptic transmission was blocked by applying the GABAAagonist muscimol to the dorsal surface of the spinal cord. Cats were anesthetized with α-chloralose and urethane, and a laminectomy was performed. With the exception of the L7dorsal root, the dorsal and ventral roots from L5to S2were sectioned on one side, and static contraction of the ipsilateral triceps surae muscle was evoked by electrically stimulating the peripheral ends of the L7and S1ventral roots. The dorsal surface of the L4–S3segments of the spinal cord were enclosed within a “well” created by applying layers of vinyl polysiloxane. Administration of a 1 mM solution of muscimol (based on dose-response data) into this well abolished the reflex pressor response to contraction (change in mean arterial blood pressure before was 47 ± 7 mmHg and after muscimol was 3 ± 2 mmHg). Muscle stretch increased mean arterial blood pressure by 30 ± 8 mmHg before muscimol, but after drug application stretch increased MAP by only 3 ± 2 mmHg. Limiting muscimol to the L7segment attenuated the pressor responses to contraction (37 ± 7 to 24 ± 11 mmHg) and stretch (28 ± 2 to 16 ± 8 mmHg). These data suggest that the dorsal horn of the spinal cord contains an obligatory synapse for the pressor reflex. Furthermore, these data support the hypothesis that branches of primary afferent neurons, not intraspinal pathways, are responsible for the multisegmental integration of the pressor reflex.
Nitric oxide does not contribute to the hypotension of heatstroke
Authors: Ryan Kathy L. , Tehrany Maria R. , Jauchem James R.
Published: December 2017

The purpose of this study was to determine whether nitric oxide (NO) contributes to the hypotensive state induced by prolonged environmental heat (EH) stress. Ketamine-anesthetized rats were instrumented for the measurement of arterial blood pressure, electrocardiogram, and temperature at four sites. Rats were exposed to EH (ambient temperature, 40 ± 1°C) until mean arterial blood pressure (MAP) decreased to 75 mmHg, which was arbitrarily defined as the induction of heatstroke. In addition to cardiovascular and temperature measurements, the time required to reach this MAP end point and the subsequent survival time were measured. In three separate experimental series, the competitive NO synthesis inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) was administered (0, 10, or 100 mg/kg) either before, during (30 min after initiation of EH), or immediately after EH. l-NAME administered at any of these times transiently increased MAP. l-NAME infusion either before or during EH did not alter the EH time required to decrease MAP to 75 mmHg, butl-NAME pretreatment did decrease the colonic temperature at which this MAP end point was reached. l-NAME infusion before or after EH did not affect subsequent survival time, butl-NAME administered during EH significantly decreased survival time. The administration of l-NAME at any time point, therefore, did not prove beneficial in either preventing or reversing heatstroke. Taken together, these data suggest that NO does not mediate the hypotension associated with heatstroke.
Overnight responses of the circulating IGF-I system after acute, heavy-resistance exercise
Authors: Nindl Bradley C. , Kraemer William J. , Marx James O. , Arciero Paul J. , Dohi Kei , Kellogg Mark D. , Loomis Gregory A.
Published: December 2017

This study evaluated the individual components of the insulin-like growth factor I (IGF-I) system [i.e., total and free IGF-I, insulin-like growth factor binding protein (IGFBP)-2 and -3, and the acid-labile subunit (ALS)] in 10 young, healthy men (age: 22 ± 1 yr, height: 177 ± 2 cm, weight: 79 ± 3 kg, body fat: 11 ± 1%) overnight for 13 h after two conditions: a resting control (Con) and an acute, heavy-resistance exercise protocol (Ex). The Ex was a high-volume, multiset exercise protocol that alternated between 10- and 5-repetition maximum sets with 90-s rest periods between sets. The Ex was performed from 1500 to 1700; blood was obtained immediately postexercise and sampled throughout the night (every 10 min for the first hour and every hour thereafter) until 0600 the next morning. For the first hour, significant differences ( P ≤ 0.05) were only observed for IGFBP-3 (Ex: 3,801 > Con: 3,531 ng/ml). For the overnight responses, no differences were observed for total or free IGF-I or IGFBP-3, whereas IGFBP-2 increased (Ex: 561 > Con: 500 ng/ml) and ALS decreased (Ex: 35 < Con: 39 μg/ml) after exercise. The results from this study suggest that the impact that resistance exercise exerts on the circulating IGF-I system is not in the alteration of the amount of IGF-I but rather of the manner in which IGF-I is partitioned among its family of binding proteins. Thus acute, heavy-resistance exercise can lead to alterations in the IGF-I system that can be detected in the systemic circulation.
Endurance training alters outward K+current characteristics in rat cardiocytes
Authors: Jew Korinne N. , Olsson M. Charlotte , Mokelke Eric A. , Palmer Bradley M. , Moore Russell L.
Published: December 2017

The effect of endurance run training on outward K+ currents with rapidly inactivating ( I to) and sustained or slowly inactivating ( I sus) characteristics was examined in left ventricular (LV) cardiocytes isolated from sedentary (Sed) and treadmill-trained (Tr) female Sprague-Dawley rats. Isolated LV cardiocytes were used in whole cell patch-clamp studies to characterize whole cell I to and I sus. Peak I to was greatest in cells isolated from the Tr group. When I to was corrected for cell capacitance to yield a current density, most, but not all, of the Sed vs. Tr differences in I to magnitude were eliminated. Regardless of how I to was expressed (e.g., I to or I todensity), the time required to achieve a peak value was markedly shortened in the cardiocytes isolated from the Tr group. Training elicited a reduction in I sus density. Action potential characteristics were determined in Sed and Tr cardiocytes in primary culture. Training did not affect resting membrane potential, whereas peak membrane potential was reduced and time to peak membrane potential was prolonged in the Tr group. In addition, time to 50% repolarization was significantly increased in cells from the Tr group. Collectively, these data indicate that I to and I sus characteristics are altered by training in isolated LV cardiocytes. These alterations in I to and I sus may be responsible, at least in part, for the training-induced alterations in action potential configuration in cardiocytes in primary culture.
Effects of vitamin E and α-lipoic acid on skeletal muscle contractile properties
Authors: Coombes Jeff S. , Powers Scott K. , Rowell Benjamin , Hamilton Karyn L. , Dodd Stephen L. , Shanely R. Andrew , Sen Chandan K. , Packer Lester
Published: December 2017

Initial experiments were conducted using an in situ rat tibialis anterior (TA) muscle preparation to assess the influence of dietary antioxidants on muscle contractile properties. Adult Sprague-Dawley rats were divided into two dietary groups: 1) control diet (Con) and 2) supplemented with vitamin E (VE) and α-lipoic acid (α-LA) (Antiox). Antiox rats were fed the Con rats' diet (AIN-93M) with an additional 10,000 IU VE/kg diet and 1.65 g/kg α-LA. After an 8-wk feeding period, no differences existed ( P > 0.05) between the two dietary groups in maximum specific tension before or after a fatigue protocol or in force production during the fatigue protocol. However, in unfatigued muscle, maximal twitch tension and tetanic force production at stimulation frequencies ≤40 Hz were less ( P < 0.05) in Antiox animals compared with Con. To investigate which antioxidant was responsible for the depressed force production, a second experiment was conducted using an in vitro rat diaphragm preparation. Varying concentrations of VE and dihydrolipoic acid, the reduced form of α-LA, were added either individually or in combination to baths containing diaphragm muscle strips. The results from these experiments indicate that high levels of VE depress skeletal muscle force production at low stimulation frequencies.
Respiratory dynamics during laughter
Authors: Filippelli Mario , Pellegrino Riccardo , Iandelli Iacopo , Misuri Gianni , Rodarte Joseph R. , Duranti Roberto , Brusasco Vito , Scano Giorgio
Published: December 2017

Lung and chest wall mechanics were studied during fits of laughter in 11 normal subjects. Laughing was naturally induced by showing clips of the funniest scenes from a movie by Roberto Benigni. Chest wall volume was measured by using a three-dimensional optoelectronic plethysmography and was partitioned into upper thorax, lower thorax, and abdominal compartments. Esophageal (Pes) and gastric (Pga) pressures were measured in seven subjects. All fits of laughter were characterized by a sudden occurrence of repetitive expiratory efforts at an average frequency of 4.6 ± 1.1 Hz, which led to a final drop in functional residual capacity (FRC) by 1.55 ± 0.40 liter ( P < 0.001). All compartments similarly contributed to the decrease of lung volumes. The average duration of the fits of laughter was 3.7 ± 2.2 s. Most of the events were associated with sudden increase in Pes well beyond the critical pressure necessary to generate maximum expiratory flow at a given lung volume. Pga increased more than Pes at the end of the expiratory efforts by an average of 27 ± 7 cmH2O. Transdiaphragmatic pressure (Pdi) at FRC and at 10% and 20% control forced vital capacity below FRC was significantly higher than Pdi at the same absolute lung volumes during a relaxed maneuver at rest ( P < 0.001). We conclude that fits of laughter consistently lead to sudden and substantial decrease in lung volume in all respiratory compartments and remarkable dynamic compression of the airways. Further mechanical stress would have applied to all the organs located in the thoracic cavity if the diaphragm had not actively prevented part of the increase in abdominal pressure from being transmitted to the chest wall cavity.
Endotoxemia increases relative perfusion to dorsal-caudal lung regions
Authors: Gerbino Anthony J. , Altemeier William A. , Schimmel Carmel , Glenny Robb W.
Published: December 2017

Changes in the spatial distribution of perfusion during acute lung injury and their impact on gas exchange are poorly understood. We tested whether endotoxemia caused topographical differences in perfusion and whether these differences caused meaningful changes in regional ventilation-to-perfusion ratios and gas exchange. Regional ventilation and perfusion were measured in anesthetized, mechanically ventilated pigs in the prone position before and during endotoxemia with the use of aerosolized and intravenous fluorescent microspheres. On average, relative perfusion halved in ventral and cranial lung regions, doubled in caudal lung regions, and increased 1.5-fold in dorsal lung regions during endotoxemia. In contrast, there were no topographical differences in perfusion before endotoxemia and no topographical differences in ventilation at any time point. Consequently, endotoxemia increased regional ventilation-to-perfusion ratios in the caudal-to-cranial and dorsal-to-ventral directions, resulting in end-capillary Po 2 values that were significantly lower in dorsal-caudal than ventral-cranial regions. We conclude that there are topographical differences in the pulmonary vascular response to endotoxin that may have important consequences for gas exchange in acute lung injury.
Ventilatory effects of impaired glial function in a brain stem chemoreceptor region in the conscious rat
Authors: Holleran Julianne , Babbie Melissa , Erlichman Joseph S.
Published: December 2017

Glia are thought to regulate ion homeostasis, including extracellular pH; however, their role in modulating central CO2 chemosensitivity is unclear. Using a push-pull cannula in chronically instrumented and conscious rats, we administered a glial toxin, fluorocitrate (FC; 1 mM) into the retrotrapezoid nucleus (RTN), a putative chemosensitive site, during normocapnia and hypercapnia. FC exposure significantly increased expired minute ventilation (V˙e) to a value 38% above the control level during normocapnia. During hypercapnia, FC also significantly increased both breathing frequency and expiredV˙e. During FC administration, maximal ventilation was achieved at ∼4% CO2, compared with 8–10% CO2 during control hypercapnic trials. RTN perfusion of control solutions had little effect on any ventilatory measures (V˙e, tidal volume, or breathing frequency) during normocapnic or hypercapnic conditions. We conclude that unilateral impairment of glial function in the RTN of the conscious rat results in stimulation of respiratory output.