bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy
Authors: Yarasheski Kevin E. , Tebas Pablo , Stanerson Barbara , Claxton Sherry , Marin Donna , Bae Kyongtae , Kennedy Michael , Tantisiriwat Woraphot , Powderly William G.
Published: December 2017

Hypertriglyceridemia, peripheral insulin resistance, and trunk adiposity are metabolic complications recently recognized in people infected with human immunodeficiency virus (HIV) and treated with highly active antiretroviral therapy (HAART). These complications may respond favorably to exercise training. Using a paired design, we determined whether 16 wk of weight-lifting exercise increased muscle mass and strength and decreased fasting serum triglycerides and adipose tissue mass in 18 HIV-infected men. The resistance exercise regimen consisted of three upper and four lower body exercises done for 1–1.5 h/day, 4 days/wk for 64 sessions. Dual-energy X-ray absorptiometry indicated that exercise training increased whole body lean mass 1.4 kg ( P = 0.005) but did not reduce adipose tissue mass ( P = NS). Axial proton-magnetic resonance imaging indicated that thigh muscle cross-sectional area increased 5–7 cm2( P < 0.005). Muscle strength increased 23–38% ( P < 0.0001) on all exercises. Fasting serum triglycerides were decreased at the end of training (281–204 mg/dl; P = 0.02). These findings imply that resistance exercise training-induced muscle hypertrophy may promote triglyceride clearance from the circulation of hypertriglyceridemic HIV-infected men treated with antiviral therapy.
Short-term 17β-estradiol decreases glucose Ra but not whole body metabolism during endurance exercise
Authors: Carter S. , McKenzie S. , Mourtzakis M. , Mahoney D. J. , Tarnopolsky M. A.
Published: December 2017

The female sex hormone 17β-estradiol (E2) has been shown to increase lipid and decrease carbohydrate utilization in animals. We administrated oral E2 and placebo (randomized, double blind, crossover) to eight human male subjects for 8 days (∼3 mg/day) and measured respiratory variables, plasma substrates, hormones (E2, testosterone, leptin, cortisol, insulin, and catecholamines), and substrate utilization during 90 min of endurance exercise. [6,6-2H]glucose and [1,1,2,3,3-2H]glycerol tracers were used to calculate substrate flux. E2 administration increased serum E2 (0.22 to 2.44 nmol/l, P < 0.05) and decreased serum testosterone (19.4 to 11.5 nmol/l, P < 0.05) concentrations, yet there were no treatment effects on any of the other hormones. Glucose rates of appearance (Ra) and disappearance (Rd) were lower, and glycerol Ra-to-Rd ratio was not affected by E2 administration. O2 uptake, CO2production, and respiratory exchange ratio were not affected by E2; however, there was a decrease in heart rate ( P < 0.05). Plasma lactate and glycerol were unaffected by E2; however, glucose was significantly higher ( P < 0.05) during exercise after E2administration. We concluded that short-term oral E2administration decreased glucose Ra and Rd, maintained plasma glucose homeostasis, but had no effect on substrate oxidation during exercise in men.
Fatigue in mammalian skeletal muscle stimulated under computer control
Authors: Wise A. K. , Morgan D. L. , Gregory J. E. , Proske U.
Published: December 2017

Functional electrical stimulation (FES) is used to provide paralyzed human subjects with postural support and a limited range of movements. Problems encountered with FES include jerky movements from tension oscillations during stimulation and rapid muscle fatigue. In this paper, we report experiments on anesthetized cats that test a new, computer-controlled method of stimulation of the muscle nerve supply, distributed across several inputs, which reduces these problems. After 5 min of continuous, distributed stimulation of the medial gastrocnemius muscle at 6 pulses per second (pps) across 6 channels, tension fell to 55.9 ± 3.9% (SE) of its original value. In comparison, after 5 min of synchronous stimulation of one muscle portion at 36 pps, tension fell to 11 ± 3.7%. At higher stimulation rates, 10 pps per channel (distributed) and 60 pps (synchronous), the differences in fatigue were even greater. Similar results were obtained when an intermittent, rather than a continuous, stimulation protocol was used. These findings indicate that distributed stimulation has important advantages over other methods for applications such as FES.
Effects of depolarization and low intracellular pH on charge movement currents of frog skeletal muscle fibers
Authors: Balog Edward M. , Fitts Robert H.
Published: December 2017

The low intracellular pH and membrane depolarization associated with repeated skeletal muscle stimulation could impair the function of the transverse tubular (t tubule) voltage sensor and result in a decreased sarcoplasmic reticulum Ca2+release and muscle fatigue. We therefore examined the effects of membrane depolarization and low intracellular pH on the t-tubular charge movement. Fibers were voltage clamped in a double Vaseline gap, at holding potential (HP) of −90 or −60 mV, and studied at an internal pH of 7.0 and 6.2. Decreasing intracellular pH did not significantly alter the maximum amount of charge moved, transition voltage, or steepness factor at either HP. Depolarizing HP significantly decreased steepness factor and maximum charge moved and shifted the transition voltage to more positive potentials. Elevated extracellular Ca2+decreased the depolarization-induced reduction in the charge movement. These results indicate that, although the decrease in intracellular pH seen in fatigued muscle does not impair the t-tubular charge movement, the membrane depolarization associated with muscle fatigue may be sufficient to inactivate a significant fraction of the t-tubular charge. However, if t-tubular Ca2+increases, some of the charge may be stabilized in the active state and remain available to initiate sarcoplasmic reticulum Ca2+release.
Interaction between vestibulosympathetic and skeletal muscle reflexes on sympathetic activity in humans
Authors: Ray Chester A.
Published: December 2017

Evidence from animals indicates that skeletal muscle afferents activate the vestibular nuclei and that both vestibular and skeletal muscle afferents have inputs to the ventrolateral medulla. The purpose of the present study was to investigate the interaction between the vestibulosympathetic and skeletal muscle reflexes on muscle sympathetic nerve activity (MSNA) and arterial pressure in humans. MSNA, arterial pressure, and heart rate were measured in 17 healthy subjects in the prone position during three experimental trials. The three trials were 2 min of 1) head-down rotation (HDR) to engage the vestibulosympathetic reflex, 2) isometric handgrip (IHG) at 30% maximal voluntary contraction to activate skeletal muscle afferents, and 3) HDR and IHG performed simultaneously. The order of the three trials was randomized. HDR and IHG performed alone increased total MSNA by 46 ± 16 and 77 ± 24 units, respectively ( P < 0.01). During the HDR plus IHG trial, MSNA increased 142 ± 38 units ( P < 0.01). This increase was not significantly different from the sum of the individual trials (130 ± 41 units). This finding was also observed with mean arterial pressure (sum = 21 ± 2 mmHg and HDR + IHG = 22 ± 2 mmHg). These findings suggest that there is an additive interaction for MSNA and arterial pressure when the vestibulosympathetic and skeletal muscle reflexes are engaged simultaneously in humans. Therefore, no central modulation exists between these two reflexes with regard to MSNA output in humans.
Dorsomedial medulla is more susceptible than rostral ventrolateral medulla to hypoxic insult in cats
Authors: Hong Ling-Zong , Kuo Jon-Son , Yen Mao-Hsiung , Chai Chok-Yung
Published: December 2017

We investigated the responses of systemic arterial pressure and vertebral sympathetic nerve activity to glutamate microinjections (0.1 M, 70 nl) in the dorsomedial (DM) and the rostral ventrolateral medulla (RVLM) before hypoxia and after reoxygenation (posthypoxia) after various degrees of hypoxia in anesthetized cats. Hypoxia was produced by ventilating 5% O2and 95% N2for different durations (hypoxia I-III). In intact cats, the glutamate-induced systemic arterial pressure and vertebral nerve activity responses of the DM were depressed after all degrees of hypoxia. Posthypoxic depression in the RVLM, however, was not observed until hypoxia II and III. Precollicular decerebration prevented depression in the RVLM, but, for the DM, it was effective only for hypoxia I. Baro- and chemoreceptor denervation abolished all posthypoxic depression in both the DM and the RVLM. Pressor responses to tyramine (100–400 μg/kg iv) remained unchanged after all degrees of hypoxia. These results suggest that the DM is more susceptible to hypoxia than the RVLM. The peripheral baro- and chemoreceptors and the suprapontine structures apparently play an important role in posthypoxic depression. Moreover, the depression is not due to the postganglionic norepinephrine depletion.
Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors
Authors: Leshnower B. G. , Potts J. T. , Garry M. G. , Mitchell J. H.
Published: December 2017

It is well known that the exercise pressor reflex (EPR) is mediated by group III and IV skeletal muscle afferent fibers, which exhibit unique discharge responses to mechanical and chemical stimuli. Based on the difference in discharge patterns of group III and IV muscle afferents, we hypothesized that activation of mechanically sensitive (MS) fibers would evoke a different pattern of cardiovascular responses compared with activation of both MS and chemosensitive (CS) fibers. Experiments were conducted in chloralose-urethane-anesthetized cats ( n = 10). Passive muscle stretch was used to activate MS afferents, and electrically evoked contraction of the triceps surae was used to activate both MS and CS muscle afferents. No significant differences were shown in reflex heart rate and mean arterial pressure (MAP) responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according to tension-time index (TTI), the peak MAP response (67 ± 4 vs. 56 ± 4 mmHg, P < 0.05) was significantly greater at higher TTI (427 ± 18 vs. 304 ± 13 kg · s, high vs. low TTI, P < 0.05), despite different modes of afferent fiber activation. When the same mode of afferent fiber activation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted by the magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s, high vs. low TTI, P < 0.05). Total sensory input from skeletal muscle ergoreceptors, as predicted by TTI and not the modality of afferent fiber activation (muscle contraction vs. passive stretch), is suggested to be the primary determinant of the magnitude of the EPR-evoked cardiovascular response.
Imaging of skeletal muscle function using 18FDG PET: force production, activation, and metabolism
Authors: Pappas George P. , Olcott Eric W. , Drace John E.
Published: December 2017

The purpose of this study was to determine whether [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used to evaluate muscle force production, create anatomic images of muscle activity, and resolve the distribution of metabolic activity within exercising skeletal muscle. Seventeen subjects performed either elbow flexion, elbow extension, or ankle plantar flexion after intravenous injection of FDG. PET imaging was performed subsequently, and FDG uptake was measured in skeletal muscle for each task. A fivefold increase in resistance during elbow flexion increased FDG uptake in the biceps brachii by a factor of 4.9. Differences in relative FDG uptake were demonstrated as exercise tasks and loads were varied, permitting differentiation of active muscles. The intramuscular distribution of FDG within exercising biceps brachii varied along the transverse and longitudinal axes of the muscle; coefficients of variation along these axes were 0.39 and 0.23, respectively. These findings suggest FDG PET is capable of characterizing task-specific muscle activity and measuring intramuscular variations of glucose metabolism within exercising skeletal muscle.
Validity of NIR spectroscopy for quantitatively measuring muscle oxidative metabolic rate in exercise
Authors: Sako Takayuki , Hamaoka Takafumi , Higuchi Hiroyuki , Kurosawa Yuko , Katsumura Toshihito
Published: December 2017

The purpose of this study was to examine the validity of the quantitative measurement of muscle oxidative metabolism in exercise by near-infrared continuous-wave spectroscopy (NIRcws). Twelve male subjects performed two bouts of dynamic handgrip exercise, once for the NIRcws measurement and once for the 31P-magnetic resonance spectroscopy (MRS) measurement as a standard measure. The resting muscle metabolic rate (RMRmus) was independently measured by 31P-MRS during 15 min of arterial occlusion at rest. During the first exercise bout, the quantitative value of muscle oxidative metabolic rate at 30 s postexercise was evaluated from the ratio of the rate of oxyhemoglobin/myoglobin decline measured by NIRcws during arterial occlusion 30 s after exercise and the rate at rest. Therefore, the absolute values of muscle oxidative metabolic rate at 30 s after exercise [V˙o 2NIR(30)] was calculated from this ratio multiplied by RMRmus. During the second exercise bout, creatine phosphate (PCr) resynthesis rate was measured by 31P-MRS at 30 s postexercise [Q(30)] under the same conditions but without arterial occlusion postexercise. To determine the validity of NIRcws, V˙o 2NIR(30) was compared with Q(30). There was a significant correlation betweenV˙o 2NIR(30), which ranged between 0.018 and 0.187 mM ATP/s, and Q(30), which ranged between 0.041 and 0.209 mM ATP/s ( r = 0.965, P < 0.001). This result supports the application of NIRcws to quantitatively evaluate muscle oxidative metabolic rate in exercise.
Invited Review: Molecular mechanisms of phenotypic plasticity in smooth muscle cells
Authors: Halayko Andrew J. , Solway Julian
Published: December 2017

Morphological, functional, molecular and cell biology studies have revealed a striking multifunctional nature of individual smooth muscle cells (SMC). SMCs manifest phenotypic plasticity in response to changes in environment and functional requirements, acquiring a range of structural and functional properties bounded by two extremes, called “synthetic” and “contractile.” Each phenotypic state is characterized by expression of a unique set of structural, contractile, and receptor proteins and isoforms that correlate with differing patterns of gene expression. Recent studies have identified signaling pathways and transcription factors (e.g., RhoA GTPase/ROCK, also known as Rho kinase, and serum response factor) that regulate the transcriptional activities of genes encoding proteins associated with the contractile apparatus. Mechanical plasticity of contractile-state smooth muscle further extends SMC functional diversity. This may also be regulated, in part, by the RhoA GTPase/ROCK pathway, via reorganization of cytoskeletal and contractile proteins. Future studies that define transcriptional and posttranscriptional mechanisms of SMC plasticity are necessary to fully understand the role of SMC in the pathogenesis and morbidity of human diseases of the airways, vasculature, and gastrointestinal tract.
Selected Contribution: Low-frequency stimulation of fast muscle affects the abundance of Ca2+-ATPase but not its oligomeric status
Authors: Harmon Shona , Froemming Gabriele R. , Leisner Elmi , Pette Dirk , Ohlendieck Kay
Published: December 2017

After chronic, low-frequency stimulation, a rapid decline in Ca2+pump activity is observed during the early stages of skeletal muscle transformation. However, this variation in enzymatic activity does not coincide with a drastic reduction in the amount of sarcoplasmic reticulum Ca2+-ATPases. To investigate whether changes in subunit interactions within Ca2+pump complexes contribute to this phenomena, we performed a chemical cross-linking analysis of 4 days continuously, and 4 days discontinuously, electrostimulated fast muscle fibers. The abundance of the slow and fast Ca2+-ATPase isoforms sarco(endo)plasmic reticulum Ca2+- ATPase types 1 and 2 was affected during the fast-to-slow transition process, demonstrating that, even after short-term stimulation, distinct changes in the isoform expression pattern of muscle proteins occur. However, the oligomeric status of both ion pump species did not change. Hence, chemical modifications of critical enzyme domains must be responsible for the rapid stimulation-induced activity changes, not variations in protein-protein interactions within Ca2+-ATPase units. Oligomerization appears to be of central importance to the proper physiological functioning of the Ca2+-ATPase and does not undergo changes during skeletal muscle conditioning.
Alteration of humoral and peripheral vascular responses during graded exercise in heart failure
Authors: Hammond Robert L. , Augustyniak Robert A. , Rossi Noreen F. , Lapanowski Karen , Dunbar Joseph C. , O'Leary Donal S.
Published: December 2017

We hypothesized that performance of exercise during heart failure (HF) would lead to hypoperfusion of active skeletal muscles, causing sympathoactivation at lower workloads and alteration of the normal hemodynamic and hormonal responses. We measured cardiac output, mean aortic and right atrial pressures, hindlimb and renal blood flow (RBF), arterial plasma norepinephrine (NE), plasma renin activity (PRA), and plasma arginine vasopressin (AVP) in seven dogs during graded treadmill exercises and at rest. In control experiments, sympathetic activation at the higher workloads resulted in increased cardiac performance that matched the increased muscle vascular conductance. There were also increases in NE, PRA, and AVP. Renal vascular conductance decreased during exercise, such that RBF remained at resting levels. After control experiments, HF was induced by rapid ventricular pacing, and the exercise protocols were repeated. At rest in HF, cardiac performance was significantly depressed and caused lower mean arterial pressure, despite increased HR. Neurohumoral activation was evidenced by renal and hindlimb vasoconstriction and by elevated NE, PRA, and AVP levels, but it did not increase at the mildest workload. Beyond mild exercise, sympathoactivation increased, accompanied by progressive renal vasoconstriction, a fall in RBF, and very large increases of NE, PRA, and AVP. As exercise intensity increased, peripheral vasoconstriction increased, causing arterial pressure to rise to near normal levels, despite depressed cardiac output. However, combined with redirection of RBF, this did not correct the perfusion deficit to the hindlimbs. We conclude that, in dogs with HF, the elevated sympathetic activity observed at rest is not exacerbated by mild exercise. However, with heavier workloads, sympathoactivation begins at lower workloads and becomes progressively exaggerated at higher workloads, thus altering distribution of blood flow.
Exposure to febrile temperature modifies endothelial cell response to tumor necrosis factor-α
Authors: Hasday Jeffrey D. , Bannerman Douglas , Sakarya Sirhan , Cross Alan S. , Singh Ishwar S. , Howard Deborah , Drysdale Beth-Ellen , Goldblum Simeon E.
Published: December 2017

Fever is an important regulator of inflammation that modifies expression and bioactivity of cytokines, including tumor necrosis factor (TNF)-α. Pulmonary vascular endothelium is an important target of TNF-α during the systemic inflammatory response. In this study, we analyzed the effect of a febrile range temperature (39.5°C) on TNF-α-stimulated changes in endothelial barrier function, capacity for neutrophil binding and transendothelial migration (TEM), and cytokine secretion in human pulmonary artery endothelial cells (EC). Permeability for [14C]BSA tracer was increased by treatment with TNF-α, and this effect was augmented by incubating EC at 39.5°C. Treating EC with 2.5 U/ml TNF-α stimulated an increase in subsequent neutrophil adherence and TEM. Incubating EC at 39.5°C caused a 30% increase in TEM but did not modify the enhancement of neutrophil adherence or TEM by TNF-α treatment. Analysis of cytokine expression in EC cultures exposed to TNF-α at either 37° or 39.5°C revealed three patterns of temperature and TNF-α responsiveness. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8 were not detectable in untreated EC but were increased after TNF-α exposure, and this increase was enhanced at 39.5°C. IL-6 expression was also increased with TNF-α exposure, but IL-6 expression was lower in 39.5°C EC cultures. Transforming growth factor-β1was constitutively expressed, and its expression was not influenced either by TNF-α or exposure to 39.5°C. These data demonstrate that clinically relevant shifts in body temperature might cause important changes in the effects of proinflammatory cytokines on the endothelium.
Modification of soft tissue vibrations in the leg by muscular activity
Authors: Wakeling James M. , Nigg Benno M.
Published: December 2017

Vibration characteristics were recorded for the soft tissues of the triceps surae, tibialis anterior, and quadriceps muscles. The frequency and damping of free vibrations in these tissues were measured while isometric and isotonic contractions of the leg were performed. Soft tissue vibration frequency and damping increased with both the force produced by and the shortening velocity of the underlying muscle. Both frequency and damping were greater in a direction normal to the skin surface than in a direction parallel to the major axis of each leg segment. Vibration characteristics further changed with the muscle length and between the individuals tested. The range of the measured vibration frequencies coincided with typical frequencies of impact forces during running. However, observations suggest that soft tissue vibrations are minimal during running. These results support the strategy that increases in muscular activity may be used by some individuals to move the frequency and damping characteristics of the soft tissues away from those of the impact force and thus minimize vibrations during walking and running.
Weight-bearing exercise and markers of bone turnover in female athletes
Authors: Creighton Dana L. , Morgan Amy L. , Boardley Debra , Brolinson P. Gunnar
Published: December 2017

Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes ( n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n= 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 ± 0.03 and 1.05 ± 0.03) than in the Non (1.05 ± 0.04 and 0.86 ± 0.04) and Con (1.03 ± 0.05 and 0.85 ± 0.05) groups and greater at the TR in the Med group (1.01 ± 0.03) than in the Non (0.86 ± 0.04) and Con (0.85 ± 0.05) groups. Total body BMD was higher in the High group (4.9 ± 0.12) than in the Med (4.5 ± 0.12), Non (4.2 ± 0.14), and Con (4.1 ± 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 ± 2.6) than in the High (30.6 ± 3.0) and Med (32.9 ± 1.9, P ≤ 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers.
Reserve capacity for ATP consumption during isometric contraction in human skeletal muscle fibers
Authors: Han Young-Soo , Proctor David N. , Geiger Paige C. , Sieck Gary C.
Published: December 2017

Maximum velocity of the actomyosin ATPase reaction ( VmaxATPase) and ATP consumption rate during maximum isometric activation (ATPiso) were determined in human vastus lateralis (VL) muscle fibers expressing different myosin heavy chain (MHC) isoforms. We hypothesized that the reserve capacity for ATP consumption [1 − (ratio of ATPisoto VmaxATPase)] varies across VL muscle fibers expressing different MHC isoforms. Biopsies were obtained from 12 subjects (10 men and 2 women; age 21–66 yr). A quantitative histochemical procedure was used to measure VmaxATPase. In permeabilized fibers, ATPisowas measured using an NADH-linked fluorometric procedure. The reserve capacity for ATP consumption was lower for fibers coexpressing MHC2Xand MHC2Acompared with fibers singularly expressing MHC2Aand MHCslow(39 vs. 52 and 56%, respectively). Tension cost (ratio of ATPisoto generated force) also varied with fiber type, being highest in fibers coexpressing MHC2Xand MHC2A. We conclude that fiber-type differences in the reserve capacity for ATP consumption and tension cost reflect functional differences such as susceptibility to fatigue.
Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects
Authors: Brieva Jorge , Wanner Adam
Published: December 2017

The purpose of the present study was to determine the responsiveness of airway vascular smooth muscle (AVSM) as assessed by airway mucosal blood flow (Q˙aw) to inhaled methoxamine (α1-agonist; 0.6–2.3 mg) and albuterol (β2-agonist; 0.2–1.2 mg) in healthy [ n = 11; forced expiratory volume in 1 s, 92 ± 4 (SE) % of predicted] and asthmatic ( n = 11, mean forced expiratory volume in 1 s, 81 ± 5%) adults. Mean baseline values for Q˙aw were 43.8 ± 0.7 and 54.3 ± 0.8 μl · min−1· ml−1of anatomic dead space in healthy and asthmatic subjects, respectively ( P < 0.05). After methoxamine inhalation, the maximal mean change in Q˙aw was −13.5 ± 1.0 μl · min−1· ml−1in asthmatic and −7.1 ± 2.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). After albuterol, the mean maximal change in Q˙aw was 3.0 ± 0.8 μl · min−1· ml−1in asthmatic and 14.0 ± 1.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). These results demonstrate that the contractile response of AVSM to α1-adrenoceptor activation is enhanced and the dilator response of AVSM to β2-adrenoceptor activation is blunted in asthmatic subjects.
Selected Contribution: Effect of chronic passive length change on airway smooth muscle length-tension relationship
Authors: Wang Lu , Paré Peter D. , Seow Chun Y.
Published: December 2017

The ability of rabbit trachealis to undergo plastic adaptation to chronic shortening or lengthening was assessed by setting the muscle preparations at three lengths for 24 h in relaxed state: a reference length in which applied force was ∼1–2% of maximal active force (Po) and lengths considerably shorter and longer than the reference. Passive and active length-tension ( L-T) curves for the preparations were then obtained by electrical field stimulation at progressively increasing muscle length. Classically shaped L-T curves were obtained with a distinct optimal length ( Lo) at which Podeveloped; however, both the active and passive L-T curves were shifted, whereas Poremained unchanged. Lowas 72% and 148% that of the reference preparations for the passively shortened and lengthened muscles, respectively. The results suggest that chronic narrowing of the airways could induce a shift in the L-T relationship of smooth muscle, resulting in a maintained potential for maximal force production.
Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans
Authors: Crandall C. G. , MacLean D. A.
Published: December 2017

Inhibition of cutaneous nitric oxide (NO) synthase reduces the magnitude of cutaneous vasodilation during whole body heating in humans. However, this observation is insufficient to conclude that NO concentration increases in the skin during a heat stress. This study was designed to test the hypothesis that whole body heating increases cutaneous interstitial NO concentration. This was accomplished by placing 2 microdialysis membranes in the forearm dermal space of 12 subjects. Both membranes were perfused with lactated Ringer solutions at a rate of 2 μl/min. In both normothermia and during whole body heating via a water perfused suit, dialysate from these membranes were obtained and analyzed for NO using the chemiluminescence technique. In six of these subjects, after the heat stress, the membranes were perfused with a 1 M solution of acetylcholine to stimulate NO release. Dialysate from these trials was also assayed to quantify cutaneous interstitial NO concentration. Whole body heating increased skin temperature from 34.6 ± 0.2 to 38.8 ± 0.2°C ( P < 0.05), which increased sublingual temperature (36.4 ± 0.1 to 37.6 ± 0.1°C; P < 0.05), heart rate (63 ± 5 to 93 ± 5 beats/min; P < 0.05), and skin blood flow over the membranes (21 ± 4 to 88 ± 10 perfusion units; P < 0.05). NO concentration in the dialysate did not increase significantly during of the heat stress (7.6 ± 0.7 to 8.6 ± 0.8 μM; P > 0.05). After the heat stress, administration of acetylcholine in the perfusate significantly increased skin blood flow (128 ± 6 perfusion units) relative to both normothermic and heat stress values and significantly increased NO concentration in the dialysate (15.8 ± 2.4 μM). These data suggest that whole body heating does not increase cutaneous interstitial NO concentration in forearm skin. Rather, NO may serve in a permissive role in facilitating the effects of an unknown neurotransmitter, leading to cutaneous vasodilation during a heat stress.
Time course of responses of human skeletal muscle to oxidative stress induced by nondamaging exercise
Authors: Khassaf Muna , Child Robert B. , McArdle Anne , Brodie David A. , Esanu Cristian , Jackson Malcolm J.
Published: December 2017

Previous studies in animals have demonstrated that a single period of aerobic exercise induces a rise in the skeletal muscle activity of the antioxidant enzymes superoxide dismutase and catalase and an increase in the muscle content of heat shock proteins (HSPs). The purpose of this study was to examine the time course of response of human skeletal muscle superoxide dismutase and catalase activities and the content of HSP60 and HSP70 after a period of exhaustive, nondamaging aerobic exercise. Seven volunteers undertook one-legged cycle ergometry at 70% maximal oxygen uptake for 45 min. Biopsies were obtained from the vastus lateralis muscle 7 days before and at 1, 2, 3, and 6 days after exercise. Muscle superoxide dismutase activity increased to a peak at 3 days postexercise, muscle catalase activities were unchanged, and muscle content of HSP60 and the inducible HSP70 increased by variable amounts to reach means of 190% and 3,100% of preexercise values, respectively, by 6 days postexercise. These data indicate that human skeletal muscle responds to a single bout of nondamaging exercise by increasing superoxide dismutase activity and provide the first evidence of an increase in HSP content of human skeletal muscle after a submaximal exercise bout.
Effects of marked hyperthermia with and without dehydration onV˙o 2 kinetics during intense exercise
Authors: Nybo Lars , Jensen Thorbjørn , Nielsen Bodil , González-Alonso José
Published: December 2017

This study determined whether marked hyperthermia alone or in combination with dehydration reduces the initial rate of rise in O2 consumption (V˙o 2on-kinetics) and the maximal rate of O2 uptake (V˙o 2 max) during intense cycling exercise. Six endurance-trained male cyclists completed four maximal cycle ergometer exercise tests (402 ± 4 W) when euhydrated or dehydrated (4% body wt) with normal (starting esophageal temperature, 37.5 ± 0.2°C; mean skin temperature, ∼31°C) or elevated (+1 and +6°C, respectively) thermal strain. In the euhydrated and normal condition, subjects reachedV˙o 2 max (4.7 ± 0.2 l/min) in 228 ± 34 s, with a mean response time of 42 ± 2 s, and fatigued after 353 ± 39 s. Hyperthermia alone or in combination with dehydration reduced mean response time (17–23%),V˙o 2 max (16%), and performance time (51–53%) (all P < 0.01) but did not alter the absolute response time (i.e., the time to reach 63% response in the control trial, 3.2 ± 0.1 l/min, 42 s). Reduction inV˙o 2 max was accompanied by proportional decline in O2 pulse and significantly elevated maximal heart rate (195 vs. 190 beats/min for hyperthermia vs. normal). Preventing hyperthermia in dehydrated subjects restoredV˙o 2 max and performance time by 65 and 50%, respectively. These results demonstrate that impaired high-intensity exercise performance with marked skin and internal body hyperthermia alone or in combination with dehydration is not associated with a diminished rate of rise in V˙o 2 but decreased V˙o 2 max.
Methodology for the measurement of mucociliary function in the mouse by scintigraphy
Authors: Foster W. Michael , Walters Dianne M. , Longphre Malinda , Macri Kristin , Miller Laura M.
Published: December 2017

The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by γ-camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., ∼60–80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and ≥80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.
Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle
Authors: Hood David A.
Published: December 2017

Chronic contractile activity produces mitochondrial biogenesis in muscle. This adaptation results in a significant shift in adenine nucleotide metabolism, with attendant improvements in fatigue resistance. The vast majority of mitochondrial proteins are derived from the nuclear genome, necessitating the transcription of genes, the translation of mRNA into protein, the targeting of the protein to a mitochondrial compartment via the import machinery, and the assembly of multisubunit enzyme complexes in the respiratory chain or matrix. Putative signals involved in initiating this pathway of gene expression in response to contractile activity likely arise from combinations of accelerations in ATP turnover or imbalances between mitochondrial ATP synthesis and cellular ATP demand, and Ca2+fluxes. These rapid events are followed by the activation of exercise-responsive kinases, which phosphorylate proteins such as transcription factors, which subsequently bind to upstream regulatory regions in DNA, to alter transcription rates. Contractile activity increases the mRNA levels of nuclear-encoded proteins such as cytochrome c and mitochondrial transcription factor A (Tfam) and mRNA levels of upstream transcription factors like c- junand nuclear respiratory factor-1 (NRF-1). mRNA level changes are often most evident during the postexercise recovery period, and they can occur as a result of contractile activity-induced increases in transcription or mRNA stability. Tfam is imported into mitochondria and controls the expression of mitochondrial DNA (mtDNA). mtDNA contributes only 13 protein products to the respiratory chain, but they are vital for electron transport and ATP synthesis. Contractile activity increases Tfam expression and accelerates its import into mitochondria, resulting in increased mtDNA transcription and replication. The result of this coordinated expression of the nuclear and the mitochondrial genomes, along with poorly understood changes in phospholipid synthesis, is an expansion of the muscle mitochondrial reticulum. Further understanding of 1) regulation of mtDNA expression, 2) upstream activators of NRF-1 and other transcription factors, 3) the identity of mRNA stabilizing proteins, and 4) potential of contractile activity-induced changes in apoptotic signals are warranted.
Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat
Authors: Armour John , Tyml Karel , Lidington Darcy , Wilson John X.
Published: December 2017

Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 ± 4 to 29 ± 2 μM) in plasma ascorbate concentration, 1,000% increase (from 46 ± 13 to 450 ± 93 μM) in urine ascorbate concentration, 20% decrease (from 115 ± 2 to 91 ± 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 ± 1 to 17 ± 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 μM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.
Influence of contraction intensity, muscle, and gender on median frequency of the quadriceps femoris
Authors: Pincivero Danny M. , Campy Robert M. , Salfetnikov Yuliya , Bright Ashley , Coelho Alan J.
Published: December 2017

The purpose of this study was to assess the effects of contraction intensity, gender, and muscle on median frequency of the three superficial portions of the quadriceps femoris muscle. Thirty healthy volunteers were assessed for isometric electromyogram activity of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscles with the knee at 60° flexion. Subjects performed 5-s isometric contractions at 10, 20, 30, 40, 50, 60, 70, 80, and 90% of the average of three maximal voluntary contractions. Median frequency ( fmed) of the three muscles was assessed through a power spectral analysis performed over 11 consecutive 512-ms epochs overlapping each other by one-half their length. The fmedfor each of the 11 epochs was then determined, followed by calculation of the mean and SD. The major findings of this study demonstrated that overall fmedwas significantly highest for the VL and lowest for the VM, whereas RF fmedwas between that of the other two muscles. Similar findings were observed for fmedvariability as the VL was significantly higher than the VM and RF, with no gender differences or differences between the latter two muscles. The results demonstrate that the largest change in fmedas a function of contraction intensity occurred for the VL in men (18.6%) and women (7.6%). These findings suggest that muscle fiber-type homogeneity may exist in the VM and RF, which displayed negligible changes in fmed, whereas the VL may possess greater morphological variability.
Treatment with endothelin-receptor antagonists increases NOS activity in hypercholesterolemia
Authors: Taner C. Burcin , Severson Sandra R. , Best Patricia J. M. , Lerman Amir , Miller Virginia M.
Published: December 2017

In experimental hypercholesterolemia, endothelium-dependent relaxations decrease, as does endothelial immunoreactivity for nitric oxide (NO) synthase (NOS; eNOS) in coronary arteries. Systemic levels of NO also decrease with concomitant elevations in systemic circulating levels of endothelin (ET)-1. Chronic treatment of hypercholesterolemic pigs with ET-receptor antagonists increases circulating NO and improves endothelium-dependent relaxations. Mechanisms causing these increases are not known. Therefore, experiments were designed to test the hypothesis that chronic administration of ET-receptor antagonists to hypercholesterolemic pigs increases NO production through increases in NOS activity. Female juvenile pigs were fed a 2% cholesterol atherogenic diet and were randomly allocated to receive no treatment (controls), a selective ETA-receptor antagonist (ABT-624), or a combined ETA+ ETB-receptor antagonist (RO-48-5695) daily for 12 wk. After 12 wk, endothelial cells from thoracic aorta were prepared for measurement of eNOS mRNA or eNOS activity. Total cholesterol, low-density-lipoprotein cholesterol, and concentrations of ET-1 were significantly higher in all three groups at 12 wk compared with baseline levels. Circulating plasma-oxidized products of NO (NOx) increased with ET-receptor blockade. NOS mRNA was similar among groups. Total and Ca-dependent NOS activity was significantly higher in aortic endothelial cells from the ETA+ ETB-treated pigs compared with those treated with ETAantagonist alone. These results suggest that changes in systemic NOx after chronic inhibition of ETA+ ETBreceptors in hypercholesterolemia may result from posttranscriptional changes in NOS.
Excitatory lung reflex may stress inspiratory muscle by suppressing expiratory muscle activity
Authors: Yu J. , Wang Y. , Soukhova G. , Collins L. C. , Falcone J. C.
Published: December 2017

Recently, a vagally mediated excitatory lung reflex (ELR) causing neural hyperpnea and tachypnea was identified. Because ventilation is regulated through both inspiratory and expiratory processes, we investigated the effects of the ELR on these two processes simultaneously. In anesthetized, open-chest, and artificially ventilated rabbits, we recorded phrenic nerve activity and abdominal muscle activity to assess the breathing pattern when the ELR was evoked by directly injecting hypertonic saline (8.1%, 0.1 ml) into lung parenchyma. Activation of the ELR stimulated inspiratory activity, which was exhibited by increasing amplitude, burst rate, and duty cycle of the phrenic activity (by 22 ± 4, 33 ± 9, and 57 ± 11%, respectively; n = 13; P < 0.001), but suppressed expiratory muscle activity. The expiratory muscle became silent in most cases. On average, the amplitude of expiratory muscle activity decreased by 88 ± 5% ( P < 0.002). The suppression reached the peak at 6.9 ± 1 s and lasted for 200 s (median). Injection of H2O2into the lung parenchyma produced similar responses. By suppressing expiration, the ELR produces a shift in the workload from expiratory muscle to inspiratory muscle. Therefore, we conclude that the ELR may contribute to inspiratory muscle fatigue, not only by directly increasing the inspiratory activity but also by suppressing expiratory activity.
Pro- and macroglycogenolysis: relationship with exercise intensity and duration
Authors: Graham T. E. , Adamo K. B. , Shearer J. , Marchand I. , Saltin B.
Published: December 2017

We examined the net catabolism of two pools of glycogen, proglycogen (PG) and macroglycogen (MG), in human skeletal muscle during exercise. Male subjects ( n = 21) were assigned to one of three groups. Group 1 exercised 45 min at 70% maximal O2 uptake (V˙o 2 max) and had muscle biopsies at rest, 15 min, and 45 min. Group 2 exercised at 85%V˙o 2 max to exhaustion (45.4 ± 3.4 min) and had biopsies at rest, 10 min, and exhaustion. Group 3 performed three 3-min bouts of exercise at 100%V˙o 2 max separated by 6 min of rest. Biopsies were taken at rest and after each bout. Group 1 had small MG and PG net glycogenolysis rates (ranging from 3.8 ± 1.0 to 2.4 ± 0.6 mmol glucosyl units · kg−1 · min−1) that did not change over time. In group 2, the MG glycogenolysis rate remained low and unchanged over time, whereas the PG rate was initially elevated (11.3 ± 2.3 mmol glucosyl units · kg−1 · min−1) and declined ( P ≤ 0.05) with time. During the first 10 min, PG concentration ([PG]) declined ( P ≤ 0.05), whereas MG concentration ([MG]) did not. Similarly, in group 3, in both the first and the second bouts of exercise [PG] declined ( P ≤ 0.05) and [MG] did not, although by the end of the second exercise period the [MG] was lower ( P ≤ 0.05) than the rest level. The net catabolic rates for PG in the first two exercises were 22.6 ± 6.8 and 21.8 ± 8.2 mmol glucosyl units · kg−1 · min−1, whereas the corresponding values for MG were 17.6 ± 6.0 and 10.8 ± 5.6. The MG pool appeared to be more resistant to mobilization, and, when activated, its catabolism was inhibited more rapidly than that of PG. This suggests that the metabolic regulation of the two pools must be different.
l-Arginine enhances aerobic exercise capacity in association with augmented nitric oxide production
Authors: Maxwell Andrew J. , Ho Hoai-Ky V. , Le Christine Q. , Lin Patrick S. , Bernstein Daniel , Cooke John P.
Published: December 2017

We tested whether supplementation with l-arginine can augment aerobic capacity, particularly in conditions where endothelium-derived nitric oxide (EDNO) activity is reduced. Eight-week-old wild-type (E+) and apolipoprotein E-deficient mice (E−) were divided into six groups; two groups (LE+and LE−) were given l-arginine (6% in drinking water), two were given d-arginine (DE+and DE−), and two control groups (NE+and NE−) received no arginine supplementation. At 12–16 wk of age, the mice were treadmill tested, and urine was collected after exercise for determination of EDNO production. NE−mice demonstrated a reduced aerobic capacity compared with NE+controls [maximal oxygen uptake (V˙o2 max) of NE−= 110 ± 2 (SE) vs. NE+= 122 ± 3 ml O2· min−1· kg−1, P < 0.001]. This decline in aerobic capacity was associated with a diminished postexercise urinary nitrate excretion. Mice given l-arginine demonstrated an increase in postexercise urinary nitrate excretion and aerobic capacity in both groups (V˙o2 maxof LE−= 120 ± 1 ml O2· min−1· kg−1, P < 0.05 vs. NE−;V˙o2 maxof LE+= 133 ± 4 ml O2· min−1· kg−1, P < 0.01 vs. NE+). Mice administered d-arginine demonstrated an intermediate increase in aerobic capacity in both groups. We conclude that administration of l-arginine restores exercise-induced EDNO synthesis and normalizes aerobic capacity in hypercholesterolemic mice. In normal mice, l-arginine enhances exercise-induced EDNO synthesis and aerobic capacity.