bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximal and submaximal forces of slow fibers in human soleus after bed rest
Authors: Yamashita-Goto Katsumasa , Okuyama Ryoko , Honda Masanori , Kawasaki Kensuke , Fujita Kazuhiko , Yamada Takahiro , Nonaka Ikuya , Ohira Yoshinobu , Yoshioka Toshitada
Published: December 2017

The effects of 2 and 4 mo of bed rest, with or without exercise countermeasures, on the contractile properties of slow fibers in the human soleus muscle were examined. Mean fiber diameters were 8 and 36% smaller after 2 and 4 mo of bed rest, respectively, than the pre-bed rest level. Maximum tetanic force (Po), maximum activated force (Fmax) per cross-sectional area (CSA), and the common-logarithm value of free Ca2+concentration required for half-maximal activation (pCa50) also decreased after 2 and 4 mo of bed rest. In contrast, maximum unloaded shortening velocity ( Vo) was increased after 2 and 4 mo of bed rest. After 1 mo of recovery, fiber diameters, Po, Fmaxper CSA ( P > 0.05), and pCa50were increased and Vodecreased toward pre-bed rest levels. Effects of knee extension/flexion exercise by wearing an anti-G Penguin suit for 10 h daily, and the effects of loading or unloading of the plantar flexors with (Penguin-1) or without (Penguin-2) placing the elastic loading elements of the suit, respectively, were investigated during ∼2 mo of bed rest. In the Penguin-1 group, mean fiber diameter, Po, Fmaxper CSA, Vo, and pCa50were similar before and after bed rest. However, the responses of fiber size and contractile properties to bed rest were not prevented in the Penguin-2 group, although the degree of the changes was less than those induced by bed rest without any countermeasure. These results indicate that long-term bed rest results in reductions of fiber size, force-generation capacity, and Ca2+sensitivity, and enhancement of shortening velocity in slow fibers of the soleus. The data indicate that continuous mechanical loading on muscle, such as stretching of muscle, is an effective countermeasure for the prevention of muscular adaptations to gravitational unloading.
Impaired distensibility of the left ventricle after stiffening of the right ventricle
Authors: Shirakabe Masanori , Yamaguchi Seiji , Tamada Yoshiaki , Baniya Gajendra , Fukui Akio , Miyawaki Hiroshi , Tomoike Hitonobu
Published: December 2017

Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.
A single-breath technique with variable flow rate to characterize nitric oxide exchange dynamics in the lungs
Authors: Tsoukias Nikolaos M. , Shin Hye-Won , Wilson Archie F. , George Steven C.
Published: December 2017

Current techniques to estimate nitric oxide (NO) production and elimination in the lungs are inherently nonspecific or are cumbersome to perform (multiple-breathing maneuvers). We present a new technique capable of estimating key flow-independent parameters characteristic of NO exchange in the lungs: 1) the steady-state alveolar concentration (Calv,ss), 2) the maximum flux of NO from the airways ( JNO,max), and 3) the diffusing capacity of NO in the airways ( DNO,air). Importantly, the parameters were estimated from a single experimental single-exhalation maneuver that consisted of a preexpiratory breath hold, followed by an exhalation in which the flow rate progressively decreased. The mean values for JNO,max, DNO,air, and Calv,ssdo not depend on breath-hold time and range from 280–600 pl/s, 3.7–7.1 pl · s−1· parts per billion (ppb)−1, and 0.73–2.2 ppb, respectively, in two healthy human subjects. A priori estimates of the parameter confidence intervals demonstrate that a breath hold no longer than 20 s may be adequate and that JNO,maxcan be estimated with the smallest uncertainty and DNO,airwith the largest, which is consistent with theoretical predictions. We conclude that our new technique can be used to characterize flow-independent NO exchange parameters from a single experimental single-exhalation breathing maneuver.
Decreased monocarboxylate transporter 1 in rat soleus and EDL muscles exposed to clenbuterol
Authors: Kitaura Takashi , Tsunekawa Naoko , Hatta Hideo
Published: December 2017

We hypothesized that a shift in muscle fiber type induced by clenbuterol would change monocarboxylate transporter 1 (MCT1) content and activity of lactate dehydrogenase (LDH) and isoform pattern and shift myosin heavy chain (MHC) pattern in soleus (Sol) and extensor digitorum longus (EDL) of male rats. In the clenbuterol-administered rats (2.0 mg · kg−1 · day−1subcutaneously for 4 wk), the ratio of muscle weight to body weight increased in the Sol ( P < 0.05) and the EDL ( P < 0.01). Clenbuterol induced the appearance of fast MHC2D and decreased slow MHC1 in Sol (13%) but had no effect on EDL. The MHC pattern of Sol changed from slow to fast type. Clenbuterol increased LDH-specific activity ( P < 0.01) and the ratio of the muscle-type isozyme of LDH to the heart type ( P < 0.05) in Sol. The LDH total activity of the EDL muscle was also increased ( P < 0.05). Furthermore, MCT1 content significantly ( P < 0.05) decreased in both Sol and EDL (27 and 52%, respectively). This study suggests that clenbuterol might mediate the shift of MHC from slow to fast type and the changes in the regulation of lactate metabolism. Novel to this study is the observation that clenbuterol decreases MCT1 content in the hindlimb muscles and that the decrease in MCT1 is not muscle-type specific. It may suggest that the genetic expressions of individual factors involving slow-type MHC, heart-type isozyme of LDH, and MCT1 are associated with one another but are regulated independently.
Inhibition of nitric oxide synthesis attenuates thermally induced asthma
Authors: Kotaru C. , Skowronski M. , Coreno A. , McFadden E. R.
Published: December 2017

To determine whether the inhibition of nitric oxide (NO) synthesis attenuates thermally induced obstruction, we had 10 asthmatic volunteers perform isocapnic hyperventilation with frigid air after inhaling 1 mg of NG-monomethyl-l-arginine (l-NMMA) or isotonic saline in a blinded fashion. The challenges were identical in all respects, and there were no differences in baseline lung function [1-s forced expiratory volume (FEV1); saline 2.8 ± 0.3 liters, l-NMMA 2.9 ± 0.3 liters; P = 0.41] or prechallenge fractional concentration of nitric oxide in the exhaled air (FeNO) [saline 23 ± 6 parts/billion (ppb),l-NMMA 18 ± 4 ppb; P = 0.51]. Neither treatment had any impact on the FEV1, pulse, or blood pressure. After l-NMMA, FeNO fell significantly ( P < 0.0001), the stimulus-response curves shifted to the right, and the minute ventilation required to reduce the FEV120% rose 53.5% over control ( P = 0.02). The results of this study demonstrate that NO generated from the airways of asthmatic individuals may play an important role in the pathogenesis of thermally induced asthma.
Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels
Authors: Bělohlávková Simona , Šimák Jan , Kokešová Alena , Hniličková Olga , Hampl Václav
Published: December 2017

The anorexic agent fenfluramine considerably increases the risk of primary pulmonary hypertension. The mechanism of this effect is unknown. The appetite-reducing action of fenfluramine is mediated by its interaction with the metabolism of serotonin [5-hydroxytryptamine (5-HT)] in the brain. We tested the hypothesis that the pulmonary vasoconstrictive action of fenfluramine is at least in part mediated by 5-HT receptor activation. In addition, we sought to determine whether pharmacological reduction of voltage-gated potassium (KV) channel activity would potentiate the pulmonary vascular reactivity to fenfluramine. Using isolated rat lungs perfused with Krebs-albumin solution, we compared the inhibitory effect of ritanserin, an antagonist of 5-HT2 receptors, on fenfluramine- and 5-HT-induced vasoconstriction. Both 5-HT (10−5 mol/l) and fenfluramine (5 × 10−4 mol/l) caused significant increases in perfusion pressure. Ritanserin at a dose (10−7 mol/l) sufficient to inhibit >80% of the response to 5-HT reduced the response to fenfluramine by ∼50%. A higher ritanserin dose (10−5 mol/l) completely abolished the responses to 5-HT but had no more inhibitory effect on the responses to fenfluramine. A pharmacological blockade of KV channels by 4-aminopyridine (3 × 10−3 mol/l) markedly potentiated the pulmonary vasoconstrictor response to fenfluramine but was without effect on the reactivity to 5-HT. These data indicate that the pulmonary vasoconstrictor response to fenfluramine is partly mediated by 5-HT receptors. Furthermore, the pulmonary vasoconstrictor potency of fenfluramine is elevated when the KV-channel activity is low. This finding suggests that preexisting KV-channel insufficiency may predispose some patients to the development of pulmonary hypertension during fenfluramine treatment.
Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA
Authors: Krzywkowski Karen , Petersen Emil Wolsk , Ostrowski Kenneth , Link-Amster Harriet , Boza Julio , Halkjaer-Kristensen Jens , Pedersen Bente Klarlund
Published: December 2017

Postexercise immune impairment has been linked to exercise-induced decrease in plasma glutamine concentration. This study examined the possibility of abolishing the exercise-induced decrease in salivary IgA through glutamine supplementation during and after intense exercise. Eleven athletes performed cycle ergometer exercise for 2 h at 75% of maximal oxygen uptake on 3 separate days. Glutamine (a total of 17.5 g), protein (a total of 68.5 g/6.2 g protein-bound glutamine), and placebo supplements were given during and up to 2 h after exercise. Unstimulated, timed saliva samples were obtained before exercise and 20 min, 140 min, 4 h, and 22 h postexercise. The exercise protocol induced a decrease in salivary IgA (IgA concentration, IgA output, and IgA relative to total protein). The plasma concentration of glutamine was decreased by 15% 2 h postexercise in the placebo group, whereas this decline was abolished by both glutamine and protein supplements. None of the supplements, however, was able to abolish the decline in salivary IgA. This study does not support that postexercise decrease in salivary IgA is related to plasma glutamine concentrations.
Exercise induces gastric ischemia in healthy volunteers: a tonometry study
Authors: Otte Johannes A. , Oostveen Ellie , Geelkerken Robert H. , Groeneveld A. B. Johan , Kolkman Jeroen J.
Published: December 2017

Heavy physical exercise may cause gastrointestinal signs and symptoms, and, although splanchnic blood flow may decrease through redistribution by more than 50%, it is unclear whether these signs and symptoms relate to gastrointestinal ischemia. In 10 healthy volunteers, we studied the effect of exercise on gastric mucosal perfusion adequacy using air tonometry. Two relatively short (10 min) exercise stages were conducted on a cycle ergometer, aiming for 80 and 100% of maximum heart rate, respectively. The intragastric-arterial Pco 2 gradient (ΔPco 2) was elevated by 1.1 ± 1.0 kPa over baseline values (−0.1 ± 0.3 kPa) only after maximal exercise ( P < 0.001). ΔPco 2positively correlated with the arterial lactate level taken as an index of exercise intensity (Spearman's rank test: r = 0.76, P < 0.0001). By bilinear regression analysis, a lactate level of 12 mmol/l, above which a sharp rise in the ΔPco 2 occurred, was calculated. We conclude that, in healthy volunteers with normal splanchnic vasculature, gastric ischemia may develop during maximal exercise as judged from intragastric Pco 2 tonometry.
Invited Review: Cross-bridge regulation by thin filament-associated proteins
Authors: Morgan Kathleen G. , Gangopadhyay Samudra S.
Published: December 2017

This minireview will cover current concepts on the identity and mechanistic function of smooth muscle actin binding proteins that may regulate actin-myosin interactions. The potential roles of tropomyosin, caldesmon, calponin, and SM22 will be discussed. The review, for purposes of brevity, will be nonexhaustive but will give an overview of available information on the in vitro biochemistry and potential in vivo function of these proteins. Preterm labor is discussed as a possible example of where thin filament regulation may be relevant. Considerable controversy surrounds the putative physiological significance of these proteins, and emphasis will be placed on the need for more experimental work to determine the degree to which tissue- and species-specific effects have clouded the interpretation of functional data.
Invited Review: Arteriolar smooth muscle mechanotransduction: Ca2+signaling pathways underlying myogenic reactivity
Authors: Hill Michael A. , Zou Hui , Potocnik Simon J. , Meininger Gerald A. , Davis Michael J.
Published: December 2017

The smooth muscle of arterioles responds to an increase in intraluminal pressure with vasoconstriction and with vasodilation when pressure is decreased. Such myogenic vasoconstriction provides a level of basal tone that enables arterioles to appropriately adjust diameter in response to neurohumoral stimuli. Key in this process of mechanotransduction is the role of changes in intracellular Ca2+. However, it is becoming clear that considerable complexity exists in the spatiotemporal characteristics of the Ca2+signal and that changes in intracellular Ca2+may play roles other than direct effects on the contractile process via activation of myosin light-chain phosphorylation. The involvement of Ca2+may extend to modulation of ion channels and release of Ca2+from the sarcoplasmic reticulum, alterations in Ca2+sensitivity, and coupling between cells within the vessel wall. The purpose of this brief review is to summarize the current literature relating to Ca2+and the arteriolar myogenic response. Consideration is given to coupling of Ca2+changes to the mechanical stimuli, sources of Ca2+, involvement of ion channels, and spatiotemporal aspects of intracellular Ca2+signaling.
Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle
Authors: Winder W. W.
Published: December 2017

AMP-activated protein kinase (AMPK) is emerging as an important energy-sensing/signaling system in skeletal muscle. This kinase is activated allosterically by 5′-AMP and inhibited allosterically by creatine phosphate. Phosphorylation of AMPK by an upstream kinase, AMPK kinase (also activated allosterically by 5′-AMP), results in activation. It is activated in both rat and human muscle in response to muscle contraction, the extent of activation depending on work rate and muscle glycogen concentration. AMPK can also be activated chemically in resting muscle with 5-aminoimidazole-4-carboxamide-riboside, which enters the muscle and is phosphorylated to form ZMP, a nucleotide that mimics the effect of 5′-AMP. Once activated, AMPK is hypothesized to phosphorylate proteins involved in triggering fatty acid oxidation and glucose uptake. Evidence is also accumulating for a role of AMPK in inducing some of the adaptations to endurance training, including the increase in muscle GLUT-4, hexokinase, uncoupling protein 3, and some of the mitochondrial oxidative enzymes. It thus appears that AMPK has the capability of monitoring intramuscular energy charge and then acutely stimulating fat oxidation and glucose uptake to counteract the increased rates of ATP utilization during muscle contraction. In addition, this system may have the capability of enhancing capacity for ATP production when the muscle is exposed to endurance training.
Maximal aerobic capacity across age in healthy Hispanic and Caucasian women
Authors: Schiller Brian C. , Casas Yoli G. , Desouza Christopher A. , Seals Douglas R.
Published: December 2017

We tested the hypothesis that the age-related decline in maximal aerobic capacity, as measured by maximal oxygen uptake (V˙o 2 max), is greater in Hispanic than in Caucasian women. We studied 146 healthy sedentary women aged 20–75 yr: 53 Hispanic (primarily of Mexican descent) and 93 Caucasian (non-Hispanic white). The groups did not differ in mean age, body mass, percent body fat, estimated physical activity-related energy expenditure, or education-based socioeconomic status (SES). During maximal exercise, respiratory exchange ratio, rating of perceived exertion, and percent predicted maximal heart rate were similar across age and ethnicity, suggesting equivalent maximum voluntary efforts in all subjects. V˙o 2 max(ml · kg−1 · min−1) was inversely related to age ( P < 0.01) in Caucasian ( r =−0.68) and Hispanic ( r = −0.61) women. The absolute rate of decline in V˙o 2 maxwith age was the same in the two groups (−0.31 ml · kg−1 · min−1 · yr−1). The relative rate of decline (% from age 25 yr) also was similar in the Caucasian (−9.0%) and Hispanic (−9.2%) women. When subjects of all ages were pooled, mean levels ofV˙o 2 max were similar in the two groups (∼28 ml · kg−1 · min−1). These results, the first to our knowledge in Hispanics, indicate that mean levels of V˙o 2 max, as well as the rate of decline in V˙o 2 max with age, are similar in healthy sedentary Hispanic and Caucasian women of similar SES. Thus it does not appear that Hispanic ethnicity per se modulates maximal aerobic capacity in this population.
Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius
Authors: Woodman Christopher R. , Schrage William G. , Rush James W. E. , Ray Chester A. , Price Elmer M. , Hasser Eileen M. , Laughlin M. Harold
Published: December 2017

We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 15) or control ( n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.
Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation
Authors: Puig-De-Morales Marina , Grabulosa Mireia , Alcaraz Jordi , Mullol Joaquim , Maksym Geoffrey N. , Fredberg Jeffrey J. , Navajas Daniel
Published: December 2017

Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Science260: 1124–1127, 1993) is a useful technique for probing cell micromechanics. The technique is based on twisting ligand-coated magnetic microbeads bound to membrane receptors and measuring the resulting bead rotation with a magnetometer. Owing to the low signal-to-noise ratio, however, the magnetic signal must be modulated, which is accomplished by spinning the sample at ∼10 Hz. Present demodulation approaches limit the MTC range to frequencies <0.5 Hz. We propose a novel demodulation algorithm to expand the frequency range of MTC measurements to higher frequencies. The algorithm is based on coherent demodulation in the frequency domain, and its frequency range is limited only by the dynamic response of the magnetometer. Using the new algorithm, we measured the complex modulus of elasticity (G*) of cultured human bronchial epithelial cells (BEAS-2B) from 0.03 to 16 Hz. Cells were cultured in supplemented RPMI medium, and ferromagnetic beads (∼5 μm) coated with an RGD peptide were bound to the cell membrane. Both the storage (G′, real part of G*) and loss (G", imaginary part of G*) moduli increased with frequency as ωα (2π × frequency) with α ≈ ¼. The ratio G"/G′ was ∼0.5 and varied little with frequency. Thus the cells exhibited a predominantly elastic behavior with a weak power law of frequency and a nearly constant proportion of elastic vs. frictional stresses, implying that the mechanical behavior conformed to the so-called structural damping (or constant-phase) law (Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ, LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619–1632, 2000). We conclude that frequency domain demodulation dramatically increases the frequency range that can be probed with MTC and reveals that the mechanics of these cells conforms to constant-phase behavior over a range of frequencies approaching three decades.
LH secretion and testosterone concentrations are blunted after resistance exercise in men
Authors: Nindl Bradley C. , Kraemer William J. , Deaver Daniel R. , Peters Jana L. , Marx James O. , Heckman Jeffrey T. , Loomis Gregory A.
Published: December 2017

This study examined the hypothesis that exercise-induced changes in circulating testosterone would be centrally mediated via hypothalamic-pituitary release of luteinizing hormone (LH). We tested this hypothesis by examining overnight LH, total and free testosterone (TT and FT), and cortisol (C) concentrations in 10 young healthy men (21 ± 1 yr) during two experimental sessions: a control and an acute heavy-resistance exercise bout (50 total sets consisting of squats, bench press, leg press, and latissimus dorsi pull-down). Exercise was performed from 1500 to 1700, and blood sampling began at 1700 and continued until 0600 the next morning. Blood was sampled every 10 min for LH and every hour for TT, FT, and C. Hormonal concentrations were determined via RIA, and the secretion characteristics of LH were analyzed with deconvolution analysis. When overnight postexercise concentrations were compared with control concentrations, no statistically significant ( P ≤ 0.05) differences were observed for LH half-life, LH pulse frequency, interpulse interval, pulse amplitude, or pulse mass. Significant differences were observed for LH production rate (13.6 ± 4 and 17.9 ± 5 IU · l distribution volume−1 · day−1 for exercise and control, respectively, a 24% reduction). For the ANOVA marginal main effect means due to condition, C was significantly elevated (5.9 ± 0.7 vs. 4.0 ± 0.4 μg/dl), while TT (464 ± 23 vs. 529 ± 32 ng/dl) and FT (15.6 ± 0.7 vs. 18.3 ± 0.9 pg/ml) were significantly decreased for the exercise condition. These data demonstrate that the decline in overnight testosterone concentrations after acute heavy-resistance exercise is accompanied by a blunted LH production rate and elevated C concentrations.
Effect of race and resistance training status on the density of fat-free mass and percent fat estimates
Authors: Millard-Stafford Melinda L. , Collins Mitchell A. , Modlesky Christopher M. , Snow Teresa K. , Rosskopf Linda B.
Published: December 2017

The impact of race and resistance training status on the assumed density of the fat-free mass (DFFM) and estimates of body fatness via hydrodensitometry (%FatD) vs. a four-component model (density, water, mineral; %FatD,W,M) were determined in 45 men: white controls (W; n = 15), black controls (B; n = 15), and resistance-trained blacks (B-RT; n = 15). Body density by hydrostatic weighing, body water by deuterium dilution, and bone mineral by dual-energy X-ray absorptiometry were used to estimate %FatD,W,M. DFFM was not different between B and W (or 1.1 g/ml); however, DFFM in B-RT was significantly lower (1.091 ± 0.012 g/ml; P < 0.05). Therefore, %FatD using the Siri equation was not different from %FatD,W,M in W (17.5 ± 5.0 vs. 18.3 ± 5.4%) or B (14.9 ± 5.6 vs. 15.7 ± 5.7%) but significantly overestimated %FatD,W,M in B-RT (14.0 ± 5.9 vs. 10.4 ± 6.0%; P < 0.05). The use of a race-specific equation (assuming DFFM = 1.113 g/ml) did not improve the agreement between %FatD and %FatD,W,M, resulting in a significantly greater mean (±SD) discrepancy for B (1.7 ± 1.8% fat) and B-RT (6.2 ± 4.3% fat). Thus race per se does not affect DFFM or estimates of %FatD; however, B-RT have a DFFMlower than 1.1 g/ml, leading to an overestimation of %FatD.
Muscle activity in the leg is tuned in response to ground reaction forces
Authors: Wakeling James M. , Von Tscharner Vinzenz , Nigg Benno M. , Stergiou Pro
Published: December 2017

During walking and running, the human body reacts to its external environment. One such response is to the impact forces that occur at heel strike. This study tested previous speculation that the levels of muscle activity in the lower extremities are adjusted in response to the loading rate of the impact forces. A pendulum apparatus was used to deliver repetitive impacts to the heels of 20 subjects. Impact forces were of similar magnitude to those experienced during running, but the loading rate was varied by 13% using different materials in the subjects' shoes. Myoelectric patterns were measured in the tibialis anterior, medial gastrocnemius, vastus medialis, and biceps femoris muscles. Wavelet analysis was used to resolve intensity of the myoelectric patterns into time and frequency space. Substantial and significant differences in the myoelectric activity occurred between the impact conditions for the 50 ms before and the 50 ms after impact, reaching 3 ms in timing, 16% in wavelet number, and 154% in the intensity of the muscle activity.
Angiotensin-converting enzyme genotype and physical performance during US Army basic training
Authors: Sonna Larry A. , Sharp Marilyn A. , Knapik Joseph J. , Cullivan Michael , Angel Karen C. , Patton John F. , Lilly Craig M.
Published: December 2017

Prior studies have suggested that angiotensin I-converting enzyme (ACE) genotype correlates with superior physical performance in highly selected populations. This study assessed whether such an association exists in a heterogeneous population. Using polymerase chain reaction techniques, we determined the ACE genotypes (insertion/insertion, deletion/insertion, or deletion/deletion) of 62 male and 85 female US Army recruits. Before and after 8 wk of basic training, we determined peak oxygen uptake and performance on the Army Physical Fitness Test (APFT), which includes standardized measures of muscular endurance (sit-ups, push-ups) and a 2-mile run. Subjects of different ACE genotypes had similar peak oxygen uptakes and APFT scores, both before and after training. Subjects with genotype II had higher APFT scores than others, but the differences were not statistically significant. Furthermore, no ACE genotype group had a performance advantage in analyses that adjusted for baseline fitness. We conclude that ACE genotype does not have a strong effect on aerobic power or muscular endurance in healthy, young American adults drawn from an ethnically and geographically diverse population.
Cytoskeletal regulation of pulmonary vascular permeability
Authors: Dudek Steven M. , Garcia Joe G. N.
Published: December 2017

The endothelial cell (EC) lining of the pulmonary vasculature forms a semipermeable barrier between the blood and the interstitium of the lung. Disruption of this barrier occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome and results in the movement of fluid and macromolecules into the interstitium and pulmonary air spaces. These processes significantly contribute to the high morbidity and mortality of patients afflicted with acute lung injury. The critical importance of pulmonary vascular barrier function is shown by the balance between competing EC contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which regulate cell shape. Both competing forces in this model are intimately linked through the endothelial cytoskeleton, a complex network of actin microfilaments, microtubules, and intermediate filaments, which combine to regulate shape change and transduce signals within and between EC. A key EC contractile event in several models of agonist-induced barrier dysfunction is the phosphorylation of regulatory myosin light chains catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase and/or through the activity of the Rho/Rho kinase pathway. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes (adherens junctions and tight junctions), which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell. Focal adhesions provide additional adhesive forces in barrier regulation by forming a critical bridge for bidirectional signal transduction between the actin cytoskeleton and the cell-matrix interface. Increasingly, the effects of mechanical forces such as shear stress and ventilator-induced stretch on EC barrier function are being recognized. The critical role of the endothelial cytoskeleton in integrating these multiple aspects of pulmonary vascular permeability provides a fertile area for the development of clinically important barrier-modulating therapies.
Dehydration and body fluid-regulating hormones during sweating in warm (38°C) fresh- and seawater immersion
Authors: Hope Arvid , Aanderud Leif , Aakvaag Asbjørn
Published: December 2017

Body weight (BW) reductions of more than 4 kg have been observed during diving with the open hot water suit, a technique in which heated seawater (SW) continuously floods the skin surface. To test the hypothesis that osmotic effects may be involved in these fluid-loss processes, head-out immersion experiments in 38°C freshwater (FW) and SW for 4 h were performed. Average BW reduction was 2.5 and 1.9 kg in SW and FW head-out immersion, respectively ( P < 0.01). Atrial natriuretic peptide increased during the first 30 min of SW immersion (5.6–13.4 pmol/l, P < 0.01) followed by a reduction to 7.6 pmol/l ( P < 0.01). This paralleled an initial decrease in aldosterone (from 427 to 306 pmol/l, P < 0.05) followed by an increase to 843 pmol/l ( P < 0.01). The effects of temperature on fluid loss were studied in thermoneutral (34.5°C) and 38°C SW for 2 h. In thermoneutral SW, calculated sweat production was negligible (0.05 kg) compared with 1.2 kg in warm SW. We recommend that, if a dive is planned to last for more than 4 h, a mandatory break for fluid intake should be incorporated in the diving regulations.
Glycogen and glycogen phosphorylase associated with sarcoplasmic reticulum: effects of fatiguing activity
Authors: Lees Simon J. , Franks Peter D. , Spangenburg Espen E. , Williams Jay H.
Published: December 2017

The purpose of the present study was to investigate the effects of fatiguing muscular activity on glycogen, glycogen phosphorylase (GP), and Ca2+uptake associated with the sarcoplasmic reticulum (SR). Tetanic contractions (100 ms, 75 Hz) of the gastrocnemius and plantaris muscles, elicited once per second for 15 min, significantly reduced force to 26.5 ± 4.0% and whole muscle glycogen to 23% of rested levels. SR glycogen levels were 415.4 ± 76.6 and 20.4 ± 2.1 μg/mg SR protein in rested and fatigued samples, respectively. The optical density of GP from SDS-PAGE was reduced to 21% of control, whereas pyridoxal 5′-phosphate concentration, a quantitative indicator of GP content, was significantly reduced to 3% of control. GP activity after exercise, in the direction of glycogen breakdown, was reduced to 4% of control. Maximum SR Ca2+uptake rate was also significantly reduced to 81% of control. These data demonstrate that glycogen and GP associated with skeletal muscle SR are reduced after fatiguing activity.
Determination of regional ventilation and perfusion in the lung using xenon and computed tomography
Authors: Kreck Thomas C. , Krueger Melissa A. , Altemeier William A. , Sinclair Scott E. , Robertson H. Thomas , Shade Erin D. , Hildebrandt Jacob , Lamm Wayne J. E. , Frazer David A. , Polissar Nayak L. , Hlastala Michael P.
Published: December 2017

We propose a model to measure both regional ventilation (V˙) and perfusion (Q˙) in which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a function of regional V˙ (increasing RD) and Q˙(decreasing RD). We studied five anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick computed tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional V˙ and Q˙. For 16 mm3, Q˙ displayed more variance than V˙: the coefficient of variance of Q˙ (CVQ˙) = 1.58 ± 0.23, the CV of V˙ (CVV˙) = 0.46 ± 0.07, and the ratio of CVQ˙ to CVV˙ = 3.5 ± 1.1. CVQ˙(1.21 ± 0.37) and the ratio of CVQ˙ to CVV˙ (2.4 ± 1.2) were smaller at 1,000-mm3 scale, but CVV˙ (0.53 ± 0.09) was not. V˙/Q˙ distributions also displayed scale dependence: log SD of V˙ and log SD of Q˙ were 0.79 ± 0.05 and 0.85 ± 0.10 for 16-mm3 and 0.69 ± 0.20 and 0.67 ± 0.10 for 1,000-mm3 regions of lung, respectively. V˙ and Q˙ measurements made with CT and Xe also demonstrate vertically oriented and isogravitational heterogeneity, which are described using other methodologies. Sequential images acquired by CT during Xe breathing can be used to determine both regional V˙ and Q˙ noninvasively with high spatial resolution.
Random walks, random sequences, and nonlinear dynamics in human optokinetic nystagmus
Authors: Trillenberg P. , Gross C. , Shelhamer M.
Published: December 2017

Optokinetic nystagmus (OKN) is a reflexive eye movement with target-following slow phases (SP) alternating with oppositely directed fast phases (FP). We measured the following from OKN in three humans: FP beginning and ending positions, amplitudes, and intervals and SP amplitudes and velocities. We sought to predict future values of each parameter on the basis of past values, using state-space representation of the sequence (time-delay embedding) and local second-order approximation of trajectories. Predictability is an indication of determinism: this approach allows us to investigate the relative contributions of random and deterministic dynamics in OKN. FP beginning and ending positions showed good predictability, but SP velocity was less predictable. FP and SP amplitudes and FP intervals had little or no predictability. FP beginnings and endings were as predictable as randomized versions that retain linear autocorrelation; this is typical of random walks. Predictability of FP intervals did not change under random rearrangement, which is characteristic of a random process. Only linear determinism was demonstrated; nonlinear interactions may exist that would not be detected by our present approach.
Women at altitude: ventilatory acclimatization at 4,300 m
Authors: Muza Stephen R. , Rock Paul B. , Fulco Charles S. , Zamudio Stacy , Braun Barry , Cymerman Allen , Butterfield Gail E. , Moore Lorna G.
Published: December 2017

Women living at low altitudes or acclimatized to high altitudes have greater effective ventilation in the luteal (L) compared with follicular (F) menstrual cycle phase and compared with men. We hypothesized that ventilatory acclimatization to high altitude would occur more quickly and to a greater degree in 1) women in their L compared with women in their F menstrual cycle phase, and 2) in women compared with men. Studies were conducted on 22 eumenorrheic, unacclimatized, sea-level (SL) residents. Indexes of ventilatory acclimatization [resting ventilatory parameters, hypoxic ventilatory response, hypercapnic ventilatory response (HCVR)] were measured in 14 women in the F phase and in 8 other women in the L phase of their menstrual cycle, both at SL and again during a 12-day residence at 4,300 m. At SL only, ventilatory studies were also completed in both menstrual cycle phases in 12 subjects (i.e., within-subject comparison). In these subjects, SL alveolar ventilation (expressed as end-tidal Pco 2) was greater in the L vs. F phase. Yet the comparison between L- and F-phase groups found similar levels of resting end-tidal Pco 2, hypoxic ventilatory response parameter A, HCVR slope, and HCVR parameter B, both at SL and 4,300 m. Moreover, these indexes of ventilatory acclimatization were not significantly different from those previously measured in men. Thus female lowlanders rapidly ascending to 4,300 m in either the L or F menstrual cycle phase have similar levels of alveolar ventilation and a time course for ventilatory acclimatization that is nearly identical to that reported in male lowlanders.
Local perfusion and metabolic demand during exercise: a noninvasive MRI method of assessment
Authors: Richardson Russell S. , Haseler Luke J. , Nygren Anders T. , Bluml Stefan , Frank Lawrence R.
Published: December 2017

A noninvasive magnetic resonance imaging (MRI) method to assess the distribution of perfusion and metabolic demand (Q˙/V˙o 2) in exercising human skeletal muscle is described. This method combines two MRI techniques that can provide accurate multiple localized measurements of Q˙/V˙o 2 during steady-state plantar flexion exercise. The first technique,31P chemical shift imaging, permits the acquisition of comparable phosphorus spectra from multiple voxels simultaneously. Because phosphocreatine (PCr) depletion is directly proportional to ATP hydrolysis, its relative depletion can be used as an index of muscle O2 uptake (V˙o 2). The second MRI technique allows the measurement of both spatially and temporally resolved muscle perfusion in vivo by using arterial spin labeling. Promising validity and reliability data are presented for both MRI techniques. Initial results from the combined method provide evidence of a large variation in Q˙/V˙o 2, revealing areas of apparent under- and overperfusion for a given metabolic turnover. Analysis of these data in a similar fashion to that employed in the assessment of ventilation-to-perfusion matching in the lungs revealed a similar second moment of the perfusion distribution and PCr distribution on a log scale (log SDQ˙ and log SDPCr) (0.47). Modeling the effect of variations in log SDQ˙ and log SDPCr in terms of attainable V˙o 2, assuming no diffusion limits, indicates that the log SDQ˙ and log SDPCr would allow only 92% of the targetV˙o 2 to be achieved. This communication documents this novel, noninvasive method for assessingQ˙/V˙o 2, and initial data suggest that the mismatch in Q˙/V˙o 2 may play a significant role in determining O2 transport and utilization during exercise.
Protective effects of estrogen on gender-specific development of diet-induced hypertension
Authors: Roberts Christian K. , Vaziri Nosratola D. , Barnard R. James
Published: December 2017

Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.
Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes
Authors: Heunks Leo M. A. , Machiels Herwin A. , Dekhuijzen P. N. Richard , Prakash Y. S. , Sieck Gary C.
Published: December 2017

In the present study, we used real-time confocal microscopy to examine the effects of two nitric oxide (NO) donors on acetylcholine (ACh; 10 μM)- and caffeine (10 mM)-induced intracellular calcium concentration ([Ca2+]i) responses in C2C12mouse skeletal myotubes. We hypothesized that NO reduces [Ca2+]iin activated skeletal myotubes through oxidation of thiols associated with the sarcoplasmic reticulum Ca2+-release channel. Exposure to diethylamine NONOate (DEA-NO) reversibly increased resting [Ca2+]ilevel and resulted in a dose-dependent reduction in the amplitude of ACh-induced [Ca2+]iresponses (25 ± 7% reduction with 10 μM DEA-NO and 78 ± 14% reduction with 100 μM DEA-NO). These effects of DEA-NO were partly reversible after subsequent exposure to dithiothreitol (10 mM). Preexposure to DEA-NO (1, 10, and 50 μM) also reduced the amplitude of the caffeine-induced [Ca2+]iresponse. Similar data were obtained by using the chemically distinct NO donor S-nitroso- N-acetyl-penicillamine (100 μM). These results indicate that NO reduces sarcoplasmic reticulum Ca2+release in skeletal myotubes, probably by a modification of hyperreactive thiols present on the ryanodine receptor channel.
Interleukin-6 response to exercise and high-altitude exposure: influence of α-adrenergic blockade
Authors: Mazzeo Robert S. , Donovan Danielle , Fleshner Monika , Butterfield Gail E. , Zamudio Stacy , Wolfel Eugene E. , Moore Lorna G.
Published: December 2017

Interleukin-6 (IL-6), an important cytokine involved in a number of biological processes, is consistently elevated during periods of stress. The mechanisms responsible for the induction of IL-6 under these conditions remain uncertain. This study examined the effect of α-adrenergic blockade on the IL-6 response to acute and chronic high-altitude exposure in women both at rest and during exercise. Sixteen healthy, eumenorrheic women (aged 23.2 ± 1.4 yr) participated in the study. Subjects received either α-adrenergic blockade (prazosin, 3 mg/day) or a placebo in a double-blinded, randomized fashion. Subjects participated in submaximal exercise tests at sea level and on days 1 and 12 at altitude (4,300 m). Resting plasma and 24-h urine samples were collected throughout the duration of the study. At sea level, no differences were found at rest for plasma IL-6 between groups (1.5 ± 0.2 and 1.2 ± 0.3 pg/ml for placebo and blocked groups, respectively). On acute ascent to altitude, IL-6 levels increased significantly in both groups compared with sea-level values (57 and 84% for placebo and blocked groups, respectively). After 12 days of acclimatization, IL-6 levels remained elevated for placebo subjects; however, they returned to sea-level values in the blocked group. α-Adrenergic blockade significantly lowered the IL-6 response to exercise both at sea level (46%) and at altitude (42%) compared with placebo. A significant correlation ( P = 0.004) between resting IL-6 and urinary norepinephrine excretion rates was found over the course of time while at altitude. In conclusion, the results indicate a role for α-adrenergic regulation of the IL-6 response to the stress of both short-term moderate-intensity exercise and hypoxia.
Estimating the size of the capillary-to-fiber interface in skeletal muscle: a comparison of methods
Authors: Hepple Russell T. , Mathieu-Costello Odile
Published: December 2017

Current evidence suggests that the size of the capillary-to-fiber (C/F) interface is a major determinant of O2 flux into muscle fibers, and methods have been developed for estimating the size of this region via the C/F perimeter ratio in perfusion-fixed material (Mathieu-Costello O, Ellis CG, Potter RF, MacDonald IC, and Groom AC. Am J Physiol Heart Circ Physiol 261: H1617–H1625, 1991) and the quotient of the individual, fiber-based C/F number ratio and fiber perimeter (C/F perimeter exchange index) in muscle biopsies (Hepple RT. Can J Appl Physiol 22: 11–22, 1997). The purpose of this study was to compare the two methods and examine how differences in muscle tissue preparation between perfusion fixation and frozen biopsy can influence the estimate of the size of the C/F interface. The left medial gastrocnemius muscle of nine purpose-bred dogs was perfusion fixed in situ, and a sample from the midportion of the midbelly was processed for microscopy. A corresponding sample from the right gastrocnemius muscle obtained by open biopsy in six of the nine animals was frozen for histochemistry. A significant correlation was found between the two estimates of the size of the C/F interface in the same sections of perfusion-fixed material ( r = 0.75, P < 0.05). However, estimates of the size of the C/F interface were smaller in biopsies than perfusion-fixed material, and there was no significant relationship between the estimates in the two preparations. This was due to differences in fiber size (33% larger fiber cross-sectional area in biopsy material after normalization for sarcomere length; P < 0.05) and muscle sampling between the two tissue preparations.