bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined in situ analysis of metabolic and myoelectrical changes associated with electrically induced fatigue
Authors: Darques J. L. , Bendahan D , Roussel M , Giannesini B , Tagliarini F , Le Fur Y , Cozzone P. J. , Jammes Y
Published: March 2015

Electrical muscle stimulation (Mstim) at a low or high frequency is associated with failure of force production, but the exact mechanisms leading to fatigue in this model are still poorly understood. Using31P magnetic resonance spectroscopy (31PMRS), we investigated the metabolic changes in rabbit tibialis anterior muscle associated with the force decline during Mstim at low (10 Hz) and high (100 Hz) frequency. We also simultaneously recorded the compound muscle mass action potential (M-wave) evoked by direct muscle stimulation, and we analyzed its post-Mstim variations. The 100-Hz Mstim elicited marked M-wave alterations and induced mild metabolic changes at the onset of stimulation followed by a paradoxical recovery of phosphocreatine (PCr) and pH during the stimulation period. On the contrary, the 10-Hz Mstim produced significant PCr consumption and intracellular acidosis with no paradoxical recovery phenomenon and no significant changes in M-wave characteristics. In addition, the force depression was linearly linked to the stimulation-induced acidosis and PCr breakdown. These results led us to conclude that force failure during 100-Hz Mstim only results from an impaired propagation of muscle action potentials with no metabolic involvement. On the contrary, fatigue induced by 10-Hz Mstim is closely associated with metabolic changes with no alteration of the membrane excitability, thereby underlining the central role of muscle energetics in force depression when muscle is stimulated at low frequency. Finally, our results further indicate a reduction of energy cost of contraction when stimulation frequency is increased from 10 to 100 Hz.
Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress
Authors: Yamamoto Kimiko , Takahashi Tomono , Asahara Takayuki , Ohura Norihiko , Sokabe Takaaki , Kamiya Akira , Ando Joji
Published: March 2015

Endothelial progenitor cells (EPCs), circulating in peripheral blood, migrate toward target tissue, differentiate, and contribute to the formation of new vessels. In this study, we report that shear stress generated by blood flow or tissue fluid flow can accelerate the proliferation, differentiation, and capillary-like tube formation of EPCs. When EPCs cultured from human peripheral blood were subjected to laminar shear stress, the cells elongated and oriented their long axes in the direction of flow. The cell density of the EPCs exposed to shear stress was higher, and a larger percentage of these cells were in the G2-M phase of the cell cycle, compared with EPCs cultured under static conditions. Shear stress markedly increased the EPC expression of two vascular endothelial growth factor receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase-1, and an intercellular adhesion molecule, vascular endothelial-cadherin, at both the protein and mRNA levels. Assays for tube formation in the collagen gels showed that the shear-stressed EPCs formed tubelike structures and developed an extensive tubular network significantly faster than the static controls. These findings suggest that EPCs are sensitive to shear stress and that their vasculogenic activities may be modulated by shear stress.
Characterization of cardiac hypertrophy and heart failure due to volume overload in the rat
Authors: Wang Xi , Ren Bin , Liu Songyan , Sentex Emmanuelle , Tappia Paramjit S. , Dhalla Naranjan S.
Published: March 2015

Alterations in general characteristics and morphology of the heart, as well as changes in hemodynamics, myosin heavy chain isoforms, and β-adrenoceptor responsiveness, were determined in Sprague-Dawley rats at 1, 2, 4, 8, and 16 wk after aortocaval fistula (shunt) was induced by the needle technique. Three stages of cardiac hypertrophy due to volume overload were recognized during the 16-wk period. Developing hypertrophy occurred within the first 2 wk after aortocaval shunt was induced and was characterized by a rapid increase of cardiac mass in both left and right ventricles. Compensated hypertrophy occurred between 2 and 8 wk after aortocaval shunt where normal or mild depression in hemodynamic function was observed. Decompensated hypertrophy or heart failure occurred between 8 and 16 wk after aortocaval shunt and was characterized by circulatory congestion, decreased in vivo and in vitro cardiac function, and a shift in myosin heavy chain isozyme expression. However, the positive inotropic effect of isoproterenol was augmented at all times during the 16-wk period. Characterization of β-adrenoceptor binding in failing hearts at 16 wk revealed a significant increase in β1-receptor density, whereas β2-receptor density was unchanged. Consistent with this, basal adenylyl cyclase activity was significantly increased, and both isoproterenol- and forskolin-stimulated adenylyl cyclase activities were also increased. These results indicate that upregulation of β-adrenoceptor signal transduction is a unique feature of cardiac hypertrophy and failure induced by volume overload.
Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles
Authors: Jessen Niels , Pold Rasmus , Buhl Esben S. , Jensen Lasse S. , Schmitz Ole , Lund Sten
Published: March 2015

Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5′-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats were allocated into three groups: an exercise group trained on treadmill for 5 days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a sedentary control group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. Both exercised and AICAR-injected animals displayed a fiber-type-specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.
Interaction between reactive oxygen species and nitric oxide in the microvascular response to systemic hypoxia
Authors: Steiner Dawn R. S. , Gonzalez Norberto C. , Wood John G.
Published: March 2015

Systemic hypoxia results in oxidative stress due to a change in the reactive oxygen species (ROS)-nitric oxide (NO) balance. These experiments explored two mechanisms for the altered ROS-NO balance: 1) decreased NO synthesis by NO synthase due to limited O2 substrate availability and 2) increased superoxide generation. ROS levels and leukocyte adherence in mesenteric venules of rats during hypoxia were studied in the absence and presence of an NO donor [spermine NONOate (SNO)] and of the NO precursorl-arginine. We hypothesized that if the lower NO levels during hypoxia were due to O2 substrate limitation,l-arginine would not prevent hypoxia-induced microvascular responses. Graded hypoxia (produced by breathing 15, 10, and 7.5% O2) increased both ROS (123 ± 6, 148 ± 11, and 167 ± 3% of control) and leukocyte adherence. ROS levels during breathing of 10 and 7.5% O2 were significantly attenuated by SNO (105 ± 6 and 108 ± 3%, respectively) andl-arginine (117 ± 5 and 115 ± 2%, respectively). Both interventions reduced leukocyte adherence by similar degrees. The fact that the effects of l-arginine were similar to those of SNO does not support the idea that NO generation is impaired in hypoxia and suggests that tissue NO levels are depleted by the increased ROS during hypoxia.
Breath-by-breath measurement of the volume displaced by diaphragm motion
Authors: Singh Bhajan , Panizza Janine A. , Finucane Kevin E.
Published: March 2015

To develop an accurate method to measure the volume displaced by diaphragm motion (ΔVdi) breath by breath, we compared ΔVdi measured by a previously evaluated biplanar radiographic method (Singh B, Eastwood PR, and Finucane KE. J Appl Physiol 91: 1913–1923, 2001) at several lung volumes during vital capacity inspirations in 10 healthy and nine hyperinflated subjects with 1) ΔVdi measured from the same chest X-rays by two previously described uniplanar methods (Petroll WM, Knight H, and Rochester DF. J Appl Physiol 69: 2175–2182, 1990; Verschakelen JA, Deschepper K, and Demendts M. J Appl Physiol 72: 1536–1540, 1992) and a proposed method that considered actual cross-sectional shape of the rib cage and spinal volume (ΔVdiS); and 2) ΔVdiS measured by lateral fluoroscopy in the same 10 healthy subjects. Relative to biplanar ΔVdi, ΔVdiS values from lateral chest X-rays and fluoroscopy were not different, whereas ΔVdi values of Petroll et al. and Verschakelen et al. were increased by (means ± SD) 1.98 ± 1.59 and 1.16 ± 0.82 liters, respectively (both P< 0.001). During quiet breathing, ΔVdiS by lateral fluoroscopy was 66 ± 16% of tidal volume and similar to that between functional residual capacity and one-half inspiratory capacity by the biplanar radiographic method. We conclude that accurate breath-by-breath measurements of ΔVdi can be made by using lateral fluoroscopy.
Concentric adaptation of the left ventricle in response to controlled upper body exercise training
Authors: Gates Phillip E. , George Keith P. , Campbell Ian G.
Published: March 2015

Upper body exercise has many applications to the rehabilitation and maintenance of cardiovascular health of individuals who are unable to exercise their lower body. The hemodynamic loads of upper body aerobic exercise are characterized by relatively high blood pressure and relatively low venous return. It is not clear how the left ventricle adapts to the specific hemodynamic loads associated with this form of exercise training. The purpose of this study was to measure left ventricular structure and function in previously sedentary men by using echocardiography before and after 12 wk of aerobic arm-crank exercise training ( n = 22) or a time control period ( n = 22). Arm-crank peak oxygen consumption (in ml · kg−1 · min−1) increased by 16% ( P < 0.05) after training, and significant differences ( P < 0.05) were found in wall thickness (from 0.86 to 0.99 cm) but not in left ventricular internal dimension in diastole or systole. This suggested a concentric pattern of left ventricular hypertrophy that persisted after scaling to changes in anthropometric characteristics. No differences ( P < 0.05) were found for any measurements of resting left ventricular function. We conclude that upper body aerobic exercise training results in a specific left ventricular adaptation that is characterized by increased left ventricular wall thickness but no change in chamber dimension.
Delayed distribution of active vasodilation and altered vascular conductance in aged skin
Authors: Pierzga Jane M. , Frymoyer Adam , Kenney W. Larry
Published: March 2015

Reflex vasodilation is attenuated in aged skin during hyperthermia. We used laser-Doppler imaging (LDI) to test the hypothesis that the magnitude of conductance and the spatial distribution of vasodilation are altered with aging. LDI of forearm skin was compared in 12 young (19- to 29-yr-old) and 12 older (64- to 75-yr-old) men during supine passive heating. Additionally, iontophoresis of bretylium tosylate was performed in a subset of subjects to explore the involvement of sympathetic vasoconstriction in limiting skin blood flow. Passive heating with water-perfused suits clamped mean skin temperature at 41.0 ± 0.5°C, causing a ramp increase in esophageal temperature (Tes) to ≤38.5°C. LDI scans were performed at baseline and at every 0.2°C increase in Tes. LDI at bretylium and control sites was identical, suggesting no influence of noradrenergic vasoconstriction. Forearm vascular conductance (venous occlusion plethysmography) was reduced in the older men ( P ≤ 0.001) at every elevated Tes. Mean cutaneous vascular conductance (CVC) of the scanned area was reduced in the older men at 0.2°C ≤ ΔTes ≤ 0.8°C. Early in heating (0.2°C ≤ ΔTes ≤ 0.6°C), older men also responded with a reduced vasodilated area ( P ≤ 0.05), implying a slower recruitment or filling of skin microvessels. The results indicate that the area of vasodilation and CVC within the vasodilated area are reduced in aged skin during early passive heating, but only CVC is reduced at ΔTes = 0.8°C.
Selected Contribution: Long-term effects of β2-adrenergic receptor stimulation on alveolar fluid clearance in mice
Authors: Sartori C. , Fang X. , McGraw D. W. , Koch P. , Snider M. E. , Folkesson H. G. , Matthay M. A.
Published: March 2015

Stimulation of active fluid transport with β-adrenergic receptor (βAR) agonists can accelerate the resolution of alveolar edema. However, chronic βAR-agonist administration may cause βAR desensitization and downregulation that may impair physiological responsiveness to βAR-agonist stimulation. Therefore, we measured baseline and terbutaline- (10−3M) stimulated alveolar fluid clearance in mice that received subcutaneously (miniosmotic pumps) either saline or albuterol (2 mg · kg−1· day−1) for 1, 3, or 6 days. Continuous albuterol administration increased plasma albuterol levels (10−5M), an effect that was associated with 1) a significant decrease in βAR density and 2) attenuation, but not ablation, of maximal terbutaline-induced cAMP production. Forskolin-mediated cAMP-release was unaffected. Continuous albuterol infusion stimulated alveolar fluid clearance on day 1 but did not increase alveolar fluid clearance on days 3 and 6. However, terbutaline-stimulated alveolar fluid clearance in albuterol-treated mice was not reduced compared with saline-treated mice. Despite significant reductions in βAR density and agonist-mediated cAMP production by long-term βAR-agonist exposure, maximal βAR-agonist-mediated increase in alveolar fluid clearance is not diminished in mice.
Increased wheel-running activity in the genetically skeletal muscle fast-twitch fiber-dominant rats
Authors: Suwa Masataka , Nakano Hiroshi , Higaki Yasuki , Nakamura Tomohiro , Katsuta Shigeru , Kumagai Shuzo
Published: March 2015

The purpose of the present study was to investigate whether genetic differences in muscle histochemical characteristics were related to the voluntary wheel-running activity level by using genetically fast-twitch fiber-dominant rats (FFDR) and control rats (CR). The rats were divided into four groups; sedentary CR (Sed-CR), wheel-running CR (WR-CR), sedentary FFDR (Sed-FFDR), and wheel-running FFDR (WR-FFDR). Wheel access was started at age 9 wk and lasted for 7 days. The FFDR showed a lower percentage of type I fibers of the deep portion of gastrocnemius and soleus muscles and a higher percentage of both type IIX fibers of the gastrocnemius muscle and type IIA fibers of the soleus muscle compared with CR. A higher capillary density and smaller fiber cross-sectional area were also observed in FFDR. The daily running distance in WR-FFDR was higher than in WR-CR for each 7 days. The total running distance for 7 days in WR-FFDR was 3.2-fold higher than in WR-CR. On day 7 of the 7-day test, the total number of active 1-min intervals for 24 h, the average rpm when they were active, and the maximum rpm for any single 1-min period in the WR-FFDR were significantly higher than in the WR-CR (1.5-, 2.9-, and 2.0-fold, respectively). These results suggest that mechanical or physiological muscle characteristics may thus affect the wheel-running activity level.
Gender differences in glucose kinetics and substrate oxidation during exercise near the lactate threshold
Authors: Ruby Brent C. , Coggan Andrew R. , Zderic Ted W.
Published: March 2015

The purpose of this investigation was to determine plasma glucose kinetics and substrate oxidation in men and women during exercise relative to the lactate threshold (LT). Subjects cycled for 25 min at 70 and 90% of O2 uptake (V˙o 2) at LT (70 and 90% LT, respectively). Plasma glucose appearance (Ra) and disappearance (Rd) were determined with a primed constant infusion of [6,6-2H]glucose. There were no significant differences in glucose Ra between men [22.6 ± 1.9 and 39.9 ± 3.9 μmol · kg fat-free mass (FFM)−1 · min−1 for 70 and 90% LT, respectively] and women (22.3 ± 2.7 and 33.9 ± 5.7 μmol · kg FFM−1 · min−1 for 70 and 90% LT, respectively). Similarly, there were no significant differences in glucose Rd between men (21.2 ± 1.9 and 38.1 ± 3.7 μmol · kg FFM−1 · min−1 for 70 and 90% LT, respectively) and women (21.3 ± 2.8 and 33.3 ± 5.6 μmol · kg FFM−1 · min−1 for 70 and 90% LT, respectively). Although there were no differences between genders in the relative contribution of carbohydrate (CHO) to total energy expenditure, the relative contribution of muscle glycogen to total CHO oxidation (75.8 ± 3.2 and 64.2 ± 8.0% for men and women, respectively, at 70% LT and 75.1 ± 2.6 and 60.1 ± 11.2% for men and women, respectively, at 90% LT) was lower in women. Consequently, the relative contribution of blood glucose to total CHO oxidation was significantly higher in women. These results indicate that although plasma glucose Ra and Rdare similar in men and women, the relative contribution of muscle glycogen and blood glucose is significantly different in women during moderate-intensity exercise relative to LT.
Heat acclimation-induced elevated glycogen, glycolysis, and low thyroxine improve heart ischemic tolerance
Authors: Eynan Mirit , Knubuvetz Tanya , Meiri Uri , Navon Gil , Gerstenblith Gary , Bromberg Zohar , Hasin Yonathan , Horowitz Michal
Published: March 2015

Based on our observations of energy sparing in heat-acclimated (AC) rat hearts, we investigated whether changes in preischemic glycogen level, glycolytic rate, and plasma thyroxine level mediate cardioprotection induced in these hearts during ischemia-reperfusion insults. Control (C) (24°C), AC (34°C, 30 days), acclimated-euthyroid (34°C + 3 ng/ml l-thyroxine), and control hypothyroid (24°C + 0.02% 6- n-propyl-2-thiouracil) groups were studied. Preischemic glycogen was higher in AC than in C hearts [39.0 ± 8.5 vs. 19.2 ± 4.2 (SE) μmol glucose/g wet wt; P < 0.0006], and the lactate produced vs. glycogen level during total ischemia (13C-NMR spectroscopy) was markedly slower (AC: −0.82 x, r = 0.98 vs. C: −4.7 x, r = 0.9). Time to onset of ischemic contracture was lengthened, and the fraction of hearts experiencing ischemic contracture was lowered. Pulse pressure recovery was improved in AC compared with C animals before, but not after, absolute sodium iodoacetate-induced glycolysis inhibition. Acclimated-euthyroid hearts exhibited decreased ischemic tolerance, whereas induced hypothyroidism in C improved cardiotolerance. Thus higher preischemic glycogen and slowed glycolysis are associated with hypothyroidism and are likely important mediators of the improved ischemic tolerance exhibited by AC hearts.
Intramyocellular lipid content is increased after exercise in nonexercising human skeletal muscle
Authors: Schrauwen-Hinderling V. B. , van Loon L. J. C. , Koopman R. , Nicolay K. , Saris W. H. M. , Kooi M. E.
Published: March 2015

Intramyocellular lipid (IMCL) content has been reported to decrease after prolonged submaximal exercise in active muscle and, therefore, seems to form an important local substrate source. Because exercise leads to a substantial increase in plasma free fatty acid (FFA) availability with a concomitant increase in FFA uptake by muscle tissue, we aimed to investigate potential differences in the net changes in IMCL content between contracting and noncontracting skeletal muscle after prolonged endurance exercise. IMCL content was quantified by magnetic resonance spectroscopy in eight trained cyclists before and after a 3-h cycling protocol (55% maximal energy output) in the exercising vastus lateralis and the nonexercising biceps brachii muscle. Blood samples were taken before and after exercise to determine plasma FFA, glycerol, and triglyceride concentrations, and substrate oxidation was measured with indirect calorimetry. Prolonged endurance exercise resulted in a 20.4 ± 2.8% ( P < 0.001) decrease in IMCL content in the vastus lateralis muscle. In contrast, we observed a substantial (37.9 ± 9.7%; P < 0.01) increase in IMCL content in the less active biceps brachii muscle. Plasma FFA and glycerol concentrations were substantially increased after exercise (from 85 ± 6 to 1,450 ± 55 and 57 ± 11 to 474 ± 54 μM, respectively; P < 0.001), whereas plasma triglyceride concentrations were decreased (from 1,498 ± 39 to 703 ± 7 μM; P < 0.001). IMCL is an important substrate source during prolonged moderate-intensity exercise and is substantially decreased in the active vastus lateralis muscle. However, prolonged endurance exercise with its concomitant increase in plasma FFA concentration results in a net increase in IMCL content in less active muscle.
Effect of position, nitric oxide, and almitrine on lung perfusion in a porcine model of acute lung injury
Authors: Richard J. C. , Janier M. , Lavenne F. , Berthier V. , Lebars D. , Annat G. , Decailliot F. , Guerin C.
Published: March 2015

In a porcine model of oleic acid-induced lung injury, the effects of inhaled nitric oxide (iNO) and intravenous almitrine bismesylate (ivALM), which enhances the hypoxic pulmonary vasoconstriction on the distribution of regional pulmonary blood flow (PBF), were assessed. After injection of 0.12 ml/kg oleic acid, 20 anesthetized and mechanically ventilated piglets [weight of 25 ± 2.6 (SD) kg] were randomly divided into four groups: supine position, prone position, and 10 ppm iNO for 40 min followed by 4 μg · kg−1 · min−1ivALM for 40 min in supine position and in prone position. PBF was measured with positron emission tomography and H2 15O. The redistribution of PBF was studied on a pixel-by-pixel basis. Positron emission tomography scans were performed before and then 120, 160, and 200 min after injury. With prone position alone, although PBF remained prevalent in the dorsal regions it was significantly redistributed toward the ventral regions ( P < 0.001). A ventral redistribution of PBF was also obtained with iNO regardless of the position ( P = 0.043). Adjunction of ivALM had no further effect on PBF redistribution. PP and iNO have an additive effect on ventral redistribution of PBF.
Lung volume effects on pharyngeal swallowing physiology
Authors: Gross Roxann Diez , Atwood Charles W. , Grayhack Judith P. , Shaiman Susan
Published: March 2015

The experiment was a prospective, repeated-measures design intended to determine how the variation of lung volume affects specific measures of swallowing physiology. Swallows were recorded in 28 healthy subjects, who ranged in age from 21 to 40 yr (mean age of 29 yr), by using simultaneous videofluoroscopy, bipolar intramuscular electromyography, and respiratory inductance plethysmography. Each subject swallowed three standardized pudding-like consistency boluses at three randomized lung volumes: total lung capacity, functional residual capacity, and residual volume. The results showed that pharyngeal activity duration of deglutition for swallows produced at residual volume was significantly longer than those occurring at total lung capacity or at functional residual capacity. No significant differences were found for bolus transit time or intramuscular electromyography of the superior constrictor. The results of this experiment lend support to the hypothesis that the respiratory system may have a regulatory function related to swallowing and that positive subglottic air pressure may be important for swallowing integrity. Eventually, new treatment paradigms for oropharyngeal dysphagia that are based on respiratory physiology may be developed.
Invited Review: Dynamic exercise performance in Masters athletes: insight into the effects of primary human aging on physiological functional capacity
Authors: Tanaka Hirofumi , Seals Douglas R.
Published: March 2015

Physiological functional capacity (PFC) is defined here as the ability to perform the physical tasks of daily life and the ease with which these tasks can be performed. For the past decade, we have sought to determine the effect of primary (healthy) adult human aging on PFC and the potential modulatory influences of gender and habitual aerobic exercise status on this process by studying young adult and Masters athletes. An initial approach to determining the effects of aging on PFC involved investigating changes in peak exercise performance with age in highly trained and competitive athletes. PFC, as assessed by running and swimming performance, decreased only modestly until age 60-70 yr but declined exponentially thereafter. A progressive reduction in maximal O2 consumption (V̇o2 max) appears to be the primary physiological mechanism associated with declines in endurance running performance with advancing age, along with a reduction in the exercise velocity at lactate threshold. Because V̇o2 max is important in mediating age-related reductions in exercise performance and PFC, we then investigated the modulatory influence of habitual aerobic exercise status on the rate of decline in V̇o2 max with age. Surprisingly, as a group, endurance-trained adults appear to undergo greater absolute rates of decline in V̇o2 max with advancing age compared with healthy sedentary adults. This appears to be mediated by a baseline effect (higher V̇o2 max as young adults) and/or a marked age-related decline in exercise training volume and intensity (stimulus) in endurance-trained adults. Thus the ability to maintain habitual physical activity levels with advancing age appears to be a critical determinant of changes in PFC in part via modulation of maximal aerobic capacity.
Handgrip-induced airway dilation in asthmatic patients with bronchoconstriction induced by MCh inhalation
Authors: Fontana Giovanni A. , Pantaleo Tito , Lavorini Federico , Bongianni Fulvia , Mannelli Massimo , Bridge Peter D. , Pistolesi Massimo
Published: March 2015

We investigated the effects of static and rhythmic handgrip on the time course of recovery of airway resistance measured with the interrupter technique (Rint) following bronchoconstriction induced by methacholine (MCh) inhalation in 17 asthmatic patients. On three separate occasions, a 100 ± 5% increase in baseline Rint was induced by MCh inhalation. Subsequently, patients either rested [control trials (CTs)] or performed 3-min bouts of static or rhythmic handgrip. Respiratory and cardiovascular variables were continuously monitored. Rint changes were assessed at 1-min intervals for 30 min after rest and both types of handgrip. Plasma catecholamine concentrations were also determined at scheduled intervals. Bronchoconstriction increased ventilation ( P < 0.01) but did not affect cardiovascular variables and plasma catecholamine concentrations. Handgrip provoked an increase in cardiovascular variables ( P < 0.01) and plasma norepinephrine concentrations ( P < 0.05) but caused no additional changes in ventilation. Rint only partially recovered within 30 min after CTs, whereas it consistently decreased 1 min after both handgrip paradigms and remained lower than after CTs ( Palways <0.01) for the whole 30-min observation period. Sympathetic activation and withdrawal of cholinergic input to the airway smooth muscle reflexly induced by activation of skeletal muscle and carotid sinus receptors may be the primary events accounting for the bronchodilator response induced by handgrip. Mediators co-released in response to sympathetic activation may also have contributed.
Geniohyoid muscle function in awake canines
Authors: Yokoba M. , Hawes H. G. , Easton P. A.
Published: March 2015

The geniohyoid (Genio) upper airway muscle shows phasic, inspiratory electrical activity in awake humans but no activity and lengthening in anesthetized cats. There is no information about the mechanical action of the Genio, including length and shortening, in any awake, nonanesthetized mammal during respiration (or swallowing). Therefore, we studied four canines, mean weight 28.8 kg, 1.5 days after Genio implantation with sonomicrometry transducers and bipolar electromyogram (EMG) electrodes. Awake recordings of breathing pattern, muscle length and shortening, and EMG activity were made with the animal in the right lateral decubitus position during quiet resting, CO2-stimulated breathing, inspiratory-resisted breathing (80 cmH2O · l-1· s), and airway occlusion. Genio length and activity were also measured during swallowing, when it shortened, showing a 9.31% change from resting length, and its EMG activity increased 6.44 V. During resting breathing, there was no phasic Genio EMG activity at all, and Genio showed virtually no movement during inspiration. During CO2-stimulated breathing, Genio showed minimal lengthening of only 0.07% change from resting length, whereas phasic EMG activity was still absent. During inspiratory-resisted breathing and airway occlusion, Genio showed phasic EMG activity but still lengthened. We conclude that the Genio in awake, nonanesthetized canines shows active contraction and EMG activity only during swallowing. During quiet or stimulated breathing, Genio is electrically inactive with passive lengthening. Even against resistance, Genio is electrically active but still lengthens during inspiration.
Shear stress levels in paralyzed legs of spinal cord-injured individuals with and without nerve degeneration
Authors: Boot Cécile R. L. , Groothuis Jan. T. , van Langen Herman , Hopman Maria T. E.
Published: March 2015

The purpose of this study was to assess the relationship between inactivity and shear stress, the frictional force of blood against the endothelium, in spinal cord injury (SCI) subjects. SCI group offers a unique “model of nature” to study the effects of inactivity. Nine SCI subjects with upper (SCI-U) and 5 with a lower (SCI-L) motoneuron lesion and 10 able-bodied controls (C) were included. A venous blood sample was withdrawn to determine blood viscosity. Red blood cell velocities and arterial diameters of the common carotid artery (CCA) and common femoral artery (CFA) were measured by using echo-Doppler ultrasound in a supine position. No differences were observed in wall shear stress in the CCA between groups. In the CFA, peak and mean wall shear stress were significantly increased in SCI (14.1 and 1.2 Pa, respectively) compared with C (10.2 and 0.9 Pa, respectively). Because SCI-U and SCI-L showed no differences in shear stress levels, inactivity and not nerve degeneration seems to cause the elevated shear stress levels in the CFA in SCI. However, the lack of central neural control as a causal factor cannot be ruled out.
Cutaneous vascular function during acute hyperglycemia in healthy young adults
Authors: Charkoudian N. , Vella A. , Reed A. S. , Minson C. T. , Shah P. , Rizza R. A. , Joyner M. J.
Published: March 2015

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia ( n = 8), 6 h when glucose was clamped at ∼7 mmol/l ( n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose ∼11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance ( n = 10). Insulin concentrations in all instances were maintained at ∼65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.
Skeletal muscle unweighting: spaceflight and ground-based models
Authors: Adams Gregory R. , Caiozzo Vincent J. , Baldwin Kenneth M.
Published: March 2015

Long-term manned spaceflight requires that flight crews be exposed to extended periods of unweighting of antigravity skeletal muscles. This exposure will result in adaptations in these muscles that have the potential to debilitate crew members on return to increased gravity environments. Therefore, the development of countermeasures to prevent these unwanted adaptations is an important requirement. The limited access to microgravity environments for the purpose of studying muscle adaptation and evaluating countermeasure programs has necessitated the use of ground-based models to conduct both basic and applied muscle physiology research. In this review, the published results from ground-based models of muscle unweighting are presented and compared with the results from related spaceflight research. The models of skeletal muscle unweighting with a sufficient body of literature included bed rest, cast immobilization, and unilateral lower limb suspension. Comparisons of changes in muscle strength and size between these models in the context of the limited results available from spaceflight suggest that each model may be useful for the investigation of certain aspects of the skeletal muscle unweighting that occur in microgravity.
Modulation of decompression sickness risk in pigs with caffeine during H2biochemical decompression
Authors: Fahlman Andreas , Lin Winston C. , Whitman William B. , Kayar Susan R.
Published: March 2015

In H2biochemical decompression, H2-metabolizing intestinal microbes remove gas stored in tissues of animals breathing hyperbaric H2, thereby reducing decompression sickness (DCS) risk. We hypothesized that increasing intestinal perfusion in pigs would increase the activity of intestinal Methanobrevibacter smithii, lowering DCS incidence further. Pigs ( Sus scrofa,17–23 kg, n = 20) that ingested caffeine (5 mg/kg) increased O2consumption rate in 1 atm air by ∼20% for at least 3 h. Pigs were given caffeine alone or caffeine plus injections of M. smithii. Animals were compressed to 24 atm (20.5–23.1 atm H2, 0.3–0.5 atm O2) for 3 h, then decompressed and observed for signs of DCS. In previous studies, DCS incidence in animals without caffeine treatment was significantly ( P < 0.05) lower with M. smithii injections (7/16) than in controls (9/10). However, contrary to our hypothesis, DCS incidence was marginally higher ( P = 0.057) in animals that received caffeine and M. smithii (9/10) than in animals that received caffeine but no M. smithii (4/10). More information on gas kinetics is needed before extending H2biochemical decompression to humans.
Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles
Authors: Suwa Masataka , Nakano Hiroshi , Kumagai Shuzo
Published: March 2015

This study was designed to determine the histological and metabolic effects of the administration of 5′-AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 14 successive days. AICAR treatment caused a significant decrease in the percentage of type IIB fibers and the concomitant increase in the percentage of type IIX fibers in extensor digitorum longus (EDL) muscle. The capillary density and the capillary-to-fiber ratio were not altered by AICAR. AICAR treatment increased the glycolytic and oxidative enzyme activities but not the antioxidant enzyme activities. The AICAR treatment increased the uncoupling protein 3 (UCP3) level in EDL and the peroxisome proliferator-activated receptor-γ coactivator-1α protein level in the soleus and EDL muscles, whereas the myogenin level was not altered by AICAR. These results seem to imply that the chronic activation of AMPK alters such muscle histochemical and metabolic characteristics.
Endogenous expression and developmental changes of HSP72 in rat skeletal muscles
Authors: Ogata Tomonori , Oishi Yasuharu , Roy Roland R. , Ohmori Hajime
Published: March 2015

The purpose of the present study was to determine whether endogenous factor(s) contributes to the expression of heat shock proteins (HSPs) during the early developmental stages of rat skeletal muscles. HSP72 was expressed in both the soleus and plantaris muscles at embryonic day 22 (E22). On the basis of myosin heavy chain (MHC) immunohistochemistry, HSP72 was specifically expressed in slow type I fibers in both muscles. These slow fibers were observed throughout the entire cross section of the soleus muscle and only in the deep region (close to the bone) of the plantaris muscle. These results indicate that the expression of HSP72 is related to endogenous factors associated with type I fibers, because E22 rats have minimal exogenous influences and the soleus and plantaris muscles of E22 rats have similar metabolic and contractile profiles at this stage of development. We then examined the changes in HSP72 and heat shock cognate (HSC) 73 in the same two muscles from E22 to postnatal day 56 via Western blotting. The level of HSP72 in the soleus muscle gradually increased in parallel with the increment in the type I MHC isoform. Compared with the soleus, only a small amount of HSP72 could be detected in the plantaris muscle throughout the developmental period. For both muscles, HSC73 reached levels observed in adult muscles at postnatal day 3, and these levels were unchanged thereafter. These results indicate that the expression of HSP72, but not HSC73, is influenced by both endogenous and exogenous factors during the embryonic and early developmental periods.
Repeated exercise paired with “imperceptible” dead space loading does not alter V˙eof subsequent exercise in humans
Authors: Moosavi S. H. , Guz A. , Adams L.
Published: March 2015

We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a “conditioning” and a “nonconditioning” session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the “control” and “test” runs) were compared for each session. Steady-state exercise end-tidal Pco2was significantly lower ( P= 0.003) during test than during control runs for both sessions (dropping by 1.8 ± 2 and 1.4 ± 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.
Effects of intervals between jumps or bouts on osteogenic response to loading
Authors: Umemura Yoshihisa , Sogo Naota , Honda Akiko
Published: March 2015

Prolonged loading repetitions can diminish the mechanosensitivity of bones, and increased intervals between loading might restore sensitivity. This study was designed to investigate the effects of intervals between loadings or bouts on osteogenic response. Forty female Fisher 344 rats aged 5 wk were divided into a control group and three exercise groups: 20 jumps in a single bout with a 3-s (S3) or 30-s (S30) jump interval, or 20 jumps in 2 bouts (10 × 2) separated by a 6-h interval with a 3-s jump interval (D3). After 8 wk of training, the bone masses per body weight of the femur and tibia were significantly greater in the three exercise groups than in the control group, and these values were also greater in S30 than in S3, although they were at the same level in D3 and S3. These data suggest that a longer interval (30 s) between individual loading had more effective anabolic effects on bone than a shorter interval (3 s).
Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women
Authors: Flynn Michael G. , McFarlin Brian K. , Phillips Melody D. , Stewart Laura K. , Timmerman Kyle L.
Published: March 2015

The purpose of this study was to examine the influence of resistive exercise training and hormone status on mRNA expression of toll-like receptor 4 (TLR4), CD14, IL-1β, IL-6, and TNF-α. Resistive exercise-trained women on “traditional” hormone replacements [hormone replacement therapy (HRT), n = 9], not taking hormones (NHR, n = 6), or taking medications known to influence bone (MIB, n = 7) were compared with untrained subjects not taking supplemental hormones (Con, n = 6). Blood was taken from trained subjects before, immediately after, and 2 h after resistive exercise (same time points for resting Con). TLR4 mRNA expression (RT-PCR) was not different among groups or across time but was significantly ( P = 0.044) lower (1.9-fold) when trained groups were collapsed and compared with Con. There was also a significant group effect ( P < 0.0001) for TLR4 mRNA when expressed per monocyte. CD14 expression was significantly ( P = 0.006) lower (2.3-fold) for training groups collapsed and compared with Con. CD14 mRNA, expressed per monocyte, was significantly lower immediately after resistive exercise for NHR, HRT, and MIB compared with Con. There were few significant effects detected for IL-6, IL-1β, and TNF-α mRNA, but there was a significant group effect ( P < 0.0001) for TNF-α mRNA expressed per monocyte (Con > HRT, NHR, MIB). These findings suggest that there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women. Further research is needed to determine whether lower TLR4/CD14 could explain the lower LPS-stimulated inflammatory cytokines observed in these women.
Direct assessment and distribution of regional portal blood flow in the pig by means of fluorescent microspheres
Authors: Thein E. , Becker M. , Anetzberger H. , Hammer C. , Messmer K.
Published: March 2015

Measurement of regional organ blood flow by means of fluorescent microspheres (FM) is an accepted method. However, determination of regional portal blood flow (RPBF) cannot be performed by microspheres owing to the entrapment of the spheres in the upstream capillary bed of the splanchnic organs. We hypothesized that an adequate experimental setting would enable us to measure RPBF by means of FM and to analyze its distribution within the pig liver. A mixing chamber for the injection of FM was developed, and its capability to distribute FM homogeneously in the blood was evaluated in vitro. The chamber was implanted into the portal vein of six anesthetized pigs (23.5 ± 2.9 kg body wt). Three consecutive, simultaneous injections of FM of two different colors into the chamber were performed. Reference portal blood samples were collected by means of a Harvard pump. At the end of the experiment, the liver was explanted and fixed in formalin before dissection. FM were isolated from the tissue samples by an automated process, and fluorescence intensity was determined. Comparison of 5,458 single RPBF values, determined by simultaneously injected FM, revealed good agreement (bias 2.5%, precision 12.7%) and high correlation ( r = 0.97, r2 = 0,95, slope = 1.04, intercept = 0.05). Median RPBF was 1.07 ± 0.78 ml · min-1 · g-1. Allocation of the blood flow values to the anatomic regions of the liver revealed a significantly higher RPBF ( P = 0.01) in the liver tissue located close to the diaphragm compared with the rest of the organ and a significantly lower RPBF ( P = 0.01) in the left liver lobe compared with the median and right lobes. The results show that the model presented makes it possible to measure RPBF by means of FM reliably and that RPBF is distributed heterogeneously in the porcine liver.
Role of nitric oxide in vasodilation in upstream muscle during intermittent pneumatic compression
Authors: Chen Long-En , Liu Kang , Qi Wen-Ning , Joneschild Elizabeth , Tan Xiangling , Seaber Anthony V. , Stamler Jonathan S. , Urbaniak James R.
Published: March 2015

This study investigated the dosage effects of nitric oxide synthase (NOS) inhibitor N G-monomethyl-l-arginine(l-NMMA) on intermittent pneumatic compression (IPC)-induced vasodilation in uncompressed upstream muscle and the effects of IPC on endothelial NOS (eNOS) expression in upstream muscle. Afterl-NMMA infusion, mean arterial pressure increased by 5% from baseline (99.5 ± 18.7 mmHg; P < 0.05). Heart rate and respiratory rate were not significantly affected. One-hour IPC application on legs induced a 10% dilation from baseline in 10- to 20-μm arterioles and a 10–20% dilation in 21- to 40-μm arterioles and 41- to 70-μm arteries in uncompressed cremaster muscle. IPC-induced vasodilation was dose dependently reduced, abolished, or even reversed by concurrently infusedl-NMMA. Moreover, expression of eNOS mRNA in uncompressed cremaster muscle was upregulated to 2 and 2.5 times normal at the end of 1- and 5-h IPC on legs, respectively, and the expression of eNOS protein was upregulated to 1.8 times normal. These increases returned to baseline level after cessation of IPC. The results suggest that eNOS plays an important role in regulating the microcirculation in upstream muscle during IPC.
Effects of age and exercise on physiological dead space during simulated dives at 2.8 ATA
Authors: Mummery H. J. , Stolp B. W. , deL. Dear G. , Doar P. O. , Natoli M. J. , Boso A. E. , Archibald J. D. , Hobbs G. W. , El-Moalem H. E. , Moon R. E.
Published: March 2015

Physiological dead space (Vds), end-tidal CO2(Pet CO2 ), and arterial CO2(PaCO2 ) were measured at 1 and 2.8 ATA in a dry hyperbaric chamber in 10 older (58–74 yr) and 10 younger (19–39 yr) air-breathing subjects during rest and two levels of upright exercise on a cycle ergometer. At pressure, Vd(liters btps) increased from 0.34 ± 0.09 (mean ± SD of all subjects for normally distributed data, median ± interquartile range otherwise) to 0.40 ± 0.09 ( P= 0.0060) at rest, 0.35 ± 0.13 to 0.45 ± 0.11 ( P = 0.0003) during light exercise, and 0.38 ± 0.17 to 0.45 ± 0.13 ( P = 0.0497) during heavier exercise. During these conditions, PaCO2 (Torr) increased from 33.8 ± 4.2 to 35.7 ± 4.4 ( P = 0.0059), 35.3 ± 3.2 to 39.4 ± 3.1 ( P < 0.0001), and 29.6 ± 5.6 to 37.4 ± 6.5 ( P < 0.0001), respectively. During exercise, Pet CO2 overestimated PaCO2 , although the absolute difference was less at pressure. Capnography poorly estimated PaCO2 during exercise at 1 and 2.8 ATA because of wide variability. Older subjects had higher Vd at 1 ATA but similar changes in Vd, PaCO2 , and Pet CO2 at pressure. These results are consistent with an effect of increased gas density.