bluuebunny/crossref_metadata_2025 huggingface dataset:
Selected Contribution: High-altitude natives living at sea level acclimatize to high altitude like sea-level natives
Authors: Rivera-Ch Maria , Gamboa Alfredo , León-Velarde Fabiola , Palacios Jose-Antonio , O'Connor David F. , Robbins Peter A.
Published: March 2015

Sea-level (SL) natives acclimatizing to high altitude (HA) increase their acute ventilatory response to hypoxia (AHVR), but HA natives have values for AHVR below those for SL natives at SL (blunting). HA natives who live at SL retain some blunting of AHVR and have more marked blunting to sustained (20-min) hypoxia. This study addressed the question of what happens when HA natives resident at SL return to HA: do they acclimatize like SL natives or revert to the characteristics of HA natives? Fifteen HA natives resident at SL were studied, together with 15 SL natives as controls. Air-breathing end-tidal Pco 2 and AHVR were determined at SL. Subjects were then transported to 4,300 m, where these measurements were repeated on each of the following 5 days. There were no significant differences in the magnitude or time course of the changes in end-tidal Pco 2 and AHVR between the two groups. We conclude that HA natives normally resident at SL undergo ventilatory acclimatization to HA in the same manner as SL natives.
Diving response and arterial oxygen saturation during apnea and exercise in breath-hold divers
Authors: Andersson Johan P. A. , Linér Mats H. , Rünow Elisabeth , Schagatay Erika K. A.
Published: March 2015

This study addressed the effects of apnea in air and apnea with face immersion in cold water (10°C) on the diving response and arterial oxygen saturation during dynamic exercise. Eight trained breath-hold divers performed steady-state exercise on a cycle ergometer at 100 W. During exercise, each subject performed 30-s apneas in air and 30-s apneas with face immersion. The heart rate and arterial oxygen saturation decreased and blood pressure increased during the apneas. Compared with apneas in air, apneas with face immersion augmented the heart rate reduction from 21 to 33% ( P < 0.001) and the blood pressure increase from 34 to 42% ( P < 0.05). The reduction in arterial oxygen saturation from eupneic control was 6.8% during apneas in air and 5.2% during apneas with face immersion ( P < 0.05). The results indicate that augmentation of the diving response slows down the depletion of the lung oxygen store, possibly associated with a larger reduction in peripheral venous oxygen stores and increased anaerobiosis. This mechanism delays the fall in alveolar and arterial Po2and, thereby, the development of hypoxia in vital organs. Accordingly, we conclude that the human diving response has an oxygen-conserving effect during exercise.
Respiratory effects of the scalene and sternomastoid muscles in humans
Authors: Legrand Alexandre , Schneider Emmanuelle , Gevenois Pierre-Alain , De Troyer André
Published: March 2015

Previous studies have shown that in normal humans the change in airway opening pressure (ΔPao) produced by all the parasternal and external intercostal muscles during a maximal contraction is approximately −18 cmH2O. This value is substantially less negative than ΔPao values recorded during maximal static inspiratory efforts in subjects with complete diaphragmatic paralysis. In the present study, therefore, the respiratory effects of the two prominent inspiratory muscles of the neck, the sternomastoids and the scalenes, were evaluated by application of the Maxwell reciprocity theorem. Seven healthy subjects were placed in a computed tomographic scanner to determine the fractional changes in muscle length during inflation from functional residual capacity to total lung capacity and the masses of the muscles. Inflation induced greater shortening of the scalenes than the sternomastoids in every subject. The inspiratory mechanical advantage of the scalenes thus averaged (mean ± SE) 3.4 ± 0.4%/l, whereas that of the sternomastoids was 2.0 ± 0.3%/l ( P < 0.001). However, sternomastoid muscle mass was much larger than scalene muscle mass. As a result, ΔPao generated by a maximal contraction of either muscle would be 3–4 cmH2O, which is about the same as ΔPao generated by the parasternal intercostals in all interspaces.
Tracer kinetic model of regional pulmonary function using positron emission tomography
Authors: Galletti Gaetano G. , Venegas José G.
Published: March 2015

To determine the spatial distributions of pulmonary perfusion, shunt, and ventilation, we developed a compartmental model of regional 13N-labeled molecular nitrogen (13NN) kinetics measured from positron emission tomography (PET) images. The model features a compartment for right heart and pulmonary vasculature and two compartments for each region of interest: 1) aerated alveolar units and 2) alveolar units with no gas content (shunting). The model was tested on PET data from normal animals (dogs and sheep) and from animals with experimentally injured lungs simulating acute respiratory distress syndrome. The analysis yielded estimates of regional perfusion, shunt fraction, and specific ventilation with excellent goodness-of-fit to the data ( R 2 > 0.99). Model parameters were estimated to within 10% accuracy in the presence of exaggerated levels of experimental noise by using a Monte Carlo sensitivity analysis. Main advantages of the present model are that 1) it separates intraregional blood flow to aerated alveolar units from that shunting across nonaerated units and 2) it accounts and corrects for intraregional tracer removal by shunting blood when estimating ventilation from subsequent washout of tracer. The model was thus found to provide estimates of regional parameters of pulmonary function in sizes of lung regions that could potentially approach the intrinsic resolution for PET images of 13NN in lung (∼7.0 mm for a multiring PET camera).
Effect of a divided caffeine dose on endurance cycling performance, postexercise urinary caffeine concentration, and plasma paraxanthine
Authors: Conway Kylie J. , Orr Rhonda , Stannard Stephen R.
Published: March 2015

This study compared the effects of a single and divided dose of caffeine on endurance performance and on postexercise urinary caffeine and plasma paraxanthine concentrations. Nine male cyclists and triathletes cycled for 90 min at 68% of maximal oxygen uptake, followed by a self-paced time trial (work equivalent to 80% of maximal oxygen uptake workload over 30 min) with three randomized, balanced, and double-blind interventions: 1) placebo 60 min before and 45 min into exercise (PP); 2) single caffeine dose (6 mg/kg) 60 min before exercise and placebo 45 min into exercise (CP); and 3) divided caffeine dose (3 mg/kg) 60 min before and 45 min into exercise (CC). Time trial performance was unchanged with caffeine ingestion ( P = 0.08), but it tended to be faster in the caffeine trials (CP: 24.2 min and CC: 23.4 min) compared with placebo (PP: 28.3 min). Postexercise urinary caffeine concentration was significantly lower in CC (3.8 μg/ml) compared with CP (6.8 μg/ml). Plasma paraxanthine increased in a dose-dependent fashion and did not peak during exercise. In conclusion, dividing a caffeine dose provides no ergogenic effect over a bolus dose but reduces postexercise urinary concentration.
Correlations using the NREM-REM sleep cycle frequency support distinct regulation mechanisms for REM and NREM sleep
Authors: Le Bon O. , Staner L. , Rivelli S. K. , Hoffmann G. , Pelc I. , Linkowski P.
Published: March 2015

Polysomnograms of most homeothermic species distinguish two states, rapid eye movement (REM) and non-REM (NREM) sleep. These alternate several times during the night for reasons and following rules that remain poorly understood. It is unknown whether each state has its own function and regulation or whether they represent two facets of the same process. The present study compared the mean REM/NREM sleep ratio and the mean number of NREM-REM sleep cycles across 3 consecutive nights. The rationale was that, if REM and NREM sleep are tightly associated, their ratio should be comparable whatever the cycle frequency in the night. Twenty-six healthy subjects of both sexes were recorded at their home for 4 consecutive nights. The correlation between the REM/NREM sleep ratio and the number of cycles was highly significant. Of the two sleep components, REM sleep was associated to the number of cycles, whereas NREM sleep was not. This suggests that the relationship between REM sleep and NREM sleep is rather weak within cycles, does not support the concept of NREM-REM sleep cycles as miniature units of the sleep process, and favors the concept of distinct mechanisms of regulation for the two components.
Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures
Authors: Dean Jay B. , Mulkey Daniel K. , Garcia Alfredo J. , Putnam Robert W. , Henderson Richard A.
Published: March 2015

As ambient pressure increases, hydrostatic compression of the central nervous system, combined with increasing levels of inspired Po2, Pco2, and N2partial pressure, has deleterious effects on neuronal function, resulting in O2toxicity, CO2toxicity, N2narcosis, and high-pressure nervous syndrome. The cellular mechanisms responsible for each disorder have been difficult to study by using classic in vitro electrophysiological methods, due to the physical barrier imposed by the sealed pressure chamber and mechanical disturbances during tissue compression. Improved chamber designs and methods have made such experiments feasible in mammalian neurons, especially at ambient pressures <5 atmospheres absolute (ATA). Here we summarize these methods, the physiologically relevant test pressures, potential research applications, and results of previous research, focusing on the significance of electrophysiological studies at <5 ATA. Intracellular recordings and tissue Po2measurements in slices of rat brain demonstrate how to differentiate the neuronal effects of increased gas pressures from pressure per se. Examples also highlight the use of hyperoxia (≤3 ATA O2) as a model for studying the cellular mechanisms of oxidative stress in the mammalian central nervous system.
Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia
Authors: Lobo Suzana M. , De Backer Daniel , Sun Qinghua , Tu Zizi , Dimopoulos George , Preiser Jean-Charles , Nagy Nathalie , Vray Bernard , Vercruy Vincent , Terzi Renato Giuseppe Giovanni , Vincent Jean-Louis
Published: March 2015

Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 μg/kg)/fluid resuscitation (12 ml · kg-1 · h-1); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml · kg-1 · h-1); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml · kg-1 · h-1 fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml · kg-1 · h-1); n = 4]. Luminal gut lactate concentrations and Pco2 gap increased in groups IV and V ( P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called “cytopathic hypoxia.”
Spectral characteristics of airway opening and chest wall tidal flows in spontaneously breathing preterm infants
Authors: Habib Robert H. , Pyon Kee H. , Courtney Sherry E. , Aghai Zubair H.
Published: March 2015

We compared the harmonic content of tidal flows measured simultaneously at the mouth and chest wall in spontaneously breathing very low birth weight infants ( n = 16, 1,114 ± 230 g, gestation age: 28 ± 2 wk). Airway opening flows were measured via face mask-pneumotachograph (P-tach), whereas chest wall flows were derived from respiratory inductance plethysmography (RIP) excursions. Next, for each, we computed two spectral shape indexes: 1) harmonic distortion ( k d; k d,P-tachand k d,RIP, respectively) defines the extent to which flows deviated from a single sine wave, and 2) the exponent of the power law ( s; s P-tachand s RIP, respectively), describing the spectral energy vs. frequency. P-tach and RIP flow spectra exhibited similar power law functional forms consistently in all infants. Also, mouth [ s P-tach = 3.73 ± 0.23% (95% confidence interval), k d,P-tach = 38.8 ± 4.6%] and chest wall ( s RIP = 3.51 ± 0.30%, k d,RIP = 42.8 ± 4.8%) indexes were similar and highly correlated ( s RIP = 1.17 × s P-tach + 0.85; r 2 = 0.81; k d,RIP = 0.90 × k d,P-tach + 8.0; r 2 = 0.76). The corresponding time to peak tidal expiratory flow-to-expiratory time ratio (0.62 ± 0.08) was higher than reported in older infants. The obtained s and k d values are similar to those reported in older and/or larger chronic lung disease infants, yet appreciably lower than for 1-mo-old healthy infants of closer age and/or size; this indicated increased complexity of tidal flows in very low birth weight babies. Importantly, we found equivalent flow spectral data from mouth and chest wall tidal flows. The latter are desirable because they avoid face mask artificial effects, including leaks around it, they do not interfere with ventilatory support delivery, and they may facilitate longer measurements that are useful in control of breathing assessment.
Effect of episodic hypoxia on upper airway mechanics in humans during NREM sleep
Authors: Shkoukani Mahdi , Babcock Mark A. , Badr M. Safwan
Published: March 2015

We hypothesized that long-term facilitation (LTF) is due to decreased upper airway resistance (Rua). We studied 11 normal subjects during stable non-rapid eye movement sleep. We induced brief isocapnic hypoxia (inspired O2fraction = 8%) (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 20 min of recovery (R20) for ventilation, timing, and Rua. In addition, nine subjects were studied in a sham study with no hypoxic exposure. During the episodic hypoxia study, inspiratory minute ventilation (V˙i) increased from 7.1 ± 1.8 l/min during the control period to 8.3 ± 1.8 l/min at R20 (117% of control; P < 0.05). Conversely, there was no change in diaphragmatic electromyogram (EMGdia) between control (16.1 ± 6.9 arbitrary units) and R20 (15.3 ± 4.9 arbitrary units) (95% of control; P > 0.05). In contrast, increasedV˙i was associated with decreased Rua from 10.7 ± 7.5 cmH2O · l−1 · s during control to 8.2 ± 4.4 cmH2O · l−1 · s at R20 (77% of control; P < 0.05). No change was noted in V˙i, Rua, or EMGdia during the recovery period relative to control during the sham study. We conclude the following: 1) increased V˙i in the recovery period is indicative of LTF, 2) the lack of increased EMGdia suggests lack of LTF to the diaphragm, 3) reduced Rua suggests LTF of upper airway dilators, and 4) increased V˙i in the recovery period is due to “unloading” of the upper airway by LTF of upper airway dilators.
Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen
Authors: Schneider Hartmut , Boudewyns An , Smith Philip L. , O'Donnell Christopher P. , Canisius Sebastian , Stammnitz Axel , Allan Lawrence , Schwartz Alan R.
Published: March 2015

We hypothesized that upper airway collapsibility is modulated dynamically throughout the respiratory cycle in sleeping humans by alterations in respiratory phase and/or airflow regimen. To test this hypothesis, critical pressures were derived from upper airway pressure-flow relationships in six tracheostomized patients with obstructive sleep apnea. Pressure-flow relationships were generated by varying the pressure at the trachea and nose during tracheostomy (inspiration and expiration) ( comparison A) and nasal (inspiration only) breathing ( comparison B), respectively. When a constant airflow regimen was maintained throughout the respiratory cycle (tracheostomy breathing), a small yet significant decrease in critical pressure was found at the inspiratory vs. end- and peak-expiratory time point [7.1 ± 1.6 (SE) to 6.6 ± 1.9 to 6.1 ± 1.9 cmH2O, respectively; P < 0.05], indicating that phasic factors exerted only a modest influence on upper airway collapsibility. In contrast, we found that the inspiratory critical pressure fell markedly during nasal vs. tracheostomy breathing [1.1 ± 1.5 (SE) vs. 6.1 ± 1.9 cmH2O; P < 0.01], indicating that upper airway collapsibility is markedly influenced by differences in airflow regimen. Tracheostomy breathing was also associated with a reduction in both phasic and tonic genioglossal muscle activity during sleep. Our findings indicate that both phasic factors and airflow regimen modulate upper airway collapsibility dynamically and suggest that neuromuscular responses to alterations in airflow regimen can markedly lower upper airway collapsibility during inspiration.
Effects of dichloroacetate on V̇o2and intramuscular31P metabolite kinetics during high-intensity exercise in humans
Authors: Rossiter H. B. , Ward S. A. , Howe F. A. , Wood D. M. , Kowalchuk J. M. , Griffiths J. R. , Whipp B. J.
Published: March 2015

Traditional control theories of muscle O2consumption are based on an “inertial” feedback system operating through features of the ATP splitting (e.g., [ADP] feedback, where brackets denote concentration). More recently, however, it has been suggested that feedforward mechanisms (with respect to ATP utilization) may play an important role by controlling the rate of substrate provision to the electron transport chain. This has been achieved by activation of the pyruvate dehydrogenase complex via dichloroacetate (DCA) infusion before exercise. To investigate these suggestions, six men performed repeated, high-intensity, constant-load quadriceps exercise in the bore of an magnetic resonance spectrometer with each of prior DCA or saline control intravenous infusions. O2uptake (V̇o2) was measured breath by breath (by use of a turbine and mass spectrometer) simultaneously with intramuscular phosphocreatine (PCr) concentration ([PCr]), [Pi], [ATP], and pH (by31P-MRS) and arterialized-venous blood sampling. DCA had no effect on the time constant (τ) of either V̇o2increase or PCr breakdown [τV̇o245.5 ± 7.9 vs. 44.3 ± 8.2 s (means ± SD; control vs. DCA); τPCr 44.8 ± 6.6 vs. 46.4 ± 7.5 s; with 95% confidence intervals averaging < ±2 s]. DCA, however, resulted in significant ( P < 0.05) reductions in 1) end-exercise [lactate] (-1.0 ± 0.9 mM), intramuscular acidification (pH, +0.08 ± 0.06 units), and [Pi] (-1.7 ± 2.1 mM); 2) the amplitude of the fundamental components for [PCr] (-1.9 ± 1.6 mM) and V̇o2(-0.1 ± 0.07 l/min, or 8%); and 3) the amplitude of the V̇o2slow component. Thus, although the DCA infusion lessened the buildup of potential fatigue metabolites and reduced both the aerobic and anaerobic components of the energy transfer during exercise, it did not enhance either τV̇o2or τ[PCr], suggesting that feedback, rather than feedforward, control mechanisms dominate during high-intensity exercise.
Postnatal expression of neurotransmitters, receptors, and cytochrome oxidase in the rat pre-Bötzinger complex
Authors: Liu Qiuli , Wong-Riley Margaret T. T.
Published: March 2015

The pre-Bötzinger complex (PBC) is postulated as the center of respiratory rhythmogenesis. Previously, we found a reduction or plateau of cytochrome oxidase (CO) activity in the PBC and other respiratory nuclei at postnatal days 3–4, despite a general increase of CO with age, suggesting a period of synaptic readjustment. The present study examined the expression of CO and a number of neurochemicals in the PBC at closer time intervals. At postnatal days 3–4 and, more prominently, at postnatal day 12, expression of CO, glutamate, and N-methyl-d-aspartate receptor subunit 1 was reduced, whereas expression of GABA, GABABreceptor, glycine receptor, and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit 2 was increased. These findings are consistent with our hypothesis that decreased CO activity is associated with an increase in inhibitory drive (mediated by GABA and glycine, their receptors, and possibly blockage of Ca2+ entry by glutamate receptor subunit 2) and a decrease in excitatory drive (mediated by glutamate and its receptors). Our findings point to two critical periods during postnatal development of the rat when their respiratory system may be more vulnerable to respiratory insults.
Determinants of metabolic cost during submaximal cycling
Authors: McDaniel J. , Durstine J. L. , Hand G. A. , Martin J. C.
Published: March 2015

The metabolic cost of producing submaximal cycling power has been reported to vary with pedaling rate. Pedaling rate, however, governs two physiological phenomena known to influence metabolic cost and efficiency: muscle shortening velocity and the frequency of muscle activation and relaxation. The purpose of this investigation was to determine the relative influence of those two phenomena on metabolic cost during submaximal cycling. Nine trained male cyclists performed submaximal cycling at power outputs intended to elicit 30, 60, and 90% of their individual lactate threshold at four pedaling rates (40, 60, 80, 100 rpm) with three different crank lengths (145, 170, and 195 mm). The combination of four pedaling rates and three crank lengths produced 12 pedal speeds ranging from 0.61 to 2.04 m/s. Metabolic cost was determined by indirect calorimetery, and power output and pedaling rate were recorded. A stepwise multiple linear regression procedure selected mechanical power output, pedal speed, and pedal speed squared as the main determinants of metabolic cost ( R 2 = 0.99 ± 0.01). Neither pedaling rate nor crank length significantly contributed to the regression model. The cost of unloaded cycling and delta efficiency were 150 metabolic watts and 24.7%, respectively, when data from all crank lengths and pedal speeds were included in a regression. Those values increased with increasing pedal speed and ranged from a low of 73 ± 7 metabolic watts and 22.1 ± 0.3% (145-mm cranks, 40 rpm) to a high of 297 ± 23 metabolic watts and 26.6 ± 0.7% (195-mm cranks, 100 rpm). These results suggest that mechanical power output and pedal speed, a marker for muscle shortening velocity, are the main determinants of metabolic cost during submaximal cycling, whereas pedaling rate (i.e., activation-relaxation rate) does not significantly contribute to metabolic cost.
Volume history and effect on airway reactivity in infants and adults
Authors: Weist A. , Williams T. , Kisling J. , Clem C. , Tepper R. S.
Published: March 2015

Volume history is an important determinant of airway responsiveness. In healthy adults undergoing airway challenge, deep inspiration (DI) provides bronchodilating and bronchoprotective effects; however, the effectiveness of DI is limited in asthmatic adults. We hypothesized that, when assessed under similar conditions, healthy infants have heightened airway reactivity compared with healthy adults and that the effectiveness of DI is limited in infants. We compared the effect of DI on reactivity by using full (DI) vs. partial (no DI) forced-expiratory maneuvers on 2 days in supine, healthy nonasthmatic infants (21) and adults (10). Reactivity was assessed by methacholine doses that decreased forced expiratory flow after exhalation of 75% forced vital capacity during a full maneuver and maximal expiratory flow at functional residual capacity during a partial maneuver by 30% from baseline. Reactivity in adults increased when DI was absent, whereas infants' reactivity was unchanged. Infants were more reactive than adults in the presence of DI; however, adult and infant reactivity was similar in its absence. Our findings indicate that healthy infants are more reactive than adults and, like asthmatic adults, do not benefit from DI; this difference may be an important characteristic of airway hyperreactivity.
Smooth muscle cells contract in response to fluid flow via a Ca2+-independent signaling mechanism
Authors: Civelek Mete , Ainslie Kristy , Garanich Jeff S. , Tarbell John M.
Published: March 2015

Smooth muscle cells (SMC) are exposed to fluid shear stress because of transmural (interstitial) flow across the arterial wall. This shear stress may play a role in the myogenic response and flow-mediated vasomotion. We, therefore, examined the effects of fluid flow on contraction of rat aortic SMC. SMC that had been serum-starved to induce a contractile phenotype were plated on quartz slides and exposed to controlled shear stress levels in a flow chamber. The area of the cells was quantified, and reduction in the cell area was reported as contraction. At 25 dyn/cm2, significant area reduction was apparent 3 min after the onset of flow and exceeded 30% at 30 min. At 1 dyn/cm2, significant contraction was not observed at 30 min. The threshold for significant shear-induced contraction appeared to be 11 dyn/cm2. The signal transduction mechanism was studied at 25 dyn/cm2. Intracellular calcium was imaged by using the calcium-sensitive fluorescent dye fura 2-AM. There was no detectable change in intracellular calcium during 10 min of exposure to shear stress, even though the cells displayed a significant calcium response to thapsigargin, calcium ionophore, and KCl. Further studies using pathway inhibitors provided evidence that the most important signal transduction pathway mediating calcium-independent contraction in response to fluid flow is the Rho-kinase pathway, although there was a suggestion that protein kinase C plays a secondary role.
Selected Contribution: Effect of acute heat shock on gene expression by human peripheral blood mononuclear cells
Authors: Sonna Larry A. , Gaffin Stephen L. , Pratt Richard E. , Cullivan Michael L. , Angel Karen C. , Lilly Craig M.
Published: March 2015

We studied the effect of heat shock on gene expression by normal human cells. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy adults. Paired samples from each subject were subjected to either 20 min of heat shock (43°C) or control (37°C) conditions and then returned to 37°C. RNA was isolated 160 min later, and five representative samples were analyzed on Affymetrix gene chip arrays containing ∼12,600 probes. A biologically meaningful effect was defined as a statistically significant, twofold or greater difference in expression of sequences that were detected in all five experiments under control (downregulated sequences) or heat shock (upregulated sequences) conditions. Changes occurred in 395 sequences (227 increased by heat shock, 168 decreased), representing 353 Unigene numbers, in every functional category previously implicated in the heat shock response. By RT-PCR, we confirmed the findings for one upregulated sequence (Rad, a G protein) and one downregulated sequence (osteopontin, a cytokine). We conclude that heat shock causes extensive gene expression changes in PBMCs, affecting all functional categories of the heat shock response.
Factors in fatigue during intermittent electrical stimulation of human skeletal muscle
Authors: Russ David W. , Vandenborne Krista , Binder-Macleod Stuart A.
Published: March 2015

During an electrically elicited isometric contraction, the metabolic cost of attaining is greater than of maintaining force. Thus fatigue produced during such stimulation may not simply be a function of the force-time integral (FTI), as previously suggested. The goal of the present study was to evaluate fatigue produced in human medial gastrocnemius by intermittent, isometric electrical stimulation with trains of different frequencies (20, 40, or 80 Hz) and durations (300, 600, or 1,200 ms) that produced different peak forces and FTIs. Each subject ( n = 10) participated in a total of six sessions. During each session, subjects received a pre- and postfatigue testing protocol and a different, 150-train fatiguing protocol. Each fatiguing protocol used only a single frequency and duration. The fatigue produced by the different protocols was correlated to the initial peak force of the fatiguing protocols ( r 2= 0.74–0.85) but not to the initial or total FTI. All of the protocols tested produced a proportionately greater impairment of force in response to low- vs. high-frequency stimulation (i.e., low-frequency fatigue). There was no effect of protocol on low-frequency fatigue, suggesting that all the protocols produced comparable levels of impairment in excitation-contraction coupling. These results suggest that, for brief stimulated contractions, peak force is a better predictor of fatigue than FTI, possibly because of the different metabolic demands of attaining and maintaining force.
Heterogeneous activity of the human genioglossus muscle assessed by multiple bipolar fine-wire electrodes
Authors: Eastwood Peter R. , Allison Garry T. , Shepherd Kelly L. , Szollosi Irene , Hillman David R.
Published: March 2015

Genioglossus (GG) electrical activity [measured by electromyogram (EMGgg)] is best measured by intramuscular electrodes; however, the homogeneity of EMGgg is undefined. We investigated the relationships between EMGgg and the site from which activity was measured to determine whether and to what extent inhomogeneity in activity occurred. Eight healthy human volunteers underwent ultrasound to determine GG depth and width. Four pairs of electrodes were then inserted percutaneously into the left and right GG muscle, anteriorly and posteriorly. Additional configurations were obtained by connecting electrodes across the midline and along each muscle belly. EMGgg activity was simultaneously recorded from these 10 configurations at rest and during various respiratory maneuvers. Heterogeneous behavior of the GG was evidenced by 1) the variable presence of phasic EMGgg at rest, which was undetectable in two subjects but evident in 65% of configurations in six subjects and present in all configurations in all subjects during voluntary hyperventilation; 2) a greater amplitude of EMGgg response to pharyngeal square-wave negative pressure in anterior than posterior configurations (14.1 ± 7.1 vs. 8.5 ± 5.1% of maximum, P < 0.05); and 3) variable (linear and alinear) relationships between EMGgg and lingual force within and between subjects. We hypothesize that regional differences in density and type of muscle fiber are the most likely sources of heterogeneity in these responses.
Red blood cell orientation in pulmonary capillaries and its effect on gas diffusion
Authors: Nabors L. Karina , Baumgartner William A. , Janke Steven J. , Rose James R. , Wagner Wiltz W. , Capen Ronald L.
Published: March 2015

When alveoli are inflated, the stretched alveolar walls draw their capillaries into oval cross sections. This causes the disk-shaped red blood cells to be oriented near alveolar gas, thereby minimizing diffusion distance. We tested these ideas by measuring red blood cell orientation in histological slides from rapidly frozen rat lungs. High lung inflation did cause the capillaries to have oval cross sections, which constrained the red blood cells within them to flow with their broad sides facing alveolar gas. Low lung inflation stretched alveolar walls less and allowed the capillaries to assume a circular cross section. The circular luminal profile permitted the red blood cells to have their edges facing alveolar gas, which increased the diffusion distance. Using a finite-element method to calculate the diffusing capacity of red blood cells in the broad-side and edge-on orientations, we found that edge-on red blood cells had a 40% lower diffusing capacity. This suggests that, when capillary cross sections become circular, whether through low-alveolar volume or through increased microvascular pressure, the red blood cells are likely to be less favorably oriented for gas exchange.
Quantifying pressure sore-related muscle damage using high-resolution MRI
Authors: Bosboom E. M. H. , Bouten C. V. C. , Oomens C. W. J. , Baaijens F. P. T. , Nicolay K.
Published: March 2015

To obtain insight into the etiology of deep pressure sores, understanding of the relationship between prolonged transverse loading and local muscle damage is required. To date, the amount and location of muscle damage have been determined by histological examination. In the present study, we determined whether T2-weighted high-resolution magnetic resonance imaging (MRI) can also be applied to evaluate muscle tissue after prolonged transverse loading. The tibialis anterior muscle and overlying skin in the right hindlimbs of five rats were compressed between an indenter and the tibia. The in vivo magnetic resonance images of the loaded and contralateral hindlimbs were obtained 24 h after load application. The tibialis anterior muscles were then processed for histological examination. In the magnetic resonance images of all five loaded hindlimbs, signal intensity appeared higher in the loaded regions of the muscle compared with the unloaded regions. The location of the higher signal intensity coincided with the location of damage assessed from histology. Also the amount of damage determined with MRI was in good agreement with the amount of damage assessed from histological examination. Because MRI is nondestructive, it is a promising alternative for histology in research on pressure sore etiology, especially in follow-up studies to evaluate the development of muscle damage in time and in clinical studies.
Exercise training preserves endothelium-dependent relaxation in brachial arteries from hyperlipidemic pigs
Authors: Woodman Christopher R. , Turk James R. , Williams Daniel P. , Laughlin M. Harold
Published: March 2015

We tested the hypothesis that exercise training (Ex) attenuates the effects of hyperlipidemia on endothelial function by enhancing NO-mediated vasorelaxation in porcine brachial (Br) arteries. Adult female pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20 wk. Four weeks after initiation of the diet, pigs underwent Ex or remained sedentary (Sed) for 16 wk. Relaxation to ACh was impaired by HF ( P = 0.03). The combination of HF and Sed impaired ACh-induced relaxation more than HF or Sed alone ( P = 0.0002). Relaxation to high doses of bradykinin (BK) was impaired by HF ( P = 0.0002). Ex significantly improved ACh-induced relaxation ( P = 0.01) and tended to improve relaxation to BK ( P = 0.38). To determine the mechanism(s) by which HF and Ex affected relaxation to ACh and BK, relaxation was assessed in the presence of N G-nitro-l-arginine methyl ester (l-NAME; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. In the presence of l-NAME, Indo, or l-NAME + Indo, ACh-induced relaxation was no longer different between HF and NF arteries; however, relaxation remained greater in Ex than in Sed arteries. In the presence of l-NAME or Indo, BK-induced relaxation was no longer altered by HF but was enhanced by Ex. In the presence of l-NAME + Indo, BK-induced relaxation was enhanced by HF and Ex. These data indicate that hyperlipidemia impairs ACh- and BK-induced relaxation by impairing NO- and PGI2-mediated relaxation. Ex attenuates the effects of HF by enhancing a vasodilator mechanism independent of NO and PGI2.
Power spectral and Poincaré plot characteristics in sinus node dysfunction
Authors: Bergfeldt Lennart , Haga Yoshiyuki
Published: March 2015

A salient feature of the normal sinus node activity is its prominent beat-to-beat variability, which shows self-similarity on different time scales (fractal dynamics). However, in patients with sinus node dysfunction, short-term time sinus cycles show exaggerated variability, the characteristics of which have not been analyzed. Therefore, Poincaré plots and power spectral analysis were applied to short-term variations of sinus cycles in 30 patients with and 30 patients without sinus node disease. Three patterns of behavior were observed in sick sinus patients: type 1, completely normal ( n = 3); type 2, randomlike pattern in the Poincaré plots with “white noise” power spectra ( n = 9); and type 3, a transitional pattern, characterized by remnants of normal behavior mixed with scattered points ( n = 18). In control subjects, only type 1 ( n = 27) and type 3 ( n = 3) patterns were observed, P < 0.0001. The power spectral changes in sinus node dysfunction are thus characterized by a loss of the inverse power law relationship, which both has implications for heart rate variability analysis and might offer a new diagnostic approach.
Selected Contribution: Differential role of nitric oxide synthase isoforms in fever of different etiologies: studies using Nosgene-deficient mice
Authors: Kozak Wieslaw , Kozak Anna
Published: March 2015

Male C57BL/6J mice deficient in nitric oxide synthase (NOS) genes (knockout) and control (wild-type) mice were implanted intra-abdominally with battery-operated miniature biotelemeters (model VMFH MiniMitter, Sunriver, OR) to monitor changes in body temperature. Intravenous injection of lipopolysaccharide (LPS; 50 μg/kg) was used to trigger fever in response to systemic inflammation in mice. To induce a febrile response to localized inflammation, the mice were injected subcutaneously with pure turpentine oil (30 μl/animal) into the left hindlimb. Oral administration (gavage) of N G-monomethyl-l-arginine (l-NMMA) for 3 days (80 mg · kg−1 · day−1in corn oil) before injection of pyrogens was used to inhibit all three NOSs ( N G-monomethyl-d-arginine acetate salt and corn oil were used as control). In normal male C57BL/6J mice, l-NMMA inhibited the LPS-induced fever by ∼60%, whereas it augmented fever by ∼65% in mice injected with turpentine. Challenging the respective NOS knockout mice with LPS and with l-NMMA revealed that inducible NOS and neuronal NOS isoforms are responsible for the induction of fever to LPS, whereas endothelial NOS (eNOS) is not involved. In contrast, none of the NOS isoforms appeared to trigger fever to turpentine. Inhibition of eNOS, however, exacerbates fever in mice treated with l-NMMA and turpentine, indicating that eNOS participates in the antipyretic mechanism. These data support the hypothesis that nitric oxide is a regulator of fever. Its action differs, however, depending on the pyrogen used and the NOS isoform.
Level and duration of developmental hyperoxia influence impairment of hypoxic phrenic responses in rats
Authors: Bavis R. W. , Olson E. B. , Vidruk E. H. , Bisgard G. E. , Mitchell G. S.
Published: March 2015

Developmental hyperoxia (1-4 wk of 60% O2) causes long-lasting impairment of hypoxic phrenic responses in rats. We hypothesized that shorter or less severe hyperoxic exposures would produce similar changes. Hypoxic phrenic responses were measured in 3- to 5-mo-old, urethane-anesthetized rats exposed to 60% O2for postnatal day 1 or week 1 or to 30% O2for postnatal week 1. Whereas 1 day of 60% O2had no lasting effects ( P > 0.05 vs. control), both 1 wk of 60% O2and 1 wk of 30% O2decreased adult hypoxic phrenic responses ( P < 0.05 vs. control), although the effects of 30% O2were smaller. Hypoxic ventilatory responses (expressed as the ratio of minute ventilation to metabolic CO2production) were also reduced in unanesthetized rats (5-10 mo old) exposed to 1 wk of 60% O2during development ( P < 0.05). An age-dependent increase toward normal hypoxic phrenic responses was observed in rats exposed to 1 wk of 60% O2( P < 0.05), suggesting a degree of spontaneous recovery not observed after 1 mo of 60% O2. These data indicate that long-lasting effects of developmental hyperoxia depend on the level and duration of hyperoxic exposure.
Prepubertal Asians have less limb skeletal muscle
Authors: Song Mi-Yeon , Kim Jaehee , Horlick Mary , Wang Jack , Pierson Richard N. , Heo Moonseong , Gallagher Dympna
Published: March 2015

Skeletal muscle mass in prepubertal Asian children has not been examined previously. The aims of this study were to test the hypotheses that 1) prepubertal Asians have less appendicular skeletal muscle (ASM) mass compared with African-Americans and Caucasians, and 2) ASM is less in prepubertal Asian girls compared with Asian boys. ASM was estimated by using dual-energy X-ray absorptiometry in healthy prepubertal girls ( n = 170) and boys ( n= 166). The results showed that, after adjusting for age, height, and body weight, 1) Asian girls and boys had less amounts of ASM than African-Americans ( P < 0.001); 2) Asian girls had less amounts of ASM than Caucasian girls ( P = 0.004); 3) there was a trend towards less ASM in Asian compared with Caucasian boys ( P = 0.07); 4) and Asian girls had significantly less ASM than Asian boys ( P < 0.001). This study indicates that skeletal muscle mass as a fraction of body weight is smaller in Asian compared with African-American and Caucasian children.
Catecholaminergic microcircuitry controlling the output of airway-related vagal preganglionic neurons
Authors: Haxhiu Musa A. , Kc Prabha , Neziri Burim , Yamamoto Bryan K. , Ferguson Donald G. , Massari V. John
Published: March 2015

In this study, we have investigated the ultrastructure and function of the catecholaminergic circuitry modulating the output of airway-related vagal preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed to characterize the nature of catecholaminergic innervation of AVPN at the ultrastructural level. In addition, immunofluorescence was used to examine the expression of the α2A-adrenergic receptor (α2A-AR) on AVPNs, and norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by using microdialysis. Physiological experiments were performed to determine the effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on airway smooth muscle tone. The results showed that 1) catecholaminergic nerve endings terminate in the vicinity of identified AVPNs but very rarely form axosomatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the α2A-AR; 3) LC stimulation-induced norepinephrine release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of α2A-AR on AVPNs diminished the inhibitory effects of LC stimulation on airway smooth muscle tone. It is concluded that a noradrenergic circuit originating within the LC is involved in the regulation of AVPN activity within the rNA, and stimulation of the LC dilates the airways by the release of norepinephrine and activation of α2A-AR expressed by AVPNs, mainly via volume transmission.
Effects of sprint training on contractility and [Ca2+]itransients in adult rat myocytes
Authors: Zhang Xue-Qian , Song Jianliang , Carl Lois L. , Shi Weixing , Qureshi Anwer , Tian Qiang , Cheung Joseph Y.
Published: March 2015

The effects of 6–8 wk of high-intensity sprint training (HIST) on rat myocyte contractility and intracellular Ca2+concentration ([Ca2+]i) transients were investigated. Compared with sedentary (Sed) myocytes, HIST induced a modest (5%) but significant ( P < 0.0005) increase in cell length with no changes in cell width. In addition, the percentage of myosin heavy chain α-isoenzyme increased significantly ( P < 0.02) from 0.566 ± 0.077% in Sed rats to 0.871 ± 0.006% in HIST rats. At all three (0.6, 1.8, and 5 mM) extracellular Ca2+concentrations ([Ca2+]o) examined, maximal shortening amplitudes and maximal shortening velocities were significantly ( P < 0.0001) lower and half-times of relaxation were significantly ( P < 0.005) longer in HIST myocytes. HIST myocytes had significantly ( P < 0.0001) higher diastolic [Ca2+]ilevels. Compared with Sed myocytes, systolic [Ca2+]ilevels in HIST myocytes were higher at 0.6 mM [Ca2+]o, similar at 1.8 mM [Ca2+]o, and lower at 5 mM [Ca2+]o. The amplitudes of [Ca2+]itransients were significantly ( P < 0.0001) lower in HIST myocytes. Half-times of [Ca2+]itransient decline, an estimate of sarcoplasmic reticulum (SR) Ca2+uptake activity, were not different between Sed and HIST myocytes. Compared with Sed hearts, Western blots demonstrated a significant ( P < 0.03) threefold decrease in Na+/Ca2+exchanger, but SR Ca2+-ATPase and calsequestrin protein levels were unchanged in HIST hearts. We conclude that HIST effected diminished myocyte contractile function and [Ca2+]itransient amplitudes under the conditions studied. We speculate that downregulation of Na+/Ca2+exchanger may partly account for the decreased contractility in HIST myocytes.
Selected Contribution: Aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries
Authors: Woodman Christopher R. , Price Elmer M. , Laughlin M. Harold
Published: March 2015

We tested the hypothesis that endothelium-dependent dilation in soleus muscle feed arteries (SFA) is impaired by aging due to attenuated nitric oxide (NO)-mediated vasodilation. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two glass micropipettes for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. Flow- and ACh-induced dilation was significantly attenuated by age, whereas dilation to SNP was not compromised. To determine the mechanism(s) by which aging affected dilator responses to flow and ACh, dilation was assessed in the presence of Nω-nitro-l-arginine (l-NNA; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), and l-NNA + Indo. In the presence of l-NNA, Indo, or l-NNA + Indo, flow-induced dilation was inhibited in young SFA, resulting in a response to flow that was no longer greater than old SFA. In the presence of l-NNA or Indo, ACh-induced dilation was not significantly inhibited in young or old SFA; however, double blockade with l-NNA + Indo inhibited ACh-induced dilation in young SFA such that the response to ACh was no longer greater than old SFA. Collectively, these data indicate that aging impairs vasodilator responses in SFA by attenuating NO- and prostacyclin-mediated, endothelium-dependent, dilation.
Endogenous nitric oxide modulates responses of tissue and airway resistance to vagal stimulation in piglets
Authors: Khassawneh Mohammad Y. , Dreshaj Ismail A. , Liu Shijian , Chang Chung-Ho , Haxhiu Musa A. , Martin Richard J.
Published: March 2015

The role of endogenous nitric oxide (NO) in modulating the excitatory response of distal airways to vagal stimulation is unknown. In decerebrate, ventilated, open-chest piglets aged 3–10 days, lung resistance (Rl) was partitioned into tissue resistance (Rti) and airway resistance (Raw) by using alveolar capsules. Changes in Rl, Rti, and Raw were evaluated during vagal stimulation at increasing frequency before and after NO synthase blockade with N ω-nitro-l-arginine methyl ester (l-NAME). Vagal stimulation increased Rl by elevating both Rti and Raw. NO synthase blockade significantly increased baseline Rti, but not Raw, and significantly augmented the effects of vagal stimulation on both Rti and Raw. Vagal stimulation also resulted in a significant increase in cGMP levels in lung tissue before, but not after, l-NAME infusion. In seven additional piglets after Rl was elevated by histamine infusion in the presence of cholinergic blockade with atropine, vagal stimulation failed to elicit any change in Rl, Rti, or Raw. Therefore, endogenous NO not only plays a role in modulating baseline Rti, but it opposes the excitatory cholinergic effects on both the tissue and airway components of Rl. We speculate that activation of the NO/cGMP pathway during cholinergic stimulation plays an important role in modulating peripheral as well as central contractile elements in the developing lung.