bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of muscle activation on fatigue and metabolism in human skeletal muscle
Authors: Russ David W. , Vandenborne Krista , Walter Glenn A. , Elliott Mark , Binder-Macleod Stuart A.
Published: March 2015

Increasing stimulation frequency has been shown to increase fatigue but not when the changes in force associated with changes in frequency have been controlled. An effect of frequency, independent of force, may be associated with the metabolic cost resulting from the additional activations. Here, two separate experiments were performed on human medial gastrocnemius muscles. The first experiment ( n = 8) was designed to test the effect of the number of pulses on fatigue. The declines in force during two repetitive, 150-train stimulation protocols that produced equal initial forces, one using 80-Hz trains and the other using 100-Hz trains, were compared. Despite a difference of 600 pulses (23.5%), the protocols produced similar rates and amounts of fatigue. In the second experiment, designed to test the effect of the number of pulses on the metabolic cost of contraction,31P-NMR spectra were collected ( n = 6) during two ischemic, eight-train stimulation protocols (80- and 100-Hz) that produced comparable forces despite a difference of 320 pulses (24.8%). No differences were found in the changes in Pi concentration, phosphocreatine concentration, and intracellular pH or in the ATP turnover produced by the two trains. These results suggest that the effect of stimulation frequency on fatigue is related to the force produced, rather than to the number of activations. In addition, within the range of frequencies tested, increasing total activations did not increase metabolic cost.
Enhancement of whole body glucose uptake during and after human skeletal muscle low-frequency electrical stimulation
Authors: Hamada Taku , Sasaki Hideki , Hayashi Tatsuya , Moritani Toshio , Nakao Kazuwa
Published: March 2015

There is considerable evidence to suggest that electrical stimulation (ES) activates glucose uptake in rodent skeletal muscle. It is, however, unknown whether ES can lead to similar metabolic enhancement in humans. We employed low-frequency ES through surface electrodes placed over motor points of quadriceps femoris muscles. In male subjects lying in the supine position, the highest oxygen uptake was obtained by a stimulation pattern with 0.2-ms biphasic square pulses at 20 Hz and a 1-s on-off duty cycle. Oxygen uptake was increased by approximately twofold throughout the 20-min stimulation period and returned to baseline immediately after stimulation. Concurrent elevation of the respiratory exchange ratio and blood lactate concentration indicated anaerobic glycogen breakdown and utilization during ES. Whole body glucose uptake determined by the glucose disposal rate during euglycemic clamp was acutely increased by 2.5 mg · kg−1 · min−1in response to ES and, moreover, remained elevated by 3–4 mg · kg−1 · min−1for at least 90 min after cessation of stimulation. Thus the stimulatory effect of ES on whole body glucose uptake persisted not only during, but also after, stimulation. Low-frequency ES may become a useful therapeutic approach to activate energy and glucose metabolism in humans.
Selected Contribution: Classical conditioning of breathing pattern after two acquisition trials in 2-day-old mice
Authors: Durand E. , Dauger S. , Vardon G. , Gressens P. , Gaultier C. , de Schonen S. , Gallego J.
Published: March 2015

The aim of the present study was to test whether breathing pattern conditioning may occur just after birth. We hypothesized that sensory stimuli signaling the resumption of maternal care after separation may trigger an arousal and/or orienting response accompanied with concomitant respiratory changes. We performed a conditioning experiment in 2-day-old mice by using an odor (lemon) as the conditioned stimulus (CS) and maternal care after 1 h without the mother as the unconditioned stimulus (US). Each pup underwent two acquisition trials, in which the CS was presented immediately before (experimental paired group, n = 30) or 30 min before (control unpaired group, n = 30) contact with the mother. Conditioning was tested by using noninvasive whole body plethysmography to measure the respiratory response to the CS for 1 min. We found significantly stronger respiratory responses to the CS in the experimental group than in the control group. In contrast, somatomotor activity did not differ significantly between groups. Our results confirm the sensitivity of breathing to conditioning and indirectly support the hypothesis that learned feedforward processes may complement feedback pathways during postnatal maturation of respiratory control.
Effect of habitual running on human Achilles tendon load-deformation properties and cross-sectional area
Authors: Hansen P. , Aagaard P. , Kjaer M. , Larsson B. , Magnusson S. P.
Published: March 2015

Whether the cross-sectional area (CSA) and mechanical properties of the human Achilles tendon change in response to habitual exercise remains largely unexplored. The present study evaluated the CSA and contraction-induced displacement of the aponeurosis-tendon complex of the triceps surae in 11 untrained subjects before ( tests 1 and 2) and after ( test 3) ∼9 mo of regular running (∼78 training sessions). Displacement of the tendon-aponeurosis complex obtained by ultrasonography; electromyography of the gastrocnemius, soleus, and dorsiflexor muscles; and joint angular rotation were recorded during graded isometric plantarflexion ramps. Tendon CSA and moment arm were measured by using MRI, and tendon force was calculated from joint moments and tendon moment arm. A treadmill test was used to determine submaximal oxygen consumption (V̇o2) at a given speed and maximal V̇o2. The total running duration was ∼43 h, distributed over 34 wk. Maximal V̇o2 increased 8.6% ( P < 0.01), and submaximal V̇o2 decreased 6.2% ( P < 0.05). Tendon-aponeurosis displacement during maximal voluntary contraction was unchanged ( tests 1–3, 5.2 ± 0.6, 5.2 ± 0.5, and 5.3 ± 0.4 mm, respectively) and yielded a structural stiffness of 365 ± 50, 358 ± 40, and 384 ± 52 N/mm for tests 1–3, respectively ( P > 0.05). Tendon CSA also remained unchanged ( tests 1–3, 34.2 ± 2.2, 33.9 ± 2.2, and 33.8 ± 2.1 mm2, respectively). In conclusion, a total training stimulus of ∼9 mo of running in previously untrained subjects was adequate to induce significant cardiovascular improvements, although it did not result in any changes in the mechanical properties of the triceps surea tendon-aponeurosis complex or in the dimensions of Achilles tendon.
Exercise training alters an anoxia-induced, glibenclamide-sensitive current in rat ventricular cardiocytes
Authors: Jew Korinne N. , Moore Russell L.
Published: March 2015

The effect of training on properties of a sarcolemmal ATP-sensitive K+ current ( I KATP ) was examined in left ventricular cardiocytes isolated from sedentary (Sed) and trained (Tr) female Sprague-Dawley rats. Whole cell patch-clamp techniques were used to characterize I KATP , an anoxia-inducible, glibencamide-sensitive current. An anoxic condition was induced by superfusing cells with a buffer that was equilibrated with 100% N2, maintained under a layer of argon, and that contained 2-deoxy-d-glucose. Over a 1-h period of anoxia, 59% of Tr cells and 85% Sed cells expressed I KATP . In those cells that did express I KATP , the time to expression of the current during the anoxic period occurred significantly later in cells from the Tr group compared with the Sed. Peak I KATP density was significantly lower in the Tr cells compared with the Sed cells. These results indicate that the onset and magnitude of I KATP were altered by training. These alterations in I KATP may be reflective of processes that contribute to training-induced cardioprotection against ischemia-reperfusion damage.
Invited Review: Neuroplasticity in respiratory motor control
Authors: Mitchell Gordon S. , Johnson Stephen M.
Published: March 2015

Although recent evidence demonstrates considerable neuroplasticity in the respiratory control system, a comprehensive conceptual framework is lacking. Our goals in this review are to define plasticity (and related neural properties) as it pertains to respiratory control and to discuss potential sites, mechanisms, and known categories of respiratory plasticity. Respiratory plasticity is defined as a persistent change in the neural control system based on prior experience. Plasticity may involve structural and/or functional alterations (most commonly both) and can arise from multiple cellular/synaptic mechanisms at different sites in the respiratory control system. Respiratory neuroplasticity is critically dependent on the establishment of necessary preconditions, the stimulus paradigm, the balance between opposing modulatory systems, age, gender, and genetics. Respiratory plasticity can be induced by hypoxia, hypercapnia, exercise, injury, stress, and pharmacological interventions or conditioning and occurs during development as well as in adults. Developmental plasticity is induced by experiences (e.g., altered respiratory gases) during sensitive developmental periods, thereby altering mature respiratory control. The same experience later in life has little or no effect. In adults, neuromodulation plays a prominent role in several forms of respiratory plasticity. For example, serotonergic modulation is thought to initiate and/or maintain respiratory plasticity following intermittent hypoxia, repeated hypercapnic exercise, spinal sensory denervation, spinal cord injury, and at least some conditioned reflexes. Considerable work is necessary before we fully appreciate the biological significance of respiratory plasticity, its underlying cellular/molecular and network mechanisms, and the potential to harness respiratory plasticity as a therapeutic tool.
Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols
Authors: Usmani Omar S. , Biddiscombe Martyn F. , Nightingale Julia A. , Underwood S. Richard , Barnes Peter J.
Published: March 2015

Aerosol particle size influences airway drug deposition. Current inhaler devices are inefficient, delivering a heterodisperse distribution of drug particle sizes where, at best, 20% reaches the lungs. Monodisperse aerosols are the appropriate research tools to investigate basic aerosol science concepts within the human airways. We hypothesized that engineering such aerosols of albuterol would identify the ideal bronchodilator particle size, thereby optimizing inhaled therapeutic drug delivery. Eighteen stable mildly to moderately asthmatic patients [mean forced expiratory volume in 1 s (FEV1) 74.3% of predicted] participated in a randomized, double-blind, crossover study design. A spinning-top aerosol generator was used to produce monodisperse albuterol aerosols that were 1.5, 3, and 6 μm in size, and also a placebo, which were inhaled at cumulative doses of 10, 20, 40, and 100 μg. Lung function changes and tolerability effects were determined. The larger particles, 6 and 3 μm, were significantly more potent bronchodilators than the 1.5-μm and placebo aerosols for FEV1and for the forced expiratory flow between exhalation of 25 and 75% of forced vital capacity. A 20-μg dose of the 6- and 3-μm aerosols produced FEV1bronchodilation comparable to that produced by 200 μg from a metered-dose inhaler. No adverse effects were observed in heart rate and plasma potassium. The data suggest that in mildly to moderately asthmatic patients there is more than one optimal β2-agonist bronchodilator particle size and that these are larger particles in the higher part of the respirable range. Aerosols delivered in monodisperse form can enable large reductions of the inhaled dose without loss of clinical efficacy.
Effect of body temperature during exercise on skeletal muscle cytochromecoxidase content
Authors: Mitchell Christopher R. , Harris M. Brennan , Cordaro Anthony R. , Starnes Joseph W.
Published: March 2015

This study determined the role of body temperature during exercise on cytochrome- c oxidase (CytOx) activity, a marker of mitochondrial content, and mitochondrial heat shock protein 70 (mtHSP70), which is required for import of nuclear-coded preproteins. Male, 10-wk-old, Sprague-Dawley rats exercised identically for 9 wk in ambient temperatures of 23°C ( n = 10), 8°C with wetted fur ( n = 8), and 4°C with wetted fur and fan ( n = 7). These conditions maintained exercising core temperature (Tc) at 40.4, 39.2, or 38.0°C (resting temperature), respectively. During weeks 3–9, exercisers ran 5 days/wk up a 6% grade at 20 m/min for 60 min. Animals were housed at 23°C. Gastrocnemius CytOx activity in Tc=38.0°C (83.5 ± 5.5 μatoms O · min−1· g wet wt−1) was greater than all other groups ( P< 0.05), exceeding sedentary ( n = 7) by 73.2%. Tcof 40.4 and 39.2°C also were higher than sedentary by 22.4 and 37.4%, respectively ( P < 0.05). Quantification of CytOx content verified that the increased activity was due to an increase in protein content. In extensor digitorum longus, a nonactive muscle, CytOx was not elevated in Tc= 38.0°C. mtHSP70 was significantly elevated in gastrocnemius of Tc= 38.0°C compared with sedentary ( P < 0.05) but was not elevated in extensor digitorum longus ( P > 0.05). The data indicate that decreasing exercise Tcmay enhance mitochondrial biogenesis and that mtHSP70 expression is not dependent on temperature.
Gender differences in upper airway compliance during NREM sleep: role of neck circumference
Authors: Rowley James A. , Sanders Carrie S. , Zahn Brian R. , Badr M. Safwan
Published: March 2015

It has been proposed that the gender difference in sleep apnea prevalence is related to gender differences in upper airway structure and function. We hypothesized that men would have smaller retropalatal cross-sectional area and higher compliance during sleep compared with women. Using upper airway imaging, we measured upper airway cross-sectional area and retropalatal compliance in wakefulness and non-rapid eye movement (NREM) sleep in 15 men and 15 women without sleep-disordered breathing. Cross-sectional area at the beginning of inspiration tended to be larger in men compared with women in both wakefulness [194.5 ± 21.3 vs. 138.8 ± 12.0 (SE) mm2] and NREM sleep (111.1 ± 17.6 vs. 83.3 ± 11.9 mm2; P = 0.058). There was no significant difference, however, after correction for body surface area. Retropalatal compliance also tended to be higher in men during both wakefulness (5.9 ± 1.4 vs. 3.1 ± 1.4 mm2/cmH2O; P = 0.006) and NREM sleep (12.6 ± 2.7 vs. 4.7 ± 2.6 mm2/cmH2O; P = 0.055). However, compliance was similar in men relative to women after correction for neck circumference. We conclude that the gender difference in retropalatal compliance is more accurately attributed to differences in neck circumference between the genders.
Estradiol increases salt intake in female normotensive and hypertensive rats
Authors: Kensicki Eric , Dunphy Gail , Ely Daniel
Published: March 2015

The objective of this study was to examine whether or not estradiol (E2) alters sodium intake in hypertensive and normotensive female rats. It was hypothesized that higher doses of E2 would increase sodium consumption and that this response would be greater in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto (WKY) rats. The study involved female SHR and WKY ( n = 12/group). All animals were ovariectomized. Six of twelve rats from each strain received three progressively larger doses of β-estradiol propionate (each dose lasting 2 wk), whereas the other six rats from each strain received sham implants. Blood E2 levels were measured by radioimmunoassay after each 2-wk period, allowing a 10-day washout period before the next E2 dose. Rats had access to 0.0, 0.5, 1.0, and 1.5% NaCl solutions to drink throughout the experiment. There was a significant positive correlation between sodium intake and plasma E2 ( r = 0.8, P < 0.001). Both strains avoided the 1.5% NaCl, and the increased sodium intake was achieved by an increase in consumption of the 0.5% NaCl. SHR females consumed more sodium than WKY females, which is similar to what has been observed in males of these strains. In conclusion, E2 was positively correlated with sodium intake in both strains of rat, with the hypertensive rats consuming more sodium than the normotensive rats.
Noradrenergic content and turnover rate in kidney and heart shows gender and strain differences
Authors: Caplea Ann , Seachrist Darcie , Daneshvar Hamid , Dunphy Gail , Ely Daniel
Published: March 2015

The objective of this study was to compare strain and gender differences in kidney and heart norepinephrine (NE) content and turnover rate in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR, SHR/a, and SHR/y). Our laboratory has shown that the Y chromosome has a significant effect on blood pressure in the SHR model of hypertension through the use of two new rat stains, SHR/a and SHR/y, to study the Y chromosome. SHR/a have a SHR autosomal genetic background with a WKY Y chromosome, whereas the SHR/y rats have a WKY autosomal genetic background with a SHR Y chromosome. Tissues were homogenized after α-methyl-dl- p-tyrosine injection and analyzed for NE. The male kidney NE content was significantly lower in the WKY compared with the SHR, SHR/y, and SHR/a. Kidney and heart NE content was significantly higher in females compared with males in all strains except the SHR/y. The WKY and SHR/y females had significantly lower kidney NE turnover rates, and the SHR and SHR/a females had significantly higher kidney NE turnover rates than strain-matched males. This study suggests both a strain and gender difference in sympathetic nervous system activity through noradrenergic neurotransmission.
Calculation of physiological acid-base parameters in multicompartment systems with application to human blood
Authors: Wooten E. Wrenn
Published: March 2015

A general formalism for calculating parameters describing physiological acid-base balance in single compartments is extended to multicompartment systems and demonstrated for the multicompartment example of human whole blood. Expressions for total titratable base, strong ion difference, change in total titratable base, change in strong ion difference, and change in Van Slyke standard bicarbonate are derived, giving calculated values in agreement with experimental data. The equations for multicompartment systems are found to have the same mathematical interrelationships as those for single compartments, and the relationship of the present formalism to the traditional form of the Van Slyke equation is also demonstrated. The multicompartment model brings the strong ion difference theory to the same quantitative level as the base excess method.
Nonreversible conductive airway ventilation heterogeneity in mild asthma
Authors: Verbanck Sylvia , Schuermans Daniël , Paiva Manuel , Vincken Walter
Published: March 2015

A multiple-breath washout technique was used to assess residual ventilation heterogeneity in the conductive and acinar lung zones of asthmatic patients after maximal β2-agonist reversibility. Reversibility was assessed in 13 patients on two separate visits corresponding to a different baseline condition in terms of forced expiratory volume in 1 s [FEV1; average FEV1 over 2 visits: 92 ± 21% of predicted (SE)]. On the visit corresponding to each patient's best baseline, 400 μg salbutamol led to normal acinar ventilation heterogeneity, normal FEV1, and normal peak expiratory flow; i.e., none was significantly different from that obtained in 13 matched controls. By contrast, conductive ventilation heterogeneity and forced expiratory flow after exhalation of 75% forced vital capacity remained significantly different from controls ( P ≤ 0.005 on both indexes). In addition, the degree of postdilation conductive ventilation heterogeneity was similar to what was previously obtained in asthmatic individuals with a 19% lower baseline FEV1and twofold larger acinar ventilation heterogeneity (Verbanck S, Schuermans D, Noppen M, Van Muylem A, Paiva M, and Vincken W. Am J Respir Crit Care Med 159: 1545–1550, 1999). We conclude that, even in the mildest forms of asthma, the most consistent pattern of non-β2-agonist-reversible ventilatory heterogeneity is in the conductive lung zone, most probably in the small conductive airways.
Mapping of movement in the isometrically contracting human soleus muscle reveals details of its structural and functional complexity
Authors: Finni Taija , Hodgson John A. , Lai Alex M. , Edgerton V. Reggie , Sinha Shantanu
Published: March 2015

It is becoming increasingly apparent that precise knowledge of the anatomic features of muscle, aponeurosis, and tendons is necessary for understanding how a muscle-tendon complex generates force and accomplishes length changes. This report presents both anatomic and functional data from the human soleus muscle acquired by using magnetic resonance imaging. The results show a strong relationship between the complex three-dimensional structure of the muscle-tendon system and the intramuscular distribution of tissue velocities during in vivo isometric contractions. The proximal region of the muscle is unipennate, whereas the midregion has a radially bipennate hemicylindrical structure, and the distal region is quadripennate. Tissue velocity mapping shows that the highest velocity regions overlay the aponeuroses connected to the Achilles tendon. These are located on the anterior and posterior surfaces of the muscle. The lowest velocities overlay the aponeuroses connected to the origin of the muscle and are generally located intramuscularly.
Extended high-frequency partial liquid ventilation in lung injury: gas exchange, injury quantification, and vapor loss
Authors: Doctor Allan , Al-Khadra Eman , Tan Puay , Watson Kenneth F. , Diesen Diana L. , Workman Lisa J. , Thompson John E. , Rose Charles E. , Arnold John H.
Published: March 2015

High-frequency oscillatory ventilation with perflubron (PFB) reportedly improves pulmonary mechanics and gas exchange and attenuates lung injury. We explored PFB evaporative loss kinetics, intrapulmonary PFB distribution, and dosing strategies during 15 h of high-frequency oscillation (HFO)-partial liquid ventilation (PLV). After saline lavage lung injury, 15 swine were rescued with high-frequency oscillatory ventilation ( n = 5), or in addition received 10 ml/kg PFB delivered to dependent lung [ n = 5, PLV-compartmented (PLV(C))] or 10 ml/kg distributed uniformly within the lung [ n = 5, PLV(U)]. In the PLV(C) group, PFB vapor loss was replaced. ANOVA revealed an unsustained improvement in oxygenation index in the PLV(U) group ( P = 0.04); the reduction in oxygenation index correlated with PFB losses. Although tissue myeloperoxidase activity was reduced globally by HFO-PLV ( P < 0.01) and regional lung injury scores (lung injury scores) in dependent lung were improved ( P = 0.05), global lung injury scores were improved by HFO-PLV ( P < 0.05) only in atelectasis, edema, and alveolar distension but not in cumulative score. In our model, markers of inflammation and lung injury were attenuated by HFO-PLV, and it appears that uniform intrapulmonary PFB distribution optimized gas exchange during HFO-PLV; additionally, monitoring PFB evaporative loss appears necessary to stabilize intrapulmonary PFB volume.
Effect of nitric oxide on exercise-induced proteinuria in rats
Authors: Gündüz Filiz , Kuru Oktay , Şentürk Ümit Kemal
Published: March 2015

Temporary proteinuria occurring after exercise is a common finding, and it is explained predominantly by alterations in renal hemodynamics. In this study, we investigated whether nitric oxide (NO), which is known to have an effect on renal hemodynamics and to increase during exercise, has a role in postexercise proteinuria. In the first step of this study, the effect of acute NO synthase blockage on exercise proteinuria was evaluated. The urinary protein levels in animals that performed acute exhaustive treadmill running exercise were considerably elevated compared with the control animals. Significantly elevated urinary protein levels were also detected in animals that received Nω-nitro-L-arginine methyl ester before exhaustion, compared with both control and exhausted groups, and mixed-type proteinuria was detected in electrophoresis, as in all exhausted animals. In the second step of the study, a NO donor (isosorbide mononitrate) was given to rats 1 h before exhaustive exercise. Mixed-type proteinuria and the elevation in urinary protein levels that occur as a consequence of exhaustive exercise were prevented by NO donor treatment. Finally, in the third step of our study, a calcium channel blocker (diltiazem), another vasodilator, was applied to the rats 1 h before exhaustive exercise. Urinary protein levels were not different in exhausted rats with or without calcium channel blocker treatment. On the other hand, in both groups, urinary protein levels were higher than in the control group. The tail-cuff blood pressure alterations caused by vasodilator drug applications before exercise were not different for NO donor and calcium channel blocker groups. These results suggest that endogenous NO might prevent the postexercise proteinuria from becoming more severe by affecting hemodynamic changes that occur during exercise.
Cerebrovascular effects of intravenous dopamine infusions in fetal sheep
Authors: Gleason Christine A. , Robinson Roderick , Harris Andrew P. , Mayock Dennis E. , Traystman Richard J.
Published: March 2015

Preterm infants are often treated with intravenous dopamine to increase mean arterial blood pressure (MAP). However, there are few data regarding cerebrovascular responses of developing animals to dopamine infusions. We studied eight near-term and eight preterm chronically catheterized unanesthetized fetal sheep. We measured cerebral blood flow and calculated cerebral vascular resistance (CVR) at baseline and during dopamine infusion at 2.5, 7.5, 25, and 75 μg · kg−1· min−1. In preterm fetuses, MAP increased only at 75 μg · kg−1· min−1(25 ± 5%), whereas in near-term fetuses MAP increased at 25 μg · kg−1· min−1(28 ± 4%) and further at 75 μg · kg−1· min−1(51 ± 3%). Dopamine infusion was associated with cerebral vasoconstriction in both groups. At 25 μg · kg−1· min−1, CVR increased 77 ± 51% in preterm fetuses and 41 ± 11% in near-term fetuses, and at 75 μg · kg−1· min−1, CVR increased 80 ± 33% in preterm fetuses and 83 ± 21% in near-term fetuses. We tested these responses to dopamine in 11 additional near-term fetuses under α-adrenergic blockade (phenoxybenzamine, n = 5) and under dopaminergic D1-receptor blockade (SCH-23390, n = 6). Phenoxybenzamine completely blocked dopamine's pressor and cerebral vasoconstrictive effects, while D1-receptor blockade had no effect. Therefore, in unanesthetized developing fetuses, dopamine infusion is associated with cerebral vasoconstriction, which is likely an autoregulatory, α-adrenergic response to an increase in blood pressure.
Mechanisms contributing to knee extensor strength loss after prolonged running exercise
Authors: Millet G. Y. , Martin V. , Lattier G. , Ballay Y.
Published: March 2015

The aim of this study was to identify the mechanisms that contribute to the decline in knee extensor (KE) muscles strength after a prolonged running exercise. During the 2 days preceding a 30-km running race [duration 188.7 ± 27.0 (SD) min] and immediately after the race, maximal percutaneous electrical stimulations (single twitch, 0.5-s tetanus at 20 and 80 Hz) were applied to the femoral nerve of 12 trained runners. Superimposed twitches were also delivered during isometric maximal voluntary contraction (MVC) to determine the level of voluntary activation (%VA). The vastus lateralis electromyogram was recorded. KE MVC decreased from pre- to postexercise (from 188.1 ± 25.2 to 142.7 ± 29.7 N · m; P < 0.001) as did %VA (from 98.8 ± 1.8 to 91.3 ± 10.7%; P < 0.05). The changes from pre- to postexercise in these two variables were highly correlated ( R = 0.88; P < 0.001). The modifications in the mechanical response after the 80-Hz stimulation and M-wave peak-to-peak amplitude were also significant ( P < 0.001 and P < 0.05, respectively). It can be concluded that 1) central fatigue, neuromuscular propagation, and muscular factors are involved in the 23.5 ± 14.9% reduction in MVC after a prolonged running bout at racing pace and 2) runners with the greatest KE strength loss experience large activation deficit.
Invited Review: Plasticity in the control of breathing following sensory denervation
Authors: Forster H. V.
Published: March 2015

The purpose of this manuscript is to review the results of studies on the recovery or plasticity following a denervation- or lesion-induced change in breathing. Carotid body denervation (CBD), lung denervation (LD), cervical (CDR) and thoracic (TDR) dorsal rhizotomy, dorsal spinal column lesions, and lesions at pontine, medullary, and spinal sites all chronically alter breathing. The plasticity after these is highly variable, ranging from near complete recovery of the peripheral chemoreflex in rats after CBD to minimal recovery of the Hering-Breuer inflation reflex in ponies after LD. The degree of plasticity varies among the different functions of each pathway, and plasticity varies with the age of the animal when the lesion was made. In addition, plasticity after some lesions varies between species, and plasticity is greater in the awake than in the anesthetized state. Reinnervation is not a common mechanism of plasticity. There is evidence supporting two mechanisms of plasticity. One is through upregulation of an alternate sensory pathway, such as serotonin-mediated aortic chemoreception after CBD. The second is through upregulation on the efferent limb of a reflex, such as serotonin-mediated increased responsiveness of phrenic motoneurons after CDR, TDR, and spinal cord injury. Accordingly, numerous components of the ventilatory control system exhibit plasticity after denervation or lesion-induced changes in breathing; this plasticity is uniform neither in magnitude nor in underlying mechanisms. A major need in future research is to determine whether “reorganization” within the central nervous system contributes to plasticity following lesion-induced changes in breathing.
Hypercapnic cerebral vascular reactivity is decreased, in humans, during sleep compared with wakefulness
Authors: Meadows Guy E. , Dunroy Helen M. A. , Morrell Mary J. , Corfield Douglas R.
Published: March 2015

During wakefulness, increases in the partial pressure of arterial CO2 result in marked rises in cortical blood flow. However, during stage III–IV, non-rapid eye movement (NREM) sleep, and despite a relative state of hypercapnia, cortical blood flow is reduced compared with wakefulness. In the present study, we tested the hypothesis that, in normal subjects, hypercapnic cerebral vascular reactivity is decreased during stage III–IV NREM sleep compared with wakefulness. A 2-MHz pulsed Doppler ultrasound system was used to measure the left middle cerebral artery velocity (MCAV; cm/s) in 12 healthy individuals while awake and during stage III–IV NREM sleep. The end-tidal Pco 2(Pet CO2 ) was elevated during the awake and sleep states by regulating the inspired CO2 load. The cerebral vascular reactivity to CO2 was calculated from the relationship between Pet CO2 and MCAV by using linear regression. From wakefulness to sleep, the Pet CO2 increased by 3.4 Torr ( P < 0.001) and the MCAV fell by 11.7% ( P < 0.001). A marked decrease in cerebral vascular reactivity was noted in all subjects, with an average fall of 70.1% ( P = 0.001). This decrease in hypercapnic cerebral vascular reactivity may, at least in part, explain the stage III–IV NREM sleep-related reduction in cortical blood flow.
Nitric oxide mediates hypoxia-induced cerebral vasodilation in humans
Authors: Van Mil Annette H. M. , Spilt Aart , Van Buchem Mark A. , Bollen Edward L. E. M. , Teppema Luc , Westendorp Rudi G. J. , Blauw Gerard J.
Published: March 2015

Nitric oxide (NO) plays a pivotal role in the regulation of peripheral vascular tone. Its role in the regulation of cerebral vascular tone in humans remains to be elucidated. This study investigates the role of NO in hypoxia-induced cerebral vasodilatation in young healthy volunteers. The effect of the NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA) on the cerebral blood flow (CBF) was assessed during normoxia and during hypoxia (peripheral O2saturation 97 and 80%, respectively). Subjects were positioned in a magnetic resonance scanner, breathing normal air (normoxia) or a N2-O2 mixture (hypoxia). The CBF was measured before and after administration of l-NMMA (3 mg/kg) by use of phase-contrast magnetic resonance imaging techniques. Administration of l-NMMA during normoxia did not affect CBF. Hypoxia increased CBF from 1,049 ± 113 to 1,209 ± 143 ml/min ( P < 0.05). After l-NMMA administration, the augmented CBF returned to baseline (1,050 ± 161 ml/min; P < 0.05). Similarly, cerebral vascular resistance declined during hypoxia and returned to baseline after administration of l-NMMA ( P < 0.05 for both). Use of phase-contrast magnetic resonance imaging shows that hypoxia-induced cerebral vasodilatation in humans is mediated by NO.
High oxygen concentrations predispose mouse lungsto the deleterious effects of high stretch ventilation
Authors: Bailey Timothy C. , Martin Erica L. , Zhao Lin , Veldhuizen Ruud A. W.
Published: March 2015

Mechanical ventilation is a necessary intervention for patients with acute lung injury. However, mechanical ventilation can propagate acute lung injury and increase systemic inflammation. The exposure to >21% oxygen is often associated with mechanical ventilation yet has not been examined within the context of lung stretch. We hypothesized that mice exposed to >90% oxygen will be more susceptible to the deleterious effects of high stretch mechanical ventilation. C57B1/6 mice were randomized into 48-h exposure of 21 or >90% oxygen; mice were then killed, and isolated lungs were randomized into a nonstretch or an ex vivo, high-stretch mechanical ventilation group. Lungs were assessed for compliance and lavaged for surfactant analysis, and cytokine measurements or lungs were homogenized for surfactant-associated protein analysis. Mice exposed to >90% oxygen + stretch had significantly lower compliance, altered pulmonary surfactant, and increased inflammatory cytokines compared with all other groups. Our conclusion is that 48 h of >90% oxygen and high-stretch mechanical ventilation deleteriously affect lung function to a greater degree than stretch alone.
Tracking cardiac electrical instability by computing interlead heterogeneity of T-wave morphology
Authors: Nearing Bruce D. , Verrier Richard L.
Published: March 2015

Oscillations in T-wave morphology, particularly T-wave alternans (TWA), have been fundamentally linked to increased susceptibility to ventricular fibrillation (VF). We investigated whether the escalation in complexity of T-wave oscillations before VF is attributable to increased spatial heterogeneity of repolarization. Peak interlead T-wave heterogeneity (TWH) was measured by second central moment analysis of T-wave morphology in epicardial electrograms in dogs during left anterior descending coronary artery occlusion. TWH differentiated cases in which myocardial ischemia provoked VF from those without VF (563 ± 56 vs. 139 ± 36 μV, P < 0.01). In the former group, progressive, significant increases in TWH above preocclusion baseline (70 ± 8 μV) began at 2.25 min after the start of occlusion and were associated successively with TWA (at 155 ± 19 μV), T-wave multupling (at 386 ± 100 μV), complex oscillatory T-wave forms (at 560 ± 76 μV), discordant TWA (at 572 ± 98 μV), and VF at 4.36 ± 0.14 min. TWH in precordial ECGs in 12 pigs during angioplasty-balloon-induced myocardial ischemia also discriminated animals that experienced VF (from 90 ± 14 at baseline to 382 ± 39 μV, P < 0.05) from those without VF (from 96 ± 17 at baseline to 199 ± 61 μV, NS). Ischemia-induced changes in ST segment and T-wave amplitude did not predict VF. Heightened spatial heterogeneity of repolarization, as assessed by second central moment analysis of TWH, underlies TWA and increased risk for ischemia-induced VF. Monitoring spatial TWH from precordial leads could prove useful in stratifying risk for life-threatening arrhythmias.
Neural correlates of voluntary breathing in humans
Authors: McKay L. C. , Evans K. C. , Frackowiak R. S. J. , Corfield D. R.
Published: March 2015

To investigate the functional neuroanatomy of voluntary respiratory control, blood O2level-dependent functional magnetic resonance imaging was performed in six healthy right-handed individuals during voluntary hyperpnea. Functional images of the whole brain were acquired during 30-s periods of spontaneous breathing alternated with 30-s periods of isocapnic hyperpnea [spontaneous vs. voluntary: tidal volume = 0.5 ± 0.01 vs. 1.3 ± 0.1 (SE) liters and breath duration = 4.0 ± 0.4 vs. 3.2 ± 0.4 (SE) s]. For the group, voluntary hyperpnea was associated with significant ( P < 0.05, corrected for multiple comparisons) neural activity bilaterally in the primary sensory and motor cortices, supplementary motor area, cerebellum, thalamus, caudate nucleus, and globus pallidum. Significant increases in activity were also identified in the medulla (corrected for multiple comparisons on the basis of a small volume correction for a priori region of interest) in a superior dorsal position ( P = 0.012). Activity within the medulla suggests that the brain stem respiratory centers may have a role in mediating the voluntary control of breathing in humans.
Effects of age and gender on finger coordination in MVC and submaximal force-matching tasks
Authors: Shinohara Minoru , Li Sheng , Kang Ning , Zatsiorsky Vladimir M. , Latash Mark L.
Published: March 2015

The objective of the study is to examine the effects of age and gender on finger coordination. Twelve young (24 ± 8 yr; 6 men and 6 women) and 12 elderly (75 ± 5 yr; 6 men and 6 women) subjects performed single-finger maximal contraction [maximal voluntary contraction (MVC)], four-finger MVC, and four-finger ramp force production tasks by pressing on individual force transducers. A drop in the force of individual fingers during four-finger MVC tasks compared with single-finger MVC tasks (force deficit) was larger, whereas unintended force production by other fingers during single-finger MVC tasks (enslaving) was smaller, in elderly than in young subjects and in women than in men. Force deficit was smaller and enslaving was larger in subjects with higher peak force. During the ramp task, the difference between the variance of total force and the sum of variances of individual forces showed a logarithmic relation to the level of total force, across all subject groups. These findings suggest that indexes of finger coordination scale with force-generating capabilities across gender and age groups.
Fibroblast growth factor mediates hypoxia-induced endothelin-A receptor expression in lung artery smooth muscle cells
Authors: Li Peng , Oparil Suzanne , Sun Ju-Zhong , Thompson John A. , Chen Yiu-Fai
Published: March 2015

We have previously demonstrated that endothelin (ET)-1 and its subtype A receptor (ET-AR) expression are increased in lung under hypoxic conditions and that activation of ET-AR by ET-1 is a major mediator of hypoxia-induced pulmonary hypertension in the rat. The present study tested the hypothesis that the hypoxia-responsive tyrosine kinase receptor-activating growth factors fibroblast growth factor (FGF)-1, FGF-2, and platelet-derived growth factor (PDGF)-BB stimulate expression of the ET-AR in pulmonary arterial smooth muscle cells (PASMCs). Quiescent rat PASMCs were incubated under hypoxia (1% O2), or with FGF-1, FGF-2, PDGF-BB, vascular endothelial growth factor, ET-1, angiotensin II, or atrial natriuretic peptide under normoxic conditions for 24 h. FGF-1 and -2 and PDGF-BB, but not hypoxia, vascular endothelial growth factor, ET-1, angiotensin II, or atrial natriuretic peptide, significantly increased ET-AR mRNA levels. FGF-1-induced ET-AR expression was inhibited by FGF-receptor inhibitor PD-166866, MEK inhibitor U-0126, transcription inhibitor actinomycin D, and translation inhibitor cycloheximide. In contrast, the stimulatory effect of FGF-1 on ET-AR mRNA expression was not altered by PI3 kinase, PKA, PKC, or adenylate cyclase inhibitors. PASMC ET-AR gene transcription, assessed by nuclear-runoff analysis, was increased by FGF-1. These results provide novel finding that ET-AR in PASMCs in vitro is unresponsive to hypoxia per se but is robustly simulated by tyrosine kinase receptor-associated growth factors (FGF-1, FGF-2, PDGF-BB) that themselves are stimulated by hypoxia in lung. This observation suggests a novel signaling mechanism that may be responsible for overexpression of ET-AR in lung, and may contribute to the hypoxia-induced pulmonary vasoconstriction, hypertension, and vascular remodeling in hypoxia-adapted animal.
Relationship of airway narrowing, compliance, and cartilage in isolated bronchial segments
Authors: Noble P. B. , Turner D. J. , Mitchell H. W.
Published: March 2015

Structural components of the airway wall may act to load airway smooth muscle and restrict airway narrowing. In this study, the effect of load on airway narrowing was investigated in pig isolated bronchial segments. In some bronchi, pieces of cartilage were removed by careful dissection. Airway narrowing was produced by maximum electrical field stimulation. An endoscope was used to record lumen narrowing. The compliance of the bronchial segments was determined from the cross-sectional area of the lumen and the transmural pressure. Airway narrowing and the velocity of airway narrowing were increased in cartilage-removed airways compared with intact control bronchi. Morphometric assessment of smooth muscle length showed greater muscle shortening to acetylcholine in cartilage-removed airways than in controls. Airway narrowing was positively correlated with airway compliance. Compliance and area of cartilage were negatively correlated. These results show that airway narrowing is increased in compliant airways and that cartilage significantly loads airway smooth muscle in whole bronchi.
Potential role of vitamin D receptor gene polymorphism in determining bone phenotype in young male athletes
Authors: Nakamura Orie , Ishii Tomoo , Ando You , Amagai Hitoshi , Oto Masakazu , Imafuji Takahiro , Tokuyama Kumpei
Published: March 2015

The genetic difference among individuals partly explains variance in adaptive response to exercise through gene-environment interaction. The aim of this cross-sectional study was to evaluate the role of the vitamin D receptor (VDR) gene polymorphism, which locates at the translation initiation site, in the adaptations of bone to long-term impact loading. The VDR genotypes, as detected by endonuclease FokI, and bone phenotypes of the lumbar spine and femoral neck were examined in 44 highly trained young male athletes and 44 age-matched nonathletic controls. As a whole, the athletes had a significantly higher bone mineral content resulting from a combination of increased volume and density at both sites than the controls. When the athletes were compared with the controls within each VDR genotype, however, the increased spinal volume was found only in the athletes with the FF but not in those with the Ff genotype(“F” for the absence of the endonuclease Fok I restriction site and “f” for its presence). Differences in bone mineral content in the lumbar spine and femoral neck between the controls and the athletes were greater in subjects with FF than those with Ff. Our results suggest a gene-environment interaction in that the bone phenotypes in individuals with FF adapt to impact loading by producing stronger bone structure than those with the Ff do.
Energy cost and muscular activity required for propulsion during walking
Authors: Gottschall Jinger S. , Kram Rodger
Published: March 2015

We reasoned that with an optimal aiding horizontal force, the reduction in metabolic rate would reflect the cost of generating propulsive forces during normal walking. Furthermore, the reductions in ankle extensor electromyographic (EMG) activity would indicate the propulsive muscle actions. We applied horizontal forces at the waist, ranging from 15% body weight aiding to 15% body weight impeding, while subjects walked at 1.25 m/s. With an aiding horizontal force of 10% body weight, 1) the net metabolic cost of walking decreased to a minimum of 53% of normal walking, 2) the mean EMG of the medial gastrocnemius (MG) during the propulsive phase decreased to 59% of the normal walking magnitude, and yet 3) the mean EMG of the soleus (Sol) did not decrease significantly. Our data indicate that generating horizontal propulsive forces constitutes nearly half of the metabolic cost of normal walking. Additionally, it appears that the MG plays an important role in forward propulsion, whereas the Sol does not.
Shortening-induced depression of voluntary force in unfatigued and fatigued human adductor pollicis muscle
Authors: De Ruiter C. J. , De Haan A.
Published: March 2015

The goals of this study were to investigate adductor pollicis muscle ( n = 7) force depression after maximal electrically stimulated and voluntarily activated isovelocity (19 and 306°/s) shortening contractions and the effects of fatigue. After shortening contractions, redeveloped isometric force was significantly ( P < 0.05) depressed relative to isometric force obtained without preceding shortening. For voluntarily and electrically stimulated contractions, relative force deficits respectively were (means ± SE) 25.0 ± 3.5 and 26.6 ± 1.9% (19°/s), 7.8 ± 2.2 and 11.5 ± 0.6% (306°/s), and 23.9 ± 4.4 and 31.6 ± 4.7% (19°/s fatigued). The relative force deficit was significantly smaller after fast compared with slow shortening contractions, whereas activation manner and fatigue did not significantly affect the deficit. It was concluded that in unfatigued and fatigued muscle the velocity-dependent relative force deficit was similar with maximal voluntary activation and electrical stimulation. These findings have important implications for experimental studies of force-velocity relationships. Moreover, if not accounted for in muscle models, they will contribute to differences observed between the predicted and the actually measured performance during in vivo locomotion.
l-NAME differentially alters ventilatory behavior in Sprague-Dawley and Brown Norway rats
Authors: Subramanian Shyam , Erokwu Bernadette , Han Fang , Dick Thomas E. , Strohl Kingman P.
Published: March 2015

Nitric oxide (NO) is a regulating factor in respiration. The question was whether NO synthase (NOS) blockade would affect posthypoxic ventilatory behavior similarly in two rat strains with known differences in steady-state hypoxic and hypercapnic responses and in posthypoxic ventilatory behavior. Ventilatory behavior [respiratory frequency (f) and minute ventilation (V˙e)] was measured by body plethysmography on unanesthetized, unrestrained adult male Sprague-Dawley (SD; n= 8) and Brown Norway rats (BN; n = 8) at baseline and 1 min after rapid transition to 100% O2after 5 min of isocapnic hypoxia (10% O2-3% CO2-balance N2). Testing was performed 30 min after intraperitoneal injection of either saline (vehicle) or 100 mg/kg of NG-nitro-l-arginine methyl ester (l-NAME). Resting f and V˙e increased after l-NAME in both strains, more markedly in SD compared with BN (77 vs. 47% for f, and 42 vs. 16% for V˙e, respectively; P < 0.05). With vehicle, posthypoxic f and V˙e decline (Dejours phenomenon) was present only in BN and was absent in SD. With l-NAME, the Dejours phenomena were still present in BN but also were apparent in SD (f: 95.3 vs. 134.4 beats/min at baseline; V˙e: 66.3 vs. 88.8 ml/min at baseline; P < 0.05). Thus NOS blockade results in a strain-specific alteration in resting ventilation and uncovers the Dejours phenomenon in the SD strain.