bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of microvascular oxygen pressure in the rat diaphragm
Authors: Geer Crystal M. , Behnke Brad J. , McDonough Paul , Poole David C.
Published: March 2015

The relative amplitudes and rates of increase of muscle blood flow (and O2 delivery) and O2 uptake responses determine the O2pressure within the muscle microvasculature (PmO2 ) across the rest-to-contraction transition. Skeletal muscle function is a primary determinant of pulmonary O2 uptake kinetics; however, it has never been determined whether the dynamics of muscle PmO2 are faster in a highly oxidative muscle [e.g., diaphragm (Dia), citrate synthase activity of 39 μmol · min−1 · g−1] compared with less oxidative muscles [e.g., spinotrapezius (Spino), citrate synthase activity of 14 μmol · min−1 · g−1, male Sprague-Dawley rats; Delp MD and Duan C, J Appl Physiol80: 261–270, 1996]. Phosphorescence quenching techniques (porphyrin dendrimer, R2) were used to determine PmO2 across the transition to electrically stimulated contractions (1 Hz) within the rat Dia. After a delay of 10.4 ± 1.3 (SE) s at the beginning of Dia contractions, PmO2 decreased close to monoexponentially from 42 ± 2 to 27 ± 3 Torr ( P < 0.05) with an extremely fast time constant of 7.1 ± 1.1 s. Thus Dia PmO2 decreased with significantly ( P < 0.05) faster kinetics than reported previously for the Spino muscle (delay, 19.2 ± 2.8 s; time constant PmO2 , 21.7 ± 2.1 s; Behnke BJ, Kindig CA, Musch TI, Koga S, and Poole DC, Respir Physiol126: 53–63, 2001). With the use of two specialized muscles with similar fiber-type composition but widely disparate oxidative capacities (Delp MD and Duan C, J Appl Physiol 80: 261–270, 1996), these data demonstrate that PmO2 kinetics are significantly faster in the highly oxidative Dia compared with the low-oxidative Spino muscle and that this effect is not dependent on muscle fiber-type composition.
Aerobic power declines with aging in rat skeletal muscles perfused at matched convective O2 delivery
Authors: Hepple Russell T. , Hagen Jason L. , Krause Daniel J. , Jackson Cory C.
Published: March 2015

Although it is well established that maximal O2 uptake (V˙o 2 max) declines from adulthood to old age, the role played by alterations in skeletal muscle is unclear. Specifically, because during whole body exercise reductions in convective O2 delivery to the working muscles from adulthood to old age compromise aerobic performance, this obscures the influence of alterations within the skeletal muscles. We sought to overcome this limitation by using an in situ pump-perfused hindlimb preparation to permit matching of muscle convective O2delivery in young adult (8 mo; muscle convective O2delivery = 569 ± 42 μmol O2 · min−1 · 100 g−1) and late middle-aged (28–30 mo; 539 ± 62 μmol O2 · min−1 · 100 g−1) Fischer 344 × Brown Norway F1 hybrid rats. The distal hindlimb muscles were electrically stimulated for 4 min (60 tetani/min), and V˙o 2 max was determined.V˙o 2 max normalized to the contracting muscle mass was 22% lower in the 28- to 30-mo-old (344 ± 17 μmol O2 · min−1 · 100 g−1) than the 8-mo-old (441 ± 20 μmol O2 · min−1 · 100 g−1; P < 0.05) rats. The flux through the electron transport chain complexes I–III was 45% lower in homogenates prepared from the plantaris muscles of the older animals. Coincident with these alterations, the tension atV˙o 2 max and lactate efflux were reduced in the 28- to 30-mo-old animals, whereas the percent decline in tension was greater in the 28- to 30-mo-old vs. 8-mo-old animals. Collectively, these results demonstrate that alterations within the skeletal muscles, such as a reduced mitochondrial oxidative capacity, contribute to the reduction in V˙o 2 max with aging.
Antigen-induced airway inflammation in the Brown Norway rat results in airway smooth muscle hyperplasia
Authors: Xu K. F. , Vlahos R. , Messina A. , Bamford T. L. , Bertram J. F. , Stewart A. G.
Published: March 2015

Asthma is characterized by chronic airways inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR). An increase in airway smooth muscle has been proposed to explain a major part of AHR in asthma. We have used unbiased stereological methods to determine whether airway smooth muscle hyperplasia and AHR occurred in sensitized, antigen-challenged Brown Norway (BN) rats. Ovalbumin (OA)-sensitized BN rats chronically exposed to OA aerosol displayed airway inflammation and a modest level of AHR to intravenously administered ACh 24 h after the last antigen challenge. However, these animals did not show an increase in smooth muscle cell (SMC) number in the left main bronchus, suggesting that short-lived inflammatory mechanisms caused the acute AHR. In contrast, 7 days after the last aerosol challenge, there was a modest increase in SMC number, but no AHR to ACh. Addition of FCS to the chronic OA challenge protocol had no effect on the degree of inflammation but resulted in a marked increase in both SMC number and a persistent (7-day) AHR. These results raise the possibility that increases in airway SMC number rather than, or in addition to, chronic inflammation contribute to the persistent AHR detected in this model.
Respiratory response to activation or disinhibition of the dorsal periaqueductal gray in rats
Authors: Hayward Linda F. , Swartz Camille L. , Davenport Paul W.
Published: March 2015

The neural substrates mediating autonomic components of the behavioral defense response have been shown to reside in the periaqueductal gray (PAG). The cardiovascular components of the behavioral defense response have been well described and are tonically suppressed by GABAergic input. The ventilatory response associated with disinhibition of the dorsal PAG (dPAG) neurons is unknown. In urethane-anesthetized, spontaneously breathing rats, electrical stimulation of the dPAG was shown to decrease the expiration time and increase respiratory frequency, with no change in time of inspiration. Baseline and the change in diaphragm electromyograph also increased, resulting in an increase in neural minute activity. Microinjection of bicuculline methobromide, a GABAA-receptor antagonist, into the dPAG produced a similar response, which was dose dependent. Disinhibition of the dPAG also produced a decrease in inspiration time. These results suggest that GABAA-mediated suppression of dPAG neurons plays a role in the respiratory component of behavioral defense responses. The respiratory change is due in part to a change in brain stem respiratory timing and phasic inspiratory output. In addition, there is an increase in tonic diaphragm activity.
Impaired substrate oxidation in healthy elderly men after eccentric exercise
Authors: Krishnan Raj K. , Evans William J. , Kirwan John P.
Published: March 2015

The metabolic response to eccentric exercise in healthy older adults is unknown. Therefore, substrate metabolism was examined in the basal state and after sustained hyperglycemia (180 min, 10 mM) in eight healthy, sedentary older [66 ± 2 yr; body mass index (BMI) of 25.5 ± 1.2 kg/m] and nine younger (23 ± 1 yr; BMI of 23.6 ± 1.7 kg/m) men, under control conditions and 48 h after eccentric exercise. Indirect calorimetry was performed to evaluate carbohydrate and lipid oxidation (Coxand Lox, respectively). Eccentric exercise caused muscle soreness and increased plasma creatine kinase in both groups of men ( P < 0.02). Although a similar level of hyperglycemia was maintained in the two groups, glucose infusion rates were lower ( P < 0.001) in the older men. Compared with basal levels, hyperglycemia stimulated an increase in Coxand a decrease in Loxduring the control and exercise trials in the younger group ( P < 0.03), but only during the control trial in the older subjects ( P < 0.007). Coxwas unchanged after eccentric exercise in the younger men [4.00 ± 0.30 vs. 3.54 ± 0.44 mg · kg fat-free mass (FFM)−1· min−1; exercise vs. control] but was suppressed by 20% in the older group (3.37 ± 0.37 vs. 4.21 ± 0.23 mg · kg FFM−1· min−1; P < 0.04). Moreover, Loxwas reduced by 38% in the younger subjects (0.47 ± 0.09 vs. 0.76 ± 0.10 mg · kg FFM−1· min−1; P< 0.03) but was augmented by 89% in the older group (0.68 ± 0.11 vs. 0.36 ± 0.08 mg · kg FFM−1· min−1; P < 0.04). In addition, hyperglycemia-stimulated Cox, Lox, and respiratory exchange ratio responses to eccentric exercise were related to abdominal adiposity ( r = −0.57, P < 0.04, r = 0.68, P < 0.02 and r = −0.60, P < 0.02, respectively). Despite normal glucose tolerance and the absence of obesity per se, older men experience a reduction in carbohydrate oxidation in response to hyperglycemia after eccentric exercise.
Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells
Authors: Frohock Jeffrey I. , Wijkstrom-Frei Corrine , Salathe Matthias
Published: March 2015

β2-Adrenergic agonists stimulate ciliary beat frequency (CBF), an integral part of mucociliary clearance. To evaluate the differential effects of albuterol enantiomers and their racemic mixture on ciliary function, CBF and intracellular calcium were measured at room temperature from single ovine airway epithelial cells with use of digital videomicroscopy. Baseline CBF was 7.2 ± 0.2 (SE) Hz ( n = 80 measurements). R-albuterol (10 μM to 1 mM) stimulated CBF in a dose-dependent manner to maximally 24.4 ± 5.4% above baseline. Racemic albuterol stimulated CBF to maximally 12.8 ± 3.6% above baseline, a significantly lower increase compared with R-albuterol alone, despite identical R-enantiomer amounts in both groups. Simultaneous recordings of intracellular calcium concentration and CBF from single cells indicated that the CBF increase in response to R-albuterol was mediated through β-receptors and stimulation of protein kinase A, in a calcium-dependent and -independent fashion. S-albuterol had a negligible effect on CBF and did not change intracellular calcium. Together, these results suggest that R-albuterol is more efficacious than racemic albuterol in stimulating CBF. Thus S-albuterol may interfere with the ability of R-albuterol to increase CBF.
Silver ions induce Ca2+release from the SR in vitro by acting on the Ca2+release channel and the Ca2+pump
Authors: Tupling R. , Green H.
Published: March 2015

Silver nitrate (AgNO3) is a sulfhydryl oxidizing agent that induces a biphasic Ca2+release from isolated sarcoplasmic reticulum (SR) vesicles by presumably oxidizing critical sulfhydryl groups in the Ca2+release channel (CRC), causing the channel to open. To further examine the effects of AgNO3on the CRC and the Ca2+-ATPase, Ca2+release was measured in muscle homogenates prepared from rat hindlimb muscle using indo 1. Cyclopiazonic acid (CPA) and ruthenium red (RR) were used to inhibit the Ca2+-ATPase and block the CRC, respectively, before inducing Ca2+release with both AgNO3and 4-chloro- m-cresol (4-CMC), a releasing agent specific for the CRC. With AgNO3and CPA, the early rapid rate of release (phase 1) was increased ( P < 0.05) by 42% (314 ± 5 vs. 446 ± 39 μmol · g protein−1· min−1), whereas the slower, more prolonged rate of release (phase 2) was decreased ( P < 0.05) by 72% (267 ± 39 vs. 74 ± 7.7 μmol · g protein−1· min−1). RR, in combination with AgNO3, had no effect on phase 1 ( P > 0.05) (314 ± 51 vs. 334 ± 43 μmol · g protein−1· min−1) and decreased phase 2 ( P < 0.05) by 65% (245 ± 34 vs. 105 ± 8.2 μmol · g protein−1· min−1). With 4-CMC, CPA had no effect ( P > 0.05) on either phase 1 or 2. With addition of RR, phase 1 was reduced ( P < 0.05) by 59% (2,468 ± 279 vs. 1,004 ± 87 μmol · g protein−1· min−1), and RR completely blocked phase 2. Both AgNO3and 4-CMC fully inhibited Ca2+-ATPase activity measured in homogenates. These findings indicate that AgNO3, but not 4-CMC, induces Ca2+release by acting on both the CRC and the Ca2+-ATPase.
Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening
Authors: Bilek Anastacia M. , Dee Kay C. , Gaver Donald P.
Published: March 2015

Airway collapse and reopening due to mechanical ventilation exerts mechanical stress on airway walls and injures surfactant-compromised lungs. The reopening of a collapsed airway was modeled experimentally and computationally by the progression of a semi-infinite bubble in a narrow fluid-occluded channel. The extent of injury caused by bubble progression to pulmonary epithelial cells lining the channel was evaluated. Counterintuitively, cell damage increased with decreasing opening velocity. The presence of pulmonary surfactant, Infasurf, completely abated the injury. These results support the hypotheses that mechanical stresses associated with airway reopening injure pulmonary epithelial cells and that pulmonary surfactant protects the epithelium from this injury. Computational simulations identified the magnitudes of components of the stress cycle associated with airway reopening (shear stress, pressure, shear stress gradient, or pressure gradient) that may be injurious to the epithelial cells. By comparing these magnitudes to the observed damage, we conclude that the steep pressure gradient near the bubble front was the most likely cause of the observed cellular damage.
Gravitational deposition in a rhythmically expanding and contracting alveolus
Authors: Haber S. , Yitzhak D. , Tsuda A.
Published: March 2015

In a previous simulation, our laboratory demonstrated that the flow induced by a rhythmically expanding and contracting alveolus is highly complex (Haber S, Butler JP, Brenner H, Emanuel I, and Tsuda A, J Fluid Mech 405: 243–268, 2000). Based on these earlier findings, we hypothesize that the trajectories and deposition of aerosols inside the alveoli differ substantially from those previously predicted. To test this hypothesis, trajectories of fine particles (0.5–2.5 μm in diameter) moving in the foregoing alveolar flow field and simultaneously subjected to the gravity field were simulated. The results show that alveolar wall motion is crucial in determining the enhancement of aerosol deposition inside the alveoli. In particular, 0.5- to 1-μm-diameter particles are sensitive to the detailed alveolar flow structure (e.g., recirculating flow), as they undergo gravity-induced convective mixing and deposition. Accordingly, deposition concentrations within each alveolus are nonuniform, with preferentially higher densities near the alveolar entrance ring, consistent with physiological observations. Deposition patterns along the acinar tree are also nonuniform, with higher deposition in the first half of the acinar generations. This is a result of the combined effects of enhanced alveolar deposition in the proximal region of the acinus due to alveoli expansion and contraction and reduction in the number of particles remaining in the gas phase down the acinar tree. We conclude that the cyclically expanding and contracting motion of alveoli plays an important role in determining gravitational deposition in the pulmonary acinus.
Effect of cold exposure on fuel utilization in humans: plasma glucose, muscle glycogen, and lipids
Authors: Haman François , Péronnet François , Kenny Glen P. , Massicotte Denis , Lavoie Carole , Scott Chris , Weber Jean-Michel
Published: March 2015

The relative roles of circulatory glucose, muscle glycogen, and lipids in shivering thermogenesis are unclear. Using a combination of indirect calorimetry and stable isotope methodology ([U-13C]glucose ingestion), we have quantified the oxidation rates of these substrates in men acutely exposed to cold for 2 h (liquid conditioned suit perfused with 10°C water). Cold exposure stimulated heat production by 2.6-fold and increased the oxidation of plasma glucose from 39.4 ± 2.4 to 93.9 ± 5.5 mg/min (+138%), of muscle glycogen from 126.6 ± 7.8 to 264.2 ± 36.9 mg glucosyl units/min (+109%), and of lipids from 46.9 ± 3.2 to 176.5 ± 17.3 mg/min (+376%). Despite the observed increase in plasma glucose oxidation, this fuel only supplied 10% of the energy for heat generation. The major source of carbohydrate was muscle glycogen (75% of all glucose oxidized), and lipids produced as much heat as all other fuels combined. During prolonged, low-intensity shivering, we conclude that total heat production is unequally shared among lipids (50%), muscle glycogen (30%), plasma glucose (10%), and proteins (10%). Therefore, future research should focus on lipids and muscle glycogen that provide most of the energy for heat production.
Greater rate of decline in maximal aerobic capacity with age in endurance-trained than in sedentary men
Authors: Pimentel Annemarie E. , Gentile Christopher L. , Tanaka Hirofumi , Seals Douglas R. , Gates Phillip E.
Published: March 2015

To determine the relation between habitual endurance exercise status and the age-associated decline in maximal aerobic capacity [i.e., maximal O2consumption (V˙o2 max)] in men, we performed a well-controlled cross-sectional laboratory study on 153 healthy men aged 20–75 yr: 64 sedentary and 89 endurance trained.V˙o2 max(ml · kg−1· min−1), measured by maximal treadmill exercise, was inversely related to age in the endurance-trained ( r = −0.80) and sedentary ( r = −0.74) men but was higher in the endurance-trained men at any age. The rate of decline inV˙o2 maxwith age (ml · kg−1· min−1) was greater ( P < 0.001) in the endurance-trained than in the sedentary men. Whereas the relative rate of decline inV˙o2 max(percent decrease per decade from baseline levels in young adulthood) was similar in the two groups, the absolute rate of decline inV˙o2 maxwas −5.4 and −3.9 ml · kg−1· min−· decade−1in the endurance-trained and sedentary men, respectively.V˙o2 maxdeclined linearly across the age range in the sedentary men but was maintained in the endurance-trained men until ∼50 yr of age. The accelerated decline inV˙o2 maxafter 50 yr of age in the endurance-trained men was related to a decline in training volume ( r = 0.46, P < 0.0001) and was associated with an increase in 10-km running time ( r = −0.84, P < 0.0001). We conclude that the rate of decline in maximal aerobic capacity during middle and older age is greater in endurance-trained men than in their sedentary peers and is associated with a marked decline in O2pulse.
Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats
Authors: Christ Christine Y. , Hunt Desmond , Hancock Joe , Garcia-Macedo Rebeca , Mandarino Lawrence J. , Ivy John L.
Published: March 2015

Exercise training improves skeletal muscle insulin sensitivity in the obese Zucker rat. The purpose of this study was to investigate whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling. Obese Zucker rats were trained for 7 wk and studied by using the hindlimb-perfusion technique 24 h, 96 h, or 7 days after their last exercise training bout. Insulin-stimulated glucose uptake (traced with 2-deoxyglucose) was significantly reduced in untrained obese Zucker rats compared with lean controls (2.2 ± 0.17 vs. 5.4 ± 0.46 μmol · g−1· h−1). Glucose uptake was normalized 24 h after the last exercise bout (4.9 ± 0.41 μmol · g−1· h−1) and remained significantly elevated above the untrained obese Zucker rats for 7 days. However, exercise training did not increase insulin receptor or insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3-kinase) activity associated with IRS-1 or tyrosine phosphorylated immunoprecipitates, or Akt serine phosphorylation. These results are consistent with the hypothesis that, in obese Zucker rats, adaptations occur during training that lead to improved insulin-stimulated muscle glucose uptake without affecting insulin receptor signaling through the PI3-kinase pathway.
Effects of resistance training on physical function in older disabled women with coronary heart disease
Authors: Brochu Martin , Savage Patrick , Lee Melinda , Dee Justine , Cress M. Elaine , Poehlman Eric T. , Tischler Marc , Ades Philip A.
Published: March 2015

We studied whether disabled older women with coronary heart disease can perform resistance training at an intensity sufficient to improve measured and self-reported physical function [ n = 30, 70.6 ± 4.5 (SD) yr]. Compared with the controls, the resistance-training group showed significant improvements in overall measured physical function score using the Continuous-Scale Physical Functional Performance Test (+24 vs. +3%). The Continuous-Scale Physical Functional Performance Test measures physical function for 15 practical activities, such as carrying groceries or climbing stairs. Resistance training led to improved measures for domains of upper body strength (+18 vs. +6%), lower body strength (+23 vs. +6%), endurance (+26 vs. +1%), balance and coordination (+29 vs. −2%), and 6-min walk (+15 vs. +7%). Women involved in the flexibility-control group showed essentially no improvement for physical function measures. No changes were observed for body composition, aerobic capacity, or self-reported physical function in either group. In conclusion, disabled older women with coronary heart disease who participate in strength training are able to train at an intensity sufficient to result in improvements in multiple domains of measured physical functional performance, despite no change in lean body mass.
Carotid baroreflex control of leg vascular conductance at rest and during exercise
Authors: Keller David M. , Wasmund Wendy L. , Wray D. Walter , Ogoh Shigehiko , Fadel Paul J. , Smith Michael L. , Raven Peter B.
Published: March 2015

We sought to test the hypothesis that the carotid baroreflex (CBR) alters mean leg blood flow (LBF) and leg vascular conductance (LVC) at rest and during exercise. In seven men and one woman, 25 ± 2 (SE) yr of age, CBR control of LBF and LVC was determined at rest and during steady-state one-legged knee extension exercise at ∼65% peak O2 uptake. The application of 5-s pulses of +40 Torr neck pressure and −60 Torr neck suction significantly altered mean arterial pressure (MAP) and LVC both at rest and during exercise. CBR-mediated changes in MAP were similar between rest and exercise ( P > 0.05). However, CBR-mediated decreases in LVC (%change) to neck pressure were attenuated in the exercising leg (16.4 ± 1.6%) compared with rest (33 ± 2.1%) and the nonexercising leg (23.7 ± 1.9%) ( P < 0.01). These data suggest CBR control of blood pressure is partially mediated by changes in leg vascular tone both at rest and during exercise. Furthermore, despite alterations in CBR-induced changes in LVC during exercise, CBR control of blood pressure was well maintained.
Effects of carotid and aortic chemoreceptor denervation in newborn piglets
Authors: Serra A. , Brozoski D. , Hodges M. , Roethle S. , Franciosi R. , Forster H. V.
Published: March 2015

The objective of the present study was to test the hypothesis that in neonatal piglets there would be no hypoventilation after sham denervation or aortic denervation (AOD) alone, but there would be transient hypoventilation after carotid body denervation (CBD) and the hypoventilation would be greatest after combined carotid and aortic denervation (CBD+AOD). There was a significant ( P < 0.05) hypoventilation in CBD and CBD+AOD piglets denervated at 5, 15, and 25 days of age. The hypoventilation in CBD+AOD piglets denervated at 5 days of age was greater ( P < 0.05) than that of all other groups. Conversely, sham-denervated and AOD piglets did not hypoventilate after denervation. Injections of sodium cyanide showed that aortic chemoreceptors were a site of recovery of peripheral chemosensitivity after CBD. This aortic sodium cyanide response was abolished by prior injection of a serotonin 5a receptor blocker. Residual peripheral chemosensitivity after CBD+AOD was localized to the left ventricle. We conclude that 1) aortic chemoreceptors contribute to eupneic breathing in piglets that were carotid denervated at 5 days of age and 2) there are multiple sites of residual peripheral chemosensitivity after CBD.
Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate
Authors: Lee Won Jun , McClung Joseph , Hand G. A. , Carson James A.
Published: March 2015

This study's purpose was to examine whether functional overload with nandrolone decanoate (ND) administration increased muscle mass and steroid receptor concentration in aged rat soleus (Sol) and plantaris (Plan) muscle. ND (6 mg/kg body wt) was administered once a week for 4 wk, whereas control rats received sesame seed oil injections. Functional overload of the hindlimb Sol and Plan was induced by synergistic gastrocnemius muscle ablation at the beginning of the fourth week. Adult (5 mo of age) and aged rats (25 mo of age) were randomly assigned to four groups: control, overload, control-ND, and overload-ND. Seven days of functional overload increased adult Sol muscle mass 27%, whereas the aged Sol muscle mass did not change. The aged overloaded Sol muscle receiving ND significantly increased muscle weight by 35% and total muscle protein by 24%. Aged Plan muscle did not increase muscle weight with overload or ND treatment. Androgen receptor protein was induced by ND treatment and functional Ov, and combining the two treatments induced Sol androgen receptor protein concentration above either alone. Sol glucocorticoid receptor protein concentration increased in overload groups of both ages. ND administration can increase aged Sol muscle mass and protein content after 7 days of functional overload, and the cooperative induction of androgen receptor may be important for this response.
Contralateral activity in a homologous hand muscle during voluntary contractions is greater in old adults
Authors: Shinohara Minoru , Keenan Kevin G. , Enoka Roger M.
Published: March 2015

This study compared the amount of contralateral activity produced in a homologous muscle by young (18–32 yr) and old (66–80 yr) adults when they performed unilateral isometric and anisometric contractions with a hand muscle. The subjects were not aware that the focus of the study was the contralateral activity. The tasks involved the performance of brief isometric contractions to six target forces, slowly lifting and lowering six inertial loads, and completing a set of 10 repetitions with a heavy load. The unintended force exerted by the contralateral muscle during the isometric contractions increased with target force, but the average force was greater for the old adults (means ± SD; 12.6 ± 15.3%) compared with the young adults (6.91 ± 11.1%). The contralateral activity also increased with load during the anisometric contractions, and the average contralateral force was greater for the old subjects (5.28 ± 6.29%) compared with the young subjects (2.10 ± 3.19%). Furthermore, the average contralateral force for both groups of subjects was greater during the eccentric contractions (4.17 ± 5.24%) compared with the concentric contractions (3.20 ± 5.20%). The rate of change in contralateral activity during the fatigue task also differed between the two groups of subjects. The results indicate that old subjects have a reduced ability to suppress unintended contralateral activity during the performance of goal-directed, unilateral tasks.
Perturbations in three medullary nuclei enhance fractionated breathing in awake goats
Authors: Feroah Thom R. , Forster H. V. , Fuentes Carlo G. , Martino Paul , Hodges M. , Wenninger Julie , Pan L. , Rice Tom
Published: March 2015

Our aim was to determine the frequency and characteristics of a fractionated pattern of diaphragm and upper airway muscle activity and airflow during wakefulness and sleep in adult goats. A fractionated breath (FBr) was defined as three or more brief (40–150 ms) interruptions in the diaphragm activity not associated with multiple swallows, eructation, mastication, or movement. During a FBr, the discharge pattern in the diaphragm and upper airway muscles showed complete cycles of inspiration and expiration. Whereas the interval between peak diaphragm activity of the breath preceding the FBr to the first diaphragm peak of the FBr was 15–20% less than the average interval of the preceding five control breaths, the breath-to-breath interval of the five breaths after a FBr did not differ from the control breaths before the FBr event. In normal goats, FBr was evident in only 4 of 18 (22%) awake goats and in only one of these goats during non-rapid eye movement sleep. In 35 goats with implanted microtubules in the medulla, FBr were present in 14 (40%) goats. In these goats with FBr, 78% (11 of 14) had one or more implantations into or near the facial, vestibular, or raphe nuclei. The effect of perturbations in these nuclei is probably nonspecific, because injections into these nuclei with mock cerebrospinal fluid or excitatory amino acid-receptor agonist or antagonist produced both increases and decreases in the frequency of the FBr while not altering their characteristics. Finally, a swallow occurred at the termination or during the first breath after 60% of the FBr. We speculate that the FBr manifest 1) the disruption of a neuronal network, which coordinates breathing and other functions (such as swallowing), utilizing the same anatomic structures, and/or 2) transient changes in synaptic inputs that increase the rate of the normal respiratory rhythm generator or allow an ectopic, anomalous generator to become dominant.
Pulmonary capillaries are recruited during pulsatile flow
Authors: Presson Robert G. , Baumgartner William A. , Peterson Amanda J. , Glenny Robb W. , Wagner Wiltz W.
Published: March 2015

Capillaries recruit when pulmonary arterial pressure rises. The duration of increased pressure imposed in such experiments is usually on the order of minutes, although recent work shows that the recruitment response can occur in <4 s. In the present study, we investigate whether the brief pressure rise during cardiac systole can also cause recruitment and whether the recruitment is maintained during diastole. To study these basic aspects of pulmonary capillary hemodynamics, isolated dog lungs were pump perfused alternately by steady flow and pulsatile flow with the mean arterial and left atrial pressures held constant. Several direct measurements of capillary recruitment were made with videomicroscopy. The total number and total length of perfused capillaries increased significantly during pulsatile flow by 94 and 105%, respectively. Of the newly recruited capillaries, 92% were perfused by red blood cells throughout the pulsatile cycle. These data provide the first direct account of how the pulmonary capillaries respond to pulsatile flow by showing that capillaries are recruited during the systolic pulse and that, once open, the capillaries remain open throughout the pulsatile cycle.
Preferential loss of omental-mesenteric fat during growth hormone therapy of HIV-associated lipodystrophy
Authors: He Qing , Engelson Ellen S. , Albu Jeanine B. , Heymsfield Steven B. , Kotler Donald P.
Published: March 2015

Lipodystrophy with increased intra-abdominal fat in human immunodeficiency virus (HIV) infection is common in the era of highly active antiretroviral therapy. It contributes to the metabolic derangements, as it does in non-HIV-related conditions. Growth hormone administration reduces intra-abdominal fat content. This study compared the relative changes in omental-mesenteric (OMAT) and retroperitoneal adipose tissues (RPAT) during therapy with recombinant human growth hormone (rhGH) in HIV-associated lipodystrophy. Of 30 subjects who began rhGH therapy (6 mg/day), 25 completed 12 wk and 19 completed 24 wk. Fourteen subjects were followed for an additional 12 wk. Volumes of OMAT and RPAT were calculated from total body MRI scans and compared by paired t-tests. Both OMAT and RPAT significantly decreased after 12 and 24 wk of rhGH treatment ( P < 0.001), but the reduction was more pronounced in OMAT than in RPAT ( P< 0.001). Both OMAT and RPAT increased significantly ( P < 0.001) after therapy was discontinued, but OMAT increased significantly more than did RPAT (122 vs. 37%, P < 0.001). There is preferential loss and regain of OMAT, compared with RPAT, in subjects with HIV-associated lipodystrophy undergoing growth hormone treatment.
Effect of exogenous growth hormone and exercise on lean mass and muscle function in children with burns
Authors: Suman Oscar E. , Thomas Steve J. , Wilkins Judy P. , Mlcak Ronald P. , Herndon David N.
Published: March 2015

We tested the hypothesis that the administration of recombinant human growth hormone (rHGH) and exercise would increase lean body mass (LBM) and muscle strength in burned children to a greater extent than rHGH or exercise separately. Children, ages 7–17 yr, with >40% body surface area burned, were randomized into groups. One group (GHEX, n = 10) participated in a 12-wk in-hospital physical rehabilitation program supplemented with an exercise program and received 0.05 mg · kg−1· day−1of rHGH. A second exercising group (SALEX, n = 13) received saline. A third group (GH, n = 10) received a similar dose of rHGH as GHEX and participated in a 12-wk, home-based physical rehabilitation program without exercise. The fourth group (Saline, n = 11) received saline and participated in a 12-wk, home-based physical rehabilitation program without exercise. The mean (±SE) percent change in lean body mass after 12 wk was not significantly different between GHEX (9.0 ± 2.1%), SALEX (5.4 ± 1.6%), and GH (5.8 ± 1.8%) groups ( P = 0.33). However, the mean percent change in muscle strength was significantly greater in the GHEX (36.2 ± 5.4%) and SALEX (42.6 ± 10.0%) groups than in the GH (−7.4 ± 4.7%) or Saline (6.7 ± 4.4%) groups ( P = 0.008). In summary, rHGH GHEX, SALEX, and GH alone produced similar improvements in LBM. However, muscle strength was only increased via exercise.
Selected Contribution: Acute and sustained ventilatory responses to hypoxia in high-altitude natives living at sea level
Authors: Gamboa Alfredo , León-Velarde Fabiola , Rivera-Ch Maria , Palacios Jose-Antonio , Pragnell Timothy R. , O'Connor David F. , Robbins Peter A.
Published: March 2015

High-altitude (HA) natives have blunted ventilatory responses to hypoxia (HVR), but studies differ as to whether this blunting is lost when HA natives migrate to live at sea level (SL), possibly because HVR has been assessed with different durations of hypoxic exposure (acute vs. sustained). To investigate this, 50 HA natives (>3,500 m, for >20 yr) now resident at SL were compared with 50 SL natives as controls. Isocapnic HVR was assessed by using two protocols: protocol 1, progressive stepwise induction of hypoxia over 5–6 min; and protocol 2, sustained (20-min) hypoxia (end-tidal Po 2 = 50 Torr). Acute HVR was assessed from both protocols, and sustained HVR from protocol 2. For HA natives, acute HVR was 79% [95% confidence interval (CI): 52–106%, P = not significant] of SL controls for protocol 1 and 74% (95% CI: 52–96%, P < 0.05) for protocol 2. By contrast, sustained HVR after 20-min hypoxia was only 30% (95% CI: −7–67%, P < 0.001) of SL control values. The persistent blunting of HVR of HA natives resident at SL is substantially less to acute than to sustained hypoxia, when hypoxic ventilatory depression can develop.
Selected Contribution: Peripheral chemoreflex function in high-altitude natives and patients with chronic mountain sickness
Authors: León-Velarde Fabiola , Gamboa Alfredo , Rivera-Ch Maria , Palacios Jose-Antonio , Robbins Peter A.
Published: March 2015

Peripheral chemoreflex function was studied in high-altitude (HA) natives at HA, in patients with chronic mountain sickness (CMS) at HA, and in sea-level (SL) natives at SL. Results were as follows. 1) Acute ventilatory responses to hypoxia (AHVR) in the HA and CMS groups were approximately one-third of those of the SL group. 2) In CMS patients, some indexes of AHVR were modestly, but significantly, lower than in healthy HA natives. 3) Prior oxygenation increased AHVR in all subject groups. 4) Neither low-dose dopamine nor somatostatin suppressed any component of ventilation that could not be suppressed by acute hyperoxia. 5) In all subject groups, the ventilatory response to hyperoxia was biphasic. Initially, ventilation fell but subsequently rose so that, by 20 min, ventilation was higher in hyperoxia than hypoxia for both HA and CMS subjects. 6) Peripheral chemoreflex stimulation of ventilation was modestly greater in HA and CMS subjects at an end-tidal Po 2= 52.5 Torr than in SL natives at an end-tidal Po 2 = 100 Torr. 7) For the HA and CMS subjects combined, there was a strong correlation between end-tidal Pco 2 and hematocrit, which persisted after controlling for AHVR.
Selected Contribution: Ventilatory response to CO2 in high-altitude natives and patients with chronic mountain sickness
Authors: Fatemian Marzieh , Gamboa Alfredo , León-Velarde Fabiola , Rivera-Ch Maria , Palacios Jose-Antonio , Robbins Peter A.
Published: March 2015

The ventilatory responses to CO2 of high-altitude (HA) natives and patients with chronic mountain sickness (CMS) were studied and compared with sea-level (SL) natives living at SL. A multifrequency binary sequence (MFBS) in end-tidal Pco 2 was employed to separate the fast (peripheral) and slow (central) components of the chemoreflex response. MFBS was imposed against a background of both euoxia (end-tidal Po 2 of 100 Torr) and hypoxia (52.5 Torr). Both total and central chemoreflex sensitivity to CO2 in euoxia were higher in HA and CMS subjects compared with SL subjects. Peripheral chemoreflex sensitivity to CO2in euoxia was higher in HA subjects than in SL subjects. Hypoxia induced a greater increase in total chemoreflex sensitivity to CO2 in SL subjects than in HA and CMS subjects, but peripheral chemoreflex sensitivity to CO2 in hypoxia was no greater in SL subjects than in HA and CMS subjects. Values for the slow (central) time constant were significantly greater for HA and CMS subjects than for SL subjects.
Inhalation of warm and cold air does not influence brain stem or core temperature in normothermic humans
Authors: Mekjavic Igor B. , Rogelj Klemen , Radobuljac Maja , Eiken Ola
Published: March 2015

The present study tested the hypothesis that inhalation rewarming provides a thermal increment to central neural structures adjacent to the nasopharyngeal region. Auditory-evoked brain stem responses of 14 subjects (7 men and 7 women) were monitored for 25 min while they inspired room air (24°C) followed by hot air (41°C) saturated with water vapor and cold dry air (−1°C). The latencies of peaks I, III, and V and the interpeak latencies(IPLs) I–III, III–V, and I–V were compared among the three conditions with a repeated-measures ANOVA. Changes in IPLs are sensitive markers of changes in brain stem temperature. Tympanic temperature (Tty) was measured with an infrared tympanic thermometer. There were no significant differences in Tty, peak latencies I, III, and V, and IPLs I–III, III–V, and I–V. The results indicate that inhalation of hot and cold air does not influence Tty, nor does it influence the temperature of the brain stem. We conclude that inhalation rewarming is not capable of warming the vital central neural structures adjacent to the naropharynx.
Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention
Authors: Billman George E.
Published: March 2015

Sudden, unexpected cardiac death due to ventricular fibrillation is the leading cause of death in most industrially developed countries. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic therapies has proven to be an elusive goal. In fact, many initially promising antiarrhythmic medications were subsequently found to increase rather than to decrease cardiac mortality. It is now known that cardiac disease alters cardiac autonomic balance and that the patients with the greatest changes in this cardiac neural regulation (i.e., decreased parasympathetic coupled with increased sympathetic activity) are also the patients at the greatest risk for sudden death. A growing body of experimental and epidemiological data demonstrates that aerobic exercise conditioning can dramatically reduce cardiac mortality, even in patients with preexisting cardiac disease. Conversely, the lack of exercise is strongly associated with an increased incidence of many chronic debilitating diseases, including coronary heart disease. Because it is well established that aerobic exercise conditioning can alter autonomic balance (increasing parasympathetic tone and decreasing sympathetic activity), a prudently designed exercise program could prove to be an effective and nonpharmacological way to enhance cardiac electrical stability, thereby protecting against sudden cardiac death.
Activation of human plantar flexor muscles increases after electromyostimulation training
Authors: Maffiuletti Nicola A. , Pensini Manuela , Martin Alain
Published: March 2015

Neuromuscular adaptations of the plantar flexor muscles were assessed before and subsequent to short-term electromyostimulation (EMS) training. Eight subjects underwent 16 sessions of isometric EMS training over 4 wk. Surface electromyographic (EMG) activity and torque obtained under maximal voluntary and electrically evoked contractions were analyzed to distinguish neural adaptations from contractile changes. After training, plantar flexor voluntary torque significantly increased under isometric conditions at the training angle (+8.1%, P< 0.05) and at the two eccentric velocities considered (+10.8 and +13.1%, P < 0.05). Torque gains were accompanied by higher normalized soleus EMG activity and, in the case of eccentric contractions, also by higher gastrocnemii EMG ( P < 0.05). There was an 11.9% significant increase in both plantar flexor maximal voluntary activation ( P < 0.01) and postactivation potentiation ( P < 0.05), whereas contractile properties did not change after training. In the absence of a change in the control group, it was concluded that an increase in neural activation likely mediates the voluntary torque gains observed after short-term EMS training.
Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography
Authors: Balanos George M. , Talbot Nicholas P. , Dorrington Keith L. , Robbins Peter A.
Published: March 2015

Hypercapnia has been shown in animal experiments to induce pulmonary hypertension. This study measured the sensitivity and time course of the human pulmonary vascular response to sustained (4 h) hypercapnia and hypocapnia. Twelve volunteers undertook three protocols: 1) 4-h euoxic (end-tidal Po 2 = 100 Torr) hypercapnia (end-tidal Pco 2 was 10 Torr above normal), followed by 2 h of recovery with euoxic eucapnia; 2) 4-h euoxic hypocapnia (end-tidal Pco 2 was 10 Torr below normal) followed by 2 h of recovery; and 3) 6-h air breathing (control). Pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by using Doppler echocardiography via the maximum tricuspid pressure gradient during systole. Results show progressive changes in pressure gradient over 1–2 h after the onset or offset of the stimuli, and sensitivities of 0.6 to 1 Torr change in pressure gradient per Torr change in end-tidal Pco 2. The human pulmonary circulatory response to changes in Pco 2 has a slower time course and greater sensitivity than is commonly assumed. Vascular tone in the normal pulmonary circulation is substantial.
Gender differences in regional body composition and somatotrophic influences of IGF-I and leptin
Authors: Nindl Bradley C. , Scoville Charles R. , Sheehan Kathleen M. , Leone Cara D. , Mello Robert P.
Published: March 2015

This study evaluated the arm, trunk, and leg for fat mass, lean soft tissue mass, and bone mineral content (BMC) assessed via dual-energy X-ray absorptiometry in a group of age-matched (∼29 yr) men ( n = 57) and women ( n = 63) and determined their relationship to insulin-like growth factor I (IGF-I) and leptin. After analysis of covariance adjustment to control for differences in body mass between genders, the differences that persisted ( P ≤ 0.05) were for lean soft tissue mass of the arm (men: 7.1 kg vs. women: 6.4 kg) and fat mass of the leg (men: 5.3 kg vs. women: 6.8 kg). Men and women had similar ( P ≥ 0.05) values for fat mass of the arms and trunk and lean soft tissue mass of the legs and trunk. Serum IGF-I and insulin-like growth factor binding protein-3 correlated ( P≤ 0.05) with all measures of BMC ( r values ranged from 0.31 to 0.39) and some measures of lean soft tissue mass for women ( r = 0.30) but not men. Leptin correlated ( P≤ 0.05) similarly for measures of fat mass for both genders ( r values ranging from 0.74 to 0.85) and for lean soft tissue mass of the trunk ( r = 0.40) and total body ( r = 0.32) for men and for the arms in women ( r = 0.56). These data demonstrate that 1) the main phenotypic gender differences in body composition are that men have more of their muscle mass in their arms and women have more of their fat mass in their legs and 2) gender differences exist in the relationship between somatotrophic hormones and lean soft tissue mass.
Facilitation of triceps brachii muscle contraction by tendon vibration after chronic cervical spinal cord injury
Authors: Ribot-Ciscar Edith , Butler Jane E. , Thomas Christine K.
Published: March 2015

One way to improve the weak triceps brachii voluntary forces of people with chronic cervical spinal cord injury may be to excite the paralyzed or submaximally activated fraction of muscle. Here we examined whether elbow extensor force was enhanced by vibration (80 Hz) of the triceps or biceps brachii tendons at rest and during maximum isometric voluntary contractions (MVCs) of the elbow extensors performed by spinal cord-injured subjects. The mean ± SE elbow extensor MVC force was 22 ± 17.5 N (range: 0–23% control force, n = 11 muscles). Supramaximal radial nerve stimuli delivered during elbow extensor MVCs evoked force in six muscles that could be stimulated selectively, suggesting potential for force improvement. Biceps vibration at rest always evoked a tonic vibration reflex in biceps, but extension force did not improve with biceps vibration during triceps MVCs. Triceps vibration induced a tonic vibration reflex at rest in one-half of the triceps muscles tested. Elbow extensor MVC force (when >1% of control force) was enhanced by vibration of the triceps tendon in one-half of the muscles. Thus triceps, but not biceps, brachii tendon vibration increases the contraction strength of some partially paralyzed triceps brachii muscles.
Enhanced baroreflex-mediated inhibition of respiration after muscimol dialysis in the rostroventral medulla
Authors: Curran Aidan K. , Peraza Daniel , Elinsky Cheryl A. , Leiter J. C.
Published: March 2015

The rostral ventral medulla (RVM) may be important in the control of cardiorespiratory interactions. We hypothesized that inhibition of the RVM would enhance inhibition of breathing associated with transient blood pressure elevations. In 25 piglets 3–16 days of age, we studied the effect of acutely increasing blood pressure, by systemic infusion of phenylephrine, on respiratory activity before and after inhibition of neural activity in the RVM by dialysis of 10 mM muscimol, a GABAA-receptor agonist. Muscimol dialysis through probes that were placed along the ventral medullary surface from ∼1 mm rostral to the facial nucleus to ∼0.5 mm caudal to the facial nucleus augmented the respiratory inhibition associated with acute increases in blood pressure. No similar enhancement of respiratory inhibition after phenylephrine treatment was seen in six control animals that did not receive muscimol dialysis. We conclude that the piglet RVM participates in cardiorespiratory interactions and that dysfunction of homologous regions in the human infant could lead to cardiorespiratory instability and may be involved in the pathogenesis of sudden infant death syndrome.