bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of arterial design on pulse wave reflection in a fractal pulmonary network
Authors: Bennett S. H. , Goetzman B. W. , Milstein J. M. , Pannu J. S.
Published: December 2017

A novel interpretation of pulmonary arterial input impedance was evaluated for the lung as a fractal vascular network. We hypothesized that local sources of reflection introduce trends of global reflection into the input impedance spectra. These trends are related to the network topology, geometry, and design according to Rb = Rdx, where Rb is the branching ratio, Rd is the diameter ratio, and x is the fractal dimension quantifying design. Simulations using values of Rd and x, which were derived morphometrically, confirmed two patterns of global reflection: a continuous trend attributed to a single effective site of reflection caused by frequency-dependent sources of impedance contrast and a discrete trend arising from a longitudinal distribution of frequency-independent sources of reflection. The continuous trend depended only on the network parameter Rd, whereas the discrete trend depended on Rd and x. Our results indicate that the impedance-matching properties of a deterministic pulmonary fractal network encode arterial geometry and topology via function and that typical values of Rd and x for the pulmonary circulation facilitate shear stress amplification in its peripheral vessels. Thus, inasmuch as shear forces may be involved in the endothelial mechanisms for pathological, or physiological, vascular remodeling, broadband input impedance analysis may reveal interactions between network organization and vascular function.
Nitric oxide effects on shortening velocity and power production in the rat diaphragm
Authors: Morrison R. J. , Miller C. C. , Reid M. B.
Published: December 2017

The present experiments tested nitric oxide (NO) effects on shortening velocity and power production in maximally activated rat diaphragm. Diaphragm fiber bundles (n = 10/group) were incubated at 37 degrees C in Krebs-Ringer solution containing no added drug (control), the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA; 10 mM), the NO donor sodium nitroprusside (SNP; 1 mM), or a combination (L-NNA + SNP) Loaded shortening velocity was measured via the load-clamp technique over a range of afterloads. Force-velocity data were fitted to the Hill equation to determine maximum velocity of shortening (Vmax). Unloaded shortening velocity was measured in control and L-NNA-treated bundles (n = 12/group) by using the slack test. Maximal isometric force and unloaded shortening velocity were not altered by L-NNA. In contrast, L-NNA decreased maximum velocity of shortening (P < 0.05), loaded shortening velocity (P < 0.0001), and power production (P < 0.0001). All L-NNA effects were prevented by coincubating fiber bundles with L-NNA + SNP. SNP alone had no effect on any variable. These data indicate that endogenous NO is essential for optimal myofilament function during active shortening.
Alveolar surface area-to-lung volume ratio in oleic acid-induced pulmonary edema
Authors: Suzuki S. , Akahori T. , Miyazawa N. , Numata M. , Okubo T. , Butler J. P.
Published: December 2017

It is unknown how the in vivo alveolar surface area-to-volume ratio (S/V) changes in low-pressure pulmonary edema. Here, the S/V is the area of the air-tissue interface per unit total volume (air plus tissue). We hypothesized that in oleic acid (OA)-induced edema inactivation of the pulmonary surfactant may increase surface tension and decrease the S/V at any given lung volume. OA (0.04 mg/kg) was intravenously injected into dogs. We measured the in vivo S/V (equivalent to the inverse of optical mean free path by light-scattering stereology and the pressure-volume (PV) curve 60-90 min after OA administration. OA administration decreased the lung volume at each transpulmonary pressure and increased the wet-to-dry weight ratio. The S/V decreased after OA administration (optical mean free path increased). The air-filled PV curves shifted downward after OA, but the saline-filled PV curves after OA administration did not differ significantly from control saline-filled curves. The difference in transpulmonary pressure between air- and saline-filled PV curves (an index of the magnitude of surface tension) was increased in OA-induced pulmonary edema. This study suggests that in OA-induced pulmonary edema the alveolar surface tension increases and the S/V decreases, presumably due to inactivation of surfactant by serum leakage to alveoli.
Respiration during acute hypoxia: angiotensin- and vasopressin-receptor blocks
Authors: Overgaard C. B. , Walker J. K. , Jennings D. B.
Published: December 2017

In normoxic conscious dogs, increased angiotensin II (ANG II), or activation (disinhibition) of the renin-angiotensin system by vasopressin (AVP) V1-receptor block, increases ventilation and decreases arterial PCO2. Both hormones can be increased during hypoxia and might modulate ventilatory drive. Six conscious dogs were studied before and during hypocapnic, isocapnic, and hypercapnic hypoxia. To study potential hormonal effects during hypocapnic hypoxia, experiment 1 included three protocols in which 12.8% O2 was breathed for 60 min: protocol 1, control studies without block; protocol 2, AVP V1 receptors were blocked at the onset of hypoxia; and protocol 3, ANG II receptors were blocked 20 min before hypoxia. To study potential effects of acid-base changes during acute hypoxia, experiment 2 included two protocols (with and without AVP V1-receptor block). A 40-min period of hypocapnic hypoxia was followed by two successive 20-min periods with hypoxia maintained but inspired CO2 progressively increased. Neither hormonal block affected respiration during the hypoxic conditions. Unlike normoxia in conscious dogs, during acute hypoxia, respiratory control by ANG II is not modulated by AVP and acid-base effects on receptors do not account for this difference.
Skeletal muscle mass: evaluation of neutron activation and dual-energy X-ray absorptiometry methods
Authors: Wang Z. M. , Visser M. , Ma R. , Baumgartner R. N. , Kotler D. , Gallagher D. , Heymsfield S. B.
Published: December 2017

Although skeletal muscle (SM) is a major body component, whole body measurement methods remain limited and inadequately investigated. The aim of the present study was to evaluate the Burkinshaw in vivo neutron activation analysis (IVNA)-whole body 40K-counting and dual-energy X-ray absorptiometry (DXA) methods of estimating SM by comparison to adipose tissue-free SM measured using multiscan computerized axial tomography (CT). In the Burkinshaw method the potassium-to-nitrogen ratios of SM and non-SM lean tissue are assumed constant; in the DXA method the ratio of appendicular SM to total SM is assumed constant at 0.75. Seventeen healthy men [77.5 +/- 13.8 (SD) kg body wt] and eight men with acquired immunodeficiency syndrome (AIDS; 65.5 +/- 7.6 kg) completed CT, IVNA, and DXA studies. SM measured by CT was 34.4 +/- 6.2 kg for the healthy subjects and 27.2 +/- 4.0 kg for the AIDS patients. Compared with CT, the Burkinshaw method underestimated SM by an average of 6.9 kg (20.1%, P = 0.0001) and 6.3 kg (23.2%, P = 0.01) in the healthy men and the men with AIDS, respectively. The DXA method minimally overestimated SM in both groups (2.0 kg and 5.8% in healthy men, P = 0.001; 1.4 kg and 5.1% in men with AIDS, P = 0.16). This overestimate could be explained by a higher actual than assumed ratio of DXA-measured appendicular SM to total body SM (actual = 0.79 +/- 0.05, assumed = 0.75). The current study results reveal that large errors are present in the Burkinshaw SM method and that substantial refinements in the models that form the basis of this IVNA approach are needed. The model on which the DXA-SM method is based also needs further minor refinements, but this is a promising in vivo approach because of less radiation exposure and lower cost than the IVNA and CT methods.
Effects of tissue fractionation on exercise-induced alterations in SR function in rat gastrocnemius muscle
Authors: Chin E. R. , Green H. J.
Published: December 2017

Because studies into exercise-induced alterations in sarcoplasmic reticulum (SR) Ca2+ sequestration have produced conflicting reports, we have hypothesized that the differences in SR Ca(2+)-adenosinetriphosphatase (ATPase) activity and Ca2+ uptake in SR fractions observed in different studies are due to different SR isolation techniques. To investigate this possibility, rat white and red gastrocnemius muscles from control and run animals were studied by using two conventional isolation techniques to obtain a crude microsomal fraction and an isolated SR vesicle (SRV) fraction. Indexes of CM and SRV function were compared with measurements from whole muscle homogenate. Treadmill running to exhaustion did not alter SR protein yields, percent SR extraction, or basal or Ca(2+)-ATPase purification in either fraction. Ca(2+)-activated ATPase activity was not altered by exercise in any of the fractions examined, but Ca2+ uptake was reduced in the homogenates (9.48 +/- 1.4 to 6.90 +/- 0.8 nmol . mg-1.min-1) and SRV fractions (84.0 +/- 11.5 to 50.7 +/- 14.0 nmol . mg-1.min-1) from the red gastrocnemius at free Ca2+ concentrations of 600-700 nM. These data indicate that reductions in SR Ca2+ uptake are dissociated from changes in Ca(2+)-ATPase in vitro and occur only in a specific population of vesicles. The mechanisms underlying these alterations are not known but may involve a reduction in the number of Ca(2+)-ATPase enzymes or a selective sedimentation of damaged vesicles in the SRV fraction.
Effect of endogenous carbohydrate availability on oral medium-chain triglyceride oxidation during prolonged exercise
Authors: Jeukendrup A. E. , Saris W. H. , Van Diesen R. , Brouns F. , Wagenmakers A. J.
Published: December 2017

The present study examined the medium-chain triglyceride (MCT) oxidation rate of oral carbohydrate (CHO) + MCT supplements after a glycogen-depletion trial [low glycogen (LG)] and in the glycogen-loaded state [normal-to-high glycogen (HG)]. Eight elite athletes cycled four times 90 min at 50% maximal workload (57% maximal O2 uptake). In two trials, they followed a LG protocol to achieve low-glycogen stores in the leg muscles the evening before the experiment, and in two trials they followed a HG protocol. Subjects received a bolus of 4 ml/kg at the start and 2 ml/kg every 20 min during exercise of either a 15% CHO (long-chain glucose polymer) solution or an equicaloric CHO + MCT suspension. Exogenous MCT oxidation was measured by adding a [1,1,1-13C]trioctanoate tracer to the MCT oil and measuring 13CO2 production in the breath. The results show that 85% of MCT ingested was oxidized in LG and 69% in HG during the 60- to 90-min period. There was no statistically significant difference in MCT utilization between LG and HG. Peak oxidation rates were 0.15 and 0.13 g/min, respectively. MCT contributed 7.6% (LG) and 6.5% (HG) to total energy expenditure during the 60- to 90-min period. Total fatty acid oxidation was significantly elevated in the LG trial but was not influenced by MCT ingestion. Concomitantly, CHO oxidation was reduced in LG but no effect of MCT was observed. We conclude that 1) the contribution of MCT to total energy expenditure was small and 2) strenuous exercise the day before the experiment, followed by a low CHO intake and leading to a low CHO availability, substantially increased total fat oxidation but did not significantly increase MCT oxidation.
Joint pressure influences synovial tissue blood flow as determined by colored microspheres
Authors: Hardy J. , Bertone A. L. , Muir W. W.
Published: December 2017

We measured regional blood flow in synovial tissue of the antebrachiocarpal, midcarpal, and metacarpophalangeal joints of six normal adult anesthetized horses by using 15-microns-diameter polystyrene colored microspheres. The midcarpal fibrous capsule and synovial membrane blood flows (SMBF) were compared, and the effect of increased intra-articular pressure (30 and 60 mmHg) on midcarpal SMBF was investigated. Dorsal, medial palmar, and lateral palmar midcarpal SMBF measured 108 +/- 36, 61 +/- 12, and 50 +/- 11 microliters.min-1.g-1, respectively. Antebrachiocarpal, dorsal, and palmar metacarpophalangeal SMBF measured 103 +/- 8, 17 +/- 3, and 26 +/- 5 microliters.min-1.g-1, respectively. Midcarpal fibrous joint capsule blood flow was significantly lower than that of the synovial membrane. An increase in midcarpal intra-articular pressure to 30 or 60 mmHg resulted in an 84% decrease in SMBF. Colored microspheres provided a useful technique to determine sequential SMBF. Increased intra-articular pressure significantly altered SMBF, suggesting a role of the regional circulation in the pathogenesis of joint disease.
A modified rebreathing technique using an infrared gas analyzer
Authors: Barazanji K. W. , Ramanathan M. , Johnson R. L. , Hsia C. C.
Published: December 2017

To lower the cost and improve accessibility of the rebreathing technique for measuring cardiopulmonary function during exercise, we implemented a fast-response infrared (IR) gas-analyzer system to simultaneously measure lung diffusing capacity, cardiac output lung tissue volume, and lung volume by a rebreathing technique in five healthy subjects at rest and during steady-state exercise. Interferences by water vapor and CO2 on the analyzer were determined and corrected for. During rebreathing, a gas mixture of 0.4% C2H2-0.3% CH4-9% He-30% O2, and either 0.3% C18O or 0.3% C16O in a balance of N2 was simultaneously sampled by both a mass spectrometer and the IR analyzer, permitting paired comparisons. Measurements obtained by the two devices were not significantly different. We conclude that this modified rebreathing technique using the IR analyzer is accurate for the measurement of cardiopulmonary function at rest and during exercise.
MHC and sarcoplasmic reticulum protein isoforms in functionally overloaded cat plantaris muscle fibers
Authors: Talmadge R. J. , Roy R. R. , Chalmers G. R. , Edgerton V. R.
Published: December 2017

To determine whether the adaptations in myosin heavy chain (MHC) isoform expression after functional overload (FO) are accompanied by commensurate adaptations in protein isoforms responsible for relaxation [sarco(endo)plasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (SERCA) and phospholamban (PHL)] in single muscle fibers, the isoforms of MHC and SERCA and the presence or absence of PHL were determined for cat plantaris fibers 3 mo after FO. In control plantaris the relative MHC isoform composition was 23% type I, 21% type IIa, and 56% type IIb. FO resulted in a shift toward slower isoforms (33% type I, 44% type IIa, and 23% type IIb). In the deep region of the plantaris the proportions of type I MHC and hybrid MHC fibers (containing type I and II MHCs) were 40 and 200% greater in FO cats, respectively. FO resulted in a 47% increase in the proportion of fibers containing only the slow SERCA isoform (SERCA2) and a 41% increase in the proportion of fibers containing PHL. The proportions of fibers containing type I MHC, SERCA2, and PHL in control and FO plantaris were linearly correlated. These data show that adaptations in MHC isoform expression are accompanied by commensurate adaptations in sarcoplasmic reticulum protein isoforms in single muscle fibers after FO.
Mass cells contribute to O3-induced epithelial damage and proliferation in nasal and bronchial airways of mice
Authors: Longphre M. , Zhang L. Y. , Harkema J. R. , Kleeberger S. R.
Published: December 2017

Ozone (O3) exposure produces inflammation in the airways of humans and animal models. However, the mechanism by which O3 affects these changes is uncertain. Mast cells are strategically located below the epithelium of the airways and are capable of releasing a number of proinflammatory mediators. We tested the hypothesis that mast cells contribute to inflammation, epithelial sloughing, and epithelial proliferation in the nasal and terminal bronchiolar murine airways after O3 exposure. Mast cell-sufficient (+/+), mast cell-deficient (W/Wv), and mast cell-repleted [bone marrow-transplanted (BMT) W/Wv] mice were exposed to 2 ppm O3 or filtered air for 3 h. Nasal and bronchoalveolar lavage fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage fluids were used as indicators of inflammation and permeability changes in the airways. O3-induced epithelial injury was assessed by light microscopy, and O3-induced DNA synthesis in airway epithelium was estimated by using a 5-bromo-2′-deoxyuridine-labeling index in the nasal and terminal bronchiolar epithelia. Relative to air control mice, O3 caused significant increases in inflammation, epithelial injury, and epithelial DNA synthesis in +/+ mice. There was no significant effect of O3 exposure on any measured parameter in the W/Wv mice. To further assess the role of mast cells in O3-induced epithelial damage, mast cells were restored in W/Wv mice by BMT from +/+ congeners. Relative to sham-transplanted W/Wv mice, O3 caused significant increases in epithelial damage and DNA synthesis as well as inflammatory indicators in BMT W/Wv mice. These observations are consistent with the hypothesis that mast cells significantly modulate the inflammatory and proliferative responses of the murine airways to O3.
Comparison of muscle near-infrared spectroscopy and femoral blood gases during steady-state exercise in humans
Authors: Costes F. , Barthelemy J. C. , Feasson L. , Busso T. , Geyssant A. , Denis C.
Published: December 2017

Near-infrared spectroscopy (NIRS) is a noninvasive way of measuring muscular oxygenation. We evaluated the relationship between NIRS signal [infrared muscle oxygen saturation (IR-SO2mus)] and the femoral venous oxygen saturation (SfvO2) during cycling exercise. Six healthy subjects performed a 30-min steady-state exercise at 80% maximal oxygen uptake in normoxia and hypoxia (inspired O2 fraction = 0.105). IR-So2mus was recorded continuously throughout the tests with the NIRS probe located on the vastus lateralis. During exercise, blood samples were withdrawn every 5 min from radial artery and femoral vein catheters. In normoxia, IR-So2mus initiated a transient nonsignificant decrease at 5 min, then returned to preexercise level, whereas SfvO2 showed a fast decrease, reaching 18% saturation at 10 min without further change. By contrast, in hypoxia, IR-SO2mus and SfvO2 demonstrated a parallel decrease then stabilized at 10 min. We conclude that IR-SO2mus appears to parallel SfvO2 when both the arterial and venous oxygen contents decrease during steady-state exercise in hypoxia, whereas IR-SO2mus does not follow SfvO2 change in normoxia.
Alterations in surfactant protein A after acute exposure to ozone
Authors: Su W. Y. , Gordon T.
Published: December 2017

The surfactant layer covering the gas-exchange region of the lung serves as the initial site of interaction with inhaled oxidant gases. Among the endogenous compounds potentially vulnerable to oxidative injury are surfactant proteins. This study focused on the effect of ozone on surfactant protein A (SP-A) function, content, and gene expression. To determine the time course of response to ozone, guinea pigs were exposed to 0.2-0.8 parts/million (ppm) ozone for 6 h and were killed up to 120 h postexposure. To determine the effect of repeated exposure, animals were exposed to 0.8 ppm ozone for 6 h/day and were killed on days 3 and 5. A significant increase in surfactant's ability to modulate the respiratory burst induced by phorbol 12-myristate 13-acetate in naive macrophages was observed at 24 h after a single 0.8 ppm ozone exposure. Because neutralizing antibodies to SP-A blunted this stimulatory effect, we hypothesized that ozone enhanced the modulatory role of SP-A in macrophage function. This alteration in function was accompanied by an influx of inflammatory cells and only marginal changes in SP-A levels as determined by an enzyme-linked immunosorbent assay. No significant changes in steady-state levels of SP-A mRNA were observed after single or repeated exposure to ozone. Thus the inflammation that accompanies in vivo ozone exposure may result in a change in the structure and thus functional role of SP-A in modulating macrophage activity.
Assessment of respiratory pressure-volume nonlinearity in rabbits during mechanical ventilation
Authors: Peslin R. , Rotger M. , Farre R. , Navajas D.
Published: December 2017

The volume dependence of respiratory elastance makes it difficult to recognize actual changes in lung and chest wall elastic properties in artificially ventilated subjects. We have assessed in six anesthetized, tracheotomized, and paralyzed rabbits whether reliable information on the static pressure-volume (PV) curve could be obtained from recordings performed during step variations of the end-expiratory pressure without interrupting mechanical ventilation. Pressure and flow data recorded during 5- and 10-hPa positive-pressure steps were analyzed in the time domain with a nonlinear model featuring a sigmoid PV curve and with a model that, in addition, accounted for tissue viscoelastic properties. The latter fitted the data substantially better. Both models provided reasonably reproducible coefficients, but the PV curves obtained from the 5- and 10-hPa steps were systematically different. When the PV curves were used to predict respiratory effective elastance, the best predictor was the curve derived from the 10-hPa step with the viscoelastic model: unsigned differences averaged 8.6 +/- 11.1, 26.9 +/- 36.4, and 5.5 +/- 5.8% at end-expiratory pressures of 0, 5, and 10 hPa, respectively. This approach provides potentially useful, although not highly accurate, estimates of respiratory effective elastance-volume dependence.
Estradiol effect on anterior crural muscles-tibial bone relationship and susceptibility to injury
Authors: Warren G. L. , Lowe D. A. , Inman C. L. , Orr O. M. , Hogan H. A. , Bloomfield S. A. , Armstrong R. B.
Published: December 2017

The study's objective was to determine whether estradiol (E2) deficiency alters the functional relationship of muscle to bone and causes a differential increase in injury susceptibility. Ovariectomized 6-wk-old mice were administered E2 (40 micrograms. day-1. kg-1; n = 8) or the oil vehicle (n = 8) for 21 days. The anterior crural muscles of the left hindlimb were then stimulated to produce 150 maximal in vivo eccentric contractions. In vitro functional measurements were then made on the extensor digitorum longus (EDL) muscle and tibia from both the exercised and unexercised legs. The maximal isometric torque produced by the anterior crural muscles before the eccentric contraction protocol and the unexercised EDL maximal isometric tetanic force (P(0)) were higher in E2-treated mice by 18 and 14%, respectively (P < or = 0.03). Both ultimate load and stiffness for the unexercised tibia were higher by 16% in E2-treated mice (P < or = 0.03). The muscle-to-bone relationship of these measurements was unaffected by E2 status (P > or = 0.59). No evidence for increased injury susceptibility was found in either tissue from E2-deficient mice. In fact, the decrement in P(0) was only 36.9 +/- 3.8% in exercised EDL muscles from E2-deficient mice compared with 50.6 +/- 4.2% in exercised muscles from E2-treated mice (P = 0.03). Tibia stiffness was 3.9% higher in bones from exercised legs than in bones from unexercised legs (72.64 +/- 2.77 vs. 69.95 +/- 2.66 N/mm; P = 0.05) with ultimate load showing a similar trend (P = 0.07); no effect of E2 status was observed on these differences (P > or = 0.53). In conclusion, the functional relationship of bone to muscle and the susceptibility to injury in bone are not altered by the presence of E2 in ovariectomized mice; however, E2 does increase injury susceptibility in the EDL muscle.
How inhomogeneities and airway walls affect frequency dependence and separation of airway and tissue properties
Authors: Lutchen K. R. , Greenstein J. L. , Suki B.
Published: December 2017

It has been proposed that during mild-to-moderate bronchoconstriction one can partition airway and tissue properties on the basis of input impedance (Zin) acquired from 0.1 to 5 Hz (K.R. Lutchen, B. Suki, Q. Zhang, F. Petak, B. Daroczy, and Z. Hantos. J. Appl. Physiol. 77: 373-385, 1994). The approach is to apply a homogeneous lung model that contains airway resistance and viscoelastic tissue damping and elastance parameters. The tissue parameters account for the frequency dependence in lung resistance (RL) and elastance (EL). We present an anatomically consistent asymmetrically branching airway model to address two key questions: 1) How will lung inhomogeneities, airway wall shunting, and tissue viscoelasticity contribute to increased frequency dependence and levels of RL and EL during lung constriction? and 2) How much can lung inhomogeneities and airway wall shunting contribute to our assessment of airway, tissue, and overall lung properties derived from Zin? The model incorporates nonrigid airway walls and allows for explicit control over the type and degree of inhomogeneous airway constriction or tissue changes. Our results indicate that, from 0.1 to 5 Hz, airway wall shunting does not become important unless the entire lung periphery experiences significant constriction. Mild-to-moderate inhomogeneous peripheral airway constriction produces a relatively minor additional frequency dependence in RL and EL beyond that due to the tissues alone. With more extreme constriction, however, there is a marked frequency-dependent increase in EL. This phenomenon may render it impossible to distinguish from a single frequency measurement whether an increase in EL during bronchoconstriction is a consequence of a true increase in tissue stiffening or simply a consequence of airway phenomena. Finally, Zin from 0.1 to 5 Hz can be used to provide a reasonable separation of airway and tissue properties for mild-to-moderate homogeneous or inhomogeneous lung constriction. However, during more severe disease, inhomogeneities and/or wall shunting will produce substantial overestimation of tissue damping and hysteretic properties. In fact, the only reliable indicator of a real change in the tissues may be a change in the estimate of tissue elastance that is based on data extending to a sufficiently low frequency.
Comparison of magnetic and electrical phrenic nerve stimulation in assessment of diaphragmatic contractility
Authors: Laghi F. , Harrison M. J. , Tobin M. J.
Published: December 2017

Unlike the standard electrical approach, cervical magnetic stimulation of the phrenic nerves is less painful and achieves a constant degree of diaphragmatic recruitment, features that should enhance its applicability in a clinical setting. An unexplained phenomenon is the greater transdiaphragmatic twitch pressure (Pditw) with magnetic vs. electrical stimulation. We hypothesized that this greater Pditw is due to coactivation of extradiaphragmatic muscles. Because impedance to rib cage expansion is increased at high lung volumes and efficiency of extradiaphragmatic muscles is less than that of the diaphragm, we reasoned that the difference between electrical Pditw and magnetic Pditw would be less evident at high volumes than at end-expiratory lung volume. In human volunteers, magnetic Pditw and electrical Pditw were 37.7 +/- 1.9 (SE) and 32.3 +/- 2.2 cmH2O, respectively, at end-expiratory lung volume (P < 0.005) and 24.0 +/- 2.9 and 27.2 +/- 2.8 cmH2O, respectively, at one-half inspiratory capacity (not significant); at total lung capacity, magnetic Pditw was less than electrical Pditw (10.6 +/- 0.8 and 16.2 +/- 2.9 cmH2O, respectively; P < 0.05). Magnetic stimulation caused significant extradiaphragmatic muscle depolarization and rib cage expansion, whereas electrical stimulation caused virtually no extradiaphragmatic muscle depolarization and rib cage deflation. Despite these differences, the induction of respiratory muscle fatigue produced reductions in both electrical and magnetic Pditw values (P < 0.01), which were of similar magnitude and closely correlated (r = 0.96). In conclusion, magnetic stimulation recruits both extradiaphragmatic and diaphragmatic muscles, and it is equally as effective as electrical stimulation in detecting diaphragmatic fatigue.
Voluntary chronic exercise augments in vivo natural immunity in rats
Authors: Jonsdottir I. H. , Asea A. , Hoffmann P. , Dahlgren U. I. , Andersson B. , Hellstrand K. , Thoren P.
Published: December 2017

The effect of chronic voluntary exercise on the immune response was studied in spontaneously hypertensive rats. Exercise consisted of voluntary running in wheels for 5 wk, and the mean running distance was 4.2 km/24 h. In vivo cytotoxicity was measured as clearance of injected 51Cr-labeled YAC-1 lymphoma cells from the lungs. The clearance of YAC-1 cells in vivo was significantly increased in runners compared with sedentary controls (P < 0.001). The total number of mononuclear cells in the spleen was significantly decreased in runners compared with controls. Analysis of splenic lymphocyte phenotypes revealed a significantly increased fraction of OX52+/CD5- natural killer cells in runners compared with sedentary controls. In contrast to changes in natural immunity, immunoglobulins G and M levels in serum, the antibody response to antigen in vivo, and the proliferation of splenic T cells in vitro were unchanged. Our data suggest that chronic voluntary exercise augments natural cytotoxicity mechanisms in vivo, whereas splenic T-cell proliferation and the antibody-mediated immune response remain unchanged.
Regulation of body fluid compartments during short-term spaceflight
Authors: Leach C. S. , Alfrey C. P. , Suki W. N. , Leonard J. I. , Rambaut P. C. , Inners L. D. , Smith S. M. , Lane H. W. , Krauhs J. M.
Published: December 2017

The fluid and electrolyte regulation experiment with seven subjects was designed to describe body fluid, renal, and fluid regulatory hormone responses during the Spacelab Life Sciences-1 (9 days) and -2 (14 days) missions. Total body water did not change significantly. Plasma volume (PV; P < 0.05) and extracellular fluid volume (ECFV; P < 0.10) decreased 21 h after launch, remaining below preflight levels until after landing. Fluid intake decreased during weightlessness, and glomerular filtration rate (GFR) increased in the first 2 days and on day 8 (P < 0.05). Urinary antidiuretic hormone (ADH) excretion increased (P < 0.05) and fluid excretion decreased early in flight (P < 0.10). Plasma renin activity (PRA; P < 0.10) and aldosterone (P < 0.05) decreased in the first few hours after launch; PRA increased 1 wk later (P < 0.05). During flight, plasma atrial natriuretic peptide concentrations were consistently lower than preflight means, and urinary cortisol excretion was usually greater than preflight levels. Acceleration at launch and landing probably caused increases in ADH and cortisol excretion, and a shift of fluid from the extracellular to the intracellular compartment would account for reductions in ECFV. Increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms. If the Gauer-Henry reflex operates during spaceflight, it must be completed within the first 21 h of flight and be succeeded by establishment of a reduced PV set point.
Primate circadian rhythms during spaceflight: results from Cosmos 2044 and 2229
Authors: Fuller C. A. , Hoban-Higgins T. M. , Klimovitsky V. Y. , Griffin D. W. , Alpatov A. M.
Published: December 2017

The circadian timing system (CTS) coordinates an animal's physiology and behavior both internally and with the 24-h day. Previous studies have suggested that the CTS is sensitive to changes in gravity. To examine this question, the expression of the CTS in four juvenile male rhesus macaques (Macaca mulatta) were studied in space. These animals were flown on the Cosmos 2044 and 2229 missions. Activity, heart rate, and axillary and brain (Cosmos 2229) temperatures were recorded. In both flights, the subjects exhibited delays in the phasing of their temperature rhythms and a decrease in mean heart rate compared with ground control studies. These data are in support of other studies that demonstrate that the CTS is sensitive to changes in the gravitational environment. Furthermore, the data also support the concept of a multioscillator organization of the primate CTS due to the differential responses of the rhythms measured.
Effects of erythrocyte infusion on VO2max at high altitude
Authors: Young A. J. , Sawka M. N. , Muza S. R. , Boushel R. , Lyons T. , Rock P. B. , Freund B. J. , Waters R. , Cymerman A. , Pandolf K. B. , Valeri C. R.
Published: December 2017

This study investigated whether autologous erythrocyte infusion would ameliorate the decrement in maximal O2 uptake (VO2max) experienced by lowlanders when they ascend to high altitude. VO2max was measured in 16 men (treadmill running) at sea level (SL) and on the 1st (HA1) and 9th (HA9) days of high-altitude (4,300 m) residence. After VO2max was measured at SL, subjects were divided into two matched groups (n = 8). Twenty-four hours before ascent to high altitude, the experimental group received a 700-ml infusion of autologous erythrocytes and saline (42% hematocrit), whereas the control group received only saline. The VO2max of erythrocyte-infused [54 +/- 1 (SE) ml.kg-1.min-1] and control subjects (52 +/- 2 ml.kg-1.min-1) did not differ at SL before infusion. The decrement in VO2max on HA1 did not differ between groups, averaging 26% overall, despite higher (P < 0.01) arterial hematocrit, hemoglobin concentration, and arterial O2 content in the erythrocyte-infused subjects. By HA9, there were no longer any differences in hematocrit, hemoglobin concentration, or arterial O2 content between groups. No change in VO2max occurred between HA1 and HA9 for either group. Thus, despite increasing arterial O2-carrying capacity, autologous erythrocyte infusion did not ameliorate the decrement in VO2max at 4,300-m altitude.
One-minute wave in body fluid volume change enhanced by postural sway during upright standing
Authors: Inamura K. , Mano T. , Iwase S. , Amagishi Y. , Inamura S.
Published: December 2017

To analyze how the 1-min oscillation in postural sway and 1-min wave in body fluid volume change contribute to human circulatory homeostasis, several levels of body circumference, foot pressure center, electromyograms, and volumes of the leg, abdomen, and thorax were measured during upright standing for 40 min in 20 healthy young men. Spectral analyses of these parameters revealed that a 1-min rhythm is found in all parameters and that the 1-min wave in body fluid volume changes in the lower leg, which occur in fluid pooling caused by gravity, propagate upward. Muscle pumping in the lower leg triggered by the postural sway was found to increase the power of this 1-min wave. A quantitative analysis of body circumferences disclosed that the 1-min wave in body fluid volume change compensates for gravitational downward fluid shift, with the volume of 6.3 +/- 5.0 ml/cycle at the heart level. We concluded that a coupling mechanism between the 1-min oscillation in postural sway and the upward propagation of 1-min wave in body fluid volume change contributes to maintain systemic blood pressure during upright standing in humans.
Relationship of oxygen content to PO2 for stabilized bubbles in the circulation: theory
Authors: Van Liew H. D. , Burkard M. E.
Published: December 2017

Stabilized bubbles can pass through capillary beds, recirculate for a few minutes or hours, and carry O2 from the lungs to the tissues. Here, we develop the theory for the O2 content-PO2 relationship of bubbles and the alterations of the bubbles that are coupled to the O2 transport. We provide examples for bubbles stabilized by a slowly permeating gas; bubbles stabilized by mechanical structures may behave similarly. Because there are two mechanisms for O2 unloading (lowering of PO2 and shrinkage), the bubbles release a large fraction of their O2 content at high PO2; when pure O2 is breathed, one-half of the content of a 3-microns-radius bubble is released before PO2 falls to 500 Torr. The possibility that stabilized bubbles could become a clinical tool for therapeutic transport of O2 raises many issues to be investigated. The highunloading PO2 offers opportunities for delivering O2 by diffusion to poorly perfused regions of the tissue but also presents a hazard of O2 toxicity to perfused tissue.
Cardiovascular responses to beta-stimulation with isoproterenol in deep hypothermia
Authors: Lauri T.
Published: December 2017

The aim of this study was to investigate the effects of beta-stimulation in deep (25 degrees C) hypothermia. Cardiac catheterization was performed on seven anesthetized beagle dogs. They were cooled between ice bags down to 25 degrees C and received isoproterenol administered intravenously three times: at the normal body temperature (37 degrees C) before cooling, after cooling at 25 degrees C, and after rewarming at 37 degrees C. Circulatory function was measured for every 1 degree C of temperature change. Isoproterenol infusion at 37 degrees C induced cardiac acceleration, including the increases of heart rate, cardiac output, and peak first derivative of the left ventricular pressure curve. Systemic vascular and mean outflow resistances and mean aortic pressure decreased. During cooling, shivering thermogenesis continued, even down to 25 degrees C. At 25 degrees C, cardiac acceleration after isoproterenol infusion did not exist but relaxation rate increased slightly. Systemic vascular and mean outflow resistances decreased, but left ventricular end-diastolic and filling pressures increased. beta-Stimulation at normal body temperature increases shivering thermogenesis during cooling. The venous return to the left ventricle at 25 degrees C increased after isoproterenol infusion while systemic vascular resistance decreased, indicating systemic vasodilatation. This increase in preload is probably due to vasoconstriction in pulmonary vessels, which may be mediated by prejunctional beta-adrenoceptors. For cardiac inotrophy, the isoproterenol had no physiologically significant effects at 25 degrees C. After rewarming at 37 degrees C, the effects of isoproterenol were physiologically similar to the effects at the same temperature before cooling.
Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats
Authors: Gute D. , Fraga C. , Laughlin M. H. , Amann J. F.
Published: December 2017

The objective of this study was to test the hypothesis that an endurance training program designed to produce recruitment of all extensor muscle fiber types during each exercise bout would stimulate capillary angiogenesis throughout rat gastrocnemius and soleus muscles. Male Sprague-Dawley rats were exercise trained 5 days/wk for 12–14 wk with exercise bouts consisting of a combination of high intensity (32 m/min on a 15% incline) and long duration (90 min/day). On completion of high-intensity endurance training (HIET) or cage activity [sedentary (Sed)], rat hindquarters were vascularly isolated and perfusion fixed with a modified Karnovsky's fixative. Capillary supply was measured in soleus and gastrocnemius muscles by using Olympus Cue 2 image-analyzer software. Capillary supply was reflected in measurements of capillary-to-fiber ratio, capillary numerical density, capillary surface area density, and capillary volume density on transversely cut tissue sections. HIET increased citrate synthase activity by 20 and 42% in the medial and long heads of the triceps brachii, respectively. Sarcomere lengths were similar in gastrocnemius and soleus muscles of Sed and HIET rats after fixation. All four indexes of capillary supply were significantly greater throughout the gastrocnemius muscle of HIET rats compared with Sed values. The relative increase in capillarity was greater in white than in red gastrocnemius muscle of HIET rats. HIET also increased capillary supply of soleus muscle. However, only capillary numerical density was statistically greater (19%) in HIET soleus compared with Sed. These results support the hypothesis that this training program would produce an increase in capillary supply in all extensor muscles.
The study of maximal nasal inspiratory flow in humans
Authors: Gold A. R. , Smith P. L. , Schwartz A. R.
Published: December 2017

During inspiration through one nostril, airflow becomes limited to a maximal level (VImax) when the transmural pressure (Ptm) at a flow-limiting site (FLS) falls below a critical level (Ptm'). We compared two methods for measuring the Ptm' of the nasal FLS. Each of six subjects (four normal and two with allergic rhinitis out of season) performed multiple inspirations through one nostril as we varied the resistance at the nasal opening. Studies were performed after application of a topical decongestant without activation of the alae nasi. We determined Ptm' by regressing the resulting values of VImax on the corresponding transnasal pressure gradients (Regression Method). We also measured Ptm' directly using pressure catheters to measure the pressure surrounding the FLS and the lateral pressure near the FLS at VImax (Catheter Method). The mean value of Ptm' by the Regression Method was -3.8 +/- 3.2 (SD) cmH2O. The value by the Catheter Method with the catheter just downstream from the nasal FLS was -3.5 +/- 2.9 cmH2O, which correlated closely with the Ptm by the Regression Method (r = 0.98). Our findings suggest that the Ptm' of the nasal airway can be determined by either method. The Catheter Method, however, requires only one inspiratory effort for each determination and simultaneously localizes the nasal FLS.
Adaptive responses of hypertrophying skeletal muscle to endurance training
Authors: Stone J. , Brannon T. , Haddad F. , Qin A. , Baldwin K. M.
Published: December 2017

We determined the effects of 6 wk of endurance running on citrate synthase (CS) activity and myosin heavy chain (MHC) expression in bilateral surgical-overloaded rodent fast-twitch plantaris and slow-twitch soleus muscles. The overload induced significant hypertrophy in both muscle types, and this response was enhanced by endurance training. The overload-induced compensatory hypertrophy was accompanied by a proportional increase in muscle CS content. Although endurance training produced significant increases in CS concentration in either muscle type of the normal-trained groups (P < 0.05), it was not effective in causing similar changes in the overloaded trained muscles. Also, overload of either the sedentary or trained groups produced an increase in slower MHC isoforms (i.e., type I in the soleus and types I and IIa in the plantaris) and a concomitant decrease in the faster MHC isoforms (type IIa in the soleus and IIb in the plantaris; P < 0.05), whereas endurance training alone produced the opposite effect, especially in the plantaris. Collectively, these data suggest that 1) increments in muscle oxidative enzyme content due to endurance training are compromised when a hypertrophying process is occurring concomitantly; and 2) the relative loading state imposed on the muscle during repetitive locomotor activity is critical in regulating the pattern of MHC plasticity.
Role of neutral endopeptidase in exercise-induced bronchoconstriction in asthmatic subjects
Authors: de Gouw H. W. , Diamant Z. , Kuijpers E. A. , Sont J. K. , Sterk P. J.
Published: December 2017

The membrane-bound metalloproteinase, neutral endopeptidase (NEP), is a degrading enzyme of both bronchoconstrictor and bronchodilator peptides within the airways. To examine the role of NEP in exercise-induced bronchoconstriction (EIB) in asthmatic subjects, we used inhaled thiorphan, a NEP inhibitor, as pretreatment to a 6-min standardized exercise challenge. Thirteen clinically stable asthmatic subjects participated in this double-blind, placebo-controlled, crossover study that was performed on 2 days separated by 48 h. Thiorphan was administered by two inhalations of 0.5 ml containing 1.25 mg/ml. Subsequently, exercise was performed on a bicycle ergometer at 40–50% of predicted maximal voluntary ventilation while inhaling dry air (20 degrees C, relative humidity 6%). The airway response to exercise was measured by forced expiratory volume in 1 s (FEV1) every 3 min, up to 30 min postexercise challenge, and was expressed both as the maximal percent fall in FEV1 from baseline and as the area under the time-response curve (AUC) (0–30 min). The acute effects of both pretreatments on baseline FEV1 were not different (P > 0.2), neither was there any difference in maximal percent fall in FEV1 between thiorphan and placebo (P > 0.7). However, compared with placebo, thiorphan reduced the AUC by, on average, 26% [AUC (0–30 min, +/-SE): 213.6 +/- 47.7 (thiorphan) and 288.6 +/- 46.0%fall.h (placebo); P = 0.047]. These data indicate that NEP inhibition by thiorphan reduces EIB during the recovery period. This suggests that bronchodilator NEP substrates, such as vasoactive intestinal polypeptide or atrial natriuretic peptide, modulate EIB in patients with asthma.
Passive tension in rat hindlimb during suspension unloading and recovery: muscle/joint contributions
Authors: Gillette P. D. , Fell R. D.
Published: December 2017

Muscle/joint stiffness associated with disuse conditions or weightlessness may seriously impair movement and work capacity. The purposes of this study were 1) to develop a noninvasive model to measure rat hindlimb passive tension, 2) to describe changes in passive tension (i.e., flexibility) during whole body suspension and weight-bearing recovery, and 3) to determine relative contributions of the posterior hindlimb to passive tension. Male Sprague-Dawley rats were suspended (14 days) and reloaded (14 days). On days 0, 7, 14, 17, 21, and 28, animals were anesthetized and hindlimb passive tension was measured during ankle dorsiflexion. Seven days of suspension significantly increased passive tension. Recovery of passive tension occurred by 14 days of weight bearing. In suspended animals, increased passive tension was due to musculotendinous units (75%) rather than to the joint (25%). Increased passive tension did not appear to be due to a shorter muscle, but changes in muscle architecture, cytoskeletal proteins, or viscoelastic properties of the muscle and its connective tissue elements cannot be excluded.
Erythropoietin under real and simulated microgravity conditions in humans
Authors: Gunga H. C. , Kirsch K. , Baartz F. , Maillet A. , Gharib C. , Nalishiti W. , Rich I. , Rocker L.
Published: December 2017

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.