bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical assessment of qualitative diagnostic calibration for respiratory inductive plethysmography
Authors: De Groote Anne , Paiva Manuel , Verbandt Yves
Published: December 2017

We present a critical assessment of qualitative diagnostic calibration (QDC), which claims to provide a relative calibration of respiratory inductive plethysmography during natural breathing (Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, and Krieger B. J Appl Physiol 66: 410–420, 1989). QDC computes the calibration factor ( K) by considering breaths of constant tidal volume (Vt) and provides a criterion to select breaths when Vt is unknown. We applied QDC on uncalibrated data constructed from simulated sets of thoracic and abdominal volumes, with a predefined K. As expected, QDC yields a correct K when applied to breaths at constant Vt. In breathing at quasi-constant Vt, the criterion for breath selection is shown to bias the results toward K = 1. For spontaneous breathing, the calculated K deviates from its predefined value and depends heavily on the selection criterion. We conclude that QDC will only provide a correct calibration factor when applied to an entire set of breaths with constant or quasi-constant Vt. More generally, physiological conclusions based on QDC should be critically evaluated on a case-by-case basis.
Effect of local acetylcholinesterase inhibition on sweat rate in humans
Authors: Shibasaki Manabu , Crandall Craig G.
Published: December 2017

ACh is the neurotransmitter responsible for increasing sweat rate (SR) in humans. Because ACh is rapidly hydrolyzed by acetylcholinesterase (AChE), it is possible that AChE contributes to the modulation of SR. Thus the primary purpose of this project was to identify whether AChE around human sweat glands is capable of modulating SR during local application of various concentrations of ACh in vivo, as well as during a heat stress. In seven subjects, two microdialysis probes were placed in the intradermal space of the forearm. One probe was perfused with the AChE inhibitor neostigmine (10 μM); the adjacent membrane was perfused with the vehicle (Ringer solution). SR over both membranes was monitored via capacitance hygrometry during microdialysis administration of various concentrations of ACh (1 × 10−7–2 M) and during whole body heating. SR was significantly greater at the neostigmine-treated site than at the control site during administration of lower concentrations of ACh (1 × 10−7–1 × 10−3 M, P < 0.05), but not during administration of higher concentrations of ACh (1 × 10−2–2 M, P > 0.05). Moreover, the core temperature threshold for the onset of sweating at the neostigmine-treated site was significantly reduced relative to that at the control site. However, no differences in SR were observed between sites after 35 min of whole body heating. These results suggest that AChE is capable of modulating SR when ACh concentrations are low to moderate (i.e., when sudomotor activity is low) but is less effective in governing SR after SR has increased substantially.
Fiber-type susceptibility to eccentric contraction-induced damage of hindlimb-unloaded rat AL muscles
Authors: Vijayan K. , Thompson J. L. , Norenberg K. M. , Fitts R. H. , Riley D. A.
Published: December 2017

Slow oxidative (SO) fibers of the adductor longus (AL) were predominantly damaged during voluntary reloading of hindlimb unloaded (HU) rats and appeared explainable by preferential SO fiber recruitment. The present study assessed damage after eliminating the variable of voluntary recruitment by tetanically activating all fibers in situ through the motor nerve while applying eccentric (lengthening) or isometric contractions. Muscles were aldehyde fixed and resin embedded, and semithin sections were cut. Sarcomere lesions were quantified in toluidine blue-stained sections. Fibers were typed in serial sections immunostained with antifast myosin and antitotal myosin (which highlights slow fibers). Both isometric and eccentric paradigms caused fatigue. Lesions occurred only in eccentrically contracted control and HU muscles. Fatigue did not cause lesions. HU increased damage because lesioned- fiber percentages within fiber types and lesion sizes were greater than control. Fast oxidative glycolytic (FOG) fibers were predominantly damaged. In no case did damaged SO fibers predominate. Thus, when FOG, SO, and hybrid fibers are actively lengthened in chronically unloaded muscle, FOG fibers are intrinsically more susceptible to damage than SO fibers. Damaged hybrid-fiber proportions ranged between these extremes.
Hypnotic manipulation of effort sense during dynamic exercise: cardiovascular responses and brain activation
Authors: Williamson J. W. , McColl R. , Mathews D. , Mitchell J. H. , Raven P. B. , Morgan W. P.
Published: December 2017

The purpose of this investigation was to hypnotically manipulate effort sense during dynamic exercise and determine whether cerebral cortical structures previously implicated in the central modulation of cardiovascular responses were activated. Six healthy volunteers (4 women, 2 men) screened for high hypnotizability were studied on 3 separate days during constant-load exercise under three hypnotic conditions involving cycling on a 1) perceived level grade, 2) perceived downhill grade, and 3) perceived uphill grade. Ratings of perceived exertion (RPE), heart rate (HR), blood pressure (BP), and regional cerebral blood flow (rCBF) distributions for several sites were compared across conditions using an analysis of variance. The suggestion of downhill cycling decreased both the RPE [from 13 ± 2 to 11 ± 2 (SD) units; P< 0.05] and rCBF in the left insular cortex and anterior cingulate cortex, but it did not alter exercise HR or BP responses. Perceived uphill cycling elicited significant increases in RPE (from 13 ± 2 to 14 ± 1 units), HR (+16 beats/min), mean BP (+7 mmHg), right insular activation (+7.7 ± 4%), and right thalamus activation (+9.2 ± 5%). There were no differences in rCBF for leg sensorimotor regions across conditions. These findings show that an increase in effort sense during constant-load exercise can activate both insular and thalamic regions and elevate cardiovascular responses but that decreases in effort sense do not reduce cardiovascular responses below the level required to sustain metabolic needs.
Selected Contribution: Chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans
Authors: Fatemian Marzieh , Robbins Peter A.
Published: December 2017

The ventilatory sensitivity to CO2, in hyperoxia, is increased after an 8-h exposure to hypoxia. The purpose of the present study was to determine whether this increase arises through an increase in peripheral or central chemosensitivity. Ten healthy volunteers each underwent 8-h exposures to 1) isocapnic hypoxia, with end-tidal Po2 (Pet O2 ) = 55 Torr and end-tidal Pco2 (Pet CO2 ) = eucapnia; 2) poikilocapnic hypoxia, with Pet O2 = 55 Torr and Pet CO2 = uncontrolled; and 3) air-breathing control. The ventilatory response to CO2 was measured before and after each exposure with the use of a multifrequency binary sequence with two levels of Pet CO2 : 1.5 and 10 Torr above the normal resting value. Pet O2 was held at 250 Torr. The peripheral (Gp) and the central (Gc) sensitivities were calculated by fitting the ventilatory data to a two-compartment model. There were increases in combined Gp + Gc (26%, P < 0.05), Gp (33%, P < 0.01), and Gc (23%, P = not significant) after exposure to hypoxia. There were no significant differences between isocapnic and poikilocapnic hypoxia. We conclude that sustained hypoxia induces a significant increase in chemosensitivity to CO2 within the peripheral chemoreflex.
Reflex control of the cutaneous circulation after acute and chronic local capsaicin
Authors: Charkoudian Nisha , Fromy Bérengère , Saumet Jean-Louis
Published: December 2017

To investigate whether local activity of capsaicin-sensitive sensory afferents in the skin has a modulatory role in the reflex cutaneous vasodilator response to hyperthermia in humans, experiments were conducted in two parts. First, low-dose topical capsaicin (0.025%) was administered acutely to stimulate local activity of these afferents. Second, we temporarily desensitized these nerves in a small area of skin using chronic capsaicin treatment (0.075% for 7 days). Each intervention was followed by whole body heating using water-perfused suits and then by local warming to 42°C for assessment of maximum cutaneous vascular conductance. Skin blood flow was measured by laser-Doppler flowmetry and divided by mean arterial pressure (Finapres) for assessment of cutaneous vascular conductance. Maximum vascular conductance was not influenced by either acute or chronic capsaicin treatment ( P > 0.10). After acute capsaicin, baseline cutaneous vascular conductance was elevated above that at control sites (25.34 ± 6.25 vs. 10.57 ± 2.42%max; P < 0.05). However, internal temperature thresholds for vasodilation were not affected by either acute or chronic capsaicin ( P > 0.10). Furthermore, neither acute (control: 112.74 ± 36.83 vs. acute capsaicin: 96.92 ± 28.92%max/°C; P > 0.10) nor chronic (control: 142.45 ± 61.89 vs. chronic capsaicin: 132.12 ± 52.60%max/°C; P > 0.10) capsaicin administration influenced the sensitivity of the reflex cutaneous vasodilator response. We conclude that local activity of capsaicin-sensitive afferents in the skin does not modify reflex cutaneous vasodilation during hyperthermia.
Effects of HRT and exercise training on insulin action, glucose tolerance, and body composition in older women
Authors: Evans Ellen M. , Van Pelt Rachael E. , Binder Ellen F. , Williams Daniel B. , Ehsani Ali A. , Kohrt Wendy M.
Published: December 2017

The independent and combined effects of exercise training and hormone replacement therapy (HRT) on body composition, fat distribution, glucose tolerance, and insulin action were studied in postmenopausal women, aged 68 ± 5 yr, assigned to control ( n = 19), exercise ( n = 18), HRT ( n = 15), and exercise + HRT ( n = 16) groups. The exercise consisted of 2 mo of flexibility exercises followed by 9 mo of endurance exercise. HRT was conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Total and regional body composition were measured by dual-energy X-ray absorptiometry. Serum glucose and insulin responses were measured during a 2-h oral glucose tolerance test. There were significant main effects of exercise on reductions in total and regional (trunk, arms, legs) fat mass, increase in leg fat-free mass, and improvements in glucose tolerance and insulin action. There were significant main effects of HRT on the reduction of total fat mass (HRT, −3.0 ± 4.0 kg; no HRT, −1.3 ± 2.6 kg), with a strong trend for reductions in trunk and leg fat mass (both P = 0.07). There was also a significant improvement in insulin action in response to HRT. These results suggest that there are independent and additive effects of exercise training and HRT on the reduction in fat mass and improvement in insulin action in postmenopausal women; the effect of HRT on insulin action may be mediated, in part, through changes in central adiposity.
Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages
Authors: Lambert G. Patrick , Broussard Lorenzo J. , Mason Benjamin L. , Mauermann William J. , Gisolfi Carl V.
Published: December 2017

The purpose of this study was to determine whether aspirin (A) ingestion combined with prolonged exercise increases gastrointestinal permeability and whether consumption of a carbohydrate-containing (CHO) or a CHO + glutamine-containing (CHO+G) beverage would reduce this effect. Seventeen subjects completed six experiments. They ingested A (1,300 mg) or placebo (P) pills the evening before and before running 60 min at 70% maximal oxygen uptake. Also, before running they ingested a solution containing 5 g lactulose (L), 5 g sucrose (S), and 2 g rhamnose (R). During each trial, either a 6% CHO beverage, a 6% CHO+G (0.6%; 41 mM) beverage, or a water placebo (WP) was consumed. For 4 h after a run, all urine was collected to measure urinary excretion of L, R, and S. S excretion (percentage of dose ingested; measure of gastroduodenal permeability) was significantly greater ( P < 0.05) during the A trial while the subjects drank the WP compared with all other trials. Administration of A also significantly increased L/R (measure of intestinal permeability) for the CHO and WP trials compared with all P trials. Ingestion the CHO or CHO+G beverages significantly reduced S excretion and L excretion when A was administered, but it did not reduce L/R. These results indicate that gastroduodenal and intestinal permeability increase after A ingestion during prolonged running and that ingestion of a CHO beverage attenuates the gastroduodenal effect but not the intestinal effect. Furthermore, addition of G to the CHO beverage provided no additional benefit in reducing gastroduodenal or intestinal permeability.
Noninvasive assessment of pulmonary arterial hypertension by MR phase-mapping method
Authors: Laffon Eric , Laurent François , Bernard Virginie , De Boucaud Laurent , Ducassou Dominique , Marthan Roger
Published: December 2017

We describe a magnetic resonance (MR) imaging method that emphasizes pressure wave velocity to noninvasively assess pulmonary arterial hypertension. Both the blood flow and the corresponding vessel cross-sectional area (CSA) were measured by MR phase mapping in the main pulmonary artery (MPA) in 15 patients. MPA pressures were also measured, in the same patients, by right-side heart catheterization. Two significant relationships were established: 1) between the pressure wave velocity in the MPA and the mean pressure in the MPA (Ppa) writing pressure wave velocity = 9.25 Ppa − 202.51 ( r = 0.82) and 2) between the ratio of pressure wave velocity to the systolic blood velocity peak in the MPA (R) and the mean pressure in the MPA writing R = 0.68 Ppa − 4.33 ( r = 0.89). Using these relationships, we estimated two pressure values to frame the actual Ppa value in each patient from the present series with a reasonable reliability percentage (87%).
Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection
Authors: Collins Brendan J. , Blum Matthew G. , Parker Richard E. , Chang Andrew C. , Blair Kelly S. A. , Zorn George L. , Christman Brian W. , Pierson Richard N.
Published: December 2017

The role of thromboxane (Tx) in hyperacute rejection of pig lung by human blood was studied in an ex vivo model, wherein lungs from juvenile piglets were perfused with fresh heparinized human blood. In this model, hyperacute lung rejection was characterized by an abrupt rise in pulmonary vascular resistance (PVR; >1 cmH2O · ml−1· min) and prolific Tx elaboration (>15 ng/ml) within 5 min and loss of function within 10 min. Although papaverine significantly blunted the rise in PVR (<0.2 cmH2O · ml−1· min), Tx production was not inhibited (>20 ng/ml), and florid tracheal edema was usually evident within 20 min. In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O · ml−1· min) but also with attenuated increase in lung wet-to-dry ratio and airway edema. In concert, elaboration of histamine and tumor necrosis factor was blunted, and median survival increased >10-fold to 2 h (SQ-30741) and >4 h (OKY-046). Depletion of the pig lung macrophages with dichloromethyl bisphosphonate in liposomes, but not Pall filtration of the human blood or liposomes alone, significantly inhibited Tx elaboration (<0.2 vs. >8 ng/ml for Pall filtration or liposomes) and blunted PVR elevation (<0.3 cmH2O · ml−1· min) during initial perfusion. C3a and histamine elaboration were inhibited, and median survival was significantly prolonged (>4 h). These findings implicate Tx in the inflammation associated with hyperacute lung rejection and demonstrate that pulmonary intravascular macrophages are critical to its elaboration.
Systemic and lung physiological changes in rats after intravascular activation of complement
Authors: Younger John G. , Sasaki Nobuyoshi , Delgado Joao , Ko Angela C. , Nghiem Trac X. , Waite Michael D. , Till Gerd O. , Ward Peter A.
Published: December 2017

Systemic complement activation has been noted in a variety of shock states, and there is growing evidence that, in addition to being proinflammatory effectors, products of complement activation contribute directly to generalized manifestations of shock, such as hypotension and acidosis. To study the effects of complement activation, we examined responses in rats to systemic activation of complement with cobra venom factor (CVF), including blood pressure, metabolic acidosis, changes in vascular permeability, and lung function. High doses of CVF produced circulatory collapse (mean arterial pressure = 110 ± 16 and 35 ± 9 mmHg in control and with CVF, respectively, P < 0.05), metabolic acidosis (HCO[Formula: see text] concentration = 27.8 ± 1.7 and 9.6 ± 3.4 meq/l in control and with CVF, respectively, P < 0.05), extravasation of albumin into the lung and gut, and modest arterial hypoxemia (Po2= 486 ± 51 and 201 ± 36 Torr in control and during 100% O2breathing, respectively, P < 0.05). Prior depletion of complement protected against these abnormalities. Other interventions, including neutrophil depletion and cyclooxygenase inhibition, prevented lung injury but had much less effect on systemic hemodynamics or gut permeability, suggesting that complement activation products induce injury by neutrophil- and cyclooxygenase-dependent pathways in the lung but not in the gut. These studies underscore the significant systemic abnormalities developing after systemic activation of complement.
Identification of respiratory vagal feedback in awake normal subjects using pseudorandom unloading
Authors: BuSha Brett F. , Judd Brooke G. , Manning Harold L. , Simon Peggy M. , Searle Brian C. , Daubenspeck J. Andrew , Leiter J. C.
Published: December 2017

Evidence of the Hering-Breuer reflex has been found in humans during anesthesia and sleep but not during wakefulness. Cortical influences, present during wakefulness, may mask the effects of this reflex in awake humans. We hypothesized that, if lung volume were increased in awake subjects unaware of the stimulus, vagal feedback would modulate breathing on a breath-to-breath basis. To test this hypothesis, we employed proportional assist ventilation in a pseudorandom sequence to unload the respiratory system above and below the perceptual threshold in 17 normal subjects. Tidal volume, integrated respiratory muscle pressure per breath, and inspiratory time were recorded. Both sub- and suprathreshold stimulation evoked a significant increase in tidal volume and inspiratory flow rate, but a significant decrease in inspiratory time was present only during the application of a subthreshold stimulus. We conclude that vagal feedback modulates respiratory timing on a breath-by-breath basis in awake humans, as long as there is no awareness of the stimulus.
Randomized trial of progressive resistance training to counteract the myopathy of chronic heart failure
Authors: Pu Charles T. , Johnson Meredith T. , Forman Daniel E. , Hausdorff Jeffrey M. , Roubenoff Ronenn , Foldvari Mona , Fielding Roger A. , Singh Maria A. Fiatarone
Published: December 2017

Chronic heart failure (CHF) is characterized by a skeletal muscle myopathy not optimally addressed by current treatment paradigms or aerobic exercise. Sixteen older women with CHF were compared with 80 age-matched peers without CHF and randomized to progressive resistance training or control stretching exercises for 10 wk. Women with CHF had significantly lower muscle strength ( P < 0.0001) but comparable aerobic capacity to women without CHF. Exercise training was well tolerated and resulted in no changes in resting cardiac indexes in CHF patients. Strength improved by an average of 43.4 ± 8.8% in resistance trainers vs. −1.7 ± 2.8% in controls ( P = 0.001), muscle endurance by 299 ± 66% vs. 1 ± 3% ( P = 0.001), and 6-min walk distance by 49 ± 14 m (13%) vs. −3 ± 19 m (−3%) ( P = 0.03). Increases in type I fiber area (9.5 ± 16%) and citrate synthase activity (35 ± 21%) in skeletal muscle were independently predictive of improved 6-min walk distance ( r 2 = 0.78; P = 0.0024). High-intensity progressive resistance training improves impaired skeletal muscle characteristics and overall exercise performance in older women with CHF. These gains are largely explained by skeletal muscle and not resting cardiac adaptations.
Validation of a new live cell strain system: characterization of plasma membrane stress failure
Authors: Stroetz Randolph W. , Vlahakis Nicholas E. , Walters Bruce J. , Schroeder Mark A. , Hubmayr Rolf D.
Published: December 2017

Motivated by our interest in lung deformation injury, we report on the validation of a new live cell strain system. We showed that the system maintains a cell culture environment equivalent to that provided by conventional incubators and that its strain ouput was uniform and reproducible. With this system, we defined cell deformation dose (i.e., membrane strain amplitude)-cell injury response relationships in alveolar epithelial cultures and studied the effects of temperature on them. Deformation injury occurred in the form of reversible, nonlethal plasma membrane stress failure events and was quantified as the fraction of cells with uptake and retention of fluorescein-labeled dextran (FITC-Dx). The undeformed control population showed virtually no FITC-Dx uptake at any temperature, which was also true for cells strained by 3%. However, when the membrane strain was increased to 18%, ∼5% of cells experienced deformation injury at a temperature of 37°C. Moreover, at that strain, a reduction in temperature to 4°C resulted in a threefold increase in the number of cells with plasma membrane breaks (from 4.8 to 15.9%; P < 0.05). Cooling of cells to 4°C also lowered the strain threshold at which deformation injury was first seen. That is, at a 9% substratum strain, cooling to 4°C resulted in a 10-fold increase in the number of cells with FITC-Dx staining (0.7 vs. 7.5%, P < 0.05). At that temperature, A549 cells offered a 50% higher resistance to shape change (magnetic twisting cytometry measurements) than at 37°C. We conclude that the strain-injury threshold of A549 cells is reduced at low temperatures, and we consider temperature effects on plasma-membrane fluidity, cytoskeletal stiffness, and lipid trafficking as responsible mechanisms.
Relationship between body heat content and finger temperature during cold exposure
Authors: Brajkovic Dragan , Ducharme Michel B. , Frim John
Published: December 2017

The purpose of the present experiment was to examine the relationship between rate of body heat storage (S˙), change in body heat content (ΔHb), extremity temperatures, and finger dexterity. S˙, ΔHb , finger skin temperature (Tfing), toe skin temperature, finger dexterity, and rectal temperature were measured during active torso heating while the subjects sat in a chair and were exposed to −25°C air. S˙ and ΔHb were measured using partitional calorimetry, rather than thermometry, which was used in the majority of previous studies. Eight men were exposed to four conditions in which the clothing covering the body or the level of torso heating was modified. After 3 h, Tfing was 34.9 ± 0.4, 31.2 ± 1.2, 18.3 ± 3.1, and 12.1 ± 0.5°C for the four conditions, whereas finger dexterity decreased by 0, 0, 26, and 39%, respectively. In contrast to some past studies, extremity comfort can be maintained, despite S˙ that is slightly negative. This study also found a direct linear relationship between ΔHb and Tfing and toe skin temperature at a negative ΔHb. In addition, ΔHb was a better indicator of the relative changes in extremity temperatures and finger dexterity over time than S˙.
Simple freezing apparatus for resolving rapid metabolic events associated with smooth muscle activation
Authors: Maass-Moreno Roberto , Burdyga Theodor , Mitchell Richard W. , Seow Chun Y. , Ragozzino Joseph , Ford Lincoln E.
Published: December 2017

A method is described for freezing thin strips of smooth muscle by replacing physiological saline in the muscle chamber with cold organic solvent in <100 ms. Calculations suggest that, with a perfectly stirred boundary at the tissue surface, freezing could occur within ∼15 ms at the center of a 200-μm-thick piece of tissue by use of acetone coolant at −78.5°C and in approximately half the time with either isopentane at its freezing point (−160°C) or aluminum chilled with liquid nitrogen. Myosin light chain phosphorylation in muscles frozen with cold acetone began to rise ∼200 ms earlier than force and increased at a much more rapid rate. The difference in onsets of the two processes reflects the delay in arresting phosphorylation plus two lags associated with force generation, attachment of phosphorylated bridges followed by force generating movements of the attached bridges. The much more rapid rise of phosphorylation, once it began, suggests that most of this delay is due to physiological lags and not to slow arrest of metabolism.
Ventilation-perfusion inhomogeneity increases gas uptake in anesthesia: computer modeling of gas exchange
Authors: Peyton Philip J. , Robinson Gavin J. B. , Thompson Bruce
Published: December 2017

Ventilation-perfusion (V˙a/Q˙) inhomogeneity was modeled to measure its effect on overall gas exchange during maintenance-phase N2O anesthesia with an inspired O2 concentration of 30%. A multialveolar compartment computer model was used based on physiological log normal distributions of V˙a/Q˙ inhomogeneity. Increasing the log standard deviation of the distribution of perfusion from 0 to 1.75 paradoxically increased O2 uptake (V˙o 2) where a low mixed venous partial pressure of N2O [high N2O uptake (V˙n 2 o)] was specified. With rising mixed venous partial pressure of N2O, a threshold was observed where V˙o 2 began to fall, whereas V˙n 2 o began to rise with increasing V˙a/Q˙ inhomogeneity. This phenomenon is a magnification of the concentrating effects thatV˙o 2 andV˙n 2 o have on each other in low V˙a/Q˙ compartments. During “steady-state” N2O anesthesia,V˙n 2 o is predicted to paradoxically increase in the presence of worseningV˙a/Q˙ inhomogeneity.
Effects of postural changes and vestibular lesions on diaphragm and rectus abdominis activity in awake cats
Authors: Cotter L. A. , Arendt H. E. , Jasko J. G. , Sprando C. , Cass S. P. , Yates B. J.
Published: December 2017

Changes in posture can affect the resting length of the diaphragm, requiring alterations in the activity of both the abdominal muscles and the diaphragm to maintain stable ventilation. To determine the role of the vestibular system in regulating respiratory muscle discharges during postural changes, spontaneous diaphragm and rectus abdominis activity and modulation of the firing of these muscles during nose-up and ear-down tilt were compared before and after removal of labyrinthine inputs in awake cats. In vestibular-intact animals, nose-up and ear-down tilts from the prone position altered rectus abdominis firing, whereas the effects of body rotation on diaphragm activity were not statistically significant. After peripheral vestibular lesions, spontaneous diaphragm and rectus abdominis discharges increased significantly (by ∼170%), and augmentation of rectus abdominis activity during nose-up body rotation was diminished. However, spontaneous muscle activity and responses to tilt began to recover after a few days after the lesions, presumably because of plasticity in the central vestibular system. These data suggest that the vestibular system provides tonic inhibitory influences on rectus abdominis and the diaphragm and in addition contributes to eliciting increases in abdominal muscle activity during some changes in body orientation.
Gender differences in leucine, but not lysine, kinetics
Authors: Lamont Linda S. , McCullough Arthur J. , Kalhan Satish C.
Published: December 2017

There is a controversy in the literature as to the effects of gender on leucine kinetics. Two research groups found that men oxidize more leucine during exercise, whereas another group showed no gender effects. The purpose of our study was to examine the effects of gender on leucine and, for comparison purposes, lysine kinetics. Our subjects ( n = 14) were seven matched pairs of men and women selected for their exercise habits and age. After 1 wk of a standardized diet, they exercised at 50% of maximal O2uptake for 1 h. There was an effect of exercise in both genders: an increased leucine oxidation and an attenuation in nonoxidative leucine disposal compared with rest ( P < 0.05). Furthermore, our study confirms that there are gender differences in leucine, but not lysine, kinetics. Men had a higher rate of leucine oxidation and a lower rate of nonoxidative leucine disposal during exercise ( P < 0.05). For women, a larger proportion of their exercise energy needs came from fat; for men, a greater fraction came from carbohydrate ( P < 0.05). We conclude that female exercisers rely to a greater extent on fat as an energy source, thereby using less carbohydrate, amino acid, and protein as a fuel source.
Assessment of dry heat exchanges in newborns: influence of body position and clothing in SIDS
Authors: Elabbassi Elmountacer Billah , Bach Véronique , Makki Malek , Delanaud Stephane , Telliez Frédéric , Leke André , Libert Jean-Pierre
Published: December 2017

A dramatic decrease of sudden infant death syndrome (SIDS) has been noted following the issuance of recommendations to adopt the supine sleeping position for infants. It has been suggested that the increased risk could be related to heat stress associated with body position. In the present study, the dry heat losses of small-for-gestational-age newborns nude or clothed were assessed and compared to see whether there is a difference in the ability to lose heat between the prone and supine positions. An anthropomorphic thermal mannequin was exposed to six environmental temperatures, ranging between 25 and 37°C, in a single-walled, air-heated incubator. The magnitudes of heat losses did not significantly differ between the two body positions for the nude (supine 103.46 ± 29.67 vs. prone 85.78 ± 34.91 W/m2) and clothed mannequin (supine 59.35 ± 21.51 vs. prone 63.17 ± 23.06 W/m2). With regard to dry heat exchanges recorded under steady-state conditions, the results show that there is no association between body position and body overheating.
Comparison of OPS imaging and conventional capillary microscopy to study the human microcirculation
Authors: Mathura Keshen R. , Vollebregt Karlijn C. , Boer Kees , De Graaff Jurgen C. , Ubbink Dirk T. , Ince Can
Published: December 2017

Orthogonal polarization spectral (OPS) imaging is a new clinical technique for observation of the microcirculation of organ surfaces. For validation purposes, we compared OPS images of the nailfold skin with those obtained from conventional capillary microscopy at rest and during venous occlusion in 10 male volunteers. These images were computer analyzed to provide red blood cell velocity and capillary diameters of the same nailfold capillaries at rest and during venous occlusion. Results showed that OPS images provided similar values for red blood cell velocity and capillary diameter as those obtained from capillary microscopy images. OPS imaging, however, provided significantly better image quality, as shown by comparison of image contrast between OPS imaging and capillary microscopy. This made image analysis better and easier to perform. It is anticipated, therefore, that OPS imaging will become a new and powerful technique in the study of the human microcirculation in vivo because it can be used on human internal organs.
Mechanical stretch promotes alveolar epithelial type II cell differentiation
Authors: Sanchez-Esteban Juan , Cicchiello Lawrence A. , Wang Yulian , Tsai Shu-Whei , Williams Lakisha K. , Torday John S. , Rubin Lewis P.
Published: December 2017

Functional maturation of pulmonary alveolar epithelial cells is crucial for extrauterine survival. Mechanical distension and mesenchymal-epithelial interactions play important roles in this process. We hypothesized that mechanical stretch simulating fetal breathing movements is an important regulator of pulmonary epithelial cell differentiation. Using a Flexercell Strain Unit, we analyzed effects of stretch on primary cultures of type II cells and cocultures of epithelial and mesenchymal cells isolated from fetal rat lungs during late development. Cyclic stretch of isolated type II cells increased surfactant protein (SP) C mRNA expression by 150 ± 30% over controls ( P < 0.02) on gestational day 18 and by 130 ± 30% on day 19 ( P< 0.03). Stretch of cocultures with fibroblasts increased SP-C expression on days 18 and 19 by 170 ± 40 and 270 ± 40%, respectively, compared with unstretched cocultures. On day 19, stretch of isolated type II cells increased SP-B mRNA expression by 50% ( P < 0.003). Unlike SP-C, addition of fibroblasts did not produce significant additional effects on SP-B mRNA levels. Under these conditions, we observed only modest increases in cellular immunoreactive SP-B, but secreted saturated phosphatidylcholine rose by 40% ( P< 0.002). These results indicate that cyclic stretch promotes developmentally timed differentiation of fetal type II cells, as a direct effect on epithelial cell function and via mesenchymal-epithelial interactions. Expression of the SP-C gene appears to be highly responsive to mechanical stimulation.
Contribution of CD54 to human eosinophil and neutrophil superoxide production
Authors: Takashi Shuji , Okubo Yoshio , Horie Shiro
Published: December 2017

We have reported that CD54 on eosinophils is involved in eosinophil degranulation. However, the role of CD54 in eosinophil and neutrophil superoxide production is still uncertain. We assessed the effect of CD54 on eosinophils and neutrophils in recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)- or phorbol myristate acetate (PMA)-induced superoxide production through CD18. Anti-CD54 monoclonal antibody attenuated leukocyte aggregation and superoxide production of rGM-CSF- or PMA-stimulated neutrophils and PMA-stimulated eosinophils. Anti-CD18 monoclonal antibody or theophylline attenuated superoxide production of eosinophils and neutrophils stimulated by either stimuli. Flow cytometric analysis demonstrated CD54 expression on freshly isolated neutrophils but not on freshly isolated eosinophils. CD54 newly expressed on eosinophils reached its peak expression 30 min after PMA stimulation. The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline. These data demonstrated that CD54 and CD18 interaction of eosinophils or neutrophils is involved in superoxide production and that the inhibition of superoxide production by theophylline may be at least partly due to the inhibition of CD54 and CD18.
Intracellular Po2decreases with increasing stimulation frequency in contracting singleXenopusmuscle fibers
Authors: Howlett Richard A. , Hogan Michael C.
Published: December 2017

There is currently some controversy regarding the manner in which skeletal muscle intracellular Po2changes with work intensity. Therefore, this study investigated the relationship between intracellular Po2and stimulation frequency in intact, isolated, single skeletal muscle fibers. Single, living muscle fibers ( n = 7) were microdissected from the lumbrical muscles of Xenopus and injected with the oxygen-sensitive probe palladium-meso-tetra(4-carboxyphenyl)porphine (0.5 mM). Fibers were mounted with platinum clips to a force transducer in a chamber, which was continuously perfused with Ringer solution (pH = 7.0) at a Po2of ∼30 Torr. Fibers were then stimulated sequentially for 3 min, followed by a 3-min rest, at each of five contraction frequencies (0.15, 0.2, 0.25, 0.33, and 0.5 Hz), in a random order, using tetanic contractions. Resting intracellular Po2averaged 31.2 ± 0.9 Torr. During steady-state stimulation, intracellular Po2declined to 21.2 ± 2.3, 17.1 ± 2.4, 15.3 ± 1.9, 9.8 ± 2.0, and 5.8 ± 1.4 Torr for 0.15, 0.2, 0.25, 0.33, and 0.5-Hz stimulation, respectively. Significant fatigue, as defined by a decrease in force to <50% of the initial force, occurred only at the highest (0.5 Hz) stimulation frequency in five of the cells and at 0.33 Hz in the other two. Regression analysis demonstrated that there was a significant ( P < 0.0001, r = 0.82) negative correlation between intracellular Po2and contraction frequency in these isolated, single cells. The linear decrease in intracellular Po2with stimulation frequency, and thus energy demand, suggests that a fall in intracellular Po2correlates with increased oxygen uptake in these single contracting cells.
Exogenous carbohydrate oxidation from drinks ingested during prolonged exercise in a cold environment in humans
Authors: Galloway Stuart D. R. , Wootton Steve A. , Murphy Jane L. , Maughan Ronald J.
Published: December 2017

Six healthy male volunteers performed four rides to exhaustion on a cycle ergometer at ∼80% of maximal oxygen consumption. Subjects ingested a bolus volume of fluid (7.14 ml/kg) immediately before exercise and additional fluid volumes (1.43 ml/kg) every 10 min during exercise. The fluids ingested were either a flavored water control or glucose-electrolyte beverages with glucose concentrations of 2, 6, or 12%. The beverages were labeled with [U-13C]glucose (99.2%: 0.05 g/l). Exercise capacity was not different ( P = 0.13) between trials; median (range) exercise time was 83.52 (79.85–89.68), 103.19 (78.82–108.22), 100.37 (80.60–124.07), and 94.76 (76.78–114.25) min in the 0, 2, 6, and 12% trials, respectively. The oxidation of exogenous glucose in each 15-min period was significantly lower in the 2% trial ( P = 0.02) than in the 6 and 12% trials where oxidation rates were between 0.5 and 0.7 g/min. No difference in endogenous glucose oxidation was observed between trials ( P = 0.71). These findings indicate that the oxidation of exogenous glucose during exercise of this intensity and duration in a cold environment is similar to that observed in warmer conditions. Thus a low oxidation of exogenous substrate is unlikely to be a factor limiting the effectiveness of carbohydrate-electrolyte drink ingestion on exercise capacity in a cold environment.
Reduced lipoprotein lipase activity in postural skeletal muscle during aging
Authors: Bey Lionel , Areiqat Enas , Sano Andrea , Hamilton Marc T.
Published: December 2017

Lipoprotein lipase (LPL) is a key enzyme for fatty acid and lipoprotein metabolism in muscle. However, the effect of aging on LPL regulation in skeletal muscle is unknown. We report the effect of aging on LPL regulation in the soleus (red oxidative postural) muscle and the tibialis anterior (white glycolytic non-weight-bearing) muscle in 4- and 24-mo-old Fischer 344 rats and 18- and 31-mo-old Fischer 344 × Brown-Norway F1 (F-344 × BN F1) rats. Total and heparin-releasable LPL (HR-LPL) activities were decreased 38% ( P< 0.01) and 52% ( P < 0.05), respectively, in the soleus muscle of the older Fischer 344 rats. There was a 32% reduction ( P < 0.05) of total LPL protein mass in the soleus muscle with aging. The results were confirmed in another strain. A decrease of total LPL activity (−50%, P < 0.05) was also found in the soleus muscle between 18- and 31-mo-old F-344 × BN F1 rats. LPL mRNA concentration in the soleus muscle was not different between ages. Total LPL protein mass was reduced by 46% ( P < 0.05) in the soleus muscle of the 31-mo-old F-344 × BN F1 rats. In the tibialis anterior muscle, neither LPL activity nor mRNA concentration was affected by age in either strain. In conclusion, LPL regulation in a non-weight-bearing muscle was not affected by aging. However, there was a pronounced reduction in LPL activity and LPL protein mass in postural muscle with aging.
Effect of l-NAME on oxygen uptake kinetics during heavy-intensity exercise in the horse
Authors: Kindig Casey A. , McDonough Paul , Erickson Howard H. , Poole David C.
Published: December 2017

There is evidence that oxidative enzyme inertia plays a major role in limiting/setting the O2 uptake (V˙o 2) response at the transition to higher metabolic rates and also that nitric oxide (NO) competitively inhibits V˙o 2 within the electron transport chain. To investigate whether NO is important in setting the dynamic response of V˙o 2 at the onset of high-intensity (heavy-domain) running in horses, five geldings were run on a treadmill across speed transitions from 3 m/s to speeds corresponding to 80% of peak V˙o 2with and without nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor (20 mg/kg; order randomized). l-NAME did not alter (both P> 0.05) baseline (3 m/s, 15.4 ± 0.3 and 16.2 ± 0.5 l/min for control and l-NAME, respectively) or end-exerciseV˙o 2 (56.9 ± 5.1 and 55.2 ± 5.8 l/min for control and l-NAME, respectively). However, in the l-NAME trial, the primary on-kinetic response was significantly ( P < 0.05) faster (i.e., reduced time constant, 27.0 ± 2.7 and 18.7 ± 3.0 s for control andl-NAME, respectively), despite no change in the gain ofV˙o 2 ( P > 0.05). The faster on-kinetic response was confirmed independent of modeling by reduced time to 50, 63, and 75% of overallV˙o 2 response (all P < 0.05). In addition, onset of the V˙o 2 slow component occurred earlier (124.6 ± 11.2 and 65.0 ± 6.6 s for control and l-NAME, respectively), and the magnitude of the O2 deficit was attenuated (both P < 0.05) in the l-NAME compared with the control trial. Acceleration of the V˙o 2kinetics by l-NAME suggests that NO inhibition of mitochondrial V˙o 2 may contribute, in part, to the intrinsic metabolic inertia evidenced at the transition to higher metabolic rates in the horse.
Laryngeal muscle response to phasic and tonic upper airway pressure and flow
Authors: Stella M. H. , England S. J.
Published: December 2017

The hypothesis that respiratory modulation due to upper airway (UA) pressure and flow is dependent on stimulus modality and respiratory phase-specific activation was assessed in anesthetized, tracheotomized, spontaneously breathing piglets. Negative pressure and flow applied to the isolated UA at room or body temperature during inspiration only enhanced posterior cricoarytenoid muscle activity from that present without UA pressure and flow (baseline) by 15–20%. Time shifting the onset of UA flow relative to tracheal flow decreased this enhancement. The same enhancement was observed with oscillatory or constant airflow. UA positive pressure and flow at room or body temperature applied during expiration only enhanced thyroarytenoid muscle activity from baseline by 50–160%. The same enhancement was observed with oscillatory or constant airflow at body temperature. Constant positive pressure and flow enhanced thyroarytenoid muscle activity more than oscillatory pressure and flow at room temperature. We conclude that the respiratory modulation of UA afferents is processed in a phase-specific fashion and is dependent on stimulus modality (tonic vs. phasic).
Selected Contribution: Time course and heterogeneity of contractile responses in cultured human airway smooth muscle cells
Authors: Fabry Ben , Maksym Geoffrey N. , Shore Stephanie A. , Moore Paul E. , Panettieri Reynold A. , Butler James P. , Fredberg Jeffrey J.
Published: December 2017

We measured the time course and heterogeneity of responses to contractile and relaxing agonists in individual human airway smooth muscle (HASM) cells in culture. To this end, we developed a microrheometer based on magnetic twisting cytometry adapted with a novel optical detection system. Ferromagnetic beads (4.5 μm) coated with Arg-Gly-Asp peptide were bound to integrins on the cell surface. The beads were twisted in a sinusoidally varying magnetic field at 0.75 Hz. Oscillatory bead displacements were recorded using a phase-synchronized video camera. The storage modulus (cell stiffness; G′), loss modulus (friction; G"), and hysteresivity (η; ratio of G" to G′) could be determined with a time resolution of 1.3 s. Within 5 s after addition of histamine (100 μM), G′ increased by 2.2-fold, G" increased by 3.0-fold, and η increased transiently from 0.27 to 0.34. By 20 s, η decreased to 0.25, whereas G′ and G" remained above baseline. Comparable results were obtained with bradykinin (1 μM). These changes in G′, G", and η measured in cells were similar to but smaller than those reported for intact muscle strips. When we ablated baseline tone by adding the relaxing agonist dibutyryl cAMP (1 mM), G′ decreased within 5 min by 3.3-fold. With relaxing and contracting agonists, G′ could be manipulated through a contractile range of 7.3-fold. Cell populations exhibited a log-normal distribution of baseline stiffness (geometric SD = 2.8) and a heterogeneous response to both contractile and relaxing agonists, partly attributable to variability of baseline tone between cells. The total contractile range of the cells (from maximally relaxed to maximally stimulated), however, was independent of baseline stiffness. We conclude that HASM cells in culture exhibit a clear, although heterogeneous, response to contractile and relaxing agonists and express the essential mechanical features characteristic of the contractile response observed at the tissue level.
Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis
Authors: Parise G. , Mihic S. , MacLennan D. , Yarasheski K. E. , Tarnopolsky M. A.
Published: December 2017

Creatine monohydrate (CrM) supplementation during resistance exercise training results in a greater increase in strength and fat-free mass than placebo. Whether this is solely due to an increase in intracellular water or whether there may be alterations in protein turnover is not clear at this point. We examined the effects of CrM supplementation on indexes of protein metabolism in young healthy men ( n = 13) and women ( n = 14). Subjects were randomly allocated to CrM (20 g/day for 5 days followed by 5 g/day for 3–4 days) or placebo (glucose polymers) and tested before and after the supplementation period under rigorous dietary and exercise controls. Muscle phosphocreatine, creatine, and total creatine were measured before and after supplementation. A primed-continuous intravenous infusion of l-[1-13C]leucine and mass spectrometry were used to measure mixed-muscle protein fractional synthetic rate and indexes of whole body leucine metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine rate of appearance. CrM supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09). CrM supplementation did not increase muscle fractional synthetic rate but reduced leucine oxidation (−19.6%) and plasma leucine rate of appearance (−7.5%, P < 0.05) in men, but not in women. CrM did not increase total body mass or fat-free mass. We conclude that short-term CrM supplementation may have anticatabolic actions in some proteins (in men), but CrM does not increase whole body or mixed-muscle protein synthesis.