bluuebunny/crossref_metadata_2025 huggingface dataset:
Selected Contribution: Circadian rhythm variation in activity, body temperature, and heart rate between C3H/HeJ and C57BL/6J inbred strains
Authors: Tankersley Clarke G. , Irizarry Rafael , Flanders Susan , Rabold Richard
Published: March 2015

Inbred mice have been routinely used in studies of genetic effects that determine behavioral variation due to circadian rhythm. In addition to activity patterns (Act), we aimed to characterize variations in the circadian rhythm of deep-body temperature (Tdb) and heart rate (HR) in a specific genetic model of differential cardiorespiratory control. Radiotelemeters were implanted in C3H/HeJ (C3; n = 11) and C57BL/6J (B6; n = 11) inbred strains. Reciprocal first-generation offspring, B6C3F1/J (B6F1; n = 8) and C3B6F1 (C3F1; n = 3) mice, were included to initiate an evaluation of heritable phenotypes. Mice were housed individually in a facility maintained at 23–24°C, and the light-dark cycle was set at 12-h intervals. In each animal, repeated measurements were obtained at 30-min intervals, and the circadian patterns of Act, Tdb, and HR were assessed by novel statistical methods that detailed the periodic function for each strain. During the dark phase, B6 mice demonstrated two distinct peaks in Act and Tdb relative to a single early peak for C3 mice. In contrast to the parental strains, B6F1 and C3F1 mice demonstrated intermediate second peaks in Act and Tdb. With respect to HR, the C3 strain demonstrated a significantly ( P < 0.01) greater daily average compared with B6 mice. The circadian rhythm in HR differed significantly from the Act and Tdb patterns in B6 mice (but not in C3 mice); that is, the periodicity in HR for B6 mice preceded the rise and fall in Act and Tdb during both peaks. The B6 phenotype was also observed in F1 mice. In conclusion, these data suggest that the circadian regulation of Act, Tdb, and HR vary significantly among C3, B6, and F1 mice. Furthermore, phenotypic differences between C3 and B6 strains can be used to explore the genetic basis for differential circadian regulation of body temperature and HR.
Invited Review: Sleeping flies don't lie: the use ofDrosophila melanogasterto study sleep and circadian rhythms
Authors: Hendricks Joan C.
Published: March 2015

During the past century, flies thoroughly proved their value as an animal model for the study of the genetics of development and basic cell processes. During the past three decades, they have also been extensively used to study the genetics of behavior. For both circadian rhythms and for sleep, flies are helping us to understand the genetic mechanisms that underlie these complex behaviors. Since 1971, discoveries in the fly have led the way to a number of significant discoveries, establishing a mechanistic framework that is now known to be conserved in the mammalian clock. The highlights of this history are described. For sleep, the use of the fly as a model is relatively new, that is, only within the past 2 yr. Nonetheless, studies have already established that two transcription factors alter rest and rest homeostasis. The implications of these advances for the future of sleep research are summarized.
Mechanistic basis for the gas exchange threshold in Thoroughbred horses
Authors: McDonough Paul , Kindig Casey A. , Erickson Howard H. , Poole David C.
Published: March 2015

The exercising Thoroughbred horse (TB) is capable of exceptional cardiopulmonary performance. However, because the ventilatory equivalent for O2(V˙e/V˙o2) does not increase above the gas exchange threshold (Tge), hypercapnia and hypoxemia accompany intense exercise in the TB compared with humans, in whom V˙e/V˙o2increases during supra-Tge work, which both removes the CO2produced by the HCO[Formula: see text] buffering of lactic acid and prevents arterial partial pressure of CO2(PaCO2) from rising. We used breath-by-breath techniques to analyze the relationship between CO2output (V˙co2) andV˙o2[V-slope lactate threshold (LT) estimation] during an incremental test to fatigue (7 to ∼15 m/s; 1 m · s−1· min−1) in six TB. Peak blood lactate increased to 29.2 ± 1.9 mM/l. However, as neither V˙e/V˙o2norV˙e/V˙co2increased, PaCO2increased to 56.6 ± 2.3 Torr at peakV˙o2(V˙o2 max). Despite the presence of a relative hypoventilation (i.e., no increase inV˙e/V˙o2orV˙e/V˙co2), a distinct Tge was evidenced at 62.6 ± 2.7%V˙o2 max. Tge occurred at a significantly higher ( P < 0.05) percentage ofV˙o2 maxthan the lactate (45.1 ± 5.0%) or pH (47.4 ± 6.6%) but not the bicarbonate (65.3 ± 6.6%) threshold. In addition, PaCO2was elevated significantly only at a workload > Tge. Thus, in marked contrast to healthy humans, pronounced V-slope (↑V˙co2/V˙o2) behavior occurs in TB concomitant with elevated PaCO2and without evidence of a ventilatory threshold.
Octanoate oxidation measured by13C-NMR spectroscopy in rat skeletal muscle, heart, and liver
Authors: Walton Marlei E. , Ebert Douglas , Haller Ronald G.
Published: March 2015

Contribution of octanoate to the oxidative metabolism of the major sites of fatty acid oxidation (heart, liver, and resting and contracting skeletal muscle) was assessed in the intact rat with13C-NMR spectroscopy. Under inhalation anesthesia, [2,4,6,8-13C4]octanoate was infused into the jugular vein and the sciatic nerve of one limb was stimulated for 1 h. Octanoate was a principal contributor to the acetyl-CoA pool in all tissues examined, with highest oxidation occurring in heart and soleus muscle followed by predominantly red portion of gastrocnemius muscle (RG), liver, and then white portion of gastrocnemius muscle (WG). Fractional contribution of13C-labeled octanoate to the acetyl-CoA pool (Fc2) was 0.563 ± 0.066 for heart and 0.367 ± 0.054 for liver. Significant differences were observed between each of the muscle types during both rest and contraction. In muscle, Fc2 was highest in soleus (0.565 ± 0.089 rested, 0.564 ± 0.096 contracted), followed by RG (0.470 ± 0.092 rested, 0.438 ± 0.072 contracted), and lowest in WG (0.340 ± 0.081 rested, 0.272 ± 0.065 contracted). Our findings demonstrate that the fractional contribution of octanoate to oxidative metabolism correlates with oxidative capacity of the tissue and that octanoate metabolism increases in contracted muscle in proportion to the overall increase in oxidative rate.
Gender differences in skeletal muscle fatigability are related to contraction type and EMG spectral compression
Authors: Clark Brian C. , Manini Todd M. , Thé Dwight J. , Doldo Neil A. , Ploutz-Snyder Lori L.
Published: March 2015

The purposes of this study were 1) to evaluate gender differences in back extensor endurance capacity during isometric and isotonic muscular contractions, 2) to determine the relation between absolute load and endurance time, and 3) to compare men [ n = 10, age 22.4 ± 0.69 (SE) yr] and women ( n = 10, age 21.7 ± 1.07 yr) in terms of neuromuscular activation patterns and median frequency (MF) shifts in the electromyogram (EMG) power spectrum of the lumbar and hip extensor muscles during fatiguing submaximal isometric trunk extension exercise. Subjects performed isotonic and isometric trunk extension exercise to muscular failure at 50% of maximum voluntary contraction force. Women exhibited a longer endurance time than men during the isometric task (146.0 ± 10.9 vs. 105.4 ± 7.9 s), but there was no difference in endurance performance during the isotonic exercise (24.3 ± 3.4 vs. 24.0 ± 2.8 repetitions). Absolute load was significantly related to isometric endurance time in the pooled sample ( R 2 = 0.34) but not when men and women were analyzed separately ( R 2 = 0.05 and 0.04, respectively). EMG data showed no differences in neuromuscular activation patterns; however, gender differences in MF shifts were observed. Women demonstrated a similar fatigability in the biceps femoris and lumbar extensors, whereas in men, the fatigability was more pronounced in the lumbar musculature than in the biceps femoris. Additionally, the MF of the lumbar extensors demonstrated a greater association with endurance time in men than in women ( R 2 = 0.45 vs. 0.19). These findings suggest that gender differences in muscle fatigue are influenced by muscle contraction type and frequency shifts in the EMG signal but not by alterations in the synergistic activation patterns.
Hemodilutional anemia is associated with increased cerebral neuronal nitric oxide synthase gene expression
Authors: Hare Gregory M. T. , Mazer C. David , Mak William , Gorczynski Reginald M. , Hum Kathryn M. , Kim Steve Y. , Wyard Leslie , Barr Aiala , Qu Rong , Baker Andrew J.
Published: March 2015

Severe hemodilutional anemia may reduce cerebral oxygen delivery, resulting in cerebral tissue hypoxia. Increased nitric oxide synthase (NOS) expression has been identified following cerebral hypoxia and may contribute to the compensatory increase in cerebral blood flow (CBF) observed after hypoxia and anemia. However, changes in cerebral NOS gene expression have not been reported after acute anemia. This study tests the hypothesis that acute hemodilutional anemia causes cerebral tissue hypoxia, triggering changes in cerebral NOS gene expression. Anesthetized rats underwent hemodilution when 30 ml/kg of blood were exchanged with pentastarch, resulting in a final hemoglobin concentration of 51.0 ± 1.2 g/l ( n = 7 rats). Caudate tissue oxygen tension (PbrO2) decreased transiently from 17.3 ± 4.1 to 14.4 ± 4.1 Torr ( P < 0.05), before returning to baseline after ∼20 min. An increase in CBF may have contributed to restoring PbrO2by improving cerebral tissue oxygen delivery. An increase in neuronal NOS (nNOS) mRNA was detected by RT-PCR in the cerebral cortex of anemic rats after 3 h ( P < 0.05, n = 5). A similar response was observed after exposure to hypoxia. By contrast, no increases in mRNA for endothelial NOS or interleukin-1β were observed after anemia or hypoxia. Hemodilutional anemia caused an acute reduction in PbrO2and an increase in cerebral cortical nNOS mRNA, supporting a role for nNOS in the physiological response to acute anemia.
Heat stress attenuates air bubble-induced acute lung injury: a novel mechanism of diving acclimatization
Authors: Huang Kun-Lun , Wu Chin-Pyng , Chen Yin-Li , Kang Bor-Hwang , Lin Yu-Chong
Published: March 2015

Diving acclimatization refers to a reduced susceptibility to acute decompression sickness (DCS) in individuals undergoing repeated compression-decompression cycles. We postulated that mechanisms responsible for the acclimatization are similar to that of a stress preconditioning. In this study, we investigated the protective effect of prior heat shock treatment on air embolism-induced lung injury and on the incidence of DCS in rats. We exposed rats ( n = 31) to a pressure cycle that induced signs of severe DCS in 48% of the rats, greater wet-to-dry ratio (W/D) of lung weight compared with the control group (5.48 ± 0.69 vs. 4.70 ± 0.17), and higher protein concentration in bronchoalveolar lavage (BAL) fluid (362 ± 184 vs. 209 ± 78 mg/l) compared with the control group. Rats with DCS expressed more heat shock protein 70 (HSP70) in the lungs than those without signs of disease. Prior heat shock ( n = 12) increased the expression of HSP70 in the lung and attenuated the elevation of W/D of lung weight (5.03 ± 0.17) after the identical decompression protocol. Prior heat shock reduced the incidence of severe DCS by 23%, but this failed to reach statistical significant (χ2= 1.94, P = 0.163). Venous air infusion (1.0 ml/40 min) caused profound hypoxemia (54.5 ± 3.8 vs. 83.8 ± 3.2 Torr at baseline; n = 6), greater W/D of lung weight (5.98 ± 0.45), and high protein concentration in BAL fluid (595 ± 129 mg/l). Prior heat shock ( n = 6) did not alter the level of hypoxemia caused by air embolism, but it accelerated the recovery to normoxemia after air infusion was stopped. Prior heat shock also attenuated the elevation of W/D of lung weight (5.19 ± 0.40) and the increase in BAL protein (371 ± 69 mg/l) in air embolism group. Our results showed that the occurrence of DCS after rapid decompression is associated with increased expression of a stress protein (HSP70) and that prior heat shock exposure attenuates the air bubble-induced lung injury. These results suggest that bubble formation in tissues activates a stress response and that stress preconditioning attenuates lung injury on subsequent stress, which may be the mechanism responsible for diving acclimatization.
Variability of ground reaction forces during treadmill walking
Authors: Masani Kei , Kouzaki Motoki , Fukunaga Tetsuo
Published: March 2015

The purpose of this study was to investigate whether or not the neuromuscular locomotor system is optimized at a unique speed by examining the variability of the ground reaction force (GRF) pattern during walking in relation to different constant speeds. Ten healthy male subjects were required to walk on a treadmill at 3.0, 4.0, 5.0, 6.0, 7.0, and 8.0 km/h. Three components [vertical (F z ), anteroposterior (F y ), and mediolateral (F x ) force] of the GRF were independently measured for ∼35 steps consecutively for each leg. To quantify the GRF pattern, five indexes (first and second peaks of F z , first and second peaks of F y , and F x peak) were defined. Coefficients of variation were calculated for these five indexes to evaluate the GRF variability for each walking speed. It became clear for first and second peaks of F z and F x peak that index variabilities increased in relation to increments in walking speed, whereas there was a speed (5.5–5.8 km/h) at which variability was minimum for first and second peaks of F y , which were related to forward propulsion of the body. These results suggest that there is “an optimum speed” for the neuromuscular locomotor system but only for the propulsion control mechanism.
Dysanaptic growth of conducting airways after pneumonectomy assessed by CT scan
Authors: Dane D. Merrill , Johnson Robert L. , Hsia Connie C. W. ,   (With the Technical Assistance of Richard T. Hogg, Heather L. Stanley, and Derric E. Lowe)
Published: March 2015

In immature dogs after pneumonectomy (PNX), pulmonary viscous resistance is persistently elevated predominantly as a result of a high airway resistance (Raw). We examined the anatomical basis for this observation by using computerized tomography scans obtained from foxhounds 4–10 mo after right PNX. Airways of the left lower lobe were followed from generations z = 0 (trachea) to z = 12. By 4 mo post-PNX, airway length increased significantly relative to sham-operated dogs, but airway cross-sectional area (CSA) did not. By 10 mo post-PNX, average airway CSA was 24% above that in controls. Theoretically, the increased airway length and CSA should reduce lobar Raw by 50%. However, post-PNX airway dilatation did not normalize total CSA, and estimated resistance due to turbulence and convective acceleration increased threefold; i.e., the 50% reduction in lobar Raw would be offset by the loss of four of seven lobes. Thus the expected reduction in work of breathing in the whole animal is only ∼30%, consistent with previously measured work of breathing in pneumonectomized dogs. We conclude that airway structure adapts slowly and incompletely, resulting in limited functional compensation.
5-HT3receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro
Authors: Moore Kimberly A. , Oh Eun Joo , Weinreich Daniel
Published: March 2015

Exogenously applied tachykinins produce no measurable electrophysiological responses in the somata of vagal afferent neurons [nodose ganglion neurons (NGNs)] isolated from naive guinea pigs. By contrast, after in vitro antigen challenge of nodose ganglia from guinea pigs immunized with chick ovalbumin, ∼60% (53 of 89) of NGNs were depolarized an average of 13 ± 1.2 mV by substance P (SP; 100 nM; n = 53). Receptor antagonists and enzyme inhibitors were utilized to screen a number of mast cell-derived mediators for their role in the uncovering or “unmasking” of functional tachykinin receptors after antigen challenge. Two chemically distinct 5-hydroxytryptamine-3-receptor antagonists significantly reduced the percentage of NGNs displaying depolarizing SP responses. Treatment with Y-25130 (1 or 10 μM) or tropisetron (1 μM) 15 min before and during antigen challenge reduced the percentage of SP-responsive neurons to ∼20 and ∼15%, respectively. These results suggest that activation of 5-hydroxytryptamine-3 receptors plays an integral role in the unmasking of functional tachykinin receptors after specific antigen challenge of nodose ganglia. The mediator(s) underlying tachykinin-receptor unmasking in the remainder of the NGNs has yet to be characterized. However, it does not appear to be histamine, prostanoids, or peptidoleukotrienes.
Adult carotid chemoafferent responses to hypoxia after 1, 2, and 4 wk of postnatal hyperoxia
Authors: Bisgard G. E. , Olson E. B. , Wang Z.-Y. , Bavis R. W. , Fuller D. D. , Mitchell G. S.
Published: March 2015

Exposing newborn rats to postnatal hyperoxia (60% O2) for 1-4 wk attenuates the ventilatory and phrenic nerve responses to acute hypoxia in adult rats. The goal of this research was to increase our understanding of the carotid chemoreceptor afferent neural input in this depressed response with different durations of postnatal hyperoxic exposure. Rats were exposed from a few days before birth to 1, 2, or 4 wk of 60% O2 and studied after 3-5 mo in normoxia. The rats were anesthetized with urethane. Whole carotid sinus nerve (CSN) responses to NaCN (40 μg/kg iv), 10 s of asphyxia and acute isocapnic hypoxia (arterial Po2 45 Torr) were determined. Mean CSN responses to stimuli after postnatal hyperoxia were reduced compared with controls. Responses in rats exposed to 1 wk of postnatal hyperoxia were less affected than those exposed to 2 and 4 wk of hyperoxia, which were equivalent to each other. These studies illustrate the importance of normoxia during the first 2 wk of life in development of carotid chemoreceptor afferent function.
Physical exercise increases urinary excretion of lipoxin A4 and related compounds
Authors: Gangemi Sebastiano , Luciotti Graziella , D'Urbano Etrusca , Mallamace Agostino , Santoro Domenico , Bellinghieri Guido , Davı̀ Giovanni , Romano Mario
Published: March 2015

Lipoxins (LX) are lipoxygenase-derived eicosanoids with potent anti-inflammatory activities and vascular bed-dependent vasodilatory actions. LX can be formed in vitro and in vivo in a number of conditions, and we have reported that immunoreactive LXA4 (iLXA4) is physiologically excreted with human urine. Using a recently developed LX extraction method coupled to an ELISA, we examined whether iLXA4 excretion was modified by strenuous exercise, which is known to trigger potential LX-forming events. Maximal exertion significantly increased iLXA4 urinary excretion in nine healthy volunteers (0.061 ± 0.023 vs. 0.113 ± 0.057 ng/mg creatinine; P = 0.028). iLXA4 levels returned to baseline after 6 h and increased, although at a smaller extent, after 24 h. A significant correlation ( r = 0.988) was denoted between iLXA4 ELISA measurements and reversed-phase high-performance liquid chromatography quantitation of a previously described urinary tetraene, confirming its LXA4-related nature. These findings show for the first time that an increase in excretion of LXA4-related compounds can be observed in response to strenuous exercise. This may be the reflection of an enhanced LX biosynthesis, which may represent a safeguard mechanism that keeps the inflammatory reaction triggered by physical stress under control.
Change in spontaneous baroreflex control of pulse interval during heat stress in humans
Authors: Lee Kichang , Jackson Dwayne N. , Cordero Douglas L. , Nishiyasu Takeshi , Peters Jochen K. , Mack Gary W.
Published: March 2015

Spontaneous baroreflex control of pulse interval (PI) was assessed in healthy volunteers under thermoneutral and heat stress conditions. Subjects rested in the supine position with their lower legs in a water bath at 34°C. Heat stress was imposed by increasing the bath temperature to 44°C. Arterial blood pressure (Finapres), PI (ECG), esophageal and skin temperature, and stroke volume were continuously collected during each 5-min experimental stage. Spontaneous baroreflex function was evaluated by multiple techniques, including 1) the mean slope of the linear relationship between PI and systolic blood pressure (SBP) with three or more simultaneous increasing or decreasing sequences, 2) the linear relationship between changes in PI and SBP (ΔPI/ΔSBP) derived by using the first differential equation, 3) the linear relationship between changes in PI and SBP with simultaneously increasing or decreasing sequences (+ΔPI/+ΔSBP or -ΔPI/-ΔSBP), and 4) transfer function analysis. Heat stress increased esophageal temperature by 0.6 ± 0.1°C, decreased PI from 1,007 ± 43 to 776 ± 37 ms and stroke volume by 16 ± 5 ml/beat. Heat stress reduced baroreflex sensitivity but increased the incidence of baroreflex slopes from 5.2 ± 0.8 to 8.6 ± 0.9 sequences per 100 heartbeats. Baroreflex sensitivity was significantly correlated with PI or vagal power ( r2 = 0.45, r2 = 0.71, respectively; P < 0.05). However, the attenuation in baroreflex sensitivity during heat stress appeared related to a shift in autonomic balance (shift in resting PI) rather than heat stress per se.
Behavior of human muscle fascicles during shortening and lengthening contractions in vivo
Authors: Reeves Neil D. , Narici Marco V.
Published: March 2015

The aim of the present study was to investigate the behavior of human muscle fascicles during dynamic contractions. Eight subjects performed maximal isometric dorsiflexion contractions at six ankle joint angles and maximal isokinetic concentric and eccentric contractions at five angular velocities. Tibialis anterior muscle architecture was measured in vivo by use of B-mode ultrasonography. During maximal isometric contraction, fascicle length was shorter and pennation angle larger compared with values at rest ( P < 0.01). During isokinetic concentric contractions from 0 to 4.36 rad/s, fascicle length measured at a constant ankle joint angle increased curvilinearly from 49.5 to 69.7 mm (41%; P < 0.01), whereas pennation angle decreased curvilinearly from 14.8 to 9.8° (34%; P < 0.01). During eccentric muscle actions, fascicles contracted quasi-isometrically, independent of angular velocity. The behavior of muscle fascicles during shortening contractions was believed to reflect the degree of stretch applied to the series elastic component, which decreases with increasing contraction velocity. The quasi-isometric behavior of fascicles during eccentric muscle actions suggests that the series elastic component acts as a mechanical buffer during active lengthening.
Phosphocreatine content of freeze-clamped muscle: influence of creatine kinase inhibition
Authors: Brault Jeffrey J. , Abraham Kirk A. , Terjung Ronald L.
Published: March 2015

The study of cellular energetics is critically dependent on accurate measurement of high-energy phosphates. Muscle values of phosphocreatine (PCr) vary greatly between in vivo measurements (i.e., by nuclear magnetic resonance) and chemical measurements determined from muscles isolated and quick-frozen. The source of this difference has not been experimentally identified. A likely cause is activation of ATPases and phosphotransfer from PCr to ADP. Therefore, rat hindlimb skeletal muscle was perfused either with or without 2 mM iodoacetamide, a creatine kinase inhibitor, and muscle was freeze-clamped either at rest or after contraction. Creatine kinase inhibition resulted in ∼6 μmol/g higher PCr and lower creatine in the freeze-clamped soleus, red gastrocnemius, and white gastrocnemius. This PCr content difference was reduced when the initial PCr content was decreased with prior contractions. Therefore, the amount of PCr artifact appears to scale with initial PCr content within a fiber-type section. This artifact directly affects the measurement and, thus, the calculations of muscle energetic parameters from studies using isolated and frozen muscle.
Effects of spontaneous swallows on breathing in awake goats
Authors: Feroah Thom R. , Forster H. V. , Fuentes Carla G. , Lang Ivan M. , Beste David , Martino Paul , Pan L. , Rice Tom
Published: March 2015

The effects of spontaneous swallows on breathing before, during, and after solitary swallows were investigated in 13 awake goats. Inspiratory (Ti) and expiratory (Te) time and respiratory output were determined from inspiratory airflow [tidal volume (Vt)] and peak diaphragmatic activity (Diapeak). The onset time for 1,128 swallows was determined from pharyngeal muscle electrical activity. During inspiration, the later the swallowing onset, the greater increase in Ti and Vt, whereas there was no significant effect on Te and Diapeak. Swallows in early expiration increased the preceding Ti and reduced Te, whereas later in expiration swallows increased Te. After expiratory swallows, Ti and Vt were reduced whereas minimal changes in Diapeak were observed. Phase response analysis revealed a within-breath, phase-dependent effect of swallowing on breathing, resulting in a resetting of the respiratory oscillator. However, the shift in timing in the breaths after a swallow was not parallel, further demonstrating a respiratory phase-dependent effect on breathing. We conclude that, in the awake state, within- and multiple-breath effects on respiratory timing and output are induced and/or required in the coordination of breathing and swallowing.
Developmental differences in pulmonary eNOS expression in response to chronic hypoxia in the rat
Authors: Chicoine Louis G. , Avitia Jose W. , Deen Cody , Nelin Leif D. , Earley Scott , Walker Benjimen R.
Published: March 2015

Chronic hypoxia (CH) increases pulmonary endothelial nitric oxide synthase (eNOS) protein levels in adult rats but decreases eNOS protein levels in neonatal pigs. We hypothesized that this differing response to CH is due to developmental rather than species differences. Adult and neonatal rats were placed in either hypobaric hypoxia or normoxia for 2 wk. At that time, body weight, hematocrit, plasma nitrite/nitrate (NOx−), and right ventricular and total ventricular heart weights were measured. Percent pulmonary arterial wall area of 20–50 and 51–100 μm arteries were also determined. Total lung protein extracts were assayed for eNOS levels by using immunoblot analysis. Compared with their respective normoxic controls, both adult and neonatal hypoxic groups demonstrated significantly decreased body weight, elevated hematocrit, and elevated right ventricular-to-total ventricular weight ratios. Both adult and neonatal hypoxic groups also demonstrated significantly larger percent pulmonary arterial wall area compared with their respective normoxic controls. Hypoxic adult pulmonary eNOS protein and plasma NOx− were significantly greater than levels found in normoxic adults. In contrast, hypoxic neonatal pulmonary eNOS protein and plasma NOx− were significantly less compared with normoxic neonates. We conclude that there is a developmental difference in eNOS expression and nitric oxide production in response to CH.
Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes
Authors: Wetter Thomas J. , Xiang Zhuzai , Sonetti David A. , Haverkamp Hans C. , Rice Anthony J. , Abbasi Adnan A. , Meyer Keith C. , Dempsey Jerome A.
Published: March 2015

We examined whether lung inflammatory mediators are increased during exercise and whether pharmacological blockade can prevent exercise-induced arterial hypoxemia (EIAH) in young athletes. Seventeen healthy athletes (9 men, 8 women; age 23 ± 3 yr) with varying degrees of EIAH completed maximal incremental treadmill exercise tests after administration of fexofenadine, zileuton, and nedocromil sodium or placebo in a randomized double-blind crossover study. Lung function, arterial blood gases, and inflammatory metabolites in plasma, urine, and induced sputum were assessed. Drug administration did not improve EIAH or gas exchange during exercise. At maximal exercise, oxygen saturation fell to 91.4 ± 2.6% (drug trial) and 91.9 ± 2.1% (placebo trial) and alveolar-arterial oxygen difference widened to 28.1 ± 6.3 Torr (drug trial) and 29.3 ± 5.7 Torr (placebo trial). Oxygen consumption, ventilation, and other exercise variables were similarly unaffected by drug treatment. Although plasma histamine increased with exercise, values did not differ between trials, and urinary leukotriene E4and 11β-prostaglandin F2αlevels were unchanged after exercise. Postexercise sputum revealed no significant changes in markers of inflammation. These results demonstrate that EIAH in young athletes is not attenuated with acute administration of drugs targeting histamine and bioactive lipids. We conclude that airway inflammation is of insufficient magnitude to cause impairments in gas exchange and does not appear to be linked to EIAH in healthy young athletes.
Muscle pump-dependent self-perfusion mechanism in legs in normal subjects and patients with heart failure
Authors: Shiotani Issei , Sato Hideyuki , Sato Hiroshi , Yokoyama Hiroshi , Ohnishi Yozo , Hishida Eiji , Kinjo Kunihiro , Nakatani Daisaku , Kuzuya Tsunehiko , Hori Masatsugu
Published: March 2015

Leg venous pressure markedly falls during upright exercise via a muscle pump effect, creating de novo perfusion pressure. We examined physiological roles of this mechanism in increasing femoral artery blood flow (FABF) and its alterations in chronic heart failure (CHF). In 10 normal subjects and 10 patients with CHF, standard hemodynamic variables, mean ankle vein pressure (MAVP), and FABF with Doppler techniques were obtained during graded upright bicycle exercise. To evaluate a nonspecific blood flow response, normal subjects also performed supine exercise. In normal subjects, MAVP rapidly declined by 45 mmHg and FABF correspondingly increased 5.3-fold without a systemic pressor response during 10 s of light upright exercise at 5 W. Approximately 67% of the blood flow response was attributed to the venous pressure drop-dependent mechanism. In CHF patients, MAVP declined by only 36 mmHg and FABF increased only 1.7-fold during the same upright exercise. The muscle venous pump has an ability to increase FABF at least threefold via the venous pressure drop-dependent mechanism. This mechanism is impaired in CHF patients.
Prolongation of the laryngeal chemoreflex after inhibition of the rostral ventral medulla in piglets: a role in SIDS?
Authors: van der Velde Liesbeth , Curran Aidan K. , Filiano James J. , Darnall Robert A. , Bartlett Donald , Leiter J. C.
Published: March 2015

We tested the hypothesis that inhibition of neurons within the rostral ventral medulla (RVM) would prolong the laryngeal chemoreflex (LCR), a putative stimulus in the sudden infant death syndrome (SIDS). We studied the LCR in 19 piglets, age 3–16 days, by injecting 0.05 ml of saline or water into the larynx during wakefulness, non-rapid eye movement (NREM) sleep, and REM sleep, before and after 1 or 10 mM muscimol dialysis in the RVM. Muscimol prolonged the LCR ( P < 0.05), and the prolongation was greater when the LCR was stimulated with water compared with saline ( P < 0.02). The LCR was longer during NREM sleep than during wakefulness and longest during REM sleep (REM compared with wakefulness). Muscimol had no effect on the likelihood of arousal from sleep after LCR stimulation. We conclude that the RVM provides a tonic facilitatory drive to ventilation that limits the duration of the LCR, and loss of this drive may contribute to the SIDS when combined with stimuli that inhibit respiration.
Energy cost of walking and gait instability in healthy 65- and 80-yr-olds
Authors: Malatesta Davide , Simar David , Dauvilliers Yves , Candau Robin , Borrani Fabio , Préfaut Christian , Caillaud Corinne
Published: March 2015

This study tested whether the lower economy of walking in healthy elderly subjects is due to greater gait instability. We compared the energy cost of walking and gait instability (assessed by stride to stride changes in the stride time) in octogenarians (G80, n = 10), 65-yr-olds (G65, n = 10), and young controls (G25, n = 10) walking on a treadmill at six different speeds. The energy cost of walking was higher for G80 than for G25 across the different walking speeds ( P < 0.05). Stride time variability at preferred walking speed was significantly greater in G80 (2.31 ± 0.68%) and G65 (1.93 ± 0.39%) compared with G25 (1.40 ± 0.30%; P < 0.05). There was no significant correlation between gait instability and energy cost of walking at preferred walking speed. These findings demonstrated greater energy expenditure in healthy elderly subjects while walking and increased gait instability. However, no relationship was noted between these two variables. The increase in energy cost is probably multifactorial, and our results suggest that gait instability is probably not the main contributing factor in this population. We thus concluded that other mechanisms, such as the energy expenditure associated with walking movements and related to mechanical work, or neuromuscular factors, are more likely involved in the higher cost of walking in elderly people.
Muscle temperature transients before, during, and after exercise measured using an intramuscular multisensor probe
Authors: Kenny G. P. , Reardon F. D. , Zaleski W. , Reardon M. L. , Haman F. , Ducharme M. B.
Published: March 2015

Seven subjects (1 woman) performed an incremental isotonic test on a Kin-Com isokinetic apparatus to determine their maximal oxygen consumption during bilateral knee extensions (V˙o 2 sp). A multisensor thermal probe was inserted into the left vastus medialis (middiaphysis) under ultrasound guidance. The deepest sensor (tip) was located ∼10 mm from the femur and deep femoral artery (Tmu 10), with additional sensors located 15 (Tmu 25) and 30 mm (Tmu 40) from the tip. Esophageal temperature (Tes) was measured as an index of core temperature. Subjects rested in an upright seated position for 60 min in an ambient condition of 22°C. They then performed 15 min of isolated bilateral knee extensions (60% of V˙o 2 sp) on a Kin-Com, followed by 60 min of recovery. Resting Tes was 36.80°C, whereas Tmu 10, Tmu 25, and Tmu 40 were 36.14, 35.86, and 35.01°C, respectively. Exercise resulted in a Tes increase of 0.55°C above preexercise resting, whereas muscle temperature of the exercising leg increased by 2.00, 2.37, and 3.20°C for Tmu 10, Tmu 25, and Tmu 40, respectively. Postexercise Tes showed a rapid decrease followed by a prolonged sustained elevation ∼0.3°C above resting. Muscle temperature decreased gradually over the course of recovery, with values remaining significantly elevated by 0.92, 1.05, and 1.77°C for Tmu 10, Tmu 25, and Tmu 40, respectively, at end of recovery ( P < 0.05). These results suggest that the transfer of residual heat from previously active musculature may contribute to the sustained elevation in postexercise Tes.
CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness
Authors: Nattie Eugene E. , Li Aihua
Published: March 2015

To evaluate the function of widely distributed central chemoreceptors during sleep and wakefulness in the rat, we focally stimulate single chemoreceptor sites during naturally occurring sleep-wake cycles by microdialysis of artificial cerebrospinal fluid equilibrated with 25% CO2. In retrotrapezoid nucleus, this increased ventilation (tidal volume) by 24% only in wakefulness (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In caudal medullary raphé, it increased ventilation (frequency) by 15–20% only in sleep (Nattie EE and Li A. J Appl Physiol 90: 1247–1257, 2001). Here, in nucleus tractus solitarius (NTS), focal acidification significantly increased ventilation by 11% in sleep and 7% in wakefulness rostrally ( n = 5) and by 16% in sleep and 28% in wakefulness caudally ( n = 5). The sleep-wake cycle was unaltered. Dialysis with 5% CO2 had no effect. Dialysis with 50% CO2 caudally did not further stimulate ventilation but did disrupt sleep. Central chemoreceptors in the NTS affect breathing in both sleep and wakefulness. The threshold for arousal in caudal NTS is greater than that for the stimulation of breathing.
Intensity-dependent tolerance to exercise after attaining V̇o2 max in humans
Authors: Coats Edward M. , Rossiter Harry B. , Day James R. , Miura Akira , Fukuba Yoshiyuki , Whipp Brian J.
Published: March 2015

The tolerable duration of high-intensity, constant-load cycle ergometry is a hyperbolic function of power, with an asymptote termed critical power (CP) and a curvature constant (W′) with units of work. It has been suggested that continued exercise after exhaustion may only be performed below CP, where predominantly aerobic energy transfer can occur and W′ can be partially replenished. To test this hypothesis, six volunteers each performed cycle-ergometer exercise with breath-by-breath determination of ventilatory and pulmonary gas exchange variables. Initially, four exercise tests to exhaustion were made: 1) a ramp-incremental and 2) three high-intensity constant-load bouts at different work rates, to estimate lactate (θ̂L) and CP thresholds, W′, and maximum oxygen uptake (V̇o2 max). Subsequently, subjects cycled to the limit of tolerance (for ∼360 s) on three occasions, each followed by a work rate reduction to 1) 110% CP, 2) 90% CP, and 3) 80% θ̂L for a 20-min target. W′ averaged 20.9 ± 2.35 kJ or 246 ± 30 J/kg. After initial fatigue, 110% CP was tolerated for only 30 ± 12 s. Each subject completed 20 min at 80% θ̂L, but only two sustained 20 min at 90% CP; the remaining four subjects fatigued at 577 ± 306 s, with oxygen consumption at 89 ± 8% V̇o2 max. The results support the suggestion that replenishing W′ after fatigue necessitates a sub-CP work rate. The variation in subjects' responses during 90% CP was unexpected but consistent with mechanisms such as reduced CP consequent to prior high-intensity exercise, variation in lactate handling, and/or regional depletion of energy substrates, e.g., muscle glycogen.
Delayed rectifier potassium channels contribute to the depressed pulmonary artery contractility in pneumonia
Authors: Yaghi Asma , Mehta Sanjay , McCormack David G.
Published: March 2015

We investigated the role of K+ channels in the attenuated pulmonary artery (PA) contractility characteristic of acute Pseudomonaspneumonia. Contractility of PA rings from the lungs of control or pneumonia rats was assessed in vitro by obtaining cumulative concentration-response curves to the contractile agonists KCl, phenylephrine, or PGF2α on PA rings before and after treatment with K+ channel blockers. In rings from pneumonia rats, paxilline (10 μM), tetraethylammonium (2 mM) (blockers of large-conductance Ca2+-activated K+ channels), and glybenclamide (ATP-sensitive K+ channel blocker, 80 μM) had no significant effect on the attenuated contractile responses to KCl, phenylephrine, and PGF2α. However, 4-aminopyridine (2 mM), a blocker of voltage-gated K+channels (delayed rectifier K+ channel) reversed this depressed contractility. Therefore, large-conductance Ca2+-activated K+ and ATP-sensitive K+ channels do not contribute to the attenuated PA contractility observed in this model of acute pneumonia. In contrast, 4-aminopyridine enhances contraction in PA rings from pneumonia lungs, consistent with involvement of a voltage-gated K+ channel in the depressed PA contractility in acute pneumonia. Unraveling the precise mechanism of attenuated contractility in pneumonia could lead to innovative therapies for the pulmonary vascular abnormalities associated with this disease.
Effects of the nasal valve on acoustic rhinometry measurements: a model study
Authors: Cankurtaran Mehmet , Çelik Hüseyin , Cakmak Ozcan , Özlüoglu Levent Naci
Published: March 2015

The influence of nasal valve on acoustic rhinometry (AR) measurements was evaluated by using simple nasal cavity models. Each model consisted of a cylindrical pipe with an insert simulating the nasal valve. The AR-determined cross-sectional areas beyond the insert were consistently underestimated, and the corresponding area-distance curves showed pronounced oscillations. The area underestimation was more pronounced in models with inserts of small passage area. The experimental results are discussed in terms of theoretically calculated “sound-power reflection coefficients” for the pipe models. The reason for area underestimation is reflection of most of the incident sound power from the barrier at the front junction between the pipe and the insert. It was also demonstrated that the oscillations are due to low-frequency acoustic resonances in the portion of the pipe beyond the insert. The results suggest that AR does not provide reliable information about the cross-sectional areas of the nasal cavity posterior to a significant constriction, such as pathologies narrowing the nasal valve area. When the passage area of the nasal valve is decreased, the role of AR as a diagnostic tool for the entire nasal cavity becomes limited.
Elevated IL-1β contributes to antibody suppression produced by stress
Authors: Moraska Albert , Campisi Jay , Nguyen Kien T. , Maier Steven F. , Watkins Linda R. , Fleshner Monika
Published: March 2015

Acute stressor exposure can facilitate innate immunity and suppress acquired immunity. The present study further characterized the potentiating effect of stress on innate immunity, interleukin-1β (IL-1β), and demonstrated that stress-induced potentiation of innate immunity may contribute to the stress-induced suppression of acquired immunity. The long-term effect of stress on IL-1β was measured by using an ex vivo approach. Sprague-Dawley rats were challenged with lipopolysaccharide (LPS) in vivo, and the IL-1β response was measured in vitro. Splenocytes, mesenteric lymphocytes, and peritoneal cavity cells had a dose- and time-dependent ex vivo IL-1β response to LPS. Rats that were exposed to inescapable shock (IS, 100 1.6 mA, 5-s tail shocks, 60-s intertrial interval) and challenged with a submaximal dose of LPS 4 days later had elevated IL-1β measured ex vivo. To test whether the acute stress-induced elevation in IL-1β contributes to the long-term suppression in acquired immunity, IL-1β receptors were blocked for 24 h after stress. Serum anti-keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) was measured. In addition, the acute elevation (2 h post-IS) of splenic IL-1β in the absence of antigen was verified. Interleukin-1 receptor antagonist prevented IS-induced suppression in anti-KLH Ig. These data support the hypothesis that stress-induced increases in innate immunity (i.e., IL-1β) may contribute to stress-induced suppression in acquired immunity (i.e., anti-KLH Ig).
Intermittent altitude exposures improve muscular performance at 4,300 m
Authors: Beidleman Beth A. , Muza Stephen R. , Fulco Charles S. , Cymerman Allen , Ditzler Dan T. , Stulz Dean , Staab Janet E. , Robinson Scott R. , Skrinar Gary S. , Lewis Steven F. , Sawka Michael N.
Published: March 2015

Chronic altitude residence improves muscular performance at altitude, but the effect of intermittent altitude exposures (IAE) on muscular performance at altitude has not been defined. The purpose of this study was to determine the effects of 3 wk of IAE, in combination with rest and cycle training, on muscular performance at altitude. Six lowlanders (23 ± 2 yr, 77 ± 6 kg; means ± SE) completed a cycle time trial and adductor pollicis endurance test at sea level and during a 30-h acute exposure to 4,300 m altitude equivalent (barometric pressure = 446 mmHg) once before (pre-IAE) and once after (post-IAE) a 3-wk period of IAE (4 h/day, 5 days/wk, 4,300 m). During each IAE, three subjects cycled for 45–60 min/day at 60%-70% of maximal O2 uptake and three subjects rested. Cycle training during each IAE did not appear to affect muscular performance at altitude. Thus data from all six subjects were combined. Three weeks of IAE resulted in 1) a 21 ± 6% improvement ( P < 0.05) in cycle time-trial performance (min) from pre-IAE (32.8 ± 3.7) to post-IAE (24.8 ± 1.2), 2) a 63 ± 26% improvement ( P < 0.05) in adductor pollicis endurance (min) from pre-IAE (9.2 ± 2.8) to post-IAE (14.8 ± 4.2), and 3) a 10 ± 4% increase ( P < 0.05) in resting arterial O2 saturation (%) from pre-IAE (82 ± 2) to post-IAE (90 ± 1). These improvements in muscular performance after IAE correlated strongly with increases in resting arterial O2 saturation and were comparable to those reported previously after chronic altitude residence. IAE may therefore be used as an alternative to chronic altitude residence to facilitate improvements in muscular performance in athletes, soldiers, mountaineers, shift workers, and others that are deployed to altitude.
Comparison of transient otoacoustic emission responses from neonatal and adult ears
Authors: Zimatore Giovanna , Hatzopoulos Stavros , Giuliani Alessandro , Martini Alessandro , Colosimo Alfredo
Published: March 2015

Transient otoacoustic emission (TEOAE) responses from neonatal (age: 48 h) and adult subjects (age: 26.6 ± 10.0 yr) were analyzed by the combined use of recurrence quantification analysis and singular value decomposition. The data from the two age groups showed significant differences and similarities. The neonatal responses presented less deterministic structures than those of the adults in terms of recurrent dynamic features. In both data sets, the same high level of individual specific dynamic features was observed. The results from the singular value decomposition analysis suggest that a large percentage of variability in all of the analyzed responses can be explained by four to five essential modes. This number is lower than that observed in simulated TEOAE responses generated by a five-component gammatone model. A possible explanation is presented, based on simple instrumental and morphoanatomic considerations.
Lung Edema Clearance: 20 Years of Progress Invited Review: Role of aquaporin water channels in fluid transport in lung and airways
Authors: Borok Zea , Verkman A. S.
Published: March 2015

Water transport across epithelial and endothelial barriers in bronchopulmonary tissues occurs during airway hydration, alveolar fluid transport, and submucosal gland secretion. Many of the tissues involved in these processes are highly water permeable and express aquaporin (AQP) water channels. AQP1 is expressed in microvascular endothelia throughout the lung and airways, AQP3 in epithelia in large airways, AQP4 in epithelia throughout the airways, and AQP5 in type I alveolar epithelial cells and submucosal gland acinar cells. The expression of some of these AQPs increases near the time of birth and is regulated by growth factors, inflammation, and osmotic stress. Transgenic mouse models of AQP deletion have provided information about their physiological role. In lung, AQP1 and AQP5 provide the principal route for osmotically driven water transport; however, alveolar fluid clearance in the neonatal and adult lung is not affected by AQP deletion nor is lung CO2 transport or fluid accumulation in experimental models of lung injury. In the airways, AQP3 and AQP4 facilitate water transport; however, airway hydration, regulation of the airway surface liquid layer, and isosmolar fluid absorption are not impaired by AQP deletion. In contrast to these negative findings, AQP5 deletion in submucosal glands in upper airways reduced fluid secretion and increased protein content by greater than twofold. Thus, although AQPs play a major physiological role outside of the airways and lung, AQPs appear to be important mainly in airway submucosal gland function. The substantially slower rates of fluid transport in airways, pleura, and lung compared with renal and some secretory epithelia may account for the apparent lack of functional significance of AQPs at these sites. However, the possibility remains that AQPs may play a role in lung physiology under conditions of stress and/or injury not yet tested or in functions unrelated to transepithelial fluid transport.