bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle glycogen resynthesis during recovery from cycle exercise: no effect of additional protein ingestion
Authors: van Hall G. , Shirreffs S. M. , Calbet J. A. L.
Published: December 2017

In the present study, we have investigated the effect of carbohydrate and protein hydrolysate ingestion on muscle glycogen resynthesis during 4 h of recovery from intense cycle exercise. Five volunteers were studied during recovery while they ingested, immediately after exercise, a 600-ml bolus and then every 15 min a 150-ml bolus containing 1) 1.67 g ⋅ kg body wt−1 ⋅ l−1 of sucrose and 0.5 g ⋅ kg body wt−1 ⋅ l−1 of a whey protein hydrolysate (CHO/protein), 2) 1.67 g ⋅ kg body wt−1 ⋅ l−1 of sucrose (CHO), and 3) water. CHO/protein and CHO ingestion caused an increased arterial glucose concentration compared with water ingestion during 4 h of recovery. With CHO ingestion, glucose concentration was 1–1.5 mmol/l higher during the first hour of recovery compared with CHO/protein ingestion. Leg glucose uptake was initially 0.7 mmol/min with water ingestion and decreased gradually with no measurable glucose uptake observed at 3 h of recovery. Leg glucose uptake was rather constant at 0.9 mmol/min with CHO/protein and CHO ingestion, and insulin levels were stable at 70, 45, and 5 mU/l for CHO/protein, CHO, and water ingestion, respectively. Glycogen resynthesis rates were 52 ± 7, 48 ± 5, and 18 ± 6 for the first 1.5 h of recovery and decreased to 30 ± 6, 36 ± 3, and 8 ± 6 mmol ⋅ kg dry muscle−1 ⋅ h−1between 1.5 and 4 h for CHO/protein, CHO, and water ingestion, respectively. No differences could be observed between CHO/protein and CHO ingestion ingestion. It is concluded that coingestion of carbohydrate and protein, compared with ingestion of carbohydrate alone, did not increase leg glucose uptake or glycogen resynthesis rate further when carbohydrate was ingested in sufficient amounts every 15 min to induce an optimal rate of glycogen resynthesis.
Estrogen modifies the temperature effects of progesterone
Authors: Stachenfeld Nina S. , Silva Celso , Keefe David L.
Published: December 2017

To test the hypothesis that progestin-mediated increases in resting core temperature and the core temperature threshold for sweating onset are counteracted by estrogen, we studied eight women (24 ± 2 yr) at 27°C rest, during 20 min of passive heating (35°C), and during 40 min of exercise at 35°C. Subjects were tested four times, during the early follicular and midluteal menstrual phases, after 4 wk of combined estradiol-norethindrone (progestin) oral contraceptive administration (OC E+P), and after 4 wk of progestin-only oral contraceptive administration (OC P). The order of the OC P and OC E+P were randomized. Baseline esophageal temperature (Tes) at 27°C was higher ( P < 0.05) in the luteal phase (37.08 ± 0.21°C) and in OC P (37.60 ± 0.31°C) but not during OC E+P (37.04 ± 0.23°C) compared with the follicular phase (36.66 ± 0.21°C). Tes remained above follicular phase levels throughout passive heating and exercise during OC P, whereas Tes in the luteal phase was greater than in the follicular phase throughout exercise ( P < 0.05). The Testhreshold for sweating was also greater in the luteal phase (38.02 ± 0.28°C) and OC P (38.07 ± 0.17°C) compared with the follicular phase (37.32 ± 0.11°C) and OC E+P (37.46 ± 0.18°C). Progestin administration raised the Testhreshold for sweating during OC P, but this effect was not present when estrogen was administered with progestin, suggesting that estrogen modifies progestin-related changes in temperature regulation. These data are also consistent with previous findings that estrogen lowers the thermoregulatory operating point.
Cardiac output during exercise by the open circuit acetylene washin method: comparison with direct Fick
Authors: Johnson B. D. , Beck K. C. , Proctor D. N. , Miller J. , Dietz N. M. , Joyner M. J.
Published: December 2017

An open-circuit (OpCirc) acetylene uptake cardiac output (Q˙t) method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated uptake vs. end-tidal change in acetylene, and OpCirc2 was based on an iterative finite difference modeling method. Six subjects [28–44 yr, peak oxygen consumption (V˙o2) = 120% predicted] performed cycle ergometry exercise to compareQ˙t using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by a 10-min rest, and subsequently subjects exercised at 85–90% of their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%, OpCirc2, 12%, Fick, 10%) but were lower at moderate to high exercise intensities (OpCirc1, 3%, OpCirc2, 3%, Fick, 5%). OpCirc1 and OpCirc2 Q˙t correlated highly with Fick Q˙t( R2= 0.90 and 0.89, respectively). There were minimal differences between OpCirc1 and OpCirc2 compared with Fick up to moderate-intensity exercise (<70% peakV˙o2); however, both techniques tended to underestimate Fick at >70% peakV˙o2. These differences became significant for OpCirc1 only. Part of the differences between Fick and OpCirc methods at the higher exercise intensities are likely related to inhomogeneities in ventilation and perfusion matching ( R2= 0.36 for Fick − OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided reproducible, reliable measurements ofQ˙t during mild to moderate exercise. However, only OpCirc2 appeared to approximate FickQ˙t at the higher work intensities.
Substrate metabolism during different exercise intensities in endurance-trained women
Authors: Romijn J. A. , Coyle E. F. , Sidossis L. S. , Rosenblatt J. , Wolfe R. R.
Published: December 2017

We have studied eight endurance-trained women at rest and during exercise at 25, 65, and 85% of maximal oxygen uptake. The rate of appearance (Ra) of free fatty acids (FFA) was determined by infusion of [2H2]palmitate, and fat oxidation rates were determined by indirect calorimetry. Glucose kinetics were assessed with [6,6-2H2]glucose. Glucose Raincreased in relation to exercise intensity. In contrast, whereas FFA Rawas significantly increased to the same extent in low- and moderate-intensity exercise, during high-intensity exercise, FFA Rawas reduced compared with the other exercise values. Carbohydrate oxidation increased progressively with exercise intensity, whereas the highest rate of fat oxidation was during exercise at 65% of maximal oxygen uptake. After correction for differences in lean body mass, there were no differences between these results and previously reported data in endurance-trained men studied under the same conditions, except for slight differences in glucose metabolism during low-intensity exercise (Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, and Wolfe RR. Am J Physiol Endocrinol Metab 265: E380–E391, 1993). We conclude that the patterns of changes in substrate kinetics during moderate- and high-intensity exercise are similar in trained men and women.
Cholinergic dopamine release from the in vitro rabbit carotid body
Authors: Bairam Aida , Néji Habib , Marchal François
Published: December 2017

The aim of this study was to test whether cholinergic mechanisms regulate dopamine (DA) release from the carotid body (CB) and interact with DA D2 autoreceptors. One hundred forty-two CBs from adult rabbits were infused in vitro in a surviving medium bubbled with O2 (Bairam A, Marchal F, Cottet-Emard JM, Basson H, Pequignot JM, Hascoet JM, and Lahiri S. J Appl Physiol 80: 20–24, 1996 ). CB DA content and release were measured after 1 h of exposure to various treatments: control, cholinergic agonist (0.1–50 μM carbachol), full muscarinic antagonist (1 and 10 μM atropine), antagonists of M1 and M2 muscarinic receptors (1 and 10 μM pirenzepine and 10 μM AFDX-116, respectively), and the DA D2 receptor antagonist domperidone (1 μM), alone and with carbachol (1 μM). Compared with control, the release of DA was significantly increased by carbachol (1–50 μM), AFDX-116, and domperidone and decreased by atropine (10 μM) and pirenzepine (10 μM). The effects of domperidone and carbachol were not significantly different but were clearly additive. It is concluded that, in the rabbit CB, M1 and M2 muscarinic receptor subtypes may be involved in the control of DA release, in addition to the DA D2 autoreceptors.
Glucose infusion attenuates endogenous glucose production and enhances glucose use of horses during exercise
Authors: Geor Raymond J. , Hinchcliff Kenneth W. , Sams Richard A.
Published: December 2017

We examined the effects of increased glucose availability on glucose kinetics and substrate utilization in horses during exercise. Six conditioned horses ran on a treadmill for 90 min at 34 ± 1% of maximum oxygen uptake. In one trial [glucose (Glu)], glucose was infused at a mean rate of 34.9 ± 1.1 μmol ⋅ kg−1⋅ min−1, whereas in the other trial [control (Con)] an equivalent volume of isotonic saline was infused. Plasma glucose increased during exercise in Glu (90 min: 8.3 ± 1.7 mM) but was largely unchanged in Con (90 min: 5.1 ± 0.4 mM). In Con, hepatic glucose production (HGP) increased during exercise, reaching a peak of 38.6 ± 2.7 μmol ⋅ kg−1⋅ min−1after 90 min. Glucose infusion partially suppressed ( P < 0.05) the rise in HGP (peak value 25.8 ± 3.3 μmol ⋅ kg−1⋅ min−1). In Con, glucose rate of disappearance (Rd) rose to a peak of 40.4 ± 2.9 μmol ⋅ kg−1⋅ min−1after 90 min; in Glu, augmented glucose utilization was reflected by values for glucose Rdthat were twofold higher ( P< 0.001) than in Con between 30 and 90 min. Total carbohydrate oxidation was higher ( P < 0.05) in Glu (187.5 ± 8.5 μmol ⋅ kg−1⋅ min−1) than in Con (159.2 ± 7.3 μmol ⋅ kg−1⋅min−1), but muscle glycogen utilization was similar between trials. We conclude that an increase in glucose availability in horses during low-intensity exercise 1) only partially suppresses HGP, 2) attenuates the decrease in carbohydrate oxidation during such exercise, but 3) does not affect muscle glycogen utilization.
Ventilatory responses to specific CNS hypoxia in sleeping dogs
Authors: Curran Aidan K. , Rodman Joshua R. , Eastwood Peter R. , Henderson Kathleen S. , Dempsey Jerome A. , Smith Curtis A.
Published: December 2017

Our study was concerned with the effect of brain hypoxia on cardiorespiratory control in the sleeping dog. Eleven unanesthetized dogs were studied; seven were prepared for vascular isolation and extracorporeal perfusion of the carotid body to assess the effects of systemic [and, therefore, central nervous system (CNS)] hypoxia (arterial [Formula: see text] = 52, 45, and 38 Torr) in the presence of a normocapnic, normoxic, and normohydric carotid body during non-rapid eye movement sleep. A lack of ventilatory response to systemic boluses of sodium cyanide during carotid body perfusion demonstrated isolation of the perfused carotid body and lack of other significant peripheral chemosensitivity. Four additional dogs were carotid body denervated and exposed to whole body hypoxia for comparison. In the sleeping dog with an intact and perfused carotid body exposed to specific CNS hypoxia, we found the following. 1) CNS hypoxia for 5–25 min resulted in modest but significant hyperventilation and hypocapnia (minute ventilation increased 29 ± 7% at arterial [Formula: see text] = 38 Torr); carotid body-denervated dogs showed no ventilatory response to hypoxia. 2) The hyperventilation was caused by increased breathing frequency. 3) The hyperventilatory response developed rapidly (<30 s). 4) Most dogs maintained hyperventilation for up to 25 min of hypoxic exposure. 5) There were no significant changes in blood pressure or heart rate. We conclude that specific CNS hypoxia, in the presence of an intact carotid body maintained normoxic and normocapnic, does not depress and usually stimulates breathing during non-rapid eye movement sleep. The rapidity of the response suggests a chemoreflex meditated by hypoxia-sensitive respiratory-related neurons in the CNS.
Light-dark differences in the effects of ambient temperature on gaseous metabolism in newborn rats
Authors: Seifert Erin L. , Mortola Jacopo P.
Published: December 2017

Body temperature (Tb) of rat pups (7–9 days old) raised under a 12:12-h light-dark (L-D) regimen (L: 0700–1900, D: 1900–0700) was consistently higher in D than in L by ∼1.1°C. We tested the hypothesis that the L-D differences in Tbwere accompanied by differences in the set point of thermoregulation. Measurements were performed on rat pups at 7–9 days after birth. O2 consumption (V˙o 2) and CO2production (V˙co 2) were measured with an open-flow method during air breathing, as ambient temperature (Ta) was decreased from 40 to 15°C at the constant rate of 0.5°C/min. At Ta ≥33°C,V˙o 2 was not significantly different between L and D, whereasV˙co 2 was higher in L, suggesting a greater ventilation. Over the 33 to 15°C range theV˙o 2 values in D exceeded those in L by ∼30%. Specifically, the difference was contributed by differences in thermogenesis at Ta = 30 to 20°C. As Ta was decreased, the critical temperature at whichV˙o 2 began to rise was lower in L. We conclude that the higher Tb of rat pups in D is accompanied by a higher set point for thermoregulation and a greater thermogenesis. These results are consistent with the idea that, in newborns, endogenous changes in the set point of thermoregulation contribute to the circadian oscillations of Tb.
Respiratory sensation during chest wall restriction and dead space loading in exercising men
Authors: O'Donnell Denis E. , Hong Harry H. , Webb Katherine A.
Published: December 2017

We mimicked important mechanical and ventilatory aspects of restrictive lung disorders by employing chest wall strapping (CWS) and dead space loading (DS) in normal subjects to gain mechanistic insights into dyspnea causation and exercise limitation. We hypothesized that thoracic restriction with increased ventilatory stimulation would evoke exertional dyspnea that was similar in nature to that experienced in such disorders. Twelve healthy young men [28 ± 2 (SE) yr of age] completed pulmonary function tests and maximal cycle exercise tests under four conditions, in randomized order: 1) control, 2) CWS to 60% of vital capacity, 3) added DS of 600 ml, and 4) CWS + DS. Measurements during exercise included cardiorespiratory parameters, esophageal pressure, and Borg scale ratings of dyspnea. Compared with control, CWS significantly reduced the tidal volume response to exercise, increased dyspnea intensity at any given work rate or ventilation, and thus limited exercise performance. DS stimulated ventilation but had minimal effects on dyspnea and exercise performance. Adding DS to CWS further increased dyspnea by 1.7 ± 0.6 standardized Borg units ( P = 0.012) and decreased exercise performance (total work) by 21 ± 6% ( P = 0.003) over CWS alone. Across conditions, increased dyspnea intensity correlated best with decreased resting inspiratory reserve volume ( r = −0.63, P < 0.0005). Dyspnea during CWS was described primarily as “inspiratory difficulty” and “unsatisfied inspiration,” similar to restrictive disorders. In conclusion, severe dyspnea and exercise intolerance were provoked in healthy normal subjects when tidal volume responses were constrained in the face of increased ventilatory drive during exercise.
Forced expiration: a test for airflow obstruction in horses
Authors: Couëtil Laurent L. , Rosenthal Frank S. , Simpson Chris M.
Published: December 2017

The purpose of this study was to assess whether our method of inducing forced expiration detects small airway obstruction in horses. Parameters derived from forced expiratory flow-volume (FEFV) curves were compared with lung mechanics data obtained during spontaneous breathing in nine healthy horses, in three after histamine challenge, and in two with chronic obstructive pulmonary disease (COPD) pre- and posttherapy with prednisone. Parameters measured in the healthy horses included forced vital capacity (FVC = 41.6 ± 5.8 liters; means ± SD) and forced expiratory flow (FEF) at various percentages of FVC (range of 20.4–29.7 l/s). Histamine challenge induced a dose-dependent decrease in FVC and FEF at low lung volume. After therapy, lung function of the two COPD horses improved to a point where one horse had normal lung mechanics during tidal breathing; however, FEF at 95% of FVC (4.9 l/s) was still decreased. We concluded that FEFV curve analysis allowed the detection of induced or naturally occurring airway obstruction.
Hypoxia regulates gene expression of alveolar epithelial transport proteins
Authors: Clerici Christine , Matthay Michael A.
Published: December 2017

Alveolar hypoxia occurs during ascent to high altitude but is also commonly observed in many acute and chronic pulmonary disorders. The alveolar epithelium is directly exposed to decreases in O2tension, but a few studies have evaluated the effects of hypoxia on alveolar cell function. The alveolar epithelium consists of two cell types: large, flat, squamous alveolar type I and cuboidal type II (ATII). ATII cells are more numerous and have a number of critical functions, including transporting ions and substrates required for many physiological processes. ATII cells express 1) membrane proteins used for supplying substrates required for cell metabolism and 2) ion transport proteins such as Na+channels and Na+-K+-ATPase, which are involved in the vectorial transport of Na+from the alveolar to interstitial spaces and therefore drive the resorption of alveolar fluid. This brief review focuses on gene expression regulation of glucose transporters and Na+transport proteins by hypoxia in alveolar epithelial cells. Cells exposed to severe hypoxia (0% or 3% O2) for 24 h upregulate the activity and expression of the glucose transporter GLUT-1, resulting in preservation of ATP content. Hypoxia-induced increases in GLUT-1 mRNA levels are due to O2deprivation and inhibition of oxidative phosphorylation. This regulation occurs at the transcriptional level through activation of a hypoxia-inducible factor. In contrast, hypoxia downregulates expression and activity of Na+channels and Na+-K+-ATPase in cultured alveolar epithelial cells. Hypoxia induces time- and concentration-dependent decreases of α-, β-, and γ-subunits of epithelial Na+channel mRNA and β1- and α1-subunits of Na+-K+-ATPase, effects that are completely reversed after reoxygenation. The mechanisms by which O2deprivation regulates gene expression of Na+transport proteins are not fully elucidated but likely involve the redox status of the cell. Thus hypoxia regulates gene expression of transport proteins in cultured alveolar epithelial type II cells differently, preserving ATP content.
L-type Ca2+channel activation regulates induction of c-fostranscription by hypoxia
Authors: Premkumar Daniel R. D. , Mishra Rangnath R. , Overholt Jeffery L. , Simonson Michael S. , Cherniack Neil S. , Prabhakar Nanduri R.
Published: December 2017

In the present study we examined the intracellular pathways that link hypoxia to activation of c- fosgene expression. Experiments were performed on rat pheocromocytoma-12 (PC-12) cells. c- fos mRNA and promoter activities were analyzed by RT-PCR and reporter gene assays, respectively. BAPTA, a Ca2+chelator, inhibited c- fos mRNA and promoter activation by hypoxia. Nitrendipine, an L-type Ca2+-channel blocker, abolished, whereas BAY K 8644, an L-type channel agonist, enhanced c- fos activation by hypoxia. Ca2+currents were augmented reversibly by hypoxia, suggesting that Ca2+influx mediated by L-type Ca2+channels is essential for c- fos activation by hypoxia. We next determined downstream pathways activated by intracellular Ca2+concentration. Immunoblot analysis revealed Ca2+/calmodulin-dependent kinase II (CaMKII) protein in PC-12 cells and revealed that hypoxia increased the enzyme activity. KN-93, a CaMK inhibitor, blocked CaMKII activation and c- fos promoter stimulation by hypoxia. Ectopic expression of an active mutant of CaMKII (pCaMKII290) stimulated c- fos promoter activity under normoxia. Hypoxia increased phosphorylation of CREB at the serine residue 133 (Ser-133), and KN-93 attenuated this effect. Point mutations at the Ca2+/cAMP-responsive cis-element (Ca/CRE) attenuated, whereas point mutations in the serum-responsive cis-element (SRE) abolished transcriptional activation of c- fos by hypoxia. These results demonstrate that c- fosactivation by hypoxia involves CaMK activation and CREB phosphorylation at Ser-133 and requires Ca/CRE and SRE. These observations demonstrate that Ca2+-dependent signaling pathways play a crucial role in induction of c- fos gene expression, which may underlie long-term adaptive responses to hypoxia.
Time course for bone formation with long-term external mechanical loading
Authors: Cullen D. M. , Smith R. T. , Akhter M. P.
Published: December 2017

Increased mechanical loading of bone with the rat tibia four-point bending device stimulates bone formation on periosteal and endocortical surfaces. With long-term loading cell activity diminishes, and it has been reported that early gains in bone size may reverse. This study examined the time course for bone cellular and structural response after 6, 12, and 18 wk of loading at 1,200–1,700 microstrain (με). Bone formation rates, measured by histomorphometry, were compared within groups, between loaded and contralateral nonloaded tibiae, and between weeks. Formation surface, mineral apposition rate, and bone formation rate on periosteal and endocortical surfaces were elevated after 6 wk of loading. By 12 wk of loading, periosteal and endocortical formation surface and endocortical mineral apposition rates were elevated. By 18 wk of loading, periosteal adaptation appeared complete, whereas endocortical mineral apposition rate remained elevated. No periosteal resorption was observed. Average thickness of new bone formed, from baseline to collection, was greater in loaded than nonloaded tibiae by week 6 and was maintained through week 18. Early increases in bone formation result in periosteal apposition of new bone that persists after formation ceases.
Ventilatory responses to ozone are reduced in immature rats
Authors: Shore S. A. , Abraham J. H. , Schwartzman I. N. , Murthy G. G. Krishna , Laporte J. D.
Published: December 2017

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.
Effects of emphysema and training on glutathione oxidation in the hamster diaphragm
Authors: Heunks Leo M. A. , Bast Aalt , van Herwaarden Cees L. A. , Haenen Guido R. M. M. , Dekhuijzen P. N. Richard
Published: December 2017

Loading of skeletal muscles is associated with increased generation of oxidants, which in turn may impair muscle contractility. We investigated whether the load on the hamster diaphragm imposed by pulmonary emphysema induces oxidative stress, as indicated by glutathione oxidation, and whether the degree of glutathione oxidation is correlated with contractility of the diaphragm. In addition, the effect of 12 wk of treadmill exercise training on contractility and glutathione content in the normal (NH) and emphysematous hamster (EH) diaphragm was investigated. Training started 6 mo after elastase instillation. After the training period, glutathione content and in vitro contractility of the diaphragm were determined. Twitch force and maximal tetanic force were significantly reduced (by ∼30 and ∼15%, respectively) in EH compared with NH. In sedentary hamsters, the GSSG-to-GSH ratio was significantly elevated in the EH compared with the NH diaphragm. A significant inverse correlation was found between GSSG-to-GSH ratio and twitch force in the diaphragm ( P < 0.01). Training improved maximal tetanic force and reduced fatigability of the EH diaphragm but did not alter its glutathione content. In conclusion, 1) emphysema induces oxidative stress in the diaphragm, 2) training improves the contractile properties of the EH diaphragm, and 3) this improvement is not accompanied by changes in glutathione redox status.
Fatiguing contractions of tongue protrudor and retractor muscles: influence of systemic hypoxia
Authors: Fuller David D. , Fregosi Ralph F.
Published: December 2017

The influence of systemic hypoxia on the endurance performance of tongue protrudor and retractor muscles was examined in anesthetized, ventilated rats. Tongue protrudor (genioglossus) or retractor (hyoglossus and styloglossus) muscles were activated via medial or lateral XII nerve branch stimulation (0.1-ms pulse; 40 Hz; 330-ms trains; 1 train/s). Maximal evoked potentials (M waves) of genioglossus and hyoglossus were monitored with electromyography. Fatigue tests were performed under normoxic and hypoxic (arterial[Formula: see text] = 50 ± 1 Torr) conditions in separate animals. The fatigue index (FI; %initial force) after 5 min of normoxic stimulation was 85 ± 6 and 79 ± 7% for tongue protrudor and retractor muscles, respectively; these values were significantly lower during hypoxia (protrudor FI = 52 ± 10, retractor FI = 18 ± 6%; P < 0.05). Protrudor and retractor muscle M-wave amplitude declined over the course of the hypoxic fatigue test but did not change during normoxia ( P < 0.05). We conclude that hypoxia attenuates tongue protrudor and retractor muscle endurance performance; potential mechanisms include neuromuscular transmission failure and/or diminished sarcolemmal excitability.
Postactivation potentiation, fiber type, and twitch contraction time in human knee extensor muscles
Authors: Hamada Taku , Sale Digby G. , MacDougall J. Duncan , Tarnopolsky Mark A.
Published: December 2017

In small mammals, muscles with shorter twitch contraction times and a predominance of fast-twitch, type II fibers exhibit greater posttetanic twitch force potentiation than muscles with longer twitch contraction times and a predominance of slow-twitch, type I fibers. In humans, the correlation between potentiation and fiber-type distribution has not been found consistently. In the present study, postactivation potentiation (PAP) was induced in the knee extensors of 20 young men by a 10-s maximum voluntary isometric contraction (MVC). Maximal twitch contractions of the knee extensors were evoked before and after the MVC. A negative correlation ( r = −0.73, P < 0.001) was found between PAP and pre-MVC twitch time to peak torque (TPT). The four men with the highest (HPAP, 104 ± 11%) and lowest (LPAP, 43 ± 7%) PAP values ( P < 0.0001) underwent needle biopsies of vastus lateralis. HPAP had a greater percentage of type II fibers (72 ± 9 vs. 39 ± 7%, P < 0.001) and shorter pre-MVC twitch TPT (61 ± 12 vs. 86 ± 7 ms, P < 0.05) than LPAP. These data indicate that, similar to the muscles of small mammals, human muscles with shorter twitch contraction times and a higher percentage of type II fibers exhibit greater PAP.
Linkage of hiccup with heartbeat
Authors: Chen B.-Y. , Vasilakos K. , Boisteanu D. , Garma L. , Derenne J.-P. H. , Whitelaw W. A.
Published: December 2017

We explored a possible link between the cardiac cycle and the timing of recurrent hiccups in 10 patients with chronic, intractable hiccups. Recordings made during daytime naps in a sleep laboratory included sleep state; electrocardiogram; and respiration by means of a thermistor to detect airflow, bands around the rib cage and abdomen to assess expansion, and a bipolar surface electrode electromyogram over parasternal intercostal muscles. Hiccups could be detected on the abdominal bands and the parasternal electromyogram. The time of occurrence of each hiccup and each R wave in a continuous tracing of 100 or more hiccups were recorded and analyzed together with semiquantitive estimates of the phase of hiccup respiration. Whereas the hiccup rate ranged from approximately one-third to one-eighth of heart rate and was more variable than heart rate, hiccups showed a tendency, stronger in some subjects than others, to occur in midsystole. Variation in R-wave-R-wave (R-R) interval in association with hiccups was found in five patients. In three of these patients, hiccups were synchronized with respiration so that the cyclic change in R-R interval posthiccup could be explained as sinus arrhythmia, but, in two patients, the hiccups were not synchronized with respiration, so that hiccups are most likely responsible for the variation in heart rate. Also, the variation of R-R interval with hiccups suggests that there is some phasic autonomic efferent activity associated with hiccups.
High-impact exercise and growing bone: relation between high strain rates and enhanced bone formation
Authors: Judex Stefan , Zernicke Ronald F.
Published: December 2017

We investigated whether high-impact drop jumps could increase bone formation in the middiaphyseal tarsometatarsus of growing rooster. Roosters were designated as sedentary controls ( n = 10) or jumpers ( n = 10). Jumpers performed 200 drop jumps per day for 3 wk. The mechanical milieu of the tarsometatarsus was quantified via in vivo strain gauges. Indexes of bone formation and mechanical parameters were determined in each of twelve 30° sectors subdividing the middiaphyseal cortex. Compared with baseline walking, drop jumping produced large peak strain rates (+740%) in the presence of moderately increased peak strain magnitudes (+30%) and unaltered strain distributions. Bone formation rates were significantly increased by jump training at periosteal (+40%) and endocortical surfaces (+370%). Strain rate was significantly correlated with the specific sites of increased formation rates at endocortical but not at periosteal surfaces. Previously, treadmill running did not enhance bone growth in this model. Comparing the mechanical milieus produced by running and drop jumps revealed that jumping significantly elevated only peak strain rates. This further emphasized the sensitivity of immature bone to high strain rates.
Effects of exercise and n–3 fatty acids on postprandial lipemia
Authors: Thomas Tom R. , Fischer Brian A. , Kist William B. , Horner Kristen E. , Cox Richard H.
Published: December 2017

Because n–3 fatty acid ingestion and aerobic exercise each has been associated with diminished postprandial lipemia (PPL), the purpose of this study was to evaluate the effect of a combination of these two factors on PPL. Sedentary men underwent a standard dietary preparation, including a 12-h fast before each trial. Six subjects performed a control trial (fat meal, 100 g fat) and an n–3 fatty acid trial (fat meal after 3 wk of n–3 fatty acid supplementation at 4 g/day). In a parallel experiment, six different subjects underwent a control trial and n–3 fatty acid supplementation + 60 min of exercise before ingestion of the fat meal. Supplementation with n–3 fatty acid significantly decreased baseline triglyceride (TG) concentrations but did not significantly affect PPL. The combination of n–3 fatty acid and exercise had no effect on the postprandial TG response. The present study suggests that n–3 fatty acid supplementation lowers resting TG concentrations but inhibits the beneficial effect of aerobic exercise on the postprandial TG response.
EP2 receptor mediates bronchodilation by PGE2 in mice
Authors: Sheller J. R. , Mitchell Daphne , Meyrick Barbara , Oates John , Breyer Richard
Published: December 2017

PGE2 is an important cyclooxygenase product that modulates airway inflammatory and smooth muscle responses. Signal transduction is mediated by four EP receptor subtypes that cause distinct effects on cell metabolism. To determine the role of EP2 receptor activation, we produced a mouse lacking the EP2 receptor by targeted gene disruption. The effect of aerosolized PGE2 and other agonists was measured using barometric plethysmography and by measurements of lung resistance in mechanically ventilated mice. Inhalation of PGE2 inhibited methacholine responses in wild-type but not in mice lacking the EP2 receptor [EP2(−/−)]. After airway constriction was induced by methacholine aerosol, PGE2reduced the airway constriction enhanced pause in wild-type mice (from 0.88 ± 0.15 to 0.55 ± 0.06) but increased it in EP2(−/−) mice (from 0.73 ± 0.08 to 1.27 ± 0.19). Similar results were obtained in mechanically ventilated mice. These data indicate that the EP2 receptor mediates the bronchodilation effect of PGE2.
Hypoxic excitation in neurons cultured from the rostral ventrolateral medulla of the neonatal rat
Authors: Mazza Emilio , Edelman Norman H. , Neubauer Judith A.
Published: December 2017

Neurons within cardiorespiratory regions of the rostral ventrolateral medulla (RVLM) have been shown to be excited by local hypoxia. To determine the electrophysiological properties of these excitatory responses to hypoxia, we developed a primary dissociated cell culture system to examine the intrinsic response of RVLM neurons to hypoxia. Neonatal rat neurons plated on medullary astrocyte monolayers were studied using the whole cell perforated patch-clamp technique. Sodium cyanide (NaCN, 0.5–10 mM) was used, and membrane potential ( Vm), firing frequency, and input resistance were examined. In 11 of 19 neurons, NaCN produced a Vmdepolarization, an increase in firing frequency, and a decrease in input resistance, suggesting the opening of a cation channel. The hypoxic depolarization had a linear dose response and was dependent on baseline Vm, with a greater response at more hyperpolarized Vm. In 8 of 19 neurons, NaCN produced a Vmhyperpolarization, decrease in firing frequency, and variable changes in input resistance. The Vmhyperpolarization exhibited an all-or-none dose response and was independent of baseline Vm. These differential responses to NaCN were retained after synaptic blockade with low Ca2+-high Mg2+or TTX. Thus hypoxic excitation 1) is maintained in cell culture, 2) is an intrinsic response, and 3) is likely due to the increase in a cation current. These hypoxia-excited neurons are likely candidates to function as central oxygen sensors.
Characterization of pharyngeal resistance during sleep in a spectrum of sleep-disordered breathing
Authors: Tamisier R. , Pepin J. L. , Wuyam B. , Smith R. , Argod J. , Levy P.
Published: December 2017

Aims of the study were 1) to compare Hudgel's hyperbolic with Rohrer's polynomial model in describing the pressure-flow relationship, 2) to use this pressure-flow relationship to describe these resistances and to evaluate the effects of sleep stages on pharyngeal resistances, and 3) to compare these resistances to the pressure-to-flow ratio (ΔP/V˙). We studied 12 patients: three with upper airway resistance syndrome (UARS), four with obstructive sleep hypopnea syndrome (OSHS), three with obstructive sleep apnea syndrome (OSAS), and two with simple snoring (SS). Transpharyngeal pressures were calculated between choanae and epiglottis. Flow was measured by use of a pneumotachometer. The pressure-flow relationship was established by using nonlinear regression and was appreciated by the Pearson's square ( r 2). Mean resistance at peak pressure (Rmax) was calculated according to the hyperbolic model during stable respiration. In 78% of the cases, the value of r 2 was greater when the hyperbolic model was used. We demonstrated that Rmax was in excellent agreement with P/V˙. UARS patients exhibited higher awake mean Rmax than normal subjects and other subgroups and a larger increase from wakefulness to slow-wave sleep than subjects with OSAS, OSHS, and SS. Analysis of breath-by-breath changes in Rmax was also a sensitive method to detect episodes of high resistance during sleep.
Free radical scavenging and antioxidant effects of lactate ion: an in vitro study
Authors: Groussard Carole , Morel Isabelle , Chevanne Martine , Monnier Michel , Cillard Josianne , Delamarche Arlette
Published: December 2017

Divergent literature data are found concerning the effect of lactate on free radical production during exercise. To clarify this point, we tested the pro- or antioxidant effect of lactate ion in vitro at different concentrations using three methods: 1) electron paramagnetic resonance (EPR) was used to study the scavenging ability of lactate toward the superoxide aion (O2−·) and hydroxyl radical (·OH); 2) linoleic acid micelles were employed to investigate the lipid radical scavenging capacity of lactate; and 3) primary rat hepatocyte culture was used to study the inhibition of membrane lipid peroxidation by lactate. EPR experiments exhibited scavenging activities of lactate toward both O2−· and ·OH; lactate was also able to inhibit lipid peroxidation of hepatocyte culture. Both effects of lactate were concentration dependent. However, no inhibition of lipid peroxidation by lactate was observed in the micelle model. These results suggested that lactate ion may prevent lipid peroxidation by scavenging free radicals such as O2−· and ·OH but not lipid radicals. Thus lactate ion might be considered as a potential antioxidant agent.
Sexually dimorphic expression of myosin heavy chains in the adult mouse masseter
Authors: Eason Jane M. , Schwartz Gail A. , Pavlath Grace K. , English Arthur W.
Published: December 2017

Little is known regarding the role of androgenic hormones in the maintenance of myosin heavy chain (MHC) composition of rodent masticatory muscles. Because the masseter is the principal jaw closer in rodents, we felt it was important to characterize the influence of androgenic hormones on the MHC composition of the masseter. To determine the extent of sexual dimorphism in the phenotype of masseter muscle fibers of adult (10-mo-old) C57 mice, we stained tissue sections with antibodies specific to type IIa and IIb MHC isoforms. Females contain twice as many fibers containing the IIa MHC as males, and males contain twice as many fibers containing the IIb MHC as females. There is a modest amount of regionalization of MHC phenotypes in the mouse masseter. The rostral portions of the masseter are composed mostly of type IIa fibers, whereas the midsuperficial and caudal regions contain mostly type IIb fibers. Using immunoblots, we showed that castration results in an increase in the expression of type IIa MHC fibers in males. Ovariectomy has no effect on the fiber type composition in females. We conclude that testosterone plays a role in the maintenance of MHC expression in the adult male mouse masseter.
Operation Everest III: role of plasma volume expansion onV˙o2maxduring prolonged high-altitude exposure
Authors: Robach Paul , Déchaux Michèle , Jarrot Sébastien , Vaysse Jenny , Schneider Jean-Christophe , Mason Nicholas P. , Herry Jean-Pierre , Gardette Bernard , Richalet Jean-Paul
Published: December 2017

We hypothesize that plasma volume decrease (ΔPV) induced by high-altitude (HA) exposure and intense exercise is involved in the limitation of maximal O2uptake (V˙o2max) at HA. Eight male subjects were decompressed for 31 days in a hypobaric chamber to the barometric equivalent of Mt. Everest (8,848 m). Maximal exercise was performed with and without plasma volume expansion (PVX, 219–292 ml) during exercise, at sea level (SL), at HA (370 mmHg, equivalent to 6,000 m after 10–12 days) and after return to SL (RSL, 1–3 days). Plasma volume (PV) was determined at rest at SL, HA, and RSL by Evans blue dilution. PV was decreased by 26% ( P < 0.01) at HA and was 10% higher at RSL than at SL. Exercise-induced ΔPV was reduced both by PVX and HA ( P < 0.05). Compared with SL, V˙o2maxwas decreased by 58 and 11% at HA and RSL, respectively.V˙o2maxwas enhanced by PVX at HA (+9%, P < 0.05) but not at SL or RSL. The more PV was decreased at HA, the moreV˙o2maxwas improved by PVX ( P < 0.05). At exhaustion, plasma renin and aldosterone were not modified at HA compared with SL but were higher at RSL, whereas plasma atrial natriuretic factor was lower at HA. The present results suggest that PV contributes to the limitation ofV˙o2maxduring acclimatization to HA. RSL-induced PVX, which may be due to increased activity of the renin-aldosterone system, could also influence the recovery ofV˙o2max.
Peripheral chemoreflex function in hyperoxia following ventilatory acclimatization to altitude
Authors: Pedersen Michala E. F. , Robach Paul , Richalet Jean-Paul , Robbins Peter A.
Published: December 2017

After a period of ventilatory acclimatization to high altitude (VAH), a degree of hyperventilation persists after relief of the hypoxic stimulus. This is likely, in part, to reflect the altered acid-base status, but it may also arise, in part, from the development during VAH of a component of carotid body (CB) activity that cannot be entirely suppressed by hyperoxia. To test this hypothesis, eight volunteers undergoing a simulated ascent of Mount Everest in a hypobaric chamber were acutely exposed to 30 min of hyperoxia at various stages of acclimatization. For the second 10 min of this exposure, the subjects were given an infusion of the CB inhibitor, dopamine (3 μg · kg−1 · min−1). Although there was both a significant rise in ventilation ( P < 0.001) and a fall in end-tidal Pco 2 ( P < 0.001) with VAH, there was no progressive effect of dopamine infusion on these variables with VAH. These results do not support a role for CB in generating the persistent hyperventilation that remains in hyperoxia after VAH.
High-abundance mRNAs in human muscle: comparison between young and old
Authors: Welle Stephen , Bhatt Kirti , Thornton Charles A.
Published: December 2017

To gain a better understanding of the potential role of altered gene expression in the diminished muscle function in old age, we performed a broad search for transcripts expressed at quantitatively different levels in younger (21–24 yr) and older (66–77 yr) human vastus lateralis muscle by serial analysis of gene expression (SAGE). Because SAGE was based on RNA pooled from muscle of several different subjects, relative concentrations of selected mRNAs also were determined in individual muscle samples by quantitative RT-PCR. There were 702 SAGE tags detected at least 10 times in one or both mRNA pools, and the detection frequency was different (at P < 0.01) between young and older muscle for 89 of these. The ratio of myosin heavy chain 2a mRNA to myosin heavy chain 1 mRNA was reduced in older muscle. The mRNAs encoding several mitochondrial proteins involved in electron transport (including several subunits of cytochrome- c oxidase and NADH dehydrogenase) and subunits of ATP synthase were ∼30% less abundant in older muscle. Several mRNAs encoding enzymes involved in glucose metabolism also were less abundant in older muscle. Analysis of individual samples revealed that the differences suggested by SAGE were not artifacts of atypical gene expression in one or a few individuals. These data suggest that some of the phenotypic changes in senescent muscle may be related to altered gene transcription.
Supraspinal fatigue during intermittent maximal voluntary contractions of the human elbow flexors
Authors: Taylor Janet L. , Allen Gabrielle M. , Butler Jane E. , Gandevia S. C.
Published: December 2017

Responses to transcranial magnetic stimulation in human subjects ( n = 9) were studied during series of intermittent isometric maximal voluntary contractions (MVCs) of the elbow. Stimuli were given during MVCs in four fatigue protocols with different duty cycles. As maximal voluntary torque fell during each protocol, the torque increment evoked by cortical stimulation increased from ∼1.5 to 7% of ongoing torque. Thus “supraspinal” fatigue developed in each protocol. The motor evoked potential (MEP) and silent period in the elbow flexor muscles also changed. The silent period lengthened by 20–75 ms (lowest to highest duty cycle protocol) and recovered significantly with a 5-s rest. The MEP increased in area by >50% in all protocols and recovered significantly with 10 s, but not 5 s, of rest. These changes are similar to those during sustained MVC. The central fatigue demonstrated by the torque increments evoked by the stimuli did not parallel the changes in the electromyogram responses. This suggests that part of the fatigue developed during intermittent exercise is “upstream” of the motor cortex.
Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance
Authors: Vaziri N. D. , Ding Y. , Sangha D. S. , Purdy R. E.
Published: December 2017

Prolonged exposure to microgravity during spaceflight or extended bed rest results in cardiovascular deconditioning, marked by orthostatic intolerance and hyporesponsiveness to vasopressors. Earlier studies primarily explored fluid and electrolyte balance and baroreceptor and vasopressor systems in search of a possible mechanism. Given the potent vasodilatory and natriuretic actions of nitric oxide (NO), we hypothesized that cardiovascular adaptation to microgravity may involve upregulation of the NO system. Male Wistar rats were randomly assigned to a control group or a group subjected to simulated microgravity by hindlimb unloading (HU) for 20 days. Tissues were harvested after death for determination of total nitrate and nitrite (NOx) as well as endothelial (e), inducible (i), and neuronal (n) NO synthase (NOS) proteins by Western blot. Separate subgroups were used to test blood pressure response to norepinephrine and the iNOS inhibitor aminoguanidine. Compared with controls, the HU group showed a significant increase in tissue NOx content and an upregulation of iNOS protein abundance in thoracic aorta, heart, and kidney and of nNOS protein expression in the brain and kidney but no discernible change in eNOS expression. This was associated with marked attenuation of hypertensive response to norepinephrine and a significant increase in hypertensive response to aminoguanidine, suggesting enhanced iNOS-derived NO generation in the HU group. Upregulation of these NOS isotypes can contribute to cardiovascular adaptation to microgravity by promoting vasodilatory tone and natriuresis and depressing central sympathetic outflow. If true in humans, short-term administration of an iNOS inhibitor may ameliorate orthostatic intolerance in returning astronauts and patients after extended bed rest.