bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia augments apnea-induced peripheral vasoconstriction in humans
Authors: Leuenberger Urs A. , Hardy J. Cullen , Herr Michael D. , Gray Kristen S. , Sinoway Lawrence I.
Published: December 2017

Obstructive apnea and voluntary breath holding are associated with transient increases in muscle sympathetic nerve activity (MSNA) and arterial pressure. The contribution of changes in blood flow relative to the contribution of changes in vascular resistance to the apnea-induced transient rise in arterial pressure is unclear. We measured heart rate, mean arterial blood pressure (MAP), MSNA (peroneal microneurography), and femoral artery blood velocity ( V FA, Doppler) in humans during voluntary end-expiratory apnea while they were exposed to room air, hypoxia (10.5% inspiratory fraction of O2), and hyperoxia (100% inspiratory fraction of O2). Changes from baseline of leg blood flow (Q˙) and vascular resistance (R) were estimated from the following relationships: Q˙ ∝ V FA, corrected for the heart rate, and R ∝ MAP/Q˙. During apnea, MSNA rose; this rise in MSNA was followed by a rise in MAP, which peaked a few seconds after resumption of breathing. Responses of MSNA and MAP to apnea were greatest during hypoxia and smallest during hyperoxia ( P < 0.05 for both compared with room air breathing). Similarly, apnea was associated with a decrease in Q˙ and an increase in R. The decrease in Q˙ was greatest during hypoxia and smallest during hyperoxia (−25 ± 3 vs. −6 ± 4%, P < 0.05), and the increase in R was the greatest during hypoxia and the least during hyperoxia (60 ± 8 vs. 21 ± 6%, P < 0.05). Thus voluntary apnea is associated with vasoconstriction, which is in part mediated by the sympathetic nervous system. Because apnea-induced vasoconstriction is most intense during hypoxia and attenuated during hyperoxia, it appears to depend at least in part on stimulation of arterial chemoreceptors.
Muscularity and the density of the fat-free mass in athletes
Authors: Prior Barry M. , Modlesky Christopher M. , Evans Ellen M. , Sloniger Mark A. , Saunders Michael J. , Lewis Richard D. , Cureton Kirk J.
Published: December 2017

The purpose of this study was to use estimates of body composition from a four-component model to determine whether the density of the fat-free mass (DFFM) is affected by muscularity or musculoskeletal development in a heterogenous group of athletes and nonathletes. Measures of body density by hydrostatic weighing, body water by deuterium dilution, bone mineral by whole body dual-energy X-ray absorptiometry (DXA), total body skeletal muscle estimated from DXA, and musculoskeletal development as measured by the mesomorphy rating from the Heath-Carter anthropometric somatotype were obtained in 111 collegiate athletes (67 men and 44 women) and 61 nonathletes (24 men and 37 women). In the entire group, DFFM varied from 1.075 to 1.127 g/cm3 and was strongly related to the water and protein fractions of the fat-free mass (FFM; r = −0.96 and 0.89) and moderately related to the mineral fraction of the FFM ( r = 0.65). Skeletal muscle (%FFM) varied from 40 to 68%, and mesomorphy varied from 1.6 to 9.6, but neither was significantly related to DFFM( r = 0.11 and −0.14) or to the difference between percent fat estimated from the four-component model and from densitometry ( r = 0.09 and −0.16). We conclude that, in a heterogeneous group of young adult athletes and nonathletes, DFFM and the accuracy of estimates of body composition from body density using the Siri equation are not related to muscularity or musculoskeletal development. Athletes in selected sports may have systematic deviations in DFFM from the value of 1.1 g/cm3 assumed in the Siri equation, resulting in group mean errors in estimation of percent fat from densitometry of 2–5% body mass, but the cause of these deviations is complex and not simply a reflection of differences in muscularity or musculoskeletal development.
Interpretation of near-infrared spectroscopy signals: a study with a newly developed perfused rat brain model
Authors: Hoshi Yoko , Kobayashi Norio , Tamura Mamoru
Published: December 2017

Using a newly developed perfused rat brain model, we examined direct effects of each change in cerebral blood flow (CBF) and oxygen metabolic rate on cerebral hemoglobin oxygenation to interpret near-infrared spectroscopy signals. Changes in CBF and total hemoglobin (tHb) were in parallel, although tHb showed no change when changes in CBF were small (≤10%). Increasing CBF caused an increase in oxygenated hemoglobin (HbO2) and a decrease in deoxygenated hemoglobin (deoxy-Hb). Decreasing CBF was accompanied by a decrease in HbO2, whereas changes in direction of deoxy-Hb were various. Cerebral blood congestion caused increases in HbO2, deoxy-Hb, and tHb. Administration of pentylenetetrazole without increasing the flow rate caused increases in HbO2 and tHb with a decrease in deoxy-Hb. There were no significant differences in venous oxygen saturation before vs. during seizure. These results suggest that, in activation studies with near-infrared spectroscopy, HbO2 is the most sensitive indicator of changes in CBF, and the direction of changes in deoxy-Hb is determined by the degree of changes in venous blood oxygenation and volume.
Oxygen uptake kinetics during treadmill running in boys and men
Authors: Williams Craig A. , Carter Helen , Jones Andrew M. , Doust Jonathan H.
Published: December 2017

The purpose of this study was to compare the kinetics of the oxygen uptake (V˙o 2) response of boys to men during treadmill running using a three-phase exponential modeling procedure. Eight boys (11–12 yr) and eight men (21–36 yr) completed an incremental treadmill test to determine lactate threshold (LT) and maximum V˙o 2. Subsequently, the subjects exercised for 6 min at two different running speeds corresponding to 80% of V˙o 2 at LT (moderate exercise) and 50% of the difference betweenV˙o 2 at LT and maximumV˙o 2 (heavy exercise). For moderate exercise, the time constant for the primary response was not significantly different between boys [10.2 ± 1.0 (SE) s] and men (14.7 ± 2.8 s). The gain of the primary response was significantly greater in boys than men (239.1 ± 7.5 vs. 167.7 ± 5.4 ml · kg−1 · km−1; P < 0.05). For heavy exercise, theV˙o 2 on-kinetics were significantly faster in boys than men (primary response time constant = 14.9 ± 1.1 vs. 19.0 ± 1.6 s; P < 0.05), and the primary gain was significantly greater in boys than men (209.8 ± 4.3 vs. 167.2 ± 4.6 ml · kg−1 · km−1; P < 0.05). The amplitude of theV˙o 2 slow component was significantly smaller in boys than men (19 ± 19 vs. 289 ± 40 ml/min; P < 0.05). The V˙o 2responses at the onset of moderate and heavy treadmill exercise are different between boys and men, with a tendency for boys to have faster on-kinetics and a greater initial increase inV˙o 2 for a given increase in running speed.
Mechanisms of recruitment in oleic acid-injured lungs
Authors: Martynowicz Marek A. , Walters Bruce J. , Hubmayr Rolf D.
Published: December 2017

Lung recruitment strategies, such as the application of positive end-expiratory pressure (PEEP), are thought to protect the lungs from ventilator-associated injury by reducing the shear stress associated with the repeated opening of collapsed peripheral units. Using the parenchymal marker technique, we measured regional lung deformations in 13 oleic acid (OA)-injured dogs during mechanical ventilation in different postures. Whereas OA injury caused a marked decrease in the oscillation amplitude of dependent lung regions, even the most dependent regions maintained normal end-expiratory dimensions. This is because dependent lung is flooded as opposed to collapsed. PEEP restored oscillation amplitudes only at pressures that raised regional volumes above preinjury levels. Because the amount of PEEP necessary to promote dependent lung recruitment increased the end-expiratory dimensions of all lung regions (nondependent AND dependent ones) compared with their preinjury baseline, the “price” for recruitment is a universal increase in parenchymal stress. We conclude that the mechanics of the OA-injured lung might be more appropriately viewed as a partial liquid ventilation problem and not a shear stress and airway collapse problem and that the mechanisms of PEEP-related lung protection might have to be rethought.
Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse
Authors: Allen David L. , Harrison Brooke C. , Maass Alexander , Bell Matthew L. , Byrnes William C. , Leinwand Leslie A.
Published: December 2017

In this paper, we describe the effects of voluntary cage wheel exercise on mouse cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 8–10 wk; n = 12) ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h, and at an average speed of 26.4 m/min. A significant increase in the ratio of heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were significantly increased in the ventricles after 4 wk of voluntary exercise. A significant increase in the percentage of fibers expressing myosin heavy chain (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA) by 2 wk, and a significant decrease in the percentage of fibers expressing IIb MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle showed a greater increase in the percentage of IIa MHC-expressing fibers than did the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for nonexercised). Finally, the number of oxidative fibers as revealed by NADH-tetrazolium reductase histochemical staining was increased in the TA but not the gastrocnemius after 4 wk of voluntary exercise. All results are relative to age-matched mice housed without access to running wheels. Together these data demonstrate that voluntary exercise in mice results in cardiac and skeletal muscle adaptations consistent with endurance exercise.
Mechanics of edematous lungs
Authors: Wilson Theodore A. , Anafi Ron C. , Hubmayr Rolf D.
Published: December 2017

Using the parenchymal marker technique, we measured pressure (P)-volume (P-V) curves of regions with volumes of ∼1 cm3 in the dependent caudal lobes of oleic acid-injured dog lungs, during a very slow inflation from P = 0 to P = 30 cmH2O. The regional P-V curves are strongly sigmoidal. Regional volume, as a fraction of volume at total lung capacity, remains constant at 0.4–0.5 for airway P values from 0 to ∼20 cmH2O and then increases rapidly, but continuously, to 1 at P = ∼25 cmH2O. A model of parenchymal mechanics was modified to include the effects of elevated surface tension and fluid in the alveolar spaces. P-V curves calculated from the model are similar to the measured P-V curves. At lower lung volumes, P increases rapidly with lung volume as the air-fluid interface penetrates the mouth of the alveolus. At a value of P = ∼20 cmH2O, the air-fluid interface is inside the alveolus and the lung is compliant, like an air-filled lung with constant surface tension. We conclude that the properties of the P-V curve of edematous lungs, particularly the knee in the P-V curve, are the result of the mechanics of parenchyma with constant surface tension and partially fluid-filled alveoli, not the result of abrupt opening of airways or atelectatic parenchyma.
Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight
Authors: Widrick J. J. , Romatowski J. G. , Norenberg K. M. , Knuth S. T. , Bain J. L. W. , Riley D. A. , Trappe S. W. , Trappe T. A. , Costill D. L. , Fitts R. H.
Published: December 2017

The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (Po) was observed for the type I fibers (0.68 ± 0.02 vs. 0.64 ± 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and Powhere significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [ Vo, in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 ± 0.03 vs. 0.76 ± 0.02 FL/s) and IIa fibers (2.33 ± 0.25 vs. 3.10 ± 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of Po. These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of Pobut increased Voafter a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in Powere less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A. Riley, M. Karhanek, S. W. Trappe, T. A. Trappe, D. L. Costill, and R. H. Fitts. J Physiol (Lond) 516: 915–930, 1999].
Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography
Authors: Peták Ferenc , Habre Walid , Donati Yves R. , Hantos Zoltán , Barazzone-Argiroffo Constance
Published: December 2017

Hyperoxia-induced lung damage was investigated via airway and respiratory tissue mechanics measurements with low-frequency forced oscillations (LFOT) and analysis of spontaneous breathing indexes by barometric whole body plethysmography (WBP). WBP was performed in the unrestrained awake mice kept in room air ( n = 12) or in 100% oxygen for 24 ( n = 9), 48 ( n = 8), or 60 ( n = 9) h, and the indexes, including enhanced pause (Penh) and peak inspiratory and expiratory flows, were determined. The mice were then anesthetized, paralyzed, and mechanically ventilated. Airway resistance, respiratory system resistance at breathing frequency, and tissue damping and elastance were identified from the LFOT impedance data by model fitting. The monotonous decrease in airway resistance during hyperoxia correlated best with the increasing peak expiratory flow. Respiratory system resistance and tissue damping and elastance were unchanged up to 48 h of exposure but were markedly elevated at 60 h, with associated decreases in peak inspiratory flow. Penh was increased at 24 h and sharply elevated at 60 h. These results indicate no adverse effect of hyperoxia on the airway mechanics in mice, whereas marked parenchymal damage develops by 60 h. The inconsistent relationships between LFOT parameters and WBP indexes suggest that the changes in the latter reflect alterations in the breathing pattern rather than in the mechanical properties. It is concluded that, in the presence of diffuse lung disease, Penh is inadequate for characterization of the mechanical status of the respiratory system.
Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model
Authors: Hayot M. , Barreiro E. , Perez A. , Czaika G. , Comtois A. S. , Grassino A. E.
Published: December 2017

Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 ± 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72–96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.
Role of thromboxane in retinal microvascular degeneration in oxygen-induced retinopathy
Authors: Beauchamp Martin H. , Martinez-Bermudez Ana Katherine , Gobeil Fernand , Marrache Anne Marilise , Hou Xin , Speranza Giovanna , Abran Daniel , Quiniou Christiane , Lachapelle Pierre , Roberts Jackson , Almazan Guillermina , Varma Daya R. , Chemtob Sylvain
Published: December 2017

Microvascular degeneration is an important event in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity. Because oxidant stress abundantly generates thromboxane A2(TxA2), we tested whether TxA2plays a role in retinal vasoobliteration of OIR and contributes to such vascular degeneration by direct endothelial cytotoxicity. Hyperoxia-induced retinal vasoobliteration in rat pups (80% O2exposure from postnatal days 5–14) was associated with increased TxB2generation and was significantly prevented by TxA2synthase inhibitor CGS-12970 (10 mg · kg−1· day−1) or TxA2-receptor antagonist CGS-22652 (10 mg · kg−1· day−1). TxA2mimetics U-46619 (EC5050 nM) and I-BOP (EC505 nM) caused a time- and concentration-dependent cell death of neuroretinovascular endothelial cells from rats as well as newborn pigs but not of smooth muscle and astroglial cells; other prostanoids did not cause cell death. The peroxidation product 8-iso-PGF2, which is generated in OIR, stimulated TxA2formation by endothelial cells and triggered cell death; these effects were markedly diminished by CGS-12970. TxA2-dependent neuroretinovascular endothelial cell death was mostly by necrosis and to a lesser extent by apoptosis. The data identify an important role for TxA2in vasoobliteration of OIR and unveil a so far unknown function for TxA2in directly triggering neuroretinal microvascular endothelial cell death. These effects of TxA2might participate in other ischemic neurovascular injuries.
Relaxation of activated airway smooth muscle: relative potency of isoproterenol vs. tidal stretch
Authors: Gump Alison , Haughney Laura , Fredberg Jeffrey
Published: December 2017

Both isoproterenol and tidal fluctuations of muscle length inhibit active force development in activated airway smooth muscle. In this study, we show that length fluctuations in the range of amplitudes expected during quiet tidal breathing produce force inhibition that is equipotent with high concentrations of isoproterenol. Active force fell to 50% of its isometric value when the amplitude of the tidal stretch was 4% of muscle length. The relaxing effects of length fluctuations were insensitive to the specific contractile agonist, suggesting that the mechanism of action is largely independent of the particular signal transduction pathway and lies instead at the level of bridge dynamics. This idea is reinforced by the results of combining the relaxation effects of tidal fluctuations with those produced by isoproterenol at all but the highest concentrations studied (10−5 M). Such a combination produces multiplicative effects, indicating largely separate modes of action. These observations suggest that the tidal muscle stretches that are attendant to spontaneous breathing comprise the first line of defense against bronchospasm and that tidal muscle stretches may be the most important of all known bronchodilating agencies.
Chronic hypoxia modulates diaphragm function in the developing rat
Authors: Kass L. J. , Bazzy A. R.
Published: December 2017

We studied the effect of chronic hypoxia on contractile properties and neuromuscular transmission in the developing rat diaphragm. We hypothesized that chronic hypoxia delays maturation of neuromuscular transmission. Phrenic nerve hemidiaphragm preparations were harvested from 3- to 26-day-old rats and littermates raised in 9.5% oxygen. Specific force, contraction time, and one-half relaxation time were measured. Each diaphragm was stimulated directly or via its nerve with 1-s trains at 10–100 Hz. Contraction time and one-half relaxation time decreased with advancing age in both groups, with a greater rate of decrease in hypoxic diaphragms. Specific force was lower for hypoxic diaphragms compared with controls. Diaphragms from the 3- to 10-day-old control and hypoxic groups generated less force in response to stimulation at frequencies >40 Hz but did so to a greater degree with nerve stimulation. Nerve stimulation of diaphragms from 11- to 18-day-old hypoxic rats showed a greater decrease in force with increasing frequency compared with age-matched controls. Diaphragms from 19- to 26-day-old rats showed no difference between the hypoxic and control groups. We conclude that chronic hypoxia leads to diaphragms that generate lower specific force as well as to a delayed maturation of mechanisms involved in neuromuscular transmission.
Glutamine induces heat shock protein and protects against endotoxin shock in the rat
Authors: Wischmeyer Paul E. , Kahana Madelyn , Wolfson Rachel , Ren Hongyu , Musch Mark M. , Chang Eugene B.
Published: December 2017

Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models of septic shock. Induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. In this study, we demonstrate that a single dose of intravenous glutamine causes a rapid and significant increase in HSP25 and HSP72 expression in multiple organs of the unstressed Sprague-Dawley rat. With the utilization of a fluid-resuscitated rat model of endotoxemia, mortality was dramatically reduced by glutamine administration concomitant with the endotoxin injury. Endotoxin-treated animals given glutamine exhibited dramatic increases in tissue HSP expression and marked reduction of end-organ damage. These data suggest glutamine may protect against mortality and attenuate end-organ injury in endotoxemic shock via enhanced HSP expression. Furthermore, glutamine confers protection when administered at the initiation of sepsis, rather than as pretreatment. Thus glutamine appears to be a clinically viable enhancer of HSP expression and may prove beneficial in the therapy of sepsis and sepsis-induced organ injury.
Effects of one-legged endurance training on femoral arterial and venous size in healthy humans
Authors: Miyachi Motohiko , Tanaka Hirofumi , Yamamoto Kenta , Yoshioka Akira , Takahashi Kouki , Onodera Sho
Published: December 2017

The cross-sectional area (CSA) of large-conductance arteries increases in response to endurance training in humans. To determine whether training-induced changes in arterial structure are systemic in nature or, rather, are confined to the arteries supplying exercising muscles, we studied 10 young men who performed one-legged cycle training [80% of one-legged peak O2 uptake (V˙o 2 peak), 40 min/day, 4 days/wk] for 6 wk and detraining for another 6 wk. There were no significant differences in baseline one-leggedV˙o 2 peak and CSA of the common femoral artery and vein (via B-mode ultrasound) between experimental and control legs. In the experimental leg, one-leggedV˙o 2 peak increased 16% [from 3.0 ± 0.1 to 3.4 ± 0.1 (SE) l/min], arterial CSA increased 16% (from 84 ± 3 to 97 ± 5 mm2), and venous CSA increased 46% (from 56 ± 5 to 82 ± 5 mm2) after endurance training. These changes returned to baseline during detraining. There were no changes in one-leggedV˙o 2 peak and arterial CSA in the control leg, whereas femoral venous CSA in the control leg significantly increased 24% (from 54 ± 5 to 67 ± 4 mm2) during training. Changes in femoral arterial and venous CSA in the experimental leg were positively and significantly related to corresponding changes in one-leggedV˙o 2 peak ( r = 0.86 and 0.76, respectively), whereas there were no such relations in the control leg ( r = 0.10 and 0.17). When stepwise regression analysis was performed, a primary determinant of change inV˙o 2 peak was change in femoral arterial CSA, explaining ∼70% of the variability. These results support the hypothesis that the regional increase in blood flow, rather than systemic factors, is associated with the training-induced arterial expansion. Femoral arterial expansion may contribute, at least in part, to improvement in efficiency of blood transport from the heart to exercising muscles and may facilitate achievement of aerobic work capacity.
Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats
Authors: Saengsirisuwan Vitoon , Kinnick Tyson R. , Schmit Melanie B. , Henriksen Erik J.
Published: December 2017

Exercise training (ET) or the antioxidant R(+)-α-lipoic acid (R-ALA) individually increases insulin action in the insulin-resistant obese Zucker rat. The purpose of the present study was to determine the interactions of ET and R-ALA on insulin action and oxidative stress in skeletal muscle of the obese Zucker rat. Animals either remained sedentary, received R-ALA (30 mg · kg body wt−1· day−1), performed ET (treadmill running), or underwent both R-ALA treatment and ET for 6 wk. During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose (26–32%) and insulin (29–30%) responses compared with sedentary controls. R-ALA alone decreased (19%) the glucose-insulin index (indicative of increased insulin sensitivity), and this parameter was reduced (48–52%) to the greatest extent in the ET and combined treatment groups. ET or R-ALA individually increased insulin-mediated glucose transport activity in isolated epitrochlearis (44–48%) and soleus (37–57%) muscles. The greatest increases in insulin action in these muscles (80 and 99%, respectively) were observed in the combined treatment group. Whereas the improvement in insulin-mediated glucose transport in soleus due to R-ALA was associated with decreased protein carbonyl levels (an index of oxidative stress), improvement because of ET was associated with decreased protein carbonyls as well as enhanced GLUT-4 protein. However, there was no interactive effect of ET and R-ALA on GLUT-4 protein or protein carbonyl levels. These results indicate that ET and R-ALA interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscle. Because the further improvement in muscle glucose transport in the combined group was not associated with additional upregulation of GLUT-4 protein or a further reduction in oxidative stress, the mechanism for this interaction must be due to additional, as yet unidentified, factors.
Gender differences in carbohydrate loading are related to energy intake
Authors: Tarnopolsky Mark A. , Zawada Carol , Richmond Lindsay B. , Carter Sherry , Shearer Jane , Graham Terry , Phillips Stuart M.
Published: December 2017

We demonstrated that female endurance athletes did not increase their muscle glycogen concentration after an increase in the dietary carbohydrate intake (58 → 74%), whereas men did (Tarnopolsky MA, SA Atkinson, SM Phillips, and JD McDougall, J Appl Physiol 78: 1360–1368, 1995). This may have been related to a lower energy or carbohydrate intake by the women or due to an inherent gender difference in glycogen storage capacity. We examined whether well-trained men ( n = 6) and women ( n = 6) increased muscle glycogen concentration after an increase in both the relative (58 → 75%) and absolute energy and carbohydrate intake and whether potential gender differences were related to muscle hexokinase enzyme activity. Subjects were randomly allocated to three diets [Hab, habitual; CHO, high carbohydrate (75%); and CHO + E, extra energy + CHO (↑∼34%)] for a 4-day period before a muscle biopsy for analysis of total and pro- and macroglycogen and hexokinase activity. Total glycogen concentration was higher for the men on the CHO and CHO + E trials compared with Hab ( P < 0.05), whereas women increased only on the CHO + E trial compared with Hab ( P < 0.05). There were no gender differences in the proportion of pro- and macroglycogen or hexokinase activity. A low energy intake may explain the previously reported lower capacity for women to glycogen load compared with men.
Influences of repetitive muscle contractions with different modes on tendon elasticity in vivo
Authors: Kubo Keitaro , Kanehisa Hiroaki , Kawakami Yasuo , Fukunaga Tetsuo
Published: December 2017

The present study aimed to investigate the effects of repetitive muscle contractions on the elasticity of human tendon structures in vivo. Before and after each endurance test, the elongation of the tendon and aponeurosis of vastus lateralis muscle ( L) was directly measured by ultrasonography while the subjects performed ramp isometric knee extension up to maximal voluntary isometric contraction (MVC). Six male subjects performed muscle endurance tests that consisted of knee extension tasks with four different contraction modes: 1) 50 repetitions of maximal voluntary eccentric action for 3 s with 3 s of relaxation (ET1), 2) three sets of 50 repetitions of MVC for 1 s with 3 s of relaxation (ET2), 3) 50 repetitions of MVC for 3 s with 3 s of relaxation (ET3), and 4) 50 repetitions of 50% MVC for 6 s with 6 s of relaxation (ET4). In ET1 and ET2, there were no significant differences in L values at any force production levels between before and after endurance tests. In the cases of ET3 and ET4, however, the extent of elongation after the completion of the tests tended to be greater. The L values above 330 N in ET3 and 440 N in ET4, respectively, were significantly greater after endurance tests than before. These results suggested that the repeated longer duration contractions would make the tendon structures more compliant and that the changes in the elasticity might be not be affected by either muscle action mode or force production level but by the duration of action.
Time delay of vagally mediated cardiac baroreflex response varies with autonomic cardiovascular control
Authors: Keyl C. , Schneider A. , Dambacher M. , Bernardi L.
Published: December 2017

To examine whether changes in autonomic activity have an effect on the latency of the vagally mediated cardiac baroreflex response in humans, we investigated the effects of neck suction fluctuating sinusoidally at 0.2 Hz on R-R intervals (known to be mediated mainly by vagal activity) in the supine position, during 15° head-down tilt and 60° head-up tilt, and during vagotonic (2 μg/kg) and vagolytic (10 μg/kg) doses of atropine while the subjects breathed at 0.25 Hz. The phase shift between fluctuations in neck chamber pressure and in R-R interval was calculated by complex transfer function analysis and was used as a measure of the time delay between carotid baroreceptor stimulation and cardiac effector response. Cardiac baroreflex responsiveness increased significantly during low-dose atropine and decreased during head-up tilt or 10 μg/kg atropine. With increasing tilt angle, the time delay between cyclic baroreceptor stimulation and oscillations in R-R interval increased from 0.32 ± 0.27 s (head down), to 0.59 ± 0.25 s (supine position, P < 0.05 vs. head down), and to 0.86 ± 0.27 s (head up, P < 0.01 vs. supine). Low-dose atropine had a similar effect to head-down tilt on baroreflex latency, whereas 10 μg/kg atropine increased the time delay markedly to 1.24 ± 0.30 s. Our results demonstrate that changes in autonomic activity, generated either by gravitational stimulus or by atropine, not only affect baroreflex responsiveness but also have a major influence on the latency of the vagally mediated carotid baroreceptor-heart rate reflex. The prolonged baroreflex latency during decreased parasympathetic function may contribute to an unstable regulation of heart rate in patients with cardiac disease.
Adenosine A1 and A2A receptors modulate sleep state and breathing in fetal sheep
Authors: Koos Brian J. , Maeda Takatsugu , Jan Calvin
Published: December 2017

This study was designed to determine the adenosine (Ado) receptor subtype that mediates the depressant effects of Ado on fetal breathing and rapid eye movements (REM). In chronically catheterized fetal sheep (>0.8 term), intra-arterial infusion of N 6-cyclopentyladenosine (CPA), an Ado A1-receptor agonist, increased the incidence of high-voltage electrocortical (ECoG) activity while virtually abolishing low-voltage activity, REM, and breathing. These effects were blocked by 9-cyclopentyl-1,3-dipropylxanthine (DPCPX), an Ado A1-receptor antagonist. Infusion of DPCPX alone increased breath amplitude but had no significant effect on inspiratory duration, breath interval, incidence of REM, or incidence of low-voltage activity. Ado A2A-receptor blockade with ZM-241385 increased the incidence of low-voltage ECoG activity, REM, and breathing but had no effect on breath amplitude or respiratory cycle. Both DPCPX and ZM-241385 eliminated the inhibitory effects of Ado on REM and breathing. We conclude that 1) Ado A1receptors tonically inhibit fetal respiratory drive, 2) Ado A2A receptors tonically inhibit REM-like behavioral state, and 3) both Ado A1 and A2A receptors mediate the depressant effects of Ado on REM and breathing.
Effects ofPseudomonas aeruginosaendotoxin on vasodilation in the intact spinotrapezius muscle
Authors: Suzuki Hideyuki , Ikezaki Hiroyuki , Chandiwala Rinku , Hong Dennis , Rubinstein Israel
Published: December 2017

The purpose of this study was to determine whether short-term exposure to clinically relevant concentrations of Pseudomonas aeruginosa lipopolysaccharide (LPS) impairs vasoreactivity of resistance arterioles in the intact spinotrapezius muscle microcirculation and, if so, to determine the mechanisms mediating this response. Using intravital microscopy, we found that 60-min suffusion of P. aeruginosa LPS (0.03–3.0 μg/ml) on the in situ hamster spinotrapezius muscle elicited an immediate, profound, and prolonged concentration-dependent vasodilation ( P < 0.05). This response was reversible once suffusion of P. aeruginosa LPS was stopped. Pretreatment with NG-nitro-l-arginine methyl ester (10.0 μM), a nonselective nitric oxide (NO) synthase inhibitor, but not NG-nitro-d-arginine methyl ester, abrogated P. aeruginosa LPS-induced vasodilation and elicited a small, albeit significant, vasoconstriction. Indomethacin had no significant effects on P. aeruginosa LPS-induced responses. P. aeruginosa LPS had no significant effects on acetylcholine- and nitroglycerin-induced vasodilation in the spinotrapezius muscle. Collectively, these data indicate that short-term exposure to clinically relevant concentrations of P. aeruginosa LPS evokes an immediate, potent, prolonged, and reversible NO-dependent, prostaglandin-independent vasodilation in skeletal muscles in vivo. We suggest this response could play an important role in the pathophysiology of the profound vasomotor dysfunction observed in the peripheral circulation of patients with P. aeruginosa sepsis syndrome.
Invited Review: Regulation of myosin phosphorylation in smooth muscle
Authors: Pfitzer Gabriele
Published: December 2017

Phosphorylation of the regulatory light chains of myosin II (rMLC) by the Ca2+/calmodulin-dependent myosin light-chain kinase (MLCK) and dephosphorylation by a type 1 phosphatase (MLCP), which is targeted to myosin by a regulatory subunit (MYPT1), are the predominant mechanisms of regulation of smooth muscle tone. The activities of both enzymes are modulated by several protein kinases. MLCK is inhibited by the Ca2+/calmodulin-dependent protein kinase II, whereas the activity of MLCP is increased by cGMP and perhaps also cAMP-dependent protein kinases. In either case, this results in a decrease in the Ca2+sensitivity of rMLC phosphorylation and force production. The activity of MLCP is inhibited by Rho-associated kinase, one of the effectors of the monomeric GTPase Rho, and protein kinase C, leading to an increase in Ca2+sensitivity. Hence, smooth muscle tone appears to be regulated by a network of activating and inactivating intracellular signaling cascades.
Acute exercise effect on postabsorptive serum leptin
Authors: Fisher Jonathan S. , Van Pelt Rachael E. , Zinder Oren , Landt Michael , Kohrt Wendy M.
Published: December 2017

We postulated that high circulating cortisol levels during intense exercise would lead to increased serum leptin concentrations. Young, lean men ate a small meal and then exercised on a cycle ergometer for 41 min or rested on a control day. Serum leptin concentration was 10% greater during exercise than in the control condition ( P < 0.05). Directly after exercise, serum leptin dropped to ∼10% less than the control level ( P < 0.05) but had recovered to the nonexercised level after ∼2 h of recovery. Rapid exercise effects on circulating leptin were related to changes in hemoconcentration rather than changes in leptin mass. When serum leptin was normalized to serum protein, leptin increased by 10% in the exercise condition compared with control by the end of recovery ( P < 0.05). Although exercise increased serum cortisol concentration threefold, there was no relation between differences in cortisol and exercise vs. control differences in normalized leptin. The increased leptin mass after exercise may have been related to greater plasma glucose concentration during recovery after exercise compared with the control condition.
Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling
Authors: Karl Thomas , Prazeller Peter , Mayr Dagmar , Jordan Alfons , Rieder Josef , Fall Ray , Lindinger Werner
Published: December 2017

Numerous publications have described measurements of breath isoprene in humans, and there has been a hope that breath isoprene analyses could be a noninvasive diagnostic tool to assess blood cholesterol levels or cholesterol synthesis rate. However, significant analytic problems in breath isoprene analysis and variability in isoprene levels with age, exercise, diet, etc., have limited the usefulness of these measurements. Here, we have applied proton transfer reaction-mass spectrometry to this problem, allowing on-line detection of breath isoprene. We show that breath isoprene concentration increases within a few seconds after exercise is started as a result of a rapid increase in heart rate and then reaches a lower steady state when breath rate stabilizes. Additional experiments demonstrated that increases in heart rate associated with standing after reclining or sleeping are associated with increased breath isoprene concentrations. An isoprene gas-exchange model was developed and shows excellent fit to breath isoprene levels measured during exercise. In a preliminary experiment, we demonstrated that atorvastatin therapy leads to a decrease in serum cholesterol and low-density-lipoprotein levels and a parallel decrease in breath isoprene levels. This work suggests that there is constant endogenous production of isoprene during the day and night and reaffirms the possibility that breath isoprene can be a noninvasive marker of cholesterologenesis if care is taken to measure breath isoprene under standard conditions at constant heart rate.
Liquid transport properties of porcine tracheal epithelium
Authors: Crews Angela , Taylor Aubrey E. , Ballard Stephen T.
Published: December 2017

Because of its possible importance to the etiology of cystic fibrosis lung disease, the ion and water transport properties of tracheal epithelium were studied. Net liquid flux ( J V) across porcine tracheal epithelium was measured in vitro using blue dextran as a volume probe. Luminal instillation of isosmotic sucrose solution (280 mM) induced a small net secretion of liquid (7.0 ± 1.7 nl · cm−2 · s−1), whereas luminal hyposmotic sucrose solutions (220 or 100 mM) induced substantial and significant ( P < 0.05) liquid absorption (34.5 ± 12 and 38.1 ± 7.3 nl · cm−2 · s−1, respectively). When the luminal solution was normal (isosmotic) Krebs buffer, liquid was absorbed at 10.2 ± 1.1 nl · cm−2 · s−1. Absorptive J V was abolished by 100 μM amiloride in the luminal solution and significantly reduced when the luminal solution was Na+-free Krebs solution. Absorptive J V was not significantly affected by 300 μM 5-nitro-2-(3-phenylpropylamino)benzoate or 100 μM diphenylamine-2-carboxylic acid, both cystic fibrosis transmembrane conductance regulator protein (CFTR) inhibitors, in the instillate but was significantly reduced by 60% when the luminal solution was Cl−-free Krebs solution. We conclude that water freely permeates porcine tracheal epithelium and that absorption of liquid is normally driven by active transcellular Na+ transport and does not require the CFTR.
Addition of protein and amino acids to carbohydrates does not enhance postexercise muscle glycogen synthesis
Authors: Jentjens Roy L. P. G. , van Loon Luc J. C. , Mann Christopher H. , Wagenmakers Anton J. M. , Jeukendrup Asker E.
Published: December 2017

Ingestion of a protein-amino acid mixture (Pro; wheat protein hydrolysate, leucine, and phenylalanine) in combination with carbohydrate (CHO; 0.8 g · kg−1· h−1) has been shown to increase muscle glycogen synthesis after exercise compared with the same amount of CHO without Pro. The aim of this study was to investigate whether coingestion of Pro also increases muscle glycogen synthesis when 1.2 g CHO · kg−1· h−1is ingested. Eight male cyclists performed two experimental trials separated by 1 wk. After glycogen-depleting exercise, subjects received either CHO (1.2 g · kg−1· h−1) or CHO+Pro (1.2 g CHO · kg−1· h−1+ 0.4 g Pro · kg−1· h−1) during a 3-h recovery period. Muscle biopsies were obtained immediately, 1 h, and 3 h after exercise. Blood samples were collected immediately after the exercise bout and every 30 min thereafter. Plasma insulin was significantly higher in the CHO+Pro trial compared with the CHO trial ( P < 0.05). No difference was found in plasma glucose or in rate of muscle glycogen synthesis between the CHO and the CHO+Pro trials. Although coingestion of a protein amino acid mixture in combination with a large CHO intake (1.2 g · kg−1· h−1) increases insulin levels, this does not result in increased muscle glycogen synthesis.
Mechanical stimulation induces pp125FAKand pp60srcactivity in an in vivo model of trabecular bone formation
Authors: Moalli Maria R. , Wang Suquing , Caldwell Nancy J. , Patil Pravin V. , Maynard Craig R.
Published: December 2017

Utilizing an in vivo model of trabecular bone formation, we demonstrated the temporal and spatial activation of pp125FAKin response to specific mechanical load stimuli. Bone chambers equipped with hydraulic actuators were aseptically inserted into each proximal tibial metaphysis of adult, male dogs under general anesthesia. The load stimulus consisted of a trapezoidal waveform, with a maximum compressive load of 17.8 N, loading rate of 89 N/s, at 1 Hz frequency. One chamber was loaded for 2 (120 cycles), 15 (900 cycles), or 30 min (1,800 cycles), whereas the contralateral chamber served as unloaded control. Bone chambers were biopsied at postload time points of 0, 15, and 45 min. Load-induced activation of FAK was rapid, and the duration of activation was dependent on the number of applied load cycles. Mechanical stimulation increased the association of FAK with Src and the time course of complex formation paralleled the temporal activation of FAK. Evaluation of cryosections revealed prominent FAK immunoreactivity among marrow fibroblasts and stromal cells.
Invited Review: Focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle
Authors: Gerthoffer William T. , Gunst Susan J.
Published: December 2017

Smooth muscle cells are able to adapt rapidly to chemical and mechanical signals impinging on the cell surface. It has been suggested that dynamic changes in the actin cytoskeleton contribute to the processes of contractile activation and mechanical adaptation in smooth muscle. In this review, evidence for functionally important changes in actin polymerization during smooth muscle contraction is summarized. The functions and regulation of proteins associated with “focal adhesion complexes” (membrane-associated dense plaques) in differentiated smooth muscle, including integrins, focal adhesion kinase (FAK), c-Src, paxillin, and the 27-kDa small heat shock protein (HSP27) are described. Integrins in smooth muscles are key elements of mechanotransduction pathways that communicate with and are regulated by focal adhesion proteins that include FAK, c-Src, and paxillin as well as proteins known to mediate cytoskeletal remodeling. Evidence that functions of FAK and c-Src protein kinases are closely intertwined is discussed as well as evidence that focal adhesion proteins mediate key signal transduction events that regulate actin remodeling and contraction. HSP27 is reviewed as a potentially significant effector protein that may regulate actin dynamics and cross-bridge function in response to activation of p21-activated kinase and the p38 mitogen-activated protein kinase signaling pathway by signaling pathways linked to integrin proteins. These signaling pathways are only part of a large number of yet to be defined pathways that mediate acute adaptive responses of the cytoskeleton in smooth muscle to environmental stimuli.
Phagocytic function in cyclists: correlation with catecholamines and cortisol
Authors: Rincón E. Ortega , Marchena J. M. , García J. J. , Schmidt A. , Schulz T. , Malpica I. , Rodríguez A. B. , Barriga C. , Michna H. , Lötzerich H.
Published: December 2017

Flow cytometer measurements were made of the basal variations in peripheral blood functional monocytes and granulocytes over the course of a training season (January to November) of a cycling team. Parallel determinations were made of plasma concentration of catecholamines (chromatography) and cortisol (RIA) in a search for neuroendocrine markers. The results showed the greatest phagocytic capacity to occur in the central months (March, May, and July), coinciding with the greatest number and highest level of competitive events with good correlation with a peak in epinephrine during these months ( r2= 0.998 for monocytes and r2= 0.674 for granulocytes). No good correlations were found between phagocytosis and norepinephrine or cortisol. The highest values for phagocytosis and epinephrine concentration were found in May. These results suggest that blood epinephrine concentration could be a good neuroendocrine marker of sportspeople's phagocytic response.