bluuebunny/crossref_metadata_2025 huggingface dataset:
Invited Review: Molecular adaptations in mammalian hibernators: unique adaptations or generalized responses?
Authors: van Breukelen Frank , Martin Sandra L.
Published: March 2015

Hibernators are unique among mammals in their ability to attain, withstand, and reverse low body temperatures. Hibernators repeatedly cycle between body temperatures near zero during torpor and 37°C during euthermy. How do these mammals maintain cardiac function, cell integrity, blood fluidity, and energetic balance during their prolonged periods at low body temperature and avoid damage when they rewarm? Hibernation is often considered an example of a unique adaptation for low-temperature function in mammals. Although such adaptation is apparent at the level of whole animal physiology, it is surprisingly difficult to demonstrate clear examples of adaptations at the cellular and biochemical levels that improve function in the cold and are unique to hibernators. Instead of adaptation for improved function in the cold, the key molecular adaptations of hibernation may be to exploit the cold to depress most aspects of biochemical function and then rewarm without damage to restore optimal function of all systems. These capabilities are likely due to novel regulation of biochemical pathways shared by all mammals, including humans.
Gender differences in the regulation of amino acid metabolism
Authors: Lamont Linda S. , McCullough Arthur J. , Kalhan Satish C.
Published: March 2015

Exercising men, compared with women, have a greater increase in leucine oxidation but not lysine rate of appearance. The cause for this sexual dimorphism is unknown; however, an inhibition of β-adrenoreceptor activity has previously been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan SC. Am J Physiol Endocrinol Metab 268: E910-E916, 1995; Lamont LS, Patel DG, and Kalhan SC. J Appl Physiol 67: 221-225, 1989). This study was a gender comparison of leucine and lysine kinetics during a β-adrenoreceptor blockade (β1,β2-blockade) and a placebo control by using a double-blind crossover protocol. Subjects exercised at 50% of their trial-specific maximal O2 consumption (1 h) after 7 days of dietary control. During exercise with β-blockade, men had an increased nonprotein respiratory exchange ratio ( P < 0.001), whereas women had an increased circulation of free fatty acids ( P < 0.001). The genders also displayed distinct differences in exercise amino acid kinetics. The men, but not the women, increased leucine oxidation ( P < 0.005) and lysine rate of appearance ( P < 0.009) when exercising during β-adrenergic blockade. This study indicates that during β-blockade, exercising men increase their need for amino acids (and carbohydrate) to fuel energy needs, whereas women increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids. Gender-specific fuel preferences during exercise are regulated by β-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders.
Effects of paranasal sinus ostia and volume on acoustic rhinometry measurements: a model study
Authors: Cakmak Ozcan , Çelik Huseyin , Cankurtaran Mehmet , Buyuklu Fuat , Özgirgin Nuri , Ozluoglu Levent Naci
Published: March 2015

We used pipe models to investigate the effects of paranasal sinus ostium size and paranasal sinus volume on the area-distance curves derived by acoustic rhinometry (AR). Each model had a Helmholtz resonator or a short neck as a side branch that simulated the paranasal sinus and sinus ostium. The AR-derived cross-sectional areas posterior to the ostium were significantly overestimated. Sinus volume affected the AR measurements only when the sinus was connected via a relatively large ostium. The experimental area-distance curve posterior to the side branch showed pronounced oscillations in association with low-frequency acoustic resonances in this distal part of the pipe. The experimental results are discussed in terms of theoretically calculated “sound-power reflection coefficients” for the pipe models used. The results indicate that the effects of paranasal sinuses and low-frequency acoustic resonances in the posterior part of the nasal cavity are not accounted for in the current AR algorithms. AR does not provide reliable information about sinus ostium size, sinus volume, or cross-sectional area in the distal parts of nasal cavity.
Activation among the elbow flexor muscles differs when maintaining arm position during a fatiguing contraction
Authors: Hunter Sandra K. , Lepers Romuald , MacGillis Carol J. , Enoka Roger M.
Published: March 2015

Twenty-four men ( n = 11) and women ( n = 13) supported an inertial load equivalent to 20% of the maximum voluntary contraction force with the elbow flexor muscles for as long as possible while maintaining a constant elbow angle at 90°. Endurance time did not differ on the three occasions that the task was performed (320 ± 149 s; P > 0.05), and there was no difference between women (360 ± 168 s) and men (273 ± 108 s; P = 0.11). The rate of increase in average electromyogram (EMG) for the elbow flexor muscles was similar across sessions ( P > 0.05). However, average EMG during the fatiguing task increased for the long head of biceps brachii, brachioradialis, and brachialis ( P < 0.05) but not for the short head of biceps brachii. Furthermore, the average EMG for the brachialis was greater at the start and end of the contraction compared with the other elbow flexor muscles. The rate of bursts in EMG activity increased during the fatiguing contraction and was greater in brachialis (1.0 ± 0.2 bursts/min) compared with the other elbow flexor muscles (0.5 ± 0.1 bursts/min). The changes in the standard deviation of acceleration, mean arterial pressure, and heart rate during the fatiguing contractions were similar across sessions. These findings indicate that the EMG activity, which reflects the net excitatory and inhibitory input received by the motoneurons in the spinal cord, was not adaptable over repeat sessions for the maintain-position task. Furthermore, these results contrast those from a previous study (Hunter SK and Enoka RM. J Appl Physiol 94: 108–118, 2003) when the goal of the isometric contraction was to maintain a constant force. These results, from a series of studies on the elbow flexor muscles, indicate that the type of load supported during the fatiguing contraction influences the extent to which endurance time can change with repeat performances of the task.
Hyperbaric oxygen may reduce gas bubbles in decompressed prawns by eliminating gas nuclei
Authors: Arieli Yehuda , Arieli Ran , Marx Amit
Published: March 2015

It is accepted that gas bubbles grow from preexisting gas nuclei in tissue. The possibility of eliminating gas nuclei may be of benefit in preventing decompression sickness. In the present study, we examined the hypothesis that hyperbaric oxygen may replace the resident gas in the nuclei with oxygen and, because of its metabolic role, eliminate the nuclei themselves. After pretreatment with oxygen, prawns were 98% saturated with nitrogen before explosive decompression at 30 m/min. Ten transparent prawns were exposed to four experimental profiles in a crossover design: 1) 10-min compression to 203 kPa with air; 2) 10-min compression with oxygen; 3) 10-min compression with oxygen to 203 kPa followed by 12 min air at 203 kPa; and 4) 10 min in normobaric oxygen followed by compression to 203 kPa with air. Bubbles were measured after explosive decompression. We found that pretreatment with hyperbaric oxygen ( profile C) significantly reduces the number of bubbles and bubble volume. We suggest that hyperbaric oxygen eliminates bubble nuclei in the prawn.
Cardiopulmonary resuscitation in the mouse
Authors: Song Lei , Weil Max Harry , Tang Wanchun , Sun Shijie , Pellis Tommaso
Published: March 2015

We sought to develop a model of cardiac arrest and resuscitation on mice that would be comparable to that of large mammals and would allow for more fundamental investigations on cardiopulmonary arrest and cardiac resuscitation. A model of cardiopulmonary resuscitation previously developed by our group on rats was adapted to anesthetized, mechanically ventilated adult male Institute of Cancer Research mice that weighed 46 ± 3 g. The trachea was intubated through the mouth, and end-tidal Pco 2(Pet CO2 ) was measured with a microcapnometer. Catheters were advanced into the aorta and into the right atrium, and coronary perfusion pressure (CPP) was computed. A 1.5-mA alternating current was delivered to the right ventricular endocardium, which produced ventricular fibrillation or a pulseless rhythm. Precordial compression was begun 4 min later. Ten sequential studies were performed, during which five animals were successfully resuscitated and five failed resuscitation efforts. Successful resuscitation was contingent on the restoration of threshold levels of CPP and Pet CO2 during chest compression. As in rats, swine, and human patients, threshold levels of mean aortic pressure, CPP, and Pet CO2 were critical determinates of resuscitability in this murine model of threshold level of cardiac arrest and resuscitation.
Luteal and follicular glucose fluxes during rest and exercise in 3-h postabsorptive women
Authors: Suh Sang-Hoon , Casazza Gretchen A. , Horning Michael A. , Miller Benjamin F. , Brooks George A.
Published: March 2015

We examined the effects of exercise intensity and menstrual cycle phase on glucose flux rates during rest and exercise in rested and fed (3-h postabsorptive) women. Eight moderately active, eumenorrheic women were studied under conditions of rest (90 min) and exercise (60 min, leg ergometer cycling at 45 and 65% peak oxygen consumption) during follicular and luteal phases. In both menstrual phases, an effect of exercise intensity was evident with glucose rates of appearance and disappearance and metabolic clearance rates: rest < 45% intensity < 65% intensity ( P < 0.05). In addition, we observed no significant effect of menstrual phase on glucose rates of appearance and disappearance and metabolic clearance rate during rest or exercise at either intensity. These results are interpreted to mean that in women fed several hours before study 1) glucose flux is directly related to exercise intensity, 2) menstrual cycle phase does not alter glucose flux during rest and exercise, and 3) the subtle effects of endogenous ovarian hormones on glucose kinetics are subordinate to the much larger effects of exercise and recent carbohydrate nutrition.
Dynamic equilibration of airway smooth muscle contraction during physiological loading
Authors: Latourelle Jeanne , Fabry Ben , Fredberg Jeffrey J.
Published: March 2015

Airway smooth muscle contraction is the central event in acute airway narrowing in asthma. Most studies of isolated muscle have focused on statically equilibrated contractile states that arise from isometric or isotonic contractions. It has recently been established, however, that muscle length is determined by a dynamically equilibrated state of the muscle in which small tidal stretches associated with the ongoing action of breathing act to perturb the binding of myosin to actin. To further investigate this phenomenon, we describe in this report an experimental method for subjecting isolated muscle to a dynamic microenvironment designed to closely approximate that experienced in vivo. Unlike previous methods that used either time-varying length control, force control, or time-invariant auxotonic loads, this method uses transpulmonary pressure as the controlled variable, with both muscle force and muscle length free to adjust as they would in vivo. The method was implemented by using a servo-controlled lever arm to load activated airway smooth muscle strips with transpulmonary pressure fluctuations of increasing amplitude, simulating the action of breathing. The results are not consistent with classical ideas of airway narrowing, which rest on the assumption of a statically equilibrated contractile state; they are consistent, however, with the theory of perturbed equilibria of myosin binding. This experimental method will allow for quantitative experimental evaluation of factors that were previously outside of experimental control, including sensitivity of muscle length to changes of tidal volume, changes of lung volume, shape of the load characteristic, loss of parenchymal support and inflammatory thickening of airway wall compartments.
Ventilation-perfusion inequality during normoxic and hypoxic exercise in the emu
Authors: Schmitt P. M. , Powell F. L. , Hopkins S. R.
Published: March 2015

Many avian species exhibit an extraordinary ability to exercise under hypoxic condition compared with mammals, and more efficient pulmonary O2transport has been hypothesized to contribute to this avian advantage. We studied six emus ( Dromaius novaehollandaie, 4–6 mo old, 25–40 kg) at rest and during treadmill exercise in normoxia and hypoxia (inspired O2fraction ≈ 0.13). The multiple inert gas elimination technique was used to measure ventilation-perfusion (V˙/Q˙) distribution of the lung and calculate cardiac output and parabronchial ventilation. In both normoxia and hypoxia, exercise increased arterial Po2and decreased arterial Pco2, reflecting hyperventilation, whereas pH remained unchanged. The V˙/Q˙ distribution was unimodal, with a log standard deviation of perfusion distribution = 0.60 ± 0.06 at rest; this did not change significantly with either exercise or hypoxia. Intrapulmonary shunt was <1% of the cardiac output in all conditions. CO2elimination was enhanced by hypoxia and exercise, but O2exchange was not affected by exercise in normoxia or hypoxia. The stability of V˙/Q˙ matching under conditions of hypoxia and exercise may be advantageous for birds flying at altitude.
Deriving heart period variability from blood pressure waveforms
Authors: McKinley Paula S. , Shapiro Peter A. , Bagiella Emilia , Myers Michael M. , De Meersman Ronald E. , Grant Igor , Sloan Richard P.
Published: March 2015

International standards for calculating heart period variability (HPV) from a series of R-wave intervals (R-R) in an electrocardiographic (ECG) recording have been widely accepted. It is possible, and potentially useful in various settings, to use systolic blood pressure waveform intervals to estimate HPV, but the validity of HPV derived from blood pressure (BP) waveforms has not been established. To test the reliability between BP- and ECG-derived HPV indexes, we evaluated data from 234 healthy adults in four studies of HPV reactivity to stress. Study conditions included resting baseline, arithmetic, Stroop test, speech presentation, and orthostatic tilt. Continuous ECG and BP recordings were sampled at a rate of 500 Hz, scored by the same methods, and used to calculate heart rate and time- and frequency-domain measures of HPV. Overall, reliability between the two methods was very high for computing heart rate and HPV indexes. High-frequency HPV indexes were somewhat less reliably computed. In conclusion, in healthy adults, with the use of appropriate methods, BP waveforms can produce reliable indexes of HPV.
Influence of acidosis and hypoxia on liver ischemia and reperfusion injury in an in vivo rat model
Authors: Heijnen Bob H. M. , Elkhaloufi Yasser , Straatsburg Irene H. , van Gulik Thomas M.
Published: March 2015

The contribution of acidosis to the development of reperfusion injury is controversial. In this study, we examined the effects of respiratory acidosis and hypoxia in a frequently used in vivo liver ischemia and reperfusion (I/R) injury rat model. Rats were anesthetized with intraperitoneal anesthetics and subjected to partial liver ischemia (70%) for 60 min and subsequent reperfusion for 90 min under the following conditions: 1) no acidosis and normoxia, maintained by controlled ventilation; 2) acidosis and normoxia, maintained by passive supply with oxygen; 3) no acidosis and hypoxia, maintained by bicarbonate administration without respiratory support; and 4) acidosis and hypoxia, i.e., without respiratory support or pH correction. Changes in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured as parameters of hepatocellular injury, and bile secretion was monitored. AST and ALT levels were lowest in the ventilated rats and highest in the bicarbonate-treated rats. No differences in bile secretion were found between groups. Our results suggest that respiratory acidosis significantly enhanced liver I/R injury under normoxic conditions, whereas respiratory acidosis significantly reduced liver I/R injury under hypoxic conditions.
Water exchange induced by unilateral exercise in active and inactive skeletal muscles
Authors: Nygren Anders T. , Kaijser Lennart
Published: March 2015

Water exchange was evaluated in active (E-leg) and inactive skeletal muscles by using1H-magnetic resonance imaging. Six healthy subjects performed one-legged plantar flexion exercise at low and high workloads. Magnetic resonance imaging measured calf cross-sectional area (CSA), transverse relaxation time (T2), and apparent diffusion capacity (ADC) at rest and during recovery. After high workload, inactive muscle decreased CSA and T2 by 2.1% ( P < 0.05) and 3.1% ( P < 0.05), respectively, and left ADC unchanged. E-leg simultaneously increased CSA, T2, and ADC by 4.2% ( P < 0.001), 15.5% ( P < 0.05), and 12.5% ( P < 0.001), respectively. In conclusion, ADC and T2 correlated highly with muscle volume, indicative of extravascular water displacement closely related to muscle activity and perfusion, which was presumably a combined effect of increased intracellular osmoles and hydrostatic forces as driving forces. A distinguishable muscle temperature release was initially detected in the E-leg after high workload, and the ensuing recovery of ADC and T2 indicated delayed interstitial restitution than restitution of the intracellular compartment. Furthermore, absorption of extravascular water was detected in inactive muscles at contralateral high-intensity exercise.
Short-term training attenuates muscle TCA cycle expansion during exercise in women
Authors: Dawson Kristen D. , Howarth Krista R. , Tarnopolsky Mark A. , Wong Nathan D. , Gibala Martin J.
Published: March 2015

Muscle glycogenolytic flux and lactate accumulation during exercise are lower after 3-7 days of “short-term” aerobic training (STT) in men (e.g., Green HJ, Helyar R, Ball-Burnett M, Kowalchuk N, Symon S, and Farrance B. J Appl Physiol 72: 484-491, 1992). We hypothesized that 5 days of STT would attenuate pyruvate production and the increase in muscle tricarboxylic acid cycle intermediates (TCAI) during exercise, because of reduced flux through the reaction catalyzed by alanine aminotransferase (AAT; pyruvate + glutamate ↔ 2-oxoglutarate + alanine). Eight women [22 ± 1 yr, peak oxygen uptake (V̇o2 peak) = 40.3 ± 4.6 ml · kg-1 · min-1] performed seven 45-min bouts of cycle exercise at 70% V̇o2 peak over 9 days (1 bout/day; rest only on days 2 and 8). During the first and last bouts, biopsies (vastus lateralis) were obtained at rest and after 5 and 45 min of exercise. Muscle glycogen concentration was ∼50% higher at rest after STT (493 ± 38 vs. 330 ± 20 mmol/kg dry wt; P ≤ 0.05), and net glycogenolysis and lactate accumulation were reduced after 5 min of exercise by 59 and 49%, respectively ( P ≤ 0.05). The net increase in four measured TCAI was ∼40% lower ( P ≤ 0.05) during exercise after training (1.68 ± 0.60 vs. 2.71 ± 0.44 mmol/kg dry wt), and the net decrease in glutamate concentration was attenuated ( P ≤ 0.05). We conclude that 1) the contraction-induced increase in flux through AAT is reduced after 5 days of aerobic training and 2) the muscle glycogenolytic response during exercise after STT in women is similar to that in men.
Lactate metabolism in resting and contracting canine skeletal muscle with elevated lactate concentration
Authors: Kelley Kevin M. , Hamann Jason J. , Navarre Christine , Gladden L. Bruce
Published: March 2015

This study was undertaken to quantitatively account for the metabolic disposal of lactate in skeletal muscle exposed to an elevated lactate concentration during rest and mild-intensity contractions. The gastrocnemius plantaris muscle group (GP) was isolated in situ in seven anesthetized dogs. In two experiments, the muscles were perfused with an artificial perfusate with a blood lactate concentration of ∼9 mM while normal blood gas/pH status was maintained with [U-14C]lactate included to follow lactate metabolism. Lactate uptake and metabolic disposal were measured during two consecutive 40-min periods, during which the muscles rested or contracted at 1.25 Hz. Oxygen consumption averaged 10.1 ± 2.0 μmol · 100 g−1· min−1(2.26 ± 0.45 ml · kg−1· min−1) at rest and 143.3 ± 16.2 μmol · 100 g−1· min−1(32.1 ± 3.63 ml · kg−1· min−1) during contractions. Lactate uptake was positive during both conditions, increasing from 10.5 μmol · 100 g−1· min−1at rest to 25.0 μmol · 100 g−1· min−1during contractions. Oxidation and glycogen synthesis represented minor pathways for lactate disposal during rest at only 6 and 15%, respectively, of the [14C]lactate removed by the muscle. The majority of the [14C]lactate removed by the muscle at rest was recovered in the muscle extracts, suggesting that quiescent muscle serves as a site of passive storage for lactate carbon during high-lactate conditions. During contractions, oxidation was the dominant means for lactate disposal at >80% of the [14C]lactate removed by the muscle. These results suggest that oxidation is a limited means for lactate disposal in resting canine GP exposed to elevated lactate concentrations due to the muscle's low resting metabolic rate.
Airway and tissue mechanics in a murine model of asthma: alveolar capsule vs. forced oscillations
Authors: Tomioka Shinichiro , Bates Jason H. T. , Irvin Charles G.
Published: March 2015

To better address the functional consequences of inflammation on bronchial responsiveness, we studied two groups of BALB/c mice: a nonimmunized control group ( n = 8) and a group immunized and challenged with inhaled ovalbumin ( n = 8). An alveolar capsule (AC) measured airway resistance (RawAC) and lung elastance (El). A forced oscillation (FO) technique independently estimated airway resistance (RawFO) and a parameter H ti related to tissue elastance. Ovalbumin-immunized and -challenged mice had increased numbers of eosinophils in bronchoalveolar lavage and increased responsiveness to methacholine (MCh). Corresponding parameters from the AC and FO techniques were correlated: RawAC vs. RawFO( r = 0.76) and El vs. H ti ( r = 0.88, P< 0.0001 in all cases). AC and FO techniques showed significant increases in tissue elastance in response to MCh but no significant increases in airway resistance. These results demonstrated that the AC and FO techniques yield essentially equivalent results in mice, even when the lung is inhomogeneous, and that the bronchoconstrictive responses to MCh and inflammation in mice are predominantly located in the lung periphery.
Selected Contribution: Acute cellular and molecular responses to resistance exercise
Authors: Haddad Fadia , Adams Gregory R.
Published: March 2015

Training protocols apply sequential bouts of resistance exercise (RE) to induce the cellular and molecular responses necessary to produce compensatory hypertrophy. This study was designed to 1) define the time course of selected cellular and molecular responses to a single bout of RE and 2) examine the effects of interbout rest intervals on the summation of these responses. Rat muscles were exposed to RE via stimulation of the sciatic nerve in vivo. Stimulated and control muscles were obtained at various time points post-RE and analyzed via Western blot and RT-PCR. A single bout of RE increased intracellular signaling (i.e., phosphorylations) and expression of mRNAs for insulin-like growth factor-I system components and myogenic markers (e.g., cyclin D1, myogenin). A rest interval of 48 h between RE bouts resulted in much greater summation of myogenic responses than 24- or 8-h rest intervals. This experimental approach should be useful for studying the regulatory mechanisms that control the hypertrophy response. These methods could also be used to compare and contrast different exercise parameters (e.g., concentric vs. eccentric, etc.).
Molecular responses of human muscle to eccentric exercise
Authors: Chen Yi-Wen , Hubal Monica J. , Hoffman Eric P. , Thompson Paul D. , Clarkson Priscilla M.
Published: March 2015

We examined the effect of eccentric exercise on the transcriptome of skeletal muscle in three male human volunteers who performed 300 concentric contractions with one leg and 300 eccentric contractions with the opposite leg. Vastus lateralis muscle biopsies were taken from both legs at 4–8 h after exercise, and expression was profiled by using 12,000 gene Affymetrix U95Av2 microarrays. We found a high concordance of expression responses to eccentric contractions between our human and rat data from a previous study (Chen YW, Nader GA, Baar KR, Fedele MJ, Hoffman EP, and Esser KA. J Physiol 545: 27–41, 2002) (∼50% of gene expression changes shared between species). Potential human-specific changes included greater inflammatory responses [chemokine (C-C motif) ligand 2, C/EBP delta, and IL-1 receptor] and vascular remodeling (tenascin C and lipocortin II). Induction of c- fos and lipocortin II were confirmed at the protein level, with c- fos localized to myofiber nuclei and lipocortin II to intramuscular capillaries. We also confirmed the eccentric-induced expression of six transcripts by quantitative RT-PCR (cardiac ankyrin-repeated protein, chemokine ligand 2, CCAAT/enhancer binding protein delta, IL-1 receptor, tenascin C, and cysteine-rich angiogenic inducer 61). These data provide the first characterization of the transcriptional response of skeletal muscle to eccentric exercise in humans and represent a preliminary step in understanding the molecular processes underlying muscle remodeling (including a new focus on rapid changes in the capillary bed) and inflammatory responses after damaging lengthening contractions.
Energetics and mechanics of human running on surfaces of different stiffnesses
Authors: Kerdok Amy E. , Biewener Andrew A. , McMahon Thomas A. , Weyand Peter G. , Herr Hugh M.
Published: March 2015

Mammals use the elastic components in their legs (principally tendons, ligaments, and muscles) to run economically, while maintaining consistent support mechanics across various surfaces. To examine how leg stiffness and metabolic cost are affected by changes in substrate stiffness, we built experimental platforms with adjustable stiffness to fit on a force-plate-fitted treadmill. Eight male subjects [mean body mass: 74.4 ± 7.1 (SD) kg; leg length: 0.96 ± 0.05 m] ran at 3.7 m/s over five different surface stiffnesses (75.4, 97.5, 216.8, 454.2, and 945.7 kN/m). Metabolic, ground-reaction force, and kinematic data were collected. The 12.5-fold decrease in surface stiffness resulted in a 12% decrease in the runner's metabolic rate and a 29% increase in their leg stiffness. The runner's support mechanics remained essentially unchanged. These results indicate that surface stiffness affects running economy without affecting running support mechanics. We postulate that an increased energy rebound from the compliant surfaces studied contributes to the enhanced running economy.
Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation
Authors: Berghoff Martin , Kathpal Madeera , Kilo Sonja , Hilz Max J. , Freeman Roy
Published: March 2015

The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex.
Effects of sustained stimulation on the excitability of motoneurons innervating paralyzed and control muscles
Authors: Butler Jane E. , Thomas Christine K.
Published: March 2015

The excitability of thenar motoneurons (reflected by F-wave persistence and amplitude) and thenar muscle force were measured during a stimulation protocol (90 s of 18-Hz supramaximal electrical stimulation of the median nerve) designed to induce muscle fatigue (force decline). Data from muscles ( n = 15) paralyzed by chronic cervical spinal cord injury were compared with those obtained from control muscles ( n = 6). The persistence of F waves in both paralyzed and control muscles increased from ∼60 to ∼76% during the first 10 s of the fatigue protocol. Persistence then declined progressively to ∼33% at 90 s. These changes in F-wave persistence suggest that similar reductions occur in the excitability of the motoneurons to paralyzed and control motor units after sustained antidromic activation. Despite this, significantly larger force declines occurred in the paralyzed muscles of spinal cord-injured subjects (∼60%) than in the muscles of control subjects (∼15%). These data suggest that the decreases in motoneuron excitability for both the spinal cord-injured and control subjects are a result of activity-dependent changes in motoneuron properties that are independent of fatigue-related processes in the muscles.
Neural adaptation to resistance training: changes in evoked V-wave and H-reflex responses
Authors: Aagaard Per , Simonsen Erik B. , Andersen Jesper L. , Magnusson Peter , Dyhre-Poulsen Poul
Published: March 2015

Combined V-wave and Hoffmann (H) reflex measurements were performed during maximal muscle contraction to examine the neural adaptation mechanisms induced by resistance training. The H-reflex can be used to assess the excitability of spinal α-motoneurons, while also reflecting transmission efficiency (i.e., presynaptic inhibition) in Ia afferent synapses. Furthermore, the V-wave reflects the overall magnitude of efferent motor output from the α-motoneuron pool because of activation from descending central pathways. Fourteen male subjects participated in 14 wk of resistance training that involved heavy weight-lifting exercises for the muscles of the leg. Evoked V-wave, H-reflex, and maximal M-wave (Mmax) responses were recorded before and after training in the soleus muscle during maximal isometric ramp contractions. Maximal isometric, concentric, and eccentric muscle strength was measured by use of isokinetic dynamometry. V-wave amplitude increased ∼50% with training ( P < 0.01) from 3.19 ± 0.43 to 4.86 ± 0.43 mV, or from 0.308 ± 0.048 to 0.478 ± 0.034 when expressed relative to Mmax (± SE). H-reflex amplitude increased ∼20% ( P < 0.05) from 5.37 ± 0.41 to 6.24 ± 0.49 mV, or from 0.514 ± 0.032 to 0.609 ± 0.025 when normalized to Mmax. In contrast, resting H-reflex amplitude remained unchanged with training (0.503 ± 0.059 vs. 0.499 ± 0.063). Likewise, no change occurred in Mmax (10.78 ± 0.86 vs. 10.21 ± 0.66 mV). Maximal muscle strength increased 23–30% ( P < 0.05). In conclusion, increases in evoked V-wave and H-reflex responses were observed during maximal muscle contraction after resistance training. Collectively, the present data suggest that the increase in motoneuronal output induced by resistance training may comprise both supraspinal and spinal adaptation mechanisms (i.e., increased central motor drive, elevated motoneuron excitability, reduced presynaptic inhibition).
Variability in the interpolated twitch torque for maximal and submaximal voluntary contractions
Authors: Oskouei M. A. E. , van Mazijk B. C. F. , Schuiling M. H. C. , Herzog W
Published: March 2015

The superimposed twitch technique is frequently used to study the degree of motor unit activation during voluntary effort. This technique is one of the preferred methods to determine the activation deficit (AD) in normal, athletic, and patient populations. One of the limitations of the superimposed twitch technique is its variability under given contractile conditions. The objective of this research was to determine the source(s) of variability in the superimposed twitch force (STF) for repeat measurements. We hypothesized that the variability in the AD measurements may be caused by the timing of the twitch force relative to the onset of muscle activation, by force transients during the twitch application, by small variations in the actual force from the nominal target force, and by variations in the resting twitch force. Twenty-eight healthy subjects participated in this study. Sixteen of these subjects participated in a protocol involving contractions at 50% of their maximal voluntary contraction (MVC) effort, whereas the remaining 12 participated in a protocol involving contractions at 100% of their MVC. Doublet-twitch stimuli were superimposed onto the 50 and 100% effort knee extensor muscle contractions, and the resting twitch forces, voluntary knee extensor forces, and STFs were then measured. The mean resting twitch forces obtained before and after 8 s of 50% of MVC were the same. Similarly, the mean STFs determined at 1, 3, 5, and 7 s into the 50% MVC were the same. The variations in twitch force were significantly smaller after accounting for the actual force at twitch application than those calculated from the prescribed forces during the 50% MVC protocol ( P < 0.05). Furthermore, the AD and the actual force showed statistically significant negative correlations for the 50% MVC tests. The interpolated twitch torque determined for the maximal effort contractions ranged from 1 to 70%. In contrast to the protocol at 50% of MVC, negative correlations were only observed in 5 of the 12 subjects during the 100% effort contractions. These results suggest that small variations in the actual force from the target force can account for the majority of the variations in the STFs for submaximal but not maximal effort contractions. For the maximal effort contractions, large variations in the STF exist due to undetermined causes.
Focal CO2/H+ alters phrenic motor output response to chemical stimulation of cat pre-Bötzinger complex in vivo
Authors: Solomon Irene C.
Published: March 2015

Microinjection ofdl-homocysteic acid (DLH), a glutamate analog, into the pre-Bötzinger complex (pre-BötC) can produce tonic excitation of phrenic nerve discharge. Although this DLH-induced tonic excitation can be modified by systemic hypercapnia, the role of focal increases in pre-BötC CO2/H+ in this modulation of the DLH-induced response remains to be determined. Therefore, we examined the effects of unilateral microinjection of DLH (10 mM; 10–20 nl) into the pre-BötC before and during increased focal pre-BötC CO2/H+ (i.e., focal tissue acidosis) in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Focal tissue acidosis was produced by blockade of carbonic anhydrase with either focal acetazolamide (AZ) or methazolamide (MZ) microinjection. For these experiments, sites were selected in which unilateral microinjection of DLH into the pre-BötC produced a nonphasic tonic excitation of phrenic nerve discharge ( n = 10). Microinjection of 10–20 nl AZ (50 μM) or MZ (50 μM) into these 10 sites in the pre-BötC increased the amplitude and/or frequency of eupneic phrenic bursts, as previously reported. Subsequent microinjection of DLH produced excitation in which phasic respiratory bursts were superimposed on tonic discharge. These DLH-induced phasic respiratory bursts had an increased frequency compared with the preinjection baseline frequency ( P < 0.05). These findings demonstrate that modulation of phrenic motor activity evoked by DLH-induced activation of the pre-BötC is influenced by focal CO2/H+chemosensitivity in this region. Furthermore, these findings suggest that focal increases in pre-BötC CO2/H+may have contributed to the modulation of the DLH-induced responses previously observed during systemic hypercapnia.
Invited Review: Alveolar edema fluid clearance in the injured lung
Authors: Berthiaume Yves , Folkesson Hans G. , Matthay Michael A.
Published: March 2015

Resolution of pulmonary edema involved active transepithelial sodium transport. Although several of the cellular and molecular mechanisms involved are relatively well understood, it is only recently that the regulation of these mechanisms in injured lung are being evaluated. Interestingly, in mild-to-moderate lung injury, alveolar edema fluid clearance is often preserved. This preserved or enhanced alveolar fluid clearance is mediated by catecholamine-dependent or -independent mechanisms. This stimulation of alveolar liquid clearance is related to activation or increased expression of sodium transport molecules such as the epithelial sodium channel or the Na+-K+-ATPase pump and may also involve the cystic fibrosis transmembrane conductance regulator. When severe lung injury occurs, the decrease in alveolar liquid clearance may be related to changes in alveolar permeability or to changes in activity or expression of sodium or chloride transport molecules. Multiple pharmacological tools such as β-adrenergic agonists, vasoactive drugs, or gene therapy may prove effective in stimulating the resolution of alveolar edema in the injured lung.
Altered diaphragm contractile properties with controlled mechanical ventilation
Authors: Sassoon Catherine S. H. , Caiozzo Vincent J. , Manka Albana , Sieck Gary C.
Published: March 2015

This study shows that, over time, diaphragm inactivity with controlled mechanical ventilation (CMV) decreases diaphragm force and produces myofibril damage contributing to the reduced force. We measured in vivo and in vitro diaphragm contractile and morphological properties in 30 sedated rabbits grouped ( n = 6) as follows: 1 or 3 days of CMV, 1 or 3 days of 0 cmH2O continuous positive airway pressure, and control. The CMV rate was set sufficient to suppress diaphragm electrical activity. Compared with the control group, phrenic-stimulated maximum transdiaphragmatic pressure did not decrease with continuous positive airway pressure but decreased to 63% after 1 day of CMV and to 49% after 3 days of CMV. The in vitro tetanic force decreased to 86% after 1 day of CMV and to 44% after 3 days of CMV. After 3 days of CMV, significant myofibril damage occurred in the diaphragm but not in the soleus. The decrease in tetanic force correlated with the volume density of abnormal myofibrils. We conclude that CMV had a detrimental effect on diaphragm contractile properties.
Exercise-induced change in type 1 cytokine-producing CD8+ T cells is related to a decrease in memory T cells
Authors: Ibfelt Tobias , Petersen Emil Wolsk , Bruunsgaard Helle , Sandmand Marie , Pedersen Bente Klarlund
Published: March 2015

In response to exercise, both CD4+ and CD8+ T cells are mobilized to the blood, but the levels of these cells decline below preexercise values in the postexercise period. T cells are functionally polarized, depending on the cytokines they produce. Type 1 cells produce, e.g., interferon (INF)-γ, whereas type 2 produce, e.g., interleukin (IL)-4. It was recently demonstrated that exercise induces a decrease in the percentage of type 1 T cells. The present study further investigated the mechanisms underlying the exercise-induced shift in the balance between type 1 and type 2 cytokine-producing cells. Seven healthy men performed 1.5 h of treadmill running with blood samples drawn before exercise, at the end of exercise, and 2 h after exercise. Intracellular expression of IFN-γ, IL-2, and IL-4 was detected in CD4+ and CD8+ T cells after stimulation with phorbol 12-myristate 13-acetate and ionomycin. Intracellular expression of IFN-γ within CD8+ cells was decreased in the postexercise period compared with values obtained immediately after exercise, whereas the expression of IL-2 and IL-4 did not change within the CD4+and CD8+ cell populations. The decrease in IFN-γ-producing CD8+ T cells postexercise was negatively correlated with a decrease in percentage of memory T cells within the CD8+ cells ( r = −0.94; P≤ 0.002). In conclusion, this study demonstrates that the exercise-induced change in type 1 cytokine-producing T cells is related to a decline in memory cells.
Respiratory-related evoked potentials elicited by inspiratory occlusions in double-lung transplant recipients
Authors: Zhao Weiying , Martin A. Daniel , Davenport Paul W.
Published: March 2015

This study investigated the role of lung vagal afferents in the respiratory-related evoked potential (RREP) response to inspiratory occlusions by using double-lung transplant recipients as a lung denervation model. Evoked potential recordings in response to inspiratory occlusions were obtained from 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects under the attend, ignore, and unoccluded conditions. Results demonstrated that early-latency RREP components (P1, P1a, Nf, and N1) were not significantly different between the DLT and the Nor groups. The late-latency RREP component (P3) was identifiable in all DLT subjects during the attend trial. However, P3 latency was significantly longer in the DLT group compared with the Nor group. The zero-to-peak amplitude of P3 was also significantly smaller in the DLT group than that in the Nor group during the attend trial. These results suggest that lung vagal afferents were not essential to elicit RREP responses, but may contribute to the cognitive processing of respiratory stimuli.
Effects of tower climbing exercise on bone mass, strength, and turnover in orchidectomized growing rats
Authors: Notomi Takuya , Okazaki Yuichi , Okimoto Nobukazu , Tanaka Yuri , Nakamura Toshitaka , Suzuki Masashige
Published: March 2015

To determine the effects of a tower climbing exercise on mass, strength, and local turnover of bone, 70 9-wk-old Sprague-Dawley rats were assigned to seven groups: a baseline control and three groups of sham-operated sedentary, orchidectomized (ORX)-sedentary and ORX-exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 4 wk, the periosteal bone formation rate (BFR), moment of inertia, bone mineral content, bone mineral density, and bending load at the midfemur were maintained in ORX-exercise rats, whereas these parameters were reduced in ORX-sedentary rats. At 8 wk, the periosteal mineral apposition rate and BFR in ORX-exercise rats were significantly higher, whereas the parameters in ORX-sedentary rats did not differ compared with sham-sedentary rats. In ORX-exercise rats, the trabecular mineralizing surface, BFR, and bone volume of the lumbar vertebrae were maintained at the same levels as those in the sham-sedentary group, whereas the osteoclast surface decreased compared with the ORX-sedentary group. However, the climbing exercise did not affect bone mineral content, bone mineral density, or the compression load of the lumbar vertebrae. These results show that, in the midfemur, the voluntary climbing exercise maintained cortical bone mass and strength by stimulating periosteal bone formation and partially prevented ORX-induced trabecular bone loss, depressing the elevation of turnover. Interestingly, in ORX rats, the climbing exercise had the opposite effect on bone formation at the periosteal femoral cortical bone, where the exercise increased the bone formation compared with vertebral trabecular bone, where the exercise decreased it.
Caffeine-induced impairment of glucose tolerance is abolished by β-adrenergic receptor blockade in humans
Authors: Thong Farah S. L. , Graham Terry E.
Published: March 2015

The caffeine-induced impairment of insulin action is commonly attributed to adenosine receptor (AR) antagonism in skeletal muscle. However, epinephrine, a potent inhibitor of insulin actions, is increased after caffeine ingestion. We tested the hypothesis that the insulin antagonistic effects of caffeine are mediated by epinephrine, and not by AR antagonism, in seven healthy men. On four separate occasions, they received 1) dextrose (placebo, PL), 2) 5 mg/kg caffeine (CAF), 3) 80 mg of propranolol (PR), and 4) 5 mg/kg caffeine + 80 mg of propranolol (CAF + PR) before an oral glucose tolerance test (OGTT). Blood glucose was similar among trials before and during the OGTT. Plasma epinephrine was elevated ( P < 0.05) in CAF and CAF + PR. Areas under the insulin and C-peptide curves were 42 and 39% greater ( P < 0.05), respectively, in CAF than in PL, PR, and CAF + PR. In the presence of propranolol (CAF + PR), these responses were similar to PL and PR. These data suggest that the insulin antagonistic effects of caffeine in vivo are mediated by elevated epinephrine rather than by peripheral AR antagonism.
Functional characteristics of dystrophic skeletal muscle: insights from animal models
Authors: Watchko Jon F. , O'Day Terrence L. , Hoffman Eric P.
Published: March 2015

Muscular dystrophies are a clinically and genetically heterogeneous group of disorders that show myofiber degeneration and regeneration. Identification of animal models of muscular dystrophy has been instrumental in research on the pathogenesis, pathophysiology, and treatment of these disorders. We review our understanding of the functional status of dystrophic skeletal muscle from selected animal models with a focus on 1) the mdx mouse model of Duchenne muscular dystrophy, 2) the Bio 14.6 δ-sarcoglycan-deficient hamster model of limb-girdle muscular dystrophy, and 3) transgenic null mutant murine lines of sarcoglycan (α, β, δ, and γ) deficiencies. Although biochemical data from these models suggest that the dystrophin-sarcoglycan-dystroglycan-laminin network is critical for structural integrity of the myofiber plasma membrane, emerging studies of muscle physiology suggest a more complex picture, with specific functional deficits varying considerably from muscle to muscle and model to model. It is likely that changes in muscle structure and function, downstream of the specific, primary biochemical deficiency, may alter muscle contractile properties.
Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function
Authors: Widrick J. J. , Trappe S. W. , Romatowski J. G. , Riley D. A. , Costill D. L. , Fitts R. H.
Published: March 2015

We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.