bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of fixatives on function of pulmonary surfactant
Authors: Bachofen H. , Gerber U. , Schürch S.
Published: March 2015

The structure of pulmonary surfactant films remains ill defined. Although plausible film fragments have been imaged by electron microscopy, questions about the significance of the findings and even about the true fixability of surfactant films by the usual fixatives glutaraldehyde (GA), osmium tetroxide (OsO4), and uranyl acetate (UA) have not been settled. We exposed functioning natural surfactant films to fixatives within a captive bubble surfactometer and analyzed the effect of fixatives on surfactant function. The capacity of surfactant to reach near-zero minimum surface tension on film compression was barely impaired after exposure to GA or OsO4. Although neither GA nor OsO4 prevented the surfactant from forming a surface active film, GA increased the equilibrium surface tension to above 30 mN/m, and both GA and OsO4 decreased film stability as seen in the slowly rising minimum surface tension from 1 to ∼5 mN/m in 10 min. In contrast, the effect of UA seriously impaired surface activity in that both adsorption and minimum surface tension were substantially increased. In conclusion, the fixatives tested in this study are not suitable to fix, i.e., to solidify, surfactant films. Evidently, however, OsO4 and UA may serve as staining agents.
Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity
Authors: MacDonald Christopher , Wojtaszewski Jørgen F. P. , Pedersen Bente Klarlund , Kiens Bente , Richter Erik A.
Published: March 2015

We tested the hypothesis that IL-6 release from muscle during exercise may be related to muscle activity of 5′-AMP-activated protein kinase (AMPK). Eight healthy, well-trained young men completed two 60-min trials on a bicycle ergometer at 70% of their peak oxygen uptake in either a glycogen-depleted or a glycogen-loaded state. IL-6 was released from the leg already after 10 min of exercise in the glycogen-depleted state, whereas no significant release was observed at any time in the loaded state. Nevertheless, plasma IL-6 increased similarly in the two trials from ∼0.8 pg/ml at rest to ∼4.5 pg/ml after 60 min of exercise. Activity of α1-AMPK (160%) and α2-AMPK (145%) was increased at rest in the glycogen-depleted compared with the loaded situation. During exercise, α1-AMPK activity did not change from resting levels in both trials, whereas α2-AMPK activity increased only in the glycogen-depleted state. After 60 min of exercise in the glycogen-depleted state, individual values of α2-AMPK activity correlated significantly ( r = 0.87, P < 0.006) with individual values of IL-6 release as well as with average IL-6 release over the entire 60 min ( r = 0.86, P < 0.006). The present data are compatible with a role for AMPK in IL-6 release during exercise or a role for IL-6 in activating AMPK. Alternatively, both AMPK and IL-6 are independent sensors of a low muscle glycogen concentration during exercise. In addition, leg release of IL-6 cannot alone explain the increase in plasma IL-6 during exercise.
Short-term training enhances endothelium-dependent dilation of coronary arteries, not arterioles
Authors: Laughlin M. Harold , Rubin Leona J. , Rush James W. E. , Price E. M. , Schrage William G. , Woodman Christopher R.
Published: March 2015

Our objective was to test the hypothesis that short-term exercise training (STR) of pigs increases endothelium-dependent dilation (EDD) of coronary arteries but not coronary arterioles. Female Yucatan miniature swine ran on a treadmill for 1 h, at 3.5 mph, twice daily for 7 days (STR; n = 28). Skeletal muscle citrate synthase activity was increased in STR compared with sedentary controls (Sed; n = 26). Vasoreactivity was evaluated in isolated segments of conduit arteries (1–2 mm ID, 3–4 mm length) mounted on myographs and in arterioles (50–100 μm ID) isolated and cannulated with micropipettes with intraluminal pressure set at 60 cmH2O. EDD was assessed by examining responses to increasing concentrations of bradykinin (BK) (conduit arteries 10−12–10−6 M and arterioles 10−13–10−6 M). There were no differences in maximal EDD or BK sensitivity of coronary arterioles from Sed and STR hearts. In contrast, sensitivity of conduit arteries (precontracted with PGF2α) to BK was increased significantly ( P < 0.05) in STR (EC50, 2.33 ± 0.62 nM, n = 12) compared with Sed animals (EC50, 3.88 ± 0.62 nM, n = 13). Immunoblot analysis revealed that coronary arteries from STR and Sed animals had similar levels of endothelial nitric oxide synthase (eNOS). In contrast, eNOS protein was increased in STR aortic endothelial cells. Neither protein nor mRNA levels of eNOS were different in coronary arterioles from STR compared with Sed animals. STR did not alter expression of superoxide dismutase (SOD-1) protein in any artery examined. We conclude that pigs exhibit increases in EDD of conduit arteries, but not in coronary arterioles, at the onset of exercise training. These adaptations in pigs do not appear to be mediated by alterations in eNOS or SOD-1 expression.
Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung
Authors: Ware Lorraine B. , Fang Xiohui , Wang Yibing , Sakuma Tsutomu , Hall Timothy S. , Matthay Michael A.
Published: March 2015

Pulmonary edema is common in organ donors and lung transplant recipients. Therefore, we assessed the responsiveness of human donor lungs to pharmacological agents that stimulate clearance of alveolar edema. Organ donors whose lungs were rejected for transplantation were studied. After resection, transport (4°C), and rewarming (37°C) of lungs, alveolar fluid clearance was measured with ( n = 8 donors) or without ( n = 23 donors) β-adrenergic stimulation. Terbutaline-stimulated clearance (10−4M) was higher than unstimulated clearance (7.1 ± 1.3 vs. 4.8 ± 2.4%/h, P < 0.01). Second, we determined whether medications given to the organ donor were associated with the extent of pulmonary edema or the rate of alveolar fluid clearance in the harvested lung. Preharvest administration of dopamine in low to moderate doses was associated with faster alveolar fluid clearance ( r = 0.62, P < 0.01). Preharvest administration of diuretics was associated with lower extravascular lung water-to-dry weight ratios. This study provides the first evidence that a β2-adrenergic agonist stimulates alveolar fluid clearance in the human donor lung. Aerosolized β2-adrenergic agonists may have therapeutic value for hastening the resolution of alveolar edema during the management of donors before resection of lungs for transplantation or in the posttransplant setting.
Angiotensin-converting enzyme activity in ovine bronchial vasculature
Authors: Moldobaeva Aigul , Wagner Elizabeth M.
Published: March 2015

Angiotensin-converting enzyme (ACE) plays a major role in the metabolism of bradykinin, angiotensin, and neuropeptides, which are all implicated in inflammatory airway diseases. The activity of ACE, which is localized on the luminal surface of endothelial cells (EC), has been well documented in pulmonary EC; however, few data exist regarding the relative activity of ACE in the airway vasculature. Therefore, we measured ACE activity in cultured EC from the sheep bronchial artery and bronchial mucosa (microvascular) and compared it with pulmonary artery EC. The baseline level of total ACE activity (cellular plus secreted) was significantly greater in bronchial microvascular EC (1.24 ± 0.24 mU/106 cells) compared with bronchial artery EC (0.59 ± 0.15 mU/106 cells; P < 0.05) and comparable to pulmonary artery EC (1.12 ± 0.14 mU/106 cells; P > 0.05). Measured ACE activity secreted into culture medium for each cell type was 64–74% of total activity and did not differ among the three EC types ( P = 0.17). Hydrocortisone (10 μg/ml; 48–72 h) treatment resulted in a significant increase in ACE activity in bronchial EC. Likewise, TNF-α (0.1 ng/ml) treatment markedly increased ACE activity in all cell lysates ( P < 0.05). We confirmed the importance of ACE activity in vivo since, at the highest dose of bradykinin studied (10–8 M), bronchial artery pressure at constant flow showed a greater decrease after captopril treatment (36% before vs. 60% after; P = 0.05). These results demonstrate high ACE expression of the bronchial microvasculature and suggest an important regulatory role for ACE in the metabolism of kinin peptides known to contribute to airway pathology.
Selected Contribution: Effects of aging on cerebrovascular tone and [Ca2+]i
Authors: Geary Greg G. , Buchholz John N.
Published: March 2015

The lower limits of cerebral blood flow autoregulation shift toward high pressures in aged compared with young rats. Intraluminal pressure stimulates contractile mechanisms in cerebral arteries that might, in part, cause an age-dependent shift in autoregulation. The present project tested two hypotheses. First, cerebral artery tone is greater in isolated arteries from aged compared with mature adult rats. Second, aging decreases the modulatory effect of endothelium-derived nitric oxide (NO) and increases vascular smooth muscle Ca2+ sensitivity. Isolated segments of middle cerebral arteries from male 6-, 12-, 20-, and 24-mo-old Fischer 344 rats were cannulated and loaded with fura-2. Diameter and Ca2+ responses to increasing pressure were measured in HEPES, during NO synthase inhibition [ NG-nitro-l-arginine methyl ester (l-NAME)], and after removal of the endothelium. Cerebral artery tone (with endothelium) increased with age. Only at the lowest pressure (20 and 40 mmHg) was intracellular Ca2+ concentration ([Ca2+]i) greater in arteries from 24-mo-old rats compared with the other age groups. l-NAME-sensitive constriction increased significantly in arteries from 6- to 20-mo-old rats but declined significantly thereafter in arteries from 24-mo-old rats. [Ca2+]i was less in arteries from 24-mo-old rats compared with the other groups after treatment with l-NAME. Another endothelial-derived factor, insensitive to l-NAME, also decreased significantly with age. For example, at 60 mmHg, the l-NAME-insensitive constriction decreased from 47 ± 10, 42 ± 5, 21 ± 2, and 3 ± 1 μm in 6-, 12-, 20-, and 24-mo-old rats, respectively. Our data suggest that aging alters cerebral artery tone and [Ca2+]i responses through endothelial-derived NO synthase-sensitive and -insensitive mechanisms. The combined effect of greater cerebral artery tone with less endothelium-dependent modulation may in part contribute to the age-dependent shift in cerebral blood flow autoregulation.
Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content
Authors: Ma Jin , Kahwaji Chadi I. , Ni Zhenmin , Vaziri Nosratola D. , Purdy Ralph E.
Published: March 2015

The aim of the present work was to investigate the alterations in nitric oxide synthase (NOS) expression and nitrate and nitrite (NOx) content of different arteries from simulated microgravity rats. Male Wistar rats were randomly assigned to either a control group or simulated microgravity group. For simulating microgravity, animals were subjected to hindlimb unweighting (HU) for 20 days. Different arterial tissues were removed for determination of NOS expression and NOx. Western blotting was used to measure endothelial NOS (eNOS) and inducible NOS (iNOS) protein content. Total concentrations of NOx, stable metabolites of nitric oxide, were determined by the chemiluminescence method. Compared with controls, isolated vessels from simulated microgravity rats showed a significant increase in both eNOS and iNOS expression in carotid arteries and thoracic aorta and a significant decrease in eNOS and iNOS expression of mesenteric arteries. The eNOS and iNOS content of cerebral arteries, as well as that of femoral arteries, showed no differences between the two groups. Concerning NOx, vessels from HU rats showed an increase in cerebral arteries, a decrease in mesenteric arteries, and no change in carotid artery, femoral artery and thoracic aorta. These data indicated that there were differential alterations in NOS expression and NOx of different arteries after hindlimb unweighting. We suggest that these changes might represent both localized adaptations to differential body fluid redistribution and other factors independent of hemodynamic shifts during simulated microgravity.
Tidal volume single-breath washin of SF6 and CH4 in transient microgravity
Authors: Dutrieue Brigitte , Paiva Manuel , Verbanck Sylvia , Le Gouic Marine , Darquenne Chantal , Prisk G. Kim
Published: March 2015

We performed tidal volume single-breath washins (SBW) by using tracers of different diffusivity and varied the time spent in microgravity (μG) before the start of the tests to look for time-dependent effects. SF6 and CH4 phase III slopes decreased by 35 and 26%, respectively, in μG compared with 1 G ( P < 0.05), and the slope difference between gases disappeared. There was no effect of time in μG, suggesting that neither the hypergravity period preceding μG nor the time spent in μG affected gas mixing at volumes near functional residual capacity. In previous studies using SF6 and He (Lauzon A-M, Prisk GK, Elliott AR, Verbanck S, Paiva M, and West JB. J Appl Physiol 82: 859–865, 1997), the vital capacity SBW showed an increase in slope difference between gases in transient μG, the opposite of the decrease in sustained μG. In contrast, tidal volume SBW showed a decrease in slope difference in both μG conditions. Because it is only the behavior of the more diffusive gas that differed between maneuvers and μG conditions, we speculate that, in the previous vital capacity SBW, the hypergravity period preceding the test in transient μG provoked conformational changes at low lung volumes near the acinar entrance.
Awake negative pressure reflex response of the genioglossus in OSA patients and normal subjects
Authors: Berry Richard B. , White David P. , Roper John , Pillar Giora , Fogel Robert B. , Stanchina Michael , Malhotra Atul
Published: March 2015

We hypothesized that the response of the genioglossus to negative pressure during wakefulness should be intact in obstructive sleep apnea (OSA) patients despite published evidence showing impairment of the response of palatal muscles (Mortimore IL and Douglas NJ. Am J Respir Crit Care Med156: 867–873, 1997). Thus the response of the genioglossus to brief nasal negative pressure applications (NPAs) in early inspiration was compared between OSA patients and an age-matched group of normal subjects at two study sites ( n = 11 per group in Long Beach, n = 14 per group in Boston). Subjects were studied in the sitting (Long Beach) or supine (Boston) posture, and the genioglossus electromyogram (EMGgg) was measured with an intraoral surface electrode (Long Beach) or intramuscular electrode (Boston). The response of the EMGgg was expressed as the percent change from baseline where the baseline EMGgg was the value at the onset of the NPA. In Long Beach, the EMGgg response was significantly higher in the OSA patients at a lower suction pressure of ∼10 cmH2O (75.2 ± 8.4 vs. 37.4 ± 4.0% increase; P < 0.001) but not at a higher suction pressure of ∼20 cmH2O. In Boston, the response in the OSA patients was also greater (107.2 ± 25.9 vs. 46.3 ± 8.3%; P < 0.05) at a suction pressure of ∼13 cmH2O. We conclude that the response of the genioglossus to NPA during wakefulness is not impaired in OSA patients compared with normal subjects and is greater at low suction pressures.
Age and contraction type influence motor output variability in rapid discrete tasks
Authors: Christou Evangelos A. , Carlton Les G.
Published: March 2015

The purpose of this study was to examine the ability to control knee-extension force during discrete isometric (IC), concentric (CC), and eccentric contractions (EC) in 24 young (mean age ± SD = 25.3 ± 2.8 yr) and 24 old (mean age ± SD = 73.3 ± 5.5 yr) healthy and active individuals. Subjects were to match a parabola with a time to peak force of 200 ms during IC, CC, and EC at six target levels of force [20, 35, 50, 65, 80, and 90% of the maximum voluntary contraction (MVC)]. ICs were performed at 90° of knee flexion, whereas CCs and ECs ranged from 90 to 80° of knee flexion (0° is full extension) at a slow velocity (25°/s). Results showed that subjects produced similar MVC forces for the three types of contractions. Young subjects produced greater MVC forces than old subjects, and within each age group, men produced greater force than women. The variability (standard deviation) of peak force and impulse in absolute values was greater for young compared with old subjects. When variability was normalized to the force produced [coefficient of variation (CV)], however, old subjects exhibited greater CV than young subjects for peak force and impulse. Both the standard deviation and CV of time to peak force and impulse duration were greater for the old adults. In general, ECs were more variable than ICs and CCs, and old adults exhibited greater CV compared with young adults during rapid, discrete ICs, CCs, and particularly ECs of the quadriceps.
Responses to ozone are increased in obese mice
Authors: Shore S. A. , Rivera-Sanchez Y. M. , Schwartzman I. N. , Johnston R. A.
Published: March 2015

Epidemiological data indicate an increased incidence of asthma in overweight adults and children. Ozone (O3) is a common trigger for asthma. Accordingly, the purpose of this study was to compare O3-induced airway hyperresponsiveness and airway inflammation in lean, wild-type (C57BL/6J) mice and mice that are obese as a consequence of a genetic defect in the gene encoding the satiety hormone leptin ( ob/ob mice). The ob/ob mice eat excessively and weighed more than twice as much as age- and gender-matched wild-type mice. Airway responsiveness to intravenous methacholine was measured by forced oscillation. In air-exposed controls, baseline pulmonary resistance was greater, and the dose of methacholine required to double pulmonary resistance was lower in ob/ob than wild-type mice. Exposure to O3(2 parts/million for 3 h) caused AHR and airway inflammation in both groups of mice, but responses to O3were enhanced in ob/ob compared with wild-type mice. Administration of exogenous leptin did not reverse the enhanced inflammatory response observed in ob/ob mice, but augmented airway inflammation in wild-type mice. The inhaled dose of O3per gram of lung tissue was greater in ob/ob than wild-type mice. Our results indicate that O3-induced airway responses are enhanced in ob/ob mice and suggest that inhaled O3dose may be one factor contributing to this difference, but other aspects of the obese phenotype may also contribute. Our results also indicate that the hormone leptin, which is increased in the obese, has the capacity to increase airway inflammation.
Invited Review: Aging and sarcopenia
Authors: Doherty Timothy J.
Published: March 2015

Aging is associated with progressive loss of neuromuscular function that often leads to progressive disability and loss of independence. The term sarcopenia is now commonly used to describe the loss of skeletal muscle mass and strength that occurs in concert with biological aging. By the seventh and eighth decade of life, maximal voluntary contractile strength is decreased, on average, by 20-40% for both men and women in proximal and distal muscles. Although age-associated decreases in strength per unit muscle mass, or muscle quality, may play a role, the majority of strength loss can be accounted for by decreased muscle mass. Multiple factors lead to the development of sarcopenia and the associated impact on function. Loss of skeletal muscle fibers secondary to decreased numbers of motoneurons appears to be a major contributing influence, but other factors, including decreased physical activity, altered hormonal status, decreased total caloric and protein intake, inflammatory mediators, and factors leading to altered protein synthesis, must also be considered. The prevalence of sarcopenia, which may be as high as 30% for those ≥60 yr, will increase as the percentage of the very old continues to grow in our populations. The link between sarcopenia and disability among elderly men and women highlights the need for continued research into the development of the most effective interventions to prevent or at least partially reverse sarcopenia, including the role of resistance exercise and other novel pharmacological and nutritional interventions.
nCPAP improves abnormal autonomic function in at-risk-for-SIDS infants with OSA
Authors: Harrington C. , Kirjavainen T. , Teng A. , Sullivan C. E.
Published: March 2015

We evaluated cardiovascular autonomic control and arousability during sleep in infants with obstructive sleep apnea (OSA) before and after 10 ± 4 (mean ± SD) days of treatment with nasal continuous positive airway pressure (nCPAP). Six OSA infants and 12 age-matched control infants were studied with polygraphic sleep studies at the age of 13 ± 4 wk. During the study, 45° head-up tilt tests were performed in slow-wave and rapid eye movement sleep. Blood pressure (BP) and heart rate (HR) were continuously monitored. All OSA infants had decreased initial BP and HR responses, followed by hypotension in two and hypertension in two. OSA infants displayed higher arousal thresholds in response to the tilt in rapid eye movement sleep ( P < 0.005) and higher baseline HR ( P < 0.05) than controls. nCPAP treatment normalized BP and HR responses as well as arousal thresholds to tilting and stabilized HR levels. OSA in infants may be linked with cardiovascular autonomic control disturbances and decreased arousability during sleep. These defects are improved by control of OSA with nCPAP.
Circulating hematopoietic progenitor cells in runners
Authors: Bonsignore Maria R. , Morici Giuseppe , Santoro Alessandra , Pagano Maria , Cascio Lucia , Bonanno Anna , Abate Pietro , Mirabella Franco , Profita Mirella , Insalaco Giuseppe , Gioia Maria , Vignola A. Maurizio , Majolino Ignazio , Testa Ugo , Hogg James C.
Published: March 2015

Because endurance exercise causes release of mediators and growth factors active on the bone marrow, we asked whether it might affect circulating hematopoietic progenitor cells (HPCs) in amateur runners [ n = 16, age: 41.8 ± 13.5 (SD) yr, training: 93.8 ± 31.8 km/wk] compared with sedentary controls ( n = 9, age: 39.4 ± 10.2 yr). HPCs, plasma cortisol, interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), and the growth factor fms-like tyrosine kinase-3 (flt3)-ligand were measured at rest and after a marathon (M; n = 8) or half-marathon (HM; n = 8). Circulating HPC counts (i.e., CD34+cells and their subpopulations) were three- to fourfold higher in runners than in controls at baseline. They were unaffected by HM or M acutely but decreased the morning postrace. Baseline cortisol, flt3-ligand, IL-6, and G-CSF levels were similar in runners and controls. IL-6 and G-CSF increased to higher levels after M compared with HM, whereas cortisol and flt3-ligand increased similarly postrace. Our data suggest that increased HPCs reflect an adaptation response to recurrent, exercise-associated release of neutrophils and stress and inflammatory mediators, indicating modulation of bone marrow activity by habitual running.
Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide
Authors: Buckwalter John B. , Curtis Valerie C. , Valic Zoran , Ruble Stephen B. , Clifford Philip S.
Published: March 2015

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution ( N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly ( P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 ± 4 vs. 60 ± 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially ( P < 0.05) shorter in thel-NAME-treated group: 539 ± 67 vs. 889 ± 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.
Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes
Authors: Townsend Nathan E. , Gore Christopher J. , Hahn Allan G. , McKenna Michael J. , Aughey Robert J. , Clark Sally A. , Kinsman Tahnee , Hawley John A. , Chow Chin-Moi
Published: March 2015

This study determined whether “living high-training low” (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8–10 h/day overnight in normobaric hypoxia (∼2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (ΔV˙e/ΔSpO2 , whereV˙e is minute ventilation and SpO2 is blood O2 saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal Pco 2(Pet CO2 ) and V˙e were measured during room air breathing at rest. HVR (l · min−1 · %−1) was higher ( P < 0.05) in LHTLc than in Con at N1 (0.56 ± 0.32 vs. 0.28 ± 0.16), N3 (0.69 ± 0.30 vs. 0.36 ± 0.24), N10 (0.79 ± 0.36 vs. 0.34 ± 0.14), N15 (1.00 ± 0.38 vs. 0.36 ± 0.23), and Post (0.79 ± 0.37 vs. 0.36 ± 0.26). HVR at N15 was higher ( P < 0.05) in LHTLi (0.67 ± 0.33) than in Con and in LHTLc than in LHTLi. Pet CO2 was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia ( P < 0.05). No significant differences were observed for V˙e at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases Pet CO2 in normoxia, without change inV˙e. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.
Kinematically irreversible acinar flow: a departure from classical dispersive aerosol transport theories
Authors: Henry F. S. , Butler J. P. , Tsuda A.
Published: March 2015

Current theories describe aerosol transport in the lung as a dispersive (diffusion-like) process, characterized by an effective diffusion coefficient in the context of reversible alveolar flow. Our recent experimental data, however, question the validity of these basic assumptions. In this study, we describe the behavior of fluid particles (or bolus) in a realistic, numerical, alveolated duct model with rhythmically expanding walls. We found acinar flow exhibiting multiple saddle points, characteristic of chaotic flow, resulting in substantial flow irreversibility. Computations of axial variance of bolus spreading indicate that the growth of the variance with respect to time is faster than linear, a finding inconsistent with dispersion theory. Lateral behavior of the bolus shows fine-scale, stretch-and-fold striations, exhibiting fractal-like patterns with a fractal dimension of 1.2, which compares well with the fractal dimension of 1.1 observed in our experimental studies performed with rat lungs. We conclude that kinematic irreversibility of acinar flow due to chaotic flow may be the dominant mechanism of aerosol transport deep in the lungs.
Cardiorespiratory effects of inelastic chest wall restriction
Authors: Miller Jordan D. , Beck Kenneth C. , Joyner Michael J. , Brice A. Glenn , Johnson Bruce D.
Published: March 2015

We examined the effects of chest wall restriction (CWR) on cardiorespiratory function at rest and during exercise in healthy subjects in an attempt to approximate the cardiorespiratory interactions observed in clinical conditions that result in restrictive lung and/or chest wall changes and a reduced intrathoracic space. Canvas straps were applied around the thorax and abdomen so that vital capacity was reduced by >35%. Data were acquired at rest and during cycle ergometry at 25 and 45% of peak workloads. CWR elicited significant increases in the flow-resistive work performed on the lung (160%) and the gastric pressure-time integral (>400%) at the higher workload, but it resulted in a decrease in the elastic work performed on the lung (56%) compared with control conditions. With CWR, heart rate increased and stroke volume (SV) fell, resulting in >10% fall in cardiac output at rest and during exercise at matched workloads ( P < 0.05). Blood pressure and catecholamines were significantly elevated during CWR exercise conditions ( P < 0.05). We conclude that CWR significantly impairs SV during exercise and that a compensatory increase in heart rate does not prevent a significant reduction in cardiac output. O2consumption appears to be maintained via increased extraction and a redistribution of blood flow via sympathetic activation.
Early postexercise muscle glycogen recovery is enhanced with a carbohydrate-protein supplement
Authors: Ivy John L. , Goforth Harold W. , Damon Bruce M. , McCauley Thomas R. , Parsons Edward C. , Price Thomas B.
Published: March 2015

In the present study, we tested the hypothesis that a carbohydrate-protein (CHO-Pro) supplement would be more effective in the replenishment of muscle glycogen after exercise compared with a carbohydrate supplement of equal carbohydrate content (LCHO) or caloric equivalency (HCHO). After 2.5 ± 0.1 h of intense cycling to deplete the muscle glycogen stores, subjects ( n = 7) received, using a rank-ordered design, a CHO-Pro (80 g CHO, 28 g Pro, 6 g fat), LCHO (80 g CHO, 6 g fat), or HCHO (108 g CHO, 6 g fat) supplement immediately after exercise (10 min) and 2 h postexercise. Before exercise and during 4 h of recovery, muscle glycogen of the vastus lateralis was determined periodically by nuclear magnetic resonance spectroscopy. Exercise significantly reduced the muscle glycogen stores (final concentrations: 40.9 ± 5.9 mmol/l CHO-Pro, 41.9 ± 5.7 mmol/l HCHO, 40.7 ± 5.0 mmol/l LCHO). After 240 min of recovery, muscle glycogen was significantly greater for the CHO-Pro treatment (88.8 ± 4.4 mmol/l) when compared with the LCHO (70.0 ± 4.0 mmol/l; P = 0.004) and HCHO (75.5 ± 2.8 mmol/l; P = 0.013) treatments. Glycogen storage did not differ significantly between the LCHO and HCHO treatments. There were no significant differences in the plasma insulin responses among treatments, although plasma glucose was significantly lower during the CHO-Pro treatment. These results suggest that a CHO-Pro supplement is more effective for the rapid replenishment of muscle glycogen after exercise than a CHO supplement of equal CHO or caloric content.
Modeling kinetics of infused 13NN-saline in acute lung injury
Authors: O'Neill K. , Venegas J. G. , Richter T. , Harris R. S. , Layfield J. D. H. , Musch G. , Winkler T. , Melo M. F. Vidal
Published: March 2015

A mathematical model was developed to estimate right-to-left shunt (Fs) and the volume of distribution of 13NN in alveolar gas (VA) and shunt tissue (Vs). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes 13NN kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of 13NN-labeled saline was injected at the onset of apnea as PET imaging and arterial 13NN sampling were initiated. The model fit the tracer kinetics well (mean r2 = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. Fs derived from the model correlated well with shunt estimates derived from O2 blood concentrations and from PET images. Fs was higher for LS (54 ± 18%) than for LP (5 ± 4%) and NP (1 ± 1%, P < 0.01). VA, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 ± 0.09) than for LP (0.96 ± 0.28, P < 0.01), whereas Vs, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 ± 0.26) than for LP (0.05 ± 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial 13NN kinetics and provides estimates of Fs, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.
Mechanisms of myocardial ischemic preconditioning are age related: PKC-ϵ does not play a requisite role in old rabbits
Authors: Przyklenk Karin , Li Guohu , Simkhovich Boris Z. , Kloner Robert A.
Published: March 2015

Data obtained from adult cohorts have implicated activation/translocation of protein kinase C (PKC)-ϵ as an important cellular mediator of myocardial infarct size reduction with ischemic preconditioning (PC). Age-related alterations in cellular signaling may, however, confound the extrapolation of mechanistic insight derived from adults to the aging population, the specific subset in which cardioprotection is undoubtedly most relevant. Accordingly, our aim was to investigate the role of PKC-ϵ as a mediator of infarct size reduction with PC in old vs. adult rabbits. In protocol 1, we assessed the effect of PKC-ϵ translocation inhibitor peptide (PKC-ϵ-TIP) and the pan-PKC inhibitor chelerythrine on infarct size reduction with PC in adult and ∼4-yr-old rabbits, a population previously shown to exhibit definitive hallmarks of cardiovascular aging. Rabbits received 5 min of PC ischemia or a matched control period followed by 30 min of coronary artery occlusion and 3 h of reperfusion, with infarct size (delineated by tetrazolium staining) serving as the primary endpoint. In protocol 2, we obtained insight (by Western immunoblotting) into the subcellular redistribution of PKC-ϵ in response to the 5-min PC stimulus in adult and old rabbits. In adults, infarct size reduction with PC was abrogated by both PKC-ϵ-TIP and chelerythrine. However, in old rabbits, 1) PC-induced cardioprotection was maintained despite inhibitor treatment and 2) brief PC ischemia was not associated with activation/translocation of PKC-ϵ. Thus the mechanisms responsible for PC are age related in the rabbit heart, with no apparent, requisite role of PKC-ϵ in aging animals.
Effect of hypoxic episode number and severity on ventilatory long-term facilitation in awake rats
Authors: McGuire Michelle , Zhang Yi , White David P. , Ling Liming
Published: March 2015

Episodic hypoxia induces a persistent augmentation of respiratory activity, termed long-term facilitation (LTF). Phrenic LTF saturates in anesthetized animals such that additional episodes of stimulation cause no further increase in LTF magnitude. The present study tested the hypothesis that 1) ventilatory LTF also saturates in awake rats and 2) more severe hypoxia and hypoxic episodes increase the effectiveness of eliciting ventilatory LTF. Minute ventilation was measured in awake, male Sprague-Dawley rats by plethysmography. LTF was elicited by five episodes of 10% O2 poikilocapnic hypoxia (magnitude: 17.3 ± 2.8% above baseline, between 15 and 45 min posthypoxia, duration: 45 min) but not 12 or 8% O2. LTF was also elicited by 10, 20, and 72 episodes of 12% O2(19.1 ± 2.2, 18.9 ± 1.8, and 19.8 ± 1.6%; 45, 60, and 75 min, respectively) but not by three or five episodes. These results show that there is a certain range of hypoxia that induces ventilatory LTF and that additional hypoxic episodes may increase the duration but not the magnitude of this response.
Changes in motor unit discharge rate are not associated with the amount of twitch potentiation in old men
Authors: Klein C. S. , Rice C. L. , Ivanova T. D. , Garland S. J.
Published: March 2015

This study examined, in nine old men (82 ± 4 yr), whether there is an association between the magnitude of change in motor unit discharge rate and the amount of twitch potentiation after a conditioning contraction (CC). The evoked twitch force and motor unit discharge rate during isometric ramp-and-hold contractions (10–18 s) of the triceps brachii muscle at 10, 20, and 30% of the maximal voluntary contraction were determined before and 10 s, 2 min, 6 min, and 11 min after a 5-s CC at 75% maximal voluntary contraction. After the CC, there was a potentiation of twitch force (approximately twofold), and the discharge rate of the 47 sampled motor units declined ( P < 0.05) an average of 1 Hz 10 s after the CC, compared with the control condition. The CC had no effect on the variability (coefficient of variation) of both force and discharge rate, as well as the electromyographic activity recorded over the triceps brachii and biceps brachii muscles. In contrast to our earlier study of young men (Klein CS, Ivanova TD, Rice CL, and Garland SJ, Neurosci Lett 316: 153–156, 2001), the magnitude of the reduction in discharge rate after the CC was not associated ( r = 0.06) with the amount of twitch potentiation. These findings suggest an age-related alteration in the neural strategy for adjusting motor output to a muscle after a CC.
iNOS activity is essential for endothelial stress gene expression protecting against oxidative damage
Authors: Hemmrich Karsten , Suschek Christoph V. , Lerzynski Guido , Kolb-Bachofen Victoria
Published: March 2015

In endothelial cells, the expression of the inducible nitric oxide synthase (iNOS) and the resulting high-output nitric oxide synthesis have often been assumed as detrimental to endothelial function, but recent publications have demonstrated a protective role resulting from iNOS espression and activity. To address this question, we used antisense-mediated iNOS knockdown during proinflammatory cytokine challenge in primary endothelial cell cultures and studied endothelial function by monitoring the expression of stress defense genes. Using antisense oligonucleotides, we achieved a block of iNOS protein formation, accompanied by a strong decrease in the expression of the protective stress response genes bcl-2, vascular endothelial growth factor, and heme oxygenase-1 (HO-1). Additionally, cells were also maintained in the presence of limited exogenous substrate concentrations during cytokine challenge, thereby mimicking a situation of low serum arginine level during inflammation. Under these conditions, cytokine addition results in full iNOS protein expression with minimal nitric oxide formation, concomitant with a significant reduction in stress response gene expression and susceptibility to cell death induced by reactive oxygen species. Taken together, our data suggest that cytokine-induced endogenous iNOS expression and activity have key functions in increasing endothelial survival and maintaining function. Thus suppression of iNOS expression or limited substrate supply, as has been reported to occur in atherosclerosis patients, appears to significantly contribute to endothelial dysfunction and death during oxidative stress.
Effect of 8-isoprostaglandin F2α on the newborn rat pulmonary arterial muscle and endothelium
Authors: Belik J. , Jankov R. P. , Pan J. , Yi M. , Pace-Asciak C. R. , Tanswell A. K.
Published: March 2015

8-Isoprostaglandin F2α (8-iso-PGF2α) is a bioactive lipid peroxidation product that is a vasoconstrictor at high concentrations. Paradoxically, at lower, and possibly physiological, concentrations, it is a pulmonary vascular muscle's relaxant. Its effects on newborn pulmonary vasculature are unknown. We hypothesized that the pulmonary arterial 8-iso-PGF2α responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2α effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 μm) mounted on a myograph. Force after 8-iso-PGF2α stimulation was greatest in the adult ( P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) ( P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A2 receptor. Whereas 8-iso-PGF2α induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 μM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2α-induced contraction was abolished by endothelium removal and l-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA2/prostaglandin H2 receptor blocker, 8-iso-PGF2α induced NO-mediated relaxation, the magnitude of which was greater in the newborn, compared with the adult ( P < 0.01). When exposed to 8-iso-PGF2α in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2α induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA2. This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.
Endothelin-induced vascular and bronchial effects in pig airways: role in acute allergic responses
Authors: Sylvin H. , Weitzberg E. , Alving K.
Published: March 2015

The effects of endothelin (ET) agonists on airway mechanics and bronchial blood flow were studied as well as the effects of mixed ET-receptor antagonist bosentan on allergen-induced airway reactions in the pig. ET agonists [ET-1, ET-3, and the ETBreceptor-selective agonist Sarafotoxin 6c (Sf6c)] were given as intravenous injections (0.4–200 pmol/kg) to eight anesthetized pigs. Bosentan (10 mg/kg iv) was then administered, and the injections were repeated. Only Sf6c caused a significant increase in airway resistance, and this response was blocked by bosentan. Sf6c and ET-1 (200 and 400 pmol/kg, respectively) were also given as aerosols to five pigs. Sf6c, but not ET-1, caused bronchoconstriction via this route. All agonists (intravenous) caused increases in bronchial vascular conductance, an effect that was blocked by an NO-synthase inhibitor ( NG-nitro-l-arginine) but unaffected by a cyxlooxygenase inhibitor (diclofenac). Fourteen pigs were sensitized with ascaris suum antigen. Under anesthesia, eight pigs were pretreated with bosentan, and six pigs were controls. They were all challenged with allergen aerosol resulting in acute bronchoconstriction and elevation of ET-1 in bronchoalveolar lavage fluid. Bosentan did not affect the maximal acute airway obstruction but markedly increased baseline bronchial vascular conductance, suggesting a basal vascular tone regulated by ETs. In conclusion, ETs induce bronchoconstriction primarily via the ETBreceptor in the pig. However, ETs are probably not involved in the allergen-induced acute bronchoconstriction in this model.
Effect of aging on human muscle architecture
Authors: Narici M. V. , Maganaris C. N. , Reeves N. D. , Capodaglio P.
Published: March 2015

The effect of aging on human gastrocnemius medialis (GM) muscle architecture was evaluated by comparing morphometric measurements on 14 young (aged 27–42 yr) and on 16 older (aged 70–81 yr) physically active men, matched for height, body mass, and physical activity. GM muscle anatomic cross-sectional area (ACSA) and volume (Vol) were measured by computerized tomography, and GM fascicle length ( Lf) and pennation angle (θ) were assessed by ultrasonography. GM physiological cross-sectional area (PCSA) was calculated as the ratio of Vol/ Lf. In the elderly, ACSA and Vol were, respectively, 19.1% ( P < 0.005) and 25.4% ( P < 0.001) smaller than in the young adults. Also, Lf and θ were found to be smaller in the elderly group by 10.2% ( P < 0.01) and 13.2% ( P < 0.01), respectively. When the data for the young and elderly adults were pooled together, θ significantly correlated with ACSA ( P < 0.05). Because of the reduced Vol and Lf in the elderly group, the resulting PCSA was found to be 15.2% ( P < 0.05) smaller. In conclusion, this study demonstrates that aging significantly affects human skeletal muscle architecture. These structural alterations are expected to have implications for muscle function in old age.
Early contributions of Russian stress and exercise physiologists
Authors: Viru Atko
Published: March 2015

In Russia, the free development of scientific ideas was suppressed in 1950 as a result of the actions of the Joint Session of the Academy of Sciences and the Academy of Medical Sciences of the USSR. Hans Selye's theory on the general adaptation syndrome was considered unscientific. From 1956 to 1958, Pjotr Anokhin and Pjotr Gorizontov presented definitive arguments for having the theory accepted by scientists while the significance of hormones in adaptation became a topic of endocrine studies (Boris Aleshin, Igor Eskin, Vassily Komissarenko, Samuel Leites, and Michael Kolpakov). Later, Felius Meerson made essential contributions to the adaptive significance of protein synthesis and stress-limiting systems. The area of exercise physiology dealing with acute and chronic adaptation to strong physiological stressors was founded by Leon Orbeli and developed by Aleksei Krestovnikov. Significant contributors to this area were Vladimir Farfel, Nikolai Yakovlev, and Nikolai Zimkin. Although the majority of their publications have remained unknown outside of Russia, it is interesting that many of their results have been “rediscovered” by others. Yakovlev also deserves recognition because he was among the founders of contemporary exercise biochemistry and because his research has provided the foundation for current investigations. Several generations of young scientists have been inspired by the above-mentioned Russian scientists. Today, however, the research activities of scientists are no longer limited by political pressures but by financial resources instead.
Oral [13C]glucose and endogenous energy substrate oxidation during prolonged treadmill running
Authors: Couture Stéphane , Massicotte Denis , Lavoie Carole , Hillaire-Marcel Claude , Péronnet François
Published: March 2015

Six male subjects were studied during running exercise (120 min, 69% maximal oxygen consumption) with ingestion of a placebo or 3.5 g/kg of [13C]glucose (∼2 g/min). Indirect respiratory calorimetry corrected for urea excretion in urine and sweat, production of 13CO2 at the mouth, and changes in plasma glucose 13C/12C were used to compute energy substrate oxidation. The oxidation rate of exogenous glucose increased from 1.02 at minute 60 to 1.22 g/min at minute 120 providing ∼24 and 33% of the energy yield (%En). Glucose ingestion did not modify protein oxidation, which provided ∼4–5%En, but significantly increased glucose oxidation by ∼7%, reduced lipid oxidation by ∼16%, and markedly reduced endogenous glucose oxidation (1.25 vs. 2.21 g/min between minutes 80 and 120, respectively). The oxidation rate of glucose released from the liver (0.38 and 0.47 g/min, or 10–13%En at minutes 60 and 120, respectively), and of plasma glucose (1.30–1.69 g/min, or 34 and 45%En and 50 and 75% of glucose oxidation) significantly increased from minutes 60 to 120, whereas the oxidation of muscle glycogen significantly decreased (1.28 to 0.58 g of glucose/min, or 34 and 16%En and 50 and 25% of glucose oxidation). These results indicate that, during moderate prolonged running exercise, ingestion of a very large amount of glucose significantly reduces endogenous glucose oxidation, thus sparing muscle and/or liver glycogen stores.