bluuebunny/crossref_metadata_2025 huggingface dataset:
Rescue of contractile abnormalities by Na+/Ca2+ exchanger overexpression in postinfarction rat myocytes
Authors: Zhang Xue-Qian , Song Jianliang , Qureshi Anwer , Rothblum Lawrence I. , Carl Lois L. , Tian Qiang , Cheung Joseph Y.
Published: March 2015

Previous studies on myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated increased cell length, reduced Na+/Ca2+ exchange (NCX1) activity, altered contractility, and intracellular Ca2+ concentration ([Ca2+]i) transients. In the present study, we investigated whether NCX1 overexpression in MI myocytes would restore contraction and [Ca2+]i transients to normal. When myocytes were placed in culture under continued electrical-field stimulation conditions, differences in contraction amplitudes and cell lengths between sham and MI myocytes were preserved for at least 48 h. Infection of both sham and MI myocytes by adenovirus expressing green fluorescent protein resulted in >95% infection, as evidenced by green fluorescent protein fluorescence, but contraction amplitudes at 6-, 24-, and 48-h postinfection were not affected. NCX1 overexpression in MI myocytes resulted in lower diastolic [Ca2+]i levels at all extracellular Ca2+ concentrations ([Ca2+]o) examined, suggesting enhanced forward NCX1 activity. At 5 mM [Ca2+]o, subnormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were restored toward normal levels by overexpressing NCX1. At 0.6 mM [Ca2+]o, supranormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were lowered by NCX1 overexpression. We conclude that overexpression of NCX1 in MI myocytes was effective in improving contractile dysfunction, most likely because of enhancement of both Ca2+ efflux and influx during a cardiac cycle. We suggest that decreased NCX1 activity may play an important role in contractile abnormalities in postinfarction myocytes.
Stiffness of the pleural surface of the chest wall is similar to that of the lung
Authors: Gouldstone Andrew , Brown Richard E. , Butler James P. , Loring Stephen H.
Published: March 2015

To address the role of the parietal pleura in reduction of mesothelial shear stresses during breathing, we measured the stiffness of the parietal pleural surface of mammalian chest walls using microindentation. The pleural surface was indented over ribs and intercostal spaces with rigid flat punches (tip radii of 0.01, 0.02, and 0.1 cm) to probe stiffness at length scales comparable with those of surface asperities. We found a tissue shear modulus of 6,700 dyn/cm2 and pleural membrane tension of 4,900 dyn/cm, with a geometric standard deviation of 0.42. These values are similar to those measured for the lung by Hajji et al., using indentation (Hajji MA, Wilson TA, and Lai-Fook SJ. J Appl Physiol Respirat Environ Exerc Physiol 47: 175–181, 1979). Surprisingly, the pleural surface over ribs and intercostal spaces exhibited similar stiffness. In addition, caudal regions exhibited lower stiffness than cranial regions. In the context of elastohydrodynamic lubrication, these results suggest that shear-induced pressures during breathing deform the chest wall and lung surfaces to a similar extent, promoting spatial uniformity of pleural fluid thickness and reducing shear stresses.
Rapid compressions in a captive bubble apparatus are isothermal
Authors: Yan Wenfei , Hall Stephen B.
Published: March 2015

Captive bubbles are commonly used to determine how interfacial films of pulmonary surfactant respond to changes in surface area, achieved by varying hydrostatic pressure. Although assumed to be isothermal, the gas phase temperature (Tg) would increase by >100°C during compression from 1 to 3 atm if the process were adiabatic. To determine the actual change in temperature, we monitored pressure (P) and volume (V) during compressions lasting <1 s for bubbles with and without interfacial films and used P · V to evaluate Tg. P · V fell during and after the rapid compressions, consistent with reductions in n, the moles of gas phase molecules, because of increasing solubility in the subphase at higher P. As expected for a process with first-order kinetics, during 1 h after the rapid compression P · V decreased along a simple exponential curve. The temporal variation of n moles of gas was determined from P · V >10 min after the compression when the two phases should be isothermal. Back extrapolation of n then allowed calculation of Tg from P · V immediately after the compression. Our results indicate that for bubbles with or without interfacial films compressed to >3 atm within 1 s, the change in Tg is <2°C.
Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy
Authors: Nearing Bruce D. , Verrier Richard L.
Published: March 2015

T-wave alternans is a marker of cardiac electrical instability with the potential for arrhythmia risk stratification. The modified moving average method was developed to measure alternans in settings with artifacts, noise, and nonstationary data. Algorithms were developed and performance characteristics were validated with simulated electrocardiograms (ECGs). Experimental laboratory ECGs with dynamically changing alternans values were analyzed. Alternans values estimated by modified moving average analysis correlated strongly with input alternans values ( r 2 = 0.9999). Rapidly changing alternans levels and phase reversals did not perturb the measurement. When heart rate was increased from 60 to 180 beats/min, with T-wave alternans apex moving from 237 to 103 ms after the R wave, the measured alternans peak varied <5% from input value. Simulated 50- to 1,000-μV motion artifact spikes typical of treadmill ECGs produced inaccuracies <2%. Alternans values in experimental laboratory study using standard electrodes tracked vulnerability to myocardial ischemia-induced ventricular fibrillation with 100% sensitivity and specificity at a cut point of 0.75 mV. Modified moving average analysis is a robust method that precisely measures T-wave alternans in settings with artifacts, noise, and nonstationary data typical of clinical ECGs and yields an accurate estimate of risk for ventricular fibrillation.
Spaceflight affects bone formation in rhesus monkeys: a histological and cell culture study
Authors: Zérath Erik , Grynpas Marc , Holy Xavier , Viso Michel , Patterson-Buckendahl Patricia , Marie Pierre J.
Published: March 2015

Using analyses of iliac crest cell and tissue, back-scattered electron imaging, and biochemical techniques, we characterized the effects of a 14-day spaceflight (Bion 11) on bone structure and bone formation in two 3- to 4-yr-old male rhesus monkeys compared with eight age-matched Earth-control monkeys. We found that postflight bone volume was 35% lower than preflight values in flight monkeys. This was associated with reduced osteoid (−40%) and mineralizing (−32%) surfaces and decreased bone formation rate (−53%). Moreover, flight monkeys exhibited trends to lower values of mineralization profile in iliac bone (back-scattered electron imaging) and to decreased osteocalcin serum levels ( P = 0.08). The initial number of trabecular bone cells yielded in cultures did not differ in flight and control animals before or after the flight. However, osteoblastic cell proliferation was markedly lower in postflight vs. preflight at 9 and 14 days of culture in one flight monkey. This study suggests that a 14-day spaceflight reduces iliac bone formation, osteoblastic activity, and/or recruitment in young rhesus monkeys, resulting in decreased trabecular bone volume.
Immunolocalization of a Na-K-2Cl cotransporter in human tracheobronchial smooth muscle
Authors: Iwamoto Lynn M. , Nakamura Kenneth T. , Wada Randal K.
Published: March 2015

Inhibition of the Na-K-2Cl (NKCC) cotransporter by loop diuretics is associated with airway relaxation, but there has been no direct evidence for the expression of this protein in airway smooth muscle. Thus we hypothesized that a NKCC cotransporter is present and functional in airway smooth muscle cells. Monoclonal and polyclonal antibodies were used first to demonstrate the presence of a NKCC cotransporter protein in isolated human fetal trachea and normal human bronchial smooth muscle cells (BSMC) by Western blotting. The cotransporter protein was then localized by immunohistochemical staining to airway smooth muscle cells in culture and in situ. The localization was confirmed by indirect immunofluorescence and laser confocal microscopy in the BSMC. Cotransporter function in BSMC was also confirmed in vitro by bumetanide-mediated inhibition of rubidium uptake. Our present findings thus document the presence of a functional NKCC cotransporter in human airway smooth muscle, providing a basis for defining the role of this ion cotransporter in airway smooth muscle function.
Validation of improved recording site to measure phrenic conduction from surface electrodes in humans
Authors: Verin Eric , Straus Christian , Demoule Alexandre , Mialon Philippe , Derenne Jean-Philippe , Similowski Thomas
Published: March 2015

Phrenic nerve stimulation, electrical (ES) or from cervical magnetic stimulation (CMS), allows one to assess the diaphragm contractile properties and the conduction time of the phrenic nerve (PNCT) through recording of an electromyographic response, traditionally by using surface electrodes. Because of the coactivation of extradiaphragmatic muscles, signal contamination can jeopardize the determination of surface PNCTs. To address this, we compared PNCTs with ES and CMS from surface and needle diaphragm electrodes in five subjects (10 phrenic nerves). At a modified recording site, lower and more anterior than usual (lowest accessible intercostal space, costochondral junction) with electrodes 2 cm apart, surface and needle PNCTs were similar (CMS: 6.0 ± 0.25 ms surface vs. 6.2 ± 0.13 ms needle, not significant). Electrodes recording the activity of the most likely sources of signal contamination, i.e., the serratus anterior and pectoralis major, showed distinct responses from that of the diaphragm, their earlier occurrence strongly arguing against contamination. With ES and CMS, apparently uncontaminated signals could be consistently recorded from surface electrodes.
Protein kinetics in stable heart failure patients
Authors: Cortes Charles W. , Thompson Paul D. , Moyna Niall M. , Schluter Margaret D. , Leskiw Maria J. , Donaldson Melissa R. , Duncan Brett H. , Stein T. Peter
Published: March 2015

Heart failure (HF) is a slow progressive syndrome characterized by low cardiac output and peripheral metabolic, biochemical, and histological alterations. Protein loss and reduced protein turnover occur with aging, but the consequences of congestive HF (CHF) superimposed on the normal aging response are unknown. This study has two objectives: 1) to determine whether there was a difference between older age-matched controls and those with stable HF (i.e., ischemic pathology) in whole body protein turnover and 2) to determine whether protein metabolism in liver and skeletal muscle protein turnover is impacted by CHF. We measured the whole body protein synthesis rate with a U-15N-labeled algal protein hydrolysate in 10 patients with CHF and in 10 age-matched controls. Muscle fractional synthesis rate of lateral vastus muscle was determined with [U-13C]alanine on muscle biopsies obtained by a standard percutaneous needle biopsy technique. Fractional synthesis rates of five plasma proteins of hepatic origin (fibrinogen, complement C-3, ceruloplasmin, transferrin, and very low-density lipoprotein apoliprotein B-100) were determined by using2H5-labeled l-phenylalanine as tracer. Results showed that whole body protein synthesis rate was reduced in CHF patients (3.09 ± 0.19 vs. 2.25 ± 0.71 g protein · kg−1 · day−1, P < 0.05) as was muscle fractional synthesis rate (3.02 ± 0.58 vs. 1.33 ± 0.71%/day, P < 0.05) and very low-density lipoprotein apoliprotein B-100 (265 ± 25 vs. 197 ± 16%/day, P < 0.05). CHF patients were hyperinsulinemic (9.6 ± 3.1 vs. 47.0 ± 7.8 μU/ml, P < 0.01). The results were compared with those found with bed rest patients. In conclusion, protein turnover is depressed in CHF patients, and both skeletal muscle and liver are impacted. These results are similar to those found with bed rest, which suggests that inactivity is a factor in depressed protein metabolism.
Mode shift of an inhaled aerosol bolus is correlated with flow sequencing in the human lung
Authors: Mills Christopher N. , Darquenne Chantal , Prisk G. Kim
Published: March 2015

We studied the effects on aerosol bolus inhalations of small changes in convective inhomogeneity induced by posture change from upright to supine in nine normal subjects. Vital capacity single-breath nitrogen washout tests were used to determine ventilatory inhomogeneity change between postures. Relative to upright, supine phase III slope was increased 33 ± 11% (mean ± SE, P < 0.05) and phase IV height increased 25 ± 11% ( P < 0.05), consistent with an increase in convective inhomogeneity likely due to increases in flow sequencing. Subjects also performed 0.5-μm-particle bolus inhalations to penetration volumes (Vp) between 150 and 1,200 ml during a standardized inhalation from residual volume to 1 liter above upright functional residual capacity. Mode shift (MS) in supine posture was more mouthward than upright at all Vp, changing by 11.6 ml at Vp = 150 ml ( P < 0.05) and 38.4 ml at Vp = 1,200 ml ( P < 0.05). MS and phase III slope changes correlated positively at deeper Vp. Deposition did not change at any Vp, suggesting that deposition did not cause the MS change. We propose that the MS change results from increased sequencing in supine vs. upright posture.
Influence of long-term spaceflight on neuromechanical properties of muscles in humans
Authors: Lambertz Daniel , Goubel Francis , Kaspranski Rustem , Pérot Chantal
Published: March 2015

Reflex and elastic properties of the triceps surae (TS) were measured on 12 male cosmonauts 28–40 days before a 3- to 6-mo spaceflight, 2 or 3 days after return (R+2/+3) and a few days later (R+5/+6). H reflexes to electrical stimulations and T reflexes to tendon taps gave the reflex excitability at rest. Under voluntary contractions, reflex excitability was assessed by the stretch reflex, elicited by sinusoidal length perturbations. Stiffness measurements concerned the musculoarticular system in passive conditions and the musculotendinous complex in active conditions. Results indicated 1) no changes ( P > 0.05) in H reflexes, whatever the day of test, and 2) increase in T reflexes ( P < 0.05) by 57%, despite a decrease ( P < 0.05) in musculoarticular stiffness (11%) on R+2/+3. T reflexes decreased ( P < 0.05) between R+2/+3 and R+5/+6 (−21%); 3) increase in stretch reflexes ( P< 0.05) on R+2/+3 by 31%, whereas it decreased ( P < 0.05) between R+2/+3 and R+5/+6 (−29%). Musculotendinous stiffness was increased ( P < 0.05) whatever the day of test (25%). Links between changes in reflex and stiffness were also studied by considering individual data. At R+2/+3, correlated changes between T reflexes and musculoarticular stiffness suggested that, besides central adaptive phenomena, musculoarticular structures took part in the reflex adaptation. This mechanical contribution was confirmed when data collected at R+2/+3 and R+5/+6 were used because correlations between changes in stretch reflexes and musculotendinous stiffness were improved. In conclusion, the present study shows that peripheral influences take part in reflex changes in gravitational unloaded muscles, but can only be revealed when central influences are reduced.
Using animal data to improve prediction of human decompression risk following air-saturation dives
Authors: Lillo R. S. , Himm J. F. , Weathersby P. K. , Temple D. J. , Gault K. A. , Dromsky D. M.
Published: March 2015

To plan for any future rescue of personnel in a disabled and pressurized submarine, the US Navy needs a method for predicting risk of decompression sickness under possible scenarios for crew recovery. Such scenarios include direct ascent from compressed air exposures with risks too high for ethical human experiments. Animal data, however, with their extensive range of exposure pressures and incidence of decompression sickness, could improve prediction of high-risk human exposures. Hill equation dose-response models were fit, by using maximum likelihood, to 898 air-saturation, direct-ascent dives from humans, pigs, and rats, both individually and combined. Combining the species allowed estimation of one, more precise Hill equation exponent (steepness parameter), thus increasing the precision associated with human risk predictions. These predictions agreed more closely with the observed data at 2 ATA, compared with a current, more general, US Navy model, although the confidence limits of both models overlapped those of the data. However, the greatest benefit of adding animal data was observed after removal of the highest risk human exposures, requiring the models to extrapolate.
A simulation study to examine the use of cross-correlation as an estimate of surface EMG cross talk
Authors: Lowery Madeleine M. , Stoykov Nikolay S. , Kuiken Todd A.
Published: March 2015

Cross-correlation between surface electromyogram (EMG) signals is commonly used as a means of quantifying EMG cross talk during voluntary activation. To examine the reliability of this method, the relationship between cross talk and the cross-correlation between surface EMG signals was examined by using model simulation. The simulation results illustrate an increase in cross talk with increasing subcutaneous fat thickness. The results also indicate that the cross-correlation function decays more rapidly with increasing distance from the active fibers than cross talk, which was defined as the normalized EMG amplitude during activation of a single muscle. The influence of common drive and short-term motor unit synchronization on the cross-correlation between surface EMG signals was also examined. While common drive did not alter the maximum value of the cross-correlation function, the correlation increased with increasing motor unit synchronization. It is concluded that cross-correlation analysis is not a suitable means of quantifying cross talk or of distinguishing between cross talk and coactivation during voluntary contraction. Furthermore, it is possible that a high correlation between surface EMG signals may reflect an association between motor unit firing times, for example due to motor unit synchronization.
Perfusion heterogeneity in rat lungs assessed from the distribution of 4-μm-diameter latex particles
Authors: Conhaim Robert L. , Watson Kal E. , Heisey Dennis M. , Leverson Glen E. , Harms Bruce A.
Published: March 2015

Pulmonary vascular perfusion has been shown to follow a fractal distribution down to a resolution of 0.5 cm3 (5E11 μm3). We wanted to know whether this distribution continued down to tissue volumes equivalent to that of an alveolus (2E5 μm3). To investigate this, we used confocal microscopy to analyze the spatial distribution of 4-μm-diameter fluorescent latex particles trapped within rat lung microvessels. Particle distributions were analyzed in tissue volumes that ranged from 1.7E2 to 2.8E8 μm3. The analysis resulted in fractal plots that consisted of two slopes. The left slope, encompassing tissue volumes less than 7E5 μm3, had a fractal dimension of 1.50 ± 0.03 (random distribution). The right slope, encompassing tissue volumes greater than 7E5 μm3, had a fractal dimension of 1.29 ± 0.04 (nonrandom distribution). The break point at 7E5 μm3 corresponds closely to a tissue volume equivalent to that of one alveolus. We conclude that perfusion distribution is random at tissue volumes less than that of an alveolus and nonrandom at tissue volumes greater than that of an alveolus.
Effect of exercise intensity on 24-h energy expenditure and nutrient oxidation
Authors: Melanson Edward L. , Sharp Teresa A. , Seagle Helen M. , Horton Tracy J. , Donahoo William T. , Grunwald Gary K. , Hamilton Jere T. , Hill James O.
Published: March 2015

The aim of this study was to determine the effects of exercise at different intensities on 24-h energy expenditure (EE) and substrate oxidation. Sixteen adults (8 men and 8 women) were studied on three occasions [sedentary day (Con), a low-intensity exercise day (LI; 400 kcal at 40% of maximal oxygen consumption) and a high-intensity exercise day (HI; 400 kcal at 70% of maximal oxygen consumption)] by using whole room indirect calorimetry. Both 24-h EE and carbohydrate oxidation were significantly elevated on the exercise days (Con < LI = HI), but 24-h fat oxidation was not different across conditions. Muscle enzymatic profile was not consistently related to 24-h fat or carbohydrate oxidation. With further analysis, it was found that, compared with men, women sustained slightly higher rates of 24-h fat oxidation (mg · kg FFM−1· min−1) and had a muscle enzymatic profile favoring fat oxidation. It is concluded that exercise intensity has no effect on 24-h EE or nutrient oxidation. Additionally, it appears that women may sustain slightly greater 24-h fat oxidation rates during waking and active periods of the day.
Measuring lung function in mice: the phenotyping uncertainty principle
Authors: Bates Jason H. T. , Irvin Charles G.
Published: March 2015

Measuring lung function in mice is essential for establishing the relevance of murine models to human lung disease. However, making such measurements presents particular technical challenges due to the small size of the animal, particularly with regard to the measurement of respiratory flows. In this review, we examine the various methods currently available for assessment of lung function in mice and contrast them in terms of a concept we call the phenotyping uncertainty principle; each method can be considered to lie somewhere along a continuum on which noninvasiveness must be traded off against experimental control and measurement precision. Unrestrained plethysmography in conscious mice represents the extreme of noninvasiveness and is highly convenient but provides respiratory measures that are so tenuously linked to respiratory mechanics that they cannot be considered as meaningful indicators of lung function. At the other extreme, the measurement of input impedance in anesthetized, paralyzed, tracheostomized mice is precise and specific but requires that an animal be studied under conditions far from natural. In between these two extremes lie methods that sacrifice some precision for a reduction in the level of invasiveness, a promising example being the measurement of transfer impedance in conscious, restrained mice. No method is optimal in all regards; therefore, the appropriate technique to use depends on the application.
Chronic centrifugation (hypergravity) disrupts the circadian system of the rat
Authors: Holley D. C. , DeRoshia C. W. , Moran M. M. , Wade C. E.
Published: March 2015

The present study was conducted to evaluate the response of rat deep body temperature (DBT) and gross locomotor activity (LMA) circadian rhythms to acute hypergravity onset and adaptation to chronic (14 day) hypergravity exposure over three gravity intensities (1.25, 1.5, and 2 G). Centrifugation of unanesthetized naive animals resulted in a dramatic acute decrease in DBT (-1.45, -2.40, and -3.09°C for the 1.25, 1.5, and 2.0 G groups, respectively). LMA was suppressed for the duration of centrifugation (vs. control period); the percent decrease for each group on days 12-14, respectively, was 1.0 G, -15.2%, P = not significant; 1.25 G, -26.9%, P < 0.02; 1.5 G, -44.5%, P < 0.01; and 2.0 G, -63.1%, P < 0.002. The time required for DBT and LMA circadian rhythmic adaptation and stabilization to hypergravity onset increased from 1.25 to 2.0 G in all circadian metrics except daily means. Periodicity analysis detected the phenomenon of circadian rhythm splitting, which has not been reported previously in response to chronic hypergravity exposure. Our analysis documents the disruptive and dose-dependent effects of hypergravity on circadian rhythmicity and the time course of adaptation to 14-day chronic centrifugation exposure.
Porcine-specific hemoglobin saturation measurements
Authors: Serianni Richard , Barash Jed , Bentley Timothy , Sharma Pushpa , Fontana John L. , Via Darin , Duhm Jochen , Bunger Rolf , Mongan Paul D.
Published: March 2015

The determination of O2consumption by using arteriovenous O2content differences is dependent on accurate oxyhemoglobin saturation measurements. Because swine are a common experimental species, we describe the validation of CO-oximeter for porcine-specific oxyhemoglobin saturation. After developing a nonlinear mathematical model of the porcine oxyhemoglobin saturation curve, we made 366 porcine oxyhemoglobin saturation determinations with a calibrated blood-gas analyzer and a porcine-specific CO-oximeter. There was a high degree of correlation with minimal variability ( r2= 0.99, SE of the estimate = 5.2%) between the mathematical model and the porcine-specific CO-oximeter measurements. Bland-Altman comparison showed that the CO-oximeter measurements were biased slightly lower (−0.4 vol%), and the limits of agreement (±2 SD) were 0.7 and −1.5 vol%. This is in contrast to a 10–20 vol% error if human-specific methods were used. The results show excellent agreement between the nonlinear model and CO-oximeter for porcine-specific oxyhemoglobin saturation measurements. In contrast, comparison of the porcine-specific oxyhemoglobin saturations with saturations obtained by using human methods highlights the necessity of species-specific measurement methodology.
Low sodium intake does not impair renal compensation of hypoxia-induced respiratory alkalosis
Authors: Höhne Claudia , Boemke Willehad , Schleyer Nora , Francis Roland C. , Krebs Martin O. , Kaczmarczyk Gabriele
Published: March 2015

Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined with increased diuresis and sodium, potassium, and bicarbonate excretion. With a low sodium intake, the excretion of the anion bicarbonate may be limited by the lower excretion rate of the cation sodium through activated sodium-retaining mechanisms. This study investigates whether the short-term renal compensation of hypoxia-induced respiratory alkalosis is impaired by a low sodium intake. Nine conscious, tracheotomized dogs were studied twice either on a low-sodium (LS = 0.5 mmol sodium · kg body wt−1· day−1) or high-sodium (HS = 7.5 mmol sodium · kg body wt−1· day−1) diet. The dogs breathed spontaneously via a ventilator circuit during the experiments: first hour, normoxia (inspiratory oxygen fraction = 0.21); second to fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During hypoxia (arterial Po234.4 ± 2.1 Torr), plasma pH increased from 7.37 ± 0.01 to 7.48 ± 0.01 ( P < 0.05) because of hyperventilation (arterial Pco225.6 ± 2.4 Torr). Urinary pH and urinary bicarbonate excretion increased irrespective of the sodium intake. Sodium excretion increased more during HS than during LS, whereas the increase in potassium excretion was comparable in both groups. Thus the quick onset of bicarbonate excretion within the first hour of hypoxia-induced respiratory alkalosis was not impaired by a low sodium intake. The increased sodium excretion during hypoxia seems to be combined with a decrease in plasma aldosterone and angiotensin II in LS as well as in HS dogs. Other factors, e.g., increased mean arterial blood pressure, minute ventilation, and renal blood flow, may have contributed.
Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study
Authors: Lanouette Christian-Marc , Chagnon Yvon C. , Rice Treva , Pérusse Louis , Muzzin Patrick , Giacobino Jean-Paul , Gagnon Jacques , Wilmore Jack H. , Leon Arthur S. , Skinner James S. , Rao D. C. , Bouchard Claude
Published: March 2015

The uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter mainly expressed in skeletal muscle that we have shown to be associated with obesity. We have analyzed UCP3 polymorphisms, Val102Ile, Tyr210Tyr, and a new microsatellite GAIVS6 located in the sixth intron, among 276 black and 503 white subjects from the HERITAGE Family Study. Linkage and association studies were undertaken with body composition variables measured in a sedentary state (baseline) and after 20 wk of endurance training (changes). Allele and genotype frequencies were found to be significantly different between whites and blacks. Suggestive linkages (0.009 ≤ P ≤ 0.033) with Tyr210Tyr were found in blacks and whites for baseline body mass index, fat mass, or leptin level and with GAIVS6 in whites for changes in fat mass and percent body fat. Associations were also found in whites between GAIVS6 and changes in the sum of eight skinfold thicknesses ( P = 0.0006), with a borderline result for body mass index ( P = 0.06). We concluded that UCP3 could be involved in body composition changes after regular exercise.
Effects of confinement (110 and 240 days) on neuroendocrine stress response and changes of immune cells in men
Authors: Choukèr A. , Smith L. , Christ F. , Larina I. , Nichiporuk I. , Baranov V. , Bobrovnik E. , Pastushkova L. , Messmer K. , Peter K. , Thiel M.
Published: March 2015

The aim of the study was to evaluate the effects of long-term confinement on stress-permissive neuroendocrine and immune responses in humans. Two groups of four male subjects were confined 240 days ( group 240) or 110 days ( group 110) in two space modules of 100 or 200 m3, respectively. During confinement, none of the volunteers developed psychic stress as could be examined and verified by a current stress test. However, in g roup 240 but not in group 110, the diurnal rhythm of cortisol secretion was slightly depressed and the urine excretion of norepinephrine significantly increased. The innate part of the immune system became activated as seen by a rise in the number of circulating granulocytes and the enhanced expression of β2-integrins. In contrast, the ratio of T-helper to T-suppressor cells decreased. All these effects, observed during confinement, were even more pronounced in both groups when values of endocrinological and immunological parameters were compared between before and 1 wk after the end of the confinement period. Hence, return to normal life exerts pronounced effects to a much higher degree, irrespective of how long or under which conditions individuals were confined. Because the delayed-type hypersensitivity skin reaction against recall antigens remained unaffected, it is to be presumed that confinement appears to induce distinct sympathoadrenergic activation and immunological changes but no clinically relevant immunosuppression.
Respiratory events and periodic breathing in cyclists sleeping at 2,650-m simulated altitude
Authors: Kinsman Tahnee A. , Hahn Allan G. , Gore Christopher J. , Wilsmore Bradley R. , Martin David T. , Chow Chin-Moi
Published: March 2015

We examined the initial effect of sleeping at a simulated moderate altitude of 2,650 m on the frequency of apneas and hypopneas, as well as on the heart rate and blood oxygen saturation from pulse oximetry (SpO2) during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep of 17 trained cyclists. Pulse oximetry revealed that sleeping at simulated altitude significantly increased heart rate (3 ± 1 beats/min; means ± SE) and decreased SpO2(−6 ± 1%) compared with baseline data collected near sea level. In response to simulated altitude, 15 of the 17 subjects increased the combined frequency of apneas plus hypopneas from baseline levels. On exposure to simulated altitude, the increase in apnea was significant from baseline for both sleep states (2.0 ± 1.3 events/h for REM, 9.9 ± 6.2 events/h for NREM), but the difference between the two states was not significantly different. Hypopnea frequency was significantly elevated from baseline to simulated altitude exposure in both sleep states, and under hypoxic conditions it was greater in REM than in NREM sleep (7.9 ± 1.8 vs. 4.2 ± 1.3 events/h, respectively). Periodic breathing episodes during sleep were identified in four subjects, making this the first study to show periodic breathing in healthy adults at a level of hypoxia equivalent to 2,650-m altitude. These results indicate that simulated moderate hypoxia of a level typically chosen by coaches and elite athletes for simulated altitude programs can cause substantial respiratory events during sleep.
Effects of microgravity on myogenic factor expressions during postnatal development of rat skeletal muscle
Authors: Inobe Manabu , Inobe Ikuko , Adams Gregory R. , Baldwin Kenneth M. , Takeda Shin'Ichi
Published: March 2015

To clarify the role of gravity in the postnatal development of skeletal muscle, we exposed neonatal rats at 7 days of age to microgravity. After 16 days of spaceflight, tibialis anterior, plantaris, medial gastrocnemius, and soleus muscles were removed from the hindlimb musculature and examined for the expression of MyoD-family transcription factors such as MyoD, myogenin, and MRF4. For this purpose, we established a unique semiquantitative method, based on RT-PCR, using specific primers tagged with infrared fluorescence. The relative expression of MyoD in the tibialis anterior and plantaris muscles and that of myogenin in the plantaris and soleus muscles were significantly reduced ( P < 0.001) in the flight animals. In contrast, MRF4 expression was not changed in any muscle. These results suggest that MyoD and myogenin, but not MRF4, are sensitive to gravity-related stimuli in some skeletal muscles during postnatal development.
Influence of delayed isotopic equilibration in urine on the accuracy of the 2H2 18O method in the elderly
Authors: Blanc Stéphane , Colligan Amanda S. , Trabulsi Jillian , Harris Tamara , Everhart James E. , Bauer Doug , Schoeller Dale A.
Published: March 2015

Isotopic determination of total energy expenditure (TEE) by the doubly labeled water (DLW) method may be affected by urine retention in the elderly. The isotopic enrichments in urine and plasma sampled simultaneously 4 h post-DLW dose were compared in a subset of 281 subjects [139 women, 142 men, 75 ± 3 (SD) yr] of the 3,075 participants in the Health, Aging, and Body Composition study. Based on analytic precisions, a ±2% urine-plasma difference was set as the cut-off value. Ten percent of the population presented a difference lower than −2%, suggesting a delay in urine isotopic equilibration. This −13 ± 10% urine-plasma difference was not linked to analytic errors, illnesses, the sampling time, or the time and quantity of water intake, suggesting that urine retention may be the main factor. The consequences are an 18 ± 13 and 21 ± 16% overestimation of the total body water and the TEE, respectively. Unexpectedly, 21% of the population presented a urine-plasma difference higher than ±2% that resulted, however, in a nonsignificant TEE underestimation of −3 ± 5%. In conclusion, the delayed isotopic equilibration observed in urine reduces the accuracy of the DLW method in the elderly. It is recommended, when blood sampling is impossible, to adopt the intercept method with urine sampling 24 h postdose.
Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space
Authors: Payne Anthony M. , Dodd Stephen L. , Leeuwenburgh Christiaan
Published: March 2015

The decline in muscle function is associated with an age-related decrease in muscle mass and an age-related decline in strength. However, decreased strength is not solely due to decreased muscle mass. The age-related decline in muscle-specific force (force/muscle cross-sectional area), a measure of intrinsic muscle function, also contributes to age-related strength decline, and the mechanisms by which this occurs are only partially known. Moreover, changes in the extracellular space could have a profound effect on skeletal muscle function. Life-long calorie restriction in rodents has shown to be a powerful anti-aging intervention. In this study, we examine whether calorie restriction is able to attenuate the loss of muscle function and elevations in extracellular space associated with aging. We hypothesize that calorie restriction attenuates the age-associated decline in specific force and increases in extracellular space. Measurements of in vitro contractile properties of the extensor digitorum longus (type II) and soleus (type I) muscles from 12-mo and 26- to 28-mo-old ad libitum-fed, as well as 27- to 28-mo-old life-long calorie-restricted male Fischer 344 rats, were performed. We found that calorie restriction attenuated the age-associated decline in muscle mass-to-body mass ratio (mg/g) and strength-to-body mass ratio (N/kg) in the extensor digitorum longus muscle ( P < 0.05) but not in the soleus muscle ( P > 0.05). Importantly, muscle-specific force (N/cm2) in the extensor digitorum longus, but not in the soleus muscle, of the old calorie-restricted rats was equal to that of the young 12-mo-old animals. Moreover, the age-associated increase in extracellular space was reduced in the fast-twitch extensor digitorum longus muscle ( P < 0.05) but not in the soleus muscle with calorie restriction. We also found a significant correlation between the extracellular space and the muscle-specific force in the extensor digitorum longus ( r = -0.58; P < 0.05) but not in the soleus muscle ( r = -0.38; P > 0.05). Hence, this study shows a loss of muscle function with age and suggests that long-term calorie restriction is an effective intervention against the loss of muscle function with age.
Effect of long-term intermittent and sustained hypoxia on hypoxic ventilatory and metabolic responses in the adult rat
Authors: Reeves Stephen R. , Gozal Evelyne , Guo Shang Z. , Sachleben Leroy R. , Brittian Kenneth R. , Lipton Andrew J. , Gozal David
Published: March 2015

The effects of chronic sustained hypoxia (SH) on ventilation have been thoroughly studied. However, the effects of intermittent hypoxia (IH), a more prevalent condition in health and disease are currently unknown. We hypothesized that the ventilatory consequences of SH and IH may differ and be related to changes in N-methyl-d-aspartate (NMDA) glutamate receptor subunit expression. To examine these issues, Sprague-Dawley adult male rats were exposed to 30 days of either SH (10% O2) or IH (21% and 10% O2alternations every 90 s) or to normoxia (RA), at the end of which ventilatory and O2consumption responses to a 20-min acute hypoxic challenge (10% O2) were conducted. In addition, dorsocaudal brain stem tissue lysates were harvested at 1 h, 6 h, 1 day, 3 days, 7 days, 14 days, and 30 days of SH and IH and analyzed for NR1, NR2A, and NR2B NMDA glutamate receptor expression by immunoblotting. Normoxic ventilation was higher after both SH and IH ( P < 0.001). Peak hypoxic ventilatory response was higher after SH but not after IH compared with RA. However, hypoxic ventilatory decline was more prominent after SH than IH ( P < 0.001). NR1 expression showed a biphasic pattern of expression over time that was essentially identical after IH and SH ( P value not significant). However, NR2A and NR2B expression was higher in IH compared with SH and RA ( P < 0.01). We conclude that long-lasting exposures to SH and IH enhance normoxic ventilation but are associated with different time domains of ventilation during acute hypoxia that may be accounted in part by changes in NMDA glutamate receptor subunit expression.
Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude
Authors: Mason Nicholas P. , Petersen Merete , Mélot Christian , Imanow Bakyt , Matveykine Olga , Gautier Marie-Therese , Sarybaev Akpay , Aldashev Almaz , Mirrakhimov Mirsaid M. , Brown Brian H. , Leathard Andrew D. , Naeije Robert
Published: March 2015

Recent work suggests that treatment with inhaled β2-agonists reduces the incidence of high-altitude pulmonary edema in susceptible subjects by increasing respiratory epithelial sodium transport. We estimated respiratory epithelial ion transport by transepithelial nasal potential difference (NPD) measurements in 20 normal male subjects before, during, and after a stay at 3,800 m. NPD hyperpolarized on ascent to 3,800 m ( P < 0.05), but the change in potential difference with superperfusion of amiloride or isoprenaline was unaffected. Vital capacity (VC) fell on ascent to 3,800 m ( P < 0.05), as did the normalized change in electrical impedance (NCI) measured over the right lung parenchyma ( P < 0.05) suggestive of an increase in extravascular lung water. Echo-Doppler-estimated pulmonary artery pressure increases were insufficient to cause clinical pulmonary edema. There was a positive correlation between VC and NCI ( R 2 = 0.633) and between NPD and both VC and NCI ( R 2 = 0.267 and 0.418). These changes suggest that altered respiratory epithelial ion transport might play a role in the development of subclinical pulmonary edema at high altitude in normal subjects.
Sympathetic vascular transduction is augmented in young normotensive blacks
Authors: Ray Chester A. , Monahan Kevin D.
Published: March 2015

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 ± 7 vs. 55 ± 18%, 81 ± 21 vs. 137 ± 42%, 174 ± 81 vs. 556 ± 98% for −5, −15, and −40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 ± 0.07 vs. 0.82 ± 0.07 U; 0.82 ± 0.11 vs. 0.64 ± 0.09 U; 0.95 ± 0.37 vs. 0.35 ± 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.
Gas bubbles in rats after heliox saturation and different decompression steps and rates
Authors: Skogland Steffen , Segadal Kåre , Sundland Harald , Hope Arvid
Published: March 2015

Effects of pressure reduction, decompression rate, and repeated exposure on venous gas bubble formation were determined in five groups (GI, GII, GIII, GIV, and GV) of conscious and freely moving rats in a heliox atmosphere. Bubbles were recorded with a Doppler ultrasound probe implanted around the inferior caval vein. Rats were held for 16 h at 0.4 MPa (GI), 0.5 MPa (GII and GIII), 1.7 MPa (GIVa), or 1.9 MPa (GIV and GV), followed by decompression to 0.1 MPa in GI to GIII and to 1.1 MPa in GIV and GV. A greater decompression step, but at the same rate (GII vs. GI and GIVb vs. GIVa), resulted in significantly more bubbles ( P< 0.01). A twofold decompression step resulted in equal amount of bubbles when decompressing to 1.1 MPa compared with 0.1 MPa. The faster decompression in GII and GVa (10.0 kPa/s) resulted in significantly more bubbles ( P < 0.01) compared with GIII and GVb (2.2 kPa/s). No significant difference was observed in cumulative bubble score when comparing first and second exposure. With the present animal model, different decompression regimes may be evaluated.
Temporal coordination of pharyngeal and laryngeal dynamics with breathing during swallowing: single liquid swallows
Authors: Martin-Harris Bonnie , Brodsky Martin B. , Price Christina Clare , Michel Yvonne , Walters Bobby
Published: March 2015

The critical integration of timing and patterning between respiratory and swallowing events was studied with simultaneous videofluoroscopic and respiratory recording during single liquid swallows. Respiratory phase patterns and the onsets and durations of 12 predetermined swallowing events and associated respiratory activities were studied. Results showed four highly repeatable, temporally oriented sequences (clusters) of swallowing and related respiratory events. Two respiratory phase patterns were identified without statistically significant differences in frequency of occurrence between age, gender, or race. These findings will aid in the identification of normal and abnormal patterns of breathing and swallowing in patients with dysphagia.
Hypoxia-induced pulmonary endothelin-1 expression is unaltered by nitric oxide
Authors: Earley Scott , Nelin Leif D. , Chicoine Louis G. , Walker Benjimen R.
Published: March 2015

Nitric oxide (NO) attenuates hypoxia-induced endothelin (ET)-1 expression in cultured umbilical vein endothelial cells. We hypothesized that NO similarly attenuates hypoxia-induced increases in ET-1 expression in the lungs of intact animals and reasoned that potentially reduced ET-1 levels may contribute to the protective effects of NO against the development of pulmonary hypertension during chronic hypoxia. As expected, hypoxic exposure (24 h, 10% O2) increased rat lung ET-1 peptide and prepro-ET-1 mRNA levels. Contrary to our hypothesis, inhaled NO (iNO) did not attenuate hypoxia-induced increases in pulmonary ET-1 peptide or prepro-ET-1 mRNA levels. Because of this surprising finding, we also examined the effects of NO on hypoxia-induced increases in ET peptide levels in cultured cell experiments. Consistent with the results of iNO experiments, administration of the NO donor S-nitroso- N-acetyl-penicillamine to cultured bovine pulmonary endothelial cells did not attenuate increases in ET peptide levels resulting from hypoxic (24 h, 3% O2) exposure. In additional experiments, we examined the effects of NO on the activity of a cloned ET-1 promoter fragment containing a functional hypoxia inducible factor-1 binding site in reporter gene experiments. Whereas moderate hypoxia (24 h, 3% O2) had no effect on ET-1 promoter activity, activity was increased by severe hypoxic (24 h, 0.5% O2) exposure. ET-1 promoter activity after S-nitroso- N-acetyl-penicillamine administration during severe hypoxia was greater than that in normoxic controls, although activity was reduced compared with that in hypoxic controls. These findings suggest that hypoxia-induced pulmonary ET-1 expression is unaffected by NO.
Intramyocellular triacylglycerol in prolonged cycling with high- and low-carbohydrate availability
Authors: Johnson N. A. , Stannard S. R. , Mehalski K. , Trenell M. I. , Sachinwalla T. , Thompson C. H. , Thompson M. W.
Published: March 2015

Vastus lateralis intramyocellular lipid (IMCL) content was assessed by1H-magnetic resonance spectroscopy before and after prolonged time trial cycling bouts of ∼3-h duration. Six highly trained male cyclists completed a double-blind, randomized, crossover design of two experimental trials after a strenuous exercise bout and 48 h of high (HC) (9.32 ± 0.08 g · kg−1 · day−1) and low (LC) (0.59 ± 0.21 g · kg−1 · day−1) dietary carbohydrate. Resting IMCL content was significantly higher after LC vs. HC ( P < 0.01) and was reduced during exercise by 64 and 57%, respectively. IMCL was not different between conditions after exercise ( P > 0.05). The approximately twofold increase in IMCL degradation in LC compared with HC suggests that higher rates of whole body lipid metabolism in LC were in part attributable to a greater IMCL utilization. Four subjects experienced reductions of IMCL in excess of 70% during exercise. To our knowledge, this is the first study to report near depletion of IMCL during prolonged cycling, indicating that IMCL, presumably the triacylglycerol component, may be exhausted by prolonged strenuous exercise.