bluuebunny/crossref_metadata_2025 huggingface dataset:
EEG1, a putative transporter expressed during epithelial organogenesis: comparison with embryonic transporter expression during nephrogenesis
Authors: Stuart Robert O. , Pavlova Anna , Beier David , Li Zhixing , Krijanovski Yelena , Nigam Sanjay K.
Published: December 2017

A screen for genes differentially regulated in a model of kidney development identified the novel gene embryonic epithelia gene 1 (EEG1). EEG1 exists as two transcripts of 2.4 and 3.5 kb that are most highly expressed at embryonic day 7 and later in the fetal liver, lung, placenta, and kidney. The EEG1 gene is composed of 14 exons spanning a 20-kb region at human chromosome 11p12 and the syntenic region of mouse chromosome 2. Six EEG1 exons have previously been assigned to a longer isoform of eosinophil major basic protein termed proteoglycan 2. Another gene distantly related to EEG1, POV1/PB39, is located 88 kb upstream from the EEG1 gene on chromosome 11. Temporal expression of 65 members of the solute carrier (SLC)-class of transport proteins was followed during kidney development using DNA arrays. POV-1 and EEG1, like glucose transporters, displayed very early maximal gene expression. In contrast, other SLC genes, such as organic anion and cation transporters, amino acid permeases, and nucleoside transporters, had maximal expression later in development. Thus, although the bulk of transporters are expressed late in kidney development, a fraction are expressed near the onset of nephrogenesis. The data raise the possibility that EEG1 and POV1 may define a new family of transport proteins involved in the transport of nutrients or metabolites in rapidly growing and/or developing tissues.
Return of the secretory kidney
Authors: Grantham Jared J. , Wallace Darren P.
Published: December 2017

The evolution of the kidney has had a major role in the emigration of vertebrates from the sea onto dry land. The mammalian kidney has conserved to a remarkable extent many of the molecular and functional elements of primordial apocrine kidneys that regulate fluid balance and eliminate potentially toxic endogenous and xenobiotic molecules in the urine entirely by transepithelial secretion. However, these occult secretory processes in the proximal tubules and collecting ducts of mammalian kidneys have remained underappreciated in the last half of the twentieth century as investigators focused, to a large extent, on the mechanisms of glomerular filtration and tubule sodium chloride and fluid reabsorption. On the basis of evidence reviewed in this paper, we propose that transepithelial salt and fluid secretion mechanisms enable mammalian renal tubules to finely regulate extracellular fluid volume and composition day to day and maintain urine formation during the cessation of glomerular filtration.
Enhanced glomerular permeability to macromolecules in the Nagase analbuminemic rat
Authors: Fujihara Clarice Kazue , Arcos-Fajardo Michelle , Prado Euthymia Brandão De Almeida , Prado Maria JoséBrandão De Almeida , Sesso Antonio , Zatz Roberto
Published: December 2017

Plasma albumin restricts capillary water filtration. Accordingly, the glomerular ultrafiltration coefficient is higher in Nagase analbuminemic rats (NAR) than in Sprague-Dawley controls. We investigated whether the glomerular permeability to macromolecules is also enhanced in NAR. SDS-PAGE fractionation of urine proteins showed several bands with molecular masses between 60 and 90 kDa in NAR only. Acute administration of BSA to NAR led to nearly complete disappearance of these proteins from urine, an effect partially reversed when most of the exogenous albumin was cleared from circulation. The fractional clearance of 70-kDa dextran was increased in NAR, indicating a size defect. Binding of cationized ferritin to the glomerular basement membrane was decreased in NAR, suggesting associated depletion of fixed anions. The magnitude of cationic ferritin binding correlated negatively with the fractional clearance of 70-kDa dextran, suggesting that the two abnormalities may share a common pathogenic mechanism. Collectively, these results suggest enhanced glomerular permeability to macromolecules in NAR. Albumin may be necessary to maintain the normal glomerular permselectivity properties.
V˙o 2 kinetics reveal a central limitation at the onset of subthreshold exercise in heart transplant recipients
Authors: Mettauer Bertrand , Zhao Quan Ming , Epailly Eric , Charloux Anne , Lampert Eliane , Heitz-Naegelen Bernadette , Piquard François , di Prampero Pietro E. , Lonsdorfer Jean
Published: December 2017

Because the cardiocirculatory response of heart transplant recipients (HTR) to exercise is delayed, we hypothesized that their O2 uptake (V˙o 2) kinetics at the onset of subthreshold exercise are slowed because of an impaired early “cardiodynamic” phase 1, rather than an abnormal subsequent “metabolic” phase 2. Thus we compared the V˙o 2 kinetics in 10 HTR submitted to six identical 10-min square-wave exercises set at 75% (36 ± 5 W) of the load at their ventilatory threshold (VT) to those of 10 controls (C) similarly exercising at the same absolute (40 W; C40W group) and relative load (67 ± 14 W; C67W group). Time-averaged heart rate, breath-by-breathV˙o 2, and O2pulse (O2p) data yielded monoexponential time constants of the V˙o 2 (s) and O2p increase. Separating phase 1 and 2 data permitted assessment of the phase 1 duration and phase 2 V˙o 2 time constant ([Formula: see text]). The V˙o 2 time constant was higher in HTR (38.4 ± 7.5) than in C40W (22.9 ± 9.6; P ≤ 0.002) or C67W (30.8 ± 8.2; P ≤ 0.05), as was the O2p time constant, resulting from a lower phase 1V˙o 2 increase (287 ± 59 vs. 349 ± 66 ml/min; P ≤ 0.05), O2p increase (2.8 ± 0.6 vs. 3.6 ± 1.0 ml/beat; P ≤ 0.0001), and a longer phase 1 duration (36.7 ± 12.3 vs. 26.8 ± 6.0 s; P≤ 0.05), whereas the[Formula: see text]was similar in HTR and C (31.4 ± 9.6 vs. 29.9 ± 5.6 s; P = 0.85). Thus the HTR have slower subthresholdV˙o 2 kinetics due to an abnormal phase 1, suggesting that the heart is unable to increase its output abruptly when exercise begins. We expected a faster[Formula: see text]in HTR because of their prolonged phase 1 duration. Because this was not the case, their muscular metabolism may also be impaired at the onset of subthreshold exercise.
Carbohydrate loading failed to improve 100-km cycling performance in a placebo-controlled trial
Authors: Burke Louise M. , Hawley John A. , Schabort Elske J. , Gibson Alan St Clair , Mujika Iñigo , Noakes Timothy D.
Published: December 2017

We evaluated the effect of carbohydrate (CHO) loading on cycling performance that was designed to be similar to the demands of competitive road racing. Seven well-trained cyclists performed two 100-km time trials (TTs) on separate occasions, 3 days after either a CHO-loading (9 g CHO ⋅ kg body mass− 1 ⋅ day− 1) or placebo-controlled moderate-CHO diet (6 g CHO ⋅ kg body mass− 1 ⋅ day− 1). A CHO breakfast (2 g CHO/kg body mass) was consumed 2 h before each TT, and a CHO drink (1 g CHO ⋅ kg.body mass− 1 ⋅ h− 1) was consumed during the TTs to optimize CHO availability. The 100-km TT was interspersed with four 4-km and five 1-km sprints. CHO loading significantly increased muscle glycogen concentrations (572 ± 107 vs. 485 ± 128 mmol/kg dry wt for CHO loading and placebo, respectively; P < 0.05). Total muscle glycogen utilization did not differ between trials, nor did time to complete the TTs (147.5 ± 10.0 and 149.1 ± 11.0 min; P = 0.4) or the mean power output during the TTs (259 ± 40 and 253 ± 40 W, P = 0.4). This placebo-controlled study shows that CHO loading did not improve performance of a 100-km cycling TT during which CHO was consumed. By preventing any fall in blood glucose concentration, CHO ingestion during exercise may offset any detrimental effects on performance of lower preexercise muscle and liver glycogen concentrations. Alternatively, part of the reported benefit of CHO loading on subsequent athletic performance could have resulted from a placebo effect.
Effects of systemic arterial blood pressure on the contractile force of a human hand muscle
Authors: Wright Julie R. , McCloskey D. I. , Fitzpatrick Richard C.
Published: December 2017

The effect of physiological changes in systemic blood pressure on the force output of working abductor pollicis (AP) muscle was studied in six normal subjects. Supramaximal tetanic stimulation at the ulnar nerve produced repeated isometric contractions at 1-s intervals. Force output declined gradually with time. During the train of contractions, subjects voluntarily contracted the knee extensors for 1 min; this raised systemic blood pressure by 29%. Force output from AP rose in parallel with blood pressure so that 18% of the contraction force lost through fatigue was recovered for each 10% increase in blood pressure. When blood pressure in the hand was kept constant despite the increased systemic pressure, force output did not rise. The results show that muscle performance is strongly affected by physiological changes in central blood pressure and suggest that sensory input concerning the adequacy of muscle performance exerts a feedback control over the increase in systemic blood pressure during muscular activity.
A new nasal acoustic reflection technique to estimate pharyngeal cross-sectional area during sleep
Authors: Huang J. , Itai N. , Hoshiba T. , Fukunaga T. , Yamanouchi K. , Toga H. , Takahashi K. , Ohya N.
Published: December 2017

The conventional acoustic reflection technique in which acoustic waves are launched through the mouth cannot be applied during sleep, nor can it be applied to the nasopharynx, which is the major site of occlusion in patients with obstructive sleep apnea syndrome. We propose a new technique of nasal acoustic reflection to measure pharyngeal cross-sectional areas including the nasopharynx. The acoustic waves are introduced simultaneously to both nostrils during spontaneous nasal breathing. A new algorithm takes into account the nasal septum with asymmetric nasal cavities on both sides and assumes prior knowledge of the cross-sectional area of the nasal cavities and the position of the nasal septum. This method was tested on an airway model with a septum and on healthy human subjects. The conventional technique gave inaccurate measurements for pharyngeal cross-sectional areas for an airway model with asymmetric branching, whereas the new technique measured them almost perfectly. The oro- and hypopharyngeal cross-sectional area measurements acquired by the new method were not different from those obtained by the conventional method in normal subjects. This new method can be used as a monitor of upper airway dimensions in nocturnal polysomnography.
Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3
Authors: Kline David D. , Yang Tianen , Premkumar Daniel R. D. , Thomas Agnes J. , Prabhakar Nanduri R.
Published: December 2017

In the present study, the role of nitric oxide (NO) generated by endothelial nitric oxide synthase (NOS-3) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-3. Experiments were performed on awake and anesthetized mutant and wild-type (WT) control mice. Respiratory responses to 100, 21, and 12% O2and 3 and 5% CO2-balance O2were analyzed. In awake animals, respiration was monitored by body plethysmography along with O2consumption (V˙o2) and CO2production (V˙co2). In anesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Under both experimental conditions, WT mice responded with greater increases in respiration during 12% O2than mutant mice. Respiratory responses to hyperoxic hypercapnia were comparable between both groups of mice. Arterial blood gases, changes in blood pressure,V˙o2, andV˙co2during hypoxia were comparable between both groups of mice. Respiratory responses to cyanide and brief hyperoxia were attenuated in mutant compared with WT mice, indicating reduced peripheral chemoreceptor sensitivity. cGMP levels in the brain stem during 12% O2, taken as an index of NO production, were greater in mutant compared with WT mice. These observations demonstrate that NOS-3 mutant mice exhibit selective blunting of the respiratory responses to hypoxia but not to hypercapnia, which in part is due to reduced peripheral chemosensitivity. These results support the idea that NO generated by NOS-3 is an important physiological modulator of respiration during hypoxia.
Combined aerobic and resistance exercise training improves functional capacity and strength in CHF
Authors: Maiorana Andrew , O'Driscoll Gerard , Cheetham Craig , Collis Julie , Goodman Carmel , Rankin Sarah , Taylor Roger , Green Daniel
Published: December 2017

This study examined the effect of a novel circuit weight training (CWT) program on cardiorespiratory fitness, muscular strength, and body composition in 13 patients with chronic heart failure (CHF), using a prospective randomized crossover protocol. Peak exercise oxygen uptake (V˙o 2 peak) increased after the 8-wk CWT program (19.5 ± 1.2 vs. 22.0 ± 1.5 ml ⋅ kg− 1 ⋅ min− 1, P < 0.01), as did exercise test duration (15.2 ± 0.9 vs. 18.0 ± 1.1 min, P < 0.001). Submaximal exercise heart rate was lower after training at 60 and 80 W (121 ± 3 vs. 134 ± 5 beats/min, P < 0.01) as was rate pressure product, whereas ventilatory threshold increased, from 52 ± 3 to 58 ± 3% of V˙o 2 peak ( P< 0.05). CWT also increased maximal isotonic voluntary contractile strength for seven different muscle groups, from 392 to 462 kg ( P= 0.001). CWT, an exercise prescription specifically targeting peripheral abnormalities in CHF, improves functional capacity and muscular strength in these patients.
Effects of exercise intensity on the sweating response to a sustained static exercise
Authors: Kondo Narihiko , Tominaga Hirotaka , Shibasaki Manabu , Aoki Ken , Okada Shuichi , Nishiyasu Takeshi
Published: December 2017

To investigate how the sweating response to a sustained handgrip exercise depends on changes in the exercise intensity, the sweating response to exercise was measured in eight healthy male subjects. Each subject lay in the supine position in a climatic chamber (35°C and 50% relative humidity) for ∼60 min. This exposure caused sudomotor activation by increasing skin temperature without a marked change in internal temperature. After this period, each subject performed isometric handgrip exercise [15, 30, 45, and 60% maximal voluntary contraction (MVC)] for 60 s. Although esophageal and mean skin temperatures did not change with a rise in exercise intensity and were similar at all exercise intensities, the sweating rate (SR) on the forearm increased significantly ( P < 0.05) from baseline (0.094 ± 0.021 mg ⋅ cm−2⋅ min−1at 30% MVC, 0.102 ± 0.022 mg ⋅ cm−2⋅ min−1at 45% MVC, 0.059 ± 0.009 mg ⋅ cm−2⋅ min−1at 60% MVC) in parallel with exercise intensity above exercise intensity at 30% MVC (0.121 ± 0.023 mg ⋅ cm−2⋅ min−1at 30% MVC, 0.242 ± 0.051 mg ⋅ cm−2⋅ min−1at 45% MVC, 0.290 ± 0.056 mg ⋅ cm−2⋅ min−1at 60% MVC). Above 45% MVC, SR on the palm increased significantly from baseline ( P < 0.05). Although SR on the forearm and palm tended to increase with a rise in exercise intensity, there was a difference in the time courses of SR between sites. SR on the palm showed a plateau after abrupt increase, whereas SR on the forearm increased progressively during exercise. These results suggest that the increase in SR with the increase in sustained handgrip exercise intensity is due to nonthermal factors and that the magnitude of these factors during the exercise may be responsible for the magnitude of SR.
Central CO-heme oxygenase pathway raises body temperature by a prostaglandin-independent way
Authors: Steiner Alexandre A. , Branco Luiz G. S.
Published: December 2017

Recently, the carbon monoxide (CO)-heme oxygenase pathway has been shown to play an important role in fever generation by acting on the central nervous system, but the mechanisms involved have not been assessed. Thus the present study was designed to determine whether prostagandins participate in the rise in body temperature (Tb) observed after induction of the CO-heme oxygenase pathway in the central nervous system. Intracerebroventricular (ICV) injection of heme-lysinate (152 nmol/4 μl), which is known to induce the CO-heme oxygenase pathway, caused an increase in Tb [thermal index (TI) = 5.3 ± 0.5°C ⋅ h], which was attenuated by ICV administration of the heme oxygenase inhibitor ZnDPBG (200 nmol/4 μl; TI = 2.5 ± 1.7°C ⋅ h; P < 0.05). No change in Tb was observed after intraperitoneal injection of the cyclooxygenase inhibitor indomethacin (5 mg/kg), whereas indomethacin at the same dose attenuated the fever induced by ICV administration of lipopolysaccharide (LPS) (10 ng/2 μl) (vehicle/LPS: TI = 4.5 ± 0.5°C ⋅ h; indomethacin/LPS: TI = 1.7 ± 1.0°C ⋅ h; P < 0.05). Interestingly, indomethacin did not affect the rise in Tb induced by heme-lysinate (152 nmol/4 μl) ICV injection (vehicle/heme: TI = 4.5 ± 1.4°C ⋅ h; indomethacin/heme: TI = 4.2 ± 1.0°C ⋅ h). Finally, PGE2 (200 ng/2 μl) injected ICV evoked a rise in Tb that lasted 1.5 h. The heme oxygenase inhibitor ZnDPBG (200 nmol/4 μl) failed to alter PGE2-induced fever. Taken together, these results indicate that the central CO-heme oxygenase pathway increases Tbindependently of prostaglandins.
Ventilation heterogeneity in excised lobes: effect of tidal volume
Authors: Emery Michael J. , Hildebrandt Jacob , Hlastala Michael P.
Published: December 2017

Although several factors are known to influence nonuniformity of ventilation, including lung mechanical properties (regional structure and compliance), external factors (chest wall, pleural pressure, heart), and ventilatory parameters (tidal and preinspiratory volume, flow rate), their relative contributions are poorly understood. We studied five excised, unperfused, canine right-middle lobes under varied levels of tidal volume (Vt), thus eliminating many factors affecting heterogeneity. Multiple-breath washouts of N2were analyzed for anatomic dead space volume (Vdanat), nonuniformity of N2washout, and nonuniformity between joined acinar regions vs. that occurring between larger joined regions. Approximately 80% of ventilation heterogeneity was found among joined acinar regions at resting levels of Vt, but increasing Vt reduced intra-acinar heterogeneity to about 25% of that found at resting levels. Increasing Vt had essentially no effect on Vdanatand heterogeneity among larger joined regions. The results indicate that the magnitude of Vt is a major influence on the dominant intra-acinar component of ventilation heterogeneity and that Vt effects on Vdanatare likely due to perfusion and/or influences normally external to the lobar structure.
Reflex control of the cutaneous circulation during passive body core heating in humans
Authors: Peters Jochen K. , Nishiyasu Takeshi , Mack Gary W.
Published: December 2017

The impact of body core heating on the interaction between the cutaneous and central circulation during blood pressure challenges was examined in eight adults. Subjects were exposed to −10 to −90 mmHg lower body negative pressure (LBNP) in thermoneutral conditions and −10 to −60 mmHg LBNP during heat stress. We measured forearm vascular conductance (FVC; ml ⋅ min−1 ⋅ 100 ml−1 ⋅ mmHg−1) by plethysmography; cutaneous vascular conductance (CVC) by laser-Doppler techniques; and central venous pressure, arterial blood pressure, and cardiac output by impedance cardiography. Heat stress increased FVC from 5.7 ± 0.9 to 18.8 ± 1.3 conductance units (CU) and CVC from 0.21 ± 0.07 to 1.02 ± 0.20 CU. The FVC-CVP relationship was linear over the entire range of LBNP and was shifted upward during heat stress with a slope increase from 0.46 ± 0.10 to 1.57 ± 0.3 CU/mmHg CVP ( P < 0.05). Resting CVP was lower during heat stress (6.3 ± 0.6 vs. 7.7 ± 0.6 mmHg; P < 0.05) but fell to similar levels during LBNP as in normothermic conditions. Data analysis indicates an increased capacity, but not sensitivity, of peripheral baroreflex responses during heat stress. Laser-Doppler techniques detected thermoregulatory responses in the skin, but no significant change in CVC occurred during mild-to-moderate LBNP. Interestingly, very high levels of LBNP produced cutaneous vasodilation in some subjects.
Exercise modulates antioxidant enzyme gene expression in rat myocardium and liver
Authors: Wilson D. O. , Johnson P.
Published: December 2017

Our previous studies have shown that exercise caused changes in the tissue activities of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. To determine whether the changes observed were due to changes in mRNA levels of the enzymes, levels of tissue mRNA were determined by quantitative RNase protection assay. Comparisons of tissue enzyme activities and mRNA levels in sedentary and exercised animals showed that, in some cases (e.g., glutathione peroxidase in SH and WKY myocardium), parallel changes in enzyme activity and mRNA levels occurred, whereas in other cases (e.g., catalase in SH and WKY liver), nonparallel changes were found. Exercise of hypertensive rats altered antioxidant enzyme mRNA levels to those seen in normotensive animals in some, but not all, cases. The results suggest that transcriptional control over changes in exercise-related antioxidant enzyme activities is operative in some cases, although in other cases posttranscriptional regulatory mechanisms may exist.
Cellular oxygen sensing by mitochondria: old questions, new insight
Authors: Chandel Navdeep S. , Schumacker Paul T.
Published: December 2017

Hypoxia elicits a variety of adaptive responses at the tissue level, at the cellular level, and at the molecular level. A physiological response to hypoxia requires the existence of an O2sensor coupled to a signal transduction system, which in turn activates the functional response. Although much has been learned about the signaling systems activated by hypoxia, no consensus exists regarding the nature of the underlying O2sensor or whether multiple sensors exist. Among previously considered mechanisms, heme proteins have been suggested to undergo allosteric modification in response to O2binding or release at different [Formula: see text] levels. Other studies suggest that ion channels may change conductance as a function of[Formula: see text], allowing them to signal the onset of hypoxia. Still other studies suggest that NADPH oxidase may decrease its generation of reactive O2species (ROS) during hypoxia. Recent data suggest that mitochondria may function as O2sensors by increasing their generation of ROS during hypoxia. These oxidant signals appear to act as second messengers in the adaptive responses to hypoxia in a variety of cell types. Such observations contribute to a growing awareness that mitochondria do more than just generate ATP, in that they initiate signaling cascades involved in adaptive responses to hypoxia and that they participate in the control of cell death pathways.
Development of the ventilatory response to hypoxia in Swiss CD-1 mice
Authors: Robinson Dean M. , Kwok Henry , Adams Brandon M. , Peebles Karen C. , Funk Gregory D.
Published: December 2017

We examined developmental changes in breathing pattern and the ventilatory response to hypoxia (7.4% O2) in unanesthetized Swiss CD-1 mice ranging in age from postnatal day 0 to 42(P0–P42) using head-out plethysmography. The breathing pattern of P0 mice was unstable. Apneas were frequent at P0 (occupying 29 ± 6% of total time) but rare by P3 (5 ± 2% of total time). Tidal volume increased in proportion to body mass (∼10–13 ml/kg), but increases in respiratory frequency (f) (55 ± 7, 130 ± 13, and 207 ± 20 cycles/min for P0, P3, and P42, respectively) were responsible for developmental increases in minute ventilation (690 ± 90, 1,530 ± 250, and 2,170 ± 430 ml ⋅ min− 1 ⋅ kg− 1for P0, P3, and P42, respectively). Between P0 and P3, increases in f were mediated by reductions in apnea and inspiratory and expiratory times; beyond P3, increases were due to reductions in expiratory time. Mice of all ages showed a biphasic hypoxic ventilatory response, which differed in two respects from the response typical of most mammals. First, the initial hyperpnea, which was greatest in mature animals, decreased developmentally from a maximum, relative to control, of 2.58 ± 0.29 in P0 mice to 1.32 ± 0.09 in P42mice. Second, whereas ventilation typically falls to or below control in most neonatal mammals, ventilation remained elevated relative to control throughout the hypoxic exposure in P0 (1.73 ± 0.31), P3 (1.64 ± 0.29), and P9 (1.34 ± 0.17) mice but not in P19 or P42 mice.
Mechanisms for isolated volume response to a bronchodilator in patients with COPD
Authors: Cerveri Isa , Pellegrino Riccardo , Dore Roberto , Corsico Angelo , Fulgoni Paola , van de Woestijne Karel P. , Brusasco Vito
Published: December 2017

We hypothesized that an altered effect of lung inflation on airway caliber may in part explain the isolated volume response to bronchodilators, i.e., an increase of forced vital capacity (FVC) without change in 1-s forced expiratory volume (FEV1). Small-airway caliber was measured by high-resolution computed tomography at functional residual capacity and total lung capacity in five chronic obstructive pulmonary disease patients with an isolated increase of FVC (FVC responders) and five with an increase of both FVC and FEV1(FVC-FEV1responders) after inhalation of salbutamol. In FVC-FEV1responders, the airway diameter increased with the cube root of increase in lung volume but was unchanged or even decreased in four of five FVC responders. FVC responders had more severe emphysema, as inferred from lung function and imaging studies, than FVC-FEV1responders. We speculate that longitudinal traction or space competition (Verbeken EK, Cauberghs M, and Van de Woestijne KP, J Appl Physiol 81: 2468–2480, 1996) are possible underlying mechanisms. We conclude that the isolated volume response to bronchodilators is associated with severe emphysema and likely results from an altered effect of lung inflation on airway caliber.
Effects of swimming exercise on red blood cell rheology in trained and untrained rats
Authors: Yalcin Ozlem , Bor-Kucukatay Melek , Senturk Umit K. , Baskurt Oguz K.
Published: December 2017

Red blood cell (RBC) mechanical properties were investigated after swimming exercise in trained and untrained rats. A group of rats was trained for 6 wk (60 min swimming, daily), and another group was kept sedentary. Blood samples were obtained either within 5 min or 24 h after 60 min swimming in both groups. In the untrained rats, the RBC aggregation index decreased to 2.60 ± 0.4 immediately after exercise from a control value of 6.73 ± 0.18 ( P < 0.01), whereas it increased to 13.13 ± 0.66 after 24 h ( P < 0.01). RBC transit time through 5-μm pores increased to 3.53 ± 0.16 ms within 5 min after the exercise from a control value of 2.19 ± 0.07 ms ( P < 0.005). A very significant enhancement (166%) in RBC lipid peroxidation was detected only after 24 h. In the trained group, the alterations in all these parameters were attenuated; there was a slight, transient impairment in RBC deformability (transit time = 2.64 ± 0.13 ms), and lipid peroxidation was found to be unchanged. These findings suggest that training can significantly limit the hemorheological alterations related to a given bout of exercise. Whether this effect is secondary to the training-induced reduction in the degree of metabolic and/or hormonal perturbation remains to be determined.
Effects of activation frequency on dynamic performance of human fresh and fatigued muscles
Authors: Lee Samuel C. K. , Binder-Macleod Stuart A.
Published: December 2017

The force-frequency relationship for an individual muscle depends on the fatigue state, the length at which it is activated, and the muscle's activation history. The relationship among stimulation frequency and dynamic (nonisometric) muscle performance measurements (e.g., excursion, work, peak power, and average power) has not been reported. The purpose of this study was to identify the relationship between stimulation frequency and dynamic performance measurements for fresh and fatigued muscles. Constant-frequency and catchlike-inducing trains (CFT and CIT, respectively) were tested. When fresh, interpulse intervals of 40–50 ms [20–25 pulses/s (pps)] produced maximum performance for CFTs. For CITs, maximum performance occurred at interpulse intervals of 50–60 ms (∼16–20 pps). Generally, CFTs produced slightly greater performance than did CITs. When fatigued, however, CITs produced greater performance than did CFTs. Maximum performance for CFTs occurred at interpulse intervals of 20–40 ms (25–50 pps) and at 30–50 ms (20–33 pps) for CITs. Enhancement of performance by CITs when fatigued may be due to less susceptibility to impairments in excitation-contraction coupling and greater ability to maintain rates of rise of force than CFTs.
Basal lung mechanics and airway and pulmonary vascular responsiveness in different inbred mouse strains
Authors: Held Heinz-Dieter , Uhlig Stefan
Published: December 2017

Little is known about interstrain variations in baseline lung functions or smooth muscle contractility in murine lungs. We therefore examined basal lung mechanics and airway, as well as vascular reactivity to methacholine, thromboxane (using U-46619), and endothelin-1 (ET-1), A/J, AKR, BALB/c, C3H/HeN, C57BL/6, and SCID mice. All experiments were performed with isolated perfused mouse lungs. Except AKR mice (which were excluded from further analysis), all other strains showed stable pulmonary compliance, pulmonary resistance, and pulmonary arterial pressure within a control period of 45 min. Among these strains, C3H/HeN mice exhibited higher dynamic pulmonary compliance and lower pulmonary resistance, whereas SCID mice had higher baseline pulmonary resistance than the other strains. Concentration-response experiments with methacholine showed a lower airway reactivity for C57BL/6 mice compared with the other strains. Perfusion with 1 μM U-46619 or 100 nM ET-1 revealed a similar pattern: the agonist-inducible broncho- and vasoconstriction was lower in C57BL/6 mice than in all other strains, whereas it tended to be higher in SCID mice. The present study demonstrates a correlation between airway and vascular responsiveness in all tested strains. SCID mice are hyperreactive, whereas C57BL/6 mice are hyporeactive, to smooth muscle constrictors. Lung mechanics, as well as airway and vascular responsiveness, appear to be genetically controlled.
Functional anatomy of the vagal innervation of the cervical trachea of the dog
Authors: Coon Robert L. , Mueller Patrick J. , Clifford Philip S.
Published: December 2017

The canine cervical trachea has been used for numerous studies regarding the neural control of tracheal smooth muscle. The purpose of the present study was to determine whether there is lateral dominance by either the left or right vagal innervation of the canine cervical trachea. In anesthetized dogs, pressure in the cuff of the endotracheal tube was used as an index of smooth muscle tone in the trachea. After establishment of tracheal tone, as indicated by increased cuff pressure, either the right or left vagus nerve was sectioned followed by section of the contralateral vagus. Sectioning the right vagus first resulted in total loss of tone in the cervical trachea, whereas sectioning the left vagus first produced either a partial or no decrease in tracheal tone. After bilateral section of the vagi, cuff pressure was recorded during electrical stimulation of the rostral end of the right or left vagus. At the maximum current strength used, stimulation of the left vagus produced tracheal constriction that averaged 28.5% of the response to stimulation of the right vagus (9.0 ± 1.8 and 31.6 ± 2.5 mmHg, respectively). In conclusion, the musculature of cervical trachea in the dog appears to be predominantly controlled by vagal efferents in the right vagus nerve.
Impaired sarcoplasmic reticulum Ca2+release rate after fatiguing stimulation in rat skeletal muscle
Authors: Ørtenblad Niels , Sjøgaard Gisela , Madsen Klavs
Published: December 2017

The purpose of the study was to characterize the sarcoplasmic reticulum (SR) function and contractile properties before and during recovery from fatigue in the rat extensor digitorum longus muscle. Fatiguing contractions (60 Hz, 150 ms/s for 4 min) induced a reduction of the SR Ca2+release rate to 66% that persisted for 1 h, followed by a gradual recovery to 87% of prefatigue release rate at 3 h recovery. Tetanic force and rate of force development (+dF/d t) and relaxation (−dF/d t) were depressed by ∼80% after stimulation. Recovery occurred in two phases: an initial phase, in which during the first 0.5–1 h the metabolic state recovered to resting levels, and a slow phase from 1–3 h characterized by a rather slow recovery of the mechanical properties. The recovery of SR Ca2+release rate was closely correlated to +dF/d t during the slow phase of recovery ( r2= 0.51; P < 0.05). Despite a slowing of the relaxation rate, we did not find any significant alterations in the SR Ca2+uptake function. These data demonstrate that the Ca2+release mechanism of SR is sensitive to repetitive in vitro muscle contraction. Moreover, the results indicate that +dF/d t to some extent depends on the rate of Ca2+release during the slow phase of recovery.
Effects of crocetin on pulmonary gas exchange in foxhounds during hypoxic exercise
Authors: Wagner Peter D. , Hsia Connie C. W. , Goel Ruchi , Fay James M. , Wagner Harrieth E. , Johnson Robert L.
Published: December 2017

The carotenoid compound crocetin has been hypothesized to enhance the diffusion of O2 through plasma, and observations in the rat and rabbit have revealed improvement in arterial Po 2 when crocetin is given. To determine whether crocetin enhances diffusion of O2 between alveolar gas and the red blood cell in the pulmonary capillary in vivo, five foxhounds, two previously subjected to sham and three to actual lobectomy or pneumonectomy, were studied while breathing 14% O2 at rest and during moderate and heavy exercise before and within 10 min after injection of a single dose of crocetin as the trans isomer of sodium crocetinate (TSC) at 100 μg/kg iv. This dose is equivalent to that used in previous studies and would yield an initial plasma concentration of 0.7–1.0 μg/ml. Ventilation-perfusion inequality and pulmonary diffusion limitation were assessed by the multiple inert gas elimination technique in concert with conventional measurements of arterial and mixed venous O2 and CO2. TSC had no effect on ventilation, cardiac output, O2 consumption, arterial Po 2/saturation, or pulmonary O2diffusing capacity. There were minor reductions in ventilation-perfusion mismatching (logarithm of the standard deviation of perfusion fell from 0.48 to 0.43, P = 0.001) and in CO2 output and respiratory exchange ratio ( P = 0.05), which may have been due to TSC or to persisting effects of the first exercise bout. Spectrophotometry revealed that TSC disappeared from plasma with a half time of ∼10 min. We conclude that, in this model of extensive pulmonary O2 diffusion limitation, TSC as given has no effect on O2 exchange or transport. Whether the original hypothesis is invalid, the dose of TSC was too low, or plasma diffusion of O2 is not rate limiting without TSC cannot be discerned from the present study.
Peak flowmeter resistance decreases peak expiratory flow in subjects with COPD
Authors: Miller Martin R. , Pedersen Ole F.
Published: December 2017

Previous studies have shown that the added resistance of a mini-Wright peak expiratory flow (PEF) meter reduced PEF by ∼8% in normal subjects because of gas compression reducing thoracic gas volume at PEF and thus driving elastic recoil pressure. We undertook a body plethysmographic study in 15 patients with chronic obstructive pulmonary disease (COPD), age 65.9 ± 6.3 yr (mean ± SD, range 53–75 yr), to examine whether their recorded PEF was also limited by the added resistance of a PEF meter. The PEF meter increased alveolar pressure at PEF (Ppeak) from 3.7 ± 1.4 to 4.7 ± 1.5 kPa ( P = 0.01), and PEF was reduced from 3.6 ± 1.3 l/s to 3.2 ± 0.9 l/s ( P = 0.01). The influence of flow limitation on PEF and Ppeak was evaluated by a simple four-parameter model based on the wave-speed concept. We conclude that added external resistance in patients with COPD reduced PEF by the same mechanisms as in healthy subjects. Furthermore, the much lower Ppeak in COPD patients is a consequence of more severe flow limitation than in healthy subjects and not of deficient muscle strength.
Ventricular motion during the ejection phase: a computational analysis
Authors: Redaelli A. , Maisano F. , Schreuder J. J. , Montevecchi F. M.
Published: December 2017

In the present paper, the study of the ventricular motion during systole was addressed by means of a computational model of ventricular ejection. In particular, the implications of ventricular motion on blood acceleration and velocity measurements at the valvular plane (VP) were evaluated. An algorithm was developed to assess the force exchange between the ventricle and the surrounding tissue, i.e., the inflow and outflow vessels of the heart. The algorithm, based on the momentum equation for a transitory flowing system, was used in a fluid-structure model of the ventricle that includes the contractile behavior of the fibers and the viscous and inertial forces of the intraventricular fluid. The model calculates the ventricular center of mass motion, the VP motion, and intraventricular pressure gradients. Results indicate that the motion of the ventricle affects the noninvasive estimation of the transvalvular pressure gradient using Doppler ultrasound. The VP motion can lead to an underestimation equal to 12.4 ± 6.6%.
Detailed flow patterns in the nasal cavity
Authors: Kelly J. T. , Prasad A. K. , Wexler A. S.
Published: December 2017

The human nasal cavity filters and conditions inspired air while providing olfactory function. Detailed experimental study of nasal airflow patterns has been limited because of the complex geometry of the nasal cavity. In this work, particle image velocimetry was used to determine two-dimensional instantaneous velocity vector fields in parallel planes throughout a model of the nasal cavity that was subjected to a nonoscillatory flow rate of 125 ml/s. The model, which was fabricated from 26 computed tomography scans by using rapid prototyping techniques, is a scaled replica of a human right nasal cavity. The resulting vector plots show that the flow is laminar and regions of highest velocity are in the nasal valve and in the inferior airway. The relatively low flow in the olfactory region appears to protect the olfactory bulb from particulate pollutants. Low flows were also observed in the nasal meatuses, whose primary function has been the subject of debate. Comparison of sequentially recorded data suggests a steady flow.
Coactivation of the antagonist muscle does not covary with steadiness in old adults
Authors: Burnett Rebecca A. , Laidlaw Douglass H. , Enoka Roger M.
Published: December 2017

The purpose of the study was to determine the association between steadiness and activation of the agonist and antagonist muscles during isometric and anisometric contractions. Young ( n = 14) and old ( n = 15) adults used the first dorsal interosseus muscle to perform constant-force and constant-load tasks (2.5, 5, 20, 50, and 75% maximum) with the left index finger. Steadiness was quantified as the coefficient of variation of force and the SD of acceleration normalized to the load lifted. The old adults were less steady at most target forces with isometric contractions (2.5, 5, and 50%) and with most loads during the anisometric contractions (2.5, 5, and 20%). Furthermore, the old adults were less steady when performing lengthening contractions (up to 50%) compared with shortening contractions, whereas there was no difference for young adults. The reduced steadiness exhibited by the old adults during these tasks was not associated with differences in the average level of agonist muscle electromyogram or with coactivation of the antagonist muscle.
Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction
Authors: Maeda Keiko , Tsutamoto Takayoshi , Wada Atsuyuki , Mabuchi Naoko , Hayashi Masaru , Hisanaga Tomoko , Kamijo Takeshi , Kinoshita Masahiko
Published: December 2017

To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI (∼12 h after the attack) ( group 1) and compared data with those obtained after 1 mo ( group 2). In both groups 1and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.
Influence of cholesterol status on blood lipid and lipoprotein enzyme responses to aerobic exercise
Authors: Grandjean Peter W. , Crouse Stephen F. , Rohack J. James
Published: December 2017

To compare postexercise changes in plasma lipids and lipoprotein enzymes in 13 hypercholesterolemic (HC) and 12 normocholesterolemic men [total cholesterol (TC) 252 ± 5 vs. 179 ± 5 mg/dl], fasting blood samples were obtained 24 h before, immediately, 24, and 48 h after a single bout of treadmill walking (70% peak O2consumption, 500 kcal expenditure). Significant findings ( P < 0.05 for all) for plasma volume-adjusted lipid and enzyme variables were that TC, low-density-lipoprotein cholesterol, and cholesterol ester transfer protein activity were higher in the HC group but did not influence the lipid responses to exercise. Across groups, TC was transiently reduced immediately after exercise but returned to baseline levels by 24 h postexercise. Decreases in triglyceride and increases in high-density-lipoprotein cholesterol (HDL-C) and HDL3-C were observed 24 h after exercise and lasted through 48 h. Lipoprotein lipase activity was elevated by 24 h and remained elevated 48 h after exercise. HDL2-C, cholesterol ester transfer protein activity, hepatic triglyceride lipase, and lecithin: cholesterol acyltransferase activities did not change after exercise. These data indicate that the exercise-induced changes in HDL-C and triglyceride are similar in HC and normocholesterolemic men and may be mediated, at least in part, by an increase in lipoprotein lipase activity.
Hemodynamic effects of pressures applied to the upper airway during sleep
Authors: Eastwood P. R. , Curran A. K. , Smith C. A. , Dempsey J. A.
Published: December 2017

The increase in systemic blood pressure after an obstructive apnea is due, in part, to sympathetically mediated vasoconstriction. We questioned whether upper airway (UA) receptors could contribute reflexly to this vasoconstriction. Four unanesthetized dogs were studied during wakefulness and non-rapid-eye-movement (NREM) sleep. The dogs breathed via a fenestrated tracheostomy tube sealed around the tracheal stoma. The snout was sealed with an airtight mask, thereby isolating the UA when the fenestration was closed and exposing the UA to negative inspiratory intrathoracic pressure when it was open. The blood pressure response to three UA perturbations was studied: 1) square-wave negative pressures sufficient to cause UA collapse with the fenestration closed during a mechanical hyperventilation-induced central apnea; 2) tracheal occlusion with the fenestration open vs. closed; and 3) high-frequency pressure oscillations (HFPO) with the fenestration closed. During NREM sleep, 1) blood pressure response to tracheal occlusion was similar with the fenestration open or closed; 2) collapsing the UA with negative pressures failed to alter blood pressure during a central apnea; and 3) application of HFPO to the UA during eupnea and resistive-loaded breaths increased heart rate and blood pressure. However, these changes were likely to be secondary to the effects of HFPO-induced reflex changes on prolonging expiratory time. These findings suggest that activation of UA pressure-sensitive receptors does not contribute directly to the pressor response associated with sleep-disordered breathing events.
Pyruvate ingestion for 7 days does not improve aerobic performance in well-trained individuals
Authors: Morrison Michael A. , Spriet Lawrence L. , Dyck David J.
Published: December 2017

The purposes of the present studies were to test the hypotheses that lower dosages of oral pyruvate ingestion would increase blood pyruvate concentration and that the ingestion of a commonly recommended dosage of pyruvate (7 g) for 7 days would enhance performance during intense aerobic exercise in well-trained individuals. Nine recreationally active subjects (8 women, 1 man) consumed 7, 15, and 25 g of pyruvate and were monitored for a 4-h period to determine whether blood metabolites were altered. Pyruvate consumption failed to significantly elevate blood pyruvate, and it had no effect on indexes of carbohydrate (blood glucose, lactate) or lipid metabolism (blood glycerol, plasma free fatty acids). As a follow-up, we administered 7 g/day of either placebo or pyruvate, for a 1-wk period to seven, well-trained male cyclists (maximal oxygen consumption, 62.3 ± 3.0 ml · kg−1 · min−1) in a randomized, double-blind, crossover trial. Subjects cycled at 74–80% of their maximal oxygen consumption until exhaustion. There was no difference in performance times between the two trials (placebo, 91 ± 9 min; pyruvate, 88 ± 8 min). Measured blood parameters (insulin, peptide C, glucose, lactate, glycerol, free fatty acids) were also unaffected. Our results indicate that oral pyruvate supplementation does not increase blood pyruvate content and does not enhance performance during intense exercise in well-trained cyclists.
Duodenal vs. gastric administration of labeled leucine for the study of splanchnic metabolism in humans
Authors: Crenn Pascal , Thuillier Francois , Rakotoambinina Benjamin , Rongier Monique , Darmaun Dominique , Messing Bernard
Published: December 2017

Low-rate (6 ml/h) intragastric infusion of stable, isotope-labeled amino acids is commonly used to assess the splanchnic handling of amino acids in humans. However, when used in the postabsorptive state, this method yields unreliable plasma isotopic enrichments, with a coefficient of variation >10%. In this metabolic condition, we confirmed in six subjects that an intragastric infusion of l-[2H3]leucine at 6 ml/h yields an unreliable isotopic steady state in plasma amino acids with a coefficient of variation of 43 ± 12% (mean ± SD). In five additional subjects, we assessed the effects of 1) increasing the rate of delivery of a leucine tracer in an isotonic plasmalike solution at 240 ml/h into the gastric site, and 2) changing the site of infusion from gastric to duodenal with this same high rate of delivery. In contrast to the gastric route, and regardless of the rate of delivery, only the intraduodenal route allowed 1) isotopic plasma steady state (i.e., coefficients of variation were <10%: 5 ± 3%), and 2) reproducible leucine extraction coefficients (22 ± 5%). We conclude that an infusion site that bypasses the gastric emptying process, i.e., the duodenal route, along with delivery of a plasmalike solution, is necessary to reach isotopic steady state in plasma when labeled leucine is infused into the gastrointestinal tract in the postabsorptive state.