bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation to hypercapnia vs. intracellular pH in cat carotid body: responses in vitro
Authors: Lahiri S. , Iturriaga R. , Mokashi A. , Botre F. , Chugh D. , Osanai S.
Published: December 2017

The hypotheses that the chemosensory discharge rate parallels the intracellular pH (pHi) during hypercapnia and that the initial change in pHi (delta pHi) is always more than the stead-state delta pHi were studied by using cat carotid bodies in vitro at 36.5 degrees C in the absence and presence of methazolamide (30-100 mg/l). Incremental acidic hypercapnia was followed by an incremental initial peak response and a greater adaptation. A given acidic hypercapnia elicited a rapid initial response followed by a slower adaptation; isohydric hypercapnia produced an equally rapid initial response but of smaller magnitude that returned to near-baseline level; alkaline hypercapnia induced a similar rapid initial response but one of still smaller magnitude that decreased rapidly to below the baseline. Methazolamide eliminated the initial overshoot, which also suggested involvement of the initial rapid pHi in the overshoot. These results show that the initial delta pHi is always greater than the steady-state delta pHi and during hypercapnia. Also, the steady-state chemoreceptor activity varied linearly with the extracellular pH, indicating a linear relationship between extracellular pH and pHi.
Effect of high-altitude hypoxia on feeding responses and hedonic matrix in rats
Authors: Singh S. B. , Sharma A. , Sharma K. N. , Selvamurthy W.
Published: December 2017

Albino male rats (n = 78) were exposed to a simulated high altitude (HA) equivalent to 7,620 m for 6 h daily, contiguously for a period of 21 days, to study their feeding behavior and gustatory responses. Their food, water intake, and body weight were recorded daily, and blood sugar and blood insulin were estimated once a week. All the parameters were recorded for a period of 3 wk each before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intakes and body weight and mild hyperglycemia and hyperinsulinemia during hypoxic exposure. The 1-h single-bottle taste solution test showed a preference for sweet solutions (13% glucose and 0.2% saccharine) over citric acid (0.16%), sodium chloride (0.9%), and quinine sulfate (0.001%) during exposure to simulated HA. The 1-h two-bottle test containing glucose (calories plus taste) and saccharine (taste but no calories) administration showed a preference for the glucose solution over the saccharine solution. The trend of the 1-h intake of all test solutions also showed a reversal to preexposure levels after termination of HA hypoxia. It would appear that high-altitude stress influences food intake in a manner that sensory cues (e.g., preference for sweet substances) become more important.
Thrombin increases fluid flux in isolated rat lungs by a hemodynamic and not a permeability mechanism
Authors: Waypa G. B. , Vincent P. A. , Morton C. A. , Minnear F. L.
Published: December 2017

Alpha-Thrombin increases endothelial protein permeability in vitro and induces weight gain in the isolated perfused lung. The objectives of this study were to determine whether thrombin increases endothelial permeability of the isolated perfused rat lung and whether a change in permeability or hemodynamics mediates the gain in lung weight. Endothelial protein permeability was assessed by regression analysis of 125I-labeled albumin clearance vs. fluid flux to determine the permeability-surface area product (PS) and the reflection coefficient (sigma). Thrombin (5 x 10(-8) or 5 x 10(-7) M) did not alter protein permeability from the control values of PS and sigma. Thrombin caused an overall increase in transvascular fluid flux, as depicted by a gain in lung weight. Pulmonary arterial and capillary pressures and arterial and venous resistances increased by 10 min after thrombin injection, and lung weight decreased due to arterial constriction. From 10 to 50 min, pressures and resistances decreased, but capillary pressure and venous resistance decreased to a lesser extent and, as a result, lung weight increased. Pretreatment with BQ-123, an endothelin-receptor antagonist, attenuated the sustained increases in pressures and resistances and the rate of lung weight gain. Indomethacin, a cyclooxygenase inhibitor, had no effect. These findings indicate that the increase in lung weight induced by thrombin results from an elevation of capillary pressure mediated, in part, by endothelin and is not due to an increase in endothelial protein permeability of the isolated perfused rat lung.
Temporal course of gas exchange and mechanical compensation after right pneumonectomy in immature dogs
Authors: Takeda S. , Wu E. Y. , Ramanathan M. , Estrera A. S. , Hsia C. C.
Published: December 2017

To determine the temporal progression and magnitude of functional compensation in immature dogs raised to maturity after extensive lung resection, we performed right pneumonectomy (R-Pnx) or right thoracotomy without pneumonectomy (Sham) in matched foxhounds at 2 mo of age. At 4, 8, 20, 40, and 60 wk after surgery, static transpulmonary pressure-lung volume relationships were determined. Lung diffusing capacity, membrane diffusing capacity, pulmonary capillary blood volume, pulmonary blood flow, septal lung tissue volume, and lung volumes were measured simultaneously by a rebreathing technique. During maturation, total lung capacity, lung volume at a given distending pressure, and compliance were lower in the R-Pnx group than in the Sham group (P < 0.05). Pulmonary viscous resistance at maturity was elevated after R-Pnx. There were no significant differences in total lung diffusing capacity, membrane diffusing capacity, pulmonary capillary blood volume, pulmonary blood flow, and septal lung tissue volume between groups. Compensation of alveolar-capillary gas exchange was complete by 4-8 wk after R-Pnx, but compensation of mechanical properties remained incomplete throughout maturation. Relative magnitude of compensation after R-Pnx was greater in immature dogs than in adult dogs studied previously by similar techniques.
A new method for the measurement of gas solubility
Authors: Snedden W. , LeDez K. , Manson H. J.
Published: December 2017

A novel technique for the measurement of gas solubility and gas content in liquids and suspensions is described. Saturation of the liquid and subsequent extraction of the test gas both took place in a specially modified gastight syringe. The test gas was extracted from the saturated liquid by bubbling an inert carrier gas through the liquid (“sparging”). All gas exiting the apparatus was directed toward a mass spectrometer that measured the volume of extracted test gas in the presence of the carrier. The technique was used to measure the solubilities of nitrogen, oxygen, carbon monoxide, carbon dioxide, and nitrous oxide in olive oil at 37 degrees C. The Bunsen solubility coefficients so obtained are in good agreement with those obtained by classic techniques.
Fractal dynamics of human gait: stability of long-range correlations in stride interval fluctuations
Authors: Hausdorff J. M. , Purdon P. L. , Peng C. K. , Ladin Z. , Wei J. Y. , Goldberger A. L.
Published: December 2017

Fractal dynamics were recently detected in the apparently “noisy” variations in the stride interval of human walking. Dynamical analysis of these step-to-step fluctuations revealed a self-similar pattern: fluctuations at one time scale are statistically similar to those at multiple other time scales, at least over hundreds of steps, while healthy subjects walk at their normal rate. To study the stability of this fractal property, we analyzed data obtained from healthy subjects who walked for 1 h at their usual, slow, and fast paces. The stride interval fluctuations exhibited long-range correlations with power-law decay for up to 1,000 strides at all 3 walking rates. In contrast, during metronomically paced walking, these long-range correlations disappeared; variations in the stride interval were random (uncorrelated) and nonfractal. The long-range correlations observed during spontaneous walking were not affected by removal of drifts in the time series. Thus the fractal dynamics of spontaneous stride interval are normally quite robust and intrinsic to the locomotor system. Furthermore, this fractal property of neural output may be related to the higher nervous centers responsible for the control of walking rhythm.
Acoustic rhinometry: influence of paranasal sinuses
Authors: Hilberg O. , Pedersen O. F.
Published: December 2017

The influence of the maxillary sinuses in acoustic rhinometry (AR) has not been evaluated, and this is the aim of the present study. We examined six subjects with AR and magnetic resonance imaging (MRI) after nasal decongestion to compare the area-distance relationships determined by the two methods. From the MRI data we obtained copies of the nasal cavities with and without maxillary sinuses, which were made in plastic by a stereolithographic method. AR curves from models without maxillary sinuses differed from AR curves with sinuses included but were in agreement with MRI curves without inclusion of sinuses. A similar difference in AR was seen in two subjects before and after the nasal cavities were flushed with saline to fill up the maxillary sinuses. The measured volume in the first 50 mm of the nasal cavity models was unaffected by the sinuses, but the volume in the first 70 mm corresponding to the length of the nasal cavity septum was increased slightly but significantly (from 10.8 to 11.3 cm3; P = 0.05). The presence of maxillary sinuses increased the volume of the epipharynx (70-100 mm from the nostril) from 12.2 to 21.3 cm3 (P < 0.01), and this increase was not due to the influence from the contralateral nasal cavity. We conclude that the maxillary sinuses may significantly contribute to the acoustically determined areas in the posterior part of the nasal cavity and the epipharynx, especially during decongestion, and may explain a part of the difference between area-distance curves obtained by AR and MRI, whereas contribution from the contralateral nasal cavity does not.
Role of viscoelasticity in the tube model of airway reopening. II. Non-Newtonian gels and airway simulation
Authors: Hsu S. H. , Strohl K. P. , Haxhiu M. A. , Jamieson A. M.
Published: December 2017

The influence of viscoelastic gels as lining fluids on the pressure-velocity relationships in an airway tube model (Gaver et al. J. Appl. Physiol. 69: 74-85, 1990) was examined. A flow instability was observed due to the occurrence of a sol-gel transition in the viscoelastic properties under flow conditions. We further report measurements of the viscoelastic properties of airway secretions. Airway secretions are gels under small strains and have a yield stress of 4-7 dyn/cm2. Secretions from the pharyngeal airway show lower elasticity than secretions from the trachea. The airway reopening process is simulated using a Weibel lung geometry by incorporating the constitutive equations from the model gel studies and utilizing the rheological data on airway secretions. In these simulations, a "popping-open" phenomenon arises from a flow instability in airway generations 8-14 when the rheological properties of the lining fluids are assumed to be similar to those of pharyngeal secretions. On the basis of these studies, the elasticity of airway secretions plays an important role in airway reopening.
Differential effects of salmeterol on lung endothelial and epithelial leakage in sheep
Authors: Peterson B. T. , Griffith D. E. , Connelly J. C. , Tate R. W.
Published: December 2017

Salmeterol has been shown to prevent the influx of proteins into the air spaces of lungs of guinea pigs given intravenous histamine. To determine whether the salmeterol acts to stabilize the epithelial or endothelial barrier, we ventilated anesthetized sheep with aerosolized salmeterol before infusing histamine intravenously at a rate of 4 micrograms.kg-1.min-1 for 3 h. Changes in endothelial permeability were assessed by measuring the flow of lymph and proteins from the lungs. The influx of proteins into the air spaces was detected by performing single-cycle lavages to measure the concentration of circulating 125I-albumin in the epithelial lining fluid. Intravenous histamine increased the lymph flow to 13.2 +/- 6.8 ml/h compared with the control value of 5.6 +/- 2.8 ml/h (P < 0.05). Histamine also increased the concentration of 125I-albumin in the epithelial lining fluid from 1.8 +/- 0.9 to 8.5 +/- 2.5% of the plasma concentration (P < 0.01) and the postmortem lung water volume from 3.5 +/- 0.5 to 5.0 +/- 0.8 mg/g dry lung wt (P < 0.05). Pretreatment with 2.5 mg of aerosolized salmeterol prevented the influx of proteins into the air spaces and the increase in the postmortem lung water volume but it also increased the lung lymph flow even further to 20.0 +/- 5.6 ml/h (P < 0.05), increased the lymph-to-plasma protein ratio from 0.77 to 0.91, and tripled the increase in alveolar-arterial oxygen gradient caused by histamine alone. Pretreatment with 2.5 mg of intravenous salmeterol had essentially the same effect as salmeterol administered by aerosol. We conclude that salmeterol decreases lung epithelial permeability but increases lung endothelial permeability due to intravenous histamine in sheep.
Diffusion of nonelectrolytes in the canine trachea: effect of tight junction
Authors: George S. C. , Babb A. L. , Deffebach M. E. , Hlastala M. P.
Published: December 2017

We recently demonstrated through theoretical modeling that the exhaled ethanol (EtOH) profile from humans is consistent with a molecular diffusion coefficient (cm2/s) in the bronchial mucosa (Dti) that is only 8% of the diffusion coefficient in water (Dw; J. Appl. Physiol. 75: 2439-2449, 1993). Because of the small oil-water partition coefficient (lambda o:w) of EtOH (lambda o:w = 0.074), the reduced diffusion coefficient may be due, in part, to the epithelial tight junction in the paracellular pathway. We hypothesized that opening the tight junction would open an aqueous pathway and increase the diffusion coefficient of small (mol wt < 100) hydrophilic compounds. We mounted the mucosa from the membranous canine trachea in an Ussing-type diffusion cell and measured the diffusion coefficient of 2-ethoxyethanol (2-Ethx; lambda o:w = 0.042), EtOH, and methyl ethyl ketone (MEK; lambda o:w = 1.04) in the presence and absence of the epithelial tight junction. The tight junction was opened using a phosphate-buffered saline free of Ca2+ and Mg2+ with 0.5 mM ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and its integrity was assessed by measuring the transepithelial electrical resistance. Dti/Dw in the presence of Ca2+ and Mg2+ was 0.39, 0.34, and 0.39 for 2-Ethx, EtOH, and MEK, respectively, and increased 24.6, 11.7, and 1.11% in the absence of Ca2+ and Mg2+. We conclude that the effect of the tight junction on Dti increases with increasing water solubility but can account for only a small portion of the reduced Dti of EtOH as predicted by exhaled profiles.
Respiratory control during volume-cycled ventilation in normal humans
Authors: Puddy A. , Patrick W. , Webster K. , Younes M.
Published: December 2017

The purpose of this study was to evaluate the extent of inhibition to respiratory rhythm associated with high volumes of ventilation during volume-cycled mechanical ventilation (neuromechanical inhibition). Two approaches were used. 1) In 18 normal awake subjects, ventilator tidal volume (VT) in the assist/control mode (A/C) was increased in steps from the minimum tolerable level up to 80% of the subject's inspiratory capacity or ventilator's maximum VT. We looked for appearance of intermittent apnea or a reduction in spontaneous rate (f). 2) Another 18 normal awake subjects were placed on controlled mechanical ventilation (CMV). When apnea was established, we abruptly terminated CMV and measured the time before the appearance of the next spontaneous effort. In the assist mode (protocol 1), we did not observe intermittent apnea because VT was increased from [from 944 +/- 198 to 1,867 +/- 277 (SD) ml], and there was only a modest reduction in f (14.1 +/- 3.9 to 12.4 +/- 4.0 breaths/min). End-tidal PCO2 (PETCO2) decreased precipitously as VT was increased. In protocol 2, we did not observe apnea after discontinuation of CMV in any subject. Total breath duration of the first breath after discontinuation did not differ significantly from total breath duration during A/C in the same subjects (4.84 +/- 2.2 vs. 5.2 +/- 2.0 s). This similarly applied regardless of route of breathing (nose vs. mouth) or PETCO2 level at time of discontinuation. We conclude that neuromechanical inhibition is quite weak and provides very little negative feedback that may help control PCO2 in the face of excessive VT and f demands of the subject.
On the existence of a lactate threshold during incremental exercise: a systems analysis
Authors: Cabrera M. E. , Chizeck H. J.
Published: December 2017

The relationship between blood lactate concentration ([La]) and O2 uptake (VO2) during incremental exercise remains controversial: does [La] increase smoothly as a function of VO2 (continuous model), or does it begin to increase abruptly above a particular metabolic rate (threshold model)? The dynamic characteristics of the underlying physiological system are investigated using system identification analysis techniques. A multivariate deterministic time series model of the [La] and VO2 response to incremental changes in work rate was fitted to simulated and experimental data. Time-varying system response parameters were determined through the application of a weighted recursive least squares algorithm. The model, using the identified time-varying parameters, provided a good fit to the data. The variation of these parameters over time was then examined. Two major transitions in the parameters were found to occur at intensity levels equivalent to 53 +/- 8% and 77 +/- 9% maximal VO2 (experimental data). These changes in the model parameters indicate that the best linear dynamic model that fits the observed system behavior has changed. This implies that the system has changed its operation in some way, by altering its structure or by moving to a different operating region. The identified parameter changes over time suggest that the exercise intensity range (from rest to maximal VO2) is divided into three main intensity domains, each with distinct dynamics. Further study of this three-phase system may help in the understanding of the underlying physiological mechanisms that affect the dynamics of [La] and VO2 during exercise.
Effects of spaceflight on rat erythroid parameters
Authors: Allebban Z. , Gibson L. A. , Lange R. D. , Jago T. L. , Strickland K. M. , Johnson D. L. , Ichiki A. T.
Published: December 2017

Hematologic studies were performed on 21 ground control rats and 21 rats flown during the Spacelab Life Sciences-2 14-day mission. Group A (n = 5) was used to collect blood in flight and 9 days postflight, group B (n = 5) was injected with recombinant human erythropoietin (rhEpo), group C (n = 5) received saline as a control, and group D (n = 6) was killed in flight and tissues were collected. Results indicated no significant changes in peripheral blood erythroid elements between flight and ground control rats. The nonadherent bone marrow on flight day 13 showed a lower number of recombinant rat interleukin-3 (rrIL-3)-responsive and rrIL-3 + rhEpo-responsive blast-forming unit erythroid (BFU-e) colonies in flight rats compared with ground control rats. On landing day, a slight increase in the number of rhEpo + rrIL-3-responsive BFU-e colonies of flight animals compared with ground control rats was evident. Nine days postflight, bone marrow from flight rats stimulated with rhEpo alone or with rhEpo + rrIL-3 showed an increase in the number of colony-forming unit erythroid colonies and a decrease in BFU-e colonies compared with ground control rats. This is the first time that animals were injected with rhEpo and subsequently blood and tissues were collected during the spaceflight to study the regulation of erythropoiesis in microgravity.
Muscle creatine loading in men
Authors: Hultman E. , Soderlund K. , Timmons J. A. , Cederblad G. , Greenhaff P. L.
Published: December 2017

The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatinine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the presupplementation value. During this period, urinary creatinine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day. In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is in the long term likely to be as effective at raising tissue levels as this higher dose.
Cardiorespiratory response patterns to afferent stimulation of muscle nerves in the rabbit
Authors: Raimondi G. , Legramante J. M. , Iellamo F. , Cassarino S. , Peruzzi G.
Published: December 2017

The aim of this study was to test the hypothesis that stimulation of thin fiber muscle afferents is capable of matching the cardiovascular and ventilatory responses. In 46 anesthetized rabbits, the central end of the gastrocnemius nerves was electrically stimulated at 3 [low-frequency stimulation (LFS)] and 100 Hz [high-frequency stimulation (HFS)]. Intensities up to 200 times motor threshold were used. LFS induced a decrease in both mean arterial pressure (-19.9 +/- 2.9%) and systemic vascular resistance (-23.9 +/- 3.2%) an increase in cardiac output (CO) (6.4 +/- 1.7%), stroke volume (7.3 +/- 3.0%) and pulmonary ventilation (VE) (26.7 +/- 2.3%); heart rate and central venous pressure were not changed significantly. HFS induced an increase in mean arterial pressure (11.1 +/- 4.9%), CO (15.8 +/- 5.4%), stroke volume (13.4 +/- 5.4%), and VE but no significant changes in heart rate, systemic vascular resistance and central venous pressure. In both response patterns, arterial and end-tidal CO2 did not change significantly. The patterns of cardiorespiratory responses to both LFS and HFS were characterized by an increase in Co and VE without concomitant decreases in arterial and end-tidal PCO2 (isocapnic hyperpnea).
Breathing during wakefulness and NREM sleep in humans without an upper airway
Authors: Morrell M. J. , Harty H. R. , Adams L. , Guz A.
Published: December 2017

The increase in PCO2 that occurs during sleep may reflect an inadequate ventilatory compensation to an increase in upper airway resistance. To address this question in humans, we examined changes in breathing during wakefulness and non-rapid-eye-movement sleep in eight laryngectomized subjects who breathed through a tracheal stoma. In these subjects, any sleep-related increase in upper airway resistance could not affect ventilation. Healthy subjects breathing via an intact upper airway were studied as controls. The mean increase in end-tidal PCO2 from wakefulness to sleep was 2.7 +/- 2.6 (SD) Torr (P = 0.05) in laryngectomized subjects and 1.6 +/- 1.4 Torr (P = 0.02) in control subjects. During wakefulness, ventilation was lower in laryngectomized subjects compared with control subjects, although this difference was not statistically significant (6.8 +/- 1.9 vs. 7.4 +/- 1.2 l/min; P > 0.05). During sleep, the fall in ventilation was similar in the two groups (1.1 +/- 2.1 vs. 0.8 +/- 2.1 l/min; P > 0.05). Our observations are not consistent with the view that increases in upper airway resistance are obligatory for sleep-related CO2 retention in humans.
Evidence for cGMP mediation of skeletal muscle arteriolar dilation to lactate
Authors: Chen Y. L. , Wolin M. S. , Messina E. J.
Published: December 2017

In this study we tested the hypothesis that lactate, independent of changes in pH, can affect skeletal muscle blood flow through arteriolar dilation that may be mediated by guanosine 3',5'-cyclic monophosphate. Isolated, cannulated, and pressurized first-order rat cremaster skeletal muscle arterioles were studied in a chamber containing Krebs-bicarbonate buffer under no-flow conditions. At pH 7.4 and PO2 of 65 Torr, neutralized lactic acid (lactate) and pyruvic acid (pyruvate) caused arteriolar dilation over the 1-10 mM concentration range. This response to lactate was not altered by 10(-5) M indomethacin, 10(-4) M NG-nitro-L-arginine, or removal of the endothelium. However, responses to 1 and 3 mM pyruvate were significantly inhibited by 100% by endothelium removal, and the response to 10 mM pyruvate was inhibited by 71%. The relaxation of endothelium-denuded arterioles to lactate was inhibited by 10 microM methylene blue, 10 microM LY-83583, hypoxia (PO2 7-10 Torr), and diphenyliodonium, an inhibitor of superoxide-producing flavo-protein enzymes. In contrast, arteriolar dilation to the acidification of the Krebs buffer to pH 7.15, produced by increasing the CO2 concentration of the gas mixture from 5 to 10%, was not inhibited by methylene blue. These results are consistent with lactate-induced skeletal muscle arteriolar dilation being dependent on H2O2-mediated activation of vascular smooth muscle guanylate cyclase and independent of endothelium-derived mediators.
A reduced lactate mass explains much of the glycogen sparing associated with training
Authors: Crowley M. A. , Willis W. T. , Matt K. S. , Donovan C. M.
Published: December 2017

Endurance training is associated with glycogen (Gly) sparing, generally attributed to less carbohydrate (CHO) oxidation. However, untrained individuals commit a greater fraction of CHO to lactate (La), accounting for a portion of the Gly "spared." We examined the effects of training (running 1 h/day at 30 m/min up an 8 degrees grade) on whole body CHO distribution and oxidation. Female Long Evans rats (n = 27) were assigned to control (Untr) and trained (Tr) groups. Two days before the experiment, animals were chronically catheterized. On the day of the experiment, animals ran for 20 min at a speed of 28 m/min and were killed with an overdose of pentobarbital sodium injection while running. Whole carcasses were then promptly freeze-clamped with a liquid N2-cooled press. Whole body carcass powder was assayed for La, Gly, and glucose. Resting whole body values were not different between groups (La = 0.78 +/- 0.06 vs. 0.83 +/- 0.07, Gly = 4.46 +/- 0.62 vs. 3.77 +/- 0.35, glucose = 0.19 +/- 0.07 vs. 0.23 +/- 0.09 mmol/body for Tr and Untr rats, respectively). However, postexercise La was higher in Untr vs. Tr group (2.01 +/- 0.28 vs. 1.13 +/- 0.09 mmol/body), and Gly was lower in the Untr vs. Tr rats (1.58 +/- 0.25 vs. 3.42 +/- 0.43 mmol/body). Similarly, Untr animals displayed higher epinephrine levels than Tr at the end of the exercise bout (4.9 +/- 1.0 vs. 1.7 +/- 0.4 ng/ml). Differences between groups in La and glucose masses (postexercise minus rest data) accounted for 60% of the Gly differences. Gly spared from oxidation and replaced by increased fat oxidation only accounted for 40% of the differences in Gly levels between Tr and Untr animals. We conclude that untrained mammals commit a significant portion of their CHO pool to La, which accounts for almost one-half of the apparent Gly spared during moderate-intensity exercise in the trained state.
Regional deposition of inhaled hygroscopic aerosols: in vivo SPECT compared with mathematical modeling
Authors: Finlay W. H. , Stapleton K. W. , Chan H. K. , Zuberbuhler P. , Gonda I.
Published: December 2017

The regional deposition patterns of inhaled hygroscopic aerosols obtained in vivo in the studies of Phipps et al. (P. R. Phipps, I. Gonda, D. L. Bailey, P. Borham, G. Bautovich, and S. D. Anderson. Am. Rev. Respir. Dis. 139: 1516, 1989; and P. R. Phipps, I. Gonda, S. D. Anderson, D. L. Bailey, and G. Bautovich. Eur. Respir. J. 7: 1474-1482, 1994) and Chan et al. (H.-K. Chan, P. R. Phipps, I. Gonda, P. Cook, R. Fulton, I. Young, and G. Bautovich. Eur. Respir. J. 7: 1483-1489, 1994) by using single-photon-emission computerized tomography (SPECT) are compared with the regional deposition predicted by the hygroscopic lung deposition model of Finlay and Stapleton (W. H. Finlay and K. W. Stapleton. J. Aerosol Sci. 26: 655-670, 1995). Three pairs of saline aerosols are considered: isotonic with small [2.6-microns mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD) 1.4] vs. large (5.5-microns MMAD, GSD 1.7) droplets; hypotonic (0.3% NaCl) vs. hypertonic (4.5% NaCl) with 3.7- to 3.8-microns MMAD (GSD 1.4), and hypotonic vs. hypertonic (3.7- to 3.8-microns MMAD, GSD 1.5-1.8) with reduced number of droplets per cubic centimeter. For each of the three pairs of aerosols, no significant difference (P > 0.05) was found between the in vivo and computational results for either the mean value or the variance of the difference in peripheral to central deposition. Thus it appears that theoretical calculations can be used to predict the pattern of lung deposition of hygroscopic aerosols in populations of normal subjects.
Effect of spaceflight on ability to sense and control roll tilt: human neurovestibular studies on SLS-2
Authors: Merfeld D. M.
Published: December 2017

To measure adaptive changes in the ability to sense tilt after spaceflight, we measured the ability of four astronauts to control roll tilt in the presence of a pseudorandom motion disturbance before and after a 14-day Spacelab mission. The subjects were tested 1) in the dark, 2) with an independent sum-of-sines visual display, and 3) by using a control condition in which the visual cues confirmed the motion cues (counterrotating). The two subjects tested on the landing day exhibited significant decrements (P < 0.05) in their ability to control roll tilt in the dark, whereas no significant performance decrements were observed in the control condition. The absence of changes in the control condition suggests that changes in the neuromuscular component of the task and postflight fatigue were not major factors contributing to the observed performance decrement in the dark. These findings indicate an adaptive change in the way the nervous system interprets tilt cues. Readaptation of all responses appeared to be rapid, with a return to preflight values within 1-2 days after landing.
Orthostatic intolerance after spaceflight
Authors: Buckey J. C. , Lane L. D. , Levine B. D. , Watenpaugh D. E. , Wright S. J. , Moore W. E. , Gaffney F. A. , Blomqvist C. G.
Published: December 2017

Orthostatic intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three space shuttle missions of 9-14 days. After spaceflight, 9 of the 14 (64%) crew members could not complete a 10-min stand test that all completed preflight. Pre- and postflight supine hemodynamics were similar in both groups except for slightly higher systolic and mean arterial pressures preflight in the finishers [15 +/- 3.7 and 8 +/- 1.2 (SE) mmHg, respectively; P < 0.05]. Postflight, finishers and nonfinishers had equally large postural reductions in stroke volume (-47 +/- 3.7 and -48 +/- 3.3 ml, respectively) and increases in heart rate (35 +/- 6.6 and 51 +/- 5.2 beats/min, respectively). Cardiac output during standing was also similar (3.6 +/- 0.4 and 4.1 +/- 0.3 l/min, respectively). However, the finishers had a greater postflight vasoconstrictor response with higher total peripheral resistance during standing (22.3 +/- 1.2 units preflight and 29.4 +/- 2.3 units postflight) than did the nonfinishers (20.1 +/- 1.1 units preflight and 19.9 +/- 1.4 units postflight). We conclude that 1) the primary systemic hemodynamic event, i.e., the postural decrease in stroke volume, was similar in finishers and nonfinishers and 2) the heart rate response and cardiac output during standing were not significantly different, but 3) the postural vasoconstrictor response was significantly greater among the finishers (P < 0.01).
Daily physical activity assessment: comparison between movement registration and doubly labeled water
Authors: Bouten C. V. , Verboeket-van de Venne W. P. , Westerterp K. R. , Verduin M. , Janssen J. D.
Published: December 2017

The use of movement registration for daily physical activity assessment was evaluated during a 7-day period in 30 free-living subjects. Body movement was registered with a Tracmor motion sensor consisting of a triaxial accelerometer and a data unit for on-line processing of accelerometer output over 1-min intervals. Average Tracmor output was correlated against four different energy estimates: 1) average daily metabolic rate (ADMR), determined with doubly labeled water; 2) ADMR-sleeping metabolic rate (SMR; determined in a respiration chamber); 3) (ADMR-SMR) per kilogram of body mass; and 4) the overall physical activity level (PAL = ADMR/SMR). The highest correlation was found for the relationship between Tracmor output and PAL (r = 0.58). After correction for Tracmor values arising from vibrations produced by transportation means, this correlation was improved to 0.73. There was no difference between Tracmor output and PAL in discriminating between overall activity levels with "low" (PAL < 1.60), "moderate" (1.60 < or = PAL < or = 1.85), and "high" (PAL > 1.85) intensity. It is concluded that the Tracmor can be used in free-living subjects to distinguish among interindividual as well as intraindividual levels of daily physical activity.
Carbohydrate ingestion and single muscle fiber glycogen metabolism during prolonged running in men
Authors: Tsintzas O. K. , Williams C. , Boobis L. , Greenhaff P.
Published: December 2017

The aim of this study was to examine the effect of carbohydrate (CHO) ingestion on glycogen degradation in type I and type II muscle fibers during prolonged running by using a quantitative biochemical method. To this end, eight male subjects ran at 70% maximal oxygen uptake to exhaustion on a motorized treadmill on two occasions, 1 wk apart. On each occasion, the subjects ingested 8 ml/kg body wt of either placebo (Pl) or a 5.5% CHO-electrolyte solution (CHO-E) immediately before the start of the run and 2 ml/kg body wt every 20 min thereafter. Needle biopsy samples were obtained from the vastus lateralis muscle before and after each trial and also at the time coinciding with Pl exhaustion in the CHO-E trial. Running time to exhaustion was longer (P < 0.01) in the CHO-E trial compared with the Pl trial (132.4 +/- 12.3 and 104.3 +/- 8.6 min, respectively). A 25% reduction in glycogen utilization in type I fibers only was observed in the CHO-E trial compared with the Pl trial (215.2 +/- 27.5 vs. 285.4 +/- 30.1 mmol/kg dry wt; P < 0.01). Furthermore, in the CHO-E trial, in contrast to the Pl trial, both muscle ATP and phosphocreatine concentrations were well maintained throughout exercise. Therefore, because in both the Pl and CHO-E trials the type I fibers were glycogen depleted at the point of exhaustion (31.6 +/- 10.3 and 28.1 +/- 7.1 mmol/kg dry wt, respectively), it is proposed that CHO ingestion improved endurance capacity by contributing to oxidative ATP production specifically in type I fibers and by doing so delayed the development of glycogen depletion in this fiber type.
Alveolar liquid clearance is increased by endogenous catecholamines in hemorrhagic shock in rats
Authors: Pittet J. F. , Brenner T. J. , Modelska K. , Matthay M. A.
Published: December 2017

The primary objective of this study was to test the hypothesis that hemorrhagic shock would stimulate alveolar liquid clearance by a catecholamine-dependent mechanism. Anesthetized rats were hemorrhaged to a mean arterial pressure of 30 mmHg for 90 min, but they were not resuscitated. Alveolar liquid clearance was measured by the concentration of labeled and unlabeled protein over 2 h in an isosmolar physiological solution of 5% albumin that had been instilled into one lung. Hemorrhaged rats developed a severe metabolic acidosis that was associated with a 5- to 10-fold rise in plasma epinephrine levels. There was a 60% increase in alveolar liquid clearance in the hemorrhaged rats compared with control rats (55 +/- 6 vs. 34 +/- 7%; P < 0.05). Amiloride (10(-4) M) or propranolol (10(-4)M) inhibited the increase in alveolar liquid clearance. Thus the endogenous release of catecholamines associated with hemorrhagic shock markedly stimulates alveolar fluid clearance by a beta-adrenergic-mediated stimulation of active sodium transport. These data suggest a new, previously unrecognized mechanism that may protect against alveolar flooding in the acute phase of hemorrhagic shock.
Shift working in the Chilean Andes (> 3,600 m) and its influence on erythropoietin and the low-pressure system
Authors: Gunga H. C. , Rocker L. , Behn C. , Hildebrandt W. , Koralewski E. , Rich I. , Schobersberger W. , Kirsch K.
Published: December 2017

It was hypothesized that, in shift workers with a history of intermittent hypoxic stress (working 10 days at > 3,600 m, then resting for 4 days at sea level) for > 5 yr, the initial erythropoietin (EPO) response and the changes in central venous pressure (CVP) are different from those in Caucasian lowlanders. We studied the kitchen personnel (n = 11) of a mine (3,600 m) and a group of Caucasian lowlanders (n = 5). Blood samples were taken, and CVP was determined several times before, during, and after a typical shift. At baseline data collection (BDC) before transition, the shift workers had EPO concentrations of 5.2 +/- 2.4 mU/ml, which increased at altitude (P < 0.01) and returned to BDC values on the recovery (day 16). The Caucasians showed the same time course. Serum transferrin receptor concentrations did not change in either group. CVP values were generally higher in the shift workers than in the Caucasians. In conclusion, the hypothesis that the initial EPO response to a hypoxic stimulus is altered in these shift workers has to be refuted. Higher hemoglobin concentrations and/or CVP values in shift workers might be responsible for the rather low EPO concentrations in shift workers at BDC.
Effects of sustained and repetitive isocapnic hypoxia on ventilation and genioglossal and diaphragmatic EMGs
Authors: McEvoy R. D. , Popovic R. M. , Saunders N. A. , White D. P.
Published: December 2017

We compared the effects of sustained isocapnic hypoxia (SIH; 20 min) and repetitive isocapnic hypoxia (RIH; 10 2-min episodes) on ventilation (VI), genioglossal (EMGgg) and diaphragmatic electromyographic (EMGdi) activities, and supraglottic airway resistance in 11 normal supine male subjects (36.6 +/- 2.2 yr) during wakefulness. Seven of the subjects had control measurements on a separate day. Desaturation was similar (arterial O2 saturation 80–84%) in the SIH and RIH protocols. SIH and RIH caused a biphasic ventilatory response: early augmentation of VI (169.5 +/- 6.9 and 168.9 +/- 4.3% of baseline, respectively; not significant) followed by a significant roll-off (VI after 20 min of cumulative hypoxia 153 +/- 4.0 and 150.8 +/- 10.2% respectively; not significant). Moving-time-average EMGdi signals (peak inspiratory and phasic) demonstrated a similar biphasic response in the two protocols. Mean EMGgg responses, however, differed. During SIH, peak inspiratory EMGgg increased early and remained elevated. Phasic and tonic EMGgg signals showed a similar trend. During RIH, early augmentation of peak inspiratory and phasic EMGgg signals was followed by a marked roll-off in activity such that by the 10th hypoxic episode neither value increased above baseline. In the 2-min periods between hypoxic episodes, there was a progressive suppression of peak inspiratory and phasic EMGgg values below baseline. Supraglottic airway resistance did not change significantly during either SIH or RIH. VI and phasic EMGs did not change during control experiments. We conclude that in awake normal male subjects SIH and RIH cause similar biphasic responses in VI and EMGdi activity. Phasic EMGgg activity responses differ between SIH and RIH: EMGgg remains augmented during SIH, whereas during RIH early augmentation is followed by marked suppression.
Effects of ranolazine on oxidative substrate preference in epitrochlearis muscle
Authors: McCormack J. G. , Baracos V. E. , Barr R. , Lopaschuk G. D.
Published: December 2017

Ranolazine is an novel investigational antianginal agent that stimulates glucose oxidation in isolated rat hearts. This study determined its effects on metabolic substrate and O2 utilization in an in vitro skeletal muscle preparation, the rat epitrochlearis muscle. Muscles were superfused with Krebs-Henseleit buffer containing 3% albumin, 0.4 mM palmitate, 5.5 mM glucose, 0.5 mM lactate, and a physiological amino acid mixture. Perfusate also contained either 1) [U-14C]glucose for measurement of glucose oxidation or 2) [9,10–3H]palmitate and [U-14C]lactate for measurement of palmitate and lactate oxidation. Addition of ranolazine (10 microM) significantly stimulated glucose oxidation and decreased palmitate oxidation but had no effect on lactate oxidation. Overall, the calculated relative contribution of glucose oxidation to aerobic ATP production increased from 12 to 33%, whereas from palmitate it decreased from 55 to 26%. Ranolazine did not alter tissue malonyl-CoA contents, making it unlikely that the decrease in palmitate oxidation caused by ranolazine is due to a decrease in the activity of acetyl-CoA carboxylase. These data demonstrate that ranolazine can shift energy substrate preference in skeletal muscle, which could potentially prove useful in ischemic disorders of skeletal muscle.
Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema
Authors: Podolsky A. , Eldridge M. W. , Richardson R. S. , Knight D. R. , Johnson E. C. , Hopkins S. R. , Johnson D. H. , Michimata H. , Grassi B. , Feiner J. , Kurdak S. S. , Bickler P. E. , Severinghaus J. W. , Wagner P. D.
Published: December 2017

Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise, especially in hypoxia. A possible explanation is subclinical interstitial edema due to high pulmonary capillary pressures. We hypothesized that this may be pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE-susceptible people with higher vascular pressures would develop more exercise-induced VA/Q mismatch. To examine this, seven healthy people with a history of HAPE and nine with similar altitude exposure but no HAPE history (control) were studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We measured cardiac output and respiratory and inert gas exchange. In both groups, VA/Q mismatch (assessed by log standard deviation of the perfusion distribution) increased with exercise. At sea level, log standard deviation of the perfusion distribution was slightly higher in the HAPE-susceptible group than in the control group during heavy exercise. At altitude, these differences disappeared. Because a history of HAPE was associated with greater exercise-induced VA/Q mismatch and higher pulmonary capillary pressures, our findings are consistent with the hypothesis that exercise-induced mismatch is due to a temporary extravascular fluid accumulation.
Endothelium-derived nitric oxide activity in forearm vessels of tennis players
Authors: Green D. J. , Fowler D. T. , O'Driscoll J. G. , Blanksby B. A. , Taylor R. R.
Published: December 2017

The aim of this study was to determine whether physical conditioning induced by a repetitive exercise stimulus would elicit changes in the response of forearm resistance vessels to an infusion of substances that modulate nitric oxide synthesis. Forearm blood flow responses to a 5-min ischemic stimulus and intrabrachial infusion of acetylcholine, sodium nitroprusside, and NG-monomethyl-L-arginine were examined in the preferred and nonpreferred limbs of eight habitual tennis players. Forearm volume, girth, and grip strength were significantly greater in the preferred limb, indicating a bilateral difference in physical condition. This was associated with an enhanced reactive hyperemic response in the preferred limb (53.5 +/- 9.4 vs. 38.8 +/- 4.7 ml.100 ml-1.min-1; P < 0.05). No differences between the limbs were evident in response to acetylcholine, sodium nitroprusside, or NG-monomethyl-L-arginine. These results suggest that exercise training enhances the peak vasodilator capacity of the vasculature without influencing basal or stimulated activity of the nitric oxide dilator system in vivo.
Oxygen respiratory gas analysis by sine-wave measurement: a theoretical model
Authors: Hahn C. E.
Published: December 2017

A sinusoidal forcing function inert-gas-exchange model (C. E. W. Hahn, A. M. S. Black, S. A. Barton, and I. Scott. J. Appl. Physiol. 75: 1863–1876, 1993) is modified by replacing the inspired inert gas with oxygen, which then behaves mathematically in the gas phase as if it were an inert gas. A simple perturbation theory is developed that relates the ratios of the amplitudes of the inspired, end-expired, and mixed-expired oxygen sine-wave oscillations to the airways' dead space volume and lung alveolar volume. These relationships are independent of oxygen consumption, the gas-exchange ratio, and the mean fractional inspired (FIO2) and expired oxygen partial pressures. The model also predicts that blood flow shunt fraction (Qs/QT) is directly related to the oxygen sine-wave amplitude perturbations transmitted to end-expired air and arterial and mixed-venous blood through two simple equations. When the mean FIO2 is sufficiently high for arterial hemoglobin to be fully saturated, oxygen behaves mathematically in the blood like a low-solubility inert gas, and the amplitudes of the arterial and end-expired sine-wave perturbations are directly related to Qs/QT. This relationship is independent of the mean arterial and mixed-venous oxygen partial pressures and is also free from mixed-venous perturbation effects at high forcing frequencies. When arterial blood is not fully saturated, the theory predicts that QS/QT is directly related to the ratio of the amplitudes of the induced-saturation sinusoids in arterial and mixed-venous blood. The model therefore predicts that 1) on-line calculation of airway dead space and end-expired lung volume can be made by the addition of an oxygen sine-wave perturbation component to the mean FIO2; and (2) QS/QT can be measured from the resultant oxygen perturbation sine-wave amplitudes in the expired gas and in arterial and mixed-venous blood and is independent of the mean blood oxygen partial pressure and oxyhemoglobin saturation values. These calculations can be updated at the sine-wave forcing period, typically 2–4 min.