bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of lung inflation and airway muscle tone on airway diameter in vivo
Authors: Brown R. H. , Mitzner W.
Published: December 2017

How normal airway dimensions change with lung volume is of great importance in determining flow limitation during the normal forced vital capacity maneuver as well as in the manifestation of obstructive lung disease. The literature presents a confusing picture, with some results suggesting that airway diameter increases linearly with the cube root of lung volume and others showing a highly nonlinear relation. The effect of smooth muscle contraction on lung-airway interdependence is even less well understood. Recent morphological work explicitly assumes that airway basement membrane is nondistensible, although the lung volume at which this maximal airway size is reached is unknown. With smooth muscle contraction, folding of the epithelium and basement membrane accounts for the changes in luminal area. In this study, we measured the effect of lung inflation on relaxed and contracted airway areas by using high-resolution computed tomography at different transpulmonary pressures, each held for 2 min. We found that fully relaxed airways are quite distensible up to a pressure of 5-7 cmH2O (P < 0.001), where they reach a maximal size with no further distension up to an airway pressure of 30 cmH2O (P = 0.49). Thus relaxed airways clearly do not expand isotropically with the lung. With smooth muscle tone, the airways in different animals responded differently to lung inflation, with some animals showing minimal airway dilation up to an airway pressure of 20 cmH2O and others showing airways that were more easily dilated with lung expansion. However, maximal diameter of these moderately constricted airways was not usually achieved even up to an airway pressure of 30 cmH2O. Thus a transient deep inspiration in vivo would be expected to have only a small effect on contracted airways.
Preservation of alveolar epithelial fluid transport mechanisms in rewarmed human lung after severe hypothermia
Authors: Sakuma T. , Suzuki S. , Usuda K. , Handa M. , Okaniwa G. , Nakada T. , Fujimura S. , Matthay M. A.
Published: December 2017

Although hypothermia abolishes alveolar fluid clearance in the in situ goat lung and in the ex vivo human lung, it is unknown whether alveolar fluid clearance resumes in lungs that are rewarmed after severe hypothermia. An isosmolar albumin solution was instilled into resected human lungs that were rewarmed to 37 degrees C after hypothermia (7 +/- 3 degrees C), and then alveolar fluid clearance was measured by the concentration of albumin in the alveolar fluid sample after 4 h. In control experiments in lungs that had not been cooled and rewarmed, alveolar fluid clearance was 11 +/- 2% over 4 h. In separate experiments, hypothermia completely abolished alveolar fluid clearance. However, alveolar fluid clearance resumed to a normal level of 12 +/- 1% over 4 h in the lungs that were rewarmed after hypothermia. Amiloride decreased alveolar fluid clearance by 47% in the rewarmed lungs. Terbutaline increased alveolar fluid clearance by nearly 300% in 2-h experiments in the rewarmed lungs (P < 0.05). The results of this study indicate that alveolar sodium-channel transport mechanisms are preserved in resected human lungs that are exposed to rewarming after hypothermia.
Lumped-parameter tissue temperature-blood perfusion model of a cold-stressed fingertip
Authors: Shitzer A. , Stroschein L. A. , Gonzalez R. R. , Pandolf K. B.
Published: December 2017

A lumped-parameter model of a fingertip is presented. The semispherical model includes the effects of heat storage, heat exchange with the environment, and heat transport by blood perfusion. The thermal insulation on the surface of the fingertip is represented by the overall heat transfer coefficient that is calculated by common engineering formulas. The model is solved analytically for the simple case of constant blood perfusion rate. The general case of variable blood perfusion rates is solved by an Euler finite difference technique. At this stage, the model does not include active control mechanisms of blood perfusion. Thus the effects of cold-induced vasodilatation have to be superimposed and are modeled by symmetrical triangular waveforms because these were found to best depict the behavior of fingers exposed to cold environments. Results of this model were compared with experimental data obtained in two separate studies. One included 60-min infrared thermograms of the dorsal surface of bare hands of sedentary subjects horizontally suspended on a fish net in a 0 degree C environment. Another study, on gloved finger temperatures, involved 0 and -6.7 degrees C environments. Fingertip (nail bed) temperatures of both these studies were compared with model predictions. Blood perfusion rates were assumed and adjusted within physiologically reasonable limits. Comparison of measured and computed temperature records showed very good conformity in both cases studied.
Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction
Authors: Lutchen K. R. , Hantos Z. , Petak F. , Adamicza A. , Suki B.
Published: December 2017

Recent studies have suggested that part of the measured increase in lung tissue resistance after bronchoconstriction is an artifact due to increased airway inhomogeneities. To resolve this issue, we measured lung impedance (ZL) in seven open-chest rats with the lungs equilibrated on room air and then on a mixture of neon and oxygen (NeOx). The rats were placed in a body box with the tracheal tube leading through the box wall. A broadband flow signal was delivered to the box. The signal contained seven oscillation frequencies in the 0.234- to 12.07-Hz range, which were combined to produce tidal ventilation. The ZL was measured before and after bronchoconstriction caused by infusion of methacholine (MCh). Partitioning of airway and tissue properties was achieved by fitting ZL with a model including airway resistance (Raw), airway inertance, tissue damping (G), and tissue elastance (H). We hypothesized that if the inhomogeneities were not significant, the apparent tissue properties would be independent of the resident gas, whereas Raw would scale as the ratio of viscosities. Indeed, during control conditions, the NeOx-to-air ratios for G and H were both 1.03 +/- 0.04. Also, there was a small increase in lung elastance (EL) between 0.234 and 4 Hz that was similar on air and NeOx. During MCh infusion, Raw and G increased markedly (45-65%), but the increase in H was relatively small ( < 13%). The NeOx-to-air Raw and H ratios remained the same. However, the NeOx-to-air G ratio increased to 1.19 +/- 0.07 (P < 0.01) and the increase in EL with frequency was now marked and dependent on the resident gas. These results provide direct evidence that for a healthy rat lung airway inhomogeneities do not significantly influence the lung resistance or EL vs. frequency data. However, during MCh-induced constriction, a large portion of the increase in tissue resistance and the altered frequency dependence of EL are virtual and a consequence of the augmented airway inhomogeneities.
Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight
Authors: Allen D. L. , Yasui W. , Tanaka T. , Ohira Y. , Nagaoka S. , Sekiguchi C. , Hinds W. E. , Roy R. R. , Edgerton V. R.
Published: December 2017

The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.
Temporal relationships of ventilatory failure, pump failure, and diaphragm fatigue
Authors: Sassoon C. S. , Gruer S. E. , Sieck G. C.
Published: December 2017

The time course of ventilatory failure, pump failure, and diaphragm peripheral fatigue was determined during the application of external inspiratory resistive loads (IRL) in anesthetized rabbits. Pump failure is defined as the inability of the diaphragm to sustain the expected force under IRL. To assess contractile fatigue, transdiaphragmatic pressures (Pdi) generated by bilateral phrenic nerve stimulation at 75 Hz (Pdi-75) and 20 Hz (Pdi-20) were measured. The amplitude of evoked diaphragm electromyographic (EMG) signals was measured to assess neurotransmission failure. The rate of rise of spontaneous diaphragm EMG was used as an index of respiratory drive. Ventilation was evaluated together with arterial blood gases. During IRL the rate of rise of spontaneous diaphragm EMG increased, and there was a progressive hypercapnic acidosis and hypoxemia, indicating ventilatory failure. In contrast, Pdi-75 and Pdi-20 were stable until the time of respiratory arrest (apnea), when they decreased by 34 and 45%, respectively. The amplitude of evoked diaphragm EMG signals remained unchanged throughout the IRL and decreased only slightly at the time of apnea. We conclude that IRL induces progressive ventilatory failure long before any contractile fatigue of the diaphragm or pump failure occurs. This suggests that ventilatory failure is due to central fatigue, whereas pump failure (apnea) is attributable to multiple factors.
Central venous pressure in humans during microgravity
Authors: Foldager N. , Andersen T. A. , Jessen F. B. , Ellegaard P. , Stadeager C. , Videbaek R. , Norsk P.
Published: December 2017

Based on the results of head-down simulation studies and the results of parabolic flights, the hypothesis was tested that central venous pressure (CVP) in humans increases during microgravity (weightlessness) compared with during the ground-based supine position. CVP was recorded with an intravascular pressure transducer in seven healthy humans during short (20-s) periods of microgravity created by parabolic-flight maneuvers and in one astronaut before, during, and up to 3 h after launch of the Spacelab D-2 mission (Space Transport System-55). When the subjects were supine during the parabolic maneuver, CVP decreased during microgravity from 6.5 +/- 1.3 to 5.0 +/- 1.4 mmHg (P < 0.05). during the Spacelab D-2 mission, CVP was 6.2 mmHg during the initial minutes of microgravity, which was very similar to the value of 6.5 mmHg in the supine position 3.5 h before launch of the space shuttle. During the subsequent 3 h of weightlessness, CVP during rest varied between 2.0 and 6.2 mmHg. We conclude that CVP during short (20-s) and longer (3-h) periods of microgravity is close to or below that of the supine position on the ground.
Patient-ventilator interaction during acute hypercapnia: pressure-support vs. proportional-assist ventilation
Authors: Ranieri V. M. , Giuliani R. , Mascia L. , Grasso S. , Petruzzelli V. , Puntillo N. , Perchiazzi G. , Fiore T. , Brienza A.
Published: December 2017

The objective of this study was to compare patient-ventilator interaction during pressure-support ventilation (PSV) and proportional-assist ventilation (PAV) in the course of increased ventilatory requirement obtained by adding a dead space in 12 patients on weaning from mechanical ventilation. With PSV, the level of unloading was provided by setting the inspiratory pressure at 20 and 10 cmH2O, whereas with PAV the level of unloading was at 80 and 40% of the elastic and resistive load. Hypercapnia increased (P < 0.001) tidal swing of esophageal pressure and pressure-time product per breath at both levels of PSV and PAV. During PSV, application of dead space increased ventilation (VE) during PSV (67 +/- 4 and 145 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001). This was due to a relevant increase in respiratory rate (48 +/- 4 and 103 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001), whereas the increase in tidal volume (VT) played a small role (13 +/- 1 and 21 +/- 2% during 20 and 10 cmH2O PSV, respectively, P < 0.001). With PAV, the increase in VE consequent to hypercapnia (27 +/- 3 and 64 +/- 4% during 80 and 40% PAV, respectively, P < 0.001) was related to the increase in VT (32 +/- 1 and 66 +/- 2% during 80 and 40% PAV, respectively, P < 0.001), respiratory rate remaining unchanged. The increase in pressure-time product per minute and per liter consequent to acute hypercapnia and the sense of breathlessness were significantly (P < 0.001) higher during PSV than during PAV. Our data show that, after hypercapnic stimulation of the respiratory drive, the capability to increase VE through changes in VT modulated by variations in inspiratory muscle effort is preserved only during PAV; the compensatory strategy used to increase VE during PSV requires greater muscle effort and causes more pronounced patient discomfort than during PAV.
Effects of positive airway pressure on upper airway dilator muscle activity and ventilatory timing
Authors: Deegan P. C. , Nolan P. , Carey M. , McNicholas W. T.
Published: December 2017

To determine upper airway (UA) and ventilatory responses to nasal continuous positive airway pressure (CPAP) and expiratory positive airway pressure (EPAP), we quantitated changes in alae nasi (AN) and genioglossus (GG) electromyographic (EMG) activity, ventilatory timing, and end-expiratory lung volume (EELV) at various levels of CPAP and EPAP in six normal subjects during wakefulness and in seven during sleep. The same measurements were also made before and after UA anesthesia in six normal subjects during wakefulness. During both wakefulness and sleep, CPAP application significantly increased EELV and decreased AN and GG EMG activities. In contrast, EPAP significantly increased EMG activities of both muscles while also increasing EELV during wakefulness. The EMG responses were less marked during sleep. Anesthesia of the UA abolished the EMG responses to CPAP but not to EPAP. These results suggest that, in normal subjects, CPAP application causes a reflex reduction in UA dilator muscle activity mediated by UA sensory receptors. In contrast, EPAP increases UA dilator muscle activity, with the response mediated by conscious influences or reflexes arising outside of the UA.
Modified control of breathing in genetically obese (ob/ob) mice
Authors: Tankersley C. , Kleeberger S. , Russ B. , Schwartz A. , Smith P.
Published: December 2017

Attenuated hypercapnic chemosensitivity and hypoventilation are characteristics periodically associated with human obesity. We tested the hypothesis that ventilatory control is altered by genetic determinants and age-dependent factors that influence the obese phenotype. To this end, the magnitude and pattern of breathing were examined before and associated with the development of obesity in C57BL/6J mice homozygous and heterozygous at the ob gene locus. Breathing frequency and tidal volume were measured using whole body plethysmography, and minute ventilation was assessed during acute hypoxic and hypercapnic challenges with intermittent room air exposures. In age- and weight-matched mice before pronounced obesity, significant (P < 0.05) reductions in hypercapnic ventilatory sensitivity occurred in mutant (ob/ob) mice relative to wild-type (+/+) homozygotes primarily because of an attenuated tidal volume. Longitudinal studies indicated that mutant ob mice developed rapid baseline breathing relative to the wild type, accompanying a twofold greater increase in body mass. Early differences between homozygotes in hypercapnic ventilatory sensitivity were maintained through 230 days. These data demonstrate that genetic determinants at or closely linked to the ob locus influence hypercapnic ventilation before the emergence of pronounced obesity, whereas changes in baseline breathing appear due to age-dependent increases in body weight.
Preexercise glucose ingestion and glucose kinetics during exercise
Authors: Marmy-Conus N. , Fabris S. , Proietto J. , Hargreaves M.
Published: December 2017

The present study was undertaken to examine the effects of glucose ingestion before exercise on liver glucose output and muscle glucose uptake during exercise. On two occasions, at least 1 wk apart, six trained men (peak pulmonary O2 uptake = 5.11 +/- 0.17 l/min) ingested 400 ml of a solution containing either 75 g glucose [carbohydrate (CHO)] or a sweet placebo [control (Con)] 30 min before 60 min of exercise at 71 +/- 1% peak pulmonary O2 uptake. Glucose kinetics (rates of appearance and disappearance) were measured by a primed continuous infusion of [6,6–2H2]glucose. Liver glucose output was derived from total glucose appearance and the appearance of ingested glucose from the gut. After glucose ingestion, plasma glucose increased to 6.4 +/- 0.4 mmol/l immediately before exercise, fell to 4.2 +/- 0.5 mmol/l after 20 min of exercise, and then increased to a higher value than in the Con group (5.4 +/- 0.3 vs. 4.7 +/- 0.1 mmol/l; P < 0.05) after 60 min of exercise. In the CHO group, plasma insulin was higher immediately before exercise (P < 0.05) and, despite falling during exercise, remained higher than in the Con group after 60 min of exercise (57.0 +/- 11.4 vs. 24.8 +/- 1.7 pmol/l; P < 0.05). The rapid fall in plasma glucose in the CHO group was the result of a higher muscle glucose uptake with the onset of exercise (P < 0.05), which could not be matched by the glucose rate of appearance. Liver glucose output was decreased by glucose ingestion, and although it increased during the early stages of exercise in the CHO group, it did not rise above the basal values and was reduced by 62% over the 60 min of exercise compared with the Con group. In summary, preexercise glucose ingestion results in increased muscle glucose uptake and reduced liver glucose output during exercise.
Pulmonary clearance and lung function: influence of acute tobacco intoxication and of vitamin E
Authors: Scherrer-Crosbie M. , Paul M. , Meignan M. , Dahan E. , Lagrue G. , Atlan G. , Lorino A. M.
Published: December 2017

Cigarette smoking increases the alveolar epithelial permeability to small solutes, as assessed by the pulmonary clearance of aerosolized 99mTc-labeled diethylenetriaminepentaacetate. The involvement of lipid peroxidation in this increased clearance was tested in eight asymptomatic young smokers by investigating the effects of a 3-wk supplementation with oral vitamin E (1,000 IU/day) on pulmonary clearance according to a protocol designed as a single-blind crossover study. Indexes of acute tobacco intoxication (exhaled CO, carboxyhemoglobin, and urinary cotinine) and lung function parameters [including Krogh factor (KCO)] were also studied. Under control conditions, pulmonary clearance was abnormally increased (2.93 +/- 0.78%/min), whereas KCO was in the normal range. Pulmonary clearance correlated strongly with expired CO (P < 0.04), HbCO (P < 0.005), urinary cotinine (P < 0.003), and KCO (P < 0.004). Supplementation with vitamin E, a highly efficient antioxidant, neither decreased the pulmonary clearance nor altered the above correlations. However, the strong correlations observed between pulmonary clearance and indexes of acute tobacco intoxication, which reflect the amount of inhaled smoke and the resultant oxidant stress, do not allow exclusion of the involvement of lipid peroxidation in the pulmonary clearance increase observed in smokers.
Cerebral oxygenation changes in response to motor stimulation
Authors: Obrig H. , Hirth C. , Junge-Hulsing J. G. , Doge C. , Wolf T. , Dirnagl U. , Villringer A.
Published: December 2017

We studied cerebral hemodynamic response to a sequential motor task in 56 subjects to investigate the time course and distribution of blood oxygenation changes as monitored by near-infrared spectroscopy (NIRS). To address whether response is modulated by different performance velocities, a group of subjects (n = 12) was examined while performing the motor task at 1, 2, and 3 Hz. The results demonstrate that 1) the NIRS response reflects localized changes in cerebral hemodynamics, 2) the response, consisting of an increase in oxygenated hemoglobin concentration [oxy-Hb] and a decrease in deoxygenated hemoglobin concentration ([deoxy-Hb]), is lateralized and increases in amplitude with higher performance rates, and 3) changes in [oxy-Hb] and [deoxy-Hb] differ in time course. Changes in [oxy-Hb] are biphasic, with a fast initial increase and a pronounced poststimulus undershoot. The stimulus-associated decrease in [deoxy-Hb] is monophasic, and response latency is greater. We conclude that NIRS is able to detect even small changes in cerebral hemodynamic response to functional stimulation.
Insulin resistance limits glucose utilization and exercise tolerance in myophosphorylase deficiency and NIDDM
Authors: Dorin R. I. , Field J. C. , Boyle P. J. , Eaton R. P. , Icenogle M. V.
Published: December 2017

Myophosphorylase deficiency [McArdle's disease (MD)] produces a defect in muscle glycogenolysis in which muscular work is limited by delivery of external sources of substrate, primarily glucose and nonesterified fatty acids, to meet energy demands associated with exercise. In the present study, we evaluated an unusual patient with both MD and non-insulin-dependent diabetes mellitus. We hypothesized that insulin resistance would limit transport of extracellular glucose to skeletal muscle during exercise, resulting in impaired exercise performance that was reversible by insulin infusion. The effect of a hyperinsulinemic "euglycemic" clamp on exercise tolerance was evaluated by in vivo 31P-magnetic resonance spectroscopy as well as total work performed. We observed that insulin infusion significantly increased the rate of systemic glucose utilization (P < 0.01) and also significantly decreased the ratio of inorganic phosphate to phosphocreatine (P < 0.001) during forearm exercise compared with the control study. Insulin clamp was also associated with an increase in total work performed (56%) during exercise. Our findings demonstrate that resistance to the biological actions of insulin, as occurs in type II diabetes mellitus, leads to a defect in glucose transport that limits the availability of extracellular glucose to exercising muscle. In our subject with a substrate-limited skeletal muscle metabolism (MD), reversal of this defect in insulin-dependent glucose transport by a hyperinsulinemic euglycemic clamp was associated with significant improvement in magnetic resonance spectroscopy parameters of skeletal muscle metabolism as well as exercise performance.
Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy
Authors: Hamaoka T. , Iwane H. , Shimomitsu T. , Katsumura T. , Murase N. , Nishio S. , Osada T. , Kurosawa Y. , Chance B.
Published: December 2017

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.
Peak calf blood flow estimates are higher with Dohn than with Whitney plethysmograph
Authors: Proctor D. N. , Halliwill J. R. , Shen P. H. , Vlahakis N. E. , Joyner M. J.
Published: December 2017

Estimates of calf blood flow with venous occlusion plethysmography vary widely between studies, perhaps due to the use of different plethysmographs. Consequently, we compared calf blood flow estimates at rest and during reactive hyperemia in eight healthy subjects (four men and four women) with two commonly used plethysmographs: the mercury-in-silastic (Whitney) strain gauge and Dohn air-filled cuff. To minimize technical variability, flow estimates were compared with a Whitney gauge and a Dohn cuff on opposite calves before and after 10 min of bilateral femoral arterial occlusion. To account for any differences between limbs, a second trial was conducted in which the plethysmographs were switched. Resting flows did not differ between the plethysmographs (P = 0.096), but a trend toward lower values with the Whitney was apparent. Peak flows averaged 37% lower with the Whitney (27.8 +/- 2.8 ml.dl-1.min-1) than with the Dohn plethysmograph (44.4 +/- 2.8 ml.dl-1.min-1; P < 0.05). Peak flow expressed as a multiple above baseline was also lower with the Whitney (10-fold) than with the Dohn plethysmograph (14.5-fold; P = 0.02). Across all flows at rest and during reactive hyperemia, estimates were highly correlated between the plethysmographs in all subjects (r2 = 0.96-0.99). However, the mean slope for the Whitney-Dohn relationship was only 60 +/- 2%, indicating that over a wide range of flows the Whitney gauge estimate was 40% lower than that for the Dohn cuff. These results demonstrate that the same qualitative results can be obtained with either plethysmograph but that absolute flow values will generally be lower with Whitney gauges.
Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs
Authors: Diaz Véronique , Kianicka Irenej , Letourneau Patrick , Praud Jean-Paul ,   (With the Technical Assistance of Bruno Gagne)
Published: December 2017

Diaz, Véronique, Irenej Kianicka, Patrick Letourneau, and Jean-Paul Praud. Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs. J. Appl. Physiol. 81(4): 1598–1604, 1996.—Newborn mammals exhibit an active expiratory upper airway closure during the first hours of extrauterine life. We have recently shown that permeability pulmonary edema led to active expiratory glottic closure in awake newborn lambs while hypoxia (inspired O2fraction 8%; 15 min) did not. In the present study, we tested the hypothesis that expiratory glottic closure was accompanied by an increase in pharyngeal constrictor muscle expiratory electromyographic (EMG) activity. We studied seven awake nonsedated lambs aged 8–20 days. Airflow (facial mask + pneumotachograph), blood gases (arterial catheter), and EMG activity of both the thyroarytenoid muscle (a glottic adductor) and the inferior pharyngeal constrictor muscle were recorded before and after intravenous injection of halothane (0.05 ml/kg) to induce a permeability pulmonary edema. A central apnea (duration 15 s to 5 min) with continuous thyroarytenoid and inferior pharyngeal constrictor activity was observed within seconds after halothane injection. One lamb died despite rescuing maneuvers. An expiratory phasic thyroarytenoid and inferior pharyngeal constrictor muscle activity with simultaneous zero airflow gradually took place and, by 30 min after halothane injection, was present at each expiration in the six remaining lambs. Expiratory glottic and pharyngeal constrictor muscle EMG activity was subsequently present during the whole study period (1.5–5 h), even after correction of the initial hypoxia. Permeability lung edema was present at postmortem examination in all seven lambs. We conclude that a permeability pulmonary edema induced by intravenous halothane in nonsedated lambs enhances both glottic and pharyngeal constrictor muscle expiratory EMG. We hypothesize that expiratory contraction of the inferior pharyngeal constrictor muscle could participate in the active expiratory upper airway closure; this, in turn, might improve alveolocapillary gas exchange by increasing the end-expiratory lung volume.
Effect of different levels of hyperoxia on breathing in healthy subjects
Authors: Becker Heinrich F. , Polo Olli , McNamara Stephen G. , Berthon-Jones Michael , Sullivan Colin E.
Published: December 2017

Becker, Heinrich F., Olli Polo, Stephen G. McNamara, Michael Berthon-Jones, and Colin E. Sullivan. Effect of different levels of hyperoxia on breathing in healthy subjects. J. Appl. Physiol. 81(4): 1683–1690, 1996.—We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal [Formula: see text]([Formula: see text]) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with[Formula: see text] being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling[Formula: see text] in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (V˙i) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on[Formula: see text] led to a 16% increase inV˙i, but[Formula: see text] decreased by 3.6 Torr (9%). There was a linear correlation ( r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, withV˙i more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial[Formula: see text]. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.
Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier
Authors: Jerome E. Heidi , Enzan Keiji , Douguet Dominique , Lei Dachuan , Jesmok Gary , Johnson Carol W. , Neuburger Maritza , Staub Norman C.
Published: December 2017

Jerome, E. Heidi, Keiji Enzan, Dominique Douguet, Dachuan Lei, Gary Jesmok, Carol W. Johnson, Maritza Neuburger, and Norman C. Staub. Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier. J. Appl. Physiol. 81(4): 1730–1738, 1996.—Interleukin-2 (IL-2) is reputed to cause a “vascular leak syndrome.” We studied pulmonary hemodynamics and lymph dynamics in six sheep treated for 7 days with IL-2 (1.8 million IU/kg twice daily or 1.8 million IU/kg each day as a continuous infusion). Lung lymph flow increased from 4.8 ± 2 ml/15 min pre-IL-2 to 14.4 ± 6.8 ml/15 min on the seventh day of IL-2. The lymph-to-plasma protein concentration ratio was unchanged (0.70 ± 0.06 vs. 0.63 ± 0.13). The plasma-to-lymph equilibration half-time of radiolabeled albumin was 2.0 ± 0.6 h pre-IL-2 and 1.0 ± 0.7 h on day 7 of IL-2. Pulmonary arterial pressure was 24 ± 7 cmH2O pre-IL-2, increased to 32 ± 4 cmH2O on the fourth day of IL-2, and returned to 29 ± 5 cmH2O on the seventh day of IL-2. Extravascular lung water was normal (4.07 ± 0.25 g/g dry lung). To clearly determine whether the increase in lung lymph flow was due to hemodynamic changes or to increased leakiness of the microvascular barrier, we volume loaded six sheep with lactated Ringer solution before and after 3 days of IL-2 treatment (1.8 million IU/kg twice daily). Lung lymph flows increased fivefold during 4 h of crystalloid infusion compared with baseline and were higher after 3 days of IL-2. However, lymph-to-plasma protein concentration ratios decreased to the same low levels pre- and post-IL-2 (0.39 ± 0.06 vs. 0.41 ± 0.10), indicating an intact microvascular barrier. Extravascular lung water was elevated (5.56 ± 0.39 g/g dry lung) but was not different from lung water in three volume-loaded control sheep (4.87 ± 0.53 g/g dry lung). We conclude that IL-2 causes minimal or no injury to the pulmonary microvascular barrier and that volume expansion during IL-2 treatment can cause hydrostatic pulmonary edema.
Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate
Authors: Roberts A. C. , Butterfield G. E. , Cymerman A. , Reeves J. T. , Wolfel E. E. , Brooks G. A.
Published: December 2017

Roberts, A. C., G. E. Butterfield, A. Cymerman, J. T. Reeves, E. E. Wolfel, and G. A. Brooks. Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate. J. Appl. Physiol. 81(4): 1762–1771, 1996.—We tested the hypothesis that exposure to altitude decreases reliance on free fatty acids (FFA) as substrates and increases dependency on blood glucose. Therefore, the effects of exercise, hypobaric hypoxia, and altitude acclimatization on FFA, glycerol and net glucose uptake and release [ = 2(leg blood flow)(arteriovenous concentration)] and on fatty acid (FA) consumption by the legs (= 3 × glycerol release + FFA uptake) were measured. Because sympathetic responses have been implicated, we utilized nonspecific β-blockade and observed responses to exercise, altitude, and altitude acclimatization. We studied six healthy β-blocked men (β) and five matched controls (C) during rest and cycle ergometry exercise (88 W) at 49% of sea-level (SL) peak O2 uptake at the same absolute power output on acute altitude exposure (A1; barometric pressure = 430 Torr) and after 3 wk of chronic altitude exposure to 4,300 m (A2). During exercise at SL, FA consumption rates increased ( P < 0.05). On arrival at 4,300 m, resting leg FFA uptake and FA consumption rates were not significantly different from those at SL. However, after acclimatization to altitude, at rest leg FA consumption decreased to essentially zero in both C and β groups. During exercise at altitude after acclimatization, leg FA consumption increased significantly, but values were less than at SL or A1 ( P < 0.05), whereas glucose uptake increased relative to SL values. Furthermore, β-blockade significantly increased glucose uptake relative to control. We conclude that 1) chronic altitude exposure decreases leg FA consumption during rest and exercise; 2) relative to SL, FFA uptake decreases while glucose uptake increases during exercise at altitude; and 3) β-blockade potentiates these effects.
Dihedral angles of septal “bend” structures in lung parenchyma
Authors: Butler J. P. , Oldmixon E. H. , Hoppin F. G.
Published: December 2017

Butler, J. P., E. H. Oldmixon, and F. G. Hoppin, Jr.Dihedral angles of septal “bend” structures in lung parenchyma. J. Appl. Physiol. 81: 1800–1806, 1996.—Alveolar parenchyma comprises two interacting tensile systems: the cable system (a network of linear condensations of connective tissue) and the membrane system (a network of quasiplanar alveolar septa). Inferences can be drawn about the mechanics of this structure from its configuration. We reported earlier (E. H. Oldmixon, J. P. Butler, and F. G. Hoppin, Jr. J. Appl. Physiol. 64: 299–307, 1988) that the angles between alveolar septa at the common three-way junctions (J) are nearly uniform, indicating that septal tensions are also nearly uniform. We now report on the interseptal angles at the next most common class of septal junction (B), a structure where two septa meet along a segment of the cable system. We find, first, that the distributions of interseptal angles at B junctions have means >120°, are narrow, and have few, if any, angles <120°. The findings of uniform 120° angles at J junctions and a cutoff below 120° at B junctions are also characteristic of soap films supported on a frame, which follows the physical principle of surface area minimization. We suggest that this principle may be operative in parenchymal development and remodeling.
Contribution of nitric oxide and prostaglandins to reactive hyperemia in the human forearm
Authors: Engelke Keith A. , Halliwill John R. , Proctor David N. , Dietz Niki M. , Joyner Michael J. ,   (With the Technical Assistance of Darrell Loeffler and Tammy Eickhoff)
Published: December 2017

Engelke, Keith A., John R. Halliwill, David N. Proctor, Niki M. Dietz, and Michael J. Joyner. Contribution of nitric oxide and prostaglandins to reactive hyperemia in the human forearm. J. Appl. Physiol. 81(4): 1807–1814, 1996.—We investigated the separate and combined contributions of nitric oxide (NO) and vasodilating prostaglandins as mediators of reactive hyperemia in the human forearm. Forearm blood flow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol ( n = 12), measurements were made before and after intra-arterial administration of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) to one forearm. In a separate protocol ( n = 7), measurements were made before and after systemic administration of the cyclooxygenase inhibitor ibuprofen and again afterl-NMMA.l-NMMA reduced baseline FBF at rest (2.7 ± 0.4 to 1.6 ± 0.2 ml ⋅ 100 ml−1⋅ min−1; P < 0.05) and had a modest effect on peak forearm vascular conductance and flow (forearm vascular conductance = 31.1 ± 3.1 vs. 25.7 ± 2.5 ml ⋅ min−1⋅ 100 ml forearm−1⋅ 100 mmHg of perfusion pressure−1⋅ min−1, P < 0.05; FBF = 26.6 ± 2.9 vs. 22.8 ± 2.6 ml ⋅ 100 ml−1⋅ min−1, P = 0.055). Total excess flow above baseline during reactive hyperemia was unaffected byl-NMMA (14.3 ± 3.0 vs. 13.1 ± 2.3 ml/100 ml; P < 0.05). Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 ± 1.9 to 20.3 ± 2.7 ml ⋅ 100 ml−1⋅ min−1( P < 0.05), but had no effect on total excess flow above baseline. Infusion ofl-NMMA after ibuprofen reduced FBF at rest by 40%, had no effect on peak flow, but reduced total excess flow above baseline from 12.0 ± 2.5 to 7.6 ± 1.3 ml/100 ml ( P < 0.05). These data demonstrate that NO synthase inhibition has a modest effect on peak vasodilation during reactive hyperemia but plays a minimal role later. Prostaglandins appear to be important determinants of peak flow. The effects of NO synthase inhibition during reactive hyperemia may also be potentiated by concurrent cyclooxygenase inhibition.
An adjustable-current swimming pool for the evaluation of endurance capacity of mice
Authors: Matsumoto Keitaro , Ishihara Kengo , Tanaka Kazunori , Inoue Kazuo , Fushiki Tohru
Published: December 2017

Matsumoto, Keitaro, Kengo Ishihara, Kazunori Tanaka, Kazuo Inoue, and Tohru Fushiki. An adjustable-current swimming pool for the evaluation of endurance capacity of mice. J. Appl. Physiol. 81(4): 1843–1849, 1996.—A new forced-swimming apparatus for determining maximum swimming time in mice was devised for use in the evaluation of the endurance capacity of Std ddY and CDF1 mice after various diet and drug treatments. With the apparatus, a water current is generated by circulating water with a pump in a swimming pool. A spout and suction slit were contrived to generate a constant current while the strength of the current is regulated by a valve. The decrease in the leg-kicking intervals of mice accompanying the increase in the current speed confirmed that the workload is adjustable by regulation of the current speed. Compared with the number of forelimb strokes, that of the hindlimb kicks was greater. The swimming time until fatigue was observed to decrease with increasing current speed in the two strains of mice. As biochemical indexes, the blood lactate and muscle glycogen levels corroborated the correlation between current speed and increase in workload. These results indicate that the apparatus employed in the present study is suitable for the evaluation of the endurance capacity of mice and that it is useful for detecting the effects of dietary differences and drug pretreatments on this capacity.
Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia
Authors: Desplanches D. , Hoppeler H. , Tüscher L. , Mayet M. H. , Spielvogel H. , Ferretti G. , Kayser B. , Leuenberger M. , Grünenfelder A. , Favier R.
Published: December 2017

Desplanches, D., H. Hoppeler, L. Tüscher, M. H. Mayet, H. Spielvogel, G. Ferretti, B. Kayser, M. Leuenberger, A. Grünenfelder, and R. Favier. Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia. J. Appl. Physiol. 81(5): 1946–1951, 1996.—Twenty healthy high-altitude natives, residents of La Paz, Bolivia (3,600 m), participated in 6 wk of endurance exercise training on bicycle ergometers, 5 times/wk, 30 min/session, as previously described in normoxia-trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl. Physiol. 59: 320–327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometric pressure = 500 mmHg; inspired O2fraction = 0.209); a second group of 10 subjects was trained in acute normoxia (NT; barometric pressure = 500 mmHg; inspired O2fraction = 0.314). The workloads were adjusted to ∼70% of peak O2consumption (V˙o2 peak) measured either in hypoxia for the HT group or in normoxia for the NT group.V˙o2 peakdetermination and biopsies of the vastus lateralis muscle were taken before and after the training program.V˙o2 peakin the HT group was increased (14%) in a way similar to that in NT sea-level natives with the same protocol. Moreover,V˙o2 peakin the NT group was not further increased by additional O2delivery during the training session. HT or NT induced similar increases in muscle capillary-to-fiber ratio (26%) and capillary density (19%) as well as in the volume density of total mitochondria and citrate synthase activity (45%). It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity; however, their training response is similar to that of sea-level residents, independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia.
Central chemoreception in the region of the ventral respiratory group in the rat
Authors: Nattie Eugene E. , Li Aihua
Published: December 2017

Nattie, Eugene E., and Aihua Li. Central chemoreception in the region of the ventral respiratory group in the rat. J. Appl. Physiol. 81(5): 1987–1995, 1996.—We injected acetazolamide (AZ; 5 × 10−6 M, 1 nl) into the region of the ventral respiratory group (VRG) of anesthetized paralyzed ventilated rats. Control injections (mock cerebrospinal fluid, n = 6, or the inactive AZ analogue 2-acetylamino-1,3,4-thiadiazole-5-sulfon- t-butylamide, n = 6) did not increase the integrated phrenic neurogram [phrenic nerve amplitude (PNA)]. The AZ injections produced a focal region of tissue acidosis with a radius < 300–400 μm and are used as a probe for sites of central chemosensitivity. Injection location is determined by anatomic analysis. Of 22 VRG injections of AZ, 14 increased the amplitude of the PNA over 15–90 min; 8 had no effect. In 17 cases, we measured medullary tissue pH at the injection center and/or at a distant site and reaffirmed the size of the acidotic region produced by such small AZ injections. Of injections with pH electrodes within 300–400 μm of the injection center, all responders showed an acid pH; three nonresponders showed an acid pH, and one an alkaline pH. In a subgroup of five rats, at VRG sites with known respiratory effects identified by prior glutamate injection (10 nl, 100 mM), all subsequent AZ injections produced a PNA response. Simultaneous measurement of PNA and tissue pH responses at the injection center of eight rats did not show a uniform correlation in time; initially, both changed with a similar time course, but PNA recovered more quickly. We conclude that 1) the region of the VRG contains sites of ventilatory chemoreception, 2) ineffective AZ injections do produce a tissue acidosis but at sites with minimal impact on breathing, and 3) tissue pH does not uniquely represent the chemoreceptor stimulus.
Analysis of respiratory water—a new method for evaluation of myocardial energy metabolism
Authors: Schwanke Uwe , Strauss Harald , Arnold Gunther , Schipke Jochen D.
Published: December 2017

Schwanke, Uwe, Harald Strauss, Gunther Arnold, and Jochen D. Schipke. Analysis of respiratory water—a new method for evaluation of myocardial energy metabolism. J. Appl. Physiol. 81(5): 2115–2122, 1996.—Aerobic ATP synthesis via oxidative phosphorylation causes a proportional production of respiratory water. Thus the amount of respiratory water produced at a given time should be a reliable measure of the current ATP demand of the mammalian myocardium. Respiratory water from isolated rabbit hearts was labeled by using the stable oxygen isotope18O. The hearts were perfused according to the method of Langendorff (O. Langendorff. Pfluegers Arch. 61: 291–332, 1895) with18O2-equilibrated Krebs-Henseleit solution. Control hearts were exclusively perfused with carbogen-equilibrated Krebs-Henseleit solution. Myocardial tissue was then lyophilized; the extracted water and samples from the coronary venous effluent were converted to CO2by using the guanidine hydrochloride technique. The δ18O values within the CO2samples were determined by mass spectrometry and related to the standard mean ocean water (smow) scale. Compared with control hearts, the18O-labeled hearts exhibited a significant increase of δ18O values from tissue water (−47.50 ± 0.64 vs. −40.35 ± 2.05‰smow; P < 0.05). The values were also significantly increased in the coronary venous effluent after a perfusion time of only 50 s (−47.50 ± 0.64 vs. −43.66 ± 0.91‰ smow; P < 0.05). Thus this first adaptation of the guanidine hydrochloride technique on microliter samples of myocardial tissue water and coronary venous effluent demonstrates that this method can be used to evaluate both respiratory activity and the kinetics of cardiac metabolic processes.