bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthritis
Authors: Baslund B. , Lyngberg K. , Andersen V. , Halkjaer Kristensen J. , Hansen M. , Klokker M. , Pedersen B. K.
Published: December 2017

The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity. Maximal O2 uptake increased significantly, whereas heart rate at stage 2 and rate of perceived exertion decreased significantly, in the training group compared with the controls. Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training. Training did not induce changes in blood mononuclear cell subpopulations, proliferative response, or natural killer cell activity. Furthermore the plasma concentrations of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in response to training. It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis.
Adaptive buffering of breath-by-breath variations of end-tidal CO2 of humans
Authors: Modarreszadeh M. , Kump K. S. , Chizeck H. J. , Hudgel D. W. , Bruce E. N.
Published: December 2017

We have designed and implemented a computer-controlled system that uses an adaptive control algorithm (generalized minimum variance) to buffer the breath-by-breath variations of the end-tidal CO2 fraction (FETCO2) that occur spontaneously or are exaggerated in certain experimental protocols (e.g., induced hypoxia, any type of induced variations in the ventilatory pattern). Near the end of each breath, FETCO2 of the following breath is predicted and the inspired CO2 fraction (FICO2) of the upcoming breath is adjusted to minimize the difference between the predicted and desired FETCO2 of the next breath. The one-breath-ahead prediction of FETCO2 is based on an adaptive autoregressive with exogenous inputs (ARX) model: FETCO2 of a given breath is related to FICO2, FETCO2 of the previous breath, and inspiratory ventilation. Adequacy of the prediction is demonstrated using data from experiments in which FICO2 was varied pseudorandomly in wakefulness and sleep. The algorithm for optimally buffering changes in FETCO2 is based on the coefficients of the ARX model. We have determined experimentally the frequency of FETCO2 variations that can be buffered adequately by our controller, testing both spontaneous variations in FETCO2 and variations induced by hypoxia in young awake human subjects. The controller is most effective in buffering variations of FETCO2 in the frequency range of <0.1 cycle/breath. Some potential applications are discussed.
Direct measurement of pulmonary microvascular distensibility
Authors: Hillier S. C. , Godbey P. S. , Hanger C. C. , Graham J. A. , Presson R. G. , Okada O. , Linehan J. H. , Dawson C. A. , Wagner W. W.
Published: December 2017

Pulmonary vascular distensibility has an important influence on pulmonary hemodynamics. Although many measurements of distensibility have been made on large pulmonary vessels, there is less information on microvascular distensibility. We have measured the distensibility of the smallest (< 70-microns-diam) precapillary arterioles and postcapillary venules. Isolated dog lobes, at 2.5 cmH2O transpulmonary pressure, were perfused at low flows, which caused the arteriovenous pressure gradient to be very small and thereby permitted accurate estimation of microvascular pressure. As microvascular pressure was systematically varied between 0 and 30 mmHg, subpleural microvascular diameters were determined from computer-enhanced images obtained by videomicroscopy. Arteriolar and venular distensibilities were not different from each other. The microvascular pressure-diameter relationship was alinear with distensibility coefficients of 1–3% mmHg-1, values that are of the same order of magnitude as previously measured distensibilities of 100- to 1,000-microns-diam canine pulmonary vessels.
Metabolic responses to head-down suspension in hypophysectomized rats
Authors: Woodman C. R. , Tipton C. M. , Evans J. , Linderman J. K. , Gosselink K. , Grindeland R. E.
Published: December 2017

Rats exposed to head-down suspension (HDS) exhibit reductions in maximal O2 consumption (VO2max) and atrophy of select hindlimb muscles. This study tested the hypothesis that an endocrine-deficient rat exposed to HDS would not exhibit reductions in VO2max or hindlimb muscle mass. Hypophysectomized (HYPX) and sham-operated (SHAM) rats were tested for VO2max before and after 28 days of HDS or cage control (CC) conditions. No significant reductions in VO2max were observed in HYPX rats. In contrast, SHAM-HDS rats exhibited a significant reduction in absolute (-16%) and relative (-29%) measures of aerobic capacity. Time course experiments revealed a reduction in VO2max in SHAM-HDS rats within 7 days, suggesting that cardiovascular adjustments to HDS occurred in the 1st wk. HDS was associated with atrophy of the soleus (-42%) in SHAM rats, whereas HYPX rats exhibited atrophy of the soleus (-36%) and plantaris (-13%). SHAM-HDS rats had significantly lower (-38%) soleus citrate synthase activities per gram muscle mass than SHAM-CC, but no significant differences existed between HYPX-HDS and -CC rats. HDS rats had an impaired ability to thermoregulate, as indicated by significantly greater temperature increases per unit run time, compared with their CC counterparts. Pretreatment plasma epinephrine levels were significantly lower in HYPX than in SHAM rats. Norepinephrine concentration was similar for all groups except HYPX-HDS, in which it was significantly higher. HDS had no significant effect on thyroxine or triiodothyronine. SHAM-HDS rats had significantly lower concentrations of testosterone and growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
Theoretical basis for time 0 correction in the rebreathing analysis
Authors: Verbanck S. , Paiva M.
Published: December 2017

The uptake of a soluble gas during rebreathing is simulated in a compartmental model. The lung is assumed to consist of two parallel units, each one divided into three compartments: a personal dead space, an alveolar space, and a tissue volume. These units are connected to the rebreathing bag via a common dead space. Gas exchange is incorporated into the model for a given cardiac output. Inert and soluble gas concentrations are computed as a function of time in the various compartments by means of differential equations. Using different initial conditions, we simulate time-dependent concentration traces “at the mouth” and estimate the errors made by traditional analysis of the end-tidal gas concentrations with respect to the “time 0” correction method as was first proposed by Sackner et al. (Am. Rev. Respir. Dis. 111:157–165, 1975). We provide a theoretical basis for this correction method and outline the conditions that need to be fulfilled for its application. We show that the tissue volume and cardiac output estimates are less affected by ventilation and perfusion inhomogeneities when the time 0 correction method is used. This is particularly relevant for the expected increase in tissue volume in microgravity where ventilation and perfusion inhomogeneities are expected to be attenuated.
Gastric intramural PCO2 as monitor of perfusion failure during hemorrhagic and anaphylactic shock
Authors: Tang W. , Weil M. H. , Sun S. , Noc M. , Gazmuri R. J. , Bisera J.
Published: December 2017

Indirect measurement of gastric intramural pH (pHG) utilizing a luminal tonometer in the stomach has been proposed for monitoring the severity and progression of perfusion failure. In the present study, we investigated gastric PCO2 and pHG as indicators and quantitators of the severity of perfusion failure in the experimental rodent model of both hemorrhagic and anaphylactic shock. Gastric intramural PCO2 (PGCO2) and pHG were directly measured with miniaturized sensors inserted into the anterior wall of the stomach. In hemorrhagic shock, animals were bled into a reservoir maintained at a pressure of 35 mmHg. pHG decreased from 7.39 +/- 0.08 to 6.67 +/- 0.11 (P < 0.01), and PGCO2 increased from 53 +/- 4 to 136 +/- 3 Torr (P < 0.01). Anaphylactic shock was induced in animals that had been sensitized 21 days before with crystallized ovalbumin. Antigen challenge produced an immediate reduction in mean aortic pressure from 144 to 60 mmHg. pHG decreased from 7.40 +/- 0.05 to 6.99 +/- 0.07 (P < 0.01), and PGCO2 increased from 48 +/- 5 to 133 +/- 9 Torr (P < 0.01). The increases in PGCO2 were highly correlated with decreases in gastric blood flow in both hemorrhagic (r = 0.96) and anaphylactic shock (r = 0.92). The correlations with pHG were more moderate. These experiments demonstrated prominent increases in PGCO2 and H+ during both hemorrhagic and anaphylactic shock. We further noted that the estimation of pHG based on the assumption that HCO3-concentrations of the stomach wall and arterial blood are the same was not fully sustained.
Effect of chronic thromboembolism on the pulmonary artery pressure-flow relationship in dogs
Authors: Olman M. A. , Gan R. Z. , Yen R. T. , Villespin I. , Maxwell R. , Pedersen C. , Konopka R. , Debes J. , Moser K. M.
Published: December 2017

To understand the hemodynamic alterations associated with chronic thromboembolic pulmonary hypertension, the large pulmonary arteries of mongrel dogs were chronically obstructed with lysis-resistant thrombi. Pulmonary hemodynamics were experimentally measured and described by multipoint pulmonary arterial pressure (PAP) vs. flow plots. In nine anesthetized chronically embolized dogs, but not in six control dogs, the PAP-flow line shifted significantly upward in a parallel fashion by 4.2 +/- 0.7 mmHg. The postembolic pulmonary circulation was further characterized by predictions from a morphometric-based elastic tube and sheet flow model of the canine pulmonary circulation. After model validation with the preembolic PAP-flow data, the derived postembolic PAP matched the in vivo results to within 1 mmHg. A detailed analysis of the model-derived PAP drop revealed that the PAP-flow line shift can be accounted for by a novel fixed resistor in the largest obstructed pulmonary artery.
Xanthine oxidase promotes neutrophil sequestration but not injury in hyperoxic lungs
Authors: Moores H. K. , Beehler C. J. , Hanley M. E. , Shanley P. F. , Stevens E. E. , Repine J. E. , Terada L. S.
Published: December 2017

Neutrophil accumulation in alveolar spaces is a conspicuous finding in hyperoxia-exposed lungs. We hypothesized that xanthine oxidase (XO)-derived oxidants contribute to retention of neutrophils in hyperoxic lungs. Rats were subjected to normobaric hyperoxia (100% O2) for 48 h, and lungs were assessed for neutrophil sequestration (morphometry and lavage cell counts) and injury (lavage albumin levels and lung weights). In rats exposed to hyperoxia, we found increased (P < 0.05) lung neutrophil retention, lavage albumin levels, and lung weights compared with normoxia-exposed control rats. Suppression of XO activity by pretreatment with allopurinol decreased (P < 0.05) lung neutrophil retention but increased (P < 0.05) lavage albumin concentrations and lung weights in hyperoxic rats. Allopurinol treatment had no effect (P > 0.05) on the numbers of macrophages or lymphocytes recoverable by lung lavage. Depletion of XO activity by an independent method, tungsten feeding, also decreased (P < 0.05) lung lavage neutrophil counts and increased (P < 0.05) lavage albumin concentrations. We conclude that XO may be involved in lung neutrophil retention but not lung injury during exposure to hyperoxia.
Differential reflex control of forearm and calf resistance vessels by chemosensitive cardiac afferent activation
Authors: Jacobsen T. N. , Lange R. A. , Olivari M. T. , Yancy C. W. , Horn V. P. , Ring W. S. , Baldwin B. J. , Cooley R. A. , Victor R. G.
Published: December 2017

The aim of this study was to determine whether chemosensitive ventricular afferent activation in humans evokes a diffuse pattern of reflex vasodilation involving the skeletal muscle circulation of all the extremities or a highly specified pattern of vasodilation that is limited to the rather small vascular bed of the forearm. In 10 patients with innervated ventricles and 7 patients with denervated ventricles resulting from heart transplantation, we performed simultaneous plethysmographic recordings of blood flow in the forearm and calf during chemosensitive ventricular afferent activation with intracoronary Renografin. In patients with innervated ventricles, intracoronary Renografin evoked directionally opposite vascular responses in the forearm and calf: forearm resistance decreased from 50 +/- 11 to 31 +/- 8 units, whereas calf resistance increased from 42 +/- 7 to 59 +/- 9 units (P < 0.05, calf vs. forearm). Forearm vasodilation was eliminated after heart transplantation, indicating that this is a reflex response caused by ventricular afferents. In contrast, calf vasoconstriction was well preserved despite ventricular deafferentation, indicating that this response is caused by mechanisms other than ventricular afferent activation, possibly the sinoaortic baroreceptors. Taken together, these findings document a remarkable degree of specificity in the effects of cardiac afferent activation on the reflex regulation of regional vasomotor tone in humans.
Effect of acceleration on the chest wall
Authors: Wilson T. A. , Liu S.
Published: December 2017

The gravitational force on the rib cage has been found to be an expiratory force of approximately 8 cmH2O. The gravitational force on the abdomen is an inspiratory force of the same magnitude. Because the compliance of the rib cage is greater than the compliance of the abdomen, it follows that gravity has a net expiratory effect on lung volume and that upward accelerations augmenting the gravitational force would have an additional expiratory effect. This conclusion is contrary to observations that functional residual capacity increases during headward accelerations in centrifuges and during intervals of upward acceleration in airplanes. We report the results of two studies of the effects of accelerations that are smaller in magnitude and of shorter duration than those studied in centrifuges and airplanes. The first was an experimental study of the effect of acceleration in an elevator. In subjects who relaxed against an occluded airway, airway pressure increased during upward accelerations and decreased during downward accelerations. The second was the modeling and analysis of the effects of the accelerations that occur during walking. The analysis predicted an initial expiratory response to the acceleration spike that occurs during footfall. The prediction agreed with data in the literature on the respiratory effect of walking. In both of these studies upward accelerations had an expiratory effect.
Changes in airway resistance during sleep onset
Authors: Kay A. , Trinder J. , Bowes G. , Kim Y.
Published: December 2017

Ventilation is lower during sleep than wakefulness. An increase in airway resistance has been proposed as the critical factor. As the change in ventilation has been shown to occur abruptly at transitions between alpha and theta electroencephalogram activity, it was of interest to determine whether the increase in airway resistance between wakefulness and sleep also occurs at these transitions. Three young healthy male subjects were run for an average of 15 sleep onsets in each of three conditions. The three conditions were 1) an esophageal balloon was put in place to allow the measurement of airway resistance, 2) in addition to an esophageal balloon the nose was occluded, and 3) there was no esophageal balloon and the nose was not occluded. Ventilation and airway resistance were measured during sleep onset and analyzed as a function of arousal state. In those conditions of the experiment in which airway resistance was affected by state, the changes, like those in ventilation, occurred at transitions between alpha and theta electroencephalogram activity. However, in the three subjects studied, the magnitude of ventilatory changes at alpha-theta transitions and the extent to which changes in ventilation were associated with changes in airway resistance differed between subjects. It was concluded that although inspiratory airway resistance is a major component affecting the state-related changes in ventilation at sleep onset, the degree of its contribution may vary over individuals.
Effects of pregnancy and chronic exercise on respiratory responses to graded exercise
Authors: Wolfe L. A. , Walker R. M. , Bonen A. , McGrath M. J.
Published: December 2017

Effects of cycle ergometer conditioning (heart rate 143 +/- 2 beats/min, 25 min/session, 3 sessions/wk) during the second and third trimesters of pregnancy were studied in 18 healthy previously sedentary women. A nonexercising control group (n = 9) was also studied. Graded exercise tests were conducted for both groups at approximately 17, 27, and 37 wk of gestation and at 20 wk postpartum. Both groups exhibited augmented ventilatory responses to exercise throughout pregnancy. Significant aerobic conditioning effects observed in the exercised group between entry and third trimester of pregnancy testing included a 17% increase in oxygen pulse at peak exercise, reduction in the respiratory exchange ratio during standard submaximal exercise, and an increase in work rate at the onset of blood lactate accumulation. Onset of blood lactate accumulation did not change significantly in the control group. Respiratory exchange ratio at peak exercise was higher in postpartum tests compared with those conducted in late gestation in both groups. Peak postexercise lactate levels were also significantly lower in second and third trimesters of pregnancy testing compared with postpartum in the control group. This effect appeared to be prevented by physical conditioning in the exercised group. The study results support the hypothesis that moderate aerobic conditioning increases maximal aerobic power and the capacity for sustained submaximal exercise. Chronic exercise also appeared to help to preserve anaerobic working capacity in late gestation.
Effect of metabolic rate on ventilatory roll-off during hypoxia
Authors: Gershan W. M. , Forster H. V. , Lowry T. F. , Korducki M. J. , Forster A. L. , Forster M. A. , Ohtake P. J. , Aaron E. A. , Garber A. K.
Published: December 2017

This study was done to determine 1) whether goats demonstrate the roll-off phenomenon, i.e., a secondary decrease in minute ventilation (VE), after an initial hyperventilation during various levels of hypoxia and, if so, 2) whether roll-off could be due to changes in metabolic rate. We hypothesized that roll-off occurs in the goat during hypoxia but is not due to hypometabolism. To answer question 1, eight unanesthetized adult goats were exposed to 15–20 min of hypoxia at 0.15, 0.12, and 0.09 inspired O2 fraction (FIO2), resulting in 60, 40, and 30 Torr arterial PO2, respectively. Goats were fitted with a face mask connected to a spirometer to measure VE, and arterial blood gas samples were obtained via carotid arterial catheters. Roll-off was seen with 0.15 and 0.12 FIO2, whereas VE steadily increased with 0.09 FIO2. During hypoxia, arterial PCO2 fell 2, 3, and 7 Torr at 0.15, 0.12, and 0.09 FIO2, respectively. In the second series of experiments, nine different goats were exposed to 30 min of 0.12 FIO2. O2 consumption and CO2 production were measured five times during baseline and hypoxia. VE increased to 32% above baseline values after 2 min of hypoxia and then gradually decreased by 18%. Changes in breathing frequency and tidal volume contributed to the roll-off. O2 consumption decreased (P = 0.0029, analysis of variance) and CO2 production increased (P = 0.0027) during hypoxia, although both changes were small (< 7%) compared with the eventual 18% decrease in VE. We conclude that the adult goat demonstrates the roll-off phenomenon during moderate levels of hypoxia. (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of alveolated duct structure on aerosol kinetics. II. Gravitational sedimentation and inertial impaction
Authors: Tsuda A. , Butler J. P. , Fredberg J. J.
Published: December 2017

We studied the effects of alveolated duct structure on deposition processes for particle diameters > or = 1 micron. For such large particles, Brownian motion is insignificant but gravity and inertial forces play an important role. A Lagrangian description of particle dynamics in an alveolated duct flow was developed, and computational analysis was performed over the physiologically relevant range. At low flow rates gravity caused deposition. Gravitational cross-streamline motion depended on the coupled effects of curvature of gas streamlines and duct orientation relative to gravity. The detailed convective flow pattern was an important factor in determining deposition. At higher flow rates, inertial impaction contributed markedly to deposition. The curved nature of streamlines again played a major role on deposition, but duct orientation had little effect. In the medium range of flow rates, both gravitational and inertial forces simultaneously influenced particle motion. Particle inertia, per se, did not cause deposition but substantially suppressed gravitational deposition. The deposition mechanism was complex; contrary to what is often assumed in past analyses, the interaction between gravitational and inertial effects could not be described in a simple additive fashion. We conclude that the structure of the alveolar duct has an important role in gravitational sedimentation and inertial impaction in the lung acinus.
Reflex effects of lung inflation on tracheomotor tone observed during apnea produced by the Hering-Breuer reflex
Authors: Coon R. L.
Published: December 2017

Reflex effects of static pressure lung inflation (SLI) on tracheomotor tone (TT) were studied during apnea produced by the Hering-Breuer expiratory-facilitatory reflex. Anesthetized dogs were placed on cardiopulmonary bypass, and diaphragm electromyogram was used as an indicator of central nervous system inspiratory output. Tracheomotor tone (TT) was reflexly produced by chemoreceptor stimulation. The volume and frequency of the ventilator [phasic lung inflation (PLI)] were adjusted to produce nearly a maximum reflex decrease in TT. The increase in TT observed while PLI was withheld (0 mmHg tracheal pressure) for 1–2 min was used as the control response. SLIs were interspersed among sets of PLIs. Although SLI produced apnea, TT returned toward the control TT recorded during 0 mmHg tracheal pressure. TT observed during apnea was reflexly sensitive to further increases in SLI and to changes in chemoreceptor stimulation, which also affected the time course of the tracheomotor responses. These results suggest that the reflex decrease in TT produced by SLI and the Hering-Breuer expiratory-facilitatory reflex are mediated by different central mechanisms but may be from the same or different pulmonary receptors.
Effects of estradiol on lipoprotein lipase activity and lipid availability in exercised male rats
Authors: Ellis G. S. , Lanza-Jacoby S. , Gow A. , Kendrick Z. V.
Published: December 2017

The effects of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1 x 100 g body wt-1) and exercise on tissue lipid content and lipoprotein lipase (LPL) activity were determined in male rats. Estradiol administration significantly (P < 0.05) increased fatty acid contents of resting adipose, plasma, and white and red vastus muscle tissues and red vastus muscle triacylglycerol. Adipose and plasma fatty acids and red and white vastus muscle triacylglycerol were significantly higher in exercised estradiol-administered animals than in exercised oil-administered animals. Estradiol administration significantly reduced resting adipocyte LPL activity by 71% and increased myocardial LPL activity by 96%. After exercise, red vastus LPL activity was significantly increased by 76% in estradiol-administered animals compared with oil-administered animals. Ratios of red vastus to adipose LPL activity and myocardial to adipose LPL activity at rest and after exercise were significantly greater in estradiol-administered than in oil-administered animals. Estradiol administration significantly increased the ratio of white vastus to adipose LPL activity of exercised animals. These data indicate that estradiol increases the availability of lipid substrate to exercising muscle from multiple sources, including adipose, plasma, and intracellular muscle triacylglycerol. The absolute increases in muscle LPL activity, combined with a greater ratio of muscle to adipose LPL activity, lead to increased distribution of plasma triacylglycerol-derived fatty acids toward muscle.
Role of epinephrine during insulin-induced hypoglycemia in fasted rats
Authors: Winder W. W. , MacLean P. S. , Chandler S. L. , Huang W. , Mills R. H.
Published: December 2017

Responses to insulin-induced hypoglycemia in fasted sham-operated (SHAM), adrenodemedullated (ADM), and epinephrine-infused ADM (ADM + E) rats were studied to ascertain the specific role of epinephrine in increasing resting skeletal muscle content of adenosine 3′,5′-cyclic monophosphate (cAMP) and fructose 2,6-bisphosphate (F-2,6-P2), which are involved in stimulation of muscle glycogenolysis and lactate production. Rats from each group were fasted for 24 h and then infused intravenously with insulin (30, 60, or 90 min) to produce plasma insulin values of approximately 92 microU/ml. One-half of the insulin-infused ADM rats were also infused with epinephrine (ADM + E). Muscle and blood lactate, muscle cAMP, and muscle F-2,6-P2 increased and muscle glycogen decreased in SHAM rats. Each of these changes was prevented or attenuated in ADM rats and restored in ADM + E rats. Liver cAMP, glycogen, and F-2,6-P2 responses to hypoglycemia were similar in SHAM, ADM, and ADM + E rats. Blood glucose decreased to 0.74 +/- 0.05 mM in ADM rats compared with 1.54 +/- 0.11 mM in SHAM and 1.34 +/- 0.15 mM in ADM + E rats after 90 min of insulin infusion. The increase in plasma epinephrine is therefore essential in the counterregulatory response to insulin-induced hypoglycemia in fasted rats. Resting skeletal muscle glycogenolysis and lactate production for hepatic gluconeogenic substrate appear to be important components of the counterregulatory response in fasted rats.
Accurate method to study static volume-pressure relationships in small fetal and neonatal animals
Authors: Suen H. C. , Losty P. D. , Donahoe P. K. , Schnitzer J. J.
Published: December 2017

We designed an accurate method to study respiratory static volume-pressure relationships in small fetal and neonatal animals on the basis of Archimedes' principle. Our method eliminates the error caused by the compressibility of air (Boyle's law) and is sensitive to a volume change of as little as 1 microliters. Fetal and neonatal rats during the period of rapid lung development from day 19.5 of gestation (term = day 22) to day 3.5 postnatum were studied. The absolute lung volume at a transrespiratory pressure of 30–40 cmH2O increased 28-fold from 0.036 +/- 0.006 (SE) to 0.994 +/- 0.042 ml, the volume per gram of lung increased 14-fold from 0.39 +/- 0.07 to 5.59 +/- 0.66 ml/g, compliance increased 12-fold from 2.3 +/- 0.4 to 27.3 +/- 2.7 microliters/cmH2O, and specific compliance increased 6-fold from 24.9 +/- 4.5 to 152.3 +/- 22.8 microliters.cmH2O-1.g lung-1. This technique, which allowed us to compare changes during late gestation and the early neonatal period in small rodents, can be used to monitor and evaluate pulmonary functional changes after in utero pharmacological therapies in experimentally induced abnormalities such as pulmonary hypoplasia, surfactant deficiency, and congenital diaphragmatic hernia.
Tissue oxygen and carbon dioxide stores and breath-hold diving in humans
Authors: Liner M. H. , Linnarsson D.
Published: December 2017

Alveolar gas exchange was studied in 11 submerged subjects during and after 75-s breath holds with or without a transient increase of ambient pressure to 3 ATA (20 msw). During surface breath holds (SBH), cardiac index fell to 73% of eupneic control but was partially restored at depth to 88% of control during breath-hold dives (BHD). O2 uptake fell to 84% of control during SBH and was restored to control level during BHD. The turnover of O2 stores was much slower during SBH than during the ensuing recovery. Carbon dioxide store dynamics were markedly slowed after BHD. We conclude that SBH and BHD are associated with large shifts in tissue O2 and CO2 stores and that much of these shifts can be explained by primary circulatory events. The changes in turnover rate for tissue O2 and CO2 stores could not be explained by the cardiac index changes alone but were compatible with peripheralization of venous blood volume and preferential peripheral vasoconstriction induced by apnea with elevated intrathoracic pressure during SBH. The transient compression during BHD reversed these central and peripheral circulatory changes by counteracting the increase in intrathoracic pressure.
Influence of exercise training on myocardial beta-adrenergic signal transduction: differential regulation with age
Authors: Scarpace P. J. , Shu Y. , Tumer N.
Published: December 2017

Exercise training is known to increase cardiovascular performance and decrease heart rate. Because activation of adenylyl cyclase is an important factor in beta-adrenergic signal transduction and in the decline in signal transduction with age, we hypothesized that some of the effects of exercise training may be mediated by changes in postreceptor activation of adenylyl cyclase. To this end, we assessed isoproterenol-, G protein-, and forskolin-mediated activation of adenylyl cyclase as well as G protein immunoreactivity in the myocardium from young and senescent F-344 rats with and without prior exercise training by treadmill running. Isoproterenol, beta-gamma-imidoguanosine 5′-triphosphate, and forskolin stimulation of adenylyl cyclase activity declined by approximately 50% with age. Training increased the stimulation in the senescent rats and decreased the stimulation in the young rats such that the age-related decline in signal transduction was no longer significant. Gs alpha protein immunoreactivity was unchanged by age or training. These data suggest that in young rats exercise training decreases beta-adrenergic signal transduction, whereas in older rats training increases signal transduction, partially offsetting the decline in signal transduction with age.
Dietary effects on exercising muscle metabolism and performance by 31P-MRS
Authors: Larson D. E. , Hesslink R. L. , Hrovat M. I. , Fishman R. S. , Systrom D. M.
Published: December 2017

To determine how diet modulates short-term exercise capacity, skeletal muscle pH and bioenergetic state were examined by 31P-magnetic resonance spectroscopy in nine healthy volunteers. Subjects performed incremental quadriceps exercise to exhaustion after 5 days of high-carbohydrate (HCHO) or high-fat (HFAT) diet randomly assigned in crossover fashion and separated by a 2.5-day period of ad libitum mixed diet. Simultaneous measurements were made of pulmonary gas exchange, minute ventilation, and quadriceps muscle pH and phosphorylation potential. At rest and peak exercise, respiratory exchange ratio and minute ventilation were higher after HCHO than after HFAT (P < 0.05), reflecting greater CHO utilization. Peak O2 consumption (VO2) was not increased after HCHO (P > 0.05), but exercise duration was (339 +/- 34 s for HCHO vs. 308 +/- 25 s for HFAT; P < 0.05). HCHO was associated with a blunted early fall of phosphocreatine (PCr)/Pi vs. VO2 (-4.1 +/- 0.7 x 10(-2) min/ml for HCHO vs. -5.6 +/- 1.2 x 10(-2) min/ml for HFAT; P < 0.05). On both study days, the slope of PCr/Pi vs. VO2, before and after the PCr threshold, was correlated with exercise time. The results suggest that a diet rich in CHO improves exercise efficiency through beneficial effects on intracellular phosphorylation potential.
Effect of an inhaled corticosteroid on airway eosinophils and allergen-induced airway hyperresponsiveness in dogs
Authors: Woolley M. J. , Wattie J. , Ellis R. , Lane C. G. , Stevens W. H. , Woolley K. L. , Dahlback M. , O'Byrne P. M.
Published: December 2017

The presence of airway eosinophils before allergen inhalation may contribute to the development of allergen-induced airway responses. We examined whether a reduction in airway eosinophil numbers before allergen inhalation as a result of inhalation of the corticosteroid budesonide would prevent allergen-induced airway hyperresponsiveness in seven dogs. Acetylcholine airway responsiveness was measured before and 24 h after inhalation of Ascaris suum allergen (10(-6)-10(-2) wt/vol) or its diluent on 4 test days separated by > or = 4 wk. Dogs were pretreated for 7 days before and on the morning of each test day with inhaled budesonide (2.69 mg/day) or a placebo (lactose). Airway eosinophil numbers were assessed by bronchoalveolar lavage. Inhaled budesonide significantly reduced the number of airway eosinophils before allergen inhalation from 3.6 +/- 2.38 x 10(4) (SE) cells/ml after inhaled lactose to 0.3 +/- 0.21 x 10(4) cells/ml after inhaled budesonide (P = 0.028). The decrease in eosinophil number was associated with a significant reduction in allergen-induced airway hyperresponsiveness (P = 0.005). These results support the hypothesis that the number of eosinophils in the airways before allergen inhalation is an important determinant in the development of allergen-induced airway hyperresponsiveness in dogs.
Downregulation of pulmonary atrial natriuretic peptide receptors in rats exposed to chronic hypoxia
Authors: Klinger J. R. , Arnal F. , Warburton R. R. , Ou L. C. , Hill N. S.
Published: December 2017

We hypothesized that a downregulation in pulmonary atrial natriuretic peptide (ANP) receptors helps raise plasma ANP levels during chronic hypoxia. We measured in vivo pulmonary uptake and plasma clearance of 125I-ANP and in vitro pulmonary binding kinetics of 125I-ANP in normoxic and chronically hypoxic rats. Exposure to 21 days of hypobaric (0.5 atm) hypoxia did not decrease specific binding of 125I-ANP in the kidney, but pulmonary binding decreased 35 and 75% after 1 and 3 days of hypoxia, respectively, and increased 200% after 3 days of normoxic recovery from 21 days of hypoxia. The total binding capacity for ANP to lung membrane fractions from normoxic rats, chronically hypoxic rats, and rats that had recovered from hypoxia was 488 +/- 59, 109 +/- 17, and 338 +/- 48 fmol/mg, respectively (P < 0.05 for hypoxic vs. normoxic or recovered lung membranes). The area under the 125I-ANP plasma concentration curve for normoxic and hypoxic rats and normoxic rats that were infused with the ANP C-receptor ligand C-ANF-(4–23) was 3,292 +/- 216, 5,022 +/- 466, and 8,205 +/- 1,059 disintegrations.min-1.ml–1, respectively [P < 0.05 for hypoxic vs. normoxic or C-ANF-(4–23)-infused rats]. We conclude that pulmonary ANP clearance is reduced during chronic hypoxia secondary to a downregulation in pulmonary ANP clearance receptors. Reduced pulmonary clearance of ANP may represent an adaptation that contributes to increased plasma ANP levels during chronic hypoxia.
Abdominal muscle activity during hypercapnia in awake dogs
Authors: Leevers A. M. , Road J. D.
Published: December 2017

We previously found the internal abdominal muscle layer to be preferentially recruited during expiratory threshold loading in anesthetized and awake dogs. Expiratory threshold loading increases end-expiratory lung volume and hence can activate reflex pathways such as tonic vagal reflexes, which could influence abdominal muscle recruitment. Our objectives in the present study were to determine the effects of hypercapnia on abdominal muscle activation and the pattern of recruitment in awake dogs. Five tracheotomized dogs were chronically implanted with sonomicrometer transducers and fine-wire electromyogram (EMG) electrodes in each of the four abdominal muscles: transversus abdominis, internal oblique, external oblique, and rectus abdominis. Muscle length changes and EMG activity were studied in the awake dog at rest and during CO2 rebreathing. CO2 rebreathing produced a tripling of tidal volume and activation of the abdominal muscles. Despite the increase in tidal volume, there was no significant change in abdominal muscle end-inspiratory length. Both tonic and phasic expiratory shortening were greater in the internal muscle layer (transversus abdominis and internal oblique) than in the external muscle layer (external oblique and rectus abdominis). We conclude that the internal abdominal muscles are preferentially recruited by hypercapnia and vagal reflexes probably do not contribute to this differential recruitment but that segmental reflexes may be involved. The mechanical consequences of this recruitment are discussed.
Reduction and uptake of methylene blue from rat air spaces
Authors: Effros R. M. , Murphy C. , Hacker A. , Schapira R. M. , Bongard R.
Published: December 2017

The use of methylene blue (MB) to estimate dilution of epithelial lining fluid, which occurs during bronchoalveolar lavage (BAL), is complicated by loss of this redox dye from the air spaces. The rate of MB uptake from the air spaces of isolated rat lungs and the effects of oxidation and reduction on this process were investigated in this study. Movement of MB from the air spaces to perfusate was compared with the corresponding transport of 125I-labeled albumin, [14C]-dextran, 99mTc-labeled diethylenetriaminepentaacetate, [3H]-sucrose, and 3H2O. By the end of 2 min, MB concentrations in the BAL had fallen by 58 +/- 4% (SE; n = 11) and 3H2O by 78 +/- 2% (n = 13), whereas concentrations of the other indicators decreased by approximately 6%. All but 10% of the 3H2O lost from the air spaces was found in the perfusate, whereas 19% of the lost MB was not recovered in the perfusate, suggesting retention of MB in the pulmonary tissues. Absorption of MB from the air spaces was slowed by 20% when the lungs were left unperfused, and absorption was accelerated threefold by reduction of MB to leukomethylene blue with Na2S2O4. In contrast, MB losses from the air space were slowed by the oxidizing agent K3Fe(CN)6 and by addition of superoxide dismutase or ascorbic oxidase. It is therefore possible that ascorbic acid and O2- entering the air spaces reduce MB to the uncharged leuko form. Lowering the pH of the BAL fluid to 3.5 also slowed MB reabsorption. This suggests that acid aspiration may stimulate release of oxidants into the air spaces.
Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma
Authors: Gao J. , Ren J. , Gulve E. A. , Holloszy J. O.
Published: December 2017

The maximal effects of insulin and muscle contractions on glucose transport are additive. GLUT-4 is the major glucose transporter isoform expressed in skeletal muscle. Muscle contraction and insulin each induce translocation of GLUT-4 from intracellular sites into the plasma membrane. The purpose of this study was to test the hypothesis that the incremental effect of contractions and insulin on glucose transport is mediated by additivity of the maximal effects of these stimuli on GLUT-4 translocation into the sarcolemma. Anesthetized rats were given insulin by intravenous infusion to raise plasma insulin to 2,635 +/- 638 microU/ml. The gastrocnemius-plantaris-soleus group was stimulated to contract via the sciatic nerve by using a protocol that maximally activates glucose transport. After treatment with insulin, contractions, or insulin plus contractions or no treatment, the gastrocnemius-plantaris-soleus muscle group was dissected out and was subjected to subcellular fractionation to separate the plasma membrane and intracellular membrane fractions. Insulin induced a 70% increase and contractions induced a 113% increase in the GLUT-4 content of the plasma membrane fraction. The effects of insulin and contractions were additive, as evidenced by a 185% increase in the GLUT-4 content of the sarcolemmal fraction. This finding provides evidence that the incremental effect of maximally effective insulin and contractile stimuli on glucose transport is mediated by additivity of their effects on GLUT-4 translocation into the sarcolemma.
Stability of alveolar capillary opening pressures
Authors: Presson R. G. , Okada O. , Hanger C. C. , Godbey P. S. , Graham J. A. , Glenny R. W. , Capen R. L. , Wagner W. W.
Published: December 2017

Little is known about the stability of the process by which pulmonary capillaries open. To investigate this process, pulmonary capillary perfusion patterns in isolated pump-perfused canine lobes were studied using video microscopy. After pump flow was set to perfuse one-half of the capillaries, the pump was turned off and all of the capillaries emptied. Turning the pump back on reopened the capillaries. The on-off cycle was repeated six times. If the same capillaries were perfused during each observation, it would demonstrate that there were stable and significant differences between individual capillary opening pressures, causing consistent recruitment of those capillaries with the lowest opening pressures. Alternatively, variable perfusion patterns would result if capillary opening pressures changed between observations, if the differences in opening pressures between capillary segments were negligible, or if experimental conditions changed between cycles. The perfusion pattern was more reproducible than expected by chance alone, which indicated the existence of stable differences among alveolar capillary opening pressures.
Lactate transport studied in sarcolemmal giant vesicles from human muscle biopsies: relation to training status
Authors: Pilegaard H. , Bangsbo J. , Richter E. A. , Juel C.
Published: December 2017

The present study examined sarcolemmal lactate transport capacity in humans of widely different training status. Muscle biopsies were obtained from m. vastus lateralis in 39 subjects divided into untrained (n = 13), trained (n = 7), and athlete [sprint runners (n = 2), endurance runners (n = 5), triathletes (n = 3), and road (n = 6) and track (n = 3) bicyclists] groups. From the biopsy sample giant vesicles were produced with collagenase treatment to determine the sarcolemmal lactate transport capacity, and histochemical analyses were made. The athletes had a higher capacity to transport lactate than the untrained and trained subjects (P < 0.01). Within the group of athletes, the bicyclists had a higher lactate transport capacity than the runners (P < 0.05), whereas there was no difference among trained subjects, runners, and triathletes. The lactate transport capacity was related to the occurrence of type I muscle fibers (r = 0.48, P < 0.01). The present results suggest that the capacity to transport lactate is higher in athletes than in untrained and less trained subjects. It might indicate that lactate transport capacity in human skeletal muscle can be changed by a high volume of training including frequent high-intensity sessions. In addition, sarcolemmal lactate transport capacity appears to be related to the fiber type distribution of a muscle.
Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men
Authors: Nakamitsu S. , Sagawa S. , Miki K. , Wada F. , Nagaya K. , Keil L. C. , Drummer C. , Gerzer R. , Greenleaf J. E. , Hong S. K. , et al.
Published: December 2017

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3′,5′-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Lung volumes during sustained microgravity on Spacelab SLS-1
Authors: Elliott A. R. , Prisk G. K. , Guy H. J. , West J. B.
Published: December 2017

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (mu G) on lung volumes has not been reported. Pulmonary function tests were performed by four subjects before, during, and after 9 days of mu G exposure. Ground measurements were made in standing and supine postures. Tests were performed using a bag-in-box-and-flowmeter system and a respiratory mass spectrometer. Measurements included functional residual capacity (FRC), expiratory reserve volume (ERV), residual volume (RV), inspiratory and expiratory vital capacities (IVC and EVC), and tidal volume (VT). Total lung capacity (TLC) was derived from the measured EVC and RV values. With preflight standing values as a comparison, FRC was significantly reduced by 15% (approximately 500 ml) in mu G and 32% in the supine posture. ERV was reduced by 10–20% in mu G and decreased by 64% in the supine posture. RV was significantly reduced by 18% (310 ml) in mu G but did not significantly change in the supine posture compared with standing. IVC and EVC were slightly reduced during the first 24 h of mu G but returned to 1-G standing values within 72 h of mu G exposure. IVC and EVC in the supine posture were significantly reduced by 12% compared with standing. During mu G, VT decreased by 15% (approximately 90 ml), but supine VT was unchanged compared with preflight standing values. TLC decreased by approximately 8% during mu G and in the supine posture compared with preflight standing. The reductions in FRC, ERV, and RV during mu G are probably due to the cranial shift of the diaphragm, an increase in intrathoracic blood volume, and more uniform alveolar expansion.