bluuebunny/crossref_metadata_2025 huggingface dataset:
Pontile regulation of ventilatory activity in the adult rat
Authors: Wang W. , Fung M. L. , St John W. M.
Published: December 2017

Our purpose was to characterize the pontile components of the brain stem ventilatory control system in rats. This study was precipitated by reports that this pontile component might differ fundamentally from that of other species. Efferent activity of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed, and ventilated adult rats. As in other species, electrical stimulations of the rostral pons caused premature terminations and/or onsets of phrenic activity in eupnea. Electrolytic lesions of rostrolateral pons resulted in apneusis, characterized by significant prolongations of the phrenic burst. Some effective lesions were in the region of the nucleus parabrachialis medialis and the Kolliker-Fuse nucleus, the site of the pneumotaxic center. Other lesions resulting in apneusis were ventral to the pneumotaxic center. As in cats, lesions in the caudal pontile reticular formation caused the duration of the apneustic neural inspiration to return toward that of eupnea. Again, as in other species, gradual alterations from eupnea to gasping in the rat were recorded during hypoxia, which was induced by ventilation with carbon monoxide. We conclude that the brain stem respiratory control system is similarly organized in rats and other mammalian species. These results have implications for contemporary hypotheses concerning the neurogenesis of ventilatory activity.
Disruption of pulmonary surfactant's ability to maintain openness of a narrow tube
Authors: Enhorning G. , Holm B. A.
Published: December 2017

Pulmonary surfactant stabilizes alveoli but, by maintaining patency of peripheral conducting airways, will also lower resistance to airflow. A small quantity of a surfactant suspension (3 mg/ml) formed a blocking liquid column in a narrow section of a glass capillary. Pressure was raised on one side of that column, whereby it was forced to move out of the narrow section, and it did not return but left the capillary open for a free airflow. The surfactant capability to maintain free airflow was lost with the addition of albumin (> 10 mg/ml) or fibrinogen (> 0.5 mg/ml). Surfactant function was seriously affected by hydrolysis with phospholipase C but not with phospholipase A2. With a small quantity of albumin added (5 mg/ml), the ability to maintain openness was seriously affected at temperatures below 25 degrees C. An inflammatory reaction due to atopy, infection, or inhalation of irritating gases characterizes a variety of airway diseases, including asthma. If the in vitro studies can be transferred to in vivo conditions, surfactant dysfunction might contribute to certain types of airway disease.
Effect of hindlimb unweighting on single soleus fiber maximal shortening velocity and ATPase activity
Authors: McDonald K. S. , Fitts R. H.
Published: December 2017

This study characterizes the time course of change in single soleus muscle fiber size and function elicited by hindlimb unweighting (HU) and analyzes the extent to which varying durations of HU altered maximal velocity of shortening (Vo), myofibrillar adenosinetriphosphatase (ATPase), and relative content of slow and fast myosin in individual soleus fibers. After 1, 2, or 3 wk of HU, soleus muscle bundles were prepared and stored in skinning solution at -20 degrees C. Single fibers were isolated and mounted between a motor arm and a transducer, and fiber force, Vo, and ATPase activity were measured. Fiber myosin content was determined by one-dimensional sodium dodecyl sulfate- (SDS) polyacrylamide gel electrophoresis. After 1, 2, and 3 wk of HU, soleus fibers exhibited a progressive reduction in fiber diameter (16, 22, and 42%, respectively) and peak force (42, 48, and 72%, respectively). Peak specific tension was significantly reduced after 1 wk of HU (18%) and showed no further change in 2–3 wk of HU. During 1 and 3 wk of HU, fiber Vo and ATPase showed a significant increase. By 3 wk, Vo had increased from 1.32 +/- 0.04 to 2.94 +/- 0.17 fiber lengths/s and fiber ATPase from 291 +/- 16 to 1,064 +/- 128 microM.min-1 x mm-3. The percent fibers expressing fast myosin heavy chain increased from 4% to 29% by 3 wk of HU, and Vo and ATPase activity within a fiber were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)
Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters
Authors: Yarasheski K. E. , Zachweija J. J. , Angelopoulos T. J. , Bier D. M.
Published: December 2017

The purpose of this study was to determine whether recombinant human growth hormone (GH) administration enhances muscle protein anabolism in experienced weight lifters. The fractional rate of skeletal muscle protein synthesis and the whole body rate of protein breakdown were determined during a constant intravenous infusion of [13C]leucine in 7 young (23 +/- 2 yr; 86.2 +/- 4.6 kg) healthy experienced male weight lifters before and at the end of 14 days of subcutaneous GH administration (40 microgram.kg-1 x day-1). GH administration increased fasting serum insulin-like growth factor-I (from 224 +/- 20 to 589 +/- 80 ng/ml, P = 0.002) but did not increase the fractional rate of muscle protein synthesis (from 0.034 +/- 0.004 to 0.034 +/- 0.002%/h) or reduce the rate of whole body protein breakdown (from 103 +/- 4 to 108 +/- 5 mumol.kg-1 x h-1). These findings suggest that short-term GH treatment does not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown, metabolic alterations that would promote muscle protein anabolism in experienced weight lifters attempting to further increase muscle mass.
Approximations in the measurement of surface tension on the oscillating bubble surfactometer
Authors: Hall S. B. , Bermel M. S. , Ko Y. T. , Palmer H. J. , Enhorning G. , Notter R. H.
Published: December 2017

This paper examines two factors, shape deformation and surface viscosity, that affect measurements of surface tension of lung surfactants with the oscillating bubble surfactometer. At lower surface tensions, the compressed bubble in this apparatus becomes deformed to an oblate ellipsoid that cannot be analyzed rigorously using the simplified (spherical) Laplace equation to calculate surface tension from interfacial pressure drop. However, for the small air bubbles present in this apparatus, analysis with more general equations for ellipsoids of revolution shows that deformation effects are limited to extremely low surface tensions, and the absolute error from the spherical approximation is minimal in practice. In contrast, this was not the case for the effects of surface dilational viscosity in oscillating bubble calculations. Direct measurements and values from the literature indicated that the surface dilational viscosities of lung surfactant, dipalmitoyl phosphatidylcholine, and palmitic acid were sufficient to give substantial errors if their effects on interfacial pressure drop were neglected during dynamic cycling. Surface tension calculations at maximum and minimum radii on the oscillating bubble apparatus remain accurate, because the time derivative of radius becomes zero and viscous effects vanish. However, surface tensions determined at points other than these extremes of bubble size should be interpreted with caution.
Hydroxylation of salicylate by the in vitro diaphragm: evidence for hydroxyl radical production during fatigue
Authors: Diaz P. T. , She Z. W. , Davis W. B. , Clanton T. L.
Published: December 2017

There is increasing evidence that oxygen-derived free radicals produced during strenuous work by the diaphragm may contribute to diaphragm fatigue and/or injury. However, the precise identity of these oxygen radicals remains unknown, inasmuch as oxygen free radicals are extremely short lived and their detection in biologic systems is quite difficult. There is recent evidence that the salicylate-trapping method may be a useful means of monitoring tissue production of hydroxyl radical (.OH). This method is predicated on the fact that salicylate's phenolic ring can be attacked by .OH at the 3 or 5 position to yield 2,3- or 2,5-dihydroxybenzoic acid (DHB). These metabolites are stable and can be identified by high-performance liquid chromatography (HPLC) coupled with electrochemical or ultraviolet detection. To test the hypothesis that hydroxylated salicylates are produced during diaphragm fatigue, we exposed in vitro rat diaphragm strips to a physiological saline solution containing 2.0 mM sodium salicylate for approximately 15 min. The solution was then removed, and the strips were fatigued (20 Hz, 200-ms train duration, 1 train/s) via phrenic nerve stimulation for 30 s-10 min. The diaphragm strips were subsequently homogenized, and the homogenate was analyzed by HPLC coupled with ultraviolet detection. Levels of 2,3-DHB were significantly higher in fatigued than in control nonfatigued strips. There was also a significant correlation between the amount of 2,3-DHB in the fatigued muscle and the accumulated tension-time product developed during fatigue. 2,5-DHB was not consistently identified in control or experimental strips.(ABSTRACT TRUNCATED AT 250 WORDS)
Diaphragm reinnervation by laryngeal motoneurons
Authors: Baldissera F. , Cavallari P. , Marini G. , Tredici G.
Published: December 2017

Inspiratory activity of the paralyzed diaphragm was restored by reinnervation with brain stem laryngeal motoneurons. In 10 anesthetized cats, the right recurrent laryngeal nerve (RLN) was cut and anastomosed to the distal stump of either one or both roots (C5-C6) of the ipsilateral phrenic nerve. Three to four months later, reinnervation was assessed under deep anesthesia by the reappearance in the paralyzed diaphragm of 1) direct electromyographic (EMG) responses after electrical stimulation of the RLN and 2) spontaneous inspiratory bursts. Serial radiography, performed on five animals, revealed diaphragmatic excursions of comparable amplitude on the normal and reinnervated sides. Six to twelve months after anastomosis, laparotomy (performed under Nembutal anesthesia) allowed inspection and EMG recording of the spontaneous inspiratory contractions of the reinnervated areas and their sustained responses to tetanic RLN stimulation. Inspiratory discharges showed a ramplike recruitment similar to that of the normal diaphragm. Although the RLN contains a number of expiratory axons, multiple-site recordings disclosed expiratory EMG discharges only once. Histological analysis confirmed the substitution of phrenic axons by regenerating RLN fibers.
Respiratory load compensation. III. Role of spinal cord afferents
Authors: Frazier D. T. , Xu F. , Lee L. Y. , Taylor R. F.
Published: December 2017

In a previous study, we reported that inspiratory tracheal occlusion (TO) significantly inhibited the motor drive to the diaphragm in a decerebellated bilaterally vagotomized preparation (J. Appl. Physiol. 75:675–681, 1993). The hypothesis to be tested in the present study was that respiratory muscle afferents activated by inspiratory TO provided the inputs responsible for the observed inhibition. Adult cats were anesthetized, tracheotomized, and instrumented with diaphragm electromyographic (EMGdi) recording electrodes. The cerebellum, vagi, and dorsal spinal cord (C2-T2) were surgically exposed. Inspiratory TO was applied before and after cold blockade of the dorsal cord (C6) or dorsal root (C3–6) transection in the intact and decerebellated vagotomized cat. Respiratory timing (inspiratory and expiratory duration) was determined from the EMGdi record, and the peak integrated EMGdi (integral of EMGdi) response was used as an index of respiratory motor drive. Our results showed that 1) cold blockade at the dorsal C6 level in an intact preparation significantly increased the peak of the integral of EMGdi response to TO and was reversible upon rewarming; 2) as previously reported, decerebellation coupled with bilateral vagotomy significantly decreased the peak integral of EMGdi response to TO with no effect on timing; 3) cold blockade (-1 degree C) of the dorsal cord at C6 significantly attenuated this inhibition, and subsequent dorsal rhizotomy at C3–6 completely abolished this inhibition; and 4) decerebellation, cold blockade of the dorsal cord (C6), and dorsal rhizotomy (C3–6) did not significantly affect baseline values in bilaterally vagotomized cats.(ABSTRACT TRUNCATED AT 250 WORDS)
Perfusion of alveolar septa in isolated rat lungs in zone 1
Authors: Conhaim R. L. , Harms B. A.
Published: December 2017

The combination of high inflation and low vascular pressures in zone 1 lungs is assumed to collapse alveolar vessels, making them inaccessible to vascular liquid. To test this assumption, we perfused isolated rat lungs in zone 1 (n = 5) with fluorescent albumin solution (inflation pressure = 25 cmH2O, pulmonary arterial pressure = 10 cmH2O, left atrial pressure = 0 cmH2O; flow = 0.11 +/- 0.06 ml.100 g body wt-1 x min-1) and rapidly froze them. Histologically, 33 +/- 19% (SD) of alveolar septa fluoresced, demonstrating that the perfusate had not been excluded. However, we could not resolve whether the fluorescence originated in the septal microvascular lumen or in the adjacent perimicrovascular interstitial space. To address this issue, we perfused an additional lung with horseradish peroxidase (HRP) and examined it by transmission electron microscopy. HRP filled interstitial spaces around septal vessels and extraseptal alveolar corner vessels, but because the septal vascular lumina were too compressed, we were unable to determine whether they also contained HRP. Therefore we perfused two additional lungs with particles of colloidal gold (0.05 microns diam). Using transmission electron microscopy, we found gold particles in 15–25% of septal vascular lumina, demonstrating that septal vessels were at least partially accessible in zone 1. Our interpretations is that filtration in zone 1 may occur from septal vessels and extraseptal alveolar vessels. Furthermore, results of the HRP study suggest that the perimicrovascular interstitial space is less compressible than the septal vascular lumen.
O2 uptake kinetics and the O2 deficit as related to exercise intensity and blood lactate
Authors: Barstow T. J. , Casaburi R. , Wasserman K.
Published: December 2017

The dynamic responses of O2 uptake (VO2) to a range of constant power output levels were related to exercise intensity [as percent maximal VO2 and as below vs. above lactic acid threshold (LAT)] and to the associated end-exercise lactate in three groups of subjects: group I, untrained subjects performing leg cycle ergometer exercise; group II, the same subjects performing arm cycle exercise; and group III, trained cyclists performing leg cycle ergometer exercise. Responses were described by a double-exponential equation, with each component having an independent time delay, which reduced to a monoexponential description for moderate (below-LAT) exercise. When a second exponential component to the VO2 response was present, it did not become evident until approximately 80–100 s into exercise. An overall time constant (tau T, determined as O2 deficit for the total response divided by net end-exercise VO2) and a primary time constant (tau P, determined from the O2 deficit and the amplitude for the early primary VO2 response) were compared. The tau T rose with power output and end-exercise lactate levels, but tau P was virtually invariant, even at high end-exercise lactate levels. Moreover the gain of the primary exponential component (as delta VO2/delta W) was constant across power outputs and blood lactate levels, suggesting that the primary VO2 response reflects a linear system, even at higher power outputs. These results suggest that elevated end-exercise lactate is not associated with any discernible slowing of the primary rise in VO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid
Authors: Gillissen A. , Birrer P. , McElvaney N. G. , Buhl R. , Vogelmeier C. , Hoyt R. F. , Hubbard R. C. , Crystal R. G.
Published: December 2017

Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, serves as the major inhibitor of neutrophil elastase (NE) on the epithelial surface of the upper airways. As a control for studies to evaluate the aerosol administration of recombinant SLPI (rSLPI) to augment the anti-NE defenses of the lung, the status of antioxidants in respiratory epithelial lining fluid (ELF) was evaluated. Unexpectedly, aerosol administration of rSLPI caused an elevation in ELF glutathione, a major component of the epithelial antioxidant screen; i.e., rSLPI may provide not only augmentation of anti-NE defenses but also antioxidant defenses. To evaluate this concept, rSLPI (100 mg) was aerosolized to sheep, and SLPI, glutathione, anti-NE capacity, and anti-H2O2 capacity were evaluated in respiratory ELF over a 30-h period. As expected, aerosolization of rSLPI increased ELF SLPI levels and anti-NE capacity. Strikingly, postaerosol levels of glutathione in ELF were also increased (5-fold 24 h after aerosol), with a concomitant increase in ELF anti-H2O2 capacity; i.e., the rSLPI augmented the antioxidant screen of ELF. This suggests that rSLPI may be particularly well suited for therapy in lung diseases characterized by excess of both serine proteases and oxidants on the respiratory epithelial surface.
Role of deflation-sensitive feedback in control of end-expiratory volume in rats
Authors: Sammon M. , Romaniuk J. R. , Bruce E. N.
Published: December 2017

Rats breathing from reduced end-expiratory volumes (EEV) exhibit transient bursting of inspiratory airflow local to the expiratory-inspiratory transition (E-I) accompanied by increases in inspiration-to-expiration duration ratio. Continuous positive (CPAP) and negative (CNAP) airway pressures (+3 to -9 cmH2O) were applied to tracheal openings of 17 unilaterally vagotomized rats (urethan anesthetized) to evaluate the feedback mechanisms associated with these oscillatory "expiratory interrupts." Whole nerve recordings of afferent vagus (Vag) were primarily inspiratory with CPAP. As tracheal pressure was reduced in a stepwise manner, progressive decreases in inspiratory peaks and increases in activity during late expiration were seen on Vag. Single-fiber recordings correlate Vag expiratory activity with slowly adapting receptors sensitive to lung deflation. With CNAP, 1) progressively earlier onsets of activity in inspiratory muscles (e.g., diaphragm, genioglossus, posterior cricoarytenoid) were observed (increased inspiratory duration, decreased expiratory duration); oscillations at E-I developed only when expiratory peaks on Vag were significant. 2) Thyroarytenoid muscle exhibited onset of electromyographic activity that immediately succeeded onset of Vag during late expiration. When the trachea is intact, these two actions might combine to produce a respiratory pattern similar to the "grunting" often seen in newborns breathing from reduced EEVs. In contrast to larger mammals, rats rely strongly on deflation reflexes for control of E-I phase switching, presumably to aid in maintenance of an elevated EEV.
NIP-121 is more effective than nifedipine in acutely reversing chronic pulmonary hypertension
Authors: Oka M. , Morris K. G. , McMurtry I. F.
Published: December 2017

To determine if NIP-121, a new antihypertensive agent with K+ channel-opening activity, would be an effective vasodilator in pulmonary hypertension, we studied its acute hemodynamic effects under normoxic conditions in conscious chronically hypoxic pulmonary hypertensive rats and in control pulmonary normotensive rats. In contrast to no pulmonary vasodilation by NIP-121 in control rats, the K+ channel activator (10–100 mg/kg i.v.) decreased both mean pulmonary arterial pressure (from 42 +/- 2 to 33 +/- 2 mmHg; P < 0.05) and total pulmonary resistance (from 278 +/- 30 to 213 +/- 32 mmHg.l-1 x min; P < 0.05) in hypertensive rats. NIP-121 produced similar dose-related decreases in mean systemic arterial pressure and total systemic resistance in both groups of rats. Both the pulmonary and the systemic vasodilations to NIP-121 were inhibited by pretreatment with the blocker of ATP-sensitive K+ channels, glibenclamide (20 mg/kg), but not with the inhibitor of endothelium-derived relaxing factor synthesis, nitro-L-arginine (10 mg/kg). The L-type voltage-gated Ca2+ channel blocker, nifedipine (10–1,000 mg/kg i.v.), failed to cause pulmonary vasodilation in normoxic hypertensive rats, although there was dose-related systemic vasodilation. These results show that in contrast to the Ca2+ channel blocker, nifedipine, the K+ channel activator, NIP-121, is a potent vasodilator of chronic hypoxia-induced pulmonary hypertension in the rat. The mechanism of its hypotensive action in the hypertensive pulmonary vasculature might be more than simply membrane hyperpolarization and indirect inhibition of the L-type voltage-gated Ca2+ channel.
Breathing route and resistive loading: influence on ventilatory response to hypoxia in conscious dogs
Authors: Cao K. Y. , Sullivan C. E. , Berthon-Jones M. , Zwillich C. W.
Published: December 2017

Unlike normal humans, the tracheostomized conscious dog does not show ventilatory adaptation in response to sustained isocapnic hypoxia. To determine whether this phenomenon is a result of the breathing route or the relatively low airflow resistance of tracheostomy breathing, we evaluated the ventilatory response to sustained isocapnic hypoxia (20 min; arterial oxyhemoglobin saturation = 80%) in five awake dogs during nasal-oral (mask) breathing, tracheal breathing, and tracheal breathing with added matched resistance of upper airway breathing. Mask breathing, like unloaded tracheal breathing, was associated with a consistent level of hyperventilation during the entire hypoxic exposure period. However, mask breathing was always less (P < 0.05) than that found during unloaded tracheal breathing. Loaded tracheal breathing during hypoxia resulted in initial hyperventilation similar to that of unloaded tracheal breathing followed by a "roll off" to a lower minute ventilation similar to that of mask breathing. Our findings demonstrate that ventilatory adaptation is only present during loaded tracheal breathing in dogs and suggest that the breathing route and upper airway resistive loading may play roles in ventilatory adaptation.
Role of tachykinins in ozone-induced acute lung injury in guinea pigs
Authors: Tepper J. S. , Costa D. L. , Fitzgerald S. , Doerfler D. L. , Bromberg P. A.
Published: December 2017

To examine the hypothesis that the acute reversible changes caused by ozone (O3) exposure are mediated by tachykinin release, guinea pigs were depleted of tachykinins by use of repeated capsaicin (CAP) injections before O3 exposure in an attempt to prevent O3-induced functional changes. Unexpectedly, CAP pretreatment caused divergent results in the functional responses to O3. Ventilatory measurements obtained from CAP-pretreated O3-exposed (CAP-O3) animals were exacerbated rather than diminished compared with the effects of O3 alone. Similarly, lavage fluid protein accumulation was enhanced in the CAP-O3 group compared with the O3-exposed group. In better agreement with our initial hypothesis, the CAP-O3 group was less responsive than the O3-exposed animals to histamine aerosol challenge. Additionally, Evans blue dye accumulation, a hallmark of tachykinin release, was increased in O3-exposed animals and was partially blocked in the CAP-O3 group. These data suggest that tachykinin-containing sensory fibers are unlikely to mediate the acute effects of O3 exposure on tidal breathing and lavage fluid protein accumulation but may play a role in causing post-O3 airway hyperreactivity and protein extravasation into the trachea.
Determination of human skeletal muscle buffer value by homogenate technique: methods of measurement
Authors: Mannion A. F. , Jakeman P. M. , Willan P. L.
Published: December 2017

The human muscle buffer value (beta) is most frequently determined by either fixed acid titration of a homogenate ["in vitro" beta (beta vit)] or measurement of the change in lactate concentration (delta [La]) relative to the change in muscle homogenate pH after high-intensity exercise ["in vitro" beta = - delta [La]/delta pH (beta viv)]. We sought to compare beta viv, determined after isometric and dynamic exercise to exhaustion (approximately 60 s), with beta vit. Resting (R) and postexercise (E) biopsy samples were taken from vastus lateralis muscles of 43 human volunteers. Freeze-dried muscle was homogenized (30 mg/ml) in NaF (0.01 M) for the measurement of muscle pH (R and E). beta vit was determined by HCl (0.01 M) titration of the homogenate over the pH range 7.1–6.5. Muscle lactate was measured by enzymatic assay. There was no significant difference between beta viv determined after isometric (n = 35) or dynamic (n = 8) exercise to fatigue (170 vs. 168 mmol H+.kg dry muscle mass-1.pH-1, respectively; P > 0.05). Values for beta vit in the corresponding muscle samples (R) were approximately 7–8% lower (156 +/- 25 vs. 157 +/- 18 mmol H+.kg dry muscle mass-1.pH-1, respectively). There was no significant difference (P = 0.278) between the measured decline in muscle homogenate pH after exercise and the reduction in pH predicted from beta vit and delta [La], indirectly confirming the lack of any significant difference between beta viv and beta vit.(ABSTRACT TRUNCATED AT 250 WORDS)
Training does not affect zero-trans lactate transport across mixed rat skeletal muscle sarcolemmal vesicles
Authors: Roth D. A. , Brooks G. A.
Published: December 2017

Hindlimb muscle sarcolemmal vesicles were purified from three age-matched groups of female Sprague-Dawley rats: sedentary control (CON; n = 10), sprint trained (ST; n = 8), and endurance trained (ET; n = 9). Membrane isolations from the three groups were not significantly different in protein yield or purification index. Blood lactate concentration was determined in resting CON rats and running ET and ST rats during the final week. Both the ST and ET groups were significantly higher in citrate synthase (vs. CON) in the soleus and mid-vastus lateralis. The time course of 1 mM L-(+)-lactate uptake in vesicles from the three groups showed no significant difference at any of the five time points tested under zero-trans conditions. Saturation kinetics were examined at nine lactate concentrations, and Lineweaver-Burk plots revealed no difference between groups in apparent Michaelis-Menten constant or maximal transport velocity. Vesicles from CON and ET rats were used to investigate cis inhibition of 0.1 mM L-(+)-lactate transport by four unlabeled monocarboxylates: L-(+)-lactate, D-(-)-lactate, pyruvate, and alpha-cyanohydroxycinnamate at 0.1, 1.0, and 10 mM. Under pH gradient-stimulated L-(+)-lactate transport conditions, cis inhibition was affected by neither D-(-)-lactate nor endurance training. We conclude that the lactate transporter has distinct cis-inhibitory specificity, is stereospecific, and is stimulated when confronted with parallel lactate and proton gradients but that spring and endurance training do not alter lactate transport rate or capacity under these conditions.
Influence of diffusion on estimations of protein reflection coefficient by double-indicator method
Authors: White P. , Brower R. G. , Sylvester J. T. , Permutt T. , Permutt S.
Published: December 2017

In isolated perfused organs, vascular protein reflection coefficients (sigma) can be calculated from the changes in hematocrit and perfusate protein concentration (CP) that occur during edema formation. This technique requires the assumption that transvascular protein flux by diffusion is negligible. To assess diffusion-induced errors in calculations of sigma, we derived an expression for CP that includes determinants of diffusive protein flux: protein permeability-surface area product (PS), transvascular fluid flux (J), true sigma, and transvascular protein concentration. We used this expression to obtain values of CP under various experimental conditions and then calculated values of sigma (measured sigma) for those conditions. Diffusion causes measured sigma to be lower than true sigma. The diffusion-induced error is larger and potentially substantial when J/PS is low and when true sigma is high. Diffusion-induced error is also larger when the amount of edema formation is greater. In recent isolated canine lung experiments where J/PS was approximately 2.7, diffusion-induced errors in measured sigma for albumin would have been approximately 0.06 (at true sigma = 0.5) and approximately 0.18 (at true sigma = 0.9). When J/PS was higher, the potential for diffusion-induced errors was much smaller. We conclude that diffusion causes underestimation of true sigma and that the error in measured sigma may be substantial when J/PS is < 5 and when true sigma is > 0.5.
Regional blood volume distribution during positive and negative airway pressure breathing in supine humans
Authors: Peters J. , Hecker B. , Neuser D. , Schaden W.
Published: December 2017

To assess the effects of continuous positive (CPAP) or negative airway pressure (CNAP) breathing (+/- 10#x2013;12 cmH2O, duration 25 min) on blood content in the body's capacitance vasculature, regional distribution of labeled red blood cells was evaluated in seven spontaneously breathing supine volunteers. Counts were acquired by whole body scans and detectors overlying the liver, intestine, left ventricle, and lower arm, and arterial pressure, heart rate, calf blood flow and vascular resistance, hematocrit, vasopressin, and atrial natriuretic peptide plasma concentrations were also obtained. With CPAP, thoracic, cardiac, and left ventricular counts diminished significantly by 7#x2013;10%, were accompanied by significant increases in counts over both the gut and liver, and remained decreased during CPAP but reversed to baseline with zero airway pressure. Calf blood flow and vascular resistance significantly decreased and increased, respectively, whereas limb counts, arterial pressure, heart rate, and hormone concentrations remained unchanged. With CNAP, in contrast, regional counts and other variables did not change. Thus, moderate levels of CPAP deplete the intrathoracic vascular bed and heart, shifting blood toward the gut and liver but not toward the limbs. No short-term compensation increasing cardiac filling during CPAP was seen. In contrast, CNAP did not alter intrathoracic or organ blood content and, therefore, does not simply mirror the effects evoked by CPAP.
Left ventricular function during dynamic exercise in untrained and moderately trained subjects
Authors: Brandao M. U. , Wajngarten M. , Rondon E. , Giorgi M. C. , Hironaka F. , Negrao C. E.
Published: December 2017

The influence of exercise training on left ventricular function at rest (R), at anaerobic threshold (AT), and during peak exercise (PE) was evaluated in 12 healthy untrained and 13 trained (T) subjects who underwent Doppler echocardiography at R and radionuclide ventriculography at R and during exercise. The end-diastolic volume and stroke volume were significantly higher in the T group than in the untrained group at R. The ejection fraction rose significantly from R to AT and from AT to PE (80.0 +/- 0.84 vs. 83.6 +/- 0.91%), but no significant difference was observed between groups. The peak diastolic filling rate rose significantly during exercise, with a further significant increase observed in the T group (AT, 6.38 +/- 0.40 vs. 5.01 +/- 0.16 end-diastolic counts/s; PE, 8.24 +/- 0.42 vs. 7.15 +/- 0.35 end-diastolic counts/s). The percent variation of minimal systolic counts fell significantly at AT and PE in relation to R. Our data demonstrate that exercise training produces a significant increase in peak diastolic filling rate but no change in systolic function during exercise and that metabolic acidosis caused by exercise does not limit systolic function.
Chemical and nonchemical stimuli during breath holding in divers are not independent
Authors: Courteix D. , Bedu M. , Fellmann N. , Heraud M. C. , Coudert J.
Published: December 2017

In the breath-hold model described by S. Godfrey and E. J. M. Campbell (Respir. Physiol. 5: 385–400, 1968), chemical and nonchemical stimuli are independent. Because these two factors are time dependent, the effect of each could not be measured by breath-holding time (BHT). The aim of this study is to dissociate chemical and nonchemical stimuli and to assess the effects of BHT and PCO2 on respiratory center output by measurement of occlusion pressure (P0.1) and mean inspiratory flow (VI). Nine well-trained divers (age 36.5 +/- 5.0 yr) took part in the study. Each subject had to hold his breath at 75% of vital capacity for 30, 50, and 70 s of BHT. Before each breath hold, the subject inspired successively two vital capacities of the same CO2-O2 gas mixture. P0.1 and VI were measured during the first reinspiration after the breath hold. For the same BHT, we observed good linear relationships between P0.1 or VI and alveolar PCO2. The slopes of these relationships increased with BHT. For alveolar PCO2 of > 50 Torr, P0.1 increased linearly with BHT. These results indicate that, during breath holding, chemical and nonchemical stimuli acted linearly on respiratory motoneuron activity, but they were not independent.
Histomorphometric analyses of cancellous bone from COSMOS 2044 rats
Authors: Vico L. , Bourrin S. , Genty C. , Palle S. , Alexandre C.
Published: December 2017

The influence of 14 days of spaceflight on cancellous bone of male Wistar rats was assessed by histomorphometric analysis. In proximal tibia, no difference was found between flight, synchronous, vivarium, and basal groups for epiphyseal bone volume or trabecular arrangement. In metaphysis, primary spongiosa width was reduced in flight rats, suggesting an alteration in bone longitudinal growth. In flight rats, secondary spongiosa evidenced a trend toward decreased bone mass, trabecular number and thickness, and osteoid surfaces, whereas there was a tendency toward increased osteoclast number compared with vivarium control but not with synchronous rats. In femoral fossa trochanteri, an area facing deep muscular insertions, no changes in bone volume or structure were noted among the different groups. However, a reduction of osteoid surfaces was seen in flight and synchronous groups compared with the other groups. Resorption activity was increased in flight rats compared with control rats. In thoracic vertebral body, osteoblastic surfaces decreased similarly in flight and synchronous rats. In lumbar vertebral body, decreased osteoblastic surfaces and increased osteoclastic parameters were observed in flight and synchronous rats. The more striking effects of spaceflight were the decrease in tibial primary spongiosa width and the increase in resorption activity of the femoral fossa trochanteri. In all other sites, cellular alterations appeared similar in flight and synchronous rats, suggesting a role for physiological stress. The time course of events would depend on initial growth and turnover rates of bone, its weight-bearing function on earth, and the presence of muscular insertions.
Important influence of respiration on human R-R interval power spectra is largely ignored
Authors: Brown T. E. , Beightol L. A. , Koh J. , Eckberg D. L.
Published: December 2017

Frequency-domain analyses of R-R intervals are used widely to estimate levels of autonomic neural traffic to the human heart. Because respiration modulates autonomic activity, we determined for nine healthy subjects the influence of breathing frequency and tidal volume on R-R interval power spectra (fast-Fourier transform method). We also surveyed published literature to determine current practices in this burgeoning field of scientific inquiry. Supine subjects breathed at rates of 6, 7.5, 10, 15, 17.1, 20, and 24 breaths/min and with nominal tidal volumes of 1,000 and 1,500 ml. R-R interval power at respiratory and low (0.06–0.14 Hz) frequencies declined significantly as breathing frequency increased. R-R interval power at respiratory frequencies was significantly greater at a tidal volume of 1,500 than 1,000 ml. Neither breathing frequency nor tidal volume influenced average R-R intervals significantly. Our review of studies reporting human R-R interval power spectra showed that 51% of the studies controlled respiratory rate, 11% controlled tidal volume, and 11% controlled both respiratory rate and tidal volume. The major implications of our analyses are that breathing parameters strongly influence low-frequency as well as respiratory frequency R-R interval power spectra and that this influence is largely ignored in published research.
Stochastic model of the pulmonary airway tree and its implications for bronchial responsiveness
Authors: Bates J. H.
Published: December 2017

The resistance of the pulmonary conducting airway tree (Raw) is a consequence of the resistances of its component airways and how they are connected together. To date, theoretical calculations of Raw have been performed with the aid of mathematical models of the airway tree that are purely deterministic. That is, the mechanical properties of the component airways in these models are precisely defined functions of generation number. Such models take no account of the fact that the airways of a given generation are not all exactly the same but rather exhibit a spectrum of wall thicknesses, amounts of smooth muscle, and number of parenchymal attachments. In the present study, the properties of a 10-generation stochastic airway tree model are investigated. The lengths and radii of the airways in the tree are drawn randomly from probability distribution functions (PDFs), the means of which are deterministic functions of generation number and the standard deviations are assigned various values. Monte Carlo simulation is used to estimate the PDF of Raw itself in various conditions. We show that the relative width of the PDF of Raw may be comparable to that of the PDFs from which the individual airway radii were drawn. It is also shown that when bronchoconstriction is simulated by narrowing each airway by a random amount the resulting PDF for Raw may increase in width many times. We conclude that the variations in airway responsiveness seen in nature can only be properly understood when the distribution of airway properties within the lung are taken into account.
Hypercapnia increases expiratory braking in preterm infants
Authors: Eichenwald E. C. , Ungarelli R. A. , Stark A. R.
Published: December 2017

In contrast to adults, newborn infants breathe from an elevated end-expiratory lung volume, determined by the interaction of airflow retardation (braking) by the diaphragm and larynx, and expiratory duration. To determine the effect of hypercapnia on this strategy, we examined changes in respiratory muscle activity and the ventilatory response to CO2 breathing in eight premature infants 33–34 wk gestational age in the first 3 postnatal days. We recorded tidal volume, airflow, and electromyograms (EMG) of the laryngeal abductor [posterior cricoarytenoid (PCA)], which abducts the vocal cords, and diaphragm during behaviorally determined quiet sleep in room air and during steady-state inhalation of 2% CO2 in air. As expected, tidal volume increased (P < 0.0005) without a change in inspiratory duration with hypercapnia. Unexpectedly, in all subjects, expiratory duration was longer during CO2 inhalation (P < 0.001), accompanied by marked changes in expiratory flow patterns consistent with increased expiratory braking. Diaphragm post-inspiratory EMG activity increased with hypercapnia (P < 0.005) with no change in baseline diaphragm or PCA EMG activity. Peak inspiratory EMG activity of the diaphragm and PCA increased with CO2 (10 and 37%, respectively; P < 0.05). We conclude that the mechanisms used to elevate end-expiratory lung volume are enhanced during hypercapnia in premature infants. This breathing strategy may be important in maintaining gas exchange in infants with lung disease.
Bronchial vascular occlusion does not attenuate or accentuate oleic acid lung injury in anesthetized sheep
Authors: Dodek P. M. , Valenzuela A. , Minshall D. K. , Baile E. M. , Pare P. D.
Published: December 2017

To determine if bronchial blood flow affects the consequences of acute pulmonary vascular injury, we studied oleic acid lung injury in 12 anesthetized sheep. In six sheep (group 1), we injected 2 ml of ethanol directly into the bronchoesophageal artery to decrease bronchial blood flow. In the control sheep (group 2), we injected 2 ml of normal saline. One hour later, oleic acid (0.1 ml/kg) was injected into the right ventricle in both groups. We measured hemodynamics and lung mechanics at baseline, 1 h after injection into the bronchoesophageal artery but just before the injection of oleic acid, and 3 h after injection of oleic acid. We measured bronchial blood flow at baseline and 3 h after injection of oleic acid and extravascular lung water at 3 h after injection of oleic acid. One hour after injection of ethanol or saline into the bronchoesophageal artery, hemodynamics and lung mechanics did not change. Three hours after injection of oleic acid, systemic arterial pressure decreased, pulmonary arterial pressure increased, cardiac output decreased, dynamic compliance decreased, pulmonary resistance increased, arterial oxygen tension decreased, and extravascular lung water was greater than normal. There were no differences in these measurements between the two groups. However, bronchial blood flow decreased only in group 1. We conclude that decreasing bronchial blood flow does not attenuate or accentuate the consequences of oleic acid lung injury.
High-resolution CT-derived measures of lung density are valid indexes of interstitial lung disease
Authors: Hartley P. G. , Galvin J. R. , Hunninghake G. W. , Merchant J. A. , Yagla S. J. , Speakman S. B. , Schwartz D. A.
Published: December 2017

To assess the validity of computer-assisted methods in analyzing the lung parenchyma imaged with high-resolution computed tomography (HRCT), we compared computer-derived estimates of lung density to other, more traditional, measures of parenchymal injury in 24 subjects with idiopathic pulmonary fibrosis (IPF) and 60 subjects with extensive occupational exposure to asbestos. Gray scale density histograms were constructed from the HRCT images. The gray scale histogram of both study groups was of a skewed unimodal distribution. However, compared with the asbestos-exposed subjects, the patients with IPF had a gray scale distribution that was significantly shifted to the right (greater density) and flatter. In a multivariate analysis, after controlling for age and cigarette smoking, we found that the mean and median gray scale densities were independently associated with the presence of moderate-to-severe dyspnea, a higher International Labour Office chest X-ray category, a lower forced vital capacity, and a higher concentration of macrophages and eosinophils in the bronchoalveolar lavage fluid. These factors accounted for > 70% of the variance of the mean and median gray scale densities. Interestingly, no differences in gray scale density measures were noted between patients with IPF and patients with asbestosis when these other factors were taken into account. Our results suggest that computer-derived density analysis of the lung parenchyma on the HRCT scan is a valid, clinically meaningful, and objective measure of interstitial lung disease.
Protein, cell, and LTB4 concentrations of lung edema fluid produced by high capillary pressures in rabbit
Authors: Tsukimoto K. , Yoshimura N. , Ichioka M. , Tojo N. , Miyazato I. , Marumo F. , Mathieu-Costello O. , West J. B.
Published: December 2017

We previously demonstrated disruptions of the pulmonary capillary endothelium and alveolar epithelium at transmural pressures (Ptm) of 52.5 cmH2O in rabbit by electron microscopy. In the present study, we determined the characteristics of the alveolar edema fluid in this condition by carrying out bronchoalveolar lavage after blood perfusion for 10 min at Ptm of 12.5 (low), 32.5 (intermediate), and 52.5 cmH2O (high). At low Ptm, where our previous studies showed no ultrastructural changes, the volume of alveolar fluid obtained by urea dilution was very small, and the concentrations of proteins, cells, and leukotriene B4 (LTB4) in the bronchoalveolar lavage fluid (BALF) were low. However, at high Ptm the volume of alveolar fluid and the concentrations of total protein and cells in the BALF were greatly increased. The amount of LTB4 in the BALF also increased substantially from 6.0 to 49.5 micrograms (P < 0.001). Intermediate changes were seen at intermediate Ptm. We concluded that exposing pulmonary capillaries to high Ptm results in a high-permeability form of edema. In addition, the presence of LTB4 suggests that chemical mediators are released, possibly as the result of exposure of the reactive capillary endothelial basement membrane, as demonstrated by electron microscopy.
Inotropic effects of aminophylline on canine diaphragm are enhanced by hyperinflation
Authors: Gayan-Ramirez G. , Palecek F. , Chen Y. , Janssens S. , Decramer M.
Published: December 2017

During acute hyperinflation, patients with chronic obstructive pulmonary disease are likely to have foreshortened inspiratory muscles. Because the effects of aminophylline on contractile properties of the foreshortened diaphragm have never been studied in vivo, we compared these effects with those obtained at functional residual capacity (FRC). In 12 anesthetized dogs, bilateral phrenic nerve stimulation (1, 10, 20, and 100 Hz) was performed at FRC and near total lung capacity (TLC) before and 1 h after each injection of aminophylline, given in cumulative doses of 20, 40, and 80 mg/kg (serum levels of 18.7 +/- 6.3, 29.9 +/- 5.9, and 60.4 +/- 11.9 mg/l, respectively). Passive diaphragm shortening from FRC to TLC, measured in eight animals, averaged 30 +/- 12% of the resting length and increased to 35 +/- 12 and 34 +/- 13% after 40 and 80 mg/kg, respectively. After aminophylline, the increase in transdiaphragmatic pressure at FRC did not reach statistical significance, whereas near TLC transdiaphragmatic pressure significantly increased with 80 mg/kg at all stimulus frequencies (e.g., at 20 Hz from 4.4 +/- 2.9 to 6.7 +/- 2.9 cmH2O) and with 40 mg/kg at 10 and 20 Hz. Diaphragm length changes during stimulation were unchanged after aminophylline both at FRC and near TLC. We conclude that aminophylline has a pronounced inotropic effect on foreshortened canine diaphragm, even at concentrations close to the therapeutic range in humans.