bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory muscle responses to changes in chemoreceptor drive in infants
Authors: Carlo W. A. , DiFiore J. M.
Published: December 2017

Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea.
Effect of maternal weight gain during pregnancy on exercise performance
Authors: Carpenter M. W. , Sady S. P. , Sady M. A. , Haydon B. , Coustan D. R. , Thompson P. D.
Published: December 2017

We examined the effect of maternal weight gain during pregnancy on exercise performance. Ten women performed submaximal cycle (up to 60 W) and treadmill (4 km/h, up to 10% grade) exercise tests at 34 +/- 1.5 (SD) wk gestation and 7.6 +/- 1.7 wk postpartum. Postpartum subjects wearing weighted belts designed to equal their body weight during the antepartum tests performed two additional treadmill tests. Absolute O2 uptake (VO2) at the same work load was higher during pregnancy than postpartum during cycle (1.04 +/- 0.08 vs. 0.95 +/- 0.09 l/min, P = 0.014), treadmill (1.45 +/- 0.19 vs. 1.27 +/- 0.20 l/min, P = 0.0002), and weighted treadmill (1.45 +/ 0.19 vs. 1.36 +/- 0.20 l/min, P = 0.04) exercise. None of these differences remained, however, when VO2 was expressed per kilogram of body weight. Maximal VO2 (VO2max) estimated from the individual heart rate-VO2 curves was the same during and after pregnancy during cycling (1.96 +/- 0.37 to 1.98 +/- 0.39 l/min), whereas estimated VO2max increased postpartum during treadmill (2.04 +/- 0.38 to 2.21 +/- 0.36 l/min, P = 0.03) and weighted treadmill (2.04 +/- 0.38 to 2.19 +/- 0.38 l/min, P = 0.03) exercise. We conclude that increased body weight during pregnancy compared with the postpartum period accounts for 75% of the increased VO2 during submaximal weight-bearing exertion in pregnancy and contributes to reduced exercise capacity. The postpartum increase in estimated VO2max during weight-bearing exercise is the result of consistently higher antepartum heart rates during all submaximal work loads.
Unchanged in vivo P50 at high altitude despite decreased erythrocyte age and elevated 2,3-diphosphoglycerate
Authors: Mairbaurl H. , Schobersberger W. , Oelz O. , Bartsch P. , Eckardt K. U. , Bauer C.
Published: December 2017

We measured hematological and erythrocyte O2 transport parameters in whole blood and density-separated erythrocytes in 11 mountaineers before and during 5 days of exposure to high altitude (4,559 m). We determined the in vivo (arterial pHblood and PCO2) and standard (pHblood = 7.4, PCO2 = 40 Torr) O2 tension at 50% O2 saturation of hemoglobin and (P50,vv and P50,st) and Bohr coefficients (BC) for fixed acid (H+) and CO2 and examined the contribution of the altered average age of circulating erythrocytes due to the stimulation of erythropoiesis on whole blood 2,3-diphosphoglycerate (2,3-DPG) and P50,st. At altitude, whole blood P50,vv remained almost unchanged, whereas P50,st and 2,3-DPG increased significantly (+4 Torr; 3.5 mumol/g hemoglobin). BCCO2 was elevated significantly at altitude. Serum erythropoietin increased transiently fourfold, iron utilization increased, and serum iron decreased by 66%. Reticulocyte counts increased, but other hematological parameters were unchanged. In density-separated erythrocytes, P50,st and 2,3-DPG increased with decreasing cell density but were higher in fractions with comparable reticulocyte counts in cells prepared at altitude than in those from control studies. Our data show that, despite the increase in 2,3-DPG and the decrease in average erythrocyte age, the in vivo hemoglobin-O2 affinity remains unchanged. P50,st values reflect the elevation of 2,3-DPG, and approximately 50% of the increase in both parameters can be ascribed to the increase in the number of reticulocytes and young erythrocytes.
Pleural pressure changes in dogs measured from suprasternal fossa movements
Authors: Sackner M. A. , Grenvik S. , Moavero N. E. , Belsito A. , Chapman G. , Yerger L. , Krieger B. P.
Published: December 2017

Movements of the suprasternal fossa during spontaneous breathing monitored with the surface inductive plethysmograph (SIP) have been shown to reflect changes of intrapleural pressure in conscious humans. Calibration of this device in anesthetized intubated dogs was accomplished by adjusting the electrical gain of its analog waveform to be equivalent to changes of airway pressure during inspiratory efforts against an occluded airway. This procedure, denoted the occlusion test, was also used to identify the site of esophageal balloon catheter placement for its recording of intrapleural pressure deflections. The validity of SIP-derived estimates of inspiratory and expiratory pulmonary resistances and lung compliance was established by finding close agreement with measurements obtained with intraesophageal pressure changes during 1) unimpeded spontaneous breathing, 2) inspiratory resistive loading, 3) bronchoprovocation with aerosolized carbachol, 4) mechanical ventilatory modalities, and 5) induced pulmonary edema. Therefore, movements of the suprasternal fossa with respiration can be reliably transformed into quantitative or semiquantitative changes of intrapleural pressure in anesthetized intubated dogs during major alterations of pulmonary mechanics.
Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects
Authors: Lai C. K. , Jenkins J. R. , Polosa R. , Holgate S. T.
Published: December 2017

The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist.
Effect of hemoglobin solution on compensation to anemia in the erythrocyte-free primate
Authors: Rosen A. L. , Gould S. A. , Sehgal L. R. , Sehgal H. L. , Levine H. D. , DeWoskin R. D. , Moss G. S.
Published: December 2017

Hemoglobin solutions are undergoing clinical trials as erythrocyte substitutes. Some of these solutions have higher O2 affinities compared with normal erythrocyte hemoglobin. Also, they appear to interact with endothelial-derived smooth muscle relaxation. The purpose of this study was to evaluate the nature and limits of compensation to acute normovolemic anemia in the erythrocyte-free primate maintained with a hemoglobin solution. The experimental group consisted of six anesthetized paralyzed adult baboons (Papio anubis) that were exchange transfused (ET) with a pyridoxylated polymerized hemoglobin solution [hemoglobin concentration [( Hb]) = 14 g/dl, O2 half-saturation pressure of hemoglobin (P50) = 19.6 Torr] until a hematocrit less than 1% was achieved. They underwent a second ET with Dextran-70 until [Hb] = 1 g/dl. A control group (n = 6) underwent an ET with Dextran-70 until [Hb] = 1 g/dl. Both groups maintained O2 consumption (VO2) until [Hb] = 3 g/dl. Both groups were stable until [Hb] less than 1 g/dl, and both groups increased their cardiac output. The relation between VO2 and O2 delivery was similar for both groups. In vivo P50 and mixed venous O2 tension were significantly lower in the experimental group. The nature and limits of compensation to diminished O2 delivery due to anemia were similar in the two groups.
Expiratory abdominal muscle activity during ventilatory chemostimulation in piglets
Authors: Watchko J. F. , O'Day T. L. , Brozanski B. S. , Guthrie R. D.
Published: December 2017

We examined abdominal muscle minute electromyographic (EMG) activity (peak moving time average EMG x respiratory rate) during eupnea, hyperoxic hypercapnia (8% CO2-40% O2-balance N2), and hypoxia (13% O2) in 12 anesthetized (0.5% halothane) newborn piglets. In addition, we assessed the role of vagal afferent pathways in the abdominal muscles' response to ventilatory chemostimulation by examining abdominal EMG activity (EMGab) before and after bilateral cervical vagotomy in five animals. Phasic expiratory EMGab was observed in 11 of 12 piglets during eupnea. Hypercapnia was associated with a sustained augmentation of minute EMGab (444 +/- 208% control). In contrast, hypoxia consistently augmented (1 min, 193 +/- 33% control) then diminished (5 min, 126 +/- 39% control) minute EMGab. Vagotomy resulted in a decline in peak moving time average EMGab by approximately one-half (48 +/- 18% control); the abdominal muscles' response to ventilatory chemostimulation, however, was qualitatively unchanged. We conclude that 1) expiration during eupnea in anesthetized newborn piglets is associated with phasic EMGab; 2) both hypercapnia and hypoxia augment minute EMGab; however, only hypercapnia is associated with sustained augmentation; and 3) although vagal afferents have a role in modulating the base-line level of EMGab, other extravagal mechanisms appear to determine the pattern of EMGab in response to ventilatory chemostimulation.
Silica directly increases permeability of alveolar epithelial cells
Authors: Merchant R. K. , Peterson M. W. , Hunninghake G. W.
Published: December 2017

Alveolar epithelial cell injury and increased alveolar-capillary membrane permeability are important features of acute silicosis. To determine whether silica particles contribute directly to this increased permeability, we measured paracellular permeability of rat alveolar epithelium after exposure to silica, in vitro, using markers of the extracellular space. Silica (Minusil) markedly increased permeability in a dose- and time-dependent manner. This was not the result of cytolytic injury, because lactate dehydrogenase release from monolayers exposed to silica was not increased. Pretreatment of the silica with serum, charged dextrans, or aluminum sulfate blocked the increase in permeability. Scanning electron microscopy demonstrated adherence of the silica to the surface of the alveolar epithelial cells. Thus silica can directly increase permeability of alveolar epithelium.
Determining deposition sites of inhaled lung particles and their effect on clearance
Authors: Langenback E. G. , Bergofsky E. H. , Halpern J. G. , Foster W. M.
Published: December 2017

An essential component of lung defense is clearance of particulates and infectious vectors from the mucus membrane of the tracheobronchial tree and the alveolar regions of the lung. To partition clearance between these areas we determined the bronchial branching pattern, the anatomical sites of particle deposition, and subsequent clearance in the same animal. Using a 2.85-microns particle tagged with 57Co for inhalation and deposition in the sheep lung, we followed clearance via a series of computer-stored gamma-scintillation lung images. The same sheep was reinhaled, and the particle distributions for both inhalations were compared. After the animals were killed, the bronchial branching pattern and length of the bronchial tree were documented. The number of particles depositing in all bronchi down to 1 mm diam was determined by scintillation counting, and the number in respiratory bronchioles and alveoli was microscopically counted. We conclude that particles deposited in bronchi greater than or equal to 1 mm diam clear in 2-4 h postdeposition. Bronchi distal to 1-mm-diam bronchi and alveoli clear evenly over 72 h, and the number of particles equal to the tracheobronchial deposition cleared after 45 h.
Adjustments in oxygen transport during head-out immersion in water at different temperatures
Authors: Choukroun M. L. , Varene P.
Published: December 2017

Respiratory gas exchange was investigated in human subjects immersed up to the shoulders in water at different temperatures (Tw = 25, 34, and 40 degrees C). Cardiac output (Qc) and pulmonary tissue volume (Vti) were measured by a rebreathing technique with the inert gas Freon 22, and O2 consumption (VO2) was determined by the closed-circuit technique. Arterial blood gases (PaO2, PaCO2) were analyzed by a micromethod, and alveolar gas (PAO2) was analyzed during quiet breathing with a mass spectrometer. The findings were as follows. 1) Immersion in a cold bath had no significant effect on Qc compared with the value measured at Tw = 34 degrees C, whereas immersion in a hot bath led to a considerable increase in Qc. Vti was not affected by immersion at any of the temperatures tested. 2) A large rise in metabolic rate VO2 was only observed at Tw = 25 degrees C (P less than 0.001). 3) Arterial blood gases were not significantly affected by immersion, whatever the water temperature. 4) O2 transport during immersion is affected by two main factors: hydrostatic pressure and temperature. Above neutral temperature, O2 transport is improved because of the marked increase in Qc resulting from the combined actions of hydrostatic counter pressure and body heating. Below neutral temperature, O2 transport is altered; an increase in O2 extraction of the tissue is even calculated.
Corticosteroids increase lipocortin I in BAL fluid from normal individuals and patients with lung disease
Authors: Ambrose M. P. , Hunninghake G. W.
Published: December 2017

Lipocortin I is a corticosteroid-inducible protein that has potent anti-inflammatory activity. To determine whether lipocortin I is present on the epithelial surface of the human lung, we used a specific polyclonal antibody by the technique of Western blotting to evaluate bronchoalveolar lavage (BAL) fluid of normal individuals and patients with idiopathic pulmonary fibrosis. Lipocortin I was a normal constituent of the epithelial surface of the normal lung and comprised 0.23 +/- 0.03% of BAL fluid proteins. Four separate immunoreactive species were detected, at 37, 36, 34, and 33 kDa, consistent with previously published results. Corticosteroids increased the amounts of lipocortin present in normal volunteers and in patients with idiopathic pulmonary fibrosis. These results demonstrate that lipocortin I is normally present in the human lung and further suggest that lipocortin I may be an important modulator of the anti-inflammatory effects of corticosteroids in the lung.
Exercise tolerance and pulmonary gas exchange after deep saturation dives
Authors: Thorsen E. , Hjelle J. , Segadal K. , Gulsvik A.
Published: December 2017

Pulmonary function and exercise tolerance were measured before and after three saturation dives to a pressure of 3.7 MPa. The atmospheres were heliox with partial pressures of oxygen of 40 kPa during the bottom phase and 50 kPa during the compression and decompression phase. The bottom times were 3, 10, and 13 days. Decompression time was 13 days. Precordial Doppler monitoring was done daily during the decompression, and an estimate of the total bubble load on the pulmonary circulation was calculated as the accumulated sum of bubble scores recorded for each diver. Nine of the 18 divers had chest symptoms with retrosternal discomfort or nonproductive cough after the dive. There were no changes in dynamic lung volumes. Transfer factor for carbon monoxide was significantly reduced from 12.3 +/- 1.2 to 10.9 +/- 1.3 mmol.kPa-1.min-1 (P less than 0.01), and maximum oxygen uptake was reduced from 3.98 +/- 0.36 to 3.42 +/- 0.37 l/min STPD (P less than 0.01) after the dives. Resting heart rate was increased from 64 +/- 6 to 75 +/- 8 min-1 (P less than 0.01). The ventilatory requirements in relation to oxygen uptake and carbon dioxide elimination were significantly increased (P less than 0.01) after the dives. The physiological dead space fraction of tidal volume was significantly higher and showed an increase with larger tidal volumes (P less than 0.05). Anaerobic threshold estimated from gas exchange data decreased from an oxygen uptake of 2.30 +/- 0.25 to 1.95 +/- 0.28 l/min STPD (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of corticosteroids on postnatal lung and airway growth in the ferret
Authors: Ellington B. , McBride J. T. , Stokes D. C.
Published: December 2017

To investigate the influence of corticosteroids on postnatal lung and airway growth, young male ferrets were given cortisone acetate (20 mg/kg im daily) beginning at 8 wk of age. At 19 wk of age pulmonary function was measured. The lungs were excised for measurements of recoil pressures and wet and dry weights. The dimensions of central and peripheral airways were estimated from analysis of bronchial casts. Corticosteroid-treated animals were shorter and tended to be lighter than control animals but were heavier in relation to length. Total lung capacity was reduced in proportion to the reduction in body size. Lung recoil and wet-to-dry weight ratios were nearly identical. Maximal expiratory flows were reduced in proportion to the reduction in body size. Size-corrected airway conductance was reduced, suggesting a sensitivity of central airways to growth suppression by corticosteroids. Peripheral airways, on the other hand, were not smaller in treated animals and were larger in proportion to body size. In the ferret corticosteroid administration is associated with a suppression of lung parenchymal growth similar to that of overall body growth. The peripheral airways may be less sensitive and the central airways more sensitive to the effect of corticosteroids on growth.
PO2 modulation of paraquat-induced microvascular injury in isolated dog lungs
Authors: Shibamoto T. , Taylor A. E. , Parker J. C.
Published: December 2017

We determined the effects of paraquat (PQ) concentrations ranging from 10(-3) to 10(-2) M and three levels of venous PO2 [hypoxia (41 +/- 3 Torr), normoxia (147 +/- 8 Torr), and hyperoxia (444 +/- 17 Torr)] in the presence of 4 x 10(-3) M PQ on microvascular permeability in isolated blood-perfused dog lungs. Capillary filtration coefficient (Kf,c) increased and isogravimetric capillary pressure (Pc,i) decreased 3 h after perfusion with 10(-2) M PQ (n = 7) and 5 h after perfusion with 4 x 10(-3) M PQ (n = 6) but not with 10(-3) M PQ (n = 4). In hyperoxic lungs perfused with 4 x 10(-3) M PQ, Kf,c increased to nine times the base-line value 5 h after PQ [0.15 +/- 0.01 to 1.35 +/- 0.25 (SE) ml.min-1.cmH2O-1.100 g-1]. Pc,i significantly decreased from a base-line value of 9.4 +/- 0.2 to 7.1 +/- 0.4 cmH2O at 3 h. In hypoxic lungs perfused with 4 x 10(-3) M PQ (n = 5), Pc,i and Kf,c changes were not significantly different from those in normoxic lungs treated with PQ. Thus both hyperoxia and an increased dose of PQ shortened the latent period and increased the severity of the PQ-induced microvascular permeability lesion, but hypoxia failed to prevent the PQ damage.
Effects of tidal volume and methacholine on low-frequency total respiratory impedance in dogs
Authors: Lutchen K. R. , Jackson A. C.
Published: December 2017

The frequency dependence of respiratory impedance (Zrs) from 0.125 to 4 Hz (Hantos et al., J. Appl. Physiol. 60: 123-132, 1986) may reflect inhomogeneous parallel time constants or the inherent viscoelastic properties of the respiratory tissues. However, studies on the lung alone or chest wall alone indicate that their impedance features are also dependent on the tidal volumes (VT) of the forced oscillations. The goals of this study were 1) to identify how total Zrs at lower frequencies measured with random noise (RN) compared with that measure with larger VT, 2) to identify how Zrs measured with RN is affected by bronchoconstriction, and 3) to identify the impact of using linear models for analyzing such data. We measured Zrs in six healthy dogs by use of a RN technique from 0.125 to 4 Hz or with a ventilator from 0.125 to 0.75 Hz with VT from 50 to 250 ml. Then methacholine was administered and the RN was repeated. Two linear models were fit to each separate set of data. Both models assume uniform airways leading to viscoelastic tissues. For healthy dogs, the respiratory resistance (Rrs) decreased with frequency, with most of the decrease occurring from 0.125 to 0.375 Hz. Significant VT dependence of Rrs was seen only at these lower frequencies, with Rrs higher as VT decreased. The respiratory compliance (Crs) was dependent on VT in a similar fashion at all frequencies, with Crs decreasing as VT decreased. Both linear models fit the data well at all VT, but the viscoelastic parameters of each model were very sensitive to VT. After methacholine, the minimum Rrs increased as did the total drop with frequency. Nevertheless the same models fit the data well, and both the airways and tissue parameters were altered after methacholine. We conclude that inferences based only on low-frequency Zrs data are problematic because of the effects of VT on such data (and subsequent linear modeling of it) and the apparent inability of such data to differentiate parallel inhomogeneities from normal viscoelastic properties of the respiratory tissues.
Selective permeability changes in the lungs and airways of sheep after toxic smoke inhalation
Authors: Barrow R. E. , Morris S. E. , Basadre J. O. , Herndon D. N.
Published: December 2017

The effect of toxic smoke inhalation on selective microvascular sieving of macro-molecules and lymph protein flux was assessed in adult sheep to determine whether the time course of microvascular dysfunction differs between the lung and trachea. Protein flux across the lung increased sixfold 48 h after inhalation of the products of incomplete cotton combustion, whereas tracheal protein flux increased fivefold 8 h after exposure and returned to near base line 48 h after exposure. The lung and trachea selectively retained some sieving to three different protein macromolecules with molecular radii of 36, 54, and 123 A. In the lungs the sieving selectivity for these macromolecules was least 48 h after injury, and in the trachea molecular selectivity was least 8 h after injury. These data suggest that the time course of microvascular injury differs for the trachea and the lung; microvascular changes are detected earlier in the trachea than in the lung. The inhalation injury described thus permits the characterization of the time course of airway and lung microvascular changes.
Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise
Authors: Brown D. R. , Forster H. V. , Pan L. G. , Brice A. G. , Murphy C. L. , Lowry T. F. , Gutting S. M. , Funahashi A. , Hoffman M. , Powers S.
Published: December 2017

Seven human spinal cord-lesioned subjects (SPL) underwent electrically induced muscle contractions (EMC) of the quadriceps and hamstring muscles for 10 min: 5 min control, 2 min with venous return from the legs occluded, and 3 min postocclusion. Group mean changes in CO2 output compared with rest were +107 +/- 30.6, +21 +/- 25.7, and +192 +/- 37.0 (SE) ml/min during preocclusion, occlusion, and postocclusion EMC, respectively. Mean arterial CO2 partial pressure (PaCO2) obtained from catheterized radial arteries at 15- to 30-s intervals showed a significant (P less than 0.05) hypocapnia (36.2 Torr) during occlusion and a significant (P less than 0.05) hypercapnia (38.1 Torr) postocclusion relative to a group mean preocclusion EMC PaCO2 of 37.5 Torr. Relative to preocclusion EMC, expired ventilation (VE) decreased during occlusion and increased after release of occlusion. However, changes in VE always occurred after changes in end-tidal PCO2 (mean 41 s after occlusion and 10 s after release of occlusion). In the two subjects investigated during hyperoxia, the VE and PaCO2 responses to occlusion and release did not differ from normoxia. We conclude that the data do not support mediation of the EMC hyperpnea in SPL by humoral mechanisms that others have proposed for mediation of the exercise hyperpnea in spinal cord-intact humans.
Modeling flux of free and protein-bound radioisotopes into the pulmonary interstitium
Authors: Riddle W. R. , Roselli R. J. , Pou N. A.
Published: December 2017

Several groups of investigators are using external detection of radiolabeled protein to study the flux of protein from plasma into the pulmonary interstitium. A basic assumption for these studies has been that the unbound (free) tracer concentration is small and insignificant. The purpose of this study is to evaluate how free tracer influences the determination of normalized slope index. A five-compartment model for the lung was used with transport equations for both unbound and bound nuclide flux. Parameters of the unbound and bound transport equations were varied to evaluate the sensitivity of normalized slope index to each parameter. The model was also compared with published protein flux data to investigate the validity of the transport model. Application of the model to external scan data provides a sensitive method for evaluating the flux of bound and unbound tracers into the pulmonary interstitium. We conclude that because the distribution volume for unbound tracer is large with respect to protein distribution volume, even a small amount of unbound tracer (2-5%) can create large errors in the determination of normalized slope index.
Selective reflex activation of the genioglossus in humans
Authors: Leiter J. C. , Daubenspeck J. A.
Published: December 2017

In anesthetized or decerebrate animals, negative pressure applied to the upper airway selectively activates the hypoglossal nerve compared with the phrenic nerve. Conversely, positive pressure reduces hypoglossal nerve activity out of proportion to any change in the phrenic neurogram. We have tested the hypothesis that analogous pressure changes applied to awake humans would selectively inhibit or activate genioglossal electromyographic (EMGge) activity relative to diaphragmatic electromyographic activity (EMGdi). We studied seven normal subjects in a head-out body plethysmograph. Pressure at the mouth was either atmospheric, +10 cmH2O, or -10 cmH2O, and lung volume was held constant by applying an identical pressure to the body surface. Thus the transmural pressure distorting the respiratory system was applied only to the upper airway. Subjects breathed CO2-enriched (2-3%) room air to stimulate phasic respiratory EMGge activity. We found that -10 cmH2O pressure applied selectively to the upper airway resulted in a 49% enhancement of peak-integrated EMGge activity, but EMGdi activity remained at control levels. Positive pressure did not result in any changes in EMGge or EMGdi activity. Neither pressure resulted in significant changes in the magnitude or pattern of ventilation. We conclude that reflex mechanisms maintaining upper airway patency are demonstrable in awake humans and probably have an important role in moment-to-moment modulation of upper airway muscle activity in normal awake humans.
Pleural pressure as a function of body position in rabbits
Authors: Olson L. E. , Wardle R. L.
Published: December 2017

Pleural pressure was measured at end expiration in spontaneously breathing anesthetized rabbits. A liquid-filled capsule was implanted into a rib to measure pleural liquid pressure with minimal distortion of the pleural space. Capsule position relative to lung height was measured from thoracic radiographs. Measurements were made when the rabbits were in the prone, supine, right lateral, and left lateral positions. Average lung heights in the prone and supine positions were 4.21 +/- 0.58 and 4.42 +/- 0.51 (SD) cm, respectively (n = 7). Pleural pressure was -2.60 +/- 1.87 (SD) cmH2O at 50.2 +/- 7.75% lung height in the prone position and -3.10 +/- 1.22 cmH2O at 51.4 +/- 6.75% lung height in the supine position. There was no difference between the values recorded in the prone and supine positions. Placement of the capsule into the right or left chest had no effect on the magnitude of the pleural pressure recorded in rabbits in right and left lateral recumbency (n = 12). Measurements over the nondependent lung were repeatable when rabbits were turned between the right and left lateral positions. Lung height in laterally recumbent rabbits averaged 4.55 +/- 0.52 (SD) cm.
Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs
Authors: Stephenson A. H. , Sprague R. S. , Dahms T. E. , Lonigro A. J.
Published: December 2017

Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.
Nontoxic and durable salt bridges using hydroxyethylmethacrylate hydrogels
Authors: Kindler D. D. , Bergethon P. R.
Published: December 2017

Polyhydroxyethylmethacrylate polymers (poly-HEMA) form hydrogels that provide an excellent alternative to agar in the production of salt bridges for use in bioelectrochemical experiments. A method for the simple production of poly-HEMA salt bridges is described. The poly-HEMA bridges were compared with agar bridges of similar geometry. Whereas poly-HEMA salt bridges have a conductivity that is 20 times lower than that of agar bridges of a similar geometry, poly-HEMA bridges are capable of dissipating twice the power compared with agar bridges. The mechanical properties of the poly-HEMA bridges make them easy to manufacture, store, and sterilize. When agar bridges were compared with poly-HEMA bridges in long-term cell culture experiments, the failure rate of the agar bridges was found to be approximately 10% per week vs. a virtually nonexistent failure rate for the poly-HEMA bridges. Because poly-HEMA salt bridges are reliable, durable, and nontoxic to cells, they are a practical alternative to agar salt bridges in certain experimental designs.
Effect of separate hemidiaphragm contraction on left phrenic artery flow and O2 consumption
Authors: Hu F. , Comtois A. , Shadram E. , Grassino A.
Published: December 2017

Phrenic arterial blood flow has been shown to increase during bilateral phrenic nerve stimulation (BPNS). However, the role of unilateral phrenic nerve stimulation [left (LPNS) or right (RPNS)] on the blood flow and O2 consumption of the contralateral hemidiaphragm is not known and is explored here. In six anesthetized, mechanically hyperventilated dogs, left phrenic arterial blood flow (Qlpha) was measured (Doppler technique). Supramaximal (10 V, 30 Hz, 0.25-ms duration) LPNS, RPNS, and BPNS at a pacing frequency 15/min and duty cycle of 0.50 were delivered in separate runs. Left hemidiaphragmatic blood samples for gas analyses were obtained by left phrenic venous cannulation. During RPNS, Qlpha and left hemidiaphragmatic O2 consumption (VO2ldi) did not change significantly compared with control. During LPNS and BPNS, there was a significant increase in Qlpha and VO2ldi (P less than 0.01). There was no significant difference in Qlpha and VO2ldi between LPNS and BPNS (P greater than 0.05). We conclude 1) that there is a complete independence of left-right hemidiaphragmatic circulation both at rest and during diaphragm pacing and 2) that during unilateral stimulation transdiaphragmatic pressure is not related to diaphragmatic blood flow.
Periodic flow at airway bifurcations. I. Development of steady pressure differences
Authors: Tsuda A. , Fredberg J. J.
Published: December 2017

In studies of large-amplitude periodic flows at an airway bifurcation, we found an appreciable steady-state pressure difference between the terminal units. To elucidate the fluid dynamic origins of such steady-state pressure differences, we studied single asymmetric bifurcation models with various area ratios and branching angles. The daughter ducts were identical in size and were terminated into identical elastic loads. Sinusoidal flow oscillations were applied at the parent duct so that the upstream Reynolds number ranged from 30 to 77,000 and the Womersley parameter from 2 to 30. The steady-state component (time averaged) of the pressure measured at the terminal with the smaller branching angle was found to be consistently higher than that at the other terminal. This steady-state pressure difference scaled approximately as a fixed fraction of the parent duct dynamic head. Guided by the results of flow-visualization studies, we modeled such behavior based on the temporal and spatial differences of head loss between the two branches of the bifurcation. Our results suggest that interlobar heterogeneity of mean alveolar-pressure observed in excised canine lungs during high frequency oscillation (Allen et al., J. Appl. Physiol. 62: 223-228, 1987) arises solely from fluid dynamic origins: differential head loss due to asymmetry of central airway branching structure.
Urinary N tau-methylimidazole acetic acid excretion in respiratory disease
Authors: Taylor I. K. , O'Malley G. , Murray S. , Turner N. , Taylor G. W. , Fuller R. W. , Pride N. , Dollery C. T.
Published: December 2017

N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.
Administration of a synthetic antiprotease reduces smoke-induced lung injury
Authors: Niehaus G. D. , Kimura R. , Traber L. D. , Herndon D. N. , Flynn J. T. , Traber D. L.
Published: December 2017

Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibitor of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive alpha 2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460% increases in flux compared with 180% in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.
Two discharge patterns of carotid body chemoreceptors in the goat
Authors: Niu W. Z. , Engwall M. J. , Bisgard G. E.
Published: December 2017

Twenty-nine single carotid body chemoreceptor units recorded during normocapnic normoxia from 20 anesthetized goats were classified into two groups by discharge pattern. Thirteen fibers, which had interspike interval distributions with a prominent peak [24.0 +/- 9.8% (SD)] at 0- to 20-ms bin, were termed bursting fibers (BF). The 16 remaining fibers were termed nonbursting fibers (NBF); these had no notable peak in the interval distributions. During hypoxia and hypercapnia, the chemoreceptor fibers continued to discharge in their established patterns. The interval distribution of most NBF spike trains could be described with the Poisson process, but none of the BF could be. However, except for the intervals in the range of 0-20 ms, the interval distribution of the BF could be described as exponential. This study suggests that 1) there are two distinct populations of the goat chemoreceptor fiber, each with an inherent discharge pattern; 2) the chemoreceptor did not code information about arterial PO2 and PCO2 in different patterns; and 3) the basic chemotransduction mechanism is likely the same in BF and NBF, and the difference in discharge pattern is more likely to reflect processes downstream from the transducer.
Depression of posttetanic twitch potentiation by low calcium and calcium channel antagonists
Authors: Williams J. H.
Published: December 2017

The purpose of this investigation was to determine if antagonizing extracellular calcium influx altered posttetanic twitch potentiation (PTP). Whole muscles and muscle fiber bundles (less than or equal to 25 fibers) dissected from frog sartorius and semitendinosus muscles were mounted at optimal length in a normal Ringer solution (NR). To determine PTP, isometric twitches were evoked every 10 s (0.1 Hz) before and after a 2.5-s tetanic contraction (80 Hz). To antagonize calcium influx, low-calcium Ringer [LCR, calcium replaced by 3 mM magnesium and 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], NR plus diltiazem (Dilt, 30 microM), NR plus nifedipine (Nif, 10 microM), and NR plus D 600 (30 microM) were also used (n = 8 for each condition). These conditions altered pretetanic twitch tension by only -1.2 +/- 2.4, 4.2 +/- 2.3, 4.7 +/- 3.7, and 1.6 +/- 3.7% (SE), (LCR, Dilt, Nif, and D 600, P greater than 0.05) but caused a noticeable decrease in tension at the end of the tetanus. Under NR conditions, twitches evoked immediately after the tetanus were potentiated by 49.5 +/- 0.4% with the peak rate of tension development (dP/dt) increased by 44.9 +/- 0.5% (P less than 0.05). Antagonizing calcium influx depressed the PTP response by 59.8 +/- 6.2, 55.9 +/- 10.1, 73.2 +/- 6.8, and 29.8 +/- 3.6% (P less than 0.05) and increased dP/dt by 65.8 +/- 11.1, 45.7 +/- 8.6, 55.6 +/- 4.4% and 49.0 +/- 10.5% (P less than 0.05). Addition of drugs immediately after the tetanus only slightly reduced PTP but accelerated recovery of the twitch.(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous opioid effects on abdominal muscle activity during inspiratory loading
Authors: Scardella A. T. , Petrozzino J. J. , Mandel M. , Edelman N. H. , Santiago T. V.
Published: December 2017

In a previous study in unanesthetized goats, we demonstrated that continuous naloxone (NLX) administration during inspiratory flow-resistive loading (IRL) significantly increased tidal volume (VT) but not diaphragm electromyogram (EMGdi). End-expiratory gastric pressure did increase with NLX, implying that increased abdominal muscle activity may have accounted for the NLX effect. In the current study we directly tested the hypothesis that endogenous opioid elaboration depresses the abdominal muscle response to a continuous inspiratory flow-resistive load. In seven unanesthetized goats, VT, arterial blood gases, EMGdi, and EMG activity of external oblique (EMGeo), transversus abdominis (EMGta), and external intercostal (EMGei) muscles were monitored. IRL (50 cmH2O.l-1.s) was continued for 3 h, after which NLX (0.1 mg/kg) or saline was given. Our results showed that VT decreased from 323 +/- 32 (SE) ml at baseline to 260 +/- 16 ml 5 min after the load was imposed (P less than 0.05) and further decreased to 229 +/- 18 and 217 +/- 15 ml by 120 and 180 min, respectively (180 vs. 5 min, P less than 0.05). EMGdi increased from 62 +/- 5 to 83 +/- 4% max at 5 min (P less than 0.05) but was unchanged thereafter. In contrast, for this same time period EMGeo increased from 35 +/- 5 to 58 +/- 11% max but decreased from 67 +/- 11% max at 120 min to 37 +/- 5% max at 180 min (P less than 0.05). NLX administration resulted in significant increases in EMGeo (91% above 180-min value). In contrast, EMGdi increased minimally after NLX (15% above 180-min value).(ABSTRACT TRUNCATED AT 250 WORDS)
Roles of absolute and relative load in skin vasoconstrictor responses to exercise
Authors: Taylor W. F. , Johnson J. M. , Kosiba W. A.
Published: December 2017

Systemic hemodynamic responses to exercise (e.g., heart rate, blood pressure) depend on the relative intensity, the active muscle mass, and the mode of exercise. It is not known whether regional vasomotor responses follow the same pattern. To answer this question, in five men we examined cutaneous vascular responses to dynamic and isometric exercise of two legs, one leg, one arm, and one hand, each at high and low work loads. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at the forearm. Mean arterial pressure (MAP) was measured each minute. Cutaneous vascular conductance (CVC) was indexed as LDF/MAP. Reductions in CVC during the 1st min of dynamic exercise were statistically significant for two-leg exercise at either level and for one-leg exercise at the higher level. Dynamic exercise of smaller muscle groups at either intensity was not associated with significant changes in CVC. The reduction in CVC correlated with external work load (r = 0.75). Work load relative to the capacity of a given muscle group had no identifiable role in the response of CVC to dynamic exercise but did have a role in the increase in MAP at the beginning of exercise. Isometric exercise did not have a measurable effect on CVC regardless of the muscle group or the intensity of the exercise. We conclude that the level of external work determines the redistribution of blood flow from skin to active muscle. Furthermore, absolute rather than relative work and dynamic rather than isometric modes of exercise are the dominant factors.
Succinylcholine potentiates responses to intravenous acetylcholine in the canine lung periphery
Authors: Kaise A. , Weinmann G. G. , Levitt R. C. , Hirshman C. A.
Published: December 2017

Using the wedged bronchoscope technique to measure collateral resistance (Rcs), we evaluated the effect of succinylcholine (SCh) on the response to acetylcholine (ACh) and methacholine (MCh) in the lung periphery in six mongrel dogs. Dogs were anesthetized, intubated, and mechanically ventilated. After a stable baseline Rcs was obtained, responses to intravenous ACh (25-200 micrograms), intravenous MCh (3-30 micrograms), and aerosolized ACh (30-100 micrograms/ml for 15 s) were measured. We compared the Rcs responses with 1) ACh alone, 2) ACh 2 min after SCh (0.5 mg/kg), 3) ACh 2 min after SCh and during hexamethonium infusion (5 mg/kg + 10 mg.kg-1.h-1), 4) MCh 2 min after SCh, and 5) ACh aerosol 2 min after SCh. SCh did not significantly alter baseline airway tone. SCh increased the Rcs response to ACh by 48 +/- 17% (SE) (P less than 0.01). SCh in the presence of hexamethonium increased the Rcs response by 10 +/- 3% (P less than 0.05), while hexamethonium itself increased the response to ACh by 69 +/- 27%. Because SCh did not increase the Rcs response to intravenous MCh or to aerosolized ACh, SCh probably enhances airway reactivity to intravenous ACh by competing for pseudocholinesterase in plasma. We conclude that the level of muscle relaxant must be taken into account in interpreting studies of airway reactivity when intravenous ACh is employed.