bluuebunny/crossref_metadata_2025 huggingface dataset:
Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma
Authors: Hardy C. C. , Bradding P. , Robinson C. , Holgate S. T.
Published: December 2017

Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.
Evaluation of Starling forces in the equine digit
Authors: Allen D. , Korthuis R. J. , Clark S.
Published: December 2017

A pump-perfused extracorporeal digital preparation was used to evaluate blood flow, arterial pressure, venous pressure, isogravimetric capillary filtration coefficient, capillary pressure, and vascular compliance in six normal horses. From these data, pre- and postcapillary resistances and pre- and postcapillary resistance ratios were determined. Vascular and tissue oncotic pressures were estimated from plasma and lymph protein concentrations, respectively. By use of the collected and calculated data, tissue pressure in the digit was calculated using the Starling equation. In the isolated equine digit, isogravimetric capillary pressure averaged 36.7 mmHg, plasma and lymph oncotic pressures averaged aged 19.12 and 6.6 mmHg, respectively, interstitial fluid pressure averaged 25.6 mmHg, and the capillary filtration coefficient averaged 0.0013 ml.min-1.mm-1.100 g-1. Our results indicate that digital capillary pressure in the laterally recumbent horse is much higher than in analogous tissues in other species such as dog and human. However, the potential edemagenic effects of this high digital capillary pressure are opposed by at least two mechanisms: 1) a high tissue pressure and 2) a low microvascular surface area for fluid exchange and/or a low microvascular permeability to filtered fluid.
Gluconeogenic pathway in liver and muscle glycogen synthesis after exercise
Authors: Johnson J. L. , Bagby G. J.
Published: December 2017

To determine whether prior exercise affects the pathways of liver and muscle glycogen synthesis, rested and postexercised rats fasted for 24 h were infused with glucose (200 mumol.min-1.kg-1 iv) containing [6-3H]glucose. Hyperglycemia was exaggerated in postexercised rats, but blood lactate levels were lower than in nonexercised rats. The percent of hepatic glycogen synthesized from the indirect pathway (via gluconeogenesis) did not differ between exercised (39%) and nonexercised (36%) rats. In red muscle, glycogen was synthesized entirely by the direct pathway (uptake and phosphorylation of plasma glucose) in both groups. However, only approximately 50% of glycogen was formed via the direct pathway in white muscle of exercised and nonexercised rats. Therefore prior exercise did not alter the pathways of tissue glycogen synthesis. To further study the incorporation of gluconeogenic precursors into muscle glycogen, exercised rats were infused with either saline, lactate (100 mumol.min-1.kg-1), or glucose (200 mumol.min-1.kg-1), containing [6-3H]glucose and [14C(U)]lactate. Plasma glucose was elevated one- to twofold and three- to fourfold by lactate and glucose infusion, respectively. Plasma lactate levels were elevated by about threefold during both glucose and lactate infusion. Glycogen was partially synthesized via an indirect pathway in white muscle and liver of glucose- or lactate-infused rats but not in saline-infused animals. Thus participation of an indirect pathway in white skeletal muscle glycogen synthesis required prolonged elevation of plasma lactate levels produced by nutritive support.
Spectral analysis of inert gas elimination data: resolution limits
Authors: Poon C. S.
Published: December 2017

A new method of analyzing inert gas data for recovery of the pulmonary ventilation-perfusion ration (VA/Q) distribution is proposed. It is shown that the conventional inert gas elimination equation takes the form of a convolution integral, and the relationship between VA/Q distribution and inert gas elimination resembles that of a noncausal low-pass filter with infinite zero-frequency gain. With the use of this formulation, characteristic features of VA/Q distribution may be represented in the frequency domain in terms of the corresponding energy spectrum. It is shown that the lack of resolution associated with finite data samples and measurement error is caused by distortions in the high-frequency contents of the resulting VA/Q distribution. With six inert gases, the technique cannot resolve a log SD less than 0.21 decade and a modal separation less than 0.87 decade. In the presence of measurement error, the degree of resolution is even less. It is suggested that for maximum resolution the number of discrete and duplicate data samples should be chosen so that the resulting noise and sampling cutoff frequencies are approximately equal.
A model for quantitative strength training of hindlimb muscles of the rat
Authors: Klitgaard H.
Published: December 2017

Rats were taught to lift up a lever to train the plantar flexors. After 2 wk of adaptation the rats were trained for 36 wk. The mass of weights on the lever rose by 85% over the 36-wk period (P less than 0.05) The estimated force that the plantar flexors had to develop to lift the lever rose by 32% (P less than 0.05), just as the work per lift rose by 28% (P less than 0.05). For the trained group of rats the soleus muscles of the right and the left limb were 34% (P less than 0.05) and 31% (P less than 0.05) heavier, respectively, after the training period than those of the control group. Similarly, the plantaris muscles of both the right and the left limb were 24% heavier (P less than 0.05). For the trained group the maximum twitch and tetanus tensions of the soleus were 63% (P less than 0.05) and 65% (P less than 0.05) higher, respectively. Relative to the plantaris these measures were 79% (P less than 0.05) and 37% (P less than 0.05), respectively. The described model, therefore, seems appropriate for the study of the skeletal muscles' adaptation to usage.
Time-dependent variations of transcutaneous PCO2 level in normal subjects
Authors: Pilsbury D. , Hibbert G.
Published: December 2017

Transcutaneous PCO2 (PtcCO2), which is linearly related to arterial PCO2, was continuously recorded in healthy, adult, normal volunteers for 8-h periods. Recording this variable with the apparatus employed permits measurement of changes in the level of ventilation while subjects are freely ambulant and unencumbered by invasive and flow-resistive respiratory apparatus. The time series obtained exhibited marked periodicities. The frequencies and amplitudes varied between subjects. Peak-to-peak variation was 10–20% of mean values. There was no apparent association between fluctuations in PCO2 and activity other than formal exercise. Visual inspection of the time series and preliminary statistical analysis of digitally converted data suggested that the time-dependent changes of PtcCO2 were normally distributed. However, more rigorous statistical examination revealed that in no case was PtcCO2 actually normally distributed.
Iron deficiency anemia and steady-state work performance at high altitude
Authors: Beard J. L. , Haas J. D. , Tufts D. , Spielvogel H. , Vargas E. , Rodriguez C.
Published: December 2017

Thirty-seven young adult male highland residents at 3,600–4,100 m in La Paz, Bolivia, performed short-duration cycle ergometry at 60, 80, and 100% of maximal voluntary O2 consumption (VO2max). Three groups of subjects representing the high-altitude population mean hemoglobin (Hb), the 10th percentile Hb, and below the 1st percentile were examined to test the hypothesis that the relationship of exercise performance to Hb concentration is similar to those relationships established at low altitude. Anemic individuals (n = 8) had 23% lower voluntary VO2max and 28% lower maximal work loads compared with controls (n = 17) or marginally anemic subjects (n = 12) although the relationship of VO2 to work load was similar. Anemic individuals maintained significantly higher arterial O2 partial pressures and Hb saturations during heavy exercise (90 +/- 0.5 vs. 85 +/- 0.6%) in conjunction with a greater heart rate up to maximal effort. A significantly decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG)-to-Hb molar ratio (0.70 +/- 0.04 vs. 1.12 +/- 0.06), suggestive of a left-shifted dissociation curve in anemics, is in contrast to the expected right-shifted curve. Moderate anemics were similar to controls. Anemic individuals did not differ in arterial lactate concentration from controls at absolute work loads; anemics had significantly lower arterial lactate concentrations at maximal effort than controls with no differences in the work load-to-lactate relationship. In conclusion, O2 transport during exercise at high altitude seems unaffected by the Hb concentrations as low as the 10th percentile of the population mean.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of food restriction and hyperoxia on rat survival and lung polyamine metabolism
Authors: Elsayed N. M. , Tierney D. F. , Hacker A. D.
Published: December 2017

We fed Sprague-Dawley rats either freely or by restricting them to 20% of their usual diet for 21 days. In one experiment, we refed half of the food-restricted rats for 12 h, then exposed the three groups to air or 85% O2 for 5 days. The mortalities in 85% O2 were 100, 33, and 0% for the food-restricted, restricted-refed, and freely fed groups, respectively. In air lung polyamine contents and glucose 6-phosphate dehydrogenase and NADP-dependent isocitrate dehydrogenase activities were significantly lower with food restriction. After hyperoxia, lung polyamine and protein contents and enzyme activities were increased in the two surviving groups, but spermine and DNA contents of refed rats did not increase. In a second experiment, we exposed rats to 60% O2 and found that DNA synthesis of food-restricted rats was lower than the freely fed rats in air and remained low after hyperoxia. We conclude that food restriction increases the mortality from 85% O2 and is associated with lower DNA synthesis and polyamine content. We speculate that food-restricted animals may accumulate greater lung injury partly because of a compromised repair process.
Role of transferrin and ceruloplasmin in antioxidant activity of lung epithelial lining fluid
Authors: Pacht E. R. , Davis W. B.
Published: December 2017

Lung epithelial lining fluid (ELF) is a thin layer of plasma ultrafiltrate and locally secreted substances that may provide antioxidant protection and serve as a "front-line" defense for the lower respiratory tract epithelium. To characterize the antioxidant properties of ELF, young, healthy, nonsmoking volunteers underwent bronchoalveolar lavage with determination of ELF volumes and ELF proteins. ELF (greater than 0.4 ml) is a potent inhibitor of lipid peroxidation as measured by malondialdehyde (MDA) production in an in vitro iron-dependent assay system. Two serum proteins, transferrin and ceruloplasmin, were quantitated in ELF and found to be potent inhibitors of lipid peroxidation. Other ELF components, including vitamin E, vitamin C, and albumin, did not function as antioxidants in this system. Several experimental observations suggest that ELF transferrin was more important than ceruloplasmin in inhibiting lipid peroxidation: 1) ELF concentrations of transferrin were 20-fold higher than those for ceruloplasmin; 2) ELF antioxidant activity was abolished by preincubation with Fe3+; 3) ELF antioxidant activity was minimally affected by sodium azide, which is known to inhibit ceruloplasmin ferroxidase activity; and 4) ELF ceruloplasmin ferroxidase activity was virtually nondetectable. ELF possesses a significant antioxidant activity that may be important in vivo in protecting the lung from oxidant injury.
A model of constant-flow ventilation in a dog lung
Authors: Ingenito E. , Kamm R. D. , Watson J. W. , Slutsky A. S.
Published: December 2017

A semiempirical model of constant-flow ventilation (CFV) is developed to test the hypothesis that a three-zone serial model with the following characteristics can explain the adequate CO2 transport observed during CFV: 1) a zone of jet recirculation immediately downstream of the catheter in which convection dominates; 2) a zone influenced by turbulence but with little or no bulk flow; and 3) a peripheral zone, free of turbulence, in which transport is governed by molecular and augmented diffusion. Interactions between turbulent eddies and cardiogenic oscillations are included using a modification of Taylor dispersion theory according to the formulation of Kamm et al. Predicted values for arterial PCO2 are reasonably similar to experimental results for He-O2, air, and SF6-O2 mixtures for catheter flow rates from 0.2 to 1.6 l/s. Specific impedance to gas exchange was found to be largest immediately proximal to the end of turbulent mixing zone, where transport is governed by low-level eddy mixing and molecular diffusion. Simulations suggest that, during CFV, cardiogenic oscillations augment gas exchange primarily by promoting turbulent eddy dispersion in the distal airways and by extending the length of the turbulent mixing zone. Even small displacements of the catheter are shown to have a dramatic effect on gas exchange.
Intra-airway thermodynamics during exercise and hyperventilation in asthmatics
Authors: Gilbert I. A. , Fouke J. M. , McFadden E. R.
Published: December 2017

To determine whether exercise and hyperventilation produce the same intrathoracic thermal events in asthmatics, we used a thermal probe to record airstream temperatures during both stimuli at multiple points within the tracheobronchial tree. From these data, the global and regionally distributed exchanges of water and heat that occurred throughout the respiratory tract were calculated. During each provocation, intra-airway temperatures fell equivalently, thereby producing similar intrathoracic water fluxes and heat transfers. Neither stimulus was associated with airway drying, and both resulted in similar distributed losses of thermal energy from the tracheobronchial tree despite small regional heat and water exchanges. The degree of airway obstruction was identical after both challenges; however, the onset of airway narrowing was earlier with hyperventilation and developed in association with more rapid rewarming. These data demonstrate that the hyperpnea of exercise and hyperventilation produce identical thermal consequences within the respiratory tract of asthmatics.
Coronary artery embolization in closed-chest canines using flexible radiopaque plugs
Authors: Herr M. D. , McInerney J. J. , Copenhaver G. L. , Morris D. L.
Published: December 2017

A new technique induces localized myocardial infarction in closed-chest dogs by placing discrete plugs in coronary arteries without using cumbersome coaxial catheters or guide wires. Flexible plugs, essential to this method, are formed by extruding a dental impression polymer, rendered radiopaque with sodium iodide, into spaghetti-like strands. Segments of these strands can be injected through a catheter into a selected coronary artery. Contact with blood or saline causes plugs to swell. The mean increase in plug diameter due to swelling was 27 +/- 20%. Eight anesthetized dogs were embolized via carotid approach [6 left anterior descending (LAD), 1 left circumflex (LCX), and 1 LAD and LCX]. Plug positions were monitored fluoroscopically. One animal died at 2 days postembolization. The remaining seven dogs were killed after 14–37 days. Autopsies showed complete vessel occlusion and localized infarction. Infarcts resulting from coronary artery occlusion with one, two, or three plugs involved 2–26% of the left ventricular mass.
Impaired muscle glycogen storage after muscle biopsy
Authors: Costill D. L. , Pearson D. R. , Fink W. J.
Published: December 2017

To assess the effects of repeated needle biopsies on the rate of muscle glycogen repletion, eight male subjects were studied immediately after and 2 days after an exhaustive cycling bout. A single biopsy was obtained from the right vastus lateralis muscle immediately after an exhaustive cycling bout. Two days later, a sample was taken 1 cm lateral or medial to sample A. In four of these subjects, additional biopsies were taken 3 cm distal and proximal. A control specimen was also taken from the left leg 2 days after the exercise. Ten days after the exercise, muscle was again sampled from each leg of these four subjects. Analysis of these samples revealed that the initial biopsy impaired glycogen storage in the muscle taken 1 cm medial or lateral to the previous site. This reduction in glycogen storage was most pronounced in the first 2 days after the exercise. Samples taken distal and proximal to the initial biopsy contained, on the average, less glycogen than the contralateral leg, but these differences were only significantly different in the distal muscle sample. Alteration in muscle glycogen storage was seen to persist for 10 days after the first biopsy, suggesting that care must be taken in selecting the site for repeated biopsies from the same muscle.
Rectal and rectal vs. esophageal temperatures in paraplegic men during prolonged exercise
Authors: Gass G. C. , Camp E. M. , Nadel E. R. , Gwinn T. H. , Engel P.
Published: December 2017

This study investigated the rectal (Tre), esophageal (Tes), and skin (Tsk) temperature changes in a group of trained traumatic paraplegic men pushing their own wheelchairs on a motor-driven treadmill for a prolonged period in a neutral environment. There were two experiments. The first experiment (Tre and Tsk) involved a homogeneous group (T10-T12/L3) of highly trained paraplegic men [maximum O2 uptake (VO2max) 47.5 +/- 1.8 ml.kg-1.min-1] exercising for 80 min at 60–65% VO2max.Tre and Tsk (head, arm, thigh, and calf) and heart rate (HR) were recorded throughout. O2 uptake (VO2), minute ventilation (VE), CO2 production (VCO2), and heart rate (HR) were recorded at four intervals. During experiment 1 significant changes in HR and insignificant changes in VCO2, VE, and VO2 occurred throughout prolonged exercise. Tre increased significantly from 37.1 +/- 0.1 degrees C (rest) to 37.8 +/- 0.1 degrees C after 80 min of exercise. There were only significant changes in arm Tsk. Experiment 2 involved a nonhomogeneous group (T5-T10/T11) of active paraplegics (VO2max 39.9 +/- 4.3 ml.kg-1.min-1) exercising at 60–65% VO2max for up to 45 min on the treadmill while Tre and Tes were simultaneously recorded. Tes rose significantly faster than Tre during exercise (dT/dt 20 min: Tes 0.050 +/- 0.003 degrees C/min and Tre 0.019 +/- 0.005 degrees C/min), and Tes declined significantly faster than Tre at the end of exercise. Tes was significantly higher than Tre at the end of exercise. Our results suggest that during wheelchair propulsion by paraplegics, Tes may be a better estimate of core temperature than Tre.
Assessment of tight junctions between pulmonary epithelial and endothelial cells
Authors: Walker D. C. , MacKenzie A. L. , Wiggs B. R. , Montaner J. G. , Hogg J. C.
Published: December 2017

This study is intended to determine whether qualitative assessment of tight junction integrity from freeze-fracture data is reliable. We used lung parenchyma from a control mongrel dog's cardiac lung lobe, from a mongrel dog subjected to vascular high-pressure pulmonary edema (HPPE), and from a dog subjected to oleic acid-induced low-pressure pulmonary edema (LPPE) (6). Quantitative assessment was done on 115 freeze-fracture micrographs of epithelial tight junctions and on another 158 freeze-fracture micrographs of endothelial junctions from the 3 dogs. Quantitative assessment showed differences between the dogs in junction depth, fibril numbers, density, and complexity. for qualitative assessment, these same 273 micrographs were assessed in a single-blind fashion by having six investigators sort first the epithelial and then the endothelial junctions into normal or damaged categories. Qualitative assessment did not agree with quantitative data, suggesting that it is unreliable.
Corticosteroid potentiation of surfactant dose response in preterm rabbits
Authors: Seidner S. , Pettenazzo A. , Ikegami M. , Jobe A.
Published: December 2017

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 days gestational age. Both corticosteroid-treated and control animals then received exogenous natural rabbit surfactant at birth at doses of 0–75 mg lipid/kg. After 10 min of ventilation at tidal volumes of 12–15 ml/kg, static pressure-volume measurements were made. At all surfactant doses there was a significantly higher maximal lung volume, higher dynamic compliance, and lower pressure requirement in the corticosteroid-treated than in the control rabbits (P less than 0.01). Control animals showed incremental improvements in dynamic compliances and maximal lung volumes up to a dose of 50 mg/kg, whereas corticosteroid treated animals improved to a maximum at the low dose of 15 mg/kg (P less than 0.01). However, surface tension as assessed by lung stability index improved with increasing surfactant dose but was not significantly different between corticosteroid-treated and control animals at a given dose. The results imply that maternal corticosteroid treatment potentiates surfactant replacement by a change in lung structure that is independent of surface tension effects.
Fatigue of mouse diaphragm muscle in isometric and isotonic contractions
Authors: Seow C. Y. , Stephens N. L.
Published: December 2017

Fatiguabilities of mouse diaphragm muscle in vitro in isometric and isotonic contractions were compared in this study. Isolated mouse diaphragm muscle was stimulated repetitively to induce fatigue during both isometric and isotonic contractions. The supramaximal electrical stimulation used was a train of 100-Hz, 0.5-ms pulses delivered to the muscle every 2 s for 0.5 s. The percentage decrease in isometric tension from beginning to end of the fatiguing process was used as the index of fatigue. The experiments were carried out at different PO2 levels in both normal and zero-glucose Ringer solutions. It was found that fatigue developed more rapidly in isotonic contractions than in isometric ones. Also, the extracellular glucose level demonstrated little effect on the muscle's short-term fatiguability, whereas reductions in the extracellular PO2 exerted a profound effect, especially in the case of isotonic fatigue.
Intrapulmonary oxygen consumption in experimental pneumococcal pneumonia
Authors: Light R. B.
Published: December 2017

To test the hypothesis that lung affected by acute bacterial pneumonia consumes significant amounts of O2, whole-body O2 consumption (VO2) was measured simultaneously by collection of expired gas (VO2exp) and by the Fick principle (VO2Fick) in five dogs with acute experimental pneumococcal pneumonia and in five uninfected controls. This approach is based on the premise that VO2Fick will not detect lung VO2, whereas the expired gas measurement represents the true whole-body VO2, including the lung. In controls VO2 exp averaged 110 +/- 20 ml/min (4.78 +/- 0.78 ml.min-1.kg-1), and VO2Fick was nearly identical at 114 +/- 21 ml/min (4.96 +/- 0.79 ml.min-1.kg-1). The VO2Fick in the pneumonia group was 127 ml/min, similar to both control group values when indexed for body weight (4.91 +/- 1.17 ml.min-1.kg-1). VO2exp, however, was 146 +/- 46 ml/min (5.74 +/- 1.57 ml.min-1.kg-1), exceeding VO2Fick by an average of 20 +/- 9 ml/min (P less than 0.01). This between-method difference of 20 +/- 9 ml/min (or 24 ml/min if the difference in the control group is assumed to apply to the pneumonia group) amounted to 13–15% of whole-body VO2 and can be attributed to VO2 in the lung, presumably by cells involved in the acute inflammatory response. Implications include the potential for significant underestimate of whole-body VO2 by the Fick method when used in the presence of lung inflammation and overestimate of blood flow to shunting or low ventilation-perfusion ratio lung units by the O2 method of measuring venous admixture-like perfusion. This observation may also explain the disproportionate hypoxemia sometimes seen in patients with severe pneumonia.
Pressure-volume and length-stress relationships in canine bronchi in vitro
Authors: Gunst S. J. , Stropp J. Q.
Published: December 2017

Intraparenchymal canine airway segments with branches tied off were mounted between two fluid-filled cannulas in an organ chamber. Airways were inflated to successive volumes ranging from 4 to 100% of the segment volume at 25 cmH2O. At each volume, pressure was monitored during isovolumetric contractions elicited by 10(-3) M acetylcholine. Small bronchi developed pressures greater than 30 cmH2O in response to acetylcholine at all volumes and were able to constrict to closure. Large bronchi developed pressures greater than 30 cmH2O only near maximal volumes and were able to constrict to only 30% of maximal volume. Maximal active pressures occurred at low volumes in small bronchi and at high volumes in large bronchi. However, maximal active circumferential tension and stress occurred at near-maximal volumes in both large and small bronchi. Circumferential length active-stress curves and maximal active-stress development for bronchi and trachealis muscle strips were similar. Similar length active-stress properties in different bronchi may produce significant differences in volume-pressure characteristics.
Hydraulic conductivity of lung venules determined by split-drop technique
Authors: Bhattacharya J.
Published: December 2017

The split-drop method has been used to determine filtration rate per unit surface area in the single pulmonary venule. In isolated perfused lungs of nine dogs, blood flow was stopped at different vascular pressures. By means of a double-micropuncture technique under stereomicroscopy, an oil drop was injected in a subpleural venule. The oil drop was then split with a solution of albumin (5.6 g/100 ml) in Ringer lactate. As the Ringer-albumin solution filtered, the distance between the menisci of the split oil drop (split-drop length) decreased. The split-drop geometry and the rate of change of split-drop length were recorded. The calculated venular filtration rate per unit surface area related linearly with vascular pressure (P less than 0.05). The slope of the line equaled venular hydraulic conductivity, which averaged 2.9 +/- 0.02 x 10(-7) ml/(cm2.s.cmH2O). Hydraulic conductivity is lower in lung than in systemic venules.
Convective exchange between the nose and the atmosphere
Authors: Haselton F. R. , Sperandio P. G.
Published: December 2017

It is generally accepted that there is little rebreathing of gas exhaled through the nose. A detailed physical model system has been used to quantify and identify the mechanisms responsible for this phenomenon. By the use of a cast of the upper respiratory tract and oscillating flows with a Reynolds number of 500 and nondimensional frequency of 1.6, corresponding to quiet tidal breathing through the nose, dye dilution measurements indicated an efficiency of tidal exchange of 0.95. Flow visualization studies performed to trace the expiratory flow, as well as the streamlines during steady inspiratory flow, support the hypothesis that the high efficiency of exchange is due to radical differences in the velocity fields between inspiratory and expiratory phases of this oscillatory flow. These findings confirm that convective gas exchange between the nose and the atmosphere is highly efficient; however, the underlying mechanism responsible for this exchange also maximizes the exposure of the respiratory system to aerosols contained in the ambient atmosphere.
Chest wall and respiratory system mechanics in cats: effects of flow and volume
Authors: Kochi T. , Okubo S. , Zin W. A. , Milic-Emili J.
Published: December 2017

The effects of inspiratory flow rate and inflation volume on the resistive properties of the chest wall were investigated in six anesthetized paralyzed cats by use of the technique of rapid airway occlusion during constant flow inflation. This allowed measurement of the intrinsic resistance (Rw,min) and overall dynamic inspiratory impedance (Rw,max), which includes the additional pressure losses due to time constant inequalities within the chest wall tissues and/or stress adaptation. These results, together with our previous data pertaining to the lung (Kochi et al., J. Appl. Physiol. 64: 441–450, 1988), allowed us to determine Rmin and Rmax of the total respiratory system (rs). We observed that 1) Rw,max and Rrs,max exhibited marked frequency dependence; 2) Rw,min was independent of flow (V) and inspired volume (delta V), whereas Rrs,min increased linearly with V and decreased with increasing delta V; 3) Rw,max decreased with increasing V, whereas Rrs,max exhibited a minimum value at a flow rate substantially higher than the resting range of V; 4) both Rw,max and Rrs,max increased with increasing delta V. We conclude that during resting breathing, flow resistance of the chest wall and total respiratory system, as conventionally measured, includes a significant component reflecting time constant inequalities and/or stress adaptation phenomena.
In situ NADH laser fluorimetry of rat fast- and slow-twitch muscles during tetanus
Authors: Duboc D. , Muffat-Joly M. , Renault G. , Degeorges M. , Toussaint M. , Pocidalo J. J.
Published: December 2017

To investigate the variations of oxidation-reduction status of fast- and slow-twitch muscles during intense contractions, we performed in situ NADH laser fluorimetry during 25-s tetanus in extensor digitorum longus (EDL) and in soleus (SOL) muscles of eight Sprague-Dawley rats anesthetized with pentobarbital sodium. At base line the compensated NADH fluorescence (F0) was not significantly different between EDL and SOL. In EDL, tetanic stimulation induced an increase of F0, which rapidly reached a plateau that was 124% over the base-line value and stable until the end of the stimulation. In SOL, after an initial shouldering there was a continuous increase of F0 until the end of tetanus, reaching 275% of the base-line value. After the stimulation the initial rate of recovery was significantly faster in SOL than in EDL. We conclude that during and after intense contraction the variation of NADH content vs. time can be evaluated by in situ NADH laser fluorimetry in different muscle types. This nondestructive method can be helpful to differentiate in situ the various physiological or pathological oxidative capabilities of skeletal muscles.
Altered angiotensin-converting enzyme in lung and extrapulmonary tissues of hypoxia-adapted rats
Authors: Oparil S. , Narkates A. J. , Jackson R. M. , Ann H. S.
Published: December 2017

The effects of exposing rats to hypoxia (10% O2) at normal atmospheric pressure for periods of 14 or 28 days on angiotensin-converting enzyme (ACE) activity and stores of angiotensin I (ANG I) and angiotensin II (ANG II) in lung, kidney, brain, and testis were examined. ACE activity was measured by spectrophotometric assay, and active sites of ACE were estimated by measuring the binding of 125I-351A [N-(1-carbonyl-3-phenyl-propyl)-L-lysyl-L-proline], a highly specific active site-directed inhibitor of ACE, to tissue homogenates and perfused lungs. Hypoxia exposure produced progressive reductions in ACE activity in lung homogenates and in ACE inhibitor binding to perfused lungs. ANG II levels in lungs from hypoxia-adapted animals were significantly less than air controls, suggesting that the reduction in intrapulmonary ACE activity was associated with reduced local generation of ANG II. ACE activity was increased in kidney and unchanged in brain and testis of hypoxia-adapted rats compared with air controls. Thus the effects of chronic hypoxia on catalytically active ACE and ACE active sites in the intact animal were organ specific. Adaptation to chronic hypoxia did not significantly alter plasma renin activity or ANG I or ANG II levels or serum ACE content. The hypoxia-induced alterations in lung and kidney ACE were reversible after return to a normoxic environment.
Adaptation of bone and tendon to prolonged hindlimb suspension in rats
Authors: Vailas A. C. , Deluna D. M. , Lewis L. L. , Curwin S. L. , Roy R. R. , Alford E. K.
Published: December 2017

The rat hindlimb suspension model was used to ascertain the importance of ground reaction forces in maintaining bone and tendon homeostasis. Young female Sprague-Dawley rats were randomly assigned to either a suspended or a nonsuspended group. After 28 days, femur bones and patellar tendons were obtained for morphological and biochemical analyses. Prolonged suspension induced a significant change in the geometric configuration of the femur middiaphysis by increasing the minimum diameter (12%) without any significant alterations in cortical area, density, mineral, and collagen concentrations. Femur wet weight, length, DNA, and uronic acid concentrations of suspended animals were not significantly different from bones of nonsuspended rats. However, the collagen and proteoglycan concentrations in patellar tendons of suspended rats were 28% lower than the concentrations of matrix proteins in tissues obtained from nonsuspended animals. These data suggest that elimination of ground reaction forces induces alterations in tendon composition and femur diaphyseal shape by changing regional rates in bone remodeling and localized tendon strain. Therefore it appears that ground reaction forces are an important factor in the maintenance of cortical bone and patellar tendon homeostasis during weight-bearing conditions.
Short-term entrainment of ventilation to the walking cycle in humans
Authors: Hill A. R. , Adams J. M. , Parker B. E. , Rochester D. F.
Published: December 2017

We describe a breath-by-breath method to test for entrainment of breathing and walking cycles. Thirty-eight normal subjects walked comfortably on a treadmill while breathing through a pneumotachograph. We analyzed the time intervals between heel strikes and the onset of inspiration (or expiration) for evidence of phase locking between steps and breaths, using Monte Carlo simulation to model the probability that n consecutive inspirations (or expirations) would begin at a constant time interval +/- 0.10 s from heel strikes by chance. We developed empirical criteria for rhythm synchronization during series of four or more breaths, while maintaining an estimated specificity of 95%. The majority of subjects showed some evidence of entrainment (29 +/- 23% of breaths on average), which occurred intermittently, usually lasting less than 10 breaths at a time. The precision of phase locking during spontaneous entrainment was similar to that in 10 subjects who attempted to maintain deliberate entrainment. The results suggest that the walking cadence provides a persuasive, but not dominant, input to the central breathing pattern generator. The present method can detect entrainment even when it occurs sporadically or with varying coupling pattern.
Relationship among EMG and contractile responses of the diaphragm elicited by hypotension
Authors: Hussain S. N. , Marcotte J. E. , Burnet H. , Collett P. , Roussos C.
Published: December 2017

In a canine model, we investigated the effects of severe hypotension on the indexes of diaphragmatic failure. We measured 1) the transdiaphragmatic pressure obtained in response to 20- and 100-Hz stimulation of phrenic nerves (Pdi20 and Pdi100), 2) the power spectrum of diaphragmatic electromyogram (EMG), 3) the ratio of integrated diaphragmatic EMG to Pdi (Edi/Pdi), and 4) the rate of relaxation of Pdi100 and Pdi20. Arterial blood pressure (Pa) was reduced to 40-50 mmHg by a balloon inflated in the inferior vena cava and was maintained at this level until Pdi100 declined to 75% of the control value (100% shock time, ST). A recovery period of 60 min at normal Pa was allowed. During hypotension, Pdi100 and Pdi20 declined only at 100% ST [95.0 +/- 13.0 (SE) min]; however, only Pdi100 recovered within 15 min. The power spectrum shifted to low frequencies early and progressively during shock period. Edi/Pdi rose significantly at 80 and 100% ST and recovered within 15 min. The relaxation rate of Pdi20 and Pdi100 increased significantly at 100% ST only. We conclude that 1) diaphragmatic contractility is depressed during severe hypotension, 2) changes in the power spectrum occurred first in the shock state, followed by alterations in Edi/Pdi, and subsequently both changes in the frequency-pressure curve and relaxation rate occurred last.
Polymorphonuclear leukocyte cytoplasts mediate acute lung injury
Authors: Antony V. B. , Owen C. L. , English D.
Published: December 2017

Injection of phorbol 12-myristate 13-acetate (PMA) into polymorphonuclear leukocyte (PMN)-depleted, PMN cytoplast-repleted New Zealand White rabbits caused the development of acute lung injury in vivo. PMN cytoplasts are nucleus- and granule-free vesicles of cytoplasm capable of releasing toxic O2 radicals but incapable of releasing granule enzymes. PMN cytoplasts when activated by PMA reduced 66 +/- 12.7 nmol of cytochrome c compared with 2.6 +/- 0.7 nmol in their resting state and did not release a significant quantity of granule enzymes (P greater than 0.05). Injection of PMA into New Zealand White rabbits caused a significant decrease (P less than 0.05) in the number of circulating cytoplasts. Increases in lung weight-to-body weight ratios in PMA-treated rabbits (9.8 +/- 0.5 X 10(-3] compared with saline-treated rabbits (5.3 +/- 0.2 X 10(-3] were also noted. Levels of angiotensin-converting enzyme in lung lavage as well as the change in alveolar-arterial O2 ratio correlated with the numbers of cytoplasts in lung lavage (P = 0.001, r = 0.84 and P = 0.0166, r = 0.73, respectively). Albumin in lung lavage increased to 1,700 +/- 186 mg/ml in PMA-treated rabbits from 60 +/- 30 mg/ml in saline-treated rabbits. These changes were attenuated by pretreatment of rabbits with dimethylthiourea (DMTU). In vitro, cytoplasts were able to mediate increases in endothelial monolayer permeability. This was evidenced by increases in fractional transit of albumin across endothelial monolayers when treated with PMA-activated cytoplasts (0.08 +/- 0.01 to 0.28 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Specific reaginic antibody IgG1-induced changes of airway smooth muscle cells
Authors: Souhrada M. , Souhrada J. F.
Published: December 2017

It was found that 1) an administration of both immunoglobulin G1 (IgG1) or immunized serum caused an immediate depolarization and an increase in the isometric force of airway smooth muscle (ASM) cells, followed by a sustained hyperpolarization and a return of the tone to the base-line values; 2) an IgG1 concentration-dependent relationship was found between a peak depolarization, a peak hyperpolarization, and a peak isometric force; for these events 50% effective dose (ED50) was found to be 0.17, 0.14, and 0.25 microgram/ml of IgG1, respectively; 3) both electrical and contractile responses to ovalbumin of ASM cells sensitized with IgG1 were also dependent on the concentration of IgG1; the ED50 values of this relationship were 0.27 and 0.25 micrograms/ml of IgG1, respectively; 4) amiloride (10(-8) to 10(-5) M) pretreatment and a sodium-deficient environment attenuated sensitized-induced electrical and contractile changes as well as the response of ASM to ovalbumin (0.1%); and 5) pretreatment of ASM with diphenhydramine (10(-5) M) or FPL 55712 (10(-6) M) had no effect on sensitization-induced changes in membrane potential but attenuated electrical and contractile response of ASM to ovalbumin (0.1%).
Ventilatory response to CO2 and O2 near eupnea in awake dogs
Authors: Hwang W. W. , Yamashiro S. M. , Sedlock D. , Grodins F. S.
Published: December 2017

The problem faced in determining the ventilatory response to CO2 near eupnea has been the difficulty of unloading metabolically produced CO2 from the subject in the steady state. Previous methods using extracorporeal circuits to unload CO2 are technically difficult and provide a limited number of experimental states per experiment. Using the method of high-frequency ventilation to unload CO2, we were able to obtain a large number of determinations in the same subject under conditions of hypoxia, normoxia, and hyperoxia. Data collected in five awake dogs show that the ventilatory response to CO2 is linear down to apnea during normoxic conditions but exhibits nonlinear behavior dependent on the level of arterial O2 tension. During hyperoxic conditions, the response was concave curvilinear, with a statistically significant decrease in slope near apnea. In contrast, mild hypoxia led to a convex curvilinear response with an increased slope near apnea.
Tracheal mucosal blood flow responses to autonomic agonists
Authors: Barker J. A. , Chediak A. D. , Baier H. J. , Wanner A.
Published: December 2017

In lightly anesthetized adult sheep, we determined tracheal mucosal blood flow (Qtr) by measuring the steady-state uptake of dimethyl ether from a tracheal chamber created by an endotracheal tube provided with two cuffs. Qtr normalized for carotid arterial pressure [Qtr(n)] was determined before and after the exposure of the tracheal mucosa to aerosolized phenylephrine (0.25-2.0 mg), isoproterenol (0.05-0.8 mg), and methacholine (2.5-20 mg). The same doses of methacholine were also administered during the intravenous infusion of vasopressin. The measurements were repeated after intravenous pretreatment with the respective antagonists phentolamine, propranolol, and atropine. Mean +/- SE base-line Qtr(n) was 1.2 +/- 0.1 ml.min-1.mmHg-1.10(2). The autonomic antagonists had no effect on mean Qtr(n). Phenylephrine produced a dose-dependent decrease in mean Qtr(n) (-70% at the highest dose), which was blunted by phentolamine, and isoproterenol produced a dose-dependent increase in mean Qtr(n) (40% at the highest dose), which was blocked by propranolol. Methacholine failed to alter mean Qtr(n) even when Qtr was first decreased by vasopressin. We conclude that in lightly anesthetized adult sheep 1) base-line Qtr(n) is not under adrenergic or cholinergic control, 2) a locally administered alpha-adrenergic agonist decreases and beta-adrenergic agonist increases Qtr(n) via specific receptor activation, and 3) a locally administered cholinergic muscarinic agonist has no effect on Qtr(n).
Metabolic responses to exercise in young and older athletes and sedentary men
Authors: Hagberg J. M. , Seals D. R. , Yerg J. E. , Gavin J. , Gingerich R. , Premachandra B. , Holloszy J. O.
Published: December 2017

This study evaluated the effects of aging and endurance training on the metabolic responses of trained and sedentary young (age 20-32 yr) and older (age 60-70 yr) men to exercise at the same relative exercise stress (70% of maximal O2 consumption). Plasma growth hormone concentrations at rest were similar in all four groups, but both older groups had an attenuated response to exercise. The older trained men appeared to have avoided the age-associated changes that were evident in their sedentary peers with respect to resting plasma insulin, C-peptide, and norepinephrine concentrations. Plasma glucagon concentrations were lower in both older subject groups at rest. Both sedentary groups decreased their plasma glucose concentrations and increased their plasma glucagon concentrations during exercise, whereas the trained groups had increases in their plasma glucose concentrations but had no change in their glucagon concentrations. Thus, although the concentrations of some hormones at rest and during submaximal exercise are unaffected by aging or by training, others are markedly altered by aging, training, or the interaction of the two. However, it appears that older healthy sedentary men undergo less physiological stress than young untrained men during submaximal exercise at the same relative exercise intensity, and they have no responses that would contraindicate their participation in exercise of the duration and intensity usually prescribed in exercise-training programs.
Stimulation of ciliary beat frequency by autonomic agonists: in vivo
Authors: Wong L. B. , Miller I. F. , Yeates D. B.
Published: December 2017

beta 2-Adrenergic bronchodilator and muscarinic cholinergic bronchoconstrictor agonists both stimulate ciliary activity in vitro. To test the hypothesis that increases in autonomic activity would result in increases in ciliary beat frequency (CBF) in vivo, a correlation analysis heterodyne laser light-scattering system was developed and validated to measure the stimulating effects of sympathomimetic and parasympathomimetic agonists on tracheal CBF in intact, anesthetized beagles. The mean baseline CBF from 42 studies of 274 measurements in 9 (5 male and 4 female) adult beagles was 6.6 +/- 1.1 Hz. The stimulating effects of a beta 2-adrenergic agonist, fenoterol, and a muscarinic cholinergic agonist, methacholine, on CBF were studied on four and eight beagles, respectively. The studies were randomized and blinded. Aerosolized 10(-5) M fenoterol stimulated the CBF from the base line of 6.8 +/- 2.5 to 32.0 +/- 17.9 Hz in four dogs. Aerosolized methacholine stimulated the CBF from the base line of 5.8 +/- 0.7 to 9.4 +/- 3.0 Hz for 10(-8) M, and to 12.6 +/- 3.1 Hz for 10(-6) M in eight dogs. These are the first data obtained in intact animals that demonstrate CBF in the lower respiratory tract is regulated by autonomic agonists.
Identification of surfactant proteolipid SP-B in human surfactant and fetal lung
Authors: Weaver T. E. , Sarin V. K. , Sawtell N. , Hull W. M. , Whitsett J. A.
Published: December 2017

Surfactant proteolipid (SP-B) is one of several hydrophobic peptides detected in organic extracts of pulmonary surfactant and associated with the dramatic surface-active properties of surfactant phospholipids. In the present study human SP-B was identified as a protein with a relative molecular weight (Mr) of 7,500-8,000 under reducing conditions; protein of Mr 18,000 was detected under nonreducing conditions by immunoblot analysis of organic extracts of bovine and human surfactant utilizing an antiserum directed against a 60-amino acid synthetic SP-B peptide. This peptide antiserum was subsequently used to identify SP-B in explant cultures of 18- to 23-wk gestation human fetal lung. Immunoprecipitation of explants labeled with [35S]methionine after 48 h of culture identified proteins of Mr 40,000-42,000, 25,000, and 18,000 after electrophoresis under nonreducing conditions. The Mr 18,000 form was reduced to Mr 7,500-8,000 in the presence of beta-mercaptoethanol. These molecular forms likely represent the SP-B precursor protein, a proteolytic intermediate, and the mature SP-B peptide, respectively. Immunocytochemistry with the peptide antiserum localized SPL(Phe) in granular inclusions in the apical region of type II-like epithelial cells, a pattern of staining similar to that observed for the major surfactant-associated protein of Mr 26,000-38,000 (SP-A). SP-B is a novel pulmonary surfactant-associated protein that is synthesized by the human alveolar type II epithelial cell as an Mr 40,000-42,000 precursor that is subsequently proteolytically processed to Mr 7,500-8,000.