bluuebunny/crossref_metadata_2025 huggingface dataset:
A set-point model with oscillatory behavior predicts the time course of 8-OH-DPAT-induced hypothermia
Authors: Zuideveld Klaas P. , Maas Hugo J. , Treijtel Nicoline , Hulshof Joost , van der Graaf Piet H. , Peletier Lambertus A. , Danhof Meindert
Published: December 2017

Agonists for the 5-hydroxytryptamine (HT)1Areceptor induce a hypothermic response that is believed to occur by lowering of the body's set-point temperature. We have developed a physiological model that can be used to predict the complex time course of the hypothermic response after administration of 5-HT1Aagonists to rats. In the model, 5-HT1Aagonists exert their effect by changing heat loss through a control mechanism with a thermostat signal that is proportional to the difference between measured and set-point temperature. Agonists exert their effect in a direct concentration-dependent manner, with saturation occurring at higher concentrations. On the basis of simulations, it is shown that, depending on the concentration and the intrinsic efficacy of a 5-HT1Aagonist, the model shows oscillatory behavior. The model was successfully applied to characterize the complex hypothermic response profiles after administration of the reference 5-HT1Aagonists R-8-hydroxy-2-(di -n-propylamino)tetralin ( R-8-OH-DPAT) and S-8-OH-DPAT. This analysis revealed that the observed difference in effect vs. time profile for these two reference agonists could be explained by a difference in in vivo intrinsic efficacy.
Role of increased circulating and renal adrenomedullin in rats with malignant hypertension
Authors: Nishikimi Toshio , Yoshihara Fumiki , Kanazawa Akio , Okano Ichiro , Horio Takeshi , Nagaya Noritoshi , Yutani Chikao , Matsuo Hisayuki , Matsuoka Hiroaki , Kangawa Kenji
Published: December 2017

Although it has been reported that the circulating adrenomedullin (AM) level is elevated in hypertension and renal failure, the pathophysiological significance of circulating and intrarenal AM in malignant hypertension remains unknown. We investigated the circulating and intrarenal AM system in rats with malignant hypertension by measuring the plasma level, renal tissue level, and mRNA abundance of AM and the mRNA abundance of AM receptor. We also investigated the effects of intravenously infused calcitonin gene-related peptide (CGRP)-(8–37), an antagonist of AM, on the hemodynamics and renal tubular function. We studied the following four groups: control Wistar-Kyoto rats (WKY), control spontaneously hypertensive rats (C-SHR), salt-loaded SHR (S-SHR), and DOCA-salt SHR (D-SHR). After 3 wk of DOCA treatment, D-SHR developed malignant hypertension. D-SHR were characterized by higher blood pressure, kidney weight, urinary protein excretion and blood urea nitrogen, and lower creatinine clearance compared with the other three groups. The plasma AM level and urinary excretion of AM were markedly higher in D-SHR than in the other three groups. In the kidney, the tissue AM level and the expression of AM mRNA in the renal medulla were significantly increased in D-SHR compared with the other three groups, whereas there were no significant differences in these levels in the renal cortex among the four groups. In the renal AM receptor system, the expression of the gene for receptor activity modifying protein 3 was significantly increased in the renal medulla in D-SHR compared with the other three groups. An immunohistochemical study revealed that AM immunostaining in renal collecting duct cells and distal tubules was more intense in D-SHR than in the other three groups. After CGRP-(8–37) infusion, blood pressure increased significantly and urinary sodium excretion and urine flow decreased significantly only in D-SHR. These results suggest that the increased circulating AM and renal AM and the increased expression of the mRNA for AM and its receptor may at least partly compensate for the malignant hypertensive state in certain forms of malignant hypertension via the hypotensive, natriuretic, and diuretic actions of AM.
Decreased hematopoiesis in bone marrow of mice with congestive heart failure
Authors: Iversen Per Ole , Woldbaek Per Reidar , Tønnessen Theis , Christensen Geir
Published: December 2017

Patients with heart failure are predisposed to infections and anemia, possibly due to reduced hematopoiesis. The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is increased in heart failure, and it inhibits normal hematopoiesis, partly due to apoptosis through the effector molecule Fas. We examined bone marrow progenitor cells of mice with heart failure induced by acute myocardial infarction. The fraction of progenitor cells in mice with heart failure was only ∼40% of control. Measured with in vitro clonal assays, the proliferative capacity of the progenitor cells in mice with heart failure was reduced to ∼50% of control. Flow cytometry with specific markers revealed a threefold increase in apoptosis among progenitor cells from mice with heart failure. In these mice, TNF-α/Fas expression was increased in bone marrow natural killer (NK) and T cells, and these lymphocytes showed increased cytolytic activity in vitro against progenitor cells. We conclude that the TNF-α/Fas pathway in lymphocytes is activated in the bone marrow during heart failure, which may play a pathogenic role in the observed decrease in hematopoiesis.
Mechanical properties of pulmonary arteries from sensitized dogs
Authors: Kong S. K. , Stephens N. L.
Published: December 2017

On the basis of isometric dose-response studies, we (J. Pharmacol. Exp. Ther. 219:551-557, 1981) have reported that the ovalbumin-sensitized (S) canine pulmonary artery (PA) is hypersensitive and hyperractive to histamine compared with that from a littermate control (C) in vitro. In this study, our aim was to determine whether the maximal velocity of shortening (Vmax) measured in strips of electrically stimulated SPA and CPA differed. Vmax (velocity at zero load) was obtained by analysis of force-velocity curves from these tissues using the equation (P + a) (V + b) = (Po + a)b, in which P is load, Po is maximum tetanic tension, V is shortening velocity, and a and b are asymptotic values in units of force and velocity. The Vmax values derived for SPA and CPA are 0.188 +/- 0.029 (SE) and 0.113 + 0.017 lo/s, respectively, lo being defined as that length at which Po is obtained. This result indicated that the Vmax value of SPA is significantly (P less than 0.05) different from that of CPA. The b values for SPA [0.034 +/- 0.003 lo/s] and for CPA [0.025 +/- 0.004 lo/s] were also significantly different. However, the force constants a and Po were unchanged in the SPA and CPA. SPA also had a greater isotonic shortening capacity than CPA. These findings indicate that mechanical properties of SPA are altered and lend an understanding of the hyperreactivity of these vessels in the sensitized model.
Hypervolemia and plasma vasopressin response during water immersion in men
Authors: Greenleaf J. E. , Morse J. T. , Barnes P. R. , Silver J. , Keil L. C.
Published: December 2017

To investigate changes in plasma volume (PV) and osmolality as stimuli for plasma vasopressin (PVP) suppression and diuresis, seven normal healthy men (22-48 yr) were immersed to the neck for 4 h in a sitting position in tap water (34.5 degrees C) after overnight food and fluid restriction. Mean +/- SE urine volume was 823 +/- 123 ml/4 h; fluid intake was 400 ml/4 h, and mean negative water balance was 944 ml/4 h. Urinary sodium excretion increased from 0.77 to 1.25 mosmol/min (P less than 0.05) and UNaV from 0.14 to 0.37 meq/min (P less than 0.05). During immersion, PV (T-1824) increased by 8.8% (P less than 0.05) during the first 30 min and declined linearly thereafter. Mean +/- SD serum osmolality (294 +/- 1.2 mosmol/kg H2O) and sodium (143.2 +/- 0.4 meq/l) were constant throughout immersion; PVP (2.3 +/- 0.5 pg/ml) and plasma renin activity [0.3 +/- 0.2 ng ANG I/(ml X h]) were not significantly changed. Thus, the composition of the fluid entering the vascular space maintained constant serum osmolality and PVP throughout immersion. These findings do not support the hypothesis that acute expansion of central volume and PV cause suppression of PVP. The results suggest a mechanism other than or in addition to PVP suppression as a contributory cause of the immersion diuresis.
Partitioning of pulmonary impedance in excised human and canine lungs
Authors: Van Brabandt H. , Cauberghs M. , Verbeken E. , Moerman P. , Lauweryns J. M. , Van de Woestijne K. P.
Published: December 2017

Partitioning of pulmonary resistance of 15 excised human and 5 canine lungs by means of a retrograde catheter demonstrated that the share of peripheral airways (with an ID of 2.4 mm or less) and of lung tissue in pulmonary resistance was markedly larger (44-96%) in humans than in dogs (41-59%). Similar percentages were found in patients with chronic obstructive pulmonary disease (COPD). The variations of resistance with volume during deflation and inflation of the lungs were due primarily to variations of peripheral resistance (Rp). The latter systematically increased at high and low lung volumes. Higher Rp values, with a more pronounced frequency dependence, were met in patients with COPD. A morphometrical study showed an inverse relationship between the value of Rp and the mean diameter of the terminal bronchioles, provided the airways density was taken into account.
Factors influencing glottic dimensions during forced expiration
Authors: Brancatisano T. , Dodd D. , Engel L. A.
Published: December 2017

To examine the relationship between expiratory effort, expiratory flow, and glottic aperture, we compared the effects of actively and passively produced changes in flow in six normal subjects. During flow transients of 1.08 +/- 0.08 l/s produced by voluntary expiratory effort, glottic width (dg) increased by 54 +/- 13% (mean +/- SE). In contrast transient increases in expiratory flow, produced passively by chest compression, were not accompanied by increases in glottic dimensions. Similarly, when subjects expired through a resistance, transient passive increases in mouth pressure of 8.1 +/- 0.8 cmH2O failed to increase glottic width. However, when similar positive-pressure transients were produced actively, dg increased by 97 +/- 36% even though the expiratory efforts were accompanied by relatively small increases in flow (0.20 +/- 0.05 l/s). During tidal breathing glottic widening commenced 160 +/- 60 ms before the onset of inspiratory flow, whereas the widening associated with active flow and pressure transients did not measurably precede the onset of the change in flow or pressure. Our results indicate that transient expulsive efforts are associated with synchronous increases in dg, regardless of whether expiratory flow increases. The findings are most readily explained by a centrally determined synchronous recruitment of intrinsic laryngeal and expiratory muscles that facilitates lung emptying by minimizing airway resistance during forced exhalation.
Red cell function at extreme altitude on Mount Everest
Authors: Winslow R. M. , Samaja M. , West J. B.
Published: December 2017

As part of the American Medical Research Expedition to Everest in 1981, we measured hemoglobin concentration, red cell 2,3-diphosphoglycerate (2,3-DPG), Po2 at which hemoglobin is 50% saturated (P50), and acid-base status in expedition members at various altitudes. All measurements were made in expedition laboratories and, with the exception of samples from the South Col of Mt. Everest (8,050 m), within 2 h of blood collection. In vivo conditions were estimated from direct measurements of arterial blood gases and pH or inferred from base excess and alveolar PCO2. As expected, increased 2,3-DPG was associated with slightly increased P50, when expressed at pH 7.4. Because of respiratory alkalosis, however, the subjects' in vivo P50 at 6,300 m (27.6 Torr) was slightly less than at sea level (28.1 Torr). The estimated in vivo P50 was progressively lower at 8,050 m (24.9 Torr) and on the summit at 8,848 m (19.4 Torr in one subject). Our data suggest that, at extreme altitude, the blood O2 equilibrium curve shifts progressively leftward because of respiratory alkalosis. This left shift protects arterial O2 saturation at extreme altitude.
Effect of experimental dysthyroidism on the enzymatic character of the diaphragm
Authors: Ianuzzo C. D. , Chen V. , O'Brien P. , Keens T. G.
Published: December 2017

This study examined the effects of long-term experimental dysthyroidism on the enzymatic character of the costal diaphragm and selected respiratory parameters. Costal diaphragms from thyroidectomized (TX), euthyroid (EU), and hyperthyroid (HT) male albino rats were used. HT was induced by subcutaneous injections of triiodothyronine on alternate days for 6 wk. Minute ventilation was greater for the HT (70%) compared with the TX rats. The enzymatic potentials of glycolysis (28%), tricarboxylic acid cycle (30%), and fatty acid oxidation (16%) were significantly increased in the HT diaphragms, whereas the potentials were lower by a similar relative extent in the TX diaphragms. The proportion of alkali-labile fibers were greater in the TX and lower in the HT diaphragm. The shifts in heart and muscle lactate dehydrogenase isoenzyme activities were consistent with the fiber type changes. These findings show that dysthyroidism modifies the overall enzymatic capacity of the diaphragm (i.e., glycolysis, tricarboxylic acid cycle, and fatty acid oxidation) along with the proportion of alkali-labile to alkali-stable fiber types. These enzymatic changes are similar to those resulting from exercise training, tracheal banding, streptozotocin diabetes, and emphysema.
Threshold of airway response to inhaled methacholine in healthy men and women
Authors: Zamel N.
Published: December 2017

Threshold of airway response to inhaled methacholine was determined using maximum expiratory partial flow-volume curves in 21 men and 36 women with similar age distribution, all of them healthy nonsmokers. Mean threshold was on average 1.3 doubling dose lower in women than men. There were no sex differences in the increase of maximum expiratory flows after a full inspiration when the airways were constricted by methacholine.
Ventrolateral medullary surface blood flow determined by hydrogen clearance
Authors: Feustel P. J. , Stafford M. J. , Allen J. S. , Severinghaus J. W.
Published: December 2017

The H2 clearance technique was used to determine the blood flow of the postulated respiratory chemosensitive areas near the ventrolateral surface of the medulla. In 12 pentobarbital sodium-anesthetized cats, flow (mean +/- SD) was measured from 25-micron Teflon-coated platinum wire electrodes implanted to a depth of 0.3–0.7 mm. Flow (in ml X min-1 X 100 g-1, n = 35) was 52.8 +/- 28.5 in hypocapnia [arterial CO2 partial pressure (PaCO2) = 21.8 +/- 1.6 Torr], 57.8 +/- 27.5 in normocapnia (PaCO2 = 31.9 +/- 2.2 Torr), and 75.0 +/- 31.7 in hypercapnia (PaCO2 = 44.5 +/- 3.0 Torr). Flow determined from 15 electrodes in adjacent pyramidal tracts (white matter) was less at all levels of CO2; 22.9 +/- 12.3 in hypocapnia, 29.1 +/- 15.9 in normocapnia, and 33.9 +/- 13.9 in hypercapnia. In hypoxia [arterial O2 partial pressure (PaO2) = 39.9 +/- 6.3 Torr] ventrolateral surface flow rose to 87.9 +/- 47.6, and adjacent white matter flow was 35.8 +/- 15.6. These results indicate that flow in the postulated central chemoreceptor areas exceeds that of white matter and is sensitive to variations in PaCO2 and PaO2.
Isotopic determination of amino acid-urea interactions in exercise in humans
Authors: Wolfe R. R. , Wolfe M. H. , Nadel E. R. , Shaw J. H.
Published: December 2017

We recently reported that in light exercise (30% VO2max) the oxidation of [1-13C]leucine was significantly increased but the rate of urea production was unchanged (J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 52: 458–466, 1982). We have therefore tested three possible explanations for this apparent incongruity. 1) We infused NaH13CO3 throughout rest and exercise and found that, although altered bicarbonate kinetics in exercise resulted in greater recovery of 13CO2, the difference between rest and recovery was small compared with the increase in the rate of 13CO2 excretion during exercise when [1-13C]leucine was infused. 2) We infused [15N]leucine and isolated plasma urea N to determine directly the rate of incorporation of the 15N. During exercise there was no increase in the rate of 15N incorporation. Simultaneously, we infused [2,3-13C]alanine and quantified the rate of incorporation of 15N in alanine. We found that [15N]alanine production from [15N] leucine more than doubled in exercise, and by deduction, alanine production from other amino acids also doubled. 3) We tested our previous assumption that [1-13C]leucine metabolism in exercise was representative of the metabolism of other essential amino acids by infusing [1-13C] and [alpha-15N]lysine throughout rest and exercise. We found that the rate of breakdown of lysine during exercise was not increased in a manner comparable to that of leucine. Thus, these data confirm our original findings that leucine decarboxylation is enhanced in light exercise but urea production is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Accurate reference measurement for postmortem lung water
Authors: Julien M. , Flick M. R. , Hoeffel J. M. , Murray J. F.
Published: December 2017

To test the hypothesis that dry blood-free lung weight is increased during pulmonary edema, thereby leading to an underestimation of the ratio of extravascular lung water-to-dry lung weight, we measured postmortem lung water, dry mass, and hydroxyproline content in 33 sheep with normal lungs (n = 10), high-pressure edema (n = 9), or increased permeability edema (n = 14). Residual blood in the lung, measured using hemoglobin as the intravascular marker in all sheep, and also using 51Cr-tagged red blood cells in 24 sheep, was not different between the two methods or among the three groups of sheep. Extravascular lung water increased 64% in sheep with high-pressure edema and 82% in those with increased permeability edema compared with control values. Dry blood-free lung weight was significantly greater (33% more than control values) in sheep with increased permeability edema, causing the ratio of extravascular lung water-to-dry blood-free lung weight to underestimate accumulated lung water by about 50%. Because hydroxyproline content of the lung was not affected by edema, the ratio of extravascular lung water-to-lung hydroxyproline content was more accurate than the ratio of extravascular lung water-to-dry blood-free lung weight in the quantification of pulmonary edema.
Autonomic regulation of viscoelasticity of cat tracheal gland secretions
Authors: Leikauf G. D. , Ueki I. F. , Nadel J. A.
Published: December 2017

The purpose of this study was to determine whether various adrenergic agonists selectively regulate the viscoelastic properties of the stimulated secretions from airway submucosal glands. Nanoliter quantities of cat tracheal secretions before and during each of three stimuli were collected directly from a single submucosal gland with a micropipette, and the viscoelastic properties of the secretions were determined using a newly developed capillary microrheometer. Under unstimulated conditions (control), the measured values of apparent viscosity and elasticity of the secretions were more reproducible than the values obtained in previous studies in which samples were collected by other methods. After muscarinic (acetylcholine), alpha-adrenergic (phenylephrine), or beta-adrenergic (isoproterenol) stimulation, the submucosal gland's secretory rate was, in each case, greater than control. The viscoelastic properties of the secretions induced by muscarinic stimulation, however, were identical to control, whereas alpha-adrenergic stimulation produced secretions of a lower apparent viscosity, and beta-adrenergic stimulation produced secretions of a higher apparent viscosity and lower elasticity than control. Thus autonomic agonists selectively regulate the viscoelastic properties of submucosal gland secretions from cat trachea.
Bubble formation in crustaceans following decompression from hyperbaric gas exposures
Authors: McDonough P. M. , Hemmingsen E. A.
Published: December 2017

In vivo bubble formation was studied in various crustaceans equilibrated with high gas pressures and rapidly decompressed to atmospheric pressure. The species varied widely in susceptibility to bubble formation, and adults were generally more susceptible than larval stages. Bubbles did not form in early brine shrimp larvae unless equilibration pressures of at least 175 atm argon or 350 atm helium were used; for adult brine shrimp, copepods, and the larvae of crabs and shrimps, 100–125 atm argon or 175–225 atm helium were required. In contrast, bubbles formed in the leg joints of megalopa and adult crabs following decompression from only 3–10 atm argon; stimulation of limb movements increased this bubble formation, whereas inhibition of movements decreased it. High hydrostatic compressions applied before gas equilibration or slow compressions did not affect bubble formation. We concluded that circulatory systems, musculature, and storage lipids do not necessarily render organisms susceptible to bubble formation and that bubbles do not generally originate as preformed nuclei. In some cases, tribonucleation appears to be the cause of the bubbles.
Pleural liquid pressure gradients and intrapleural distribution of injected bolus
Authors: Miserocchi G. , Pistolesi M. , Miniati M. , Bellina C. R. , Negrini D. , Giuntini C.
Published: December 2017

In supine anesthetized dogs we measured pleural liquid pressure (Pliq) in mediastinal, diaphragmatic, apical, and costal regions at different lung heights during eupneic breathing. At end expiration and at a given height, Pliq was similar in the costal and apical regions, but it was lower in the diaphragmatic and mediastinal compartments. Inspiratory swings toward lower values were progressively greater with increasing height and moving from costal to apical, diaphragmatic and mediastinal compartments. Thus during inspiration, at any height, the costomediastinal and costodiaphragmatic Pliq difference increased while a costoapical difference developed. One minute after injection of 0.5–1 ml of saline at different points within the cavity, end-expiratory liquid pressure became higher on the average by 0.45, 1.55, and 0.55 cmH2O in the apical, mediastinal, and diaphragmatic compartments, respectively, while no change was observed on costal side. These results suggested liquid accumulation in the compartments displaying a lower Pliq. This was confirmed by following, with a gamma camera, on a frontal projection of the lung, the intrapleural distribution of a bolus containing 99mTc-labeled albumin injected at various places.
Mechanisms of gas transport during ventilation by high-frequency oscillation
Authors: Chang H. K.
Published: December 2017

Ventilation by high-frequency oscillation (HFO) presents some difficulties in understanding exactly how gas is transported in the lung. However, at a qualitative level, five modes of transport may be identified: 1) direct alveolar ventilation in the lung units situated near the airway opening; 2) bulk convective mixing in the conducting airways as a result of recirculation of air among units of inhomogeneous time constants; 3) convective transport of gases as a result of the asymmetry between inspiratory and expiratory velocity profiles; 4) longitudinal dispersion caused by the interaction between axial velocities and radial transports due to turbulent eddies and/or secondary swirling motions; and 5) molecular diffusion near the alveolocapillary membrane. These modes of transport are not mutually exclusive and certainly interact. It is therefore difficult to make quantitative predictions about the overall rate of transport. Qualitatively, it may now be stated with confidence that convective transport in the tracheobronchial tree is very important during HFO as in normal breathing and that increasing tidal volume is more effective than increasing frequency in improving gas exchange during HFO. To optimize the gas transport efficiency of HFO, future research should focus on identifying the rate-limiting mode of transport for a given set of geometric and dynamic conditions.
Interaction between histamine and vagal stimulation on tracheal smooth muscle in dogs
Authors: Kikuchi Y. , Okayama H. , Okayama M. , Sasaki H. , Takishima T.
Published: December 2017

We examined the interaction between histamine and vagal efferent activity on airway smooth muscle reactivity in 11 anesthetized vagotomized dogs using an isolated closed segment of the intrathoracic trachea filled with Tyrode solution under an isovolumetric condition. Intratracheal pressure change was measured as an index of tracheal smooth muscle tone. The administration into the tracheal segment of histamine (0.1 or 1.0 mg/ml) in six dogs and methacholine chloride (0.001 or 0.01 mg/ml) in the other five dogs elevated intratracheal pressure by about 5 cmH2O. The electrical stimulation of the peripheral ends of both of the cut cervical vagus nerves in the presence of histamine produced significantly greater responses than the additive responses of these two stimuli applied individually (two-way analysis of variance, P less than 0.025). However, the combined effects of vagal stimulation and methacholine were not significantly different from the additive responses of these two stimuli applied individually. The average values of intratracheal pressure elevated by the combined effects of vagal stimulation and histamine were significantly higher than those obtained by the combination of vagal stimulation and methacholine (two-way analysis of variance, P less than 0.01). This suggests that histamine potentiates tracheal smooth muscle reactivity to electrical vagal stimulation, which may contribute to the hyperreactivity observed in patients with asthma.
Effects of exercise on collateral development in myocardial ischemia in pigs
Authors: Bloor C. M. , White F. C. , Sanders T. M.
Published: December 2017

To study the effects of exercise on collateral development in myocardial ischemia, we induced coronary arterial stenosis of the left circumflex coronary artery (LCCA) in 18 of 30 pigs. During that surgery, we identified the coronary bed at risk. Nine of these pigs were then subjected to 5 mo of exercise training on a treadmill. After exercise training, we determined regional collateral and myocardial blood flow using radiolabeled microspheres. At autopsy, all animals had complete occlusion of the LCCA. Infarct size in the exercise-trained pigs was significantly less than in the sedentary pigs (5.9 +/- 1.0 vs. 11.7 +/- 1.0% of the left ventricle). The exercise-trained animals had a greater increase in collateral flow, 35.1 +/- 3.0 vs. 28.7 +/- 4.1 ml X min-1 X 100 g-1, in the noninfarcted jeopardized zone of the LCCA bed. The major findings of the study were the following: 1) chronic coronary artery stenosis progressing to occlusion stimulated development of the collateral circulation and salvaged tissue in the jeopardized myocardium of an animal model with sparse collaterals; 2) development of the collateral circulation and tissue salvage is increased by exercise training; 3) collaterals develop primarily in or near the ischemic zone; and 4) all collateral beds develop a circumferential flow gradient following occlusion.
Factors affecting expired waveform for carbon monoxide
Authors: Rubin D. Z. , Lewis S. M. , Mittman C.
Published: December 2017

We previously presented a method based on a computer lung model for determining the distribution of both specific ventilation and specific diffusing capacity. These argon and carbon monoxide (CO) washin and washout studies were obtained in 12 normal subjects and 24 patients with varying degrees of obstructive lung disease. In addition to end-tidal and mixed expired gas concentrations, the expired waveform for both gases was sampled. In patients we found that this method failed to adequately describe CO dynamics during the early part of expiration; predicted concentrations were higher than actual data. Modifications of the original model that satisfy all data are presented. This new model suggests that CO uptake occurs in spaces with ventilatory properties of dead space. The accuracy and reliability of these observations were established by computer simulation studies as well as by repeated testing in one subject. These proved to be highly reproducible over a period of 5 mo. Standard parameter sensitivity tests showed parameters to vary by less than 10% and to be stable even when realistic levels of noise were added to the data. We conclude that studies involving ventilation of insoluble gases are insufficient to describe gas exchange in the lung. The addition of an exchangeable gas adds significant understanding of lung function, particularly in disease.
Breathing pattern in humans: elevated CO2 or low O2 on positive airway pressure
Authors: Hirsch J. A. , Bishop B.
Published: December 2017

The purpose of this study was to determine effects on breathing pattern of pressure breathing alone and in combination with chemical stimulation. We analyzed ventilatory responses to elevated airway pressures (positive-pressure breathing, PPB) in subjects breathing air, 12% O2, or elevated CO2. Each subject sat in a body box and breathed via mouth-piece from a bag-in-box. Responses to PPB on air were increased minute ventilation (VI), tidal volume (VT), frequency (f), mean inspiratory (VT/TI) and expiratory (VT/TE) flows, decreased expiratory duration (TE) and end-tidal CO2. If end-tidal CO2 were held constant, VI, VT, and VT/TI increased less. Responses greater than predicted from summing responses to either stimulus alone were observed for VT, f, VT/TI, and VT/TE during 3 and 5% CO2 and for VT, f, and VT/TE during isocapnic hypoxia. Responses to other combined stimuli were sums of responses to the individual stimuli. Thus ventilatory responses to combined PPB and chemical stimuli cannot be predicted simply from summating responses to each independently imposed stimulus, suggesting that sensory information arises from and is integrated at multiple sites.
Laser-Doppler measurement of skin blood flow: comparison with plethysmography
Authors: Johnson J. M. , Taylor W. F. , Shepherd A. P. , Park M. K.
Published: December 2017

We compared laser-Doppler velocimetry with plethysmographically determined changes in skin blood flow (SkBF) in five studies on four men. Increments in SkBF were induced by raising whole-body skin temperature to 39 degrees C for 50–70 min. We found laser-Doppler blood flow (LDF) to correlate well with total forearm blood flow (FBF) within each study (r = 0.94–0.98), but the relationship varied among studies. Thus the slopes for the LDF vs. FBF relationship varied from 40 to 122 mV X ml-1 X 100 ml X min. The value for LDF at zero FBF, extrapolated from the regression relationships, ranged from 246 to 599 mV above the value for LDF set with the probe on a stationary object. The value for LDF when blood flow to the arm was mechanically occluded ranged from 110 to 230 mV. In a second series, we measured the LDF values from six sites on forearms of each of four normothermic men. There was marked regional variation, with 1.8- to 5.7-fold ranges in LDF within a given subject. Values for LDF during occlusion of the forearm were more consistent within and between subjects. Thus LDF appears to provide a good indicator of the response pattern of SkBF from the region of illuminated skin. However, variability in the relationship to total SkBF (probably arising from variation in the number of perfused capillaries in the small volume of tissue) and uncertainties in the value of LDF at zero SkBF make quantitative use difficult.
In-phase rejection requirements for measuring respiratory input impedance
Authors: Peslin R. , Jardin P. , Duvivier C. , Begin P.
Published: December 2017

Respiratory flow is commonly obtained by measuring the pressure difference across a pneumotachograph. When respiratory input impedance is studied, that pressure difference may be very small with respect to the absolute pressure swings inside the pneumotachograph. Then the in-phase rejection of the differential pressure transducer is expected to markedly influence the accuracy of the data. The problem was investigated by computer simulation and by measurements on a mechanical analog of the respiratory system made of a resistance, an inertance, and a compliance arranged in series. Both studies demonstrated that comparatively small differences in the volumes of the chambers or in the lengths or diameters of the connecting tubes led to artifactual frequency dependence of resistance and serious misestimation of compliance and inertance. Errors were larger when the resistance of the pneumotachograph was smaller and the impedance of the subject larger. In practice, with usual pneumotachographs accurate impedance measurements require using the most symmetrical transducers presently available (common-mode rejection ratio of about 70 dB at 30 Hz).
A model of embolic chronic pulmonary hypertension in the dog
Authors: Shelub I. , van Grondelle A. , McCullough R. , Hofmeister S. , Reeves J. T.
Published: December 2017

Despite numerous efforts, a reliable model of chronic embolic pulmonary hypertension has not been established. To develop such a model five conscious mongrel dogs were embolized repeatedly over 16–30 wk with Sephadex microspheres 286 +/- 70 micron in diameter. Hemodynamic and respiratory measurements were obtained just prior to each embolization. Chronic pulmonary hypertension developed in all dogs. Pulmonary hypertension was not accounted for by increased cardiac output, wedge pressure, right atrial pressure, or systemic arterial pressure. Gas exchange was little altered. Lung histological study revealed microspheres clustered within vessels. In three dogs increased pulmonary arterial pressure was sustained despite cessation of embolization for up to 5 mo. Reembolization in one of these caused further pulmonary hypertension. In two dogs acute pulmonary vasodilation by O2 breathing and administration of prostaglandin E1 reduced, but did not abolish, the increased pulmonary vascular resistance, suggesting some vascular tone was present. An embolic model of chronic pulmonary hypertension in awake dogs allows further investigation into the evolution of pulmonary hypertension.
Effects of acute exposure to high altitude on ventilatory drive and respiratory pattern
Authors: Burki N. K.
Published: December 2017

To assess changes in ventilatory regulation in terms of central drive and timing, on exposure to high altitude, and the effects of induced hyperoxia at high altitude, six healthy normal lowland subjects (mean age 19.5 +/- 1.64 yr) were studied at low altitude (518 m) and on the first 4 days at high altitude (3,940 m). The progressive increase in resting expired minute ventilation (VE; control mean 9.94 +/- 1.78 to 14.25 +/- 2.67 l/min on day 3, P less than 0.005) on exposure to high altitude was primarily due to a significant increase in respiratory frequency (f; control mean 15.6 +/- 3.5 breaths/min to 23.8 +/- 6.2 breaths/min on day 3, P less than 0.01) with no significant change in tidal volume (VT). The increase in f was due to significant decreases in both inspiratory (TI) and expiratory (TE) time per breath; the ratio of TI to TE increased significantly (control mean 0.40 +/- 0.08 to 0.57 +/- 0.14, P less than 0.025). Mouth occlusion pressure did not change significantly, nor did the ratio of VE to mouth occlusion pressure. The acute induction of hyperoxia for 10 min at high altitude did not significantly alter VE or the ventilatory pattern. These results indicate that acute exposure to high altitude in normal lowlanders causes an increase in VE primarily by an alteration in central breath timing, with no change in respiratory drive. The acute relief of high altitude hypoxia for 10 min has no effect on the increased VE or ventilatory pattern.
Effect of aerosol histamine on lung lymph in awake sheep
Authors: Hutchison A. A. , Bernard G. R. , Snapper J. R. , Brigham K. L.
Published: December 2017

This study examined the effect of aerosol histamine on lung lymph in the awake sheep. Eleven sheep were chronically instrumented for measurement of lung lymph, lung mechanics, and vascular pressures. Aerosol histamine was given by use of a Collison nebulizer and delivered via a tracheostomy tube. Five breaths of a 30 mg/ml histamine solution caused lung lymph flow (QL) to increase from a base line of 5.5 +/- 0.5 (SE) ml/h to 14.3 +/- 1.5 (P less than 0.05) and the lymph-to-plasma protein concentration ratio (L/P) to increase from 0.63 +/- 0.02 to 0.72 +/- 0.02 (P less than 0.05). The concentration of aerosol histamine required to change QL by 30% (ED130QL) was determined by giving increasing concentrations of aerosol histamine every 15 min. The mean ED130QL was 22.2 mg/ml. The dose of histamine required to increase QL by 30% did not correlate (r = 0.04, n = 7) with the dose required to decrease dynamic compliance by 35%. The increase in QL lasted 100 +/- 19 min. Hourly exposure to five breaths of 30 mg/ml for 5 h caused a sustained increase in QL in two sheep and a waning effect in two sheep. The combination of aerosol histamine and elevated microvascular pressure (achieved by inflating a Foley catheter situated in the left atrium) caused changes in QL and L/P not totally consistent with the hypothesis that histamine increased pulmonary vascular permeability. Increased vascular permeability in the bronchial circulation was considered a likely explanation of the data.
Relation between respiratory neural output and tidal volume
Authors: Younes M. , Riddle W.
Published: December 2017

We recently described a model for the relation between respiratory neural and mechanical outputs (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 963–1001, 1981). In this communication we utilize the model to address the following questions. 1) How sensitive is tidal volume (VT) to shape and timing of respiratory neural output (N)? 2) How effective are shape and timing characteristics of N in load compensation? 3) For a given VT, what is the most economical shape and timing of N? Using different values of passive respiratory mechanics, we generated the VT profiles associated with theoretical N waveforms having different shape and timing parameters. We found that 1) with normal mechanics VT is moderately sensitive to inspiratory time (TI) but not to shape of N, whereas with high resistance and short TI, VT is very sensitive to shape and timing; 2) changes in shape, within the physiological range, can serve as potent load-compensatory mechanisms; and 3) for a given VT, the most economical (lowest mean pressure) N pattern is one with a very short TI and a rising phase that is convex to time axis. This holds true even with high resistance.
Filtration coefficient obtained by stepwise pressure elevation in isolated dog lung
Authors: Ehrhart I. C. , Granger W. M. , Hofman W. F.
Published: December 2017

The base-line capillary filtration coefficient (Kf) obtained from rates of lobe weight gain during stepwise vascular pressure elevation is reported to be threefold greater in isolated than in intact dog lung. To further evaluate the stepwise pressure elevation technique, we obtained Kf in control and oleic acid-injured isolated lung. The left lower lung lobe was removed, placed on a balance, ventilated, and pump perfused with autogenous blood. Saline (n = 6) or oleic acid (n = 6) was infused, and rate of lobe weight gain was obtained during stepwise pressure elevation. Kf averaged 0.071 +/- 0.012 and 0.243 +/- 0.027 ml X min-1 X Torr-1 X 100 g-1 in the control and injured lobes, respectively. Stepwise pressure elevation can yield a base-line Kf in isolated lung similar to Kf's obtained from this and other gravimetric methods in intact and isolated lung. Furthermore, Kf increased severalfold following lung injury with oleic acid. The stepwise pressure elevation technique for Kf determination in isolated lung can be a useful tool for quantitating changes in vascular permeability.
Pressure-volume curve of lung and lobes in kittens
Authors: Mortola J. P. , Rossi A. , Zocchi L.
Published: December 2017

In the neonatal period, the incomplete aeration of the lung parenchyma and the presence of some pulmonary fluid could determine inequalities in the mechanical behavior of lung regions, favoring unevenness of ventilation distribution. We studied the pressure-volume (PV) curve of excised lungs of kittens in the 1st wk of life 1) by changing the volume a known amount and measuring the corresponding changes in transpulmonary pressure (PL) and 2) by ventilating them at a fixed PL at a rate of 20 cycles/min. An expiratory load equal to the value of PL at the resting volume of the respiratory system was added to avoid the collapse of the lung. A lobar bronchus was then tied, and the measurements were repeated. The difference in PV curves before and after ligature therefore represented the PV curve of the lobe. This was done for all the lobes (upper and middle right, lower right, lower left, upper left) in a random order. A total of 20 lungs and 61 lobes have been studied. Individual lobes were not different in terms of dry-to-wet weight ratio, compliance per unit weight, or per maximal volume and shape of the PV curve, indicating a similar mechanical behavior. Dynamic lung compliance averaged 76% +/- 15 SD of the static value, suggesting some degree of asynchronous behavior of lung regions or viscoelastic properties of the tissue.
Peak oxygen uptake during arm cranking for men and women
Authors: Washburn R. A. , Seals D. R.
Published: December 2017

To determine upper body peak O2 uptake (VO2) in a group of young females and to obtain information on possible sex differences, 40 subjects, 20 females and 20 males, mean age 26 +/- 4 (SD) and 31 +/- 6 yr, respectively, were studied during maximal arm-cranking exercise. Peak values for power output, VO2, minute ventilation (VE), and heart rate (HR) were determined for each subject. In addition, arm-shoulder volume (A-SV) was measured before exercise. Significant differences between males and females (P less than 0.05) were found for peak power output (134 +/- 18 vs. 86 +/- 13 W), peak VO2 expressed in liters per minute (2.55 +/- 0.45 vs. 1.81 +/- 0.36) and milliliters per kilogram per minute (34.2 +/- 5.3 vs. 29.2 +/- 4.9), peak VE (95.4 +/- 14.5 vs. 70.1 +/- 19.2 1 X min-1), and A-SV (3,126 +/- 550 vs. 2,234 +/- 349 ml), whereas peak HR was not significantly different between the two groups (174 +/- 14 vs. 174 +/- 36 beats X min-1). However, when peak VO2 was corrected for arm and shoulder size there was no significant difference between the groups (0.82 +/- 0.13 vs. 0.78 +/- 0.13 ml X ml A-SV-1 X min-1). These results suggest that the observed differences between men and women for peak VO2 elicited during arm cranking when expressed in traditional terms (1 X min-1 and ml X kg-1 X min-1) are a function of the size of the contracting muscle mass and are not due to sex-related differences in either O2 delivery or the O2 utilization capacity of the muscle itself.
Effect of aging on ventilatory response to exercise and CO2
Authors: Brischetto M. J. , Millman R. P. , Peterson D. D. , Silage D. A. , Pack A. I.
Published: December 2017

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.
Level of physical fitness and adipocyte lipolysis in humans
Authors: Despres J. P. , Bouchard C. , Savard R. , Tremblay A. , Marcotte M. , Theriault G.
Published: December 2017

The present experiment was conducted to study the influence of exercise training on adipose tissue lipolytic activity and to identify the amount of training required to induce maximal adaptation in humans. Fifty-one male subjects were divided into three groups according to their training regimen: 1) sedentary subjects (SS) (n = 21); 2) trained subjects (TS) (n = 15) who had exercised during a period of 20 wk, 5 days/wk, 45 min/session; and 3) experienced marathon runners (MR) (n = 15) who ran an average of 120 km/wk for many years. Biopsies of fat were performed in the suprailiac region after an overnight fast. Adipocyte diameter (AD) and epinephrine-stimulated lipolysis ( ESL ) were assessed on collagenase-isolated fat cells. A lower AD was noted in the MR group compared with the two other groups. Basal lipolysis (BL) and ESL were significantly higher in TS and MR than in controls. Moreover, BL values were comparable in the two trained groups, whereas ESL in the TS group was higher than in the MR group. These results indicate that training increases suprailiac fat cell lipolysis, which seems to adapt maximally within about 4 mo.
How alterations in pleural pressure influence esophageal pressure
Authors: Hurewitz A. N. , Sidhu U. , Bergofsky E. H. , Chanana A. D.
Published: December 2017

Although esophageal pressures have been substituted for direct pleural pressure measurement in humans, we have investigated the validity of this approach under circumstances when left and right pleural pressures are not equal. Esophageal and bilateral pleural pressures in awake sheep were compared by using matched balloon catheters in close proximity. In standing sheep, both end-expiratory pressures and inspiratory pressure swings were similar in all three catheter systems. However, when pleural pressures were made unequal, as during lateral recumbency or unilateral pneumothorax, the esophageal pressure reflected predominantly the right pleural pressure. These results suggest that esophageal pressures are useful estimates of pleural pressure under normal conditions when pleural pressures are equal bilaterally. However, the usefulness of esophageal pressures is limited in the presence of unilateral pneumothorax or other conditions where left and right pleural pressures are unequal. In the lateral decubitus position, positive end-expiratory pleural pressures were consistently observed. This was believed to be due to a combination of contraction of expiratory muscles, rapid respiratory rate resulting in insufficient expiratory time to reach an equilibrium pressure, and increased airways resistance resulting from compression of the dependent lung by the abdominal viscera. A single study in a paralyzed ventilated sheep showed less positive expiratory pressures, which were further reduced to zero or less when the respiratory rate was slowed to 10 breaths/min.