bluuebunny/crossref_metadata_2025 huggingface dataset:
A computerized respiratory system including test functions of lung and circulation
Authors: Jansen J. R. , Hoorn E. , Van Goudoever J. , Versprille A.
Published: December 2017

The design of a microcomputer-controlled ventilator for automatic performance of lung function and circulatory tests has been described. It incorporates the characteristics of normal mechanical ventilation and also allows one to perform a multitude of test procedures for lung function and circulatory studies in paralyzed animals. The major components of the setup are a pump assembly with solenoid valves to direct gas flow, an electromechanical servo system, and a MS-DOS microcomputer system. The pump assembly has been constructed as a relatively simple device. Great versatility is created by the use of a microcomputer for the control of the ventilator. The software can be easily adapted to several other types of experimental studies. Besides the keyboard input the ventilator can be controlled by a remote computer system. This allows one to run an experimental protocol automatically and to use it in closed-loop servo ventilation. The flexibility in the choice of the respiratory parameters makes the ventilator suitable for lung function and circulatory studies during artificial ventilation. The ventilator has been successfully used in different animal studies during the last 6 yr.
Display of the alveolar plateau of single-breath tests in "dilution index" format
Authors: Van Liew H. D. , Mahajan R. K.
Published: December 2017

In 1949, Fowler (J. Appl. Physiol. 2: 283–299) advocated calculation of a "dilution index" from data of the alveolar plateau of single-breath tests; the calculation provides an estimate of the dilution of resident gas in the lung that gave rise to the observed concentrations. In this communication, we show that the calculation can be applied to conventional single-breath tests where O2 is inhaled by air-breathing persons, and we illustrate the principle with vital capacity breaths of a mixture that contained a low concentration of neon. The dilution was approximately 3:1 in young subjects (20–30 yr), as if a vital capacity of 6 liters were mixed with a residual volume of 2 liters. The dilution was less, 2:1, in older subjects (56 yr) and tended to become as low as 1:1 during emptying of the closing volume. In addition to being more informative, the dilution index format allows common sense comparison of alveolar plateau levels and slopes when single-breath tests are done by various methods.
Pulmonary transvascular flux of transferrin
Authors: Cooper J. A. , Malik A. B.
Published: December 2017

We compared the pulmonary transvascular fluxes of transferrin and albumin in the intact sheep lung. Anesthetized sheep were prepared with lung lymph fistulas. The vascular blood pool was marked with 99mTc-erythrocytes, autologous transferrin was labeled with 113mIn, and albumin was labeled with 125I. Samples of blood, plasma, lymph, and lung were obtained up to 180 min after tracer infusion. Lymph tissue radioactivities were corrected for the intravascular component and expressed as extravascular-to-plasma concentration ratios. Clearance of transferrin and albumin from the plasma space followed a two-compartment model. The clearance rate constant was 2.1 +/- 0.1 x 10(-3) min for albumin and 2.4 +/- 0.1 x 10(-3) min for transferrin (P less than 0.05). Lymph-to-plasma ratios for albumin and transferrin were not different. However, the extravascular-to-plasma ratio for albumin was greater than transferrin (P less than 0.05). The lymph and lung data were deconvoluted for the plasma input function and fit to a two-compartment model. The results indicate that albumin and transferrin have similar permeabilities across the vascular barrier but have different pulmonary circulation to lymph kinetics because the extravascular volume of distribution of albumin is greater than transferrin.
Sonomicrometric regional diaphragmatic shortening in awake sheep after thoracic surgery
Authors: Torres A. , Kimball W. R. , Qvist J. , Stanek K. , Kacmarek R. M. , Whyte R. I. , Montalescot G. , Zapol W. M.
Published: December 2017

Through a right thoracotomy in seven sheep we chronically implanted sonomicrometry crystals and electromyographic electrodes in the costal and crural diaphragmatic regions. Awake sheep were studied during recovery for 4-6 wk, both during quiet breathing (QB) and during CO2 rebreathing. Tidal volume, respiratory frequency, and esophageal and gastric pressures were studied before and after surgery. Normalized resting length (LFRC) was significantly decreased for the costal segment on postoperative day 1 compared with postoperative day 28. Fractional costal shortening both during QB and at 10% end-tidal CO2 (ETCO2) increased significantly from postoperative days 1 to 28, whereas crural shortening did not change during QB but progressively increased at 10% ETCO2. Maximal costal shortening during electrophrenic stimulation was constant at 40% LFRC during recovery, although maximal crural shortening increased from 23 to 32% LFRC. Minute ventilation, tidal volume, and transdiaphragmatic pressure at 10% ETCO2 increased progressively after thoracotomy until postoperative day 28. Our results suggest there is profound diaphragmatic inhibition after thoracotomy and crystal implantation in sheep that requires at least 3-4 wk for stable recovery.
Reduced erythrocyte deformability alters pulmonary hemodynamics
Authors: Doyle M. P. , Galey W. R. , Walker B. R.
Published: December 2017

Isolated rat lungs were perfused with suspensions containing normal and stiffened erythrocytes (RBCs) to assess the effect of altered RBC deformability on pulmonary hemodynamics. RBC suspensions were prepared using cells previously incubated in isosmolar phosphate-buffered saline with or without 0.0125 or 0.01875% glutaraldehyde. Washed RBCs were resuspended in isosmolar 4% albumin saline solution. Isolated rat lungs were perfused with control and stiffened cells by the use of a perfusion system that allowed rapid switching between suspensions. Pressure-flow (P/Q) curves were constructed by measuring pulmonary arterial pressure (Ppa) over a range of flow rates. In a second set of experiments, P/Q curves were generated for perfusion with control and stiffened cells (0.0125% glutaraldehyde) before and after vasoconstriction with a synthetic prostaglandin analogue (U 46619). RBC deformability was quantified in all experiments by determination of filtration time of a dilute cell suspension through a 4.7 microns Nuclepore filter. Incubation with 0.0125 or 0.01875% glutaraldehyde produced a 6 or 21% decrease in RBC deformability, respectively. These decreases in deformability were associated with significant increases in Ppa at each flow rate. The increases in Ppa correlated significantly with the degree of RBC stiffening. With 0.0125% glutaraldehyde, the P/Q curve was shifted upward without a change in slope, whereas incubation with 0.01875% glutaraldehyde resulted in a significant increase in slope. Vasoconstriction and perfusion with stiffened RBCs had additive effects on Ppa. These findings suggest that decreases in RBC deformability cause physiologically significant elevations in hemodynamic resistance in the pulmonary circuit independent of vasoactivity.
Responses to negative pressure surrounding the neck in anesthetized animals
Authors: Wolin A. D. , Strohl K. P. , Acree B. N. , Fouke J. M.
Published: December 2017

Continuous positive pressure applied at the nose has been shown to cause a decrease in upper airway resistance. The present study was designed to determine whether a similar positive transmural pressure gradient, generated by applying a negative pressure at the body surface around the neck, altered upper airway patency. Studies were performed in nine spontaneously breathing anesthetized supine dogs. Airflow was measured with a pneumotachograph mounted on an airtight muzzle placed over the nose and mouth of each animal. Upper airway pressure was measured as the differential pressure between the extrathoracic trachea and the inside of the muzzle. Upper airway resistance was monitored as an index of airway patency. Negative pressure (-2 to -20 cmH2O) was applied around the neck by using a cuirass extending from the jaw to the thorax. In each animal, increasingly negative pressures were transmitted to the airway wall in a progressive, although not linear, fashion. Decreasing the pressure produced a progressive fall in upper airway resistance, without causing a significant change in respiratory drive or respiratory timing. At -5 cmH2O pressure, there occurred a significant fall in upper airway resistance, comparable with the response of a single, intravenous injection of sodium cyanide (0.5-3.0 mg), a respiratory stimulant that produces substantial increases in respiratory drive. We conclude that upper airway resistance is influenced by the transmural pressure across the airway wall and that such a gradient can be accomplished by making the extraluminal pressure more negative.(ABSTRACT TRUNCATED AT 250 WORDS)
Fatigue of single motor units in human masseter
Authors: Nordstrom M. A. , Miles T. S.
Published: December 2017

The spike-triggered averaging technique was used to determine the time course and extent of fatigue of single motor unit twitches in the human masseter. This is the first report of a fatigue test having been applied to masseter motor units in either animals or humans. The human masseter was found to be comprised predominantly of fast-twitch motor units with a broad spectrum of fatigability. Very few physiological type S units were found, despite histochemical evidence for a substantial population of type I fibers in the masseter. In addition, there was no significant correlation between fatigability and either twitch amplitude or contractile speed in the motor units studied. The latter observations are consistent with the unusual histological features of the masseter. Comparison with other human fatigue data suggests that the extent of fatigue in the present population of masseter motor units after approximately 3,000 activations is similar to that reported for populations of units in first dorsal interosseous and medial gastrocnemius.
Plasma free and sulfoconjugated catecholamines during sustained exercise
Authors: Sothmann M. S. , Blaney J. , Woulfe T. , Donahue-Fuhrman S. , Lefever K. , Gustafson A. B. , Murthy V. S.
Published: December 2017

Previous research established a relationship between circulating sulfoconjugated norepinephrine (NE-SO4) and oxygen consumption at various exercise intensities. In this study, the stability of the NE-SO4 response was examined during sustained exercise at a constant relative intensity. Seven trained men bicycled at 78 +/- 3% of their maximal O2 consumption for 28 min and then rested on the ergometer for a comparable duration. After a 30-min rest, plasma samples were collected through an indwelling catheter at 7-min intervals during the exercise and recovery periods. Free NE and epinephrine increased sixfold during exercise. These changes were accompanied by increases in sulfoconjugated catecholamines, but only NE-SO4 achieved statistical significance (rest, 712 +/- 602; exercise, 1,329 +/- 1,163 pg/ml). This occurred at three collection periods (14, 21, and 28 min). Approximately 35, 52, and 95% of NE, epinephrine, and dopamine, respectively, existed as sulfoconjugated during exercise. Subject variation was present in the sulfoconjugated catecholamine response that could not be attributed to corresponding differences in circulating free catecholamine release. These findings implicate blood flow as a factor in the sulfoconjugation of NE, but not epinephrine or dopamine.
Effect of body weight gain on insulin sensitivity after retirement from exercise training
Authors: Dolkas C. B. , Rodnick K. J. , Mondon C. E.
Published: December 2017

The objectives of this study were to determine how long increased insulin sensitivity, elicited by exercise training, persists after the end of training and what the effect of weight gain is on this retention. Exercise-trained (ET) rats ran voluntarily in freely rotating wheel cages, and insulin sensitivity was assessed by oral glucose tolerance tests (OGTT) and insulin suppression tests (IST). After training, ET rats were retired for 1, 3, or 7 days (R1, R3, or R7). Initial OGTT and IST studies indicated that sensitivity to insulin-induced glucose uptake was increased in ET rats compared with sedentary control (C) rats and was progressively lost with retirement: ET greater than R1 and R3 greater than R7 and C rats, and this reaction was generally associated with a rapid gain in body weight. Subsequent IST tests were performed on C and R7 rats fed laboratory chow or a hypocaloric diet consisting of equal parts of cellulose and chow for 7 days before the test. The results of these tests showed that steady-state serum glucose (SSSG) levels averaged 165 +/- 12 mg/dl for chow-fed C rats and 172 +/- 11 mg/dl for chow-fed R7 rats that gained body weight at rates twice those of C rats. Chow-fed R7 rats, gaining weight at rates comparable to C rats, had SSSG levels of 104 +/- 6 mg/dl. C and R7 rats fed the hypocaloric diet had SSSG values of 102 +/- 6 and 59 +/- 4 mg/dl, respectively. Muscle glycogen levels were comparable in all groups, and liver glycogen was lower in C and R7 rats fed the hypocaloric diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of age on changes in flow rates and airway conductance after a deep breath
Authors: Berry R. B. , Pai U. P. , Fairshter R. D.
Published: December 2017

The effects of aging on changes in maximal expiratory flow rates and specific airway conductance after a deep breath were evaluated in 64 normal subjects. Flow rates (Vp) on partial expiratory flow-volume curves (PEFV), initiated from 60-70% of the vital capacity (VC), were compared with those (Vc) on maximal flow-volume curves (MEFV), initiated from total lung capacity (TLC), at a lung volume corresponding to 25% of VC on the MEFV curves. Specific airway conductance was measured before (sGaw) and after a deep inspiration (sGawDI). Bronchodilation after inspiration to TLC was inferred by Vp/Vc less than 1 and sGaw/sGawDI less than 1. The mean Vp was less than Vc. However, the ratio Vp/Vc increased significantly with age (r = 0.75, P less than 0.001). Specific conductance also increased after a deep inspiration (sGaw less than sGawDI). The ratio sGaw/sGawDIj increased slightly but significantly with age (r = 0.28, P less than 0.02). Measurement of lung elastic recoil pressures before and after a deep breath in a subgroup of patients (n = 14) suggested that the age-related increase in Vp/Vc was secondary to a decrement in the ability of a deep breath to decrease the upstream airway resistance. These findings suggest that even though changes in airway size after a deep breath as measured by sGaw/sGawDI have minimal age dependence, aging diminishes expiratory flow rates of MEFV curves relative to PEFV curves because of a decrease in the ability of a deep breath to increase the size of the peripheral airways.
Effects of continuous positive airway pressure breathing on lung volume and distensibility
Authors: Duggan C. J. , Castle W. D. , Berend N.
Published: December 2017

In this study the effects on lung elastic behavior of 10 min of breathing at a continuous positive airway pressure (CPAP) of 10 cmH2O were examined in 10 normal subjects. To investigate whether any changes were induced by release of prostaglandins, the subjects were also pretreated with the cyclooxygenase inhibitor indomethacin. CPAP produced a significant (P less than 0.001) upward shift of the pressure-volume (PV) curve [change in total lung capacity (delta TLC) 374 +/- 67 (SE) ml, mean delta volume at a transpulmonary pressure of 15 cmH2O (delta VL15) 279 +/- 31 ml] with no change in K, an index of lung distensibility. After CPAP the PV curves returned to normal base line within 20 min. The same pattern was observed after indomethacin, but the increase in TLC was significantly less (P less than 0.01) (mean delta TLC 206 +/- 42 ml) mainly because of a slight and not statistically significant increase in base-line TLC. In five subjects further PV curves with and without CPAP were obtained greater than or equal to 7 days after indomethacin. The responses were not significantly different from those obtained before indomethacin (mean delta TLC 366 +/- 89, mean delta VL15 296 +/- 42 ml). We conclude that CPAP produces an upward shift of the PV curve without a change in lung distensibility. In addition, there may be a small degree of resting alveolar duct tone that is influenced by indomethacin.
Effect of aminophylline on mechanical activity of rat diaphragm bundles
Authors: Delbono O. , Kotsias B. A.
Published: December 2017

We studied the effect of aminophylline (0.1-1 mM) on the mechanical and electrical activity of rat diaphragm bundles in vitro (25 degrees C). The main findings are the following. 1) Aminophylline potentiates the twitch tension. The tetanus tension is not modified, although the rate of decay is decreased. 2) The relation between K contracture tension and resting membrane potential (Vm) is shifted toward more negative values of the Vm in the aminophylline-containing solution. 3) The mechanical threshold measured by direct visualization of the fiber is also lowered in the fibers equilibrated in aminophylline. These effects are reversible by washing out the preparation with normal solution. 4) The shift in the relation between tension and Vm induced by aminophylline is reversed by 1 microM nifedipine. 5) The generation of action potential is not modified by aminophylline. We suggest that the shift in the mechanical threshold is the principal factor involved in the potentiating effect of aminophylline. We speculate that theophylline acts to augment tension by enhancing calcium release from the sarcoplasmic reticulum and that nifedipine blocks this release (E. Rios, and G. Brum. Nature Lond. 325: 717-720, 1987).
Leukotriene B4 increases pulmonary transvascular filtration by a neutrophil-independent mechanism
Authors: Burgess C. A. , McCandless B. K. , Cooper J. A. , Malik A. B.
Published: December 2017

We examined the role of circulating granulocytes in the pulmonary microvascular response to leukotriene B4 (LTB4) by prior depletion of circulating granulocytes using hydroxyurea. LTB4 (2 micrograms/kg injection followed by infusion of 2 micrograms/kg over 15 min) produced transient increases in pulmonary arterial pressure and pulmonary vascular resistance, indicating that neutrophils were not required for the pulmonary hemodynamic effects of LTB4. Infusion of LTB4 in granulocyte-depleted sheep also resulted in transient increases in pulmonary lymph flow (QL) with no significant change in the lymph-to-plasma protein concentration ratio (L/P), findings similar to those in control animals. In vitro studies indicated that LTB4 (10(-7) or 10(-9) M) produced a transient adherence of neutrophils to cultured pulmonary artery endothelial monolayers. Maximal responses occurred at 10 min after the addition of LTB4 to the endothelial cell-neutrophil coculture system, and the adherence decreased to base line within 60 min. LTB4 infusion in sheep also produced a transient uptake of autologous 111In-oxine-labeled neutrophils. The results indicate that LTB4-mediated increase in pulmonary transvascular protein clearance (QL x L/P) is independent of circulating granulocytes.
Group I afferent fibers: effects on cardiorespiratory system
Authors: Orani G. P. , Decandia M.
Published: December 2017

In anesthetized cats, we examined cardiorespiratory activity during excitation of large afferent fibers from muscle proprioceptors. We found that selective stimulation of group I fibers with electric impulses at 200-300 Hz induces an increase in pulmonary ventilation from control value (mean +/- SE) of 486 +/- 8 to a maximum of 544 +/- 8 ml/min and an increase in mean systemic arterial pressure from control value of 151 +/- 2 to a maximum of 160 +/- 2 mmHg. Neither of these increases was produced by the same stimulation when applied during anodal block of volleys of group I fibers. Hyperpnea could be obtained independently from changes in cardiovascular activity, and the pressor response could be obtained during artificial ventilation at constant tidal volume after curarization. Consequently, it appears that respiratory and cardiovascular responses to stimulation of group I fibers can be independent of each other.
Pathogenesis of pulmonary edema associated with intracisternal endotoxin in dogs
Authors: Nahum A. , Wood L. D. , Crawford G. , Ripper R. , Segil L. , Sznajder J. I.
Published: December 2017

To examine the role of central nervous system injury in the pathogenesis of pulmonary edema, we injected Escherichia coli endotoxin (5 mg/kg) into the cisterna magna of six dogs (group E) and compared, over 4 h, both the pulmonary edema and cerebrospinal fluid (CSF) abnormalities with those in six control dogs (group C). In group E, intracisternal endotoxin raised intracranial pressure from 21 +/- 6 to 38 +/- 8 cmH2O (P less than 0.001), CSF total protein from 18 +/- 6 to 54 +/- 19 mg/dl (P less than 0.001), and CSF malondialdehyde from 0.12 +/- 0.11 to 0.61 +/- 0.35 nmol/ml (P less than 0.05); all were unchanged in group C. When the pulmonary wedge pressure was maintained at 10 mmHg by fluid infusion, extravascular thermal volume in group E increased from 7.2 +/- 1.2 to 12.0 +/- 2.7 ml/kg (P less than 0.005) at 4 h when the excised lungs weighed 13.6 +/- 1.5 g/kg; in group C, extravascular thermal volume did not increase, and the excised lungs weighed less (10.8 +/- 1.3 g/kg, P less than 0.05) than those in group E. The dry weights of the lungs were not different between groups, and the alveolar lining fluid-to-plasma albumin ratio in both groups remained low, 0.1-0.2. Fluid infusion in group E (9.2 +/- 2.9 liters) caused colloid oncotic pressure to decrease 4.5 +/- 2.8 mmHg; colloid oncotic pressure fell less (0.8 +/- 1.9 mmHg, P less than 0.001) in group C as less fluid (2.2 +/- 1.5 liters, P less than 0.001) was required to maintain pulmonary wedge pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Determinants of restrictive lung function in asbestos-induced pleural fibrosis
Authors: Schwartz D. A. , Galvin J. R. , Dayton C. S. , Stanford W. , Merchant J. A. , Hunninghake G. W.
Published: December 2017

We evaluated whether restrictive lung function among asbestos-exposed individuals with pleural fibrosis was caused by radiographically inapparent parenchymal inflammation and/or parenchymal fibrosis. All 24 study participants were sheet metal workers who were nonsmokers with normal parenchyma on posteroanterior chest radiograph. These subjects had either normal pleura (n = 7), circumscribed plaques (n = 9), or diffuse pleural thickening (n = 8). After controlling for age, years in the trade, and pack-years of smoking, we found that sheet metal workers with diffuse pleural thickening had a lower forced vital capacity (P less than 0.001), total lung capacity (P less than 0.01), and CO-diffusing capacity of the lung (P less than 0.05) than those with normal pleura. Similarly, sheet metal workers with circumscribed plaques were found to have a reduced forced vital capacity; however, because of the small number of study subjects, this difference (regression coefficient = -11.0) was only marginally significant (P = 0.06). Although circumscribed plaque and diffuse pleural thickening were both associated with a lymphocytic alveolitis and a higher prevalence of parenchymal fibrosis on high-resolution computerized tomography (HRCT) scan, neither a lymphocytic alveolitis nor the finding of parenchymal fibrosis on HRCT scan influenced the relationship between pleural fibrosis and restrictive lung function. We conclude that pleural fibrosis is associated with restrictive lung function and abnormally low diffusion that appears to be independent of our measures of parenchymal injury (chest X-ray, bronchoalveolar lavage, and HRCT scan).(ABSTRACT TRUNCATED AT 250 WORDS)
Leukotrienes and prostaglandins in fetal lung liquid
Authors: Cassin S. , Stenmark K. R. , Gause G. , Zapp L. M. , Kuck H. , Westcott J. Y.
Published: December 2017

Several recent studies have suggested that peptidoleukotrienes are involved in or responsible for the pulmonary pressor response to hypoxia as well as the normally high pulmonary vascular resistance of fetal lambs. The present studies were carried out to test these hypotheses. Fetal lambs were prepared with indwelling vascular catheters and tracheal catheters for access to lung liquid. We measured lung liquid levels of leukotrienes C4 (LTC4) and D4 (LTD4) in control unanesthetized fetal lambs with blood gases and pH in the normal range. In the control series, LTC4 and LTD4 were either not detectable or their levels were close to the limit of resolution (LTC4, less than 80 pg/ml; LTD4, less than 50 pg/ml) of the techniques utilized. Leukotriene E4 was measured in a separate study by using pooled samples, and it was also found to be below the detection limit of that assay (10 pg/ml). In a second series of animals, a level of acute hypoxia was induced to decrease fetal arterial PO2 to 12 Torr for 20 min. After hypoxia, tracheal fluid levels of leukotrienes were again below detection limits of the assays used (LTC4, less than 80 pg/ml; LTD4, less than 142 pg/ml). In another study, methodology was altered to lower the detection limits of leukotrienes in lung fluid and to allow the measurement of total peptidoleukotriene concentrations. In this study, even when hypoxia was extended for up to 1 h, leukotriene levels were consistently below the limit of detection of the assay (less than 20 pg/ml for the sum of all leukotrienes).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of the chest wall in detection of added elastic loads
Authors: Younes M. , Jung D. , Puddy A. , Giesbrecht G. , Sanii R.
Published: December 2017

Changes in respiratory mechanical loads are readily detected by humans. Although it is widely believed that respiratory muscle afferents serve as the primary source of information for load detection, there is, in fact, no convincing evidence to support this belief. We developed a shell that encloses the body, excluding the head and neck. A special loading apparatus altered pressure in proportion to respired volume (elastic load) in one of three ways: 1) at the mouth only (T), producing a conventional load in which respiratory muscles are loaded and airway and intrathoracic pressures are made negative in proportion to volume, 2) both at the mouth and in the shell (AW), where the same pattern of airway and intrathoracic pressure occurs but the muscles are not loaded because Prs (i.e., mouth pressure minus pressure in the shell is unchanged, and 3) positive pressure in proportion to volume at the shell only, loading the chest wall but causing no change in airway or thoracic pressures (CW). The threshold for detection (delta E50) with the three types of application was determined in seven normal subjects: 2.16 +/- 0.22, 2.65 +/- 0.54, and 6.21 +/- 0.85 (SE) cmH2O/l for T, AW, and CW, respectively. Therefore the active chest wall, including muscles, is a much less potent source of information than structures affected by the negative airway and intrathoracic pressure. The latter account for the very low threshold for load detection.
Local gas transport in eucapnic ventilation: effects of gravity and breathing frequency
Authors: Venegas J. G. , Yamada Y. , Burnham C. , Hales C. A.
Published: December 2017

The effects of body position and respiratory frequency (f) on regional gas transport during eucapnic conventional ventilation (CV) and high-frequency ventilation (HFV) were assessed from the washout of nitrogen 13 (13NN) using positron-emission tomography. In one protocol, six dogs were ventilated with CV or HFV at f = 6 Hz and tidal volume (VT) selected supine for eucapnia. A coronal cross section of the lung base was studied in the supine, prone, and right and left lateral decubitus positions. In a second protocol, six dogs were studied prone: apical and basal cross sections were studied in CV and in HFV with f = 3 and 9 Hz at eucapnic VT. Regional alveolar ventilation per unit of lung volume (spVr) was calculated for selected regions and analyzed for gravity-dependent cephalocaudal and right-to-left gradients. In both CV and HFV, nonuniformity in spVr was highest supine and lowest prone. In CV there were vertical gradients of spVr in all body positions: nondependent less ventilated than dependent regions, particularly in the supine position. In HFV there was a moderate vertical gradient in spVr in addition to a preferentially ventilated central region in all body positions. Overall lung spV was unaffected by body position in CV but in HFV was highest supine and lowest prone. Nonuniformity in eucapnic prone HFV was unaffected by f and always higher than in CV.(ABSTRACT TRUNCATED AT 250 WORDS)
How countercurrent blood flow and uneven perfusion affect the motion of inert gas
Authors: Homer L. D. , Weathersby P. K. , Survanshi S.
Published: December 2017

Monte Carlo simulations of the passage of inert gas through muscle tissue reveal that countercurrent gas exchange is more important than heterogeneity of flow in determination of the shape of inert gas washout curves. Semilog plots of inert gas washout are usually curved rather than straight. Two explanations often offered are that countercurrent flow may distort the shape and that uneven perfusion of the tissue gives rise to nonuniform washout. The curvature of the semilog plot may be summarized by the relative dispersion (RD), which is the ratio of the standard deviation of transit times to the mean transit time. For straight semilog plots, RD is 1. Semilog plots of data showing xenon washout from dog tissues are curved and have and RD of approximately 2. We have simulated the transit of gas particles through a vascular bed composed of repeating units of 100 mg of tissue perfused by three small vessels 80 microns in diameter and several levels of branching that direct flow through 190,000 capillaries. Geometric distribution of flow is important. Similar degrees of flow heterogeneity affect the curvature of the washout curve more if regions of heterogeneous flow are widely spaced than if they are close together. Diffusion blunts the effects of heterogeneous flow by mixing particles in high-flow regions with particles in low-flow regions. Because of this mixing, alternating regions of high flow and low flow spaced at intervals of less than 0.5 cm are unlikely explanations for the curved semilog plots.(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous AA metabolites and their possible role in tracheal smooth muscle tone in guinea pigs
Authors: Yamane K. , Kobayashi T.
Published: December 2017

The effects of endogenous arachidonic acid (AA) metabolites on inherent tone and histamine-induced constriction were studied in guinea pig tracheal smooth muscle. Inhibitors of either cyclooxygenase (indomethacin) or lipoxygenase (AA 861) significantly diminished the inherent tone of the muscle. Antagonists of prostaglandins (SC 19220) or leukotrienes (FPL 55712) also diminished the inherent tone, whereas an inhibitor of thromboxane synthase (OKY 046) had no significant effect. These results show that the metabolites of the lipoxygenase pathway as well as prostaglandins also participate in the maintenance of inherent tone. To reexamine the previously reported augmentation of histamine constriction induced by the inhibitors and the antagonists, we compared the active tension of the muscle measured from the maximum relaxed level as the base line to eliminate the fluctuation of inherent tone. Such comparison revealed that the inhibitors and the antagonists have no augmentative effect on either the maximum response to histamine or the concentration required to produce 50% of maximum active tension and that there is functional synergism between the exogenously added histamine and the endogenously produced AA metabolites. Therefore the zero active tension is useful as a base line to compare the contractile response of a drug-treated preparation with that of a nontreated preparation.
Ozone inhalation effects in females varying widely in lung size: comparison with males
Authors: Messineo T. D. , Adams W. C.
Published: December 2017

It has been suggested that lung size accounts for observed gender differences in responsiveness to the same total inhaled dose of O3. To test the hypothesis that lung size is a determinant of magnitude of response within a gender, two groups of 14 healthy young adult females differing significantly in forced vital capacity [FVC; i.e., small-lung group mean = 3.74 liters (range 3.2-4.0) and large-lung group mean = 5.11 liters (range 4.5-6.2] were exposed for 1 h to filtered air (FA) and to 0.18 and 0.30 ppm O3. On each occasion, subjects exercised continuously on a cycle ergometer at a work rate that elicited a mean minute ventilation of approximately 47 l/min. For the small-lung group [mean total lung capacity (TLC) = 4.52 liters] exercise O2 uptake was 67% of maximal O2 uptake (VO2max), and that for the large-lung group (TLC 6.37 liters) was 61% of VO2max. Statistical analysis revealed significant decrements for both groups in FVC, forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate in the middle half of FVC on exposure to 0.18 and 0.30 ppm O3. Exercise respiratory frequency increased, and tidal volume decreased significantly in both groups in response to 0.18 and 0.30 ppm O3 exposure. On exposure to 0.30 ppm O3, the number of individual subjective symptoms reported and their severity were significantly greater for both groups than those reported for the FA and 0.18 ppm O3 exposures. Both groups evidenced similar percent changes in pulmonary function and exercise ventilation response, and in subjective symptom response.(ABSTRACT TRUNCATED AT 250 WORDS)
Slow phase of transvascular fluid flux reviewed
Authors: Hancock B. J. , Landolfo K. P. , Hoppensack M. , Oppenheimer L.
Published: December 2017

In six circuit experiments using a clinical hemofiltration device, we validated a colorimetric technique to measure transvascular volume exchange (VE). In 12 isolated excised canine left lower lobes, continuous colorimetric measurements of VE correlated well with calculations of VE from changes in microhematocrit obtained simultaneously. We introduced step increases in microvascular hydrostatic pressure (Pc) of 9 +/- 4.8 (SD) cmH2O and followed the time course of weight and continuous hematocrit changes measured colorimetrically for 40 min, after which Pc was returned to base line, while measurements were continuously obtained. This procedure was repeated for an additional 30 min. VE was calculated from the hematocrit signals and compared with the time course of the weight signal. After increases in Pc, followed by a rapid weight gain, weight signals followed a slow exponential time course, whereas the calculated VE changed linearly. VE reflected approximately 60% of the slow weight gain. When Pc was decreased, weight signals decreased exponentially, whereas VE continued to increase linearly at a slower rate. These results suggest that a significant component of the slow weight signal represents slow vascular volume changes. Contrary to what the weight signal suggested, edema was never reabsorbed over the range of Pc measured.
Human dose-response relationship for decompression and endogenous bubble formation
Authors: Eckenhoff R. G. , Olstad C. S. , Carrod G.
Published: December 2017

The dose-response relationship for decompression magnitude and venous gas emboli (VGE) formation in humans was examined. Pressure exposures of 138, 150, and 164 kPa (12, 16, and 20.5 ft of seawater gauge pressure) were conducted in an underwater habitat for 48 h. The 111 human male volunteer subjects then ascended directly to the surface in less than 5 min and were monitored for VGE with a continuous-wave Doppler ultrasound device over the precordium or the subclavian veins at regular intervals for a 24-h period. No signs or symptoms consistent with decompression sickness occurred. However, a large incidence of VGE detection was noted. These data were combined with those from our previously reported experiments at higher pressures, and the data were fit to a Hill dose-response equation with nonlinear least-squares or maximum likelihood routines. Highly significant fits of precordial VGE incidences were obtained with the Hill equation (saturation depth pressure at which there is a 50% probability of detectable VGE [D(VGE)50] = 150 +/- 1.2 kPa). Subclavian monitoring increased the sensitivity of VGE detection and resulted in a leftward shift [D(VGE)50 = 135 +/- 2 kPa] of the best-fit curve. We conclude that the reduction in pressure necessary to produce bubbles in humans is much less than was previously thought; 50% of humans can be expected to generate endogenous bubbles after decompression from a steady-state pressure exposure of only 135 kPa (11 ft of seawater). This may have significant implications for decompression schedule formulation and for altitude exposures that are currently considered benign. These results also imply that endogenous bubbles arise from preexisting gas collections.
Pulmonary vascular reactivity and permeability to alveolar hypoxia in the dog
Authors: Hofman W. F. , Ehrhart I. C.
Published: December 2017

Hemodynamics and vascular permeability were studied during acute alveolar hypoxia in isolated canine lung lobes perfused at constant flow with autogenous blood. Hypoxia was induced in the presence (COI + Hypox, n = 6) or absence (Hypox, n = 6) of cyclooxygenase inhibition (COI) with indomethacin or meclofenamate. Hypoxic ventilation reduced blood PO2 from 143 to 25-29 Torr without a change in PCO2. During hypoxia a capillary filtration coefficient (Kf) was obtained gravimetrically as an index of vascular permeability to water. In COI + Hypox, pulmonary arterial pressure (Pa) increased from 11.5 +/- 0.7, post-COI normoxia, to a peak of 22.1 +/- 2.3 during hypoxia (P less than 0.01) without a change in capillary pressure (Pc). In contrast, hypoxia changed neither Pa nor Pc in Hypox relative to an untreated normoxic control group (Normox, n = 6, P greater than 0.05). Kfs (means +/- SE in ml.min-1.Torr-1.100 g-1) for Normox (0.070 +/- 0.014), Hypox (0.082 +/- 0.024), and COI + Hypox (0.057 +/- 0.017) did not differ from one another (P greater than 0.05). Although COI markedly enhanced the pressor response to acute alveolar hypoxia, hypoxia increased neither Pc nor vascular permeability regardless of COI.
Contractile and endurance properties of geniohyoid and diaphragm muscles
Authors: van Lunteren E. , Salomone R. J. , Manubay P. , Supinski G. S. , Dick T. E.
Published: December 2017

Despite the wealth of information about the neural control of pharyngeal dilator muscles, little is known about their intrinsic physiological properties. In the present study the in situ isometric contractility and endurance of a pharyngeal dilator, the geniohyoid muscle, were compared with properties of the diaphragm in 12 anesthetized artificially ventilated cats. The contraction time (means +/- SE) of the geniohyoid (27 +/- 2 ms) was shorter than that of the diaphragm (36 +/- 3 ms; P less than 0.0005), as was the half-relaxation time (29 +/- 2 vs. 45 +/- 4 ms; P less than 0.002). The faster contraction and relaxation of the geniohyoid compared with the diaphragm were appropriately reflected in the shape of the force-frequency curves for the two muscles, with that of the geniohyoid located to the right of the diaphragm force-frequency curve. The endurance properties of the two muscles were assessed using repetitive stimulation at 40 Hz in trains lasting 0.33 s, with one train repeated every second. The ratio of force at the end of 2 min of repetitive stimulation to initial force was 0.67 +/- 0.06 for the geniohyoid and 0.15 +/- 0.03 for the diaphragm (P less than 0.00001). After the repetitive stimulation, the muscle force generated in response to a range of stimulus frequencies was reduced to a greater extent for the diaphragm than for the geniohyoid muscle. These results indicate that the geniohyoid muscle has a faster physiological profile than does the diaphragm yet is relatively resistant to fatigue when driven at high rates.
Effects of PEEP on pulmonary hemodynamics in intact dogs with oleic acid pulmonary edema
Authors: Leeman M. , Lejeune P. , Closset J. , Vachiery J. L. , Melot C. , Naeije R.
Published: December 2017

The effects of positive end-expiratory pressure (PEEP) on the pulmonary circulation were studied in 14 intact anesthetized dogs with oleic acid (OA) lung injury. Transmural (tm) mean pulmonary arterial pressure (Ppa)/cardiac index (Q) plots with transmural left atrial pressure (Pla) kept constant were constructed in seven dogs, and Ppa(tm)/PEEP plots with Q and Pla(tm) kept constant were constructed in seven other dogs. Q was manipulated by using a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated using a balloon catheter placed by thoracotomy in the left atrium. Ppa(tm)/Q plots were essentially linear. Before OA, the linearly extrapolated pressure intercept of the Ppa(tm)/Q relationship approximated Pla(tm). OA (0.09 ml/kg into the right atrium) produced a parallel shift of the Ppa(tm)/Q relationship to higher pressures; i.e., the extrapolated pressure intercept increased while the slope was not modified. After OA, 4 Torr PEEP (5.4 cmH2O) had no effect on the Ppa(tm)/Q relationship and 10 Torr PEEP (13.6 cmH2O) produced a slight, not significant, upward shift of this relationship. Changing PEEP from 0 to 12 Torr (16.3 cmH2O) at constant Q before OA led to an almost linear increase of Ppa(tm) from 14 +/- 1 to 19 +/- 1 mmHg. After OA, Ppa(tm) increased at 0 Torr PEEP but changing PEEP from 0 to 12 Torr did not significantly affect Ppa(tm), which increased from 19 +/- 1 to 20 +/- 1 mmHg. These data suggest that moderate levels of PEEP minimally aggravate the pulmonary hypertension secondary to OA lung injury.
Regional blood flow to canine parietal pleura and internal intercostal muscle
Authors: Townsley M. I. , Negrini D. , Ardell J. L.
Published: December 2017

Transcapillary Starling forces in the parietal pleura and the underlying interstitium may potentially contribute to the exchange of fluid across this barrier. However, the extent of blood flow to the parietal pleura has not been measured. Thus, using standard microsphere techniques, we compared blood flow to the parietal pleura, including the subpleural interstitium, with blood flow to the adjacent internal intercostal muscle, as well as with flows to other serous tissues, including mediastinal pleura, pericardium, and parietal peritoneum, in anesthetized dogs that were either breathing spontaneously (n = 9) or ventilated to control arterial PCO2 (n = 5). Blood flow (ml.min-1.g-1) was measured after 20 min of equilibration in four successive body positions: right lateral decubitus, supine, left lateral decubitus, and prone. Overall, flow to parietal pleura was not different in spontaneous [1.07 +/- 0.14 (SE)] and mechanically ventilated animals (0.74 +/- 0.11). Flow to the internal intercostal muscle was significantly less than pleural blood flow, averaging 0.24 +/- 0.03 and 0.16 +/- 0.03 in the same groups, although again there was no effect of ventilation mode. Blood flow to other serous tissues in the thoracic cavity, specifically the mediastinal pleura (0.67 +/- 0.14) and pericardium (0.88 +/- 0.22), was similar to parietal pleural flow, whereas that to the parietal peritoneum was an order of magnitude lower (0.09 +/- 0.02, P less than 0.05). Changing body position had no effect on blood flow to any of the sampled tissues. Blood flow to the dorsal aspect of the chest wall muscle in spontaneously breathing animals tended to be greater than that to lateral or ventral portions of the chest wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Aerosol-derived lung morphometry: comparisons with a lung model and lung function indexes
Authors: Blanchard J. D. , Heyder J. , O'Donnell C. R. , Brain J. D.
Published: December 2017

This study evaluated the ability of aerosol-derived lung morphometry to noninvasively probe airway and acinar dimensions. Effective air-space diameters (EAD) were calculated from the time-dependent gravitational losses of 1-microns particles from inhaled aerosol boluses during breath holding. In 17 males [33 +/- 7 (SD) yr] the relationship between EAD and volumetric penetration of the bolus into the lungs (Vp) could be expressed by the linear power-law function, log (EAD) alpha beta log (Vp). Our EAD values were consistent with Weibel's symmetric lung model A for small airways and more distal air spaces. As lung volume increased from 57 to 87% of total lung capacity (TLC), EAD at Vp of 160 and 550 cm3 increased 70 and 41%, respectively. At 57% TLC, log (EAD) at 160 cm3 was significantly correlated with airway resistance (r = -0.57, P less than 0.0204) but not with forced expired flow between 25 and 75% of vital capacity. Log (EAD) at 400 cm3 was correlated with deposition of 1-micron particles (r = -0.73, P less than 0.0009). We conclude that aerosol-derived lung morphometry is a responsive noninvasive probe of peripheral air-space diameters.
Heparin reversal by protamine in humans--complement, prostaglandins, blood cells, and hemodynamics
Authors: Hobbhahn J. , Conzen P. F. , Habazettl H. , Gutmann R. , Kellermann W. , Peter K.
Published: December 2017

Fourteen noncardiac surgical patients received heparin (10,000 IU), which was neutralized by 100 mg protamine injected within 2 min during steady-state anesthesia. After protamine application, plasma complement C3a, thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and KH2PGF2 alpha increased significantly, whereas prostacyclin (6-keto-PGF2 alpha) levels did not change. This mediator response was associated with transient leukopenia and thrombocytopenia. Arterial pressure, pulmonary arterial pressure, and transpulmonary pressure gradient increased significantly. Heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial PO2 remained constant. Positive correlations of plasma C3a were observed with pulmonary leukosequestration and plasma TxB2. Inverse correlations of C3a were noted with the counts of leukocytes and of platelets. A positive correlation was found between TxB2 and pulmonary arterial pressure. Our results indicate that marked activation of the complement system and the cyclooxygenase pathway is common after heparin reversal by protamine in anesthetized patients. This is in contrast to previous human studies performed after cardiopulmonary bypass but agrees well with results obtained in animal experiments. The mediator response in our patients, however, was not accompanied by hemodynamic instability, suggesting appropriate compensatory mechanisms.
Ventilatory afterdischarge in the awake goat
Authors: Engwall M. J. , Daristotle L. , Niu W. Z. , Dempsey J. A. , Bisgard G. E.
Published: December 2017

Ventilatory afterdischarge (VAD) has been defined as a persistent gradually diminishing elevation of ventilatory activity that occurs after withdrawal of a variety of respiratory stimuli. The phenomenon has been well documented in the anesthetized cat, piglet, and lamb in response to electrical stimulation of the carotid sinus nerve. We sought to determine whether VAD could be demonstrated in the standing awake goat (n = 7) by use of an extracorporeal circuit to provide square-wave physiological stimulation of the carotid chemoreceptor (carotid body PO2 40 Torr). After 5 min of isolated carotid body stimulation, the mean time constants for diminishing inspired minute ventilation, tidal volume, and respiratory frequency were 27.7, 34.5, and 25.5 s, respectively. These results indicate that VAD does exist in the awake goat model. A critical factor for the demonstration of VAD is the maintenance of systemic arterial PCO2 (isocapnia) during the period of increased ventilatory activity. If arterial PCO2 is allowed to decrease even slightly during the hyperventilation, the magnitude and duration of VAD are greatly attenuated.