bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle proton T2 relaxation times and work during repetitive maximal voluntary exercise
Authors: Fleckenstein J. L. , Watumull D. , McIntire D. D. , Bertocci L. A. , Chason D. P. , Peshock R. M.
Published: December 2017

We studied the effects of progressive maximal voluntary handgrip contractions (MVCs) on muscle proton spin-spin (T2) relaxation times and work, measured as the integrated force vs. time curve (FTI). Six healthy volunteers performed 10, 20, 40, and 80 MVCs in a 0.35-T magnet on four separate occasions. Repeated measures analyses of variance of increases in T2 and FTI during successive bouts were significant (P < 0.005 and P < 0.001, respectively). FTI increased with successive bouts to a greater extent than did muscle T2 (P < 0.05). For T2, the Helmert contrast judged the 10-MVC response lower than the mean of the remaining responses (P < 0.005), and the differences between all others compared with the means of subsequent responses were not significant, indicating a “flattening” of the T2 response after the increase from 10 to 20 repetitions. For FTI, all the single degree of freedom Helmert contrasts were significant (P < 0.001), indicating a continual increase in response over increased MVCs. The curved nature of the T2 response conformed best to a hyperbolic function, suggesting that a limit of approximately 32% exists for the change in T2 during progressively longer bouts of MVCs. A limit in the T2 response is consistent with the existence of a limit in the amount of water that muscle can take up from the vasculature during exertion.
Effect of water immersion on renal natriuretic peptide (urodilatin) excretion in humans
Authors: Norsk P. , Drummer C. , Johansen L. B. , Gerzer R.
Published: December 2017

We examined 1) the effect of thermoneutral (34.5 +/- 0.5 degrees C) water immersion to the neck (WI) in humans on the temporal profile of renal urodilatin [atrial natriuretic peptide- (ANP) (95–,126)] excretion and 2) the relationship between urodilatin and urinary fluid (V) and sodium (UNaV) excretion. Eight normal subjects underwent 12 h of WI, and another group of eight were studied during seated control conditions. The subjects ingested 200 ml of tap water hourly. WI induced an increase in renal urodilatin and guanosine 3′,5′-cyclic monophosphate (cGMP) excretion, V, and UNaV. After peak values were attained between the 2nd and 5th h of WI, urodilatin and cGMP excretion, V, and UNaV returned toward preimmersion and control levels. At the 12th h of WI, urodilatin and cGMP excretion and V were indistinguishable from preimmersion values but were significantly elevated compared with the control values. UNaV was maintained elevated compared with both preimmersion and control values. During WI, positive and statistically significant linear correlations could be established between V and renal urodilatin excretion in six subjects and between UNaV and urodilatin excretion in four subjects. We conclude that WI induces an increase in the rate of renal urodilatin excretion, attaining a peak value at the 3rd h followed by an attenuation toward preimmersion and control levels. Furthermore, urodilatin might participate as one of several mechanisms of the natriuresis and diuresis of WI in humans.
Mucociliary clearance of inhaled particles measured at 2 h after ozone exposure in humans
Authors: Gerrity T. R. , Bennett W. D. , Kehrl H. , DeWitt P. J.
Published: December 2017

Acute exposure of humans to ozone is known to acutely cause pulmonary function decrements, inflammation, and increased permeability of pulmonary epithelium. A single study in humans has also shown that mucociliary transport increases during acute ozone exposure. Because different responses have shown a different time course of recovery after exposure, it was important to examine mucociliary transport at a different time after the cessation of ozone exposure. We exposed 15 healthy male and female nonsmoking subjects, on different occasions, to clean air and 0.4 ppm ozone for 1 h while they exercised continuously. Pulmonary function was measured immediately before and after exposure and 90 min and 24 h after exposure. Between 2 and 5 h after each exposure, retention of inhaled 5-microns mass median aerodynamic diameter 99mTc-labeled Fe2O3 particles was measured. Each subject returned the next day for a final particle retention measurement. Despite significant changes in pulmonary function, there was no difference in mean whole lung retention time of particles between clean air [77.9 +/- 0.8 (SE) min] and ozone (78.0 +/- 0.8 min) exposures, indicating that mucociliary transport is unaffected by ozone exposure when it is measured 2 h after exposure.
Allergen-induced airway hyperresponsiveness in Brown-Norway rat: role of parasympathetic mechanisms
Authors: Elwood W. , Sakamoto T. , Barnes P. J. , Chung K. F.
Published: December 2017

Enhanced parasympathetic mechanisms may contribute to airway hyperresponsiveness. The present study examined whether the in vivo increase in airway responsiveness seen 18–24 h after either a single or chronic aerosolized allergen challenge protocol in actively sensitized Brown-Norway rats was due to altered parasympathetic mechanisms. The roles of central and reflex vagal mechanisms were studied by performing bilateral cervical vagotomy before measurement of airway responsiveness. Bilateral vagotomy failed to reduce the increase in airway responsiveness after either a single or chronic allergen challenge. The roles of increased neural release of acetylcholine (ACh) and increased end organ responsiveness were studied in vitro. The isometric responses of tracheal and bronchial strips to both electrical field stimulation and exogenously applied ACh from rats exposed both to single and chronic allergen challenges were compared with those from saline-exposed rats. The responses to electrical field stimulation and to exogenous ACh were not significantly enhanced 18–24 h after either protocol. We conclude that the airway hyperresponsiveness observed in this allergic rat model is not mediated through an enhancement of parasympathetic mechanisms.
Tritium dilution space measurement is not modified by a doubling in fluid intake
Authors: Brigant L. , Rozen R. , Apfelbaum M.
Published: December 2017

The purpose of this study was to examine the effects of a doubling in water intake on the total body water measured by the tritium dilution technique. Overdrinking was obtained by presenting tap water and sweet water to the rats. Total body water was measured twice, tritium dilution vs. dessication. Body water volumes differed between the two methods but not between the two groups. Thus the isotopic dilution technique can be used to measure total body water regardless of the flux of fluid through the subject.
Lemakalim attenuates hypocapnia- and dry air-induced bronchoconstriction in canine peripheral airways
Authors: Lindeman K. S. , Freed A. N.
Published: December 2017

To determine the effect of changes in potassium (K+) flux on airway constriction, we studied effects of lemakalim, a K+ channel opener, and glibenclamide, an ATP-sensitive K+ channel blocker. A wedged bronchoscope technique was used to measure peripheral airway resistance (Rp) in anesthetized dogs. Rp was measured before and after constriction of the airways by hypocapnic challenge, acetylcholine aerosol, or dry air hyperpnea. Lemakalim (5 micrograms/kg i.v.) was administered, and the challenge was repeated. Lemakalim attenuated responses to hypocapnia by 72 +/- 7% (n = 6, P = 0.0007) and to dry air challenge by 37 +/- 8% (n = 6, P = 0.005) but not to acetylcholine. On separate days, sublobar segments were pretreated with aerosolized glibenclamide (2 mg/ml), and responses to hypocapnic challenge were measured before and after lemakalim (5 micrograms/kg i.v.), nifedipine (20 micrograms/kg i.v.), or albuterol (1 microgram/kg i.v.). In the presence of glibenclamide, lemakalim had no significant effect on responses to hypocapnia; however, both nifedipine (n = 6, P = 0.0003) and albuterol (n = 6, P = 0.0001) attenuated responses to hypocapnic challenge. These findings suggest that lemakalim attenuated hypocapnic bronchoconstriction by promoting K+ efflux through ATP-sensitive K+ channels.
Effects of hypoxia and atrial natriuretic peptide on aldosterone secretion in healthy subjects
Authors: Westendorp R. G. , Roos A. N. , Simons M. , Wertheim W. , Bosch F. H. , Frolich M. , Meinders A. E.
Published: December 2017

To evaluate the inhibitory effect of hypoxia and atrial natriuretic peptide (ANP) on aldosterone secretion, 11 healthy male subjects were infused with 5 ng.kg-1 x min-1 ANP or placebo. The subjects were exposed in a stepwise fashion to incremental hypobaric hypoxia, which decreased arterial oxygen saturation to 79 +/- 2% in the placebo and 84 +/- 2% in the ANP condition (P < 0.05). In the placebo condition, the plasma ANP concentration increased from 13.8 +/- 1.0 to 19.6 +/- 2.3 pmol/l (P < 0.01) at the lowest barometric pressure. Plasma renin activity did not change, whereas the plasma aldosterone levels increased consequent to the increase of plasma adrenocorticotropic hormone (ACTH). Continuous infusion of ANP increased the plasma levels twofold (P < 0.001) and the level of guanosine 3',5'-cyclic monophosphate threefold (P < 0.001). However, the plasma aldosterone concentrations were not different in the two experimental conditions. Administration of supplementary oxygen significantly decreased ACTH to baseline values (P < 0.01) together with a decrease in aldosterone. Free water clearance (P = 0.05) but not sodium excretion (P = NS) increased during continuous ANP infusion. The data indicate that the aldosterone secretion in hypoxia is not inhibited by (patho)physiological plasma ANP levels. The inhibition of aldosterone secretion may well be explained by a direct effect of hypoxia on the adrenal cells. ACTH is a major stimulus of aldosterone secretion in hypoxia, which overrides the natriuretic effect of ANP.
Respiratory load compensation. II. Role of the cerebellum
Authors: Xu F. , Taylor R. F. , Lee L. Y. , Frazier D. T.
Published: December 2017

Effects of inspiratory tracheal occlusion (TO) on respiratory duration (inspiratory and expiratory duration), ventilation, and the peak integrated diaphragm electromyographic (integral of EMGdi) response were tested in 16 anesthetized cats before and after decerebellation with and without vagal input. The same protocols were repeated in the decerebrate preparation. Decerebellation did not significantly affect the baseline or the loaded values [tracheal occlusion (TO)] for respiratory duration, tidal volume, or magnitude of the integral of EMGdi response. Vagal blockade eliminated the load-compensating responses in the intact and the decerebrate preparation. However, vagal blockade in concert with decerebellation resulted in a significant (P < 0.05) reversible inhibition of the peak integral of EMGdi response during inspiratory TO. This suggests that removal of vagal and cerebellar influences during loaded breathing unmasked inhibitory inputs to the respiratory pattern generator. With vagus intact, decerebellation before or after decerebration abolished the attenuation of the peak integral of EMGdi response to TO observed with decerebration alone. We conclude that the cerebellum does play a role in determining the pattern of the respiratory response to TO. This influence may be direct and/or indirect via interaction with information emanating from suprapontine, vagal, and nonvagal sources.
Pulmonary arterial elasticity in awake dogs
Authors: Grant B. J. , Canty J. M. , Srinivasan G. , Brody A. S.
Published: December 2017

We measured the relationship between pulmonary arterial pressure (Ppa), diameter (D), and length of a segment of the main pulmonary artery (MPA) in chronically instrumented conscious dogs breathing spontaneously (CCC). There were no physiologically significant changes in Ppa or D in the CCC dogs postoperatively, and the cross-sectional MPA shape measured by fast computed tomography was nearly circular. These results suggest that the MPA was not distorted by chronic instrumentation. We compared measurements made in the CCC dogs with previous measurements in acutely instrumented anesthetized dogs with open chests (AAO). The elasticity of MPA in the CCC animals was frequency dependent between 1 and 14 Hz and was similar to that in the AAO dogs. Oscillations of D preceded Ppa at cardiac frequencies in the AAO animals, but the D and Ppa oscillations were in phase in the CCC animals. The oscillations of length relative to D were significantly less in the CCC than in the AAO dogs. We conclude that, with limitations, the hemodynamic properties of the MPA can be measured in the CCC subjects. We suggest that the discrepancies between the AAO and CCC dogs can be attributed to differences in extrinsic loading of the MPA.
Effects of high-frequency oscillating pressures on upper airway muscles in humans
Authors: Henke K. G. , Sullivan C. E.
Published: December 2017

We examined the effects of high-frequency- (30-Hz) low-pressure oscillations (< 1 cmH2O) applied to the upper airway, via a nose mask, on genioglossus (EMGgg), sternomastoid (EMGsm), and diaphragm electromyogram (EMGdia) activity in sleeping humans. Ten patients with sleep apnea and six normal subjects were studied. The pressure oscillations were applied through the mask for a single breath. The subjects were studied in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. In the normal subjects, during NREM sleep, peak EMGgg, EMGsm, and EMGdia activity increased significantly in response to the oscillations in 63, 51, and 46%, respectively, of all trials. During REM sleep, significant increases occurred in 73, 88, and 13%, respectively, of all trials. Similar responses were observed in the patients with obstructive sleep apnea. Peak EMGgg, EMGsm, and EMGdia activity increased significantly in 74, 50, and 67%, respectively, of all NREM sleep trials and in 55, 81, and 76%, respectively, of all REM sleep trials. An important finding was that in 46% of the trials in the patients with sleep apnea the oscillation-induced increase in EMGgg activity was associated with a partial or complete reversal of the upper airway obstruction with an increase in tidal volume. This was observed in NREM and REM sleep. We conclude that there are upper airway receptors that respond to low-pressure-high-frequency oscillations applied to the upper airway that have input to the genioglossus and other muscles of respiration. These responses may be utilized in future treatment for sleep apnea.
Hemodynamic effects of brief pulmonary hemostasis
Authors: Yang G. G. , Sadurski R. , Bhattacharya J.
Published: December 2017

We determined the hemodynamic effects of brief hemostasis in isolated blood-perfused rat lungs held at constant inflation pressure. Three periods of hemostasis, each lasting 20 min, alternated with equal durations of perfusion. Pulmonary vascular resistance (PVR), calculated as the ratio of the pulmonary arterial- (Ppa) left atrial (Pla) pressure difference to flow, was determined at baseline and after the third hemostasis period. Hemostasis increased PVR by 127% above baseline at constant Ppa and Pla (n = 8; P < 0.05) and by 71% at constant Pla and constant flow (n = 16; P < 0.05). The PVR increases were significantly attenuated by platelet (n = 5) or red blood cell (n = 4) removal from the lung perfusion, mechanical ventilation (n = 5), indomethacin (2 X 10(-6) M; n = 5), papaverine (10(-5) M; n = 4), and the thromboxane blocker SQ-29548 (7.8 X 10(-5) M; n = 4). By micropuncture we determined that the posthemostasis increase of the total pressure drop was 66% due to an increase of the venous pressure drop (P < 0.05). Isogravimetric pressure and lung water were not significantly altered by hemostasis. We conclude that brief hemostasis in the rat lung induces platelet- and red blood cell-dependent increase of vascular resistance. This effect may be attributable to hemostasis-induced platelet activation leading to thromboxane release.
Peripheral chemoreceptors respond to hypoxia in pontine-lesioned fetal lambs in utero
Authors: Johnston B. M. , Gluckman P. D.
Published: December 2017

Acute hypoxia inhibits, rather than stimulates, fetal breathing movements (FBM), but there has been controversy as to the activity and role of the peripheral arterial chemoreceptors in the regulation of breathing movements in the unanesthetized fetus in utero. However, after midcollicular brain stem transection or lateral pontine lesion, hypoxia causes FBM to become continuous and stimulated in rate and depth. To determine whether this stimulatory response involves peripheral chemoreceptors, we used a two-stage approach to examine the response to hypoxia after peripheral chemodenervation in lateral pontine-lesioned fetal lambs. The lateral pons was lesioned at 119–121 days, and the response to hypoxia was tested in the unanesthetized fetus 4 days afterward. Fourteen fetuses in which hypoxia stimulated FBM underwent either peripheral chemodenervation or sham denervation in a second operation. Hypoxia had no effect when the fetus was tested 4–5 days after peripheral chemodenervation, and the basal incidence of FBM was significantly lower. The stimulatory response was unchanged by sham denervation. We conclude that the peripheral chemoreceptors are active in fetal life and that they mediate the stimulation of FBM seen in response to hypoxia after removal of the lateral pontine inhibition. In addition, after pontine lesion there is evidence of tonic chemoreceptor-mediated influences on FBM, which are normally overriden in the intact fetus.
Tenotomy and repair of latissimus dorsi muscles in rats: implications for transposed muscle grafts
Authors: Kadhiresan V. A. , Guelinckx P. J. , Faulkner J. A.
Published: December 2017

The functional properties of latissimus dorsi (LTD) muscles were evaluated 160 to 180 days after tenotomy and repair, when grafts had stabilized. Our hypothesis was that, compared with control LTD muscles, LTD grafts would develop less absolute force and power but that the specific force and normalized power would not differ. Expressed as a percentage of the value for control LTD muscles, values for grafts were 67% for muscle mass, 74% for mean single fiber cross-sectional area, 56% for maximum absolute isometric tetanic force, 64% for maximum absolute average force during shortening, and 70% for maximum absolute power. Compared with control LTD muscles, grafts showed no significant differences either in the number of fibers in the total muscle cross section or in the optimum velocity for the development of power. When force and power of grafts were normalized for total fiber cross-sectional area and mass, respectively, only the value for maximum specific force (84% of control value) was significant. The mechanisms responsible for the decrease in specific force after tenotomy and repair are not known. In contrast to the deficit in maximum specific force, the 30% deficit in maximum absolute power of grafts compared with control LTD muscles was explained completely by the 33% smaller muscle mass.
Effects of indomethacin on newborn pig pial arteriolar responses to PCO2
Authors: Mirro R. , Pharris L. J. , Armstead W. M. , Shibata M. , Leffler C. W.
Published: December 2017

The present experiments were designed to determine whether hypocapnic cerebral vasoconstriction, like hypercapnic dilation, involves prostanoids and, if not, whether alternative mechanisms are related to the absolute arterial PCO2 (PaCO2) or the direction of change. We determined effects of indomethacin (5 mg/kg iv) on pial arteriolar responses to 1) increased PCO2 from normal, 2) decreased PCO2 from normal, and 3) increased PCO2 from hypocapnia to normocapnia in anesthetized newborn pigs. Pial arterioles constricted in response to hypocapnia (PaCO2 = 15–24 Torr) similarly before (-13 +/- 3%) and after (-16 +/- 2%) indomethacin. Cortical periarachnoid cerebrospinal fluid prostanoids were not increased by hypocapnia. As previously reported, cerebral vascular responses to hypercapnia (which increases cerebrospinal fluid prostanoids) were lost after indomethacin. To determine whether the failure of indomethacin to affect the responses to hypocapnia was due to the direction of change (decreasing) or the absolute level of PCO2, piglets were hyperventilated to approximately 15 Torr PaCO2. Increasing PaCO2 in these piglets to approximately 44 Torr caused pial arteriolar dilation (46 +/- 7%) that was not blocked by indomethacin (33 +/- 5%). Cortical periarachnoid prostanoids were not altered when PaCO2 was raised from hypocapnia to normocapnia. Therefore the relationship between CO2 and piglet cerebral vascular tone appears to involve multiple mechanisms. Specifically, dilation in response to CO2 above the normal range appears to involve prostanoids but changes in pial arteriolar diameter at low PaCO2 do not.
Effect of ozone exposure in vivo on response of bronchial rings in vitro: role of intracellular Ca2+
Authors: Montano L. M. , Jones G. L. , O'Byrne P. M. , Daniel E. E.
Published: December 2017

In this study we investigated the role of intracellular Ca2+ in ozone- (O3) induced airway hyperresponsiveness. Acetylcholine-induced airway responses were measured before and after inhalation of O3 (3 ppm, 30 min) or dry air. In vitro experiments were performed with intact ring segments of third- to fifth-order bronchi. Bronchial responses to carbachol (CCh) were evaluated in Krebs solution (2.5 mM Ca2+) and in Ca(2+)-free [0.1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)] Krebs solution with or without indomethacin (IDM, 10(-5) M) and were expressed as percentage of the maximal KCl response (60 mM). Inhalation of O3, but not dry air, caused airway hyperresponsiveness to acetylcholine in vivo. Responses to 50% effective concentrations of CCh were similar in bronchial preparations from O3 and control animals (with or without IDM) in normal Krebs solution. In Ca(2+)-free solution, CCh induced a sustained (20-min) bronchial contraction. These contractions relaxed immediately when nifedipine or a high EGTA concentration was added to the organ bath. The sustained contraction was abolished when the tissues had been incubated with cyclopiazonic acid (10(-5) M), a novel inhibitor of the sarcoplasmic reticulum Ca2+ pump. After O3 exposure, responses of the bronchial smooth muscle (in Ca(2+)-free medium without IDM) were increased (P < 0.05) compared with controls during the first and second CCh stimulations. This O3-induced increase in response to CCh in Ca(2+)-free solution was abolished when the tissues were incubated with IDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Alveolar liquid pressure measured in the intact rabbit chest by micropuncture
Authors: Ganesan S. , Lai-Fook S. J.
Published: December 2017

Previous measurements in isolated lung showed that alveolar liquid pressure was near the pleural pressure at a lung volume near functional residual capacity (FRC). In this study we verified that alveolar liquid pressure in vivo was similar to that of the isolated lung. In anesthetized paralyzed rabbits (3#x2013;4 kg, n = 9) ventilated with 100% O2 in the left lateral position, we made a pleural window between the fifth and sixth ribs near midchest by removing tissue down to the parietal pleura. Window height was 6 cm above the base of the lung. During apnea, alveolar liquid and pleural pressures were measured by puncturing through the pleural window with micropipettes connected to a servo-nulling pressure-measuring system. Pressures were measured at airway pressures of 0 (FRC) and 10 cmH2O both in vivo and postmortem. In vivo, alveolar liquid and pleural pressures relative to ambient pressure averaged -2.3 +/- 1.4 (SD) and -1.8 +/- 0.9 cmH2O at FRC and increased to 3.3 +/- 1.8 and 1.8 +/- 1.6 cmH2O after inflation to an airway pressure of 10 cmH2O, respectively. Similar values were obtained postmortem. These results were similar to previous measurements in the isolated lung.
Effect of lung lavage on the stress relaxation of the respiratory system
Authors: Perez Fontan J. J.
Published: December 2017

To test the hypothesis that lowering the concentrations of surfactant molecules at the gas-liquid interface increases viscoelastic dissipation in the lungs, the amplitude and time course of stress relaxation were quantified before and after lavage of the lungs with warm saline in five newborn and five 8-wk-old anesthetized piglets. Stress relaxation was separated from other dissipative pressure losses by fitting the pressure decays that follow airway occlusions performed during a period of constant inspiratory flow to a double-exponential regression. The amplitude of stress relaxation (defined by the term of the regression with the longest time constant) related linearly to the changes in respiratory system volume and elastic recoil preceding the occlusions both before and after the lavage. Lung lavage increased the slope of both relationships without altering the time course of the relaxations. In addition to being consistent with the proposed hypothesis, these results suggest that viscoelastic pressure losses remain linked to the elastic stresses generated during lung inflation, as proposed by Fredberg and Stamenovic's structural dumping theory (J. Appl. Physiol. 67: 2408#x2013;2419, 1989).
Active transport and passive liquid movement in isolated perfused rat lungs
Authors: Rutschman D. H. , Olivera W. , Sznajder J. I.
Published: December 2017

The isolated perfused liquid-filled rat lung in a "pleural bath" was the model used to study liquid exchange across the lung epithelium. Active transport and passive solute movement between the air space, the vascular perfusate, and the bath result in concentration changes of the three markers (Evans blue-tagged albumin, 22Na+, and [3H]mannitol) instilled in the air space. A mathematical model was developed to estimate the active and passive solute transports and to interpret the results. Rat lungs were perfused at left atrial and pulmonary arterial pressures of 0 and 8 mmHg, respectively. Six rat lung experiments were conducted at 37 degrees C and six at 4 degrees C. The normothermic experiments demonstrate that active transport accounts for 26% of the Na+ movement out of the air space (17.3 +/- 0.7 nm/s) and that passive mechanisms account for the remaining 74% (48.0 +/- 5.7 nm/s). Hypothermia inhibits lung liquid clearance but does not affect passive solute movement, suggesting that lung liquid clearance is effected by active Na+ transport mechanisms.
Dynamic behavior of alveolar surface-to-volume ratio in live dogs by light-scattering stereology
Authors: Akahori T. , Suzuki S. , Suzuki M. , Okubo T.
Published: December 2017

To investigate the behavior of the surface-to-volume ratio (S/V) in lung lobes of live dogs, we measured the backscattered light pattern produced by applying a laser beam to the pleural surface. This pattern was used to estimate the optical mean free path, which is approximately proportional to the inverse square of the geometric S/V. Measurements were performed in mechanically ventilated animals with the chest widely opened. We found that during quasi-static large volume excursion, S/V changed approximately as the one-third power of lung volume but with hysteresis such that S/V during deflation was higher than during inflation. This finding is consistent with a relatively large stress hysteresis of surface tension compared with that of the tissue. During tidal breathing, however, the geometric hysteresis was inconsistent among animals at low frequency but was consistently changed at higher frequencies in a direction suggesting a lesser role of surface tension relative to tissue stress hysteresis.
Exposure to ozone alters regional function and particle dosimetry in the human lung
Authors: Foster W. M. , Silver J. A. , Groth M. L.
Published: December 2017

Effects of experimental exposure to O3 (0.33 ppm) or filtered air on regional lung function were assessed in nine healthy male subjects. Immediately after 2-h chamber exposures, regional ventilation and particle dosimetry were measured by gamma camera imaging. The vertical distributions of a radiolabeled gas (133Xe) and aerosol (3.5-microns-diam insoluble 99mTc-tagged Fe2O3 particles) were quantitated for upper, middle, and lower lung regions; distribution data were corrected for regional differences in lung volume and tissue attenuation. Indexes of mechanical function, inspiratory capacity, and mid-maximal expiratory flow rates were significantly reduced after O3, but functional residual capacity remained unchanged. Exposure to O3 significantly enhanced the fraction of respired aerosol retained by the lung and altered the distribution pattern of deposited aerosol by increasing particle deposition to the middle lung region (P < 0.05). Aerosol penetration indexes, i.e., ratio of particle deposition in central lung regions to that in peripheral lung regions, and particle retention 24 h postinhalation (an index of aerosol deposition within alveoli and slowly clearing bronchioles) indicated that particle filtration efficiency had increased for tracheobronchial and parenchymal lung regions. For seven of the nine subjects, regional ventilation after O3 was reduced by 14% to the lung base and enhanced by 8 and 6% to the upper and middle lung regions, respectively; these changes were significant (P < 0.02) compared with ventilation after filtered air.(ABSTRACT TRUNCATED AT 250 WORDS)
Swim training alters renal and cardiovascular responses to stress in borderline hypertensive rats
Authors: McCoy D. E. , Steele J. E. , Cox R. H. , Wiley R. L. , McGuire G. J.
Published: December 2017

The present study assessed the effects of 40 min of tail shock stress (1-s shock, 0.2 mA every 30 s) on renal and cardiovascular function in swim-trained (T), water-immersed (IM), and untrained (UT) borderline hypertensive rats (BHR). T BHR swam for 2 h/day 5 days/wk for 10–12 wk, whereas IM BHR on the same schedule were placed in water at neck level and were not permitted to swim. Age-matched sedentary controls were paired one each with the exercise group (group 1) and the immersion group (group 2). Heart rate was significantly greater in UT than in T BHR (P = 0.09) during baseline (rest). Heart rate responses during stress were not different between UT and IM BHR (group 2). Systolic and diastolic blood pressures during stress and recovery were not different between UT BHR and T or IM BHR. Urine flow rate was significantly increased from baseline during the first 20 min of stress in UT and IM BHR only. Changes in glomerular filtration rate were not consistent across studies. Renal blood flow decreased significantly from baseline during tail shock stress in UT but not T BHR. Plasma glucose levels were significantly increased above baseline during the second 20 min of stress in UT BHR only and were significantly greater than those in the T BHR. Plasma insulin levels in UT BHR were significantly decreased from baseline during tail shock stress and recovery but were unchanged from baseline in T BHR. These observations suggest that swim training independent of water immersion alters the effect that stress exerts on renal and cardiovascular function in BHR, which results in better fluid and electrolyte conservation in T BHR.
Faster O2 uptake kinetics at onset of supine exercise with than without lower body negative pressure
Authors: Hughson R. L. , Cochrane J. E. , Butler G. C.
Published: December 2017

The kinetics of oxygen uptake (VO2) were observed at the onset of submaximal cycling exercise in seven men and one woman [mean age 22.6 +/- 0.9 (SE) yr] in the upright and supine positions and the supine position with -40 mmHg lower body negative pressure (LBNP). There was no significant difference for peak VO2 and ventilatory threshold between the supine (3,081 +/- 133 and 1,954 +/- 138 ml/min, respectively) and the supine + LBNP positions (3,062 +/- 152 and 1,973 +/- 122 ml/min); however, both were reduced compared with upright exercise (3,483 +/- 200 and 2,353 +/- 125 ml/min). Kinetic analysis applied to six repetitions by each subject indicated a slowing from a mean total lag time (time required to achieve 63% of the difference in VO2 between baseline and new steady state) of 36.3 +/- 2.7 s in upright exercise to 44.1 +/- 3.5 s in the supine position. However, total lag time for the supine + LBNP position (36.0 +/- 2.8 s) did not differ from upright exercise but was significantly faster than supine exercise. These data have been interpreted in support of an O2 transport limitation to VO2 kinetics at the onset of supine exercise that is countered by LBNP, likely through a more rapid increase in perfusion to the exercising muscle at these submaximal work rates.
Effect of humidity on hyperoxic toxicity
Authors: Lin Y. , Jamieson D.
Published: December 2017

Time to onset of hyperbaric oxygen-induced convulsions was measured in mice and rats exposed to hyperbaric oxygen (515–585 kPa) under conditions of low humidity (dry gas, < 10% relative humidity) or in a humidified environment (60% relative humidity). At all pressures tested, the duration of convulsive activity was markedly increased (P < 0.001), because of the earlier onset of severe generalized convulsions, in the groups of rodents exposed to the higher humidity. Pulmonary oxygen poisoning was determined by increases in lung wet and dry weights. Such pulmonary damage was also significantly (P < 0.001) increased in the humidified groups. Hyperoxic toxicity was also measured in rats and mice exposed to approximately 100% oxygen (normobaric hyperoxia) under conditions of 30 or 62% relative humidity. In contrast to the results obtained with hyperbaric oxygen exposure, there was slightly less toxicity in the rodents maintained at 62% compared with 30% humidity in normobaric hyperoxia.
Cell-free hemoglobin potentiates acetylcholine-induced coronary vasoconstriction in rabbit hearts
Authors: Motterlini R. , Macdonald V. W.
Published: December 2017

Cell-free hemoglobin (Hb) preparations have been shown to alter vascular tone in vitro and in vivo. The high affinity of Hb for nitric oxide, the putative endothelium-derived relaxing factor (EDRF), may be primarily responsible for this activity, but the contribution of tissue-damaging oxygen-derived free radicals has not been established. We investigated the effects of human Hb interdimerically cross-linked with bis-(3,5-dibromosalicyl)fumarate (alpha alpha Hb) on the coronary vasomotor response to acetylcholine (ACh) in isolated perfused rabbit hearts. Infusion of 0.1 g/dl alpha alpha Hb altered the dose-dependent response to ACh, decreasing the calculated IC50 (ACh concn at which coronary pressure is 50% of its maximal value) from 3.96 +/- 0.34 to 0.85 +/- 0.06 microM (P < 0.01). This augmented sensitivity to ACh was only partially reversed upon washout of alpha alpha Hb (IC50 1.93 +/- 0.13 microM). Simultaneous infusion of 60 microM deferoxamine mesylate with alpha alpha Hb attenuated this response (IC50 decreased from 3.86 +/- 0.27 to 1.73 +/- 0.38 microM), which was completely reversed after removal of alpha alpha Hb (IC50 3.41 +/- 0.17 microM). NG-nitro-L-arginine methyl ester (50 microM) and cross-linked cyanomethemoglobin (CNmet alpha alpha Hb, 0.1 g/dl) induced a significant (P < 0.05) increase in ACh-induced vasoconstriction accompanied by a reduction in myocardial functions in the same range as that caused by alpha alpha Hb. Infusion of deferoxamine mesylate (60 microM) with CNmet alpha alpha Hb completely prevented the reduction in IC50 elicited by the infusion of CNmet alpha alpha Hb alone. These data demonstrate that alpha alpha Hb can alter coronary vasomotor responsiveness and suggest the involvement of at least two mechanisms, one that is related to an accessible ferrous heme and is reversible and another that does not require an open heme site and is irreversible.
Macrophage-specific eicosanoid synthesis inhibition and lipocortin-1 induction by glucocorticoids
Authors: De Caterina R. , Sicari R. , Giannessi D. , Paggiaro P. L. , Paoletti P. , Lazzerini G. , Bernini W. , Solito E. , Parente L.
Published: December 2017

It has been suggested that the induction of lipocortin-1, a phospholipase A2-inhibitory protein, may mediate the anti-inflammatory action of glucocorticoids. We assessed the production of prostaglandin E2, thromboxane B2, and leukotriene B4 and the expression of lipocortin-1 in different populations of blood leukocytes and in alveolar macrophages (obtained by bronchoalveolar lavage) from patients with inflammatory lung diseases (bronchial asthma, n = 21; interstitial lung disease, n = 6) undergoing glucocorticoid treatment at clinically effective doses. No inhibition of eicosanoid production was observed in either whole blood or single populations of blood leukocytes (granulocytes and monocytes) stimulated with ionophore A-23187, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, or zymosan. Conversely, eicosanoid production from alveolar macrophages (assessed in 9 cases) was significantly inhibited by glucocorticoids. After ionophore stimulation, eicosanoid production was as follows (in ng/ml): prostaglandin E2, 0.19 +/- 0.06 and 0.06 +/- 0.01; thromboxane B2, 2.9 +/- 0.9 and 0.5 +/- 0.1; leukotriene B4, 6.6 +/- 1.1 and 3.6 +/- 1.0, before and after treatment, respectively (P < 0.05 for all differences). Lipocortin-1 expression, determined by Western blot and enzyme immunoassay, was significantly (P < 0.05) stimulated in alveolar macrophages, but not in blood leukocytes, by glucocorticoid treatment. These results indicate that alveolar macrophages, at variance from blood leukocytes, are the most likely cell target for glucocorticoid-induced eicosanoid inhibition and lipocortin expression. We suggest that cell responsiveness to glucocorticoids is acquired during differentiation from monocyte to tissue macrophage.
Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity
Authors: Haddad F. , Herrick R. E. , Adams G. R. , Baldwin K. M.
Published: December 2017

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.
Inferior vena caval pressure increase contributes to sodium and water retention during PEEP in awake dogs
Authors: Rossaint R. , Krebs M. , Forther J. , Unger V. , Falke K. , Kaczmarczyk G.
Published: December 2017

This study compared the hemodynamic, renal, and hormonal effects of an experimentally induced increase in inferior vena caval pressure (IVCP) [to the same extent as during controlled mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP)] with those of CMV with PEEP. Six volume-expanded conscious chronically tracheotomized dogs were studied under three conditions: Control: 4 h of spontaneous breathing at 4 cmH2O continuous positive airway pressure (CPAP); CMV: CPAP for the 1st and 4th h and CMV with PEEP for the 2nd and 3rd h, resulting in a mean airway pressure of 20 cmH2O; and Increased IVCP: 4 h of CPAP, with IVCP increased during the 2nd and 3rd h by inflation of a chronically implanted cuff. Urine volume, sodium excretion, and fractional sodium excretion decreased during the 2nd and 3rd h of CMV and during increased IVCP compared with Control. Glomerular filtration rate, mean arterial pressure, and antidiuretic hormone, atrial natriuretic peptide, and aldosterone plasma concentrations were not affected by CMV or Increased IVCP. Plasma renin activity decreased during Control and Increased IVCP conditions but remained elevated during the 2nd and 3rd h of CMV. We conclude that, in conscious extracellular volume-expanded dogs, IVCP elevation contributes considerably to the water- and sodium-retaining effect of short-term CMV with PEEP.
Comparative study of mechanical interdependence: effect of lung volume on Raw during induced constriction
Authors: Nagase T. , Martin J. G. , Ludwig M. S.
Published: December 2017

The mechanical load imposed by the parenchyma can decrease the magnitude of agonist-induced airway constriction. To examine whether variability in mechanical interdependence could account for differences in airway narrowing among different species, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in rats and guinea pigs. Direct measurements of Raw were made under baseline conditions at different levels of end-expiratory transpulmonary pressure (PL = 3–11 cmH2O). Then aerosolized MCh was delivered (128 mg/ml in rats, 8 mg/ml in guinea pigs), and measurements were obtained at different levels of PL (3–11 cmH2O). We measured tracheal flow and tracheal and alveolar pressure (using alveolar capsules) in open-chest animals during mechanical ventilation (tidal volume 6 ml/kg, frequency 1 Hz) and calculated Raw by subtracting tissue from total lung resistance. For interspecies comparisons, data were standardized using percent change in Raw (delta % Raw) at PL of 3 cmH2O during baseline and, after MCh, log-scaled delta % Raw at PL of 3 cmH2O. We found that increasing lung volume decreased Raw both at baseline and after MCh in both species. However, changes were far smaller in guinea pigs. During baseline, the slope of the delta % Raw/delta PL was -3.37 and -12.48 %/cmH2O for guinea pigs and rats, respectively (P < 0.001). After MCh, the slope of delta log %Raw/delta PL was -0.065 and -0.154 cmH2O-1 for guinea pigs and rats, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of positive end-expiratory pressure on lung tissue mechanics in rabbits
Authors: Shardonofsky F. R. , McDonough J. M. , Grunstein M. M.
Published: December 2017

The effects of positive end-expiratory pressure (PEEP) on lung tissue resistance (Rti) and dynamic elastance (Edyn,L) were examined separately during histamine-induced lung constriction and after saline lung lavage in anesthetized paralyzed New Zealand White rabbits. During mechanical ventilation in the open-chest state, Rti and Edyn,L were estimated by fitting the appropriate signals to the equation of motion of the single-compartment linear model of the lung. Data were analyzed in relation to the structural damping hypothesis, which assumes that energy dissipation (Rti) and energy storage (Edyn,L) within the lung tissues are coupled at a fundamental level; the coupling parameter, termed hysteresivity (eta), = Rti.omega/Edyn,L, where omega is angular frequency. Under baseline conditions, elevation in PEEP resulted in significant increases in both Rti and Edyn,L, with eta remaining unchanged. During induced constriction and after lung lavage, Rti and Edyn,L significantly increased relative to their baseline values. During histamine-induced constriction, increasing PEEP was associated with increases in Edyn,L, whereas Rti and eta were reduced. After lung lavage, elevation in PEEP from 5 to 7 cmH2O was associated with proportional increases in Rti and Edyn,L, resulting in a relative constancy of eta. By contrast, when PEEP was decreased from 5 to 3 cmH2O, the values of Rti increased, whereas Edyn,L remained unchanged, resulting in significant increases in eta. Collectively, these findings suggest that the effects of PEEP on Rti during agonist-induced constriction and after perturbations of the gas-liquid interface are dependent on the state of alveolar/airway stability.
Exercise-induced hypoxemia in older athletes
Authors: Prefaut C. , Anselme F. , Caillaud C. , Masse-Biron J.
Published: December 2017

To determine whether exercise induces hypoxemia in highly trained older “master” athletes (MA), as it does in certain elite endurance-trained young athletes (YA), 10 MA (65.3 +/- 2.6 yr), 10 control subjects (CS; 68.3 +/- 2.2 yr), and 10 endurance-trained YA (23.3 +/- 1.1 yr) performed an incremental exercise test. During testing, blood samples for arterial blood gas analysis were drawn during the last 20 s of each load. Lung exchanges were measured using a breath-by-breath automated exercise device. Exercise-induced hypoxemia (EIH) appeared in all MA and 8 of 10 YA, whereas there were no changes in the blood gases of CS. In MA, arterial PO2 decreased significantly from 40% of maximal O2 uptake onward and was associated with a significant increase in the ideal alveolar-arterial O2 difference from 60% onward. The MA also showed a lower ventilation for a given absolute load compared with CS. In all subjects arterial PCO2 rose slightly but significantly during the work, but this increase was most marked in MA. The EIH differed between MA and YA in the following ways: 1) all MA showed a drop in arterial PO2 during exercise, 2) this drop appeared earlier and was significantly greater for a given load in MA, and 3) EIH appeared at a lower level of training regimen in MA. This hypoxemia was at first isolated, probably at least partially due to relative hypoventilation, and then was associated with a widened ideal alveolar-arterial O2 difference, which may have been due to an increase in extravascular lung water.(ABSTRACT TRUNCATED AT 250 WORDS)
PMN adherence to cat ischemic-reperfused mesenteric vascular endothelium under flow: role of P-selectin
Authors: Lefer A. M. , Ma X. L.
Published: December 2017

We studied polymorphonuclear leukocyte (PMN) adherence to cat ischemic-reperfused mesenteric artery and vein endothelia under conditions of flow in vitro. Under physiological shear rates, only a few PMNs adhered to non-ischemic-reperfused arterial and venous endothelia (11 +/- 2 and 20 +/- 3 PMN/mm2, respectively). However, after 60 min of ischemia and 20 or 120 min of reperfusion, a significant increase in PMN adherence to arterial endothelium was observed. At 20 min of reperfusion, 44 +/- 4 PMN/mm2 adhered, and at 120 min postreperfusion, 63 +/- 12 PMN/mm2 adhered (P < 0.01 from control). Moreover, a greater degree of PMN adherence occurred on the venous than on the arterial endothelium. Thus, 159 +/- 10 and 198 +/- 12 PMN/mm2 adhered to mesenteric venous endothelium isolated after 20 and 120 min reperfusion, respectively (P < 0.01 vs. arteries). Furthermore, addition of PB 1.3 (20 micrograms/ml), a monoclonal antibody against P-selectin, 5 min before perfusion with PMNs significantly attenuated the increase in PMN adherence to both arterial and venous endothelia (P < 0.01). These results indicate that PMN-endothelial interaction also occurs in conduit vessels after ischemia and reperfusion, although a more profound PMN adherence occurs in veins.