bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-related immunosenescence in Fischer 344 rats: influence of exercise training
Authors: Nasrullah I. , Mazzeo R. S.
Published: December 2017

The present investigation examined the extent to which 15 wk of endurance training could influence immune function in young, middle-aged, and older animals. Forty-eight male Fischer 344 rats were divided into trained and untrained groups. Training consisted of treadmill running at 75% maximal running capacity for 1 h/day, 5 days/wk, for 15 wk. Animals were killed at 8, 17, and 27 mo, at which time splenocytes were isolated. The capacity for lymphocyte proliferation in response to mitogen (concanavalin A, ConA), interleukin-2 (IL-2) production, and cytolytic activity against YAC-1 target cells was determined. ConA-induced proliferation declined significantly with age. Training suppressed the proliferative response in the young (-41%) and middle-aged animals (-27%) compared with the age-matched controls; however, training improved this response (+58%) in the older group. IL-2 production followed a pattern similar to that for mitogen-induced proliferation, such that production declined with age and was reduced with training in young and middle-aged animals but was significantly more improved in the older animals than in age-matched controls. The ability to lyse target cells, measured as percent cytotoxicity, declined steadily with advancing age at all effector-to-target cell ratios tested: 52, 14, and -16% for 8-, 17-, and 27-mo-old rats, respectively. It was concluded that the capacity for ConA-induced splenocyte proliferation, IL-2 production, and cytolytic activity declines significantly with advancing age. Furthermore, 15 wk of endurance training suppressed proliferation and IL-2 production in young animals but improved these responses in older animals. Training had no effect on cytolytic activity.
Kinetics of NO2 air space absorption in isolated rat lungs
Authors: Postlethwait E. M. , Langford S. D. , Bidani A.
Published: December 2017

We previously showed, during quasi-steady-state exposures, that the rate of inhaled NO2 uptake displays reaction-mediated characteristics (J. Appl. Physiol. 68: 594–603, 1990). In vitro kinetic studies of pulmonary epithelial lining fluid (ELF) demonstrated that NO2 interfacial transfer into ELF exhibits first-order kinetics with respect to NO2, attains [NO2]-dependent rate saturation, and is aqueous substrate dependent (J. Appl. Physiol. 71: 1502–1510, 1991). We have extended these observations by evaluating the kinetics of NO2 gas phase disappearance in isolated ventilating rat lungs. Transient exposures (2–3/lung at 25 degrees C) employed rebreathing (NO2-air) from a non-compliant continuously stirred closed chamber. We observed that 1) NO2 uptake rate is independent of exposure period, 2) NO2 gas phase disappearance exhibited first-order kinetics [initial rate (r*) saturation occurred when [NO2] > 11 ppm], 3) the mean effective rate constant (k*) for NO2 gas phase disappearance ([NO2] < or = 11 ppm, tidal volume = 2.3 ml, functional residual capacity = 4 ml, ventilation frequency = 50/min) was 83 +/- 5 ml/min, 4) with [NO2] < or = 11 ppm, k* and r* were proportional to tidal volume, and 5) NO2 fractional uptakes were constant across [NO2] (< or = 11 ppm) and tidal volumes but exceeded quasi-steady-state observations. Preliminary data indicate that this divergence may be related to the inspired PCO2. These results suggest that NO2 reactive uptake within rebreathing isolated lungs follows first-order kinetics and displays initial rate saturation, similar to isolated ELF.(ABSTRACT TRUNCATED AT 250 WORDS)
Estimation of blood pressure-related parameters by electrical impedance measurement
Authors: Muntinga J. H. , Visser K. R.
Published: December 2017

In 13 healthy volunteers a computerized experimental set-up was used to measure the electrical impedance of the upper arm at changing cuff pressure, together with the finger arterial blood pressure in the contralateral arm. On the basis of a model for the admittance response, the arterial blood volume per centimeter length (1.4 +/- 0.3 ml/cm), the venous blood volume as a percentage of the total blood compartment (49.2 +/- 12.6%), and the total arterial compliance as a function of mean arterial transmural pressure were estimated. The effective physiological arterial compliance amounted to 2.0 +/- 1.3 microliters.mmHg-1.cm-1 and the maximum compliance to 33.4 +/- 12.0 microliters.mmHg-1.cm-1. Additionally, the extravascular fluid volume expelled by the occluding cuff (0.3 +/- 0.3 ml/cm) was estimated. These quantities are closely related to patient-dependent sources of an unreliable blood pressure measurement and vary with changes in cardiovascular function, such as those found in hypertension. Traditionally, a combination of several methods is needed to estimate them. Such methods, however, usually neglect the contribution of extravascular factors.
Enhanced microvascular permeability of PMA-induced acute lung injury is not mediated by cyclooxygenase products
Authors: Wurtz M. M. , Stephenson A. H. , Sprague R. S. , Lonigro A. J.
Published: December 2017

Products of cyclooxygenase activity have been proposed to mediate the pulmonary hypertension and increased microvascular permeability associated with phorbol myristate acetate- (PMA) induced acute lung injury. Previously, we reported that thromboxane (Tx) does not mediate PMA-induced pulmonary hypertension in intact anesthetized dogs. In the present study, PMA was administered to isolated canine lungs perfused with autologous blood at constant flow to investigate a possible role for Tx in the PMA-induced increase in microvascular permeability. Changes in permeability were assessed by determining changes in the capillary filtration coefficient (Kfc). In lobes pretreated with papaverine to prevent PMA-induced increases in pulmonary vascular resistance, Kfc increased from a baseline value of 0.2 +/- 0.03 to 1.5 +/- 0.29 ml.min-1.cmH2O-1.100 g wet lobe wt-1 (P < 0.01) 30 min after PMA (5.8 x 10(-8) M, n = 10). Concomitantly, TxB2, the stable metabolite of TxA2, increased from 138 +/- 44 to 1,498 +/- 505 pg/ml (P < 0.05) in the blood. Both the selective Tx synthase inhibitor, OKY-046 (7 x 10(-4) M, n = 6), and the cyclooxygenase inhibitor, indomethacin (10(-4) M, n = 7), prevented the PMA-induced increase in TxB2, but neither compound attenuated the PMA-induced increase in Kfc. ONO-3708 (10(-6) M), a selective prostaglandin (PG) H2/TxA2 receptor antagonist, prevented the vasoconstriction resulting from administration of U-46619, a stable PGH2/TxA2 receptor agonist, but it did not prevent the PMA-induced increases in Kfc (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise training-induced coronary vascular adaptation
Authors: Laughlin M. H. , McAllister R. M.
Published: December 2017

Aerobic exercise training induces an increase in coronary vascular transport capacity. This increased transport capacity is the result of increases in both blood flow capacity and capillary exchange capacity. These functional changes are the result of two major types of adaptive responses, structural vascular adaptation and altered control of vascular resistance. Structural vascular adaptation occurs in response to exercise training in at least two forms, increases in the cross-sectional area of the proximal coronary arteries and angiogenesis. Angiogenesis has been demonstrated in that training causes moderate cardiac hypertrophy while maintaining or increasing capillary density and increasing arteriolar density. Training-induced changes in coronary vascular control have been shown to include altered coronary responses to vasoactive substances, changes in endothelium-mediated vasoregulation, and alterations in the cellular-molecular control of intracellular free Ca2+ in both endothelial and vascular smooth muscle cells isolated from coronary arteries of exercise-trained animals. The signal or signals for these adaptive responses remain unknown. The hypothesis that the adaptive strategy entails maintenance of normal shear stress in coronary arterial vessels is discussed. We propose that as a result of training-induced structural vascular adaptations and alterations in the control of vascular resistance, shear stress throughout the coronary vasculature is returned to the level present in sedentary animals. The signal for adaptation may be peak shear stress during exercise and/or average shear stress over a 24-h period of time.
Computer simulation of O2 transport and utilization mechanisms at the onset of exercise
Authors: Cochrane J. E. , Hughson R. L.
Published: December 2017

During transitions in work rate, O2 uptake (VO2) kinetics at the working tissue level might be rate limited by O2 transport and/or by O2 utilization. A computer model with parallel working and non-working tissue compartments, connected to an ideal lung by a variable-sized venous blood volume, was developed to study this. The time constant for working tissue O2 demand (tau T) was set by a first-order linear metabolic response. The model attempted to replicate the VO2 response at the alveolar level of a single subject performing step transitions on a cycle ergometer from 25 to 105 W [total lag time (equivalent to 63% increase above baseline) = 40.2 s]. Measured cardiac output kinetics (total lag time = 44.1 s) were used as a model parameter. Blood flow to the nonworking tissue (QNW) was kept constant at 4.5 or 5.0 l/min. A critical PO2 of 20 Torr was set, and the Bohr effect on the O2-hemoglobin dissociation curve was included. The “best” simulation had tau T = 36 s, QNW = 4.5 l/min, and venous blood volume = 2 liters and was not O2 transport limited. The approximation to the real data was good in all but the phase 1 response, where the model underpredicted the measured response. However, when QNW was increased to 5.0 l/min, the model was O2 transport limited; yet the predicted VO2 response at the alveolar level was not notably different from the subject's data.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of neutrophil depletion and repletion on PAF-induced hyperresponsiveness of canine trachea
Authors: Bethel R. A. , Worthen G. S. , Henson P. M. , Lien D. C.
Published: December 2017

Platelet-activating factor (PAF) has been implicated as a mediator of airway hyperresponsiveness. PAF, infused intra-arterially into the canine cervical trachea, causes adherence of neutrophils to vascular endothelium, increases vascular permeability, and increases the responsiveness of tracheal muscle to parasympathetic stimulation. We hypothesized that the increase in airway responsiveness induced by PAF in this model depends on the presence of neutrophils. To test this hypothesis, we perfused a cervical tracheal segment with autologous blood depleted of leukocytes or with similar leukocyte-depleted blood that had been repleted with its neutrophils. Fifteen minutes after the onset of perfusion with either leukocyte-depleted or neutrophil-repleted blood, PAF infusion was begun into the tracheal arterial vasculature. The contractile response of the tracheal muscle to parasympathetic stimulation was measured before and 15 and 30 min after the onset of PAF infusion. PAF did not significantly change the response of tracheal muscle during perfusion with neutrophil-depleted blood but increased the response of tracheal muscle during perfusion with neutrophil-repleted blood. We conclude that the increase in canine tracheal muscle response induced by intra-arterial PAF depends on neutrophils.
Carotid chemoreceptor discharge during epinephrine infusion in anesthetized cats
Authors: Linton R. A. , Band D. M. , Wolff C. B.
Published: December 2017

It is known that during exercise there is an increase in plasma epinephrine. The purpose of the present investigation was to determine whether stimulation of carotid chemoreceptors by epinephrine is a direct effect or secondary to epinephrine-induced increases in arterial plasma [K+] and whole body CO2 production (VCO2). Chemoreceptor discharge was recorded from single fiber preparations of the carotid sinus nerves in anesthetized cats ventilated to a constant arterial PCO2 (PaCO2). Infusion of epinephrine (1 microgram.kg-1 x min-1) caused arterial [K+] to increase from a mean of 2.7 to 3.8 mM. VCO2 increased so that ventilation had to be increased by 60% to maintain PaCO2 constant. Mean chemoreceptor discharge increased by 50%, but this was no greater than would be predicted on the basis of the increases in arterial [K+] and VCO2. In a further group of experiments epinephrine was infused at 0.1 microgram.kg-1 x min-1 and produced no significant increase in chemoreceptor firing. These experiments provide no evidence for epinephrine having a direct effect on the carotid chemoreceptor.
Adaptation to fatigue of long duration in human wrist movements
Authors: Lucidi C. A. , Lehman S. L.
Published: December 2017

Subjects made fast, accurate, consistent wrist flexions under normal conditions and under conditions of low-frequency fatigue. Movements made 1 h after fatiguing exercise were indistinguishable from those made before exercise, even though twitch tensions were only approximately 60% of their fresh values. Electromyograms (EMGs) recorded from the fatigued muscles were, however, different from those recorded before exercise. EMGs during unfatigued movements showed multiple bursts typical for rapid movements. In the presence of low-frequency fatigue, the duration of the first burst was longer than that under normal conditions, and its onset occurred earlier relative to the initiation of movement. The area of the second agonist burst and, in some cases, the antagonist burst, was increased, although changes in their timings were unclear. We conclude that subjects adapted to low-frequency fatigue by changing the neural patterns controlling their muscles and present a simple model of excitation-contraction coupling that demonstrates how the observed changes in excitation can produce the same kinematics.
Role of platelet-activating factor in the ovine heparin-protamine reaction
Authors: Montalescot G. , Huerta J. M. , Braquet P. , Zapol W. M.
Published: December 2017

Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF.
Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m)
Authors: Huang S. Y. , Sun S. , Droma T. , Zhuang J. , Tao J. X. , McCullough R. G. , McCullough R. E. , Micco A. J. , Reeves J. T. , Moore L. G.
Published: December 2017

Cerebral blood flow increases with acute exposure to high altitude, but the effect of hypoxia on the cerebral circulation at rest and during exercise appears influenced by the duration of high-altitude exposure. To determine whether internal carotid artery flow velocity increased with exercise in long-term residents of high altitude and whether resting values and the response to exercise differed in lifelong vs. acclimatized newcomer male residents of high altitude, we studied 15 native Tibetan and 11 Han (“Chinese”) 6 +/- 2-yr residents of Lhasa (3,658 m), Tibet Autonomous Region, China. Noninvasive Doppler ultrasound was used to measure internal carotid artery diameter, mean flow velocity, and, in combination, hemoglobin and arterial O2 saturation to assess cerebral O2 delivery. Tibetan and Han groups were similar in body size and resting internal carotid artery diameter, blood pressure, hemoglobin concentration, internal carotid artery mean flow velocity, and calculated cerebral O2 delivery. Submaximal exercise increased internal carotid artery mean flow velocity and cerebral O2 delivery in the Tibetan and Han subjects. At peak exercise, the Tibetans sustained the increase in flow velocity and cerebral O2 delivery, whereas the Hans did not. Across all exercise levels up to and including peak effort, the Tibetans demonstrated a greater increase in internal carotid artery flow velocity and cerebral O2 delivery relative to resting values than did the Hans. The greater cerebral O2 delivery was accompanied by increased peak exercise capacity in the Tibetan compared with the Han group. Our findings suggest that the cerebral blood flow response to exercise is maintained in Tibetan lifelong residents of high altitude.
Lung volume, pressure, flow, and density relationships during constant-flow ventilation in dogs
Authors: Brampton W. , Young J. D.
Published: December 2017

Lung volume changes during constant-flow ventilation (CFV) using cannulas in the main stem bronchi were examined in six beagle dogs. The increase in lung volume was found to depend mainly on the outflow resistance to gas flow in the trachea and tracheal tube. The resistance changed with gas flow, indicating that gas flow was transitional between laminar and turbulent flow (resistance varies; is directly proportional to flow1.5). There was a small pressure gradient between trachea and alveoli (1.1–1.3 cmH2O) that was independent of flow rate or gas velocity out of the CFV cannulas. This was attributed to momentum transfer from the gas jet from the CFV cannulas modified by friction between the gas jet and the airway wall.
Influence of signal processing on estimation of respiratory impedance
Authors: Lorino H. , Mariette C. , Karouia M. , Lorino A. M.
Published: December 2017

Respiratory impedance was estimated between 4 and 30 Hz by spectral analysis of the mouth flow and pressure signals measured in spontaneously breathing subjects when applying a pseudorandom pressure excitation at the mouth. The signals were submitted to antialiasing low-pass filtering followed by digital preprocessing before the calculation of spectra by a fast Fourier transform algorithm. The effectiveness of signal preprocessing in eliminating the leakage error due to breathing noise was illustrated in both a mechanical analogue and a patient. Five preprocessing techniques that combined high-pass filtering and windowing were then compared in 32 randomly selected patients by examining the influence of these techniques on 1) the values of impedance at 5, 10, and 20 Hz, and 2) the parameters of linear models fitting the real (Zr) and imaginary (Zi) parts of impedance for coherence values higher than a preset threshold. The impedance values and derived parameters were either the mean of the estimates separately obtained in the three data recordings (PA) or the single estimate obtained from average spectra (SP). Small but significant differences between filtering and windowing, as well as between SP and PA, were evidenced for the Zr, whereas Zi was only slightly sensitive to the type of averaging technique. We conclude that the signal preprocessing and data averaging techniques selected in this study have similar effects on spectral estimation of respiratory impedance.
Cl- replacement alters the ventilatory response to central chemoreceptor stimulation
Authors: Davidson T. L. , Sullivan M. P. , Swanson K. E. , Adams J. M.
Published: December 2017

To determine whether cerebrospinal fluid (CSF) Cl- has a role in determining the stimulus to the central respiratory chemoreceptors under conditions of constant CSF pH, CO2, and HCO3- concentrations, the ventral medullary surface of the anesthetized rat was perfused with mock CSF of various ion composition and pH. Four mock CSF perfusates were used: two normal pH control perfusions and two acidic solutions. One acidic perfusate was formulated in the traditional manner by substituting Cl- for HCO3-. The second acidic perfusate, and one of the normal pH control perfusates, had approximately 15% of the Cl- replaced with isethionate, an impermeant strong anion. When the two acidic solutions were perfused over the ventral medulla, consistently larger increases in both tidal volume and minute ventilation were observed with the isethionate-containing acidic solution, despite conditions of identical pH and PCO2. The unequal ventilatory effects of the two acidic perfusions suggest that Cl- transport may be a factor determining the stimulus to the central respiratory chemoreceptors.
Orthostatic intolerance during a 13-day bed rest does not result from increased leg compliance
Authors: Melchior F. M. , Fortney S. M.
Published: December 2017

Increased leg compliance (LC) has been proposed as a mechanism for orthostatic intolerance after spaceflight or bed rest. Using venous occlusion plethysmography with mercury-in-Silastic strain gauge, we evaluated LC before, during, and after a 13-day head-down (-6 degrees) bed rest in 10 men. LC was measured by the relationship between the increased calf areas (in cm2) at thigh cuff occlusions of 20, 30, 50, 70, and 80 mmHg. Orthostatic tolerance was evaluated by a presyncopal-limited lower body negative pressure test (PSL-LBNP) before and after bed rest. The 10 subjects were divided into TOL (n = 5) and INT (n = 5) groups for which the orthostatic tolerance was similar and lower after bed rest, respectively. For TOL (INT) before bed rest, calf area increases were 2.2 +/- 0.5 (SE) (1.3 +/- 0.4), 3.5 +/- 0.7 (2.3 +/- 0.5), 5.0 +/- 0.9 (3.5 +/- 0.6), 5.6 +/- 0.9 (4.4 +/- 0.6), and 6.4 +/- 1.1 (4.7 +/- 0.6) cm2 for thigh occlusion pressures of 20, 30, 50, 70, and 80 mmHg, respectively. Neither for INT nor for TOL were these results significantly changed by bed rest. These results suggest that other mechanisms than increased LC have to be taken into account to explain the decreased orthostatic tolerance induced by this 13-day bed rest.
Nonadrenergic noncholinergic neurotransmitter of feline trachealis: VIP or nitric oxide?
Authors: Fisher J. T. , Anderson J. W. , Waldron M. A.
Published: December 2017

We tested the hypothesis that vasoactive intestinal peptide (VIP) or nitric oxide (NO) is the nonadrenergic noncholinergic (NANC) neurotransmitter in feline trachealis. Isometric tension was measured in trachealis (open or closed tracheal rings) in vitro. Propranolol (10 microM) and atropine (1 microM) were present throughout the experiment, and smooth muscle tone was increased to 60–90% maximal with 5-hydroxytryptamine. We used three methodologies to reduce the relaxation function of VIP, which in turn should reduce NANC-mediated relaxation. 1) The putative VIP antagonist peptide T (10 microM) did not affect VIP concentration-response curves or electrical field stimulation- (EFS) induced NANC responses. 2) Incubation of tissue in specific VIP antiserum (16 h at 4 degrees C) did not reduce EFS-induced NANC relaxations relative to tissue incubated in normal rabbit serum (P > 0.05). On the basis of our passive immunization techniques, it is not possible to absolutely reject VIP as the NANC transmitter. We speculate that nonspecific peptidases present in normal serum and VIP antiserum reduce EFS-induced responses similarly. 3) VIP desensitization, confirmed by a significant rightward shift (P < 0.01) in the VIP concentration-response curve, was achieved by exposing tissues (n = 11) to 1.0 microM VIP for 30 min. Desensitization did not reduce the EFS-induced NANC relaxatory response (P < 0.05) compared with control tissues, suggesting that VIP is not the NANC mediator.(ABSTRACT TRUNCATED AT 250 WORDS)
Higher levels of erythrocyte membrane fluidity in sprinters and long-distance runners
Authors: Kamada T. , Tokuda S. , Aozaki S. , Otsuji S.
Published: December 2017

Erythrocyte membrane fluidity was measured in male sprinters and long-distance runners by a spin-label method. The membrane fluidity was higher in long-distance runners than in sedentary subjects for both measurements by use of two stearic acid spin labels (SAL), 12- and 16-SAL, which represent the fluidity at two different depths of lipid bilayer. In the 12-SAL measurement, higher levels were also evident in sprinters than in sedentary subjects. Increases in the C20:5, C22:5, and total polyunsaturated acyl chains were evident in membrane phospholipids, whereas the C18 and total saturated acyl chains were decreased in long-distance runners compared with sedentary subjects. Only levels of C22:5 were higher in the sprinters than the sedentary subjects. Membrane cholesterol and phospholipid classes did not differ among the three groups. A higher level of erythrocyte membrane fluidity was observed in the athletes, more obviously in the long-distance runners, which was related to the altered phospholipid acyl chain composition. The change may contribute to the beneficial effects on erythrocyte functions related to microcirculation in athletes.
Effect of posture on static lung volumes and pulmonary mechanics in pneumonectomized rabbits
Authors: Olson L. E.
Published: December 2017

Static lung volumes, lung (CL) and respiratory system compliance (Crs), and the slope of phase III of the single-breath O2 test (slope III) were measured in rabbits in the prone, supine, and right and left lateral positions. Control rabbits, rabbits that had the left lung removed (Px), and rabbits that had the left lung removed and replaced with wax (Px + W) were studied. Surgeries were performed > or = 7 wk before study. Lung volumes, Crs, and slope III were not different among groups. Total lung capacity, vital capacity, residual volume, Crs, and slope III were smallest in all rabbits in the prone position. Functional residual capacity and expiratory reserve volume were unaffected by posture in control rabbits but were larger in Px and Px + W rabbits in the left lateral position. CL was unaffected by posture but was smaller in Px and Px + W rabbits than in control rabbits. Pneumonectomy-induced changes in lung shape altered the effect of posture on functional residual capacity but not on regional lung function, as assessed by the single-breath O2 test.
Water-sealed spirometer for measurements in newborns and infants
Authors: Merth I. T. , Verschragen G. J. , Olievier I. C. , De Winter P. J. , Quanjer P. H.
Published: December 2017

Details are given of two spirometers for use in neonates and infants < 12 mo old. The minimum volumes are 520 and 670 ml, respectively. The maximum volume changes that can be recorded are 250 and 450 ml, respectively. The minimal detectable volume changes are 0.4 and 0.6 ml, respectively. Rebreathing of dead space gas is prevented by a fan producing a flow of 6.2 and 10.2 l/min, respectively; 100% gas mixing after injecting a gas bolus in the two spirometers is achieved in 5.7 and 6.6 s, respectively. Resistance to airflow is 0.2 kPa.l-1.s (2 cmH2O.l-1.s) at 150 ml/s in both spirometers. The frequency response of both instruments is flat to 6 cycles/s. The instruments can be easily cleaned and are suitable for bedside measurements.
Lung volume and effectiveness of inspiratory muscles
Authors: Brancatisano A. , Engel L. A. , Loring S. H.
Published: December 2017

We related inspiratory muscle activity to inspiratory pressure generation (Pmus) at different lung volumes in five seated normal subjects. Integrated electromyograms were recorded from diaphragmatic crura (Edi), parasternals (PS), and lateral external intercostals (EI). At 20% increments in the vital capacity (VC) subjects relaxed and then made graded and maximal inspiratory efforts against an occluded airway. At any given level of pressure generation, Edi, PS, and EI increased with increasing lung volume. The Pmus generated at total lung capacity as a fraction of that at a low lung volume (between residual volume and 40% VC) was 0.39 +/- 0.15 (SD) for the diaphragm, 0.20 +/- 0.06 for PS, and 0.22 +/- 0.04 for the lateral EI muscles. Our results indicate a lesser volume dependence of the Pmus-EMG relationship for the diaphragm than for PS and EI muscles. This difference in muscle effectiveness with lung volume may reflect differences in length-tension and/or geometric mechanical advantage between the rib cage muscles and the diaphragm.
Effect of chronic hypoxia and socioeconomic status on VO2max and anaerobic power of Bolivian boys
Authors: Obert P. , Bedu M. , Fellmann N. , Falgairette G. , Beaune B. , Quintela A. , Van Praagh E. , Spielvogel H. , Kemper H. , Post B. , et al.
Published: December 2017

The aim of this work was to analyze the effects of altitude and socioeconomic and nutritional status on maximal oxygen uptake (VO2max) and anaerobic power (P) in 11-yr-old Bolivian boys. At both high (HA) (3,600 m) and low (LA) (420 m) altitudes, the boys were divided into high (HA1, n = 23, LA1, n = 48) and low (HA2, n = 44, LA2, n = 30) socioeconomic levels. Anthropometric characteristics, VO2max, and P [maximal P (Pmax) during a force-velocity test and mean P (P) during a 30-s Wingate test] were measured. Results showed that 1) anthropometric parameters were not different between HA1 and LA1 and HA2 and LA2 boys, but HA2 and LA2 boys were two years behind HA1 and LA1 boys in development; 2) VO2max was not different in boys from the same altitude, but at HA VO2max was 10% lower than at LA (HA1 = 37.2 +/- 5.6, HA2 = 38.9 +/- 6.4, LA1 = 42.5 +/- 5.8, LA2 = 42.5 +/- 5.3 ml.min-1 x kg-1 body wt); and 3) Pmax and P were higher in well-nourished than in undernourished boys, but there was no difference in Pmax and P between HA1 and LA1 and HA2 and LA2 boys (HA1 = 6.8 +/- 1.0, HA2 = 5.5 +/- 0.8, LA1 = 7.1 +/- 1.0, LA2 = 5.3 +/- 0.9 W/kg for Pmax; HA1 = 5.2 +/- 0.8, HA2 = 4.5 +/- 0.9, LA1 = 5.2 +/- 0.7, LA2 = 4.0 +/- 0.6 W/kg for P).(ABSTRACT TRUNCATED AT 250 WORDS)
Embolus size affects gas exchange in canine autologous blood clot pulmonary embolism
Authors: Delcroix M. , Melot C. , Vanderhoeft P. , Naeije R.
Published: December 2017

Embolic pulmonary hypertension is associated with alterations in gas exchange of variable severity, which we hypothesized to be related to embolus size. We therefore examined the effects of different-size autologous blood clot embolization on pulmonary arterial pressure-cardiac output relationships (Ppa/Q) and on the distribution of ventilation-perfusion ratios (VA/Q) in 18 intact anesthetized and ventilated (inspired fraction of O2 0.4) dogs. Multipoint Ppa/Q plots were generated by a manipulation of venous return before and 60 min after sufficient amounts of small (1 mm, n = 6 dogs), medium (5 mm, n = 6 dogs), or large (10 mm, n = 6 dogs) clots to increase Ppa to 50 mmHg. The distribution of VA/Q was determined by the multiple inert gas elimination technique at the same intermediate Q in each of these experimental conditions. All three sizes of emboli resulted in an 82–92% mean angiographic pulmonary vascular obstruction and increased both the extrapolated pressure intercepts and the slopes of the linear Ppa/Q plots. Gas exchange was altered the most after large clots, which were associated with lower arterial pH, higher physiological and inert gas dead spaces, higher dispersion of ventilation, and also lower mean VA/Q of perfusion distributions. In contrast, inert gas dead space was decreased after small clots. We conclude that, in autologous blood clot embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size but that gas exchange is affected differently, mainly in high-VA/Q regions and most often after the largest clots.
Renin-angiotensin system stimulates respiration during acute hypotension but not during hypercapnia
Authors: Ohtake P. J. , Walker J. K. , Jennings D. B.
Published: December 2017

We reported that intravenous infusion of angiotensin II (ANG II) stimulated ventilation (VE) in conscious dogs. Other studies in our laboratory have demonstrated that increases in respiration occurred in association with activation of the renin-angiotensin system during acute hypotension and during hypercapnia. Therefore, in conscious dogs (n = 5), we examined the effects of ANG II receptor blockade with intravenous saralasin (0.5 micrograms.kg-1.min-1) on respiratory responses during progressive nitroprusside-induced hypotension and during the ventilatory response to increased inspired fraction of CO2 (VRC). During hypotension (mean arterial pressure decreased approximately 20%) combined with ANG II receptor blockade, VE, heart rate, and arginine vasopressin increases were attenuated compared within unblocked studies. With ANG II receptor blockade during hypotension, alveolar ventilation and arterial PCO2 (PaCO2) were unchanged, which contrasted with a doubling of alveolar ventilation and a decrease of 4.8 +/- 1 Torr in PaCO2 in unblocked studies. During hypercapnia, the slope of the VRC was not affected by ANG II receptor blockade, but with 6.5% inspired CO2 fraction, VE and PaCO2 were lower than in unblocked studies. These results indicated that ANG II contributed to the respiratory response to a modest hypotension but did not affect respiratory sensitivity to CO2.
Selective brain cooling is affected by wearing headgear during exercise
Authors: Rasch W. , Cabanac M.
Published: December 2017

The purpose of this work is to relate the concept of selective brain cooling (SBC) during exercise to heat loss from the head while either bare or covered. During hyperthermia, SBC is considered to occur if tympanic temperature (Tty) is lower than esophageal temperature (Tes). In experiment I the head heat loss was measured with and without headgear. Each of four subjects took part in three sessions of exercise on a cycle ergometer. The face was cooled to simulate outdoor conditions. The first session (no headgear) served as control for the two following sessions in which a headband and a woolen cap were worn. Evaporative and radiative-convective heat loss were monitored from the head. Wearing a cap significantly reduced the heat loss from the head compared with the control condition. During the headband session the heat loss was not significantly lower than the control values. Tty, Tes, and head skin temperatures (T(sk)) were also recorded. Tty was significantly lower (-0.55 +/- 0.15 degrees C) than Tes at the end of exercise (150-W exercise load) when no headgear was worn. During headgear sessions, Tty was no longer significantly lower than Tes, either during the headband (-0.15 +/- 0.31 degrees C) or during the cap session (-0.30 +/- 0.13 degrees C). In experiment II the influence of wearing headgear on temperature regulation was studied. Hand skin blood flow, hand T(sk), and heat loss from the hand were recorded in addition to the variables monitored in experiment I. Wearing headgear elevated Tty and peripheral vasomotor responses, whereas Tes evolved in the opposite direction.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiopulmonary adaptations to pneumonectomy in dogs. II. VA/Q relationships and microvascular recruitment
Authors: Hsia C. C. , Herazo L. F. , Ramanathan M. , Johnson R. L. , Wagner P. D.
Published: December 2017

Ventilation-perfusion relationships, diffusing capacity for O2, and hemodynamic response were measured at rest and during exercise while five adult dogs breathed air and 15% O2 2 mo (Pnx-A, n = 2) or 12 mo (Pnx-B, n = 3) after right pneumonectomy (removal of 58% of lung tissue). Results were compared with those in five sham-operated controls. The multiple inert gas elimination technique was employed. Maximal O2 uptake was reduced by 50% in Pnx-A and by 15% in Pnx-B. Ventilation-perfusion matching was impaired in Pnx-A but not in Pnx-B. The increase in O2 diffusing capacity during exercise was significantly restricted in Pnx-A but was partially restored in Pnx-B. Mean pulmonary arterial pressure at a given blood flow through the remaining lung was normal in Pnx-A but lower than normal in Pnx-B compared with control values for a single lung. Stroke volume and cardiac output were lower in both Pnx-A and Pnx-B than in controls at a given exercise level. All functional abnormalities were more severe at 2 mo than at 12 mo postpneumonectomy. Gas phase diffusion resistance was present in both Pnx-A and Pnx-B but not in controls. We conclude that physiological compensation postpneumonectomy is progressive. Inability to recruit pulmonary vascular bed with incremental perfusion pressure or flow appears to be the major pathophysiological process that limits early functional capacity after right pneumonectomy.
Quantifying the effect of intravascular perfluorocarbon on xenon elimination from canine muscle
Authors: Novotny J. A. , Bridgewater B. J. , Himm J. F. , Homer L. D.
Published: December 2017

Intravenous infusions of perfluorocarbon (PFC) may improve decompression sickness outcome in animals by accelerating inert gas elimination from tissue, but any such effect has not been quantified experimentally. In this study we used an animal model of tissue Xe kinetics to test this hypothesis and to quantify the effect of PFC. Eight dogs were ventilated with dilute 133Xe in air for 4 h of Xe uptake. Four dogs were then given an infusion (20 ml/kg iv) of a 40% (vol/vol) perfluorodecalin-glycerol emulsion, and four control dogs were given only isotonic glycerol. All were then switched to open-circuit air breathing for 4 h of Xe elimination. During this time Xe radioactivity-time curves were recorded from two intact hind leg muscles, and the Xe mean residence times during elimination were estimated using an analysis by moments and compared by group. Tissue blood flows were measured using microspheres once during Xe uptake and twice during Xe elimination, and cardiac outputs were measured by thermodilution at 30-min intervals. In the PFC group the measured circulating PFC fraction increased the calculated Xe solubility by an average factor of 1.77 and so was expected to increase the Xe elimination rate by 77%. The observed Xe mean residence times on elimination for the PFC group averaged 33.5 min [95% confidence interval (CI) 19.5 (5547.6] compared with the glycerol control average of 70.1 min (95% CI 56.1 (5584.2), representing an increase in the rate of Xe elimination by a factor of 2.09 or 109%.(ABSTRACT TRUNCATED AT 250 WORDS)
Withdrawal of placental prostaglandins permits thermogenic responses in fetal sheep brown adipose tissue
Authors: Gunn T. R. , Ball K. T. , Gluckman P. D.
Published: December 2017

Significant nonshivering thermogenesis cannot be demonstrated in fetal sheep cooled in utero but can be induced by supplemental oxygenation and umbilical cord occlusion, which suggests the presence of inhibitor(s) of placental origin. To test the hypothesis that an ecosanoid could be such an inhibitor, we studied eight fetal sheep at 136–141 days gestation. Thermistors were placed in the fetal esophagus, a cooling tube was placed around the trunk, a tracheal cannula and carotid catheters were inserted, and a snare was placed loosely around the umbilical cord. After indomethacin infusion for 18 h, the fetuses were cooled by 2.13 +/- 0.13 degrees C by circulating cold water through the coil. Within 60 min plasma free fatty acid levels rose threefold to 245 +/- 82 mu eq/l (P < 0.01) and glycerol levels rose to 197 +/- 17 mumol/l (P < 0.01). Ventilation caused a further rise in thermogenic indexes, and fetal oxygen consumption rose to 19.9 +/- 1.2 ml.kg-1.min-1. In four fetuses we ceased cooling, which caused thermogenic indexes to fall and oxygen consumption to fall to 6.9 +/- 1.1 ml.kg-1.min-1. We continued to cool three fetuses and infused prostaglandin E2 into the fetuses for 60 min; thermogenic indexes and oxygen consumption fell rapidly on infusion and rose rapidly when infusion ceased. We suggest that placental prostaglandins inhibit brown adipose tissue thermogenesis before birth and that withdrawal after placental separation is one factor in the initiation of nonshivering thermogenesis at birth.
Antigen-induced contraction of guinea pig isolated pulmonary arteries and lung parenchyma
Authors: Kelly L. J. , Undem B. J. , Adams G. K.
Published: December 2017

We characterized the kinetics of and determined the mediators involved in antigen-induced contraction of pulmonary arteries (PA) and lung parenchyma isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml) induced contractions of PA rings, which reached maximum amplitude by 2 min and decayed to 50% of maximum by 4–6 min. Pyrilamine (10(-6) M) delayed the onset of contraction and decreased the peak of the response by > 50%. Metiamide (10(-4) M) partially reversed this effect. The addition of indomethacin (10(-6) M) to the combination of pyrilamine and metiamide had no significant effect. The further addition of the leukotriene (LT) D4/LTE4 receptor antagonist SKF 104353 (10(-5) M) reduced the contraction by > 80%. The maximum amplitude of antigen-induced contraction of parenchymal strips was reached by 15 min and was sustained for > 60 min. In these tissues, SKF 104353 inhibited the contraction by approximately 35%, but the histamine receptor antagonists and indomethacin had no significant effect. These results suggest that both histamine and sulfidopeptide LTs mediate antigen-induced contraction of PA, whereas sulfidopeptide LTs, but not histamine, are involved in the parenchymal response.
Lung and chest wall mechanics in mechanically ventilated COPD patients
Authors: Guerin C. , Coussa M. L. , Eissa N. T. , Corbeil C. , Chasse M. , Braidy J. , Matar N. , Milic-Emili J.
Published: December 2017

By use of the technique of rapid airway occlusion, the effects of inspiratory flow, volume, and time on lung and chest wall mechanics were investigated in 10 chronic obstructive pulmonary disease (COPD) patients mechanically ventilated for acute respiratory failure. We measured the interrupter resistance (Rint), which in humans reflects airway resistance; the additional resistances due to time constant inequality and viscoelastic pressure dissipations within the lungs (delta RL) and the chest wall; and the static and dynamic elastances of lung and chest wall. We observed that 1) static elastances of lung and chest wall in COPD patients were similar to those of normal subjects; 2) Rint of the lung was markedly increased and flow dependent in COPD patients, whereas Rint of the chest wall was negligible as in normal subjects; and 3) in COPD patients, delta RL was markedly increased at all inflation flows and volumes, reflecting increased time constant inequalities within the lungs and/or altered viscoelastic behavior. The results imply increased dynamic work due to Rint and delta RL and marked time dependency of pulmonary resistance and elastance in COPD patients.
Intralysosomal pH and release of lysosomal enzymes in the rat liver after exhaustive exercise
Authors: Tsuboi M. , Harasawa K. , Izawa T. , Komabayashi T. , Fujinami H. , Suda K.
Published: December 2017

The mechanism underlying exhaustive exercise-induced release of lysosomal enzymes was studied in the rat liver. Exhaustive exercise resulted in the release of beta-glucuronidase and cathepsin D, but not beta-glucosidase and acid phosphatase, into the blood and cytosol, suggesting that the release of lysosomal enzymes is not due to disruption of lysosomal membranes. The intralysosomal pH of the liver, which was approximately 5.5 at the resting level, rose significantly after exhaustive exercise to pH 6.3. In vitro, beta-glucuronidase and cathepsin D were released at an intralysosomal pH exceeding 6.2. In contrast, beta-glucosidase and acid phosphatase were not released. The elevation of intralysosomal pH reduced the aggregation of beta-glucuronidase and cathepsin D. The rate of ammonia accumulation increased markedly in the lysosome-enriched subcellular fraction after exercise. There was a positive relationship between the rate of ammonia accumulation and the elevation of intralysosomal pH in vitro. Lysosomes isolated after exhaustive exercise showed significantly increased osmotic fragility. Our findings suggest that, during exhaustive exercise, the accumulation of ammonia in lysosomes leads to the elevation of intralysosomal pH, resulting in the reduced aggregation of certain lysosomal enzymes. Thus, less aggregated lysosomal enzymes may be released into the cytosol through the lysosomal membrane, the permeability of which has been increased.
Diaphragmatic failure during loaded breathing: role of neuromuscular transmission
Authors: Bazzy A. R. , Donnelly D. F.
Published: December 2017

To determine whether central or peripheral mechanisms are responsible for diaphragmatic failure during loaded breathing, phrenic nerve activity (iENG), diaphragm muscle electromyogram (iEMG), and transdiaphragmatic pressure (Pdi) were measured in unanesthetized chronically instrumented sheep during inspiratory flow-resistive (IFR) loaded breathing. After placement of the IFR load, Pdi increased initially and remained relatively stable for 10–30 min [Pdi = 69.9 +/- 6.3 (SE) cmH2O, n = 6]; arterial PCO2 also increased from baseline (35.8 +/- 0.9 Torr) to 55.1 +/- 4.7 Torr. During IFR loading, iEMG and iENG also increased from baseline, but during the plateau phase of Pdi, iENG continued to increase at the same time while iEMG was stable, and the M wave, evoked by phrenic nerve stimulation, decreased during this period. After the plateau phase, Pdi decreased and arterial PCO2 increased, at which point the study was terminated (at 82.1 +/- 20.6 min). The observation that iENG increased while Pdi and iEMG were stable demonstrates a reduced efficiency of neuromuscular transmission and suggests that the neuromuscular junction is an important site of diaphragmatic failure in unanesthetized sheep during IFR loaded breathing.
Cationic proteins alter smooth muscle function by an epithelium-dependent mechanism
Authors: Coyle A. J. , Mitzner W. , Irvin C. G.
Published: December 2017

Using a perfused guinea pig tracheal tube preparation, which allows the selective application of agonists to either the serosal or luminal surface, we have investigated whether two synthetic cationic proteins, poly-L-arginine and poly-L-lysine, can modify epithelium-dependent responses. With an intact epithelium, methacholine was approximately 150 times less potent when applied intraluminally than when applied extraluminally. This difference was abolished by chemically removing the epithelium with the detergent CHAPS. Intraluminal application of KCl induced a dose-related relaxation of a precontracted trachea, which was also abolished by epithelium removal. Perfusion of the luminal surface with cationic proteins for 1 h (10 micrograms/ml) increased the potency of intraluminally applied methacholine without modifying the responses to extraluminally applied methacholine. Cationic proteins also attenuated the relaxant effects of intraluminally applied KCl. These effects occurred in the absence of any overt epithelial cell damage. In contrast, when the serosal surface of the trachea was treated with poly-L-arginine, there was no modification of either methacholine-induced contraction or KCl-induced relaxation. The effects of poly-L-arginine were inhibited by coperfusion with the polyanions albumin (10 micrograms/ml) or heparin (100 micrograms/ml). In contrast to cationic proteins, intraluminal perfusion with a polyanion, poly-L-aspartate (10 micrograms/ml), failed to modify either methacholine-induced contraction or KCl-induced relaxation. Our data demonstrate that cationic proteins can modify epithelium-dependent responses in the airways. Although the precise mechanisms are unclear, a role is suggested for a charge-mediated interaction with the respiratory epithelium, resulting in airway smooth muscle dysfunction.