bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered function of pulmonary surfactant in fatty acid lung injury
Authors: Hall S. B. , Notter R. H. , Smith R. J. , Hyde R. W.
Published: December 2017

To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids.
Modeling human performance in running
Authors: Morton R. H. , Fitz-Clarke J. R. , Banister E. W.
Published: December 2017

This paper focuses on the characteristics of a model interpreting the effect of training on athletic performance. The model theory is presented both mathematically and graphically. In the model, a systematically quantified impulse of training produces dual responses: fitness and fatigue. In the absence of training, both decay exponentially with time. With repetitive training, these responses satisfy individual recurrence equations. Fitness and fatigue are combined in a simple linear difference equation to predict performance levels appropriate to the intensity of training being undertaken. Significant observed correlation of model-predicted performance with a measure of actual performance during both training and tapering provides validation of the model for athletes and nonathletes alike. This enables specific model parameters to be estimated and can be used to optimize future training regimens for any individual.
Tachyphylaxis to inhaled methacholine in normal but not asthmatic subjects
Authors: Stevens W. H. , Manning P. J. , Watson R. M. , O'Byrne P. M.
Published: December 2017

Methacholine inhalation tests measure airway responsiveness in asthmatic and normal subjects. Tachyphylaxis occurs with repeated methacholine inhalations in normal subjects. The purpose of this study was to examine the time course and mechanisms of methacholine tachyphylaxis in normal subjects and to determine whether this occurs in mildly asthmatic subjects. Fifteen normal and nine asthmatic subjects were studied on 2 study days, at least 48 h apart. Each day, two inhalation tests were carried out. On one day, subjects performed two methacholine inhalation tests 3 h later by a methacholine test. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1), (PC20). All normal subjects developed methacholine tachyphylaxis. The mean PC20 increased from 47.3 mg/ml (%SE 1.34) to 115.6 (%SE 1.51) (P less than 0.0001) in a 3-h interval. This increase lasted for greater than or equal to 6 h (P = 0.012). Asthmatic subjects did not develop methacholine tachyphylaxis. Their mean methacholine PC20s were 1.6 mg/ml (%SE 1.4) and 1.5 (%SE 1.4) (P = 0.75) 3 h later. In two other series of experiments, normal subjects were pretreated with the cyclooxygenase inhibitors indomethacin (100 mg/day) or flurbiprofen (150 mg/day) or a placebo for 3 days before two methacholine tests 3 h apart. Both indomethacin and flurbiprofen significantly inhibited the development of methacholine tachyphylaxis. These results confirm that methacholine tachyphylaxis occurs in normal subjects, lasts greater than or equal to 6 h, and may occur through the release of inhibitory prostaglandins. By contrast, methacholine tachyphylaxis does not occur in asthmatic subjects.
A theoretical study of the effect of airway smooth muscle orientation on bronchoconstriction
Authors: Bates J. H. , Martin J. G.
Published: December 2017

If airway smooth muscle shortened in vivo to the extent that it does in vitro, then maximal bronchoconstriction would result in complete closure of virtually all airways. The fact that this does not happen indicates the existence of inhibitory mechanisms preventing maximal muscle shortening. There are many factors potentially limiting shortening in vivo. In this study we investigated one of these factors, the orientation of the smooth muscle around the airway wall. The airway was modeled as a cylinder of given wall thickness around which the muscle was wound as a spiral. The longitudinal and circumferential elasticities of the airway were embodied in a 2 x 2 matrix of elastic coefficients. We investigated smooth muscle shortening under three conditions: 1) a longitudinally stiff airway, 2) a circumferentially stiff airway, and 3) a longitudinally and circumferentially compressible airway. In case 1, for a given degree of smooth muscle shortening, airway resistance increased markedly with increasing pitch of the smooth muscle spiral. On the other hand, the muscle tension required to elicit a given change in resistance also increased markedly with pitch. In case 2, the effect with increasing pitch was reversed. In case 3, resistance first increased and then decreased as spiral pitch increased. Similarly, the muscle tension required to elicit a given change in resistance first increased and then decreased with pitch. These results suggest that the orientation of the smooth muscle about the airway may be very important in determining airway responsiveness.
The alphastat hypothesis in respiratory control and acid-base balance
Authors: Nattie E. E.
Published: December 2017

This selective review 1) evaluates recent interpretations that broaden the definition of the alphastat hypothesis, 2) proposes that central chemoreception and acid-base regulation via ion transport involve proteins conforming to the alphastat hypothesis, and 3) describes, using recent evidence, possible candidates for these proteins. The alphastat hypothesis states that proteins that contain appropriate function-determining titratable groups maintain a constant charge state and unaltered function with temperature-dependent pH changes but can be very sensitive to isothermal pH changes. Appropriate groups, e.g., imidazole histidine, are determined by the pK and the effect of temperature on the pK. The hypothesis explains how protein structure and function can be conserved among a diversity of vertebrate and invertebrate pH values. It also suggests a mechanism for sensing or regulating temperature-independent pH changes, e.g., in central chemosensitivity and transmembrane ion exchange. Possible candidates for such alphastat-conforming proteins include two, the glutamate receptor and the Na(+)-H+ antiporter, for which recent evidence indicates the presence of numerous histidines at probable function-determining sites and demonstrates pH sensitivity inhibitable by the histidine blocker diethylpyrocarbonate (DEPC).
Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease
Authors: Sahlin K. , Areskog N. H. , Haller R. G. , Henriksson K. G. , Jorfeldt L. , Lewis S. F.
Published: December 2017

Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.
Body water and electrolyte responses to acetazolamide in humans
Authors: Brechue W. F. , Stager J. M. , Lukaski H. C.
Published: December 2017

Acetazolamide (ACZ), a potent carbonic anhydrase inhibitor, is a known diuretic and causal agent in metabolic acidosis. Its diuretic qualities are well established with respect to urine flow and electrolyte excretion. However, the impact of ACZ on body hydration status has not been adequately quantified. Thus, to establish the influence of ACZ treatment on body water, nine healthy males were evaluated for hydration status after clinically prescribed doses of ACZ. The drug was administered in three 250-mg oral doses 14, 8, and 2 h before determination of body water compartments. ACZ led to a significant 1.7-liter reduction in total body water (3.4%). A significant reduction in extracellular water of 3.3 liters is partitioned as the loss of total body water and a significant increase in intracellular water (1.6 liters). Venous blood pH and plasma HCO3- were significantly reduced 0.09 units and 5.9 mM, respectively, with ACZ. Plasma protein concentration was increased, but plasma osmolality did not change. Plasma Na+, K+, and Cl- concentrations were not different with ACZ, but total electrolyte content was significantly decreased 45.2, 1.17, and 44.1 meq, respectively, for all three. Urine K+, HCO3-, flow, and pH were elevated after ACZ treatment, whereas Na+ and Cl- were the same as placebo levels. In conclusion, acute clinical doses of ACZ reduce body fluid compartments, leading to a moderate isosmotic hypovolemia with an intracellular volume expansion as well as metabolic acidosis.
Human auditory brain stem response during induced hyperthermia
Authors: Kohshi K. , Konda N.
Published: December 2017

A continuous monitoring of auditory brain stem response (ABR) and esophageal (Tes) and rectal temperatures (Tre) were recorded in male undergraduate subjects to investigate a relationship between the interpeak latencies (IPLs) and core temperature. The average change of Tes (36.8-39.5 degrees C) was achieved by immersing the subjects in a temperature-controlled water bath (30-42 degrees C). The IPLs became shorter with the rise in body temperature and were correlated with both Tes and Tre. The average slopes for IPL(I-III) and IPL(I-V) were significantly higher than those for IPL(III-V). The present study of humans indicated that changes of IPL(I-III) and IPL(I-V) were 0.11 and 0.16 ms, respectively, per 1 degree C change in core temperature during induced hyperthermia.
Effects of ligation and embolization on Kf and multiple tracer measurements in dog lungs
Authors: Bradley J. D. , Parker R. E. , Harris T. R. , Overholser K. A.
Published: December 2017

In isolated blood-perfused dog lungs, the capillary filtration coefficient (Kf) and the permeability-surface area product of urea (PS) were measured to determine their responses to two different methods of altering filtration area: lobe ligation (LL, n = 5) and glass bead embolization (GBE, n = 4) during constant perfusion rates (700 +/- 45 ml/min). When two of three lobes were ligated, Kf decreased (1.36 +/- 0.13 to 0.58 +/- 0.23 g.min-1.cmH2O-1; P less than 0.05), but PS did not change (2.02 +/- 0.4 to 1.71 +/- 0.3 ml/s). Kf per gram of perfused blood-free dry lung weight was unchanged by LL (0.051 +/- 0.17 to 0.052 +/- 0.18 g.min-1.cmH2O-1), indicating that surface area per gram measured by Kf remained the same. However, PS per gram dry lung doubled (0.07 +/- 0.016 to 0.146 +/- 0.06 ml/s; P less than 0.05) after LL, suggesting that recruitment occurred in the remaining lobe. When three lobes were embolized with 200-microns glass beads (0.48 +/- 0.01 g beads/kg body wt), PS decreased (2.1 +/- 0.22 to 0.94 +/- 0.09 ml/s; P less than 0.05), but Kf was not altered (1.01 +/- 0.17 to 1.04 +/- 0.18 g.min-1.cmH2O-1). The constancy of Kf after GBE implies that the vascular pressure increase during the Kf measurement was transmitted to both blocked and flowing vessels and thereby measured the same filtration area before and after GBE. PS decreased significantly after GBE because of a loss of perfused surface area by the beads blocking flow in small arterial vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Exponential fitting of pressure-volume curves: confidence limits and sensitivity to noise
Authors: Eidelman D. H. , Ghezzo H. , Bates J. H.
Published: December 2017

It has recently become common to model the static pressure-volume curve of the lung as a monoexponential function of the form V = A - Be-KP, where V is volume and P is transpulmonary pressure. The parameters A, B, and particularly K have been employed as descriptors of the intrinsic mechanical properties of the lung. The purpose of the present study was to investigate the sensitivities of A, B, and K to noise in measurements of P and V and to incompleteness of data. Using Monte-Carlo simulation, we found that the presence of typical levels of noise in P led to biased estimates of K and that the 95% confidence intervals about A and K were large compared with the parameter values themselves. These effects were increased as points were systematically removed from either end of the data set. These findings show that values of K estimated from PV data are difficult to interpret without accompanying confidence intervals.
Distribution of blood flow during exercise after blood volume expansion in swine
Authors: Norton K. I. , Delp M. D. , Jones M. T. , Duan C. , Dengel D. R. , Armstrong R. B.
Published: December 2017

To study the distribution of blood flow after blood volume expansion, seven miniature swine ran at high speed (17.6-20 km/h, estimated to require 115% of maximal O2 uptake) on a motor-driven treadmill on two occasions: once during normovolemia and once after an acute 15% blood volume expansion (homologous whole blood). O2 uptake, cardiac output, heart rate, mean arterial pressure, and distribution of blood flow (with radiolabeled microspheres) were measured at the same time during each of the exercise bouts. Maximal heart rate was identical between conditions (mean 266); mean arterial pressure was elevated during the hypovolemic exercise (149 +/- 5 vs. 137 +/- 6 mmHg). Although cardiac output was higher and arterial O2 saturation was maintained during the hypervolemic condition (10.5 +/- 0.7 vs. 9.3 +/- 0.6 l/min), O2 uptake was not different (1.74 +/- 0.08 vs. 1.74 +/- 0.09 l/min). Mean blood flows to cardiac (+12.9%), locomotory (+9.8%), and respiratory (+7.5%) muscles were all elevated during hypervolemic exercise, while visceral and brain blood flows were unchanged. Calculated resistances to flow in skeletal and cardiac muscle were not different between conditions. Under the experimental conditions of this study, O2 uptake in the miniature swine was limited at the level of the muscles during hypervolemic exercise. The results also indicate that neither intrinsic contractile properties of the heart nor coronary blood flow limits myocardial performance during normovolemic exercise, because both the pumping capacity of the heart and the coronary blood flow were elevated in the hypervolemic condition.
Interaction of chemical and high vascular pressure injury in isolated canine lung
Authors: Townsley M. I. , Lim E. H. , Sahawneh T. M. , Song W.
Published: December 2017

Because both chemical and mechanical insults to the lung may occur concomitantly with trauma, we hypothesized that the pressure threshold for vascular pressure-induced (mechanical) injury would be decreased after a chemical insult to the lung. Normal isolated canine lung lobes (N, n = 14) and those injured with either airway acid instillation (AAI, n = 18) or intravascular oleic acid (OA, n = 25) were exposed to short (5-min) periods of elevated venous pressure (HiPv) ranging from 19 to 130 cmH2O. Before the HiPv stress, the capillary filtration coefficient (Kf,c) was 0.12 +/- 0.01, 0.27 +/- 0.03, and 0.31 +/- 0.02 ml.min-1.cmH2O-1 x 100 g-1 and the isogravimetric capillary pressure (Pc,i) was 9.2 +/- 0.3, 6.8 +/- 0.5, and 6.5 +/- 0.3 cmH2O in N, AAI, and OA lungs, respectively. However, the pattern of response to HiPv was similar in all groups: Kf,c was no different from the pre-HiPv value when the peak venous pressure (Pv) remained less than 55 cmH2O, but it increased reversibly when peak Pv exceeded 55 cmH2O (P less than 0.05). The reflection coefficient (sigma) for total proteins measured after pressure exposure averaged 0.60 +/- 0.03, 0.32 +/- 0.04, and 0.37 +/- 0.09 for N, AAI, and OA lobes respectively. However, in contrast to the result expected if pore stretching had occurred at high pressure, in all groups the sigma measured during the HiPv stress when Pv exceeded 55 cmH2O was significantly larger than that measured during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung mechanics and airway reactivity in sheep during development of oxygen toxicity
Authors: Fukushima M. , King L. S. , Kang K. H. , Banerjee M. , Newman J. H.
Published: December 2017

The causes of respiratory distress in O2 toxicity are not well understood. The purpose of this study was to better define the airway abnormalities caused by breathing 100% O2. Sheep were instrumented for measurements of dynamic compliance (Cdyn), functional residual capacity by body plethysmography (FRC), hemodynamics, and lung lymph flow. Each day Cdyn and FRC were measured before, during, and after the application of 45 min continuous positive airway pressure (CPAP) at 15 cmH2O. The amount of aerosol histamine necessary to reduce Cdyn 35% from baseline (ED35) was measured each day as was the response to aerosol metaproterenol. Cdyn decreased progressively from 0.083 +/- 0.005 (SE) 1/cmH2O at baseline to 0.032 +/- 0.004 l/cm H2O at 96 h of O2. Surprisingly, FRC did not decrease (1,397 +/- 153 ml at baseline vs. 1,523 +/- 139 ml at 96 h). The ED35 to histamine did not vary among days or from air controls. Metaproterenol produced a variable inconsistent increase in Cdyn. We also measured changes in Cdyn during changes in respiratory rate and static pressure-volume relationships in five other sheep. We found a small but significant frequency dependence of compliance and an increase in lung stiffness with O2 toxicity. We conclude that in adult sheep O2 toxicity reduces Cdyn but does not increase airway reactivity. The large reduction in Cdyn in O2 toxicity results from processes other than increased airway reactivity or reduced lung volume, and Cdyn decreases before the development of lung edema.
Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium
Authors: Vogelmeier C. , Buhl R. , Hoyt R. F. , Wilson E. , Fells G. A. , Hubbard R. C. , Schnebli H. P. , Thompson R. C. , Crystal R. G.
Published: December 2017

In a variety of lung diseases the respiratory epithelial surface must contend with an increased burden of neutrophil elastase (NE). One candidate for augmenting epithelial anti-NE protection is the secretory leukoprotease inhibitor (SLPI). In vitro evaluation demonstrated that 96 +/- 1% of the recombinant SLPI (rSLPI) molecules were capable of inhibiting NE, with an association rate constant of 7.1 +/- 0.1 X 10(6) M-1.s-1. Evaluation of rSLPI after in vitro and in vivo aerosolization showed that aerosolization did not alter rSLPI. Aerosolization of a single dose of 50 mg rSLPI to sheep resulted in a fourfold increase of the anti-NE capacity in epithelial lining fluid (ELF) at 3 h, with a half-life in ELF of 12 h. After aerosolization some rSLPI appeared in lung lymph. Simultaneous aerosolization of rSLPI and recombinant alpha 1-antitrypsin (rAAT) demonstrated a molar ratio of the concentration in lymph to the concentration in ELF 3 h after the aerosol eightfold higher for rAAT than for rSLPI. Overall, these observations demonstrate that it is feasible to use aerosolized rSLPI to directly augment the anti-NE capacity of the lung, particularly on the pulmonary epithelial surface.
Determinants of transdiaphragmatic pressure in dogs
Authors: Hubmayr R. D. , Sprung J. , Nelson S.
Published: December 2017

We measured the transdiaphragmatic pressure (Pdi) during bilateral phrenic nerve stimulation and evaluated the determinants of its change with lung volume, chest wall geometry, and respiratory system impedance in supine dogs. Four rows of radiopaque markers were sewn onto muscle bundles of the costal and crural diaphragm between their origin on the central tendon and their insertion on the rib cage and spine. The length of the diaphragm (L) was determined from the projection images of marker rows using biplane fluoroscopy. Measurements were made at lung volumes between total lung capacity and functional residual capacity before and after the infusion of Ringer lactate solution into the abdominal cavity. In contrast to relaxation, during tetanic stimulation the active lengths of the muscle bundles were similar at all volumes, but the diaphragm assumed different shapes. Although the small differences in active muscle length with volume and liquid loads are consistent with only small changes in muscle force output, Pdi varied by a factor of greater than or equal to 5. There was no single L/Pdi curve that fitted all data during 50-Hz stimulations. We conclude that under these experimental conditions Pdi is not a unique measure of the force produced by the diaphragm and that lung volume, chest wall geometry, and respiratory system impedance are important determinants of the mechanical efficiency of the diaphragm as a pressure generator.
Attenuated Hering-Breuer inflation reflex 4 years after pulmonary vagal denervation in ponies
Authors: Forster H. V. , Pan L. G. , Flynn C. , Bisgard G. E.
Published: December 2017

The purpose of this study was to determine whether there was any recovery of the Hering-Breuer inflation reflex in ponies between 2-4 wk and 3-4 yr after hilar nerve denervation (HND). Under anesthesia and before HND, airway occlusion after a 3-liter lung inflation lengthened the subsequent occluded breath by nearly 10 times the control breath duration. Between 2 wk and 3-4 yr after HND, this maneuver increased the duration of the occluded breath by only 2.5 times the control breath duration. Also under anesthesia, the airway was occluded at end expiration. This maneuver increased the duration of the subsequent inspiratory effort by 71% in hilar nerve intact ponies but by only 20-25% 2-4 wk and 3-4 yr after HND. For both tests, the pre- and post-HND differences were statistically significant (P less than 0.05), but there were no significant differences (P greater than 0.10) between 2-4 wk and 3-4 yr post-HND. In awake ponies, at rest and during mild and moderate treadmill exercise, breathing frequency was generally lower and inspiratory time was greater after relative to before HND. The inspiratory time-to-total cycle duration ratio was consistently increased by 0.10-0.15 after HND (P less than 0.05). There was no significant change in this ratio between 2-4 wk and 3-4 yr post-HND (P greater than 0.10). We conclude that the surgical procedure for HND used in this study does not permit any significant reinnervation, and there are no significant changes within the ventilatory control system to compensate for loss of hilar nerve afferents.
No evidence for mesothelial cell contact across the costal pleural space of sheep
Authors: Albertine K. H. , Wiener-Kronish J. P. , Bastacky J. , Staub N. C.
Published: December 2017

Pleural space width was measured by four morphological approaches using either frozen hydrated or freeze-substituted blocks of chest wall and lung. Anesthetized sheep were held in the lateral (n = 2), sternal recumbent (n = 2), or vertical (head-up; n = 2) position for 30 min. The ribs and intercostal muscles were excised along a 20-cm vertical distance of the chest wall region, which was sprayed with liquid Freon 22, cooled with liquid nitrogen, to facilitate the fastest possible freezing of the visceral and parietal pleura. We measured pleural space width in frozen hydrated blocks by reflected-light and low-temperature scanning electron microscopy and in freeze-substituted, fixed, and embedded tissue blocks by light and transmission electron microscopy. We combined the data from the two groups of sheep held sternally recumbent and vertical because the results were comparable. The average arithmetic mean data for pleural space width determined by reflected-light analysis for samples near the top (18.5 microns) and bottom (20.3 microns) of the chest, separated by 15 cm of lung height, varied inversely with lung height (n = 4; P less than 0.009). The average harmonic mean data demonstrated a similar gravity-dependent gradient (17.3 and 18.8 microns, respectively; P less than 0.02). Therefore a slight vertical gradient of approximately -0.10 micron/cm of lung height was found for costal pleural space width. Pleural space width in the most dependent recesses, such as the costodiaphragmatic recess, reached 1–2 mm. We never found any contacts between the visceral and parietal pleura with either of the frozen hydrated preparations. No points of mesothelial cell contact were revealed in the light- and transmission electron microscopic views of the freeze-substituted tissue, despite an apparent narrower pleural space associated with the tissue-processing steps. We conclude that the pleural space has a slightly nonuniform width, contacts if they occur must be very infrequent, and pleural liquid clearance is probably facilitated by liquid accumulation in dependent regions where lymphatic pathways exist.
Preservation of oscillations in postocclusive reactive hyperemia
Authors: Schmedtje J. F. , Eckberg D. L.
Published: December 2017

Oscillations in skin blood flow (SkBF) during postocclusive reactive hyperemia are believed to be due to locally mediated events in the microcirculation. We characterized the activity of these oscillations in nine healthy young men who underwent 0, 10, and 40 Torr of lower body negative pressure (LBNP). Postocclusive SkBF was estimated in both forearms simultaneously in a stable thermal environment with laser-Doppler velocimetry. Periodic behavior of SkBF was characterized by frequency-domain power spectral analysis. LBNP at 40 Torr increased heart rate, decreased forearm blood flow, and decreased postocclusive SkBF amplitude but did not change the periodicity of SkBF in the frequency response range that is characteristic of postischemic SkBF oscillations (0.11 +/- 0.04 Hz). We observed that LBNP did not alter the frequency response of the postocclusive SkBF as quantified in the periodogram, even though the amplitude of the SkBF was markedly diminished as a part of the general decrease in arm blood flow. We found inferential evidence for a disseminated common pacemaker mechanism that performs similarly at distant sites. We conclude that the LBNP baroreflex-mediated modulation of SkBF reduces the amplitude but does not change the frequency behavior of postocclusive SkBF. We propose on the basis of our findings that the preservation of vasomotion suggests that this phenomenon is an adaptation to the ischemic changes induced by disruption of blood flow.
Multireceptor activation of the pulmonary chemoreflex
Authors: Strong E. B. , Green J. F.
Published: December 2017

Schertel et al. (J. Appl. Physiol. 61: 1237–1240, 1984) reported that pulmonary C fibers initiate the prompt apnea followed by rapid shallow breathing evoked by pulmonary arterial injections of capsaicin. However, doubt has remained as to whether these changes in breathing pattern are induced exclusively by direct stimulation of pulmonary C fibers or whether secondary stimulation of slowly adapting pulmonary stretch receptors by capsaicin-induced reflex bronchoconstriction also contributes to the response. To determine the contribution of this secondary mechanism to changes in breathing pattern, we evoked the pulmonary chemoreflex in spontaneously breathing dogs before and after blockade of muscarinic receptors with atropine. Right atrial injections of capsaicin before the administration of atropine induced a classical pulmonary chemoreflex, i.e., apnea, hypotension, and bradycardia followed by rapid shallow breathing and bronchoconstriction. After atropine, all components of the pulmonary chemoreflex induced by right atrial injections of capsaicin remained intact except bronchoconstriction. However, the absolute magnitude of the change in each component of the reflex except apnea was significantly attenuated. We conclude that the classic pulmonary chemoreflex is a complex phenomenon initiated primarily by stimulation of pulmonary C fibers but significantly influenced by secondary stimulation of slowly adapting pulmonary stretch receptors.
Attenuating effects of intrathecal clonidine on the exercise pressor reflex
Authors: Hill J. M. , Kaufman M. P.
Published: December 2017

We tested the hypothesis that intrathecal injection of clonidine, an alpha 2-adrenergic agonist, attenuated the reflex cardiovascular and ventilatory responses to static muscular contraction in cats. Before clonidine (1 microgram in 0.2 ml), contraction-induced reflex increases (n = 10) in mean arterial pressure and ventilation averaged 25 +/- 3 mmHg and 359 +/- 105 ml/min, respectively, whereas after clonidine these increases averaged 8 +/- 4 mmHg and 200 +/- 114 ml/min, respectively (P less than 0.05). Clonidine had no effect on the heart rate response to contraction. Intrathecal injection of yohimbine (10 micrograms; n = 5), an alpha 2-adrenergic antagonist, but not prazosin (10 micrograms; n = 3), an alpha 1-adrenergic antagonist, prevented the attenuating effects of clonidine on the reflex pressor and ventilatory responses to contraction. Our findings were not due to the spread of clonidine to the medulla, because the reflex pressor and ventilatory responses to contraction were not attenuated by injection of clonidine (1 microgram) onto the medulla (n = 3). In addition, our findings were not due to a clonidine-induced withdrawal of sympathetic outflow, because intrathecal injection of clonidine (1 microgram) did not attenuate increases in arterial pressure and ventilation evoked by high-intensity electrical stimulation of the cut central end of the sciatic nerve (n = 5). Furthermore, our findings were not due to a local anesthetic action of clonidine, because application of this agent to the dorsal roots had no effect on the discharge of group IV muscle afferents. We conclude that stimulation of alpha 2-adrenergic receptors in the spinal cord attenuates the reflex pressor and ventilatory responses to static contraction.
Pulmonary vascular response to endothelin in rats
Authors: Raffestin B. , Adnot S. , Eddahibi S. , Macquin-Mavier I. , Braquet P. , Chabrier P. E.
Published: December 2017

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of quasi-static tissue hysteresis to the dynamic alveolar pressure-volume loop
Authors: Robatto F. M. , Romero P. V. , Fredberg J. J. , Ludwig M. S.
Published: December 2017

We obtained dynamic and flow-interrupted (quasi-static) pressure-volume loops from the lungs of anesthetized paralyzed open-chest mongrel dogs by measuring tracheal flow and pressure and alveolar pressure (PA) in three different regions using alveolar capsules. We used continuous tidal ventilation to obtain dynamic PA-volume loops and used the single-breath-interrupter technique to construct quasi-static pressure-volume loops for the same tidal volume (VT). We used three different VT's (15 and 20 ml/kg and inspiratory capacity) under control conditions and a VT of 15 ml/kg after methacholine-induced bronchoconstriction. We found that quasi-static hysteresis was negligible under control conditions for VT of 15 and 20 ml/kg. Quasi-static hysteresis became more important (36 +/- 11% of the corresponding dynamic PA-volume loop) during inspiratory capacity ventilation and after induced bronchoconstriction (27 +/- 12% of the corresponding dynamic PA-volume loop). We conclude that during tidal breathing near functional residual capacity "true" static hysteresis is negligible and that purely viscoelastic processes can explain lung mechanical behavior. For higher volume ventilation and after methacholine-induced constriction, quasi-static hysteresis accounted for a more important portion of dynamic tissue hysteresis. This suggests either that a more complex model, e.g., one including plastic processes, should be invoked or that the lung exhibits longer viscoelastic time constants as peak distending stresses become greater.
Effect of increased inspired CO2 on respiratory dead space in ponies
Authors: Lowry T. F. , Forster H. V. , Forster M. A. , Murphy C. L. , Brice A. G. , Pan L. G.
Published: December 2017

The objective of the present study was to determine the effect of elevated inspired CO2 on respiratory dead space (VD) of 12 normal, 8 carotid body-denervated (CBD), 7 hilar nerve-denervated (HND), and 6 CBD+HND ponies. The Fowler technique was used to determine VD on a breath-by-breath basis while the ponies breathed room air and inspired CO2 at 3 and 6%. During room air breathing, tidal volume (VT) and VD were greater in HND ponies than in normal and CBD ponies (P less than 0.05), and VT was less and VD/VT was greater after CBD than before CBD. For all groups. VD, VT, and breathing frequency (f) increased and VD/VT decreased significantly (P less than 0.01) with increasing inspired CO2. During CO2 breathing, VT and VD were higher (P less than 0.05) in the HND ponies than in all other groups, the decrease (P less than 0.05) in VD/VT was greatest in the CBD+HND group, and f was lower in the HND and HND+CBD than in the normal and CBD ponies. In addition, when inspired CO2 was increased from 0 to 6%, the decrease in VD/VT was greater and the increase in arterial PCO2 was less (P less than 0.05) after CBD than before CBD. For 70% of the ponies in all groups, VD increased linearly with increases in VT; for most of the remainder, VD tended to plateau at higher values of VT.
Abdominal muscle activity during CO2 rebreathing in sleeping neonates
Authors: Praud J. P. , Egreteau L. , Benlabed M. , Curzi-Dascalova L. , Nedelcoux H. , Gaultier C.
Published: December 2017

Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.
Impedance electrodes positioned on proximal portions of limbs quantify fluid compartments in dogs
Authors: Scheltinga M. R. , Helton W. S. , Rounds J. , Jacobs D. O. , Wilmore D. W.
Published: December 2017

Body resistance and reactance to the conduction of an alternating electrical current were measured using electrodes attached to distal and proximal portions of limbs in anesthetized dogs. Body impedance was calculated from these measurements obtained at 30-min time intervals during a control period and after intravenous administration of 0.9% saline. Extracellular (ECW) and total body water (TBW) were determined by bromide and heavy water dilution techniques, respectively. Baseline impedance obtained from proximal electrodes was related to ECW (r = 0.95, P less than 0.001) and TBW (r = 0.80, P less than 0.02). After saline infusion, proximal electrodes detected a significant fall in impedance (P less than 0.001), whereas distal electrodes did not (P = 0.06). Furthermore, ECW and TBW could be estimated from the drop of proximal impedance after this bolus infusion (r = 0.82, P less than 0.02, and r = 0.86, P less than 0.01, respectively), but not from distal impedance measurements. Proximally placed impedance electrodes are superior to traditionally used distal electrodes for assessment of body fluid changes in the dog.
Mechanisms by which endothelin 1 induces pulmonary vasoconstriction in the rabbit
Authors: Mann J. , Farrukh I. S. , Michael J. R.
Published: December 2017

To investigate the mechanisms by which endothelin 1 (ET-1) causes pulmonary vasoconstriction, we studied the effect of synthetic ET-1 on pulmonary vascular tone in the buffer-perfused isolated rabbit lung. In nanomolar concentrations (1.2–8 nM), ET-1 causes a dose-dependent increase in pulmonary arterial pressure that persists for greater than or equal to 1 h (increase in pressure 19 +/- 2 mmHg with ET-1 vs. 2 +/- 1 with vehicle, P less than 0.0001). Reduction of calcium availability with verapamil, cadmium, or a calcium-free buffer significantly blunts the increase in pressure caused by ET-1. Pretreatment with a calcium-free buffer plus the chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N′, N′-tetraacetic acid (EGTA) completely eliminates the vasoconstriction. Three different inhibitors of protein kinase C, phloretin, staurosporine, and dihydrosphingosine, significantly diminish the response to ET-1. Indomethacin and a thromboxane synthase inhibitor partially decrease the response to the highest concentration of ET-1. Isoproterenol and dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP) are significantly more effective in preventing the vasoconstriction caused by ET-1 than are nitroprusside and guanosine 5′-cyclic monophosphate (cGMP) analogues. ET-1 in doses of 1.2–8 nM is a potent pulmonary vasoconstrictor in the isolated rabbit lung. ET-1 appears to cause pulmonary vasoconstriction by increasing calcium entry and by activating protein kinase C. Vasodilators that increase cAMP are substantially more effective in preventing the increase in pressure than are drugs that increase cGMP.
Relative bronchoconstrictor activity of neurokinin A and neurokinin A fragments in guinea pigs
Authors: Shore S. A. , Drazen J. M.
Published: December 2017

We examined the effect of rapid intravenous infusion of neurokinin A (NKA) and selected COOH-terminal NKA fragments on pulmonary conductance (GL) and dynamic compliance in anesthetized mechanically ventilated guinea pigs. The rank order of the dose of peptide required to reduce GL by 50% (ED50GL) was NKA = NKA2–10 = NKA3–10 = NKA4–10 less than NKA5–10 much less than NKA6–10. The time course of bronchoconstriction induced by NKA2–10, NKA3–10, and NKA4–10 was similar to that induced by NKA, whereas NKA5–10 and NKA6–10 each had a shorter duration of action than NKA for a similar induced maximal change in GL. To determine whether degradation of these NKA fragments by neutral endopeptidase (NEP) modulates their bronchoconstrictor activity as it does for native NKA, we examined the effect of the NEP inhibitor SCH32615 on NKA3–10-, NKA5–10-, and NKA6–10-induced changes in GL. We have previously reported that the ED50GL for NKA was approximately 20-fold lower in animals pretreated with SCH32615 (1 mg/kg) than in control guinea pigs. SCH32615 caused a 16-fold decrease in ED50GL for NKA3–10 (P less than 0.001) but had no effect on airway responses to NKA5–10 or NKA6–10. The results demonstrate that the magnitude and duration of bronchoconstriction induced by potential aminopeptidase degradation products of NKA are similar to those of the native peptide. Aminopeptidases do not, therefore, have the capacity to modulate the bronchoconstriction induced by this peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of increased acceleration on regional pleural pressure in dogs
Authors: Lai-Fook S. J. , Brown L. V. , Maudgalya V. S. , Knapp C. F. , Ganesan S.
Published: December 2017

The variation of pleural pressure was measured in anesthetized spontaneously breathing dogs subjected to increased acceleration (0–4 G) in a centrifuge. Two groups of animals were studied. In one group, the resultant acceleration was in a direction either ventral-to-dorsal (+Gx) or dorsal-to-ventral (-Gx), with a relatively small residual cranial-to-caudal acceleration. In the other group, the resultant acceleration was either cranial-to-caudal (+Gz) or caudal-to-cranial (-Gz), with a relatively small residual dorsal-to-ventral acceleration. Pleural liquid pressure (Ppl) was measured by two rib capsules that were separated by 7–9 cm and oriented either in the dorsal-to-ventral or cranial-to-caudal direction. At functional residual capacity, Ppl in the nondependent lung region became more negative when the acceleration was in the +Gx or +Gz direction. Thus the lung would be susceptible to damage that results from overexpansion in these acceleration directions. By contrast, acceleration in the -Gx or -Gz direction produced values of Ppl at functional residual capacity that were positive. Thus, in these acceleration directions, the respiratory muscles must provide greater force during inspiration to overcome lung compression before lung ventilation can occur. The Ppl gradients with respect to the acceleration directions increased approximately in proportion to acceleration in the +Gx, -Gx, and -Gz directions but remained relatively constant in the +Gz direction.
Effect of carbohydrate supplements and water on exercise metabolism in the heat
Authors: Yaspelkis B. B. , Ivy J. L.
Published: December 2017

Carbohydrate (CHO) supplements of different concentrations were compared with water to determine their effects on thermal regulation and plasma volume maintenance while subjects exercised for 2 h in the heat and to determine their impact on carbohydrate utilization. Trained cyclists (n = 12) rode at 48.8 +/- 0.8% maximal O2 consumption in an environmental chamber maintained at 33.0 +/- 0.1 degree C and 51.7 +/- 1.4% relative humidity on three separate occasions. During each exercise bout the subjects received 3 ml/kg body wt of H2O, a 2.0% glucose polymer (LC) solution, or an 8.5% glucose polymer (HC) solution every 15 min. Muscle biopsies from the vastus lateralis were obtained before and after the H2O and HC trials only. Rectal temperature and heart rate, but not O2 consumption, rose from the 10- to 120-min period of exercise. No differences among treatments were found for these variables. There were also no significant differences among treatments for percent changes in plasma volume and blood volume. Plasma glucose and insulin were unchanged during the H2O and LC trials but were significantly elevated during the HC trial. In addition, CHO oxidation was significantly greater during the HC trial than during the H2O trial from 60 to 120 min of exercise. However, the reduction in muscle glycogen during the HC trial (206.5 +/- 23.6 mumol/g protein) was significantly less (P less than 0.05) than during the H2O trial (342.3 +/- 41.9 mumol/g protein).(ABSTRACT TRUNCATED AT 250 WORDS)
Does the pressor response to ischemic exercise improve blood flow to contracting muscles in humans?
Authors: Joyner M. J.
Published: December 2017

The purpose of this study was to determine in humans 1) the gain for the reflex pressor response that occurs when perfusion pressure to rhythmically contracting muscles is reduced and 2) whether the pressor response improves blood flow to the contracting muscles. Six normal subjects performed light, moderate, and heavy rhythmic forearm contractions (30/min) with the forearm enclosed in a Plexiglas box. Pressure in the box was increased 10 mmHg each minute up to 50 mmHg to reduce transmural pressure in the arterial system of the forearm. Mean arterial pressure (MAP) was measured continuously. During light exercise no reflex increase in MAP occurred until box pressure was 50 mmHg. During moderate and heavy exercise MAP began to increase with only 10- to 20-mmHg increases in box pressure. The slope of this increase was 3.5–3.9 mmHg per 10 mmHg of box pressure (approximately 60% of that in dogs). In a further study on six subjects a deep vein draining the active forearm muscles was cannulated and deep venous O2 saturation measured to assess how a 50-mmHg increase in box pressure and subsequent reflex increase in MAP altered blood flow to the contracting muscles during heavy rhythmic exercise. The increase in box pressure reduced blood flow to contracting forearm muscles by 20–25% and was followed by a 19-mmHg increase in MAP that did not appear to improve perfusion of the active muscles. This finding was unexpected, because studies in dogs suggest that the pressor response to rhythmic exercise with restricted muscle blood flow can improve perfusion of the active muscles.(ABSTRACT TRUNCATED AT 250 WORDS)