bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between frequency and amplitude dependence in the lung: a nonlinear block-structured modeling approach
Authors: Suki B. , Zhang Q. , Lutchen K. R.
Published: December 2017

During lung constriction, there is an increase in both the frequency and tidal volume (VT) dependences of lung tissue resistance (Rti) and elastance (Eti). This suggests that 1) significant alterations take place in the mechanisms contributing to both the linear and nonlinear characteristics of lung tissues; and 2) the frequency and VT dependences of Rti and Eti are coupled. We examined these issues for the case of sine wave and special pseudorandom inputs by utilizing the theory of nonlinear block-structured systems. Two basic model structures were considered: the Hammerstein and the Wiener structures. The Hammerstein structure is a cascade connection of a nonlinear zero-memory (N) system and a linear dynamic process (L). This structure predicts that frequency and VT dependences of Rti and Eti are decoupled. The Wiener structure is an inverse cascade of these two blocks (i.e., L-N) in which the frequency and VT dependences of Rti and Eti are coupled. These two structures were combined with a nonlinear airway compartment and fitted to measured airway opening and alveolar capsule pressure-flow time domain data in dogs before and after histamine-induced constriction. The best lung model was a linear airway compartment combined with a Wiener structure consisting of a constant-phase linear tissue impedance in cascade with a polynomial nonlinearity, suggesting that frequency and VT dependences of Rti and Eti are indeed coupled during control and constricted conditions. Moreover, histamine caused much larger changes in the linear tissue parameters than in the nonlinear coefficients.
Oxidation of exogenous [13C]galactose and [13C]glucose during exercise
Authors: Leijssen D. P. , Saris W. H. , Jeukendrup A. E. , Wagenmakers A. J.
Published: December 2017

The present study examined the oxidation of exogenous galactose or glucose during prolonged submaximal cycling exercise. Eight highly trained volunteers exercised on two occasions on a cycle ergometer at 65% of maximal workload for 120 min, followed by a 60-min rest period and a second exercise bout of 30 min at 60% maximal workload. At random, subjects ingested a 8% galactose solution to which an [1–13C]galactose tracer was added or a 8% glucose solution to which an [U-13C]glucose tracer was added. Drinks were provided at the end of the warm-up period (8 ml/kg) and every 15 min (2 ml/kg) during the first 120 min of the test. Blood and breath samples were collected every 30 and 15 min, respectively, during the test. The exogenous carbohydrate (CHO) oxidation was calculated from the 13CO2/12CO2 ratio and CO2 production of the expired air. Peak exogenous CHO oxidation during exercise for galactose and glucose was 0.41 +/- 0.03 and 0.85 +/- 0.04 g/min, respectively. Total CHO and fat oxidation were not significantly different between the treatments. Forty-six percent of the ingested glucose was oxidized, whereas only 21% of the ingested galactose was oxidized. As a consequence, more endogenous CHO was utilized with galactose than with glucose (124.4 +/- 6.7 and 100.1 +/- 3.6 g, respectively). These results indicate that the oxidation rate of orally ingested galactose is maximally approximately 50% of the oxidation rate of a comparable amount of orally ingested glucose during 120 min of exercise.
In vitro responses of lung arteries to acute hypoxia after NO synthase blockade or chronic hypoxia
Authors: Teng G. Q. , Barer G. R.
Published: December 2017

Responses to hypoxia of lung arteries (200–350 microns) from control (C) and chronically hypoxic (CH) rats were compared in a myograph before and after blockade of NO synthase with NG-nitro-L-arginine methyl ester (L-NAME). After precontraction with prostaglandin F2 alpha (PGF2 alpha), hypoxia caused a four-phase tension change: brief dilation, transient contraction, prolonged dilation, and slow contraction (we studied the first three phases). In CH rats, the first dilation and first contraction were significantly reduced. After L-NAME, the first dilation was reduced in C rats and abolished in CH rats; thus the first phase is attributable to NO release and is affected by chronic hypoxia. The first contractile phase was significantly reduced by L-NAME in C but not in CH rats, where it was small. Thus NO synthase inhibition inhibits hypoxic constriction in isolated vessels, whereas it enhances hypoxic constriction in perfused lungs. The third dilator phase was unaffected by chronic hypoxia; it was increased after L-NAME in CH rats. Thus, in vitro, responses to hypoxia are complex; there is a balance between two dilator and two constrictor processes.
Analysis of low-frequency lung impedance in rabbits with nonlinear models
Authors: Peslin R. , Saunier C. , Duvivier C. , Marchand M.
Published: December 2017

Lung mechanics was studied in six paralyzed tracheotomized rabbits ventilated with a specially devised computer-controlled ventilator. The target flow waveform contained noninteger multiple frequencies ranging from 0.83 to 6–10 Hz and met a neither-sum-nor-difference criterion to minimize the effects of nonlinearity (B. Suki and K. Lutchen. IEEE Trans. Biomed. Eng. 39: 1142–1151, 1992). The actual flow, however, contained harmonics of the two lowest frequencies. Measurements were performed at mean airway pressure (Paw) levels of 8 and 12 hPa and during histamine-induced bronchoconstriction. Smooth impedance curves were observed in unchallenged rabbits at low mean Paw levels. In contrast, unrealistic impedance fluctuations, suggestive of cross talk from the unwanted frequency components in the flow input, were seen at high mean Paw levels and during acute bronchoconstriction. Model analysis was performed by using the actual flow signal as an input to various nonlinear models. The impedance fluctuations observed at high mean Paw levels were well simulated by a model featuring a volume-dependent elastance, and those observed after histamine were almost perfectly reproduced by a model where resistance increased with the reciprocal of lung volume. We conclude that impedance data biased by cross talk may provide useful information on the presence and nature of respiratory system nonlinearities.
Effect of capillary pressure and lung distension on capillary recruitment
Authors: Godbey P. S. , Graham J. A. , Presson R. G. , Wagner W. W. , Lloyd T. C.
Published: December 2017

To investigate the effect of capillary pressure and alveolar distension on capillary recruitment, we used video-microscopy to quantify capillary recruitment in individual subpleural alveolar walls. Canine lobes were perfused with autologous blood either while inflated by positive airway pressure or while inflated by negative intrapleural pressure in the intact thorax with airway pressure remaining atmospheric. Low flow rates minimized the arteriovenous pressure gradient (< 5 mmHg), permitting capillary pressure estimation by averaging these pressures. Capillary pressure was varied stepwise from airway pressure to 30 mmHg above airway pressure. Capillary recruitment always began as capillary pressure exceeded airway pressure. At low positive airway pressures, the capillaries of the excised lobes opened suddenly over a narrow pressure range. AT higher airway pressures and in the intact thorax, recruitment occurred over a wide range of capillary pressures. We conclude that capillary perfusion begins when intracapillary pressure just exceeds alveolar pressure but that further increases in capillary pressure recruit capillaries depending on tension in the alveolar wall, whether imposed by positive airway pressure or by gravity when the lung is suspended in an intact thorax.
Pulmonary vascular impedance response to hypoxia in dogs and minipigs: effects of inhaled nitric oxide
Authors: Maggiorini M. , Brimioulle S. , De Canniere D. , Delcroix M. , Wauthy P. , Naeije R.
Published: December 2017

The pig has been reported to present with a stronger hypoxic pulmonary vasoconstriction (HPV) than many other species, including dogs. We investigated [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (Ppao)] vs. pulmonary blood flow (Q) relationships and pulmonary vascular impedance (PVZ) spectra in nine minipigs and nine weight-matched dogs. The animals were anesthetized and ventilated in hyperoxia [inspired O2 fraction 0.4] or hypoxia (inspired O2 fraction 0.12). PVZ was computed from the Fourier series for Ppa and Q. In hyperoxia, the pigs had a higher Ppa (26 +/- 1 vs. 16 +/- 1 mmHg), a higher first-harmonic impedance (Z1), and a more negative low-frequency phase angle but no different characteristic impedance (Zc) compared with the dogs at the same Q. Hypoxia in the dogs increased (Ppa-Ppao) at all levels of Q studied by an average of 2 mmHg but did not affect Z1 or Zc. Hypoxia in the pigs increased (Ppa-Ppao) at all levels of Q by an average of 13 mmHg and increased Z1 and Zc. Inhaled NO (150 ppm) reversed the hypoxia-induced changes in (Ppa-Ppao)/Q plots and PVZ in the dogs and pigs. However, differences in (Ppa-Ppao)/Q plots and PVZ between the dogs and pigs in hyperoxia and hypoxia were not affected by inhaled NO. We conclude 1) that minipigs present with an elevated pulmonary vascular resistance and impedance in hypoxia more than in hyperoxia and 2) that baseline differences in pulmonary hemodynamics between dogs and minipigs are structural rather than functional.
ET-3 is extracted by and induces potent vasoconstriction in human splanchnic and renal vasculatures
Authors: Weitzberg E. , Hemsen A. , Lundberg J. M. , Ahlborg G.
Published: December 2017

To investigate splanchnic and renal vascular effects and elimination of endothelin-3 (ET-3), ET-3 (10 pmol.kg-1.min-1 iv for 20 min) was given to six healthy male volunteers. Arterial plasma ET-3-like immunoreactivity (ET-3-Li) increased 10-fold to 111 +/- 31 pmol/l (P < 0.01). The initial half-life of plasma ET-3-Li determined in three subjects was 1.7 +/- 0.2 min. The fractional extraction of ET-3-Li was 68 +/- 7% in the splanchnic and 63 +/- 4% in the renal vascular beds. Mean arterial blood pressure fell from 86 +/- 4 to 94 +/- 4 mmHg (10%) (P < 0.05). Splanchnic and renal blood flows fell by 43 +/- 3% (P < 0.05) and 29 +/- 4% (P < 0.05), respectively, during the infusion. Splanchnic and renal vascular resistances rose by 92 +/- 22% (P < 0.05) and 58 +/- 7% (P < 0.05). In conclusion, ET-3 infusion in humans induces splanchnic and renal vasoconstriction of similar magnitude as previously shown during endothelin-1 infusion, presumably by ETB receptor activation. Plasma ET-3 is efficiently extracted in the splanchnic and renal vascular regions.
Bubbles in circulating blood: stabilization and simulations of cyclic changes of size and content
Authors: Van Liew H. D. , Burkard M. E.
Published: December 2017

Surface tension, blood pressure, and inherent unsaturation due to O2 metabolism promote diffusion of gases out of bubbles in the bloodstream. We review the mechanisms that can overcome the absorptive tendencies so small spherical bubbles can persist. One general type of stabilizer is a mechanical structure at the gas-liquid interface that can support a negative pressure so that gases inside can be in diffusion equilibrium with their counterparts outside; one possibility for mechanical stabilizers are surfactant films. We show that a slowly permeating gas is analogous to a mechanical stabilizer; it allows equilibration of other gases inside-to-outside by diluting the gases inside. By using numerically solved equations based on physics of diffusion, we demonstrate how nonrigid stabilized bubbles change size as they move through the circulatory system. In small pulmonary vessels, the bubbles enlarge because blood pressure is low, there is no inherent unsaturation, and O2 and N2 diffuse from lung gas into the bubble; these gases diffuse out again in the systemic circulation.
Intrapulmonary CO2-rise time and ventilation in ducks
Authors: Furilla R. A. , Bernstein M. H.
Published: December 2017

Many investigators have reported finding intrapulmonary chemoreceptors (IPCs) in several species of birds and reptiles; however, the role of IPCs in ventilatory control in birds has not been identified. This study was undertaken to assess the role of intrapulmonary CO2 dynamics on the control of breathing. Ducks were unidirectionally ventilated, and their breathing was monitored with a pneumotachograph connected to a personal computer. A gas-mixing system controlled by the computer adjusted the rate of rise of airway CO2 concentration ([CO2]). On inspiration, the computer removed CO2 from the ventilating gas for 1.5 s, followed by a controlled [CO2] rise. Breathing frequency was directly related to the rate of rise of airway [CO2]. Tidal volume, however, was not correlated with CO2-rise time but was related to the peak airway [CO2]. This response is likely mediated by IPCs because preventing airway [CO2] from falling during inspiration immediately altered that breath. An increase in CO2 production (as in exercise) will lead to an increase in the rate of CO2 excretion into the lung. The resulting alteration of breathing frequency would thus maintain acid-base balance. The observed response, therefore, may represent a link between ventilation and metabolism.
Dehydration reduces cardiac output and increases systemic and cutaneous vascular resistance during exercise
Authors: Gonzalez-Alonso J. , Mora-Rodriguez R. , Below P. R. , Coyle E. F.
Published: December 2017

This investigation determined the manner in which the cardiovascular system copes with the dehydration-induced reductions in cardiac output (Q) during prolonged exercise in the heat. On two separate occasions, seven endurance-trained subjects (maximal O2 consumption 4.70 +/- 0.41 l/min) cycled in the heat (35 degrees C) for 2 h, beginning at 62 +/- 2% maximal O2 consumption. During exercise, they randomly received either 0.2 liter of fluid and became dehydrated by 4.9 +/- 0.2% of their body weight [i.e., dehydration trial (DE)] or 3.6 +/- 0.4 liter of fluid and replaced 95% of fluid losses [i.e., euhydration trial (EU)]. During the 10- to 120-min period of EU, Q, mean arterial pressure (MAP), systemic vascular resistance (SVR), cutaneous vascular resistance (CVR), and plasma catecholamines did not change while esophageal temperature stabilized at 38.0 +/- 0.1 degrees C. Conversely, after 120 min of DE, Q and MAP were reduced 18 +/- 3 and 5 +/- 2%, respectively, compared with EU (P < 0.05). This was associated with a significantly higher SVR (17 +/- 6%) and plasma norepinephrine concentration (50 +/- 19%, P < 0.05). In addition, CVR was also significantly higher (126 +/- 16 vs. 102 +/- 6% of 20-min value; P < 0.05) during DE despite a 1.2 +/- 0.1 degrees C greater esophageal temperature (P < 0.05). In conclusion, significant reductions in Q are accompanied by significant increases in SVR and plasma norepinephrine and a slight although significant decline in MAP. The cutaneous circulation participates in this systemic vasoconstriction as indicated by increases in CVR despite significant hyperthermia.
Repeated force production and metabolites in two medial gastrocnemius muscle compartments of the rat
Authors: De Ruiter C. J. , De Haan A. , Sargeant A. J.
Published: December 2017

The most proximal and distal motor nerve branches in the rat medial gastrocnemius innervate discrete muscle compartments dominated by fast-twitch oxidative and fast-twitch glycolytic fibers, respectively. The functional consequences of the difference in oxidative capacity between these compartments were investigated. Wistar rats were anesthetized with pentobarbital sodium (90 mg/kg ip). Changes in force of both compartments during 21 isometric contractions (train duration 200 ms, stimulation frequency 120 Hz, 3 s between contractions) were studied in situ with and without blood flow. Without blood flow, force and phosphocreatine declined to a greater extent in the proximal than the distal compartment compared with the run with intact flow. After the protocol without blood flow, when flow was restored, the time constants for force recovery (which were closely associated to the recovery of phosphocreatine) were 37 +/- 7 (SD) (proximal compartment) and 148 +/- 20 s (distal compartment). It was concluded that the proximal compartment had a four times higher oxidative capacity and, therefore, a superior ability for repeated force production.
Cutaneous vascular and sudomotor responses to isometric exercise in humans
Authors: Crandall C. G. , Musick J. , Hatch J. P. , Kellogg D. L. , Johnson J. M.
Published: December 2017

To identify whether isometric handgrip exercise (IHG) affects cutaneous vasoconstrictor and/or active vasodilator activities, seven subjects (6 men and 1 woman) performed 30% maximal voluntary contraction of a forearm under normothermic (1 bout) and hyperthermic (2 bouts) conditions. Skin blood flow was indexed by laser-Doppler flowmetry at a contralateral forearm site at which adrenergic vasoconstrictor function was blocked by iontophoresis of bretylium tosylate (BT) and therefore only has active vasodilation as a mechanism for reflex control. Skin blood flow was also monitored at an adjacent untreated site. Cutaneous vascular conductance (CVC) was calculated from the flow signal and noninvasive blood pressure. CVC was normalized to the value obtained from maximal vasodilation at that site. Sweat rate (SR) was measured at the same locations. During normothermia, IHG did not affect CVC at the control or BT-treated sites, nor did IHG affect SR (P > 0.05). The second bout of IHG in hyperthermia evoked significant reductions in CVC at the untreated (69.4 +/- 3.4 to 58.9 +/- 2.5% of maximum, P < 0.05) and BT-treated sites (75.4 +/- 6.1 to 64.4 +/- 6.2% of maximum, P < 0.05), whereas SR significantly increased (0.62 +/- 0.16 to 0.70 +/- 0.17 mg.cm-2.min-1, P < 0.05). These findings uniquely show that, in hyperthermia, IHG reduces active vasodilator activity while at the same time sudomotor activity is increasing. This suggests independent control of these effectors.
Respiratory response to CO2 in the hypocapnic range in awake humans
Authors: Patrick W. , Webster K. , Puddy A. , Sanii R. , Younes M.
Published: December 2017

The response of respiratory motor output to CO2 in the hypocapnic range (< 36 Torr PCO2) in the absence of hypoxemia is not well characterized in awake normal humans. We induced hypocapnia with hyperoxia in 16 normal volunteers by placing them on a volume-cycled ventilator in the assist mode. Subjects were not aware of the purpose of the study. All subjects continued rhythmic breathing despite high tidal volumes and severe hypocapnia (approximately 25 Torr alveolar PCO2). Inspired CO2 fraction was increased in steps, and changes in respiratory motor output were quantitated from changes in airway pressure at constant volume and flow, changes in respiratory rate, and change in rate of decline in airway pressure before triggering (dP/dt). There was a significant increase in respiratory muscle pressure, but not in respiratory rate, from 26 to 36 Torr PCO2. The slope of the response increased gradually from 26 to 41 Torr PCO2. Respiratory rate significantly increased only above 36 Torr. We conclude that the response to PCO2 in the hypocapnic range is basically nonlinear with no clear CO2 threshold and the CO2 responsiveness extends well below eupneic CO2 levels.
Evidence for central chemoreception in the midline raphe
Authors: Bernard D. G. , Li A. , Nattie E. E.
Published: December 2017

We injected acetazolamide (AZ; 5 x 10(-6) M; 1 nl; n = 14), its inactive analogue 2-acetylamino-1,3,4-thiadiazole-5-sulfon-t-butylamide (5 x 10(-5) M; n = 6), or mock cerebrospinal fluid (n = 5) into the caudal raphe in the midline brain stem of anesthetized paralyzed ventilated rats. These AZ injections have been shown to produce a focal region of tissue acidosis with a radius < 350 microns and are used as a probe for sites of central chemosensitivity. Compared with control injections, AZ injection into the raphe, as demonstrated by anatomic analysis of injection location, significantly increased the amplitude of the integrated phrenic neurogram over 10-40 min. Not all raphe injections produced such a response. AZ injections identified as responders (n = 8 of 14) increased integrated phrenic amplitude 43.3 +/- 10.7% (SE) of baseline 20 min after the injection. We conclude that the midline caudal raphe contains sites of ventilatory chemoreception.
Rebound increase in fetal breathing movements after 24-h prostaglandin E2 infusion in fetal sheep
Authors: Hollingworth S. A. , Jones S. A. , Adamson S. L.
Published: December 2017

We investigated the hypothesis that the precipitous decrease in prostaglandin E2 (PGE2), a potent inhibitor of fetal breathing, from high plasma concentrations during labor causes a rebound stimulation of breathing without newborn concentrations falling below prelabor fetal values. Fetal plasma PGE2 concentration was gradually increased from 384 +/- 82 (SE) pg/ml in 2-h steps [0 (baseline), 1.5, 3, and 6 micrograms/min] to labor levels (1,230 +/- 381 pg/ml at 6 micrograms/min) and then was maintained for 24 h (n = 9). PGE2 at 1.5 micrograms/min significantly decreased breathing incidence [from 42 +/- 4 (baseline) to 14 +/- 4%] and breath amplitude (from 2.1 +/- 0.5 to 1.5 +/- 0.2 arbitrary units) and increased breath-to-breath interval (from 1.16 +/- 0.07 to 1.56 +/- 0.06 s). No further dose-related changes were observed. During the first 2 h after PGE2 infusion was stopped, PGE2 concentration returned to basal (352 +/- 64 pg/ml) but breathing incidence and amplitude were significantly higher (74 +/- 8% and 2.4 +/- 0.3 arbitrary units, respectively) and breath-to-breath interval was significantly lower (0.95 +/- 0.10 s) than were basal levels. Changes arose within approximately 15 min and were maintained for at least 4 h. Breathing did not change significantly in the saline-treated group (n = 7). Results suggest that the rapid decrease in plasma PGE2 concentration at birth promotes the onset of breathing.
Changes in dietary protein intake fail to prevent decrease in muscle growth induced by severe hypoxia in rats
Authors: Bigard A. X. , Douce P. , Merino D. , Lienhard F. , Guezennec C. Y.
Published: December 2017

Muscle growth, fiber size, muscle and liver glycogen, plasma hormones, and muscle glutamine concentration were evaluated in rats chronically exposed (26 days) to a simulated hypobaric altitude (HA; 6,000 m) and fed diets of varying protein concentrations (10, 20, or 40 g protein/100 g of dry matter; LP, MP, and HP, respectively). Values were compared with those measured in animals maintained under normobaric conditions and either fed ad libitum (SL groups) or pair fed equivalent quantities of food consumed by HA animals (PF groups). There was marked anorexia in response to HA exposure for all protein diets (P < 0.001). A specific effect of hypoxia on the decrease in muscle growth has been identified by comparison of the values of the muscle weight-to-body weight ratio between HA and PF groups (P < 0.05 for all dietary protein levels). Plasma insulin concentrations were lower in HA than in SL and PF rats (P < 0.05). Liver glycogen was significantly decreased by exposure to HA (P < 0.001) and high dietary protein content (P < 0.005). Hypoxia per se and decreased food intake had additive effects on soleus muscle glycogen concentrations. An increase in muscle glutamine was observed in rats fed the LP diet in comparison with the MP diet, especially in SL and PF groups (P < 0.05). These results clearly demonstrate that 1) hypobaric hypoxia per se decreases growth rate in rats and 2) increasing the dietary protein intakes in rat had no effect on the depression of muscle growth related to high altitude but had deleterious effects on glycogen deposition in liver and fast muscle.
Splenic contraction, catecholamine release, and blood volume redistribution during diving in the Weddell seal
Authors: Hurford W. E. , Hochachka P. W. , Schneider R. C. , Guyton G. P. , Stanek K. S. , Zapol D. G. , Liggins G. C. , Zapol W. M.
Published: December 2017

The spleen of the Weddell seal (Leptonychotes weddelli) may contract and inject red blood cells (RBCs) into the peripheral circulation during diving, but evidence for this hypothesis is indirect. Accordingly, we measured splenic dimensions by ultrasonography, plasma catecholamine concentrations, hemoglobin concentration, and hematocrit in five Weddell seals before and after intravenous epinephrine during halothane anesthesia and while awake at the surface after voluntary dives. Spleen size was reduced immediately after epinephrine injection or after the seal surfaced. Within the first 2 min after the seal surfaced, cephalocaudal splenic length was 71 +/- 2% (mean +/- SD; P < 0.05) and splenic thickness was 71 +/- 4% (P < 0.05) of the maximal resting values. Splenic size increased (half-time = 6-9 min) after the seal surfaced and was inversely correlated with plasma epinephrine and norepinephrine concentrations. Hemoglobin concentration increased from 17.5 +/- 5.3 g/dl (measured during general anesthesia) to 21.9 +/- 3.7 g/dl (measured in the first 2 min after surfacing). At these same times, the hematocrit increased from 44 +/- 12 to 55 +/- 8%. These values decreased (half-time = 12-16 min) after the seal surfaced. We estimate 20.1 liters of RBCs were sequestered at rest, presumably in the spleen, and released either on epinephrine injection or during diving. Catecholamine release and splenic contraction appear to be an integral part of the voluntary diving response of Weddell seals.
Methacholine-induced bronchoconstriction and airway smooth muscle in the guinea pig
Authors: Opazo Saez A. , Du T. , Wang N. S. , Martin J. G.
Published: December 2017

We examined the role of airway smooth muscle (ASM) as a determinant of the site and extent of methacholine (MCh)-induced airway narrowing in anesthetized and mechanically ventilated guinea pigs. The sites of airway narrowing and ASM were determined in animals (n = 4) bronchoconstricted to 75, 60, 40, or 15% of the maximal lung resistance (RL,max) induced by aerosolized MCh and compared with a saline-challenged animal. The median luminal area of each animal was significantly inversely correlated to the percentage of RL,max (r = -0.95; P < 0.01). However, there was no correlation between the degree of narrowing of any given airway and the quantity of ASM of any given airway. The relationship between the amount of ASM and responsiveness to MCh was studied in different animals (n = 13). The range of the concentration of MCh required to reach 50% of RL,max (EC50) varied by 254-fold, but the RL,max had only a 3.6-fold range. There was no correlation between RL,max and ASM. However, there was a correlation between the log EC50 and ASM (r = -0.541; P<0.05) in intraparenchymal cartilaginous airways. In conclusion, morphometric measurements of airway narrowing are correlated with pulmonary resistance. Variability in the quantity of ASM does not appear to be a determinant of the heterogeneity of airway narrowing or of maximal bronchoconstriction among normal guinea pigs. However, the sensitivity to MCh is associated with differences in the amount of ASM in intraparenchymal cartilaginous airways.
Dynamics of respiratory gas exchange during exercise after correction of congenital heart disease
Authors: Reybrouck T. , Mertens L. , Kalis N. , Weymans M. , Dumoulin M. , Daenen W. , Gewillig M.
Published: December 2017

In pediatric exercise testing, conventional measures of aerobic exercise function such as maximal O2 uptake or the ventilatory anaerobic threshold (VAT) use only one value for the assessment of exercise capacity. We studied a more comprehensive approach to evaluate aerobic exercise function by analyzing the steepness of the slope of CO2 production (VCO2) vs. VO2 above the VAT (S3). This was calculated in 32 patients operated on for congenital heart disease [16 for transposition of the great arteries (TGA) and 16 for tetralogy of Fallot (TF)] and was compared with 16 age-matched controls (nl). The results show that the reproducibility of this new assessment method was excellent (coefficient of variation for S3: 8.6%). S3 was significantly steeper (P<0.05) in the patients (1.31 +/- 0.22 for TGA and 1.28 +/- 0.16 for TF) compared with the nl (1.10 +/- 0.22). Also, the difference between S3 and the slope of VCO2 vs. VO2 below the VAT was significantly higher in the patients (0.37 +/- 0.22 for TGA and 0.31 +/- 0.10 for TF) than in controls (0.22 +/- 0.06). The steeper slopes were associated with lower than normal values for VAT and O2 during exercise. It is concluded that the analysis of the steepness of the slope of CO2 is a sensitive, reproducible, and objective approach to evaluate the integrative cardiopulmonary response to exercise. It complements the assessment of a subnormal VAT by reflecting the extent of anaerobic metabolism.
Effect of intracellular pH on ferret pulmonary arterial smooth muscle cell calcium homeostasis and pressure
Authors: Farrukh I. S. , Hoidal J. R. , Barry W. H.
Published: December 2017

In this study, we investigated the role of Na+/H+ antiport in regulating cytosolic (intracellular) pH (pHi) in isolated and cultured ferret pulmonary arterial smooth muscle cells (PSMC). We also studied the effects of modulating pHi on the cytosolic (intracellular) calcium concentration ([Ca2+]i) in the PSMC and on the pulmonary arterial pressure (Ppa) of isolated ferret lungs. pHi was modulated by the NH4Cl washout method. To eliminate the contribution of Cl-/HCO3- exchangers, the PSMC and isolated lungs were perfused in HCO3- free buffer. Blocking the Na+/H+ antiporter decreased baseline pHi and prevented the recovery from NH4Cl washout-induced intracellular acidosis. Intracellular alkalinization caused an initial transient increase in both [Ca2+]i and Ppa that were dependent on extracellular Ca2+ entry. Maintaining cytosolic alkalinization caused another increase in Ppa that was not associated with an increase in [Ca2+]i. Intracellular acidosis also caused an increase in [Ca2+]i and Ppa. The cytosolic acidosis-induced increase in [Ca2+]i and Ppa were mediated by both extracellular Ca2+ influx and release of stored intracellular Ca2+. Cytosolic acidosis also appears to have a direct effect on the smooth muscle contractile elements. Both cytosolic alkalosis and acidosis increased vascular reactivity.
Rates of free fatty acid appearance and fat oxidation in healthy younger and older men
Authors: Toth M. J. , Arciero P. J. , Gardner A. W. , Calles-Escandon J. , Poehlman E. T.
Published: December 2017

Alterations in the mobilization and oxidation of fat may partially account for age-related alterations in body composition. To investigate age-related alterations in fat metabolism, we compared basal rate of appearance of free fatty acids (FFAapp) and total body fat oxidation as measured by infusions of [14C] palmitate and indirect calorimetry, respectively, in 18 younger (23 +/- 1 yr) and 30 older (69 +/- 1 yr) men. We also examined whether age-related differences in body composition, body fat distribution, peak oxygen consumption, dietary intake, and/or fasting insulin levels may explain age-related variation in FFAapp and total body fat oxidation. The FFAapp showed a tendency to be higher in older compared with younger men (1,134 +/- 184 vs. 680 +/- 105 mu mol/min; P = 0.07), whereas total body fat oxidation was similar between groups (257 +/- 25 vs. 222 +/- 9 mu mol/min). The estimated rate of nonoxidative disposal of free fatty acids showed a tendency to be higher in the older (913 +/- 182 mu mol/min) than in younger men (423 +/- 103 mu mol/min; P = 0.06). Fat-free mass was the most significant predictor of FFAapp in younger (r = 0.63; P < 0.01) and older (r = 0.41; P < 0.05) men. These results suggest that older men recruit fatty acids from adipose tissue stores in excess of the energy needs of respiring tissue. However, variation in FFAapp between the age groups could not be explained by differences in body habitus or fasting insulin levels.
TNF-alpha and the pathophysiology of endotoxin-induced acute respiratory failure in sheep
Authors: Perkowski S. Z. , Sloane P. J. , Spath J. A. , Elsasser T. H. , Fisher J. K. , Gee M. H.
Published: December 2017

We studied changes in cardiovascular and pulmonary function during prolonged endotoxemia in conscious sheep. Sheep with chronic lung lymph fistulas received a 12-h infusion of Escherichia coli endotoxin (10 ng x kg-1 x min-1) and allowed to recover for 12 h. Supportive therapies were withheld. Prolonged endotoxemia without volume support caused systemic hypotension associated with reduced cardiac output and increased systemic vascular resistance, pulmonary hypertension, and acute lung injury with progressive respiratory failure. Plasma tumor necrosis factor-alpha (TNF-alpha) concentrations increased transiently. Sustained pulmonary hypertension and increased pulmonary and systemic vascular resistances contributed to a poor outcome in 9 of 34 sheep (26%). Plasma TNF-alpha concentrations were significantly greater in survivors with sustained pulmonary hypertension and in nonsurviving sheep than in surviving sheep without pulmonary hypertension. Endotoxin (1 ng/ml) increased neutrophil expression of TNF-alpha in vitro. Addition of interleukin-6 prevented this response. Synthesis and release of TNF-alpha may be an important proximal event influencing the development of sustained pulmonary hypertension and progressive respiratory failure with endotoxemia. Interleukin-6 may contribute to the phasic nature of the TNF-alpha response.
Pathophysiological effects of hemodilution in chronic mountain sickness in rats
Authors: Du H. K. , Lee Y. J. , Colice G. L. , Leiter J. C. , Ou L. C.
Published: December 2017

We examined the effect of isovolemic hemodilution in a rat model of chronic mountain sickness (CMS). After 30 days at simulated high altitude (5,500 m), Hilltop rats had developed evidence of CMS: severe hypoxemia, polycythemia, and pulmonary arterial hypertension. Isovolemic hemodilution to a mean hematocrit of 46 +/- 5% was well tolerated by both the hypoxia-sensitive Hilltop rats and the companion Madison rat strain that does not develop CMS. After hemodilution, we found no evidence of sustained improvements in ventilation or gas exchange in either strain. Despite the fall in blood viscosity, cardiac output increased only marginally, and pulmonary arterial hypertension persisted in the Hilltop rats. Vascular hindrance increased after hemodilution, preventing a significant decline in pulmonary and systemic vascular resistances in the Hilltop rats. Blood O2 content and the coefficient of O2 delivery fell after hemodilution, but O2 consumption was sustained at a normal level after hemodilution by increasing the extraction fraction in the Hilltop strain. There was systemic hypotension through the first day of hemodilution, but this was the only apparent adverse effect of hemodilution. We conclude that isovolemic hemodilution was well tolerated despite the reduction in tissue O2 delivery. However, hemodilution failed to improve any of the respiratory and cardiovascular manifestations of CMS in Hilltop rats.
Resting metabolic rate is influenced by anxiety in college men
Authors: Schmidt W. D. , O'Connor P. J. , Cochrane J. B. , Cantwell M.
Published: December 2017

The effects of psychological parameters on resting metabolic rate (RMR) have been inadequately researched. The purpose of this study was to investigate relationships between anxiety and RMR. Seventy-nine male college students completed the trait portion (form Y-2) of the State-Trait Anxiety Inventory (C. D. Spielberger, R. L. Gorsuch, R. Lushene, P. R. Vagg, and G. A. Jacobs. Self-evaluation questionnaire (form Y). In: Manual for the State-Trait Anxiety Inventory. Palo Alto, CA, Consulting Psychologists Press, 1983) as a screening. Volunteers whose trait anxiety scores were = or = 1 SD above (52.7 +/- 2.7, n = 9) or below (26.5 +/- 3.0, n = 11) the male college student normal values (38 +/- 9) participated in the study. Fat-free weight was assessed using a seven-site skinfold equation (A. S. Jackson and M. L. Pollock. Phys. Sports Med. 13: 76-90, 1985). Resting metabolism was measured (Sensormedics metabolic cart model 2900) at two separate trials (1-2 wk apart) in the early morning after a 12-h fast and 36 h postexercise. An analysis of covariance with fat-free weight as the covariate revealed a significantly greater (P < 0.005) RMR in the high trait anxious group than in the low trait anxious group. State anxiety (form Y-1) assessments made before and after each RMR measurement revealed a significant main effect of group such that state anxiety was higher in the high trait anxious than in the low trait anxious group for both trials before and after RMR measurement. Moreover, a significant (P < 0.003) main effect for the time factor was found showing that state anxiety was reduced after the RMR procedure. The results of this study show that a statistically significant portion of the variance in RMR can be accounted for by individual differences in anxiety.
Effects of coca chewing on hormonal and metabolic responses during prolonged submaximal exercise
Authors: Favier R. , Caceres E. , Koubi H. , Sempore B. , Sauvain M. , Spielvogel H.
Published: December 2017

The effects of coca chewing on prolonged submaximal exercise responses were investigated in chronic coca chewers and compared with a group of nonchewers. At rest, coca chewing during a 1-h period was followed by a significant increase in blood glucose, free fatty acid, and norepinephrine concentrations and a significant reduction in insulin plasma level. During prolonged (1-h) submaximal (65-70% peak O2 uptake) exercise, chewers displayed a significantly greater adrenergic activation (as evidenced by a higher level of plasma epinephrine) and an increased use of fat (as evidenced by a lower respiratory exchange ratio). The gradual increase in oxygen uptake (O2 drift) commonly observed during prolonged exercise was blunted in coca chewers. This blunting in O2 drift is not related to coca-induced changes in ventilatory or lactate responses to exercise but could possible be related to an enhanced glucose utilization by chewers during the late phase of exercise. The present results provide experimental evidence of the physiological effects of coca chewing that could explain the better ability of coca users to sustain strenuous work for an extended period of time.
Hyperdynamic sepsis depresses circulatory compensation to normovolemic anemia in conscious rats
Authors: Morisaki H. , Sibbald W. , Martin C. , Doig G. , Inman K.
Published: December 2017

This study was designed to determine whether sepsis modifies the ability to preserve vital organ O2 delivery (QO2) across a clinically relevant range of hematocrits. Ninety rats were randomly allocated to cecal ligation and perforation (CLP) or a sham (Sham) procedure. With the use of rat plasma, rat whole blood, or packed rat red blood cells, respectively, randomization into three different hematocrit subgroups followed: low (21-28%), middle (33-40%), and high (45-52%). Organ blood flow values (Q) were measured by the radioactive microsphere technique, and organ QO2 values were calculated. Twenty-four hours after laparotomy, the hematocrit grouping had not modified the interorgan distribution of Q or QO2 in either the CLP or Sham rats. To characterize overall metabolic O2 reserve, rats were then exposed to hypoxia (inspired O2 fraction, 0.08) for 20 min. Whereas cardiac output increased significantly during hypoxia in all experimental groups, myocardial QO2 failed to increase in the low hematocrit Sham subgroup and fell significantly in both the middle- and low-hematocrit CLP subgroups. There was also a lesser redistribution of QO2 away from the small intestine in the low-hematocrit compared with the high-hematocrit CLP subgroup. We conclude that myocardial QO2 is more effectively maintained in septic hypoxic rats if the hematocrit is maintained at levels =45%.
Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles
Authors: Tsakiridis T. , Wong P. P. , Liu Z. , Rodgers C. D. , Vranic M. , Klip A.
Published: December 2017

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.
Carnitine metabolism in human muscle fiber types during submaximal dynamic exercise
Authors: Constantin-Teodosiu D. , Howell S. , Greenhaff P. L.
Published: December 2017

The effect of prolonged exhaustive exercise on free carnitine and acetylcarnitine concentrations in mixed-fiber skeletal muscle and in type I and II muscle fibers was investigated in humans. Needle biopsy samples were obtained from the vastus lateralis of six subjects immediately after exhaustive one-legged cycling at approximately 75% of maximal O2 uptake from both the exercised and nonexercised (control) legs. In the resting (control) leg, there was no difference in the free carnitine concentration between type I and II fibers (20.36 +/- 1.25 and 20.51 +/- 1.16 mmol/kg dry muscle, respectively) despite the greater potential for fat oxidation in type I fibers. However, the acetylcarnitine concentration was slightly greater in type I fibers (P < 0.01). During exercise, acetylcarnitine accumulation occurred in both muscle fiber types, but accumulation was greatest in type I fibers (P < 0.005). Correspondingly, the concentration of free carnitine was significantly lower in type I fibers at the end of exercise (P < 0.001). The sum of free carnitine and acetylcarnitine concentrations in type I and II fibers at rest was similar and was unchanged by exercise. In conclusion, the findings of the present study support the suggestion that carnitine buffers excess acetyl group formation during exercise and that this occurs in both type I and II fibers. However, the greater accumulation of acetylcarnitine in type I fibers during prolonged exercise probably reflects the greater mitochondrial content of this fiber type.
Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk
Authors: Ishihara H. , McNally D. S. , Urban J. P. , Hall A. C.
Published: December 2017

The intervertebral disk is routinely subjected to compressive loads that alter with posture and muscle activity and can produce pressures = 2 MPa in human lumbar disks in vivo (A. Nachemson and G. Elfstrom. Scand. J. Rehabil. Med. 2, Suppl. 1:1-40, 1979; A. Nachemson and J. M. Morris. J. Bone Jt. Surg. Am. Vol. 46A: 1077-1092, 1964). We measured the effect of load on hydrostatic pressures in bovine caudal disks. With increase in applied load, pressure increased linearly in the nucleus and inner annulus. The resting pressure measured after slaughter (0.19 +/- 0.05 MPa) and the pressure at failure (34 MPa, estimated from the vertebrae/disk segment failure load of 7,430 +/- 590 N) define the limits that can occur in vivo. Because hydrostatic pressure influences matrix synthesis in articular cartilage, we have examined the effects of pressures in the range 1-10 MPa applied for 20 s or 2 h on proteoglycan synthesis in bovine caudal and human lumbar intervertebral disks in vitro. In the nucleus pulposus and inner annulus of bovine disks, application of hydrostatic pressure in the range of 1-7.5 MPa for only 20 s stimulated matrix synthesis over the following 2 h at atmospheric pressure. The maximum stimulation in the bovine disks was seen in the inner annulus after application of 2.5 MPa, where proteoglycan synthesis rates doubled. Exposure to 2.5 MPa also stimulated synthesis in the nucleus pulposus of human disks taken at surgery, whereas 7.5 MPa inhibited synthesis in five out of six specimens. With 2-h continuous exposure to the same levels of pressure, no stimulation was seen in the nucleus of bovine disks, and significant stimulation was only observed at 5.0 MPa in the inner annulus. Exposure to 10 MPa for either 20 s or 2 h inhibited proteoglycan synthesis in these regions of the disks. In contrast, in the outer annulus, where loading does not lead to a rise in hydrostatic pressure in vivo, there was no significant response to hydrostatic pressure over the range of 1-10 MPa in bovine or human disks.
Effect of lung volume on the respiratory action of the canine sternomastoid
Authors: Muza S. R. , Criner G. J. , Kelsen S. G.
Published: December 2017

We tested the hypothesis that because the resting length of the canine sternomastoid (SM) muscles is relatively insensitive to lung volume change, the SM may maintain its inspiratory force generation regardless of lung volume. The relationships between SM pre- and postcontraction in situ fiber lengths and SM-produced inspiratory pressure generation [i.e., esophageal (Pes)] and rib cage displacements were examined in adult supine anesthetized dogs at residual volume (RV), functional residual capacity, and total lung capacity. SM muscle contraction was produced by isolated bilateral supramaximal electrical stimulation during hyperventilation-induced apnea. In all animals, SM contraction produced negative change in Pes (i.e., an inspiratory action). Passively increasing lung volume from RV to total lung capacity decreased (P < or = 0.01) the SM-produced Pes by -66 +/- 4% but had a relatively small effect on SM in situ pre- and postcontraction fiber length (< 3%). Whereas SM contraction at RV produced a cranial displacement of the sternum and increased the upper rib cage cross-sectional area, passively elevating lung volume diminished the SM-produced expansion of the upper rib cage. Hyperinflation did not increase the impedance of the sternum to cranial displacement during SM contraction, suggesting that hyperinflation caused a dissociation between the mechanical action of the sternum and the upper rib cage. These results suggest that mechanical dissociation of the ribs and sternum may diminish the contribution of the SM to inspiratory volume generation when breathing is done from elevated end-expiratory lung volumes.