bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a chronic aortopulmonary shunt on pulmonary hemodynamics in piglets
Authors: De Canniere D. , Stefanidis C. , Brimioulle S. , Naeije R.
Published: December 2017

Systemic-to-pulmonary shunting in growing pigs has been proposed as an experimental model of high-flow pulmonary hypertension associated with congenital heart defects. We investigated multipoint pulmonary arterial pressure (Ppa) vs. cardiac output (Q) plots and pulmonary vascular impedance spectra in 13 piglets aged approximately 4 mo and ventilated alternatively in hyperoxia (inspired O2 fraction 0.4) and in hypoxia (inspired O2 fraction 0.12). The measurements were done 8 wk after either an anastomosis between the thoracic aorta and the pulmonary trunk (n = 7 piglets) or a sham operation (n = 6). Cardiac output was altered by a manipulation of venous return. In the sham-operated piglets, hypoxia increased Ppa by an average of 12 mmHg over the entire range of Q studied, from 60 to 120 ml/kg, and increased both 0 Hz (Z0) and characteristic (Zc) pulmonary vascular impedance. In the shunted piglets compared with the sham-operated piglets in hyperoxia, Ppa was increased by an average of 5–6 mmHg at all levels of Q studied, from 60 to 120 ml/kg (P < 0.01), and Zc was also increased (P < 0.01), whereas Z0 was unchanged. In the shunted piglets, hypoxia increased Ppa at all levels of Q studied only to an average of 3 mmHg, and neither Z0 nor Zc was altered by hypoxia. We conclude that an aortopulmonary shunt of 2-mo duration in growing pigs increases both pulmonary vascular resistance and impedance and is associated with a blunting of pulmonary vascular reactivity to hypoxia.
Force-velocity and power characteristics of rat soleus muscle fibers after hindlimb suspension
Authors: McDonald K. S. , Blaser C. A. , Fitts R. H.
Published: December 2017

The effects of 1, 2, and 3 wk of hindlimb suspension (HS) on force-velocity and power characteristics of single rat soleus fibers were determined. After 1, 2, or 3 wk of HS, small fiber bundles were isolated, placed in skinning solution, and stored at -20 degrees C until studied. Single fibers were isolated and placed between a motor arm and force transducer, functional properties were studied, and fiber protein content was subsequently analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Additional fibers were isolated from soleus of control and after 1 and 3 wk of HS, and fiber type distribution and myosin light chain stoichiometry were determined from SDS-PAGE analysis. After 1 wk of HS, percent type I fibers declined from 82 to 74%, whereas hybrid fibers increased from 10 to 18%. Percent fast type II fibers increased from 8% in control and 1 wk of HS to 26% by 3 wk of HS. Most fibers showed an increased unloaded maximal shortening velocity (Vo), but myosin heavy chain remained entirely slow type I. The mechanism for increased Vo is unknown. There was a progressive decrease in fiber diameter (14, 30, and 38%) and peak force (38, 56, and 63%) after 1, 2, and 3 wk of HS, respectively. One week of HS resulted in a shift of the force-velocity curve, and between 2 and 3 wk of HS the curve shifted further such that Vo was higher than control at all relative loads < 45% peak isometric force. Peak absolute power output of soleus fibers progressively decreased through 2 wk of HS but showed no further change at 3 wk.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium transport and fluid balance in lungs from normal and dystrophic hamsters
Authors: Waltz W. F. , Burbach J. A. , Schlenker E. H. , Goodman B. E.
Published: December 2017

Gravimetric and sodium transport characteristics of lungs from BIO 14.6 (dystrophic) hamsters were compared with those of lungs from golden Syrian (normal) hamsters at 30 and 150 days of age. Isolated perfused lungs were used to determine lung permeability and fluid balance differences between normal and dystrophic animals at both ages. Apparent permeability-surface area products for air space-to-vascular space sodium, sucrose, and fluorescein isothiocyanate-labeled dextran fluxes were compared in the four groups of hamsters. Morphometric analysis of fixed lungs of representative hamsters from each group was also performed. Dystrophic hamsters exhibited higher lung wet-to-dry weight ratios than normal hamsters at both ages. Lungs from dystrophic hamsters were less sensitive to inhibition of sodium transport by amiloride than lungs from age-matched normal hamsters. Dystrophic hamster lungs had higher absolute permeabilities of the passively transported solutes, lower permeability values for sodium, and only one-half of the amiloride-sensitive sodium transport of lungs from age-matched normal hamsters. Differences in lung fluid balance between dystrophic and normal hamsters may be related to differences in sodium clearance.
Mechanics of human quadriceps muscle
Authors: Coirault C. , Riou B. , Pery-Man N. , Suard I. , Lecarpentier Y.
Published: December 2017

Mechanics of human quadriceps muscle strips (vastus lateralis; n = 10) were investigated over the whole load continuum. Mechanical experiments were performed at 29 degrees C and in both twitch and tetanus modes. For a given level of isotonic total load (P) and over a large part of the contraction phase, instantaneous velocity (V) was shown to be a unique function of instantaneous length (L), regardless of time and initial length. By considering this time- and initial length-independent mechanical property between instantaneous L and instantaneous V over the whole P continuum, a three-dimensional P-V-L relationship was constructed. Any variations in stimulation conditions modified the time-independent P-V-L diagram. Such modifications in the P-V-L relationship were characteristics of changes in contractile performance. Moreover, characteristics of the P-V relationship were investigated in both twitch and tetanus modes. The curvature of the P-V hyperbola was significantly higher in tetanus at 30 Hz than in twitch mode (P < 0.001). In conclusion, our study indicates that, in human quadriceps muscles, contractility can be defined as the time- and initial length-invariant part of a three-dimensional P-V-L relationship. Moreover, our data are consistent with an increase in economy of force generation in tetanus contractions compared with that in twitches.
Bioenergetic approach to transfer function of human skeletal muscle
Authors: Binzoni T. , Cerretelli P.
Published: December 2017

A mathematical model analogous to Chance's “transfer function” was derived on the basis of the energy consumption principle, which is suitable to describe the energetics of human skeletal muscle during aerobic activity. The implications and the characteristics of this model are that 1) the half time of phosphocreatine (PCr) hydrolysis at the onset of a mechanical constant-load exercise is independent of the imposed charge, 2) the changes of O2 consumption in the muscle at steady state when changing workload are linearly related to PCr concentration, 3) the kinetics of the intracellular oxygen consumption during a rest-to-work transient are influenced by anaerobic glycolysis, 4) it may explain the PCr-time relationship of different muscles types (e.g., skeletal, heart, trained vs. untrained), 5) it allows one to interpret correctly the significance of the oxygen consumption kinetics in the rest-to-work transient at the lung level, and 6) it is conceived for in vivo applications.
Modification of forearm resistance vessels by exercise training in young men
Authors: Green D. J. , Cable N. T. , Fox C. , Rankin J. M. , Taylor R. R.
Published: December 2017

The aim of this study was to determine whether a 4-wk handgrip training program would elicit changes in endothelium-dependent and endothelium-independent vasodilatation in resistance vessels of the human forearm. Minimum vascular resistance after a 10-min ischemic stimulus, an index of peak vasodilator capacity, was also determined. Forearm blood flow response to the endothelium-dependent vasodilator methacholine chloride did not change over the 4-wk-intervention period either in the group undertaking training (n = 11) or in control subjects (n = 6). Similarly, the response to sodium nitroprusside was not influenced by the handgrip training program. Peak vasodilator capacity of the trained forearms significantly increased, whereas no change was evident in the untrained limbs. These results suggest that 4 wk of forearm exercise training enhances peak vasodilator capacity of the vasculature without influencing stimulated activity of the nitric oxide dilator system.
Costal and crural diaphragm function during panting in awake canines
Authors: Easton P. A. , Abe T. , Young R. N. , Smith J. , Guerraty A. , Grassino A. E.
Published: December 2017

During natural panting for thermal regulation, the pattern of activation of the major respiratory muscles, including costal and crural diaphragm segments, is not known. We measured diaphragm segmental length, shortening, and electromyographic (EMG) activity in five chronically implanted canines awake and breathing spontaneously at rest and during a mild dry heat stress. During panting, minute ventilation increased fourfold from 5.07 l/min and respiratory rate increased from 16.9 to 192.8 breaths/min or 3.2 Hz. During panting, end-expiratory length of both costal and crural segments decreased, concurrent with significant increases in end-expiratory EMG. With the onset of panting, tidal costal shortening decreased significantly from 6.29% of end-expiratory length to 3.54%, whereas crural shortening decreased from 6.04 to 2.46%. Meanwhile, segmental EMG tended to increase during panting. During panting, intrabreath costal and crural segmental function revealed differential activation; the costal segment shortened in concert with inspiratory flow, whereas peak crural shortening occurred in expiration, almost 180 degrees out of phase with costal. The divergence in segmental shortening during panting was accompanied by a lesser shift in timing of segmental EMG. In the awake spontaneously panting canine, asynchronous costal and crural shortening may enhance gas mixing in a manner analogous to high-frequency ventilation.
Modulation of bronchial smooth muscle function in horses with heaves
Authors: Yu M. F. , Wang Z. W. , Robinson N. E. , Derksen F. J.
Published: December 2017

Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway obstructive disease heaves. Results were compared with data from historical controls studied by the same personnel in the same laboratory. Rings from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension were measured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electrical field stimulation (EFS) induced little or no relaxation, indicating iNANC dysfunction in horses with heaves. Bronchi from animals with heaves were hyporesponsive to EFS and acetylcholine. Epithelial removal augmented the contractile response of small bronchi to acetylcholine more in animals with heaves than in control animals, indicating an enhanced function of epithelial-derived relaxing factor. In contrast, cyclooxygenase inhibition with meclofenamate (10(-6) M) increased the EFS-induced contraction of small bronchi less in affected horses than in control horses, suggesting a change in prostaglandin production in favor of excitatory prostanoids. We conclude that in the bronchi of horses with heaves; the iNANC function is defective, the response of smooth muscle to cholinergic activation is diminished, the production of epithelial-derived relaxing factor is enhanced, and the inhibitory function of prostanoids is reduced.
Changes in potential controllers of human skeletal muscle respiration during incremental calf exercise
Authors: Barstow T. J. , Buchthal S. D. , Zanconato S. , Cooper D. M.
Published: December 2017

The purpose of this study was to evaluate the consequences of non-linear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (delta GATP). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P(i) metabolism (PCr, P(i), ATP) and pH were followed using 31P-nuclear magnetic resonance spectroscopy. Changes in ADP and delta GATP were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P(i) showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60–100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/- 17.1 microM ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. delta GATP rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through delta GATP under these conditions (incremental exercise by human calf muscle).(ABSTRACT TRUNCATED AT 250 WORDS)
Airway surface liquid thickness as a function of lung volume in small airways of the guinea pig
Authors: Yager D. , Cloutier T. , Feldman H. , Bastacky J. , Drazen J. M. , Kamm R. D.
Published: December 2017

The average thickness and distribution of airway surface liquid (ASL) on the luminal surface of peripheral airways were measured in normal guinea pig lungs frozen at functional residual capacity (FRC) and total lung capacity (TLC). Tissue blocks containing cross sections of airways of internal perimeter 0.188–3.342 mm were cut from frozen lungs and imaged by low-temperature scanning electron microscopy (LTSEM). Measurements made from LTSEM images were found to be independent of freezing rate by comparison of measurements at rapid and slow freezing rates. At both lung volumes, the ASL was not uniformly distributed in either the circumferential or longitudinal direction; there were regions of ASL where its thickness was < 0.1 micron, whereas in other regions ASL collected in pools. Discernible liquid on the surfaces of airways frozen at FRC followed the contours of epithelial cells and collected in pockets formed by neighboring cells, a geometry consistent with a low value of surface tension at the air-liquid interface. At TLC airway liquid collected to cover epithelial cells and to form a liquid meniscus, a geometry consistent with a higher value of surface tension. The average ASL thickness (h) was approximately proportional to the square root of airway internal perimeter, regardless of lung volume. For airways of internal perimeter 250 and 1,800 microns, h was 0.9 and 1.8 microns at FRC and 1.7 and 3.7 microns at TLC, respectively. For a given airway internal perimeter, h was 1.99 times thicker at TLC than at FRC; the difference was statistically significant (P < 0.01; 95% confidence interval 1.29–3.08).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis
Authors: Le Page C. , Ferry A. , Rieu M.
Published: December 2017

We examined whether physical exercise affected the development of an autoimmune response, experimental autoimmune encephalomyelitis (EAE), which is a demyelinating disease leading to paralysis. EAE was inducted on day 0, in rats of both sexes, by injecting them with spinal cord tissue in adjuvant. From days 1 to 10 after injection, exercised rats (n = 55) ran on a treadmill (60–120 min/day) before the onset of the paralytic disease. Clinical signs of the disease (ataxia, paralysis, and body mass loss) were examined in exercised and control rats (n = 54). Three types of EAE were induced: monophasic, acute, and chronic relapsing (CR)-EAE (3 bouts of disease, CR-EAE 1, 2, and 3, separated by remissions). Exercise significantly delayed the onset of CR-EAE 1 (P = 0.001) and the 1st day of maximum severity of CR-EAE 1 (P = 0.001) and CR-EAE 2 (P = 0.002). Moreover, the duration of CR-EAE 1 was significantly decreased in exercised rats compared with control rats (P = 0.004). The peak severity of the different types of EAE was not modified by exercise. The present study indicates that endurance exercise during the phase of induction of EAE diminished lightly only one type of EAE (CR-EAE) and therefore did not exacerbate the autoimmune disease.
Cardiovascular and renal nerve responses to static muscle contraction of decerebrate rabbits
Authors: Wilson L. B. , Dyke C. K. , Pawelczyk J. A. , Wall P. T. , Mitchell J. H.
Published: December 2017

The purpose of this study was to determine whether the biphasic arterial blood pressure responses elicited by static muscle contraction of decerebrate rabbits are mediated, at least in part, by an initial decrease and a subsequent increase in sympathetic outflow. Renal sympathetic nerve activity (RSNA) was used as an index of sympathetic outflow. Static contraction of the triceps surae muscle (n = 14) initially decreased mean arterial blood pressure (MAP) -20 +/- 3 mmHg and heart rate (HR) -15 +/- 5 beats/min (nadir values). After this initial decrease, MAP increased 12 +/- 2 mmHg (peak increase) above baseline and there was a tendency for HR to be elevated (6 +/- 3 beats/min). The changes in RSNA during muscle contraction (n = 6) mirrored the nadir and peak responses of MAP (-50 +/- 9 and 32 +/- 11%). Muscle stretch (n = 11) also evoked similar nadir and peak responses of MAP (-20 +/- 5 and 9 +/- 1 mmHg), HR (-17 +/- 7 and 3 +/- 3 beats/min), and RSNA (-43 +/- 9 and 46 +/- 15%). These data suggest that the initial depressor and subsequent pressor responses elicited by skeletal muscle contraction and stretch are mediated, at least in part, by biphasic changes in sympathetic outflow.
Artifacts associated with acoustic rhinometric assessment of infants and young children: a model study
Authors: Buenting J. E. , Dalston R. M. , Smith T. L. , Drake A. F.
Published: December 2017

The present study was undertaken to determine in model studies whether currently available acoustic rhinometry instrumentation might be used to analyze the nasal cavity configuration of infants and children. A simple nasal cavity model was constructed using eight Lucite inserts that were placed between standard nosepieces provided by the manufacturer and a 35-cm-long polyvinyl chloride pipe closed at its distal end. To simulate the nasal valve, the inserts were 12 mm in length and had apertures ranging in diameter from 2 to 9 mm. A series of experiments was conducted to evaluate the accuracy with which the acoustic rhinometer measured the size of each insert aperture and the configuration of the model system distal to that aperture. Transmission losses caused errors in the area measurement of the insert aperture and the tube distal to the insert. When the insert aperture was < 6 mm in diameter (0.28 cm2), the aperture area was overestimated by > 10%, whereas the area of the distal tube was underestimated by > 10%. As a result of response lags, the acoustic rhinometer also failed to provide an accurate indication of insert length. Finally, oscillation artifacts caused estimates of the distal pipe area to fluctuate. These three systematic errors are described, and their potential impact on acoustic rhinometry in children is discussed.
Cisternal Na+ transport inhibition and the ventilatory response to CO2
Authors: Sullivan M. P. , Adams J. M.
Published: December 2017

When PCO2 rises transiently, glia or neurons may move ions across their cell membranes to restore intracellular pH, in the process changing extracellular pH. Inhibiting ion transport would result in a different extracellular fluid pH (a putative stimulus for the medullary chemoreceptors) and, therefore, in an altered ventilation in response to PCO2. We infused two ion transport inhibitors, amiloride and bumetanide, into the cisterna magna of anesthetized rabbits and compared their ventilatory response to a rebreathing maneuver with sham rabbits receiving no inhibitor. Amiloride (10(-5)-10(-3) M) had no effect; 3 h of 10(-2) M amiloride increased the frequency of breathing and decreased tidal volume but had no net effect on minute ventilation. Bumetanide (10(-3) M) had no effect after 1 h of infusion, but by 3 h it had decreased tidal volume and minute ventilation at 6 and 7% end-tidal CO2 fraction, respectively, during the rebreathe. Three hours of infusion of amiloride and bumetanide did not affect ventilation in a manner consistent with our predictions from previous studies of ionic changes in cerebrospinal fluid. During the 1st h, when neuronal and glial ion transport in the ventrolateral medulla should be inhibited, we found no effect of ion transport inhibition. We conclude that, during the transient hypercapnia of a rebreathing maneuver, Na+/H+ exchange and Na(+)-K(+)-2Cl- cotransport do not play a significant role in immediate rapid pH homeostasis by cellular ion transport in the microenvironment of the medullary chemoreceptors.
Longitudinal distribution of ozone absorption in the lung: comparison of nasal and oral quiet breathing
Authors: Kabel J. R. , Ben-Jebria A. , Ultman J. S.
Published: December 2017

Employing a bolus inhalation system, we noninvasively measured the fraction of inhaled ozone (O3) that is absorbed during a single breath (lambda) as a function of bolus penetration volume into the respiratory tract (Vp). During nasal breathing at a constant respiratory flow of 250 ml/s, lambda increased smoothly as Vp increased with 80% of the inhaled O3 absorbed in the upper airways and 90% absorbed at the distal end of the trachea. Oral breathing caused a distal shift of the lambda-Vp distribution to the extent that absorption in the upper airways was reduced to 50% and inhaled O3 was 90% absorbed only after a bolus reached the 13th bronchial generation. Therefore, an exercise-induced change from nasal to oral breathing can render the distal lung more susceptible to O3 damage because of an elevation in O3 dose. We also found that changing the peak inhaled bolus concentration over a 10-fold range of 0.4–4 ppm O3 did not affect the lambda-Vp distribution. This finding implies that the diffusion and chemical reaction dynamics that dictate O3 absorption are linear processes.
Quantitation of neutrophil migration in acute bacterial pneumonia in rabbits
Authors: Doerschuk C. M. , Markos J. , Coxson H. O. , English D. , Hogg J. C.
Published: December 2017

The circulating neutrophils must slow down, adhere to the vessel walls, and migrate out of the microvasculature into the tissue and air spaces to defend the lung against microorganisms. The present study was designed to provide quantitative information about each of these steps. Streptococcus pneumoniae was instilled into the left lower lobe of New Zealand White rabbits to induce a pneumonia, and this lobe was compared with the same region of the opposite lung. The distribution of blood flow was determined by using radiolabeled macroaggregated albumin, and the patterns of perfusion within the capillary bed were quantitated using Monastral blue. The number of neutrophils delivered to the pneumonic site was determined by multiplying the circulating neutrophil count and blood flow. The results show that retention of 51Cr-labeled neutrophils was increased in the pneumonic region 2, 4, and 8 h after instillation of the organisms. The number of intracapillary neutrophils was increased in the pneumonic regions at all time points and in the control regions at 1 and 4 h. Neutrophil migration occurred in the pneumonic site, but only 1–2% of the total neutrophils delivered to the region migrated out of the pulmonary vessels into the air space. We conclude that the circulating neutrophils undergo a generalized response that increases their margination throughout the lung, that increased margination in the pneumonic site changes the distribution of capillary flow, and that the majority of neutrophils delivered to a pneumonic site are returned to the circulation without migrating into the air space.
Effect of Na+ and K+ channel blockade on baseline and anoxia-induced catecholamine release from rat carotid body
Authors: Doyle T. P. , Donnelly D. F.
Published: December 2017

Ionic membrane currents are hypothesized to play a major role in determining secretion from carotid body glomus cells, and increased secretion likely mediates the increase in nerve activity in response to hypoxia. The hypothesis that Na+ and K+ channels play an important role in determining secretion and nerve activity was tested by measuring single-fiber afferent nerve activity along with an estimate of free tissue catecholamine using Nafion-covered carbon-fiber micro-electrodes placed in rat carotid bodies in vitro. Baseline and anoxia-stimulated (1 min duration; PO2 of approximately 0 Torr at nadir) levels were quantified. Sham treatment had no significant effect. Tetrodotoxin (2 microns) ablated the nerve activity and reduced peak catecholamine (19.5 +/- 3.1 to 14.5 +/- 3.4 microM; P < 0.05). Cesium (10 microns) had no effect on catecholamine but reduced the nerve response (19.8 +/- 2.7 to 7.8 +/- 2.0 Hz; P < 0.05). 4-Aminopyridine (4 mM) significantly reduced the nerve response (17.2 +/- 3.7 to 4.9 +/- 1.9 Hz; P < 0.05) and increased the baseline (0.9 +/- 0.2 to 3.1 +/- 0.8 microM; P < 0.05) and reduced the peak catecholamine (10.0 to 4.3 +/- 0.8 microM; P < 0.05) levels. These results demonstrate that Na+ and K+ channels play an important role in modulating the secretory and nerve responses. However, channel blockers do not emulate severe hypoxia, suggesting that hypoxia transduction procedes, at least in part, through an alternate pathway.
Time course of blood volume changes in an isolated lung lobe after venous pressure elevation
Authors: Maron M. B. , Lane S. M.
Published: December 2017

The elevation of venous pressure (Pv) in isolated perfused organs causes organ weight to increase in a biphasic manner. The initial rapid phase results primarily from an increase in blood volume (BV), whereas the second slower phase is generally considered to reflect fluid filtration. Recent studies have suggested, however, that BV may continue to increase during the slow weight gain phase. To address this question, we made serial measurements of circulating BV by indicator dilution with indocyanine green dye in a canine isolated perfused left lower lung lobe (LLL) preparation during 40 min of Pv elevation. Pv was raised to approximately 18 Torr in six LLLs beginning an average of 28 min after the start of perfusion. After an initial rapid increase, BV continued to increase at a slower rate for approximately 30 min. The increase in BV observed between 3 and 40 min of Pv elevation [4.3 +/- 0.3 (SE) ml] was 47.9 +/- 9.1% of the weight gain that occurred during this period. In six additional LLLs, Pv elevation was delayed until approximately 70 min after the perfusion was started. In these LLLs, BV generally achieved constancy 3 min after Pv was elevated. These data indicate that the dynamics of the BV response of this preparation to Pv elevation is time dependent and that gravimetric determinations of the rate of fluid filtration may substantially overestimate the true filtration rate in the presence of continuing increases in BV. The increases in BV observed in the first group of LLLs appear to be due to vascular recruitment rather than stress relaxation.
Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations
Authors: Koos B. J. , Mason B. A. , Punla O. , Adinolfi A. M.
Published: December 2017

Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.
Hamsters vs. rats: metabolic and ventilatory response to development in chronic hypoxia
Authors: Frappell P. B. , Mortola J. P.
Published: December 2017

The postnatal developments of the rat and hamster were compared after the animals were raised from birth for 21 days either in normoxia (control animals) or chronic hypoxia (PO2 of 80–90 Torr). Compared with control rats, hypoxic rats had a reduction in body mass. Hypoxic rats had lowered O2 consumption (VO2) and increased (67%) ventilation (VE), whereas hypoxic hamsters maintained the same metabolic rate as control hamsters but increased VE by 100%. As a result, when raised in hypoxia both species increased VE/VO2 to the same extent. When acutely exposed to hypoxia, control animals of both species increased VE (54–58%) and lowered VO2 (26%). Thus, whether the exposure to hypoxia is acute or chronic, both species hyperventilated (i.e., increased VE/VO2) to approximately the same degree. However, in the rat VO2 decreased similarly in both acute and chronic hypoxia, whereas in the hamster VO2 decreased with acute hypoxia but was maintained under chronic hypoxia. Within 1 day of the animals being returned to normoxia, metabolic and ventilatory parameters of hypoxic animals returned to control values. In conclusion, the semifossorial hamster seems better suited to development in chronic hypoxia than the surface-dwelling rat because by avoiding prolonged hypometabolism it can better maintain body growth.
Exercise, potassium, and muscle deconditioning post-thoracic organ transplantation
Authors: Hall M. J. , Snell G. I. , Side E. A. , Esmore D. S. , Walters E. H. , Williams T. J.
Published: December 2017

Although muscle deconditioning appears to significantly limit peak exercise performance post-thoracic organ transplantation, few confirmatory data exist. Potassium (K+) regulation during exercise may reflect muscle deconditioning, since both peak plasma K+ concentration ([K+]) and the increase in plasma [K+] relative to energy expenditure (delta [K+]/W) are reduced in healthy individuals after training. This study compares delta [K+]/W during graded exercise and the change in [K+] (delta [K+]) during both exercise and recovery in 12 heart transplant (HT) recipients, 14 lung transplant (LT) recipients, and 7 healthy subjects. Plasma [K+] was determined from arterial blood sampled at rest; during the final 15 s of each power output; and at 1, 2, and 5 min postexercise. Peak oxygen consumption was significantly lower (P < 0.0001), whereas delta [K+]/W was significantly higher (P < 0.002) among the HT and LT groups. When delta [K+] during recovery was expressed relative to delta [K+] detected during activity, no difference at 1, 2, or 5 min postexercise was detected, although the absolute fall in plasma [K+] was greater among the healthy subjects in the 1st min (P < 0.0001). The rate of delta [K+] during recovery appears to reflect the rise seen during activity in all groups. These results suggest that [K+] regulation is altered during exercise in both HT and LT recipients and may reflect muscle deconditioning.
Oxygen transport to tissue by persistent bubbles: theory and simulations
Authors: Burkard M. E. , Van Liew H. D.
Published: December 2017

Persistent gas bubbles able to traverse capillaries can be prepared from a slowly permeating gas or with a mechanical structure surrounding a gas phase. If they are permeable to gases, such bubbles will carry O2 from the lungs to the tissues via the blood stream. Using a mathematical model based on physical laws, we present simulations of the behavior of bubbles stabilized by a slowly permeating gas (gas X). We show that the bubble persists longer if the tissue and venous blood contain N2 to dilute gas X and slow its outward diffusion. A 6-microns -diam bubble carries 0.11 pl of O2 during the breathing of pure O2, so 4.6 x 10(8) bubbles/ml in the blood will supply a normal arteriovenous difference. In conditions used for hyperbaric O2 therapy, a bubble carries approximately 0.26 pl of O2. Stabilized bubbles have the potential to transport O2 efficiently; they release O2 to tissue at high PO2 and require injection of only small amounts of a foreign substance.
Time course for exercise-induced alterations in insulin action and glucose tolerance in middle-aged people
Authors: King D. S. , Baldus P. J. , Sharp R. L. , Kesl L. D. , Feltmeyer T. L. , Riddle M. S.
Published: December 2017

The purposes of this study were 1) to investigate glucose tolerance and insulin action immediately after exercise and 2) to determine how long the improved glucose homeostatic mechanisms observed 12–16 h after exercise persist. Nine (seven men, two women) moderately trained middle-aged (51 +/- 3 yr) subjects performed 45 min of exercise at 73 +/- 2% of peak O2 uptake for 5 days, followed by 7 days of inactivity. Oral glucose tolerance tests (OGTT; 75 g) were performed immediately postexercise (IPE; approximately 30 min) after the final exercise bout and 1, 3, 5, and 7 days after exercise. The incremental area under the plasma glucose curve was markedly higher IPE (355 +/- 82 mM.min) compared with those on days 1 (136 +/- 57 mM.min; P < 0.05) and 3 (173 +/- 62 mM.min; P < 0.05). The glucose area was significantly higher on days 5 (213 +/- 80 mM.min) and 7 (225 +/- 84 mM.min) compared with those on days 1 and 3 (P < 0.05). The incremental insulin area IPE (3,729 +/- 1,104 microU.ml–1.min) was 43% higher compared with that on day 1 (2,603 +/- 635 microU.ml–1.min; P < 0.05) and 66% higher compared with that on day 3 (2,240 +/- 517 microU.ml–1.min; P < 0.05). The insulin area increased to 3,616 +/- 617 microU.ml–1.min after 5 days of inactivity (P < 0.05). An additional 48 h of inactivity did not result in any further increase in the plasma insulin response.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of muscle glycogen on glycogenolysis and glucose uptake during exercise in humans
Authors: Hargreaves M. , McConell G. , Proietto J.
Published: December 2017

To examine the effects of alterations in preexercise muscle glycogen availability on glycogenolysis and glucose uptake during exercise, 12 active but untrained men [22.8 +/- 1.6 (SE) yr, 71.7 +/- 2.0 kg, peak pulmonary oxygen uptake 3.85 +/- 0.16 l/min] were studied during 40 min of cycle ergometer exercise at 65–70% peak pulmonary oxygen uptake on two separate occasions, at least 1 wk apart. Preexercise muscle glycogen concentrations were manipulated by having the subjects perform glycogen-lowering exercise either 24 or 48 h before a trial, in combination with either high or low dietary carbohydrate intake. In series 1 (n = 7), increasing muscle glycogen from 90.3 +/- 6.0 to 124.7 +/- 10.8 mmol/kg wet wt increased muscle glycogenolysis during exercise (62.7 +/- 7.9 vs. 49.1 +/- 6.6 mmol/kg; P < 0.05). Similarly, in series 2 (n = 5) when muscle glycogen was reduced from 96.2 +/- 6.6 to 53.7 +/- 6.0 mmol/kg, glycogen utilization during exercise was reduced from 51.8 +/- 4.6 to 28.3 +/- 3.8 mmol/kg (P < 0.05). The altered muscle glycogen utilization was associated with alterations in carbohydrate oxidation during exercise, without effect on tracer ([3H]glucose)-determined glucose uptake. These results indicate that preexercise muscle glycogen availability influences muscle glycogenolysis, but not glucose uptake, during exercise.
Mechanical load affects growth and maturation of skeletal muscle grafts
Authors: Esser K. A. , White T. P.
Published: December 2017

The purpose of our study was to determine whether the early patterns of growth and maturation of regenerating soleus muscle grafts are sensitive to alterations in mechanical load. We hypothesized that decreased and increased mechanical loading of grafts would reduce and accelerate, respectively, the rate and magnitude of growth and impair and enhance, respectively, the pattern of maturation. On day 0, soleus muscles were grafted and rats were assigned to one of three groups: cage sedentary (normal load), hindlimb suspension (decreased load), or ablation of synergist muscle (increased load). From days 7 to 35, graft mass in cage-sedentary rats increased at a rate of 1.85 mg mass/day. Rates were less for grafts of suspended rats and greater in grafts of ablated rats (-1.06 and 3.89 mg mass/day, respectively; P < 0.01). Neonatal myosin heavy chain (MHC) in grafts reached 10 +/- 1.6% of total MHC at day 7 for cage-sedentary rats, whereas in the suspended animals it reached 11 +/- 2.4% of total MHC at day 14. At days 21 and 35, grafts from the suspended animals had a lower proportion of slow MHC (45 +/- 2.4%) than did grafts from the control and ablated groups (95 +/- 1.5%; P < 0.05). Decreased mechanical load impaired the rate and degree of growth and maturation during regeneration, whereas increased mechanical load enhanced growth characteristics but not maturation.
Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitus
Authors: Braun B. , Zimmermann M. B. , Kretchmer N.
Published: December 2017

Exercise enhances insulin sensitivity in people with non-insulin-dependent diabetes mellitus (NIDDM), but the intensity of exercise necessary to optimize the effect is unknown. Eight women with NIDDM were studied on a metabolic ward in each of three conditions: 1) low-intensity exercise (LO) that consisted of treadmill walking at 50% of maximal O2 consumption on days 1 and 2, 2) high-intensity exercise (HI) that consisted of walking at 75% of maximal O2 consumption, and 3) no exercise (NX). The duration of exercise was adjusted so that energy expenditure was equal in both exercise conditions. On day 3, glucose, [6,6–2H]glucose, and insulin were infused at fixed rates for 3 h. Insulin sensitivity was determined both by steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin. Steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin were almost identical after LO or HI; values were significantly greater than after NX. Plasma glucose response to a test meal was the same among the three conditions, but plasma insulin response was lower for HI and LO compared with NX. We conclude that under these conditions LO is as effective as HI in enhancing insulin sensitivity in people with NIDDM.
Human pulmonary vascular and venous compliances are reduced before and during left-sided heart failure
Authors: Hirakawa S. , Suzuki T. , Gotoh K. , Ito H. , Tanaka T. , Ohsumi Y. , Yagi Y. , Terashima Y. , Fujiwara H. , Nagashima K. , et al.
Published: December 2017

Human pulmonary vascular and venous compliances were measured in 41 patients with or without left-sided heart failure. Two methods were used. Method 1 was based on analysis of pulmonary capillary wedge (PCW) pressure tracings according to Cv,PCW = (SF/100)(0.075PCW + 0.90)SV/[(v - d)PCW + 1], where Cv,PCW is compliance of pulmonary venous system, SF is systolic fraction of pulmonary venous flow [related to pulmonary capillary wedge pressure (PCW) as SF = 82 – 2.01PCW], (v - d)PCW is pulse pressure in PCW position, and SV is stroke volume. The (0.075PCW + 0.90) term equals k “, i.e., systolic run-off ratio. Method 2 was used to measure to pulmonary vascular volume-pressure (V-P) relationship and pulmonary vascular compliance (Cvasc) and is based on measurement of pulmonary blood volume (PBV) and its increase with passive elevation of the legs to calculate Cvasc. Assuming the proportion of blood entering pulmonary venous system (in increase of PBV) during passive leg elevation to be 0.8, pulmonary venous compliance (Cv,PBV) was calculated as Cv,PBV = 0.8Cvasc. Cv,PCW correlated fairly closely with Cv,PBV (r = 0.81, coefficient of variation = 31%). This fair agreement between two independent methods suggests strongly that both methods may be valid, although other interpretations are possible. Cv,PCW, Cvasc, and Cv,PBV decreased going from New York Heart Association class I to classes II and III. When PBV was plotted vs. PCW, average V-P line for class II patients was flatter and shifted downward to the right compared with that for class I. This suggests pulmonary vasoconstriction as well as other factors. Average V-P line for class III patients is flatter but not displaced compared with that for class II. Another previously reported series of 50 patients, most of whom had ischemic heart disease, are included in this study.
Is walking a random walk? Evidence for long-range correlations in stride interval of human gait
Authors: Hausdorff J. M. , Peng C. K. , Ladin Z. , Wei J. Y. , Goldberger A. L.
Published: December 2017

Complex fluctuations of unknown origin appear in the normal gait pattern. These fluctuations might be described as being 1) uncorrelated white noise, 2) short-range correlations, or 3) long-range correlations with power-law scaling. To test these possibilities, the stride interval of 10 healthy young men was measured as they walked for 9 min at their usual rate. From these time series, we calculated scaling indexes by using a modified random walk analysis and power spectral analysis. Both indexes indicated the presence of long-range self-similar correlations extending over hundreds of steps; the stride interval at any time depended on the stride interval at remote previous times, and this dependence decayed in a scale-free (fractallike) power-law fashion. These scaling indexes were significantly different from those obtained after random shuffling of the original time series, indicating the importance of the sequential ordering of the stride interval. We demonstrate that conventional models of gait generation fail to reproduce the observed scaling behavior and introduce a new type of central pattern generator model that successfully accounts for the experimentally observed long-range correlations.
BW-755C diminishes smoke-induced pulmonary edema
Authors: Hales C. A. , Musto S. , Hutchison W. G. , Mahoney E.
Published: December 2017

Pulmonary edema following smoke inhalation is due to the chemical toxins in smoke and not to the heat. We have shown that acrolein, a common component of smoke, induces pulmonary edema, perhaps via release of leukotrienes. We, therefore, hypothesized that acrolein, a component of smoke from burning cotton, might have a major role in producing pulmonary edema in sheep after cotton smoke inhalation and that BW-755C, a combined cyclo- and lipoxygenase inhibitor, would prevent the edema, whereas indomethacin, a cyclooxygenase inhibitor, would not. In control anesthetized sheep (n = 7), 128 breaths of cotton smoke induced no change in pulmonary arterial pressure but induced increases (P < 0.05) in pulmonary lymph flow from 4.4 +/- 0.8 (SE) to 15 +/- 2.7 ml/h, lymph protein flux from 0.25 +/- 0.08 to 0.80 +/- 0.16 g/h, and blood-corrected wet-to-dry weight ratios from a normal value of 3.8 +/– 0.07 (n = 9) to 4.5 +/- 0.18. Indomethacin (n = 6) did not significantly prevent these changes, whereas BW-755C decreased lung lymph flow change from 5 +/- 1 to 7 +/- 2 ml/h (P = NS), lymph protein flux from 0.25 +/- 0.08 to 0.35 +/- 0.1 g/h (P = NS), and weight-to-dry ratio from normal to 3.9 +/- 2.1 (P = NS). These data suggest leukotrienes may have a role in producing cotton smoke-induced noncardiogenic pulmonary edema.
Heart-lung interactions determined by electron beam X-ray CT in laterally recumbent rabbits
Authors: Olson L. E. , Hoffman E. A.
Published: December 2017

Electron beam X-ray computed tomography (CT) was used to measure lung air content and its distribution within the lung as well as lung shape and heart position in rabbits in right and left lateral recumbency. Sham-operated control (S) rabbits and left-pneumonectomized rabbits with wax plombage were studied at functional residual capacity (FRC) and total lung capacity. Results were obtained for both lungs and for the right lung only of S rabbits. FRC of both lungs and the right lung only of the S rabbits and of the remaining right lung of the pneumonectomized rabbits was smaller in rabbits in right lateral recumbency than in those in left lateral recumbency. The reduction in right lung volume at FRC was accompanied by an overall reduction in lung size, although the lung shape remained similar, and was accompanied by movement of the heart centroid toward the dependent chest and spine. Application of a positive tracheal pressure of 25 cmH2O increased lung volume and reduced the dependency of lung volume and shape on posture. Lung inflation in the right lateral position was accompanied by movement of the heart centroid away from the dependent chest and spine. Gravitational gradients in regional air content did not differ between the cranial half of the lung, which was in contact with the heart, and the caudal half of the right lung, which was not in contact with the heart. Likewise, the cephalocaudal gradient in regional air content was similar when the right lung was dependent and nondependent. The location of the heart in the cranial half of the thorax does not appear to induce differences in regional air content between the cranial and caudal lung halves.
Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip
Authors: Fontana G. A. , Pantaleo T. , Bongianni F. , Cresci F. , Lavorini F. , Guerra C. T. , Panuccio P.
Published: December 2017

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart rate (HR) elicited by 3 min of static handgrip at 30% of the maximum voluntary contraction in 12 healthy volunteers. Before each handgrip trial, subjects were treated with intravenous administration of either saline placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and integrated electromyographic activity of exercising muscles remained fairly constant during each trial. In agreement with our earlier findings, during control handgrip minute ventilation progressively increased (P < 0.01) due to a rise in tidal volume and, to a lesser extent, in respiratory frequency. Mean inspiratory flow, MBP, and HR also increased (P < 0.01). End-tidal PCO2 decreased (P < 0.05) during the late phases of control handgrip bouts. Ketoprofen administration reduced serum thromboxane B2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01) and significantly attenuated mean increases in minute ventilation (40.25 +/- 0.60%), tidal volume (37.78 +/- 7.48%), respiratory frequency (55.94 +/- 17.92%), inspiratory flow (42.66 +/- 5.11%), MBP (22.33 +/- 6.82%), and HR (11.04 +/- 2.75%) during the 3rd min of handgrip. End-tidal PCO2 remained close to normocapnic levels. In agreement with previous animal investigations, the present results show that arachidonic acid metabolites are involved in the regulation of the cardiovascular responses to static efforts in humans, possibly through a stimulatory action on muscle receptors. Furthermore, they provide the first experimental evidence that products of the cyclooxygenase metabolic pathway play a role in the mediation of the respiratory adjustments elicited by this form of exercise.