bluuebunny/crossref_metadata_2025 huggingface dataset:
Head and body positions affect thermoregulatory tonus in deltoid muscles
Authors: Meigal A. Y. , Lupandin Y. V. , Hanninen O.
Published: December 2017

The aim of the present study as to investigate whether increased central hypervolemia induced by tail suspension (TS) in the rat is an appropriate model of cardiovascular deconditioning (CVD). First, the physiological relationship between central venous pressure (CVP) and extracellular fluid volume (ECFV) was studied. TS (20 degrees) increased CVP (5.8 +/- 0.7 vs. 2.8 +/- 0.8 mmHg; P < 0.01). After 24 h of TS, CVP had returned to control range while ECFV was reduced by 19%. CVP kinetics during 24 h of TS was not affected by either reduction (-20%) or augmentation (/35%) of the ECFV. The normalization of CVP is likely to be a consequence of ECFV reduction, which itself is reduced by increased urinary excretion of water and sodium. Second, recovery from TS was studied. Resumption of the horizontal position was shown to be associated with a significant increase of heart rate (HR) and a slight reduction of blood pressure (BP); there was an apparent delay between increased HR and reduced BP. This imbalance between HR and BP is compatible with CVD. A model of simulated orthostatism (SO) was developed to further investigate the responses of HR and BP. Interestingly, SO (90 degrees rotation) in the normal rat was associated with significant tachycardia and a slight increase of BP. This pattern remained stable for at least 3 h. In rats that were tail suspended for 48 h, episodes of hypotension and bradycardia (5 +/- 1 in 3 h) suggested a defect in adaptation to increased hydrostatic pressure. In conclusion, TS appears to be an appropriate model of CVD. Reduction process. Return to horizontal position in TS rats induced a tachycardia with minimal effects on BP; this pattern is close to that observed in humans assuming upright posture. SO in previously TS rats disclosed episodes of hypotension and bradycardia that deserve further investigation.
Two- and three-dimensional simulations of aerosol transport and deposition in alveolar zone of human lung
Authors: Darquenne C. , Paiva M.
Published: December 2017

We simulate two- and three-dimensional (2D and 3D) aerosol transport for different particle diameters within alveolated ducts. In agreement with previous studies (W. J. Federspiel and J. J. Fredberg. J. Appl. Physiol. 64: 2614-2621, 1988; A. Tsuda, J. P. Butler, and J. J. Fredberg. J. Appl. Physiol. 76: 2497-2509, 1994), the 2D-computed velocity field shows that the flow inside the alveoli is negligible compared with that in the central channel of the ducts and that a recirculation zone is set up in each alveolus. The calculated particle trajectories indicate that in the 2D and 3D simulations the particles do not deposit uniformly on the alveolar walls. For <0.5-microns-diameter particles, simulations show that particles are mainly located near the entrance of alveoli. This suggests that local and mean aerosol concentrations may be substantially different. For large particles we show that the gravity field significantly affects deposition. Aerosol dispersion is also computed, and the simulations are compared with the classical one-dimensional (1D) approach with use of the trumpet model, with additional terms for deposition. The 3D model simulates total deposition that is intermediate between 1D and 2D models. The differences between 2D and 3D data are attributed to the inclusion of azimuthal alveolar walls in the 3D duct and the change from 2D- to 3D-particle motions. Finally, our work suggests that the 1D model may introduce large errors in the location of deposited particles.
Mass-transport models to predict toxicity of inhaled gases in the upper respiratory tract
Authors: Hubal E. A. , Fedkiw P. S. , Kimbell J. S.
Published: December 2017

Mass transport (the movement of a chemical species) plays an important role in determining toxic responses of the upper respiratory tract (URT) to inhaled chemicals. Mathematical dosimetry models incorporate physical characteristics of mass transport and are used to predict quantitative uptake (absorption rate) and distribution of inhaled gases and vapors in the respiratory tract. Because knowledge of dose is an essential component of quantitative risk assessment, dosimetry modeling plays an important role in extrapolation of animal study results to humans. A survey of existing mathematical dosimetry models for the URT is presented, limitations of current models are discussed, and adaptations of existing models to produce a generally applicable model are suggested. Reviewed URT dosimetry models are categorized as early, lumped-parameter, and distributed- parameter models. Specific examples of other relevant modeling work are also presented.
Alveolar epithelial clearance of protein
Authors: Folkesson H. G. , Matthay M. A. , Westrom B. R. , Kim K. J. , Karlsson B. W. , Hastings R. H.
Published: December 2017

Substantial progress has been made in understanding the rate, the pathways, and the mechanisms regulating alveolar protein removal from the uninjured lung. Whole animal studies and cellular studies have demonstrated that the majority of alveolar epithelial protein clearance occurs by passive nondegradative diffusional pathways. Some evidence, however, has been recently presented that alveolar epithelial cells express an albumin-binding receptor as well as a polymeric immunoglobulin receptor, both of which might be important for alveolar epithelial clearance of protein. However, the contribution of these receptors requires further studies. Little is known about alveolar clearance of protein during pathological conditions; further studies are required to determine the roles of the different cell types in the lung for removal of protein from the alveolar spaces of the lung. Alveolar macrophages are likely to play an important role in the degradation and removal of insoluble protein from the distal air spaces after acute lung injury. In conclusion, the present data suggest that most proteins and peptides deposited on the epithelial surfaces in the distal air spaces are cleared as intact molecules, predominantly via paracellular routes. The contribution of pinocytic processes appear to be of minor importance for translocation of bulk quantities of proteins or peptides across the alveolar epithelium.
Cardiorespiratory interactions during fixed-pace resistive breathing
Authors: Blaber A. P. , Hughson R. L.
Published: December 2017

We tested the hypothesis that the arterial baroreflex was important in the origin of respiratory sinus arrhythmia (RSA) under conditions of normal and resistive breathing. That is, mechanical effects of breathing [indicated by instantaneous lung volume (ILV)] would directly influence left ventricular stroke volume (LVSV), which in turn would influence systolic arterial blood pressure (SABP), causing variation in R-R interval through the baroreflex. Eight healthy young subjects (four men and four women) were monitored in the supine position while breathing with a fixed frequency (0.2 Hz) and tidal volume for 15 min through each of three resistances (R0, R1, and R2) producing inspiratory (-) and expiratory (+) pressures of +/- 1.6, +/- 5.4, and +/- 16.6 cmH2O, respectively. LVSV was estimated by stroke distance [(SDist); by Doppler ultrasound]. There were no differences across R0, R1, and R2 for the mean values of R-R interval, SDist, or SABP. Cross-spectral analysis showed that, at R0, each value of R-R interval, SDist, and SABP lagged ILV by approximately 80 degrees. At R1 and R2, phase was reduced from ILV to SDist and R-R interval, and the transfer magnitude for SDist (R2 only), SABP, and R-R interval increased. The transfer magnitude from SDist to SABP significantly increased as a function of resistance breathing, whereas that from SABP to R-R interval significantly decreased. There were no changes in phase relationships from SDist to SABP to R-R interval. Thus the magnitude of RSA (ILV to R-R interval) was increased, but the transfer through the arterial baroreflex (SABP to R-R interval) was reduced. Although factors other than the arterial baroreflex are probably involved in the genesis of RSA, the constant phase relationship across the levels of breathing resistance among SDist, SABP, and R-R interval suggests an important functional link caused by mechanical effects of breathing.
Lung mechanics and pulmonary but not systemic vascular responses to ET-1 are Tx and infusion rate dependent
Authors: Faltin D. L. , Weber A. , Lacroix J. S. , Jorge-Costa M. , Morel D. R.
Published: December 2017

The role of cyclooxygenase metabolites formation in the systemic and pulmonary vascular and airway responses to different intravenous infusion rates of endothelin-1 (ET-1) was investigated in eight barbiturate-anesthetized mechanically ventilated adult sheep. ET-1 (20, 200, and 400 pmol/kg) was infused into the femoral vein over either 1, 10, or 180 s before and after pretreatment with indomethacin (1.5 mg/kg i.v.). ET-1 infusion produced a dose-dependent systemic vasoconstriction that was similar with all three infusion rates. In contrast, the pulmonary vascular and airways responses to ET-1 were not only dose dependent but also infusion rate dependent so that consistent effects on the pulmonary vasculature and airways were observed only when the peptide was injected over 1 s. At the highest dosage and at the fastest rate of administration, ET-1 produced a fivefold rise in pulmonary vascular resistance, a twofold rise in airway resistance, and a 45% decrease in dynamic pulmonary compliance, whereas no changes were observed when the peptide was injected over 180 s. Plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) increased 20-fold when ET-1 was administered over 1 s but only 5-fold when it was administered over 180 s. Thromboxane B2 (TxB2) increased 5-fold when ET-1 was administered over 1 s and did not increase when ET-1 was given over 180 s. Plasma TxB2 levels were linearly correlated with pulmonary vascular or airway resistance during the bolus ET-1 infusion. Pretreatment with indomethacin completely prevented the ET-1-induced rise in TxB2 and 6-keto-PGF1 alpha and blocked pulmonary vaso- and bronchoconstriction observed, whereas it enhanced systemic vasoconstriction. These results demonstrate that in adult sheep intravenous ET-1 produces pulmonary vaso- and bronchoconstriction that is infusion rate dependent and is associated with the rate-dependent production of thromboxane. In contrast, the increase in systemic vascular tone elicited by ET-1 is not affected by its rate of infusion and does not depend on the secondary generation of cyclooxygenase metabolites.
Pulmonary capillary pressure during exercise in horses
Authors: Sinha A. K. , Gleed R. D. , Hakim T. S. , Dobson A. , Shannon K. J.
Published: December 2017

The object of this study was to relate pulmonary capillary pressure to arterial and wedge pressures during exercise. Pulmonary vascular pressures were measured in six standardbred horses exercising at speeds equivalent to 75, 90, and 100% of maximal heart rate. Vascular pressures were measured with transducer-tip catheters and expressed relative to esophageal pressure. Pulmonary capillary pressure was estimated by the arterial-occlusion technique modified for exercise. Mean pulmonary arterial, capillary and wedge pressures increased from 30.5 +/- 6.3, 17.8 +/- 4.3, and 13.4 +/- 1.6 mmHg, respectively, at rest, to 70.5 +/- 5.2, 42.1 +/- 5.3, and 38.4 +/- 5.6 mmHg, respectively, at maximal exercise. The largest part of the increase occurred during the first level of exertion. With exercise, the pressure across the lung barely doubled at a time when the cardiac output would have increased at least fivefold. Thus the absolute resistance in both pre- and postcapillary segments must have decreased. The capillary and wedge pressures rose similarly, whereas the difference between them did not change with exertion. The fractional resistance of the precapillary segment increased with exercise. The postcapillary resistance, initially 28% of the total pulmonary vascular resistance, fell to 9% at maximal exercise. The rise (to approximately 45 mmHg) in pulmonary capillary pressure with exertion is consistent with an increase in transvascular filtration.
Effect of inspired O2 concentration on leg lactate release during incremental exercise
Authors: Knight D. R. , Poole D. C. , Hogan M. C. , Bebout D. E. , Wagner P. D.
Published: December 2017

The normal rate of blood lactate accumulation during exercise is increased by hypoxia and decreased by hyperoxia. It is not known whether these changes are primarily determined by the lactate release in locomotory muscles or other tissues. Eleven men performed cycle exercise at 20, 35, 50, 92, and 100% of maximal power output while breathing 12, 21, and 100% O2. Leg lactate release was calculated at each stage of exercise as the product of femoral venous blood flow (thermodilution method) and femoral arteriovenous difference in blood lactate concentrations. Regression analysis showed that leg lactate release accounted for 90% of the variability in mean arterial lactate concentration at 20-92% maximal power output. This relationship was described by a regression line with a slope of 0.28 +/- 0.02 min/l and a y-intercept of 1.06 +/- 0.38 mmol/l (r2 = 0.90). There was no effect of inspired O2 concentration on this relationship (P > 0.05). We conclude that during continuous incremental exercise to fatigue the effect of inspired O2 concentration on blood lactate accumulation is principally determined by the rate of net lactate release in blood vessels of the locomotory muscles.
Cardiovascular response to submaximal exercise in sustained microgravity
Authors: Shykoff B. E. , Farhi L. E. , Olszowka A. J. , Pendergast D. R. , Rokitka M. A. , Eisenhardt C. G. , Morin R. A.
Published: December 2017

Cardiac output (Q), heart rate (HR), blood pressure, and oxygen consumption (VO2) were measured repeatedly both at rest and at two levels of exercise in six subjects during microgravity exposure. Exercise was at 30 and 60% of the workload producing the individual's maximal VO2 in 1 G. Three of the subjects were on a 9-day flight, Spacelab Life Sciences-1, and three were on a 15-day flight, Spacelab Life Sciences-2. We found no temporal differences during the flights. Thus we have combined all microgravity measurements to compare in-flight values with erect or supine control values. At rest, Q in flight was 126% of Q erect (P < 0.01) but was not different from Q supine, and HR in flight was 81% of HR erect (P < 0.01) and 91% of HR supine (P < 0.05). Thus resting stroke volume (SV) in flight was 155% of SV erect (P < 0.01) and 109% SV supine (P < 0.05). Resting mean arterial blood pressure and diastolic pressure were lower in flight than erect (P < 0.05). Exercise values were considered as functions of VO2. The increase in Q with VO2 in flight was less than that at 1 G (slope 3.5 vs. 6.1 x min-1.l-1.min-1). SV in flight fell with increasing VO2, whereas SV erect rose and SV supine remained constant. The blood pressure response to exercise was not different in flight from erect or supine. We conclude that true microgravity causes a cardiovascular response different from that seen during any of its putative simulations.
Progressive changes in airway resistance during sleep
Authors: Kay A. , Trinder J. , Kim Y.
Published: December 2017

Ventilation (V) decreases during sleep while upper airway resistance (UAR) increases. A number of studies have suggested that in normal healthy individuals the changes in the two variables are reciprocal. Other findings, however, suggest that the relationship between V and UAR may change as non-rapid-eye-movement (NREM) sleep progresses such that most of the change in V occurs early during the sleep period, whereas the most marked changes in UAR occur later during established NREM sleep. However, no study has examined the progressive development of changes in both V and UAR over the NREM sleep period. This study examined V and UAR over one NREM sleep period in two groups of healthy young male subjects: a "slow-wave sleep (SWS) group" (n = 8) in which the subjects obtained the full range of NREM sleep stages from wakefulness to stage 4 NREM sleep and a "no-SWS group" (n = 5) in which the subjects did not attain SWS but spent a prolonged period in stage 2 NREM sleep that was repeatedly interrupted by arousals. Results showed that the most marked changes in V occurred early during the sleep period in association with relatively small increases in UAR. Once NREM sleep became established, further attenuation of V was minimal despite marked and progressive increases in UAR. The progressive increase in UAR occurred in association with increasing delta (0.4- to 3.0-Hz) electroencephalographic activity and did not occur in the no-SWS group. We interpret these findings to indicate that factors in addition to UAR contribute to the reduction in V early in sleep onset, whereas later, during NREM sleep, compensatory mechanisms are activated to allow for maintenance of V in the context of larger increases in UAR.
Distinct effects of aerobic exercise training and weight loss on glucose homeostasis in obese sedentary men
Authors: Dengel D. R. , Pratley R. E. , Hagberg J. M. , Rogus E. M. , Goldberg A. P.
Published: December 2017

The decline in glucose homeostasis with aging may be due to the physical deconditioning and obesity that often develop with aging. The independent and combined effects of aerobic exercise training (AEX) and weight loss (WL) on glucose metabolism were studied in 47 nondiabetic sedentary older men. There were 14 men in a weekly behavioral modification/WL program, 10 in a 3 times/wk AEX program, 14 in an AEX+WL program, and 9 in the control (Con) group. The 10-mo intervention increased maximal oxygen consumption (VO2max) in both the AEX and AEX+WL groups [0.33 +/- 0.05 and 0.37 +/- 0.09 (SE) l/min, respectively], but VO2max did not significantly change in the WL (0.01 +/- 0.06 l/min) and Con groups (-0.04 +/- 0.05 l/min; P > 0.05). The AEX+WL and WL groups had comparable reductions in body weight (-8.5 +/- 0.9 and -8.8 +/- 1.2 kg, respectively) and percent fat (-5.5 +/- 0.7 and -5.9 +/- 1.1%, respectively) that were significantly greater than those in the Con and AEX groups. Oral glucose tolerance tests showed significant reductions in insulin responses in the AEX, WL, and AEX+WL groups, but the decrease in insulin response in the AEX+WL group was significantly greater than that in the other three groups. The glucose area decreased significantly in the WL and AEX+WL groups but did not change in the Con or AEX groups. There were significant increases in insulin-mediated glucose disposal rates as measured by the hyperinsulinemic (600 pmol.m-2.min-1) euglycemic clamps in the AEX and AEX+WL groups [1.66 +/- 0.50 and 1.76 +/- 0.41 mg.kg fat-free mass (FFM)-1.min-1, respectively] that were significantly greater than those in the WL (0.13 +/- 0.31 mg.kg FFM-1.min-1) and Con groups (-0.05 +/- 0.51 mg.kg FFM-1.min-1; n = 5). These data suggest that AEX and WL improve glucose metabolism through different mechanisms and that the combined intervention of AEX+WL is necessary to improve both glucose tolerance and insulin sensitivity in older men.
Expression of adhesion molecules on circulating PMN during hyperdynamic endotoxemia
Authors: Holzer K. , Thiel M. , Moritz S. , Kreimeier U. , Messmer K.
Published: December 2017

In a porcine model of hyperdynamic endotoxemia, we studied the numerical expression of L-selectin and beta 2-integrins on circulating polymorphonuclear leukocytes (PMN). Functional changes of beta 2-integrins were determined by the adhesion of PMN to C3-coated zymosan particles. Anesthesized pigs received a continuous infusion of Salmonella abortus-equi endotoxin (5 micrograms.kg body wt-1.h-1) for 270 min (endotoxin group; n = 7). A control group received 0.9% NaCl (n = 6). L-selectin had decreased 30 min after the induction of endotoxemia [59.1 +/- 11.9 vs. 91.6 +/- 15.5 relative fluorescence units (RFU) at baseline; P < 0.05], reaching minimal values after 150 min (23.9 +/- 3.9 RFU in endotoxin group vs. 95.2 +/- 30.4 RFU in control group; P < 0.05). PMN adhesion to C3-coated zymosan increased at 30 min (41.3 +/- 9.9% in endotoxin group vs. 2.4 +/- 1.1% in control group; P < 0.05) and remained significantly elevated thereafter. In contrast to the rapid shedding of L-selectin and functional upregulation of beta 2-integrins, the numerical expression of beta 2-integrins remained unchanged until 60 min (44.8 +/- 2.8 vs. 32.2 +/- 1.7 RFU at baseline; P < 0.05); compared with the control group, significantly elevated values were observed 150 min after the start of endotoxin (48.9 +/- 2.4 RFU in endotoxin group vs. 36.5 +/- 2.7 RFU in control group; P < 0.05). We conclude that numerical and functional expressions of beta 2-integrins are dissociated during endotoxemia. Although upregulation of beta 2-integrins might render PMN more adhesive to the vascular endothelium, the presence of activated PMN in the circulation suggests that low expression of L-selectin might impede adhesion.
Acute cold stress induces suppressor macrophages in mice
Authors: Kizaki T. , Oh-ishi S. , Ohno H.
Published: December 2017

To elucidate mechanisms underlying acute cold stress-induced immunosuppression, functions of murine peritoneal cells of monocyte/ macrophage lineage from acute cold-stressed mice (exposed to 5 degrees C for 24 h) were investigated. Proliferative responses of spleen cells from control mice (reared at 25 degrees C) stimulated with concanavalin A (ConA) were significantly suppressed by adding peritoneal exudate cells from mice immediately after acute cold stress. The proportion of adherent cells was markedly increased in the peritoneal exudate cells from acute cold-stressed mice. These adherent cells from acute cold-stressed mice were shown to be the cells responsible for the suppressor activity for ConA responses of control spleen cells. Nonadherent cells did not suppress the ConA responses. The adherent cells in peritoneal exudate cells from control mice also suppressed the ConA responses, the inhibitory effect being considerably lower than that from acute cold-stressed mice. Addition of a nitric oxide synthase substrate analogue, NG-monomethyl-L-arginine, to the mixed cell cultures of normal spleen cells and adherent cells from acute cold-stressed mice inhibited nitric oxide release and completely abolished the suppressive effect of the adherent cells, suggesting that reactive nitrogen oxide released from the activated macrophages is apparently involved in the downregulation of proliferative responses of T cells. Thus the present findings suggest that acute cold stress induces macrophages with suppressor function and that this may contribute to the immune-suppressive state seen in spleen cells from acute cold-stressed mice.
Tactile influences on astronaut visual spatial orientation: human neurovestibular studies on SLS-2
Authors: Young L. R. , Mendoza J. C. , Groleau N. , Wojcik P. W.
Published: December 2017

Human spatial orientation in spaceflight is initially disturbed by the absence of usable graviceptor information from the otolithic organs. Experiments measuring astronaut visually induced motion (vection) strength on various flight days during the first 10 days of the Spacelab Life Sciences-2 mission demonstrated two new phenomena in addition to confirming the initial increased weighting of visual and localized tactile cues. The reliance on tactile and visual noninertial cues apparently declined after a week in space, as the crew became able to utilize their internal reference frame. Subjects also showed that even nondirectional tactile cues served as a direction anchor and inhibited visually induced roll sensation relative to a new loosely tethered test condition. Individual perceptual styles were again revealed among the four astronauts tested. The readaptation to 1 G similarly shows a period of reinterpretation of inertial and visual cues to spatial orientation. The results are discussed in terms of an internal-model representation of body orientation, with time-varying weights applied to extrinsic and intrinsic signals.
Growth and neutralization of sulfate aerosols in human airways
Authors: Sarangapani R. , Wexler A. S.
Published: December 2017

Evidence derived from in vivo and in vitro laboratory experiments, controlled human exposure studies, and epidemiological studies on mortality and morbidity point to a positive correlation between acid aerosol inhalation and lung impairment. The lung has two important lines of defense against acid aerosols: 1) neutralization by oral or nasal airway ammonia and 2) buffering by mucus lining of the airway. A mathematical model is developed to study the growth and endogenous ammonia neutralization of sulfate-containing aerosol particles in the human respiratory tract. It is shown that an accurate prediction of the luminal ammonia concentration and relative humidity in each generation is essential for quantifying the degree of neutralization of the acidic particles. The model predicts substantial growth and neutralization for small particles (< 0.1 micron), whereas larger particles (> 1.0 micron) experience negligible neutralization. The predicted neutralization of intermediate-sized particles depends on the parameter values used in the model. Water supersaturations that occur in the respiratory tract when ambient conditions are cool and humid cause rapid particle growth and consequently enhance neutralization. Thus the neutralization depends on the particle size as well as on ambient conditions.
Exogenous infusion of adenosine depresses whole body O2 use in fetal/neonatal sheep
Authors: Karimi A. , Ball K. T. , Power G. G.
Published: December 2017

To examine a possible metabolic regulatory role for adenosine, infusions of adenosine and adenosine deaminase were given to 11 near-term fetal sheep during the simulation of birth in utero. Fetal arterial blood gases, the concentration of a number of metabolites, insulin, and whole body O2 consumption (VO2) were measured. After intrauterine ventilation and cord occlusion, fetal/neonatal VO2, measured by closed-circuit respirometry, averaged 11.0 +/- 1.1 (SE) ml (STPD).min-1.kg fetal wt-1 and plasma adenosine concentration ([Ado]) was 1.29 +/- 0.21 microM. Infusion of adenosine (1.5 mumol.min-1.kg-1) during the next 30-min interval increased [Ado] to 1.57 +/- 0.28 microM (not significant) and decreased VO2 to 7.7 +/- 0.5 ml.min-1.kg-1 (P < 0.05). The infusion reduced systolic blood pressure by 19% (P < 0.01) and diastolic blood pressure by 25% (P < 0.01) and increased heart rate by 19% (P < 0.01). At the highest rate of adenosine infusion studied (6 mumol.min-1.kg-1), [Ado] increased to 4.27 +/- 0.46 microM (P < 0.001) and VO2 did not measurably decline further, although there were further decreases in blood pressure and increases in heart rate. After administration of adenosine deaminase, [Ado] decreased to 0.58 +/- 0.13 microM (P < 0.05), whereas VO2 increased to 11.2 +/- 0.8 ml.min-1.kg-1 (P < 0.05); blood pressure and heart rate returned to basal levels. The dependence of VO2 on [Ado] is described by the relationship VO2 = 6.14 + 4.89 exp(-0.45[Ado]) (n = 144; r = 0.34; P < 0.001). Throughout the experiment, arterial O2 content and plasma glucose, lactate, glycerol, and fatty acid concentrations were normal or elevated, and, therefore, O2 lack and substrate deficiency were unlikely to have caused the reduction in VO2. We conclude that plasma adenosine may act as a messenger of energy status for the ovine fetus/neonate and may contribute thereby to a maintenance of a balance between O2 supply and O2 demand.
Altitude acclimatization and blood volume: effects of exogenous erythrocyte volume expansion
Authors: Sawka M. N. , Young A. J. , Rock P. B. , Lyons T. P. , Boushel R. , Freund B. J. , Muza S. R. , Cymerman A. , Dennis R. C. , Pandolf K. B. , Valeri C. R.
Published: December 2017

We studied sea-level residents during 13 days of altitude acclimatization to determine 1) altitude acclimatization effects on erythrocyte volume and plasma volume, 2) if exogenous erythrocyte volume expansion alters subsequent erythrocyte volume and plasma volume adaptations, 3) if an increased blood oxygen content alters erythropoietin responses during altitude acclimatization, and 4) mechanisms responsible for plasma loss at altitude. Sixteen healthy men had a series of hematologic measurements made at sea level, on the first and ninth days of altitude (4,300 m) residence, and after returning to sea level. Twenty-four hours before the ascent to altitude, one group received a 700-ml infusion of autologous erythrocytes (42% hematocrit), whereas the other group received only a saline infusion. Erythrocyte infusion increased erythrocyte volume by approximately 10%, whereas saline infusion had no effect; in addition, initially at altitude, blood oxygen content was 8% higher in erythrocyte-infused than in saline-infused subjects. The new findings regarding altitude acclimatization are summarized as follows: 1) erythrocyte volume does not change during the first 13 days and is not affected by prior exogenous expansion, 2) a modest increase in blood oxygen content does not modify erythropoietin responses, 3) plasma losses are related to vascular protein losses, and 4) exogenous erythrocyte volume expansion coincides with transient increases in plasma loss, vascular protein loss, and mean arterial pressure elevation. These findings better define human blood volume responses during altitude acclimatization.
Direct measurement of nitric oxide release from vascular endothelial cells
Authors: Guo J. P. , Murohara T. , Buerke M. , Scalia R. , Lefer A. M.
Published: December 2017

A nitric oxide (NO)-selective electrode was used to directly measure NO release from isolated rat aortic endothelium and cultured rat aortic endothelial cells (RAECs). Basal release of NO was significantly attenuated by a NO synthase inhibitor NG-nitro-L-arginine methyl ester (1 mM) to 42 +/- 14 pmol/1 x 10(5) cells (P < 0.01). The basal release of NO was also significantly inhibited by a calmodulin antagonist W-7 at 15 microM (P < 0.01). L-Arginine (1 mM), significantly stimulated NO release (P < 0.05 vs. control basal release). Stimulation of cultured RAECs with two endothelium-dependent vasodilators, acetylcholine (100 nM) and A-23187 (1 microM), significantly increased NO release [574 +/- 112 pmol/1 x 10(5) cells (n = 5) and 658 +/- 119 pmol/1 x 10(5) cells (n = 5) in acetylcholine- and A-23187-stimulated RAECs, respectively]. Basal release of NO was also detectable in isolated rat aortic rings with intact endothelium. NO release was significantly attenuated by NG-nitro-L-arginine methyl ester and augmented by human superoxide dismutase. These data indicate the physiological usefulness of the amperometric measurement of NO employing a NO-specific electrode in biological systems.
Sarcomere relaxation in hamster diaphragm muscle
Authors: Coirault C. , Chemla D. , Suard I. , Pourny J. C. , Lecarpentier Y.
Published: December 2017

We characterized instantaneous sarcomere relaxation over the load continuum in isolated hamster diaphragm muscles by means of laser diffraction. In afterloaded twitches, sarcomere relaxation displayed two consecutive phases. The bulk of sarcomere lengthening occurred during the first phase and corresponded in time to muscle lengthening. The second phase of sarcomere relaxation was slower and corresponded in time to tension decay. At initial muscle length, the peak velocity of sarcomere lengthening (SVL) was linearly related to both the maximum extent of sarcomere shortening (delta SL) and sarcomere length at peak shortening (SLmin; each P < 0.01). Varying preload modified the SVL vs. SLmin relationship but not the SVL vs. delta SL relationship. At a given preload, muscle tension decay began at a similar sarcomere length, regardless of the afterload level. In conclusion, our results support the role played by sarcomere length in regulating the diaphragm muscle-lengthening rate but not the rate of tension decline.
Influence of upper airway pressure oscillations on soft palate muscle electromyographic activity
Authors: Brancatisano A. , Van der Touw T. , O'Neill N. , Amis T. C.
Published: December 2017

Snoring is characterized by high-frequency (30-50 Hz) pressure oscillations (HFPO) in the upper airway (UA). The soft palate is a major oscillating structure during snoring, and soft palate muscle (SPM) activity is an important determinant of velopharyngeal patency. Consequently, we examined the effect of artificial HFPO applied to the UA on the integrated electromyographic (EMG) activity of the SPMs in 11 supine mouth-closed anesthetized (pentobarbital sodium/chloralose) dogs breathing spontaneously via a tracheostomy. The EMGs of the palatinus (Pal; n = 11), levator veli palatini (LP; n = 9), and tensor veli palatini (TP; n = 8) were monitored with intramuscular fine-wire electrodes. Peak inspiratory and peak expiratory EMG activity was measured in arbitrary units (au) as the mean of five consecutive breaths. HFPO [+/- 4.5 +/- 0.4 (SE) cmH2O; 30 Hz inverted question mark applied at the laryngeal end of the isolated UA increased peak inspiratory EMG from 3.3 +/- 2.0 to 8.4 +/- 1.7 au (P < 0.05) for Pal and from 2.0 +/- 1.1 to 7.3 +/- 2.7 au (P < 0.05) for LP. For the TP, increases were evident in four dogs, but mean values for the group did not change (5.8 +/- 2.4 to 11.0 +/- 4.1 au, P = 0.5). The peak expiratory EMG did not change for any SPM (all P > 0.3). Thus HFPO applied to the UA augments inspiratory SPM activity. Reflex augmentation of SPM activity by HFPO may serve to dilate the retropalatal airway and/or stiffen the soft palate during inspiration in an attempt to stabilize UA geometry during snoring.
Production of hydroxyl radicals in contracting skeletal muscle of cats
Authors: O'Neill C. A. , Stebbins C. L. , Bonigut S. , Halliwell B. , Longhurst J. C.
Published: December 2017

Reactive oxygen species increase during exhaustive contraction of skeletal muscle, but characterization of the specific species involved and their rates of production during nonexhaustive muscle contraction have not been investigated. We hypothesized that the production rate of hydroxyl radical (.OH) increases in contracting muscle and that this rate is attenuated by pretreatment with deferoxamine (Def) or dimethylthiourea (DMTU). We measured the rate of production of .OH before, during, and after 5 min of intermittent static contraction of the triceps surae muscles in cats (n = 6) using the formation of p-, m-, and o-tyrosines by hydroxylation of phenylalanine. L-Phenylalanine (30 mg/kg i.v.) was administered to each animal 3 min before contraction. Blood samples were collected from the popliteal vein 1 min before contraction; 1, 3, and 4.5 min during contraction; and 1 min after contraction. During and after contraction, the cumulative production rates of p-, m-, and o-tyrosines were elevated by 42.84 +/- 5.41, 0.25 +/- 0.04, and 0.21 +/- 0.03 nmol.min-1.g-1, respectively, compared with noncontracting triceps surae muscles. Pretreatment with Def (10 mg/kg i.v.; n = 5) or DMTU (10 mg/kg i.v.; n = 4) decreased the cumulative rates of production of p-, m-, and o-tyrosines during and after contraction. Additionally, the rate of tyrosine production increased in proportion to the percentage of maximal tension developed by the triceps surae muscles. These results directly demonstrate that .OH is produced in vivo in the skeletal muscle of cats during intermittent static contraction and that production can occur before the onset of fatigue.
Endotoxin alters hypoxic pulmonary vasoconstriction in isolated rat lungs
Authors: Frank D. U. , Lowson S. M. , Roos C. M. , Rich G. F.
Published: December 2017

Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism for maintaining oxygenation, which may be altered by endotoxin. We determined that acute endotoxemia alters the HPV response secondary to changes in endothelium-derived vasoactive products. Rats were treated with Salmonella typhimurium lipopolysaccharide (LPS; 15 mg/kg i.p.) either 1 to 6 h before lung isolation and compared with control rats (no LPS). Additional 6-h LPS-treated and control rats were pretreated with either indomethacin (15 mg/kg i.p.), a cyclooxygenase inhibitor, or bosentan (10 mg/kg po), a nonselective endothelin-receptor antagonist. The rats lungs were isolated and challenged with 3% O2 for 10 min to elicit HPV responses before and after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME; 100 microM). LPS (6 h) significantly increased the peak HPV responses by 108%. L-NAME had no significant effect in LPS-treated lungs but increased the peak HPV response in control lungs to levels equal to LPS-treated lungs. Bosentan increased the peak HPV response in all lungs, and indomethacin increased the peak HPV in LPS-treated lungs. The HPV response was sustained in control lungs at 10 min and in additional 20-min studies. In contrast, in LPS-treated lungs the HPV response faded after 10 min to levels equal to control, and in 20-min studies it faded by 82% to levels significantly less than in control lungs. The 10-min fade in LPS-treated lungs was attenuated by indomethacin (51%) and bosentan (80%) but not by L-NAME. In conclusion, acute endotoxemia with LPS increased the peak HPV response, but this effect was not sustained and by 20 min was nearly abolished. Inhibition of endogenous NO by LPS may explain the increased peak HPV response, but NO is not involved in the fade. The fade is at least partially due to increased vasodilating cyclooxygenase products and endothelins.
Sherpa brain glucose metabolism and defense adaptations against chronic hypoxia
Authors: Hochachka P. W. , Clark C. M. , Monge C. , Stanley C. , Brown W. D. , Stone C. K. , Nickles R. J. , Holden J. E.
Published: December 2017

The brain of hypoxia-tolerant vertebrates is known to survive extreme oxygen limitation at least in part because of very low rats of ATP utilization and ATP production. To asses whether similar adaptations are involved in healthy humans during hypoxia adaptation over generational time, we initially used positron-emission tomography measurements of glucose metabolic rates in the brain of Quechuas, whose ancestors have been indigenous to the Andes at altitudes between approximately 3,300 and 4,500 m for several hundred years. Workers in this field generally believe that the lineage of Sherpas has been indigenous to the Himalayas for even longer and that Sherpas and other peoples indigenous to the Tibetan plateau are perhaps the most exquisitely hypoxia adapted of all humans. For this reason, in this study we extended our database to include Sherpas. With the use of the same protocol as before, two metabolic states were analyzed: 1) the presumed normal (hypoxia-adapted) state, monitored as soon as possible after subjects left the Himalayas and 2) the deacclimated state, monitored after 3 wk at low altitudes. Positron-emission tomography measurements of 2-[18F]deoxy-2-fluoro-D-glucose metabolic rates, quantified in 26 regions of the brain, indicated that the Sherpas' brain metabolism differed significantly from that of Quechuas but was essentially identical to that of lowlanders. Region-by-region patterns were similar in all three groups, indicating that the regional organization of glucose metabolism in the brain is a conservative, relatively constant characteristic.
Influence of bipolar esophageal electrode positioning on measurements of human crural diaphragm electromyogram
Authors: Beck J. , Sinderby C. , Lindstrom L. , Grassino A.
Published: December 2017

We aimed to describe how the human diaphragm electromyogram (EMGdi) is filtered at different positions within the esophageal hiatus, i.e., in the close proximity of the diaphragm, when obtained with an array of bipolar electrode pairs mounted on an esophageal catheter. We defined the electrically active crural diaphragm musculature that covers the esophagus as the electrically active region of the diaphragm (EARdi) and its center as the EARdi center. EMGdi signals were obtained via a multiple-array esophageal catheter consisting of seven sequential electrode pairs with three different electrode configurations. Subjects (n = 5) performed voluntary contractions of the diaphragm at functional residual capacity. Visual inspection of the signals revealed reversal of signal polarity on either side of the EARdi center. Extreme correlation values (r values close to -1 at 0-ms time offset) were observed for the correlation of signals on either side of the EARdi center. The root mean square (RMS) was reduced at the EARdi center; moving peripherally from the EARdi center (caudally and cephalad), the RMS increased to a peak (range of 2.1-4.1 dB for the different electrode configurations) and then decreased for the most peripheral electrode pairs. From a position where the RMS values peaked, center frequency values increased at the EARdi center (range of 26-29 Hz for the different electrode configurations). Computer simulation yielded similar data to the experimental results. We conclude that electrode positioning within the EARdi severely influences center frequency and RMS values and that the center of the EARdi can be identified via cross-correlation analysis.
Abdominal muscle fatigue after maximal ventilation in humans
Authors: Kyroussis Dimitris , Mills Gary H. , Polkey Michael I. , Hamnegard Carl-Hugo , Koulouris Nicholaos , Green Malcolm , Moxham John
Published: December 2017

Kyroussis, Dimitris, Gary H. Mills, Michael I. Polkey, Carl-Hugo Hamnegard, Nicholaos Koulouris, Malcolm Green, and John Moxham. Abdominal muscle fatigue after maximal ventilation in humans. J. Appl. Physiol. 81(4): 1477–1483, 1996.—Abdominal muscles are the principal muscles of active expiration. To investigate the possibility of abdominal muscle low-frequency fatigue after maximal ventilation in humans, we stimulated the nerve roots supplying the abdominal muscles. We used a magnetic stimulator (Magstim 200) powering a 90-mm circular coil and studied six normal subjects. To assess the optimum level of stimulation and posture, we stimulated at each intervertebral level between T7 and L1 in the prone, supine, and seated positions. At T10, we used increasing power outputs to assess the pressure-power relationship. Care was taken to avoid muscle potentiation. Twitch gastric pressure (Pga) was recorded with a balloon-tipped catheter. Mean (±SD) baseline twitch Pga measured with the subjects in the prone position at T10 was 23.5 ± 5.4 cmH2O. Within-occasion mean twitch Pga coefficient of variation was 4.6 ± 1.1%. Twitch Pga was measured with the subjects in the prone position with stimulation over T10 before and after 2 min of maximal isocapnic ventilation (MIV). Twenty minutes after MIV, mean twitch Pga fell by 17 ± 9.1% ( P = 0.03) and remained low 90 min after MIV. We conclude that after maximal ventilation in humans there is a reduction of twitch Pga and, therefore, of low-frequency fatigue in abdominal muscles.
Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans
Authors: Shoemaker J. K. , Naylor H. L. , Pozeg Z. I. , Hughson R. L.
Published: December 2017

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans. J. Appl. Physiol. 81(4): 1516–1521, 1996.—The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter ( D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (γ˙ = 8 ⋅ MBV/ D), and forearm blood flow (FBF = MBV ⋅ π r 2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (∼10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and γ˙ was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min) ( P < 0.05) without change to MPP. With placebo, D increased in both arm positions from ∼4.3 mm at rest to ∼4.5 mm at 5 min of exercise ( P < 0.05). This response was not altered with Ibu ( P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow ( P > 0.05) in either arm position. The γ˙ was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise ( P < 0.05). Because PG inhibition altered the time course ofγ˙ at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.
Association of chest wall motion and tidal volume responses during CO2 rebreathing
Authors: Yan Sheng , Sliwinski Pawel , Macklem Peter T.
Published: December 2017

Yan, Sheng, Pawel Sliwinski, and Peter T. Macklem.Association of chest wall motion and tidal volume responses during CO2 rebreathing. J. Appl. Physiol. 81(4): 1528–1534, 1996.—The purpose of this study is to investigate the effect of chest wall configuration at end expiration on tidal volume (Vt) response during CO2 rebreathing. In a group of 11 healthy male subjects, the changes in end-expiratory and end-inspiratory volume of the rib cage (ΔVrc,e and ΔVrc,i, respectively) and abdomen (ΔVab,eand ΔVab,i, respectively) measured by linearized magnetometers were expressed as a function of end-tidal[Formula: see text]([Formula: see text]). The changes in end-expiratory and end-inspiratory volumes of the chest wall (ΔVcw,e and ΔVcw,i, respectively) were calculated as the sum of the respective rib cage and abdominal volumes. The magnetometer coils were placed at the level of the nipples and 1–2 cm above the umbilicus and calibrated during quiet breathing against the Vt measured from a pneumotachograph. The ΔVrc,e/[Formula: see text]slope was quite variable among subjects. It was significantly positive ( P < 0.05) in five subjects, significantly negative in four subjects ( P < 0.05), and not different from zero in the remaining two subjects. The ΔVab,e/[Formula: see text]slope was significantly negative in all subjects ( P < 0.05) with a much smaller intersubject variation, probably suggesting a relatively more uniform recruitment of abdominal expiratory muscles and a variable recruitment of rib cage muscles during CO2rebreathing in different subjects. As a group, the mean ΔVrc,e/[Formula: see text], ΔVab,e/[Formula: see text], and ΔVcw,e/[Formula: see text]slopes were 0.010 ± 0.034, −0.030 ± 0.007, and −0.020 ± 0.032 l / Torr, respectively; only the ΔVab,e/[Formula: see text]slope was significantly different from zero. More interestingly, the individual ΔVt/[Formula: see text]slope was negatively associated with the ΔVrc,e/[Formula: see text]( r = −0.68, P = 0.021) and ΔVcw,e/[Formula: see text]slopes ( r = −0.63, P = 0.037) but was not associated with the ΔVab,e/[Formula: see text]slope ( r = 0.40, P = 0.223). There was no correlation of the ΔVrc,e/[Formula: see text]and ΔVcw,e/[Formula: see text]slopes with age, body size, forced expiratory volume in 1 s, or expiratory time. The group ΔVab,i/[Formula: see text]slope (0.004 ± 0.014 l / Torr) was not significantly different from zero despite the Vt nearly being tripled at the end of CO2 rebreathing. In conclusion, the individual Vtresponse to CO2, although independent of ΔVab,e, is a function of ΔVrc,e to the extent that as the ΔVrc,e/[Formula: see text]slope increases (more positive) among subjects, the Vt response to CO2 decreases. These results may be explained on the basis of the respiratory muscle actions and interactions on the rib cage.