bluuebunny/crossref_metadata_2025 huggingface dataset:
Chest wall mechanics in sustained microgravity
Authors: Wantier Muriel , Estenne Marc , Verbanck Sylvia , Prisk G. Kim , Paiva Manuel
Published: December 2017

We assessed the effects of sustained weightlessness on chest wall mechanics in five astronauts who were studied before, during, and after the 10-day Spacelab D-2 mission ( n = 3) and the 180-day Euromir-95 mission ( n= 2). We measured flow and pressure at the mouth and rib cage and abdominal volumes during resting breathing and during a relaxation maneuver from midinspiratory capacity to functional residual capacity. Microgravity produced marked and consistent changes (Δ) in the contribution of the abdomen to tidal volume [ΔVab/(ΔVab + ΔVrc), where Vab is abdominal volume and Vrc is rib cage volume], which increased from 30.7 ± 3.5 (SE)% at 1 G head-to-foot acceleration to 58.3 ± 5.7% at 0 G head-to-foot acceleration ( P < 0.005). Values of ΔVab/(ΔVab + ΔVrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects ΔVab/(ΔVab + ΔVrc) was greater on postflight day 1 than on subsequent postflight days or preflight. In the two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations are similar to those previously reported during short periods of weightlessness inside aircrafts flying parabolic trajectories. They are also qualitatively similar to those observed on going from upright to supine posture; however, in contrast to microgravity, such postural change reduces rib cage compliance.
Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro
Authors: Villablanca Amparo C.
Published: December 2017

Nicotine is a major component of cigarette smoke and has been postulated to play an important role in atherogenesis and malignancy. Endothelial cell growth may be regulated by nicotine, yet operative mechanisms at the endothelial level are poorly understood. We studied the effects of nicotine (10−14-10−4M) on endothelial DNA synthesis, DNA repair, proliferation, and cytotoxicity by using cultures of bovine pulmonary artery endothelial cells. Assays were performed on cells incubated with nicotine in the presence and absence of hydroxyurea (an inhibitor of scheduled DNA synthesis), serum, human platelet-poor plasma, and platelet-derived growth factor and endothelial cell growth factor (PDGF and PDECGF, respectively). Nicotine significantly stimulated endothelial cell DNA synthesis and proliferation at concentrations lower than those obtained in blood after smoking (<10−8M). The stimulatory effects of nicotine were enhanced by serum (0.5%) and PDECGF and were blocked by the nicotinic-receptor antagonist hexamethonium. The response to nicotine was bimodal because cytotoxicity was observed at higher concentrations (>10−6M). This study has implications for understanding cellular mechanisms of nicotine action. The results may be important in tumor angiogenesis, atherogenesis, and vascular dysfunction in smokers.
Asymmetry in reflex responses of nasal muscles in anesthetized guinea pigs
Authors: Sekizawa Shin-Ichi , Ishikawa Teruhiko , Sant’Ambrogio Giuseppe
Published: December 2017

Nasal reflexes elicited by mechanical or electrical stimulation of nasal afferents were studied in anesthetized guinea pigs. Probing the nasal cavity of one side evoked a greater activation of the contralateral than the ipsilateral nasal muscles and, occasionally, sneezing. Similarly, electrical stimulation of the ethmoidal nerve often caused sneezing, with a greater activation of the nasal muscles and a greater increase in resistance on the contralateral side. Asymmetrical activation of the nasal muscles in response to mechanical stimuli induces asymmetrical airflows, especially during sneezing, between the two sides of the nasal cavity. Most of the expired air is forcibly blown out through the ipsilateral nostril, thus improving the elimination of irritants from the nose.
Human thermoregulatory responses during serial cold-water immersions
Authors: Castellani John W. , Young Andrew J. , Sawka Michael N. , Pandolf Kent B.
Published: December 2017

This study examined whether serial cold-water immersions over a 10-h period would lead to fatigue of shivering and vasoconstriction. Eight men were immersed (2 h) in 20°C water three times (0700, 1100, and 1500) in 1 day (Repeat). This trial was compared with single immersions (Control) conducted at the same times of day. Before Repeat exposures at 1100 and 1500, rewarming was employed to standardize initial rectal temperature. The following observations were made in the Repeat relative to the Control trial: 1) rectal temperature was lower and heat debt was higher ( P < 0.05) at 1100; 2) metabolic heat production was lower ( P < 0.05) at 1100 and 1500; 3) subjects perceived the Repeat trial as warmer at 1100. These data suggest that repeated cold exposures may impair the ability to maintain normal body temperature because of a blunting of metabolic heat production, perhaps reflecting a fatigue mechanism. An alternative explanation is that shivering habituation develops rapidly during serially repeated cold exposures.
A theoretical study of surfactant and liquid delivery into the lung
Authors: Halpern D. , Jensen O. E. , Grotberg J. B.
Published: December 2017

A computational study is presented for the transport of liquids and insoluble surfactant through the lung airways, delivered from a source at the distal end of the trachea. Four distinct transport regimes are considered: 1) the instilled bolus may create a liquid plug that occludes the large airways but is forced peripherally during mechanical ventilation; 2) the bolus creates a deposited film on the airway walls, either from the liquid plug transport or from direct coating, that drains under the influence of gravity through the first few airway generations; 3) in smaller airways, surfactant species form a surface layer that spreads due to surface-tension gradients, i.e., Marangoni flows; and 4) the surfactant finally reaches the alveolar compartment where it is cleared according to first-order kinetics. The time required for a quasi-steady-state transport process to evolve and for the subsequent delivery of the dose is predicted. Following fairly rapid transients, on the order of seconds, steady-state transport develops and is governed by the interaction of Marangoni flow and alveolar kinetics. Total delivery time is ∼24 h for a typical first dose. Numerical solutions show that both transit and delivery times are strongly influenced by the strength of the preexisting surfactant and the geometric properties of the airway network. Delivery times for follow-up doses can increase significantly as the level of preexisting surfactant rises.
Functional diameters of alveolar microvessels at high lung volume in zone II
Authors: Conhaim Robert L. , Rodenkirch Lance A.
Published: December 2017

To estimate the functional diameter of alveolar microvessels, we perfused isolated rat lungs with fluorescent latex particles (1 diameter/lung) at inflation, pulmonary arterial, and left atrial pressures of 25, 30, and 0 cmH2O, respectively. We used confocal microscopy to count latex particles within septal microvessels and flow cytometry to count particle concentrations in venous outflow. We found 1-, 2-, and 4-μm-diameter particles within septal vessels of 45 ± 12, 31 ± 12, and 25 ± 9%, respectively, of examined alveoli. Particles of 5-μm diameter were absent from septal vessels but were present within a small percentage of corner vessels. Particle concentrations in the venous outflow for 1-, 2-, 4-, and 5-μm-diameter particles were 54 ± 28, 67 ± 32, 2.2 ± 0.3, and 0.4 ± 0.3%, respectively, of the arterial inflow. Particles with diameters of 6 or 10 μm were absent from venous outflow. Our results suggest that, under these conditions, the functional diameter of the septal microvessels is ∼4 μm and that the diameter of the adjacent corner vessels is slightly larger but <6 μm.
Spectrum of aerobic endurance running performance in eleven inbred strains of rats
Authors: Barbato John C. , Koch Lauren Gerard , Darvish Ahmad , Cicila George T. , Metting Patricia J. , Britton Steven L.
Published: December 2017

The goal of this study was to identify inbred rat strains that could serve as useful models for exploration of the genetic basis of aerobic endurance performance. Six rats of each gender from 11 different inbred strains were tested for 1) maximal running capacity on a treadmill and 2) isolated cardiac performance. Running performance was estimated from 1) duration of the run, 2) distance run, and 3) vertical work performed. Cardiac output, during constant preload and afterload, was taken as a measure of cardiac performance from an isolated working heart preparation. The COP rats were the lowest performers and the DA rats were the best performers by all estimates of running performance. Across the 11 strains, the distance run correlated positively with isolated cardiac performance ( r = 0.87). Estimates of performance were as follows (COP vs. DA strain, respectively): duration of run, 19.9 ± 1.8 vs. 41.5 ± 2.2 min; distance run, 298 ± 30 vs. 840 ± 64 m; vertical work, 15 ± 1.7 vs. 40 ± 4.4 kg/m. These ∼2.5-fold differences in running performance between the COP and DA suggest that these strains could serve as models for evaluation of the genetic basis of variance in aerobic performance.
A model for the regulation of cerebral oxygen delivery
Authors: Hyder Fahmeed , Shulman Robert G. , Rothman Douglas L.
Published: December 2017

On the basis of the assumption that oxygen delivery across the endothelium is proportional to capillary plasma[Formula: see text], a model is presented that links cerebral metabolic rate of oxygen utilization ([Formula: see text]) to cerebral blood flow (CBF) through an effective diffusivity for oxygen (D) of the capillary bed. On the basis of in vivo evidence that the oxygen diffusivity properties of the capillary bed may be altered by changes in capillary[Formula: see text], hematocrit, and/or blood volume, the model allows changes in D with changes in CBF. Choice in the model of the appropriate ratio of Ω ≡ (ΔD/D)/(ΔCBF/CBF) determines the dependence of tissue oxygen delivery on perfusion. Buxton and Frank ( J. Cereb. Blood Flow. Metab. 17: 64–72, 1997) recently presented a limiting case of the present model in which Ω = 0. In contrast to the trends predicted by the model of Buxton and Frank, in the current model when Ω > 0, the proportionality between changes in CBF and[Formula: see text] becomes more linear, and similar degrees of proportionality can exist at different basal values of oxygen extraction fraction. The model is able to fit the observed proportionalities between CBF and[Formula: see text] for a large range of physiological data. Although the model does not validate any particular observed proportionality between CBF and[Formula: see text], generally values of ([Formula: see text]/[Formula: see text])/(ΔCBF/CBF) close to unity have been observed across ranges of graded anesthesia in rats and humans and for particular functional activations in humans. The model’s capacity to fit the wide range of data indicates that the oxygen diffusivity properties of the capillary bed, which can be modified in relation to perfusion, play an important role in regulating cerebral oxygen delivery in vivo.
A two-compartment model of pulmonary nitric oxide exchange dynamics
Authors: Tsoukias Nikolaos M. , George Steven C.
Published: December 2017

The relatively recent detection of nitric oxide (NO) in the exhaled breath has prompted a great deal of experimentation in an effort to understand the pulmonary exchange dynamics. There has been very little progress in theoretical studies to assist in the interpretation of the experimental results. We have developed a two-compartment model of the lungs in an effort to explain several fundamental experimental observations. The model consists of a nonexpansile compartment representing the conducting airways and an expansile compartment representing the alveolar region of the lungs. Each compartment is surrounded by a layer of tissue that is capable of producing and consuming NO. Beyond the tissue barrier in each compartment is a layer of blood representing the bronchial circulation or the pulmonary circulation, which are both considered an infinite sink for NO. All parameters were estimated from data in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of the elimination rate of NO at end exhalation (ENO) vs. the exhalation flow rate (V˙E). The model is able to simulate the shape of the NO exhalation profile and to successfully simulate the following experimental features of endogenous NO exchange: 1) an inverse relationship between exhaled NO concentration and V˙E, 2) the dynamic relationship between the phase III slope andV˙E, and 3) the positive relationship between ENOandV˙E. The model predicts that these relationships can be explained by significant contributions of NO in the exhaled breath from the nonexpansile airways and the expansile alveoli. In addition, the model predicts that the relationship between ENOand V˙Ecan be used as an index of the relative contributions of the airways and the alveoli to exhaled NO.
Effects of four different single exercise sessions on lipids, lipoproteins, and lipoprotein lipase
Authors: Ferguson Michael A. , Alderson Nathan L. , Trost Stewart G. , Essig David A. , Burke Jeanmarie R. , Durstine J. Larry
Published: December 2017

The purpose of this study was to determine the threshold of exercise energy expenditure necessary to change blood lipid and lipoprotein concentrations and lipoprotein lipase activity (LPLA) in healthy, trained men. On different days, 11 men (age, 26.7 ± 6.1 yr; body fat, 11.0 ± 1.5%) completed four separate, randomly assigned, submaximal treadmill sessions at 70% maximal O2consumption. During each session 800, 1,100, 1,300, or 1,500 kcal were expended. Compared with immediately before exercise, high-density lipoprotein cholesterol (HDL-C) concentration was significantly elevated 24 h after exercise ( P < 0.05) in the 1,100-, 1,300-, and 1,500-kcal sessions. HDL-C concentration was also elevated ( P < 0.05) immediately after and 48 h after exercise in the 1,500-kcal session. Compared with values 24 h before exercise, LPLA was significantly greater ( P < 0.05) 24 h after exercise in the 1,100-, 1,300-, and 1,500-kcal sessions and remained elevated 48 h after exercise in the 1,500-kcal session. These data indicate that, in healthy, trained men, 1,100 kcal of energy expenditure are necessary to elicit increased HDL-C concentrations. These HDL-C changes coincided with increased LPLA.
Effect of tryptophan and of glucose on exercise capacity of horses
Authors: Farris James W. , Hinchcliff Kenneth W. , McKeever Kenneth H. , Lamb David R. , Thompson Donald L.
Published: December 2017

We hypothesized that central fatigue may have a role in limiting the endurance capacity of horses. Therefore, we tested the effect of infusing tryptophan and/or glucose on endurance time and plasma concentrations of free tryptophan and other substrates thought to affect tryptophan uptake into the brain of seven mares (3–4 yr of age, 353–435 kg) that ran on a treadmill at 50% of maximal O2consumption to fatigue. With use of a counterbalanced crossover design, the horses were infused with tryptophan (100 mg/kg in saline solution) or a similar volume of saline solution (placebo) before exercise. During exercise, horses received infusions of glucose (2 g/min, 50% wt/vol) or a similar volume of saline. Thus the treatments were 1) tryptophan and glucose (T & G), 2) tryptophan and placebo (T & P), 3) placebo and glucose (P & G), and 4) placebo and placebo (P & P). Mean heart rate, hematocrit, and concentration of plasma total solids before and during exercise were similar for all trials. Mean time to exhaustion was reduced ( P < 0.05) for T & P and T & G compared with P & P [86.1 ± 6.9 and 87.1 ± 6.8 vs. 102.3 ± 10.3 (SE) min], whereas endurance for P & G (122.4 ± 11.9 min) was greater than for all other trials ( P < 0.05). Compared with nontryptophan trials, during the tryptophan trials plasma prolactin increased ( P < 0.05) nearly threefold before exercise and almost twofold early in exercise. Muscle glycogen concentrations were reduced ( P < 0.05) below preexercise values in the P & G and P & P trials only. However, glucose infusions (P & G) did not affect ( P > 0.05) concentrations of plasma free fatty acids or ratios of branched-chain amino acids to free tryptophan. In conclusion, tryptophan infusion reduced endurance time, which was consistent with the central fatigue hypothesis. The failure of glucose infusion to alleviate the effects of tryptophan and the absence of significant muscle glycogen reduction in the tryptophan trials suggest that the early onset of fatigue in the tryptophan trials is not due to a lack of readily available substrate.
Muscle coordination in cycling: effect of surface incline and posture
Authors: Li Li , Caldwell Graham E.
Published: December 2017

The purpose of the present study was to examine the neuromuscular modifications of cyclists to changes in grade and posture. Eight subjects were tested on a computerized ergometer under three conditions with the same work rate (250 W): pedaling on the level while seated, 8% uphill while seated, and 8% uphill while standing (ST). High-speed video was taken in conjunction with surface electromyography (EMG) of six lower extremity muscles. Results showed that rectus femoris, gluteus maximus (GM), and tibialis anterior had greater EMG magnitude in the ST condition. GM, rectus femoris, and the vastus lateralis demonstrated activity over a greater portion of the crank cycle in the ST condition. The muscle activities of gastrocnemius and biceps femoris did not exhibit profound differences among conditions. Overall, the change of cycling grade alone from 0 to 8% did not induce a significant change in neuromuscular coordination. However, the postural change from seated to ST pedaling at 8% uphill grade was accompanied by increased and/or prolonged muscle activity of hip and knee extensors. The observed EMG activity patterns were discussed with respect to lower extremity joint moments. Monoarticular extensor muscles (GM, vastus lateralis) demonstrated greater modifications in activity patterns with the change in posture compared with their biarticular counterparts. Furthermore, muscle coordination among antagonist pairs of mono- and biarticular muscles was altered in the ST condition; this finding provides support for the notion that muscles within these antagonist pairs have different functions.
Deposition and dispersion of 1-μm aerosol boluses in the human lung: effect of micro- and hypergravity
Authors: Darquenne Chantal , West John B. , Prisk G. Kim
Published: December 2017

We performed bolus inhalations of 1-μm particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (μG) and in ∼1.6 G. Boluses of ∼70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp ≥400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in μG to 56.9% and 573 ml at ∼1.6 G, respectively ( P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in μG than in 1 G and ∼1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.
Augmenting expiratory neuronal activity in sleep and wakefulness and in relation to duration of expiration
Authors: Orem John
Published: December 2017

Augmenting expiratory cells ( n = 23) were recorded in the rostral medulla of five cats in sleep and wakefulness. The objective was to determine the relationship of their activity to the duration of expiration (Te) and, particularly, to Te in rapid-eye-movement (REM) sleep, when expirations are short and may even cause fractionated breathing. Correlation analysis (Kendall’s τ) showed no consistent relationship in any state between the breath-by-breath mean activity of augmenting expiratory cells and Te. This result contradicts predications of an inverse relationship between augmenting expiratory activity and Te. Some cells (11 of 23) were more active in REM than in non-REM sleep and were active during fractionated breathing. This suggests that fractionated breathing in REM sleep is caused by short expiratory phases and not by intermittent inhibition of an ongoing inspiration.
Superoxide dismutase restores endothelium-dependent arteriolar dilatation during acute infusion of nicotine
Authors: Mayhan William G. , Sharpe Glenda M.
Published: December 2017

We previously showed [ Am. J. Physiol. 272 ( Heart Circ. Physiol. 41): H2337–H2342, 1997] that nicotine impairs endothelium-dependent arteriolar dilatation. However, mechanisms that accounted for the effect of nicotine on endothelium-dependent vasodilatation were not examined. Thus the goal of this study was to examine the role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity. We measured diameter of cheek pouch resistance arterioles (∼50 μm diameter) in response to endothelium-dependent (ACh and ADP) and -independent (nitroglycerin) agonists before and after infusion of vehicle or nicotine in the absence or presence of superoxide dismutase. ACh, ADP, and nitroglycerin produced dose-related dilatation of cheek pouch arterioles before infusion of vehicle or nicotine. Infusion of vehicle, in the absence or presence of superoxide dismutase (150 U/ml), did not alter endothelium-dependent or -independent arteriolar dilatation. In contrast, infusion of nicotine (2 μg ⋅ kg−1⋅ min−1) impaired endothelium-dependent, but not -independent, arteriolar dilatation. In addition, the effect of nicotine on endothelium-dependent vasodilatation was reversed by topical application of superoxide dismutase. We suggest that nicotine impairs endothelium-dependent arteriolar dilatation via an increase in the synthesis/release of oxygen-derived free radicals.
O2 uptake kinetics after acetazolamide administration during moderate- and heavy-intensity exercise
Authors: Scheuermann Barry W. , Kowalchuk John M. , Paterson Donald H. , Cunningham David A.
Published: December 2017

Inhibition of carbonic anhydrase (CA) is associated with a lower plasma lactate concentration ([La−]pl) during fatiguing exercise. We hypothesized that a lower [La−]plmay be associated with faster O2uptake (V˙o 2) kinetics during constant-load exercise. Seven men performed cycle ergometer exercise during control (Con) and acute CA inhibition with acetazolamide (Acz, 10 mg/kg body wt iv). On 6 separate days, each subject performed 6-min step transitions in work rate from 0 to 100 W (below ventilatory threshold, V˙eT). Gas exchange was measured breath by breath. Trials were interpolated at 1-s intervals and ensemble averaged to yield a single response. The mean response time (MRT, i.e., time to 63% of total exponential increase) for on- and off-transients was determined using a two- (V˙eT). Arterialized venous blood was sampled from a dorsal hand vein and analyzed for [La−]pl. MRT was similar during Con (31.2 ± 2.6 and 32.7 ± 1.2 s for on and off, respectively) and Acz (30.9 ± 3.0 and 31.4 ± 1.5 s for on and off, respectively) for work rates V˙eT, MRT was similar between Con (69.1 ± 6.1 and 50.4 ± 3.5 s for on and off, respectively) and Acz (69.7 ± 5.9 and 53.8 ± 3.8 s for on and off, respectively). On- and off-MRTs were slower for >V˙eT than for <V˙eT exercise. [La−]plincreased above 0-W cycling values during V˙eT exercise but was lower at the end of the transition during Acz (1.4 ± 0.2 and 7.1 ± 0.5 mmol/l for V˙eT, respectively) than during Con (2.0 ± 0.2 and 9.8 ± 0.9 mmol/l for V˙eT, respectively). CA inhibition does not affect O2 utilization at the onset of V˙eT exercise, suggesting that the contribution of oxidative phosphorylation to the energy demand is not affected by acute CA inhibition with Acz.
Peripheral O2 diffusion does not affect V˙o 2 on-kinetics in isolated in situ canine muscle
Authors: Grassi Bruno , Gladden L. Bruce , Stary Creed M. , Wagner Peter D. , Hogan Michael C.
Published: December 2017

To test the hypothesis that muscle O2 uptake (V˙o 2) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined theV˙o 2 on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles ( n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60–70% peakV˙o 2). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q˙), at a level measured at steady state during contractions in preliminary trials with spontaneous Q˙. Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q˙. Q˙ was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, andV˙o 2 was calculated asQ˙ ⋅ arteriovenous O2 content difference.[Formula: see text] at 50% Hbo 2saturation (P50) was calculated. Mean capillary [Formula: see text](P [Formula: see text]) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 ± 1 (SE) Torr] than in Control and in Hyperoxia (31 ± 1 Torr). After 15 s of contractions,P [Formula: see text]was higher in Hyperoxia (97 ± 9 Torr) vs. Control (53 ± 3 Torr) and in Hyperoxia+RSR-13 (197 ± 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-stateV˙o 2 during contractions was 24.7 ± 2.7 s in Control, 26.3 ± 0.8 s in Hyperoxia, and 24.7 ± 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increasedP [Formula: see text]at constant O2 delivery) during the rest-to-contraction (60–70% of peakV˙o 2) transition did not affect muscle V˙o 2on-kinetics.
Spaceflight and development of immune responses
Authors: Sonnenfeld Gerald , Foster Mareva , Morton Darla , Bailliard Frederique , Fowler Nina A. , Hakenewerth Anne M. , Bates Roge , Miller Edwin S.
Published: December 2017

The NIH.R1 Space Shuttle experiment was designed to study the effects of spaceflight on rodent development. Pregnant rats were flown on the Space Shuttle for 11 days, and pregnant control rats were maintained in animal enclosure modules in a ground-based chamber under conditions approximating those in flight. Additional controls were in standard housing. The effects of the flight on immunological parameters of dams, fetuses, and pups were determined. Blastogenesis of spleen cells in response to mitogen was inhibited in flown dams but was not inhibited in cells from their pups. Interferon-γ production by spleen cells showed a trend toward inhibition in flown dams but not in their pups. The response of bone marrow cells to colony-stimulating factor showed a trend toward inhibition after spaceflight in dams, but the response of fetus and pup liver cells was not inhibited. Total serum IgG was not affected by spaceflight. None of the examined immune parameters that were altered in rat dams after spaceflight was found to be altered in their offspring.
Effect of exercise timing on postprandial lipemia and HDL cholesterol subfractions
Authors: Zhang John Q. , Thomas Tom R. , Ball Stephen D.
Published: December 2017

The purpose of the study was to examine the effect of exercise timing on postprandial lipemia responses. Subjects were 21 recreationally trained men (ages 27 ± 1.7 yr). Each subject performed four trials: 1) Control (fat meal only), 2) Post (exercise 1 h after a fat meal), 3) 1 h-Pre (exercise 1 h before a fat meal), and 4) 12 h-Pre (exercise 12 h before a fat meal). In each trial, subjects had a standard fat meal to induce postprandial hypertriglyceridemia. Blood samples were taken at 0 h (immediately before the fat meal) and at 2, 4, 6, 8, and 24 h after the meal. In the exercise trials, each subject exercised at 60% of maximal O2 consumption for 1 h. The results indicated that triglyceride area under the curve scores in premeal-exercise trials were lower ( P< 0.05) than those in Post and Control. At 24 h, total high-density lipoprotein (HDL)-cholesterol in the premeal-exercise trials was higher ( P < 0.05) than that at 0 h, whereas total HDL-cholesterol was not changed in Control and Post. At 24 h, HDL subtype 2-cholesterol was higher ( P< 0.05) in the premeal-exercise trials than in Control, which did not differ from Post. These results suggest that exercising before a fat meal may have a beneficial effect on the triglyceride response and HDL metabolism, which may blunt atherosclerotic process induced by the fat meal.
Effects of prior exercise on exercise-induced arterial hypoxemia in young women
Authors: St. Croix Claudette M. , Harms Craig A. , McClaran Steven R. , Nickele Glenn A. , Pegelow David F. , Nelson William B. , Dempsey Jerome A.
Published: December 2017

Twenty-eight healthy women (ages 27.2 ± 6.4 yr) with widely varying fitness levels [maximal O2consumption (V˙o 2 max), 31–70 ml ⋅ kg−1 ⋅ min−1] first completed a progressive incremental treadmill test toV˙o 2 max (total duration, 13.3 ± 1.4 min; 97 ± 37 s at maximal workload), rested for 20 min, and then completed a constant-load treadmill test at maximal workload (total duration, 143 ± 31 s). At the termination of the progressive test, 6 subjects had maintained arterial [Formula: see text] [Formula: see text]) near resting levels, whereas 22 subjects showed a >10 Torr decrease in[Formula: see text] [78.0 ± 7.2 Torr, arterial O2 saturation[Formula: see text]), 91.6 ± 2.4%], and alveolar-arterial O2 difference (A-[Formula: see text], 39.2 ± 7.4 Torr). During the subsequent constant-load test, all subjects, regardless of their degree of exercise-induced arterial hypoxemia (EIAH) during the progressive test, showed a nearly identical effect of a narrowed A-[Formula: see text](−4.8 ± 3.8 Torr) and an increase in[Formula: see text] (+5.9 ± 4.3 Torr) and[Formula: see text] (+1.6 ± 1.7%) compared with at the end point of the progressive test. Therefore, EIAH during maximal exercise was lessened, not enhanced, by prior exercise, consistent with the hypothesis that EIAH is not caused by a mechanism which persists after the initial exercise period and is aggravated by subsequent exercise, as might be expected of exercise-induced structural alterations at the alveolar-capillary interface. Rather, these findings in habitually active young women point to a functionally based mechanism for EIAH that is present only during the exercise period.
Histamine H3 activation depresses cardiac function in experimental sepsis
Authors: Li X. , Eschun G. , Bose D. , Jacobs H. , Yang J. J. , Light R. B. , Mink S. N.
Published: December 2017

In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P< 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker–sepsis group compared with values obtained in a nonsepsis–time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.
Does the application of ground force set the energetic cost of cross-country skiing?
Authors: Bellizzi Matthew J. , King Kellin A. D. , Cushman Sara K. , Weyand Peter G.
Published: December 2017

We tested whether the rate at which force is applied to the ground sets metabolic rates during classical-style roller skiing in four ways: 1) by increasing speed (from 2.5 to 4.5 m/s) during skiing with arms only, 2) by increasing speed (from 2.5 to 4.5 m/s) during skiing with legs only, 3) by changing stride rate (from 25 to 75 strides/min) at each of three speeds (3.0, 3.5, and 4.0 m/s) during skiing with legs only, and 4) by skiing with arms and legs together at three speeds (2.0–3.2 m/s, 1.5° incline). We determined net metabolic rates from rates of O2consumption (gross O2consumption − standing O2consumption) and rates of force application from the inverse period of pole-ground contact [1/ tp(arms)] for the arms and the inverse period of propulsion [1/ tp(legs)] for the legs. During arm-and-leg skiing at different speeds, metabolic rates changed in direct proportion to rates of force application, while the net ground force to counteract friction and gravity (F) was constant. Consequently, metabolic rates were described by a simple equation (E˙metab=F ⋅ 1/ tp⋅ C, where E˙metabis metabolic rates) with cost coefficients ( C) of 8.2 and 0.16 J/N for arms and legs, respectively. Metabolic rates predicted from net ground forces and rates of force application during combined arm-and-leg skiing agreed with measured metabolic rates within ±3.5%. We conclude that rates of ground force application to support the weight of the body and overcome friction set the energetic cost of skiing and that the rate at which muscles expend metabolic energy during weight-bearing locomotion depends on the time course of their activation.
Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects
Authors: Meza Sonia , Mendez Manuel , Ostrowski Michele , Younes Magdy
Published: December 2017

Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (Vt) and elastance (Vt sp ⋅ E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the[Formula: see text] (difference between eupneic[Formula: see text] and CO2 apneic threshold) and by ΔRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2–5 min each) until PB developed or the subject awakened. End-tidal [Formula: see text], Vt, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(ΔPaw + Pmus)/Pmus], where ΔPaw is peak Paw − continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. [Formula: see text]ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to −3.5 min−1). With use of stepwise regression, PSV(PB) was significantly correlated with Vt sp( P = 0.001), E ( P = 0.00009),[Formula: see text]( P = 0.007), and ΔRR ( P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 Vt sp + 0.3E − 0.4 [Formula: see text] − 0.34 ΔRR − 3.4 ( r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5–3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a[Formula: see text] apneic threshold exists during sleep at 1.5–5.8 Torr below eupneic[Formula: see text], 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.
Force-velocity-power and force-pCa relationships of human soleus fibers after 17 days of bed rest
Authors: Widrick J. J. , Norenberg K. M. , Romatowski J. G. , Blaser C. A. , Karhanek M. , Sherwood J. , Trappe S. W. , Trappe T. A. , Costill D. L. , Fitts R. H.
Published: December 2017

Soleus muscle fibers from the rat display a reduction in peak power and Ca2+ sensitivity after hindlimb suspension. To examine human responses to non-weight bearing, we obtained soleus biopsies from eight adult men before and immediately after 17 days of bed rest (BR). Single chemically skinned fibers were mounted between a force transducer and a servo-controlled position motor and activated with maximal (isotonic properties) and/or submaximal (Ca2+ sensitivity) levels of free Ca2+. Gel electrophoresis indicated that all pre- and post-BR fibers expressed type I myosin heavy chain. Post-BR fibers obtained from one subject displayed increases in peak power and Ca2+ sensitivity. In contrast, post-BR fibers obtained from the seven remaining subjects showed an average 11% reduction in peak power ( P < 0.05), with each individual displaying a 7–27% reduction in this variable. Post-BR fibers from these subjects were smaller in diameter and produced 21% less force at the shortening velocity associated with peak power. However, the shortening velocity at peak power output was elevated 13% in the post-BR fibers, which partially compensated for their lower force. Post-BR fibers from these same seven subjects also displayed a reduced sensitivity to free Ca2+( P < 0.05). These results indicate that the reduced functional capacity of human lower limb extensor muscles after BR may be in part caused by alterations in the cross-bridge mechanisms of contraction.
The myth of maximal airway responsiveness in vivo
Authors: Brown Robert H. , Mitzner Wayne
Published: December 2017

A sine qua non of hyperresponsive airway disease in asthmatic subjects is the lack of a maximal response with increasing doses of aerosol agonist challenge. Normal subjects, however, often appear to exhibit an airway response plateau effect even when challenged with high concentrations of agonist. To investigate this question of maximal narrowing in individual airways in vivo, we used high-resolution computed tomography to visualize canine airways narrowed by two routes of agonist challenge. We compared airway narrowing induced by methacholine (MCh) via the conventional aerosol route to that caused by local atomization of MCh directly to individual airways. Our results showed that, with aerosol challenge, airway responses never reached a truly flat plateau even at the highest possible nebulizer concentrations. Airway closure was never observed. However, when MCh was delivered directly to the airway luminal surface, airways could be easily narrowed to complete closure at modest (10 mg/ml) agonist concentrations. Thus neither the elastic recoil of the lung nor limitations of smooth muscle shortening can be responsible for the apparent plateauing of dose-response curves. We suggest that the plateau results from limitations associated with the delivery of high concentration of agonists via the aerosol route.
Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia
Authors: Fewell James E. , Smith Francine G.
Published: December 2017

Failure to autoresuscitate by hypoxic gasping during prolonged sleep apnea has been suggested to play a role in sudden infant death. Furthermore, maternal smoking has been repeatedly shown to be a risk factor for sudden infant death. The present experiments were carried out on newborn rat pups to investigate the influence of perinatal exposure to nicotine (the primary pharmacological and addictive agent in tobacco) on their time to last gasp during a single hypoxic exposure and on their ability to autoresuscitate during repeated exposure to hypoxia. Pregnant rats received either nicotine (6 mg ⋅ kg−1⋅ 24 h−1) or vehicle continuously from day 6 of gestation to days 5 or 6 postpartum via an osmotic minipump. On days 5 or 6 postpartum, pups were exposed either to a single period of hypoxia (97% N2-3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp, but it did impair the ability of pups to autoresuscitate from primary apnea. After vehicle, the pups were able to autoresuscitate from 18 ± 1 (SD) periods of hypoxia, whereas, after nicotine, the pups were able to autoresuscitate from only 12 ± 2 periods ( P < 0.001) of hypoxia. Thus our data provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea during repeated exposure to hypoxia, such as may occur during episodes of prolonged sleep apnea.
Short-term exercise enhances insulin-stimulated GLUT-4 translocation and glucose transport in adipose cells
Authors: Ferrara Cynthia M. , Reynolds Thomas H. , Zarnowski Mary Jane , Brozinick Joseph T. , Cushman Samuel W.
Published: December 2017

This investigation examined the effects of short-term exercise training on insulin-stimulated GLUT-4 glucose transporter translocation and glucose transport activity in rat adipose cells. Male Wistar rats were randomly assigned to a sedentary (Sed) or swim training group (Sw, 4 days; final 3 days: 2 × 3 h/day). Adipose cell size decreased significantly but minimally (∼20%), whereas total GLUT-4 increased by 30% in Sw vs. Sed rats. Basal 3- O-methyl-d-[14C]glucose transport was reduced by 62%, whereas maximally insulin-stimulated (MIS) glucose transport was increased by 36% in Sw vs. Sed rats. MIS cell surface GLUT-4 photolabeling was 44% higher in the Sw vs. Sed animals, similar to the increases observed in MIS glucose transport activity and total GLUT-4. These results suggest that increases in total GLUT-4 and GLUT-4 translocation to the cell surface contribute to the increase in MIS glucose transport with short-term exercise training. In addition, the results suggest that the exercise training-induced adaptations in glucose transport occur more rapidly than previously thought and with minimal changes in adipose cell size.
Changes in respiratory control during and after 48 h of isocapnic and poikilocapnic hypoxia in humans
Authors: Tansley John G. , Fatemian Marzieh , Howard Luke S. G. E. , Poulin Marc J. , Robbins Peter A.
Published: December 2017

Ventilatory acclimatization to hypoxia is associated with an increase in ventilation under conditions of acute hyperoxia (V˙e hyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). This study compares 48-h exposures to isocapnic hypoxia ( protocol I) with 48-h exposures to poikilocapnic hypoxia ( protocol P) in 10 subjects to assess the importance of hypocapnic alkalosis in generating the changes observed in ventilatory acclimatization to hypoxia. During both hypoxic exposures, end-tidal [Formula: see text] was maintained at 60 Torr, with end-tidal [Formula: see text] held at the subject’s prehypoxic level ( protocol I) or uncontrolled ( protocol P).V˙e hyperoxiaand AHVR were assessed regularly throughout the exposures.V˙e hyperoxia( P < 0.001, ANOVA) and AHVR ( P < 0.001) increased during the hypoxic exposures, with no significant differences between protocols I and P. The increase inV˙e hyperoxiawas associated with an increase in slope of the ventilation-end-tidal [Formula: see text] response ( P < 0.001) with no significant change in intercept. These results suggest that changes in respiratory control early in ventilatory acclimatization to hypoxia result from the effects of hypoxia per se and not the alkalosis normally accompanying hypoxia.
Two-step, predictive, isometric force model tested on data from human and rat muscles
Authors: Ding Jun , Binder-Macleod Stuart A. , Wexler Anthony S.
Published: December 2017

Functional electrical stimulation can assist paralyzed individuals to perform functional movements, but muscle fatigue is a major limitation to its practical use. An accurate and predictive mathematical model can facilitate the design of stimulation patterns that optimize aspects of the force transient while minimizing fatigue. Solution nonuniqueness, a major shortcoming in previous work, was overcome with a simpler model. The model was tested on data collected during isometric contractions of rat gastrocnemius muscles and human quadriceps femoris muscles under various physiological conditions. For each condition tested, parameter values were identified using the force response to one or two stimulation trains. The parameterized model was then used to predict forces in response to other stimulation patterns. The predicted forces closely matched the measured forces. The model was not sensitive to initial parameter estimates, demonstrating solution uniqueness. By predicting the force that develops in response to an arbitrary pattern of stimulation, we envision the present model helping identify optimal stimulation patterns for activation of skeletal muscle during functional electrical stimulation.
Is there evidence for an age-related reduction in metabolic rate?
Authors: Piers Leonard S. , Soares Mario J. , McCormack Leanne M. , O’Dea Kerin
Published: December 2017

To determine whether the age-related reduction in basal metabolic rate (BMR) is explained by a quantitative and/or qualitative change in the components of lean tissue, we conducted a cross-sectional study in groups of young ( n = 38, 18–35 yr) and older ( n = 24, 50–77 yr) healthy individuals. BMR was measured by indirect calorimetry. Body composition was obtained by using dual-energy X-ray absorptiometry (DEXA), which permitted four compartments to be quantified [bone mineral mass, fat mass (FM), appendicular lean tissue mass (ALTM), and nonappendicular lean tissue mass (NALTM)]. Absolute BMR and ALTMwere lower, whereas FM was significantly higher in the older, compared with young, subjects. BMR, adjusted for differences in FM, ALTM, and NALTM,was significantly lower in the older subjects by 644 kJ/day. In separate regression analyses of BMR on body compartments, older subjects had significantly lower regression coefficients for ALTMand NALTM, compared with young subjects. Hence, the age-related decline in BMR is partly explained by a reduction in the quantity, as well as the metabolic activity, of DEXA-derived lean tissue components.