bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal tract, hepatic, hindlimb, and renal recovery of CO2in vivo
Authors: Gresham Jennifer D. , Okamura Koji , Williams Phillip E. , Jabbour Kareem , Flakoll Paul J.
Published: December 2017

Whole body oxidative rates of labeled substrates are often measured by collecting expired air and determining the amount of labeled CO2that is produced. However, the CO2produced may not be completely recovered under all circumstances, and there is a wide variation in values reported under different experimental conditions (∼50–100%). The potential contribution of specific organs to this variation has not been defined. In vivo studies using healthy, postabsorptive, multicatheterized conscious canines were conducted to determine gastrointestinal tract, hepatic, hindlimb, and renal recoveries of NaH14CO3during a 180-min constant infusion [0.022 ± 0.002 (SE) μCi · kg−1· min−1]. Before the constant infusion period, a bolus infusion of NaH14CO3(1.76 ± 0.16 μCi/kg) was given, and the rate of decay in blood was measured over a 15-min period to determine pool size. The pool size for the distribution of14CO2was ∼80% of the total body pool (16.0 ± 1.7 liters). Whole body recovery was 97.2 ± 6.7%. The recoveries across the liver, gut, leg, and kidney were 99.9 ± 1.3, 98.0 ± 1.4, 96.7 ± 2.6, and 99.9 ± 2.1%, respectively. In conclusion, hepatic, gastrointestinal tract, hindlimb, and renal recoveries of CO2in vivo were near 100%, suggesting that CO2loss is not greater in gluconeogenic organs and that corrections for incomplete recovery of CO2, when measuring oxidation of substrates across these organs under normal postabsorptive conditions, would be very minor.
The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins
Authors: Dunbar Stacey L. , Berkowitz Dan E. , Brooks-Asplund Esther M. , Shoukas Artin A.
Published: December 2017

Microgravity is associated with an impaired cardiac output response to orthostatic stress. Mesenteric veins are critical in modulating cardiac filling through venoconstriction. The purpose of this study was to determine the effects of simulated microgravity on the capacitance of rat mesenteric small veins. We constructed pressure-diameter relationships from vessels of 21-day hindlimb-unweighted (HLU) rats and control rats by changing the internal pressure and measuring the external diameter. Pressure-diameter relationships were obtained both before and after stimulation with norepinephrine (NE). The pressure-diameter curves of HLU vessels were shifted to larger diameters than control vessels. NE (10−4 M) constricted veins from control animals such that the pressure-diameter relationship was significantly shifted downward (i.e., to smaller diameters at equal pressure). NE had no effect on vessels from HLU animals. These results indicate that, after HLU, unstressed vascular volume may be increased and can no longer decrease in response to sympathetic stimulation. This may partially underlie the mechanism leading to the exaggerated fall in cardiac output and stroke volume seen in astronauts during an orthostatic stress after exposure to microgravity.
Invited Review: Engineering approaches to cytoskeletal mechanics
Authors: Stamenović Dimitrije , Wang Ning
Published: December 2017

An outstanding problem in cell biology is how cells sense mechanical forces and how those forces affect cellular functions. Various biophysical and biochemical mechanisms have been invoked to answer this question. A growing body of evidence indicates that the deformable cytoskeleton (CSK), an intracellular network of interconnected filamentous biopolymers, provides a physical basis for transducing mechanical signals into biochemical signals. Therefore, to understand how mechanical forces regulate cellular functions, it is important to know how cells respond to changes in the CSK force balance and to identify the underlying mechanisms that control transmission of mechanical forces throughout the CSK and bring it to equilibrium. Recent developments of new experimental techniques for measuring cell mechanical properties and novel theoretical models of cellular mechanics make it now possible to identify and quantitate the contributions of various CSK structures to the overall balance of mechanical forces in the cell. This review focuses on engineering approaches that have been used in the past two decades in studies of the mechanics of the CSK.
Selected Contribution: Mechanical strain increases force production and calcium sensitivity in cultured airway smooth muscle cells
Authors: Smith Paul G. , Roy Chaity , Fisher Steven , Huang Qi-Quan , Brozovich Frank
Published: December 2017

Cultured airway smooth muscle cells subjected to cyclic deformational strain have increased cell content of myosin light chain kinase (MLCK) and myosin and increased formation of actin filaments. To determine how these changes may increase cell contractility, we measured isometric force production with changes in cytosolic calcium in individual permeabilized cells. The pCa for 50% maximal force production was 6.6 ± 0.4 in the strain cells compared with 5.9 ± 0.3 in control cells, signifying increased calcium sensitivity in strain cells. Maximal force production was also greater in strain cells (8.6 ± 2.9 vs. 5.7 ± 3.1 μN). The increased maximal force production in strain cells persisted after irreversible thiophosphorylation of myosin light chain, signifying that increased force could not be explained by differences in myosin light chain phosphorylation. Cells strained for brief periods sufficient to increase cytoskeletal organization but insufficient to increase contractile protein content also produced more force, suggesting that strain-induced cytoskeletal reorganization also increases force production.
Plasma vasopressin and aldosterone responses to oral and intravenous saline rehydration
Authors: Kenefick Robert W. , Maresh Carl M. , Armstrong Lawrence E. , Castellani John W. , Riebe Deborah , Echegaray Marcos E. , Kavorous Stavros A.
Published: December 2017

This investigation examined plasma arginine vasopressin (AVP) and aldosterone (Ald) responses to 1) oral and intravenous (IV) methods of rehydration (Rh) and 2) different IV Rh osmotic loads. We hypothesized that AVP and Ald responses would be similar between IV and oral Rh and that the greater osmolality and sodium concentration of a 0.9% IV saline treatment would stimulate a greater AVP response compared with a 0.45% IV saline treatment. On four occasions, eight men (age: 22.1 ± 0.8 yr; height: 179.6 ± 1.5 cm; weight: 73.6 ± 2.5 kg; maximum O2consumption: 57.9 ± 1.6 ml · kg−1 · min−1, body fat: 7.7 ± 0.9%) performed a dehydration (Dh) protocol (33°C) to establish a 4–5% reduction in body weight. After Dh, subjects underwent each of three randomly assigned Rh (back to −2% body wt) treatments (0.9 and 0.45% IV saline, 0.45% oral saline) and a no Rh treatment during the first 45 min of a 100-min rest period. Blood samples were obtained pre-Dh, immediately post-Dh, and at 15, 35, and 55 min post-Rh. Before Dh, plasma AVP and Ald were not different among treatments but were significantly elevated post-Dh. In general, at 15, 35, and 55 min post-Rh, AVP, Ald, osmolality, and plasma volume shifts did not differ between IV and oral fluid replacement. These results demonstrated that the manner in which plasma AVP and Ald responded to oral and IV Rh or to different sodium concentrations (0.9 vs. 0.45%) was not different given the degree of Dh (−4.5% body wt) and Rh and amount of time after Rh (55 min).
Effects of hypoxia and hypercapnia on circadian rhythms in the golden hamster (Mesocricetus auratus)
Authors: Jarsky Tim M. , Stephenson Richard
Published: December 2017

This study was designed to determine whether respiratory stimuli can influence the mammalian circadian timing system. Three-hour pulses of hypoxia (inspired O2concentration = 8%) or hypercapnia (inspired CO2concentration = 11%) were presented for 7 days at mid-subjective day (circadian time 6–9) under constant darkness. Hypoxic and hypercapnic pulses caused cumulative phase delays of 46.4 ± 6.9 and 25.9 ± 12.3 min, respectively. Distance run per day was significantly reduced on hypoxic and hypercapnic pulse days, compared with nonpulsed days. Phase shifts were correlated with the reduction in daily running activity (multiple r2= 0.521, P = 0.036), metabolic depression (multiple r2= 0.772, P < 0.001), and reduction in body temperature (multiple r2= 0.539, P = 0.027), but not lung ventilation (multiple r2= 0.306, P = 0.414) during pulses. We conclude that hypoxia and hypercapnia can influence the phase and quantity of activity in free-running hamsters.
Muscle volume, MRI relaxation times (T2), and body composition after spaceflight
Authors: LeBlanc Adrian , Lin Chen , Shackelford Linda , Sinitsyn Valentine , Evans Harlan , Belichenko Oleg , Schenkman Boris , Kozlovskaya Inessa , Oganov Victor , Bakulin Alexi , Hedrick Thomas , Feeback Daniel
Published: December 2017

Postflight changes in muscle volume, calf muscle transverse relaxation time, and total body composition were measured in 4 crewmembers after a 17-day mission and in 14–16 crewmembers in multiple shuttle/Mir missions of 16- to 28-wk duration. During the 17-day mission, all muscle regions except the hamstrings significantly decreased 3–10% compared with baseline. During the shuttle/Mir missions, there were significant decreases in muscle volume (5–17%) in all muscle groups except the neck. These changes, which reached a new steady state by 4 mo of flight or less, were reversed within 30–60 days after landing. Postflight swelling and elevation of calf muscle transverse relaxation time persisted for several weeks after flight, which suggests possible muscle damage. In contrast to the 17-day flight, in which loss in fat, but not lean body mass, was found (25), losses in bone mineral content and lean body mass, but not fat, were seen after the longer shuttle/Mir missions. The percent losses in total body lean body mass and bone mineral content were similar at ∼3.4–3.5%, whereas the pelvis demonstrated the largest regional bone loss at 13%.
Macromolecule transfer through mesothelium and connective tissue
Authors: Bodega Francesca , Zocchi Luciano , Agostoni Emilio
Published: December 2017

Diffusional permeability ( P) to inulin ( P in), albumin ( P alb), and dextrans [70 ( P dx 70), 150 ( P dx 150), 550 ( P dx 550), and 2,000 ( P dx 2,000)] was determined in specimens of parietal pericardium of rabbits, which may be obtained with less damage than pleura. P in, P alb, P dx 70, P dx 150, P dx 550, and P dx 2,000 were 0.51 ± 0.06 (SE), 0.18 ± 0.03, 0.097 ± 0.021, 0. 047 ± 0.011, 0.025 ± 0.004, and 0.021 ± 0.005 × 10−5cm/s, respectively. P in, P alb, and P dx 70 of connective tissue, obtained after removal of mesothelium from specimens, were 10.3 ± 1.42, 2.97 ± 0.38, and 2.31 ± 0.16 × 10−5 cm/s, respectively. Hence, P in, P alb, and P dx 70 of mesothelium were 0.54, 0.20, and 0.10 × 10−5 cm/s, respectively. Inulin (like small solutes) fitted the relationship P-solute radius for restricted diffusion with a 6-nm “pore” radius, whereas macromolecules were much above it. Hence, macromolecule transfer mainly occurs through “large pores” and/or transcytosis. In line with this, the addition of phospholipids on the luminal side (which decreases pore radius to ∼1.5 nm) halved P in but did not change P alband P dx 70. P in is roughly similar in mesothelium and capillary endothelium, whereas P to macromolecules is greater in mesothelium. The albumin diffusion coefficient through connective tissue was 17% of that in water. Mesothelium provides 92% of resistance to albumin diffusion through the pericardium.
Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing
Authors: Kamijo Y. , Takeno Y. , Sakai A. , Inaki M. , Okumoto T. , Itoh J. , Yanagidaira Y. , Masuki S. , Nose H.
Published: December 2017

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac−]p) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (−15 cmH2O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac−]p for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 ( P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise ( P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WLmax) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity ( P < 0.01) except for MBF at 70% WLmax, whereas the increase in MAP for N2 was attenuated compared with that in C2 ( P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac−]p might be caused, at least partially, by the increased MBF.
Nonlinear summation of force in cat soleus muscle results primarily from stretch of the common-elastic elements
Authors: Sandercock Thomas G.
Published: December 2017

The complex connective tissue structure of muscle and tendon suggests that forces from two parts of a muscle may not summate linearly. This study measured the nonlinear summation of force (Fnl) in whole cat soleus during isometric and ramp movements. In six anesthetized cats, the soleus was attached to a servomechanism to control muscle length and record force. The ventral roots were divided into two bundles, each innervating about half the soleus; thus the two parts could be stimulated alone or together. In all experiments, Fnl was small (<6% of maximum tetanic tension). Peak Fnl occurred during changes in muscle force, either as a result of imposed muscle movement or the onset or offset of a stimulus train. The data were fit to a model in which both parts of the muscle were assumed to stretch to a common elasticity. The servomechanism was programmed to compensate for reduced stretch of the common elasticity during partial compared with whole muscle activation. These compensatory movements showed how the model could account for most, but not all, of Fnl.
Paraxanthine, a caffeine metabolite, dose dependently increases [Ca2+]iin skeletal muscle
Authors: Hawke Thomas J. , Allen D. G. , Lindinger M. I.
Published: December 2017

It was hypothesized that the caffeine derivative paraxanthine results in subcontracture increases in intracellular calcium concentration ([Ca2+]i) in resting skeletal muscle. Single fibers obtained from mouse flexor digitorum brevis were loaded with a fluorescent Ca2+indicator, indo 1-acetoxymethyl ester. After a stable baseline was recorded, the fiber was superfused with physiological salt solution (Tyrode) containing 0.5, 1.0, 2.5, or 5 mM paraxanthine, resulting in [Ca2+]iincreases of 6.4 ± 2.5, 9.7 ± 3.6, 26.8 ± 11.7, and 39.6 ± 9.6 nM, respectively. The increases in [Ca2+]iwere transient and were also observed with exposure to 5 mM theophylline and theobromine. Six fibers were exposed to 5 mM paraxanthine followed by 5 mM paraxanthine in the presence of 10 mM procaine (sarcoplasmic reticulum Ca2+release channel blocker). There was no increase from baseline [Ca2+]iwhen fibers were superfused with paraxanthine and procaine, suggesting that the sarcoplasmic reticulum is the primary Ca2+source in the paraxanthine-induced response. In separate experiments, intact flexor digitorum brevis ( n = 13) loaded with indo 1-acetoxymethyl ester had a significant increase in [Ca2+]iwith exposure to 0.01 mM paraxanthine. It is concluded that physiological and low pharmacological concentrations of paraxanthine result in transient, subcontracture increases in [Ca2+]iin resting skeletal muscle, the magnitude of which is related to paraxanthine concentration.
Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury
Authors: Boyd Steven K. , Matyas John R. , Wohl Greg R. , Kantzas Apostolos , Zernicke Ronald F.
Published: December 2017

The present study measured early-stage adaptation of bone mineral (BMD) in the periarticular cancellous bone of the canine knee (stifle) joint after anterior cruciate ligament (ACL) transection (ACLX). Regional changes in BMD in the tibia and femur were analyzed by using quantitative computed tomography (qCT) at 3 wk and 12 wk after unilateral ACLX to determine whether there were focal points for BMD changes and whether these changes occurred early after the induced knee injury. BMD decreased rapidly after ACLX, and the more pronounced response was in the femur. In the 3-wk group, there were decreases in BMD in the tibia and the femur, and these changes were significant in the posterior-medial region of the femur, which showed a decrease of BMD in the ACLX limb (−0.048 ± 0.011 g/cm3). In the 12-wk group, all regions in the tibia and femur exhibited significant decreases in BMD, and the average decrease was greatest in the posterior-medial region of the femur (−0.142 ± 0.021 g/cm3). The regions of pronounced periarticular cancellous BMD adaptation corresponded to observed focal cartilage defects. Early decreases in BMD in the injured knee may be related to altered loading and kinematics in the knee and may be an important link in the pathogenesis of posttraumatic osteoarthritis.
Site and mechanics of spontaneous, sleep-associated obstructive apnea in infants
Authors: Don Garrick W. , Kirjavainen Turkka , Broome Catherine , Seton Chris , Waters Karen A.
Published: December 2017

To examine the mechanics of infantile obstructive sleep apnea (OSA), airway pressures were measured using a triple-lumen catheter in 19 infants (age 1–36 wk), with concurrent overnight polysomnography. Catheter placement was guided by correlations between measurements of magnetic resonance images and body weight of 70 infants. The level of spontaneous obstruction was palatal in 52% and retroglossal in 48% of all events. Palatal obstruction predominated in infants treated for OSA (80% of events), compared with 38.6% from infants with infrequent events ( P = 0.02). During obstructive events, successive respiratory efforts increased in amplitude (mean intrathoracic pressures −11.4, −15.0, and −20.4 cmH2O; ANOVA, P < 0.05), with arousal after only 29% of the obstructive and mixed apneas. The soft palate is commonly involved in the upper airway obstruction of infants suffering OSA. Postterm, infant responses to upper airway obstruction are intermediate between those of preterm infants and older children, with infrequent termination by arousal but no persisting “upper airway resistance” and respiratory efforts exceeding baseline during the event.
Sound transmission between 50 and 600 Hz in excised pig lungs filled with air and helium
Authors: Leung Aiken , Sehati Sepe , Young J. Duncan , McLeod Chris
Published: December 2017

This study measured transit time (TT) and attenuation of sound transmitted through six pairs of excised pig lungs. Single-frequency sounds (50–600 Hz) were applied to the tracheal lumen, and the transmitted signals were monitored on the tracheal and lung surface using microphones. The effect of varying intrapulmonary pressure (Pip) between 5 and 25 cmH2O on TT and sound attenuation was studied using both air and helium (He) to inflate the lungs. From 50 to ∼200 Hz, TT decreased from 4.5 ms at 50 Hz to 1 ms at 200 Hz (at 25 cmH2O). Between ∼200 and 600 Hz, TT was relatively constant (1.1 ms at upper and 1.5 ms at lower sites). Gas density had very little effect on TT (air-to-He ratio of ∼1.2 at upper sites and ∼1 at lower sites at 25 cmH2O). Pip had marked effects (depending on gas and site) on TT between 50 and 200 Hz but no effect at higher frequencies. Attenuation was frequency dependent between 50 and 600 Hz, varying between −10 and −35 dB with air and −2 and −28 dB with He. Pip also had strong influence on attenuation, with a maximum sensitivity of 1.14 (air) and 0.64 dB/cmH2O (He) at 200 Hz. At 25 cmH2O and 200 Hz, attenuation with air was about three times higher than with He. This suggests that sound transmission through lungs may not be dominated by parenchyma but by the airways. The linear relationship between increasing Pip and increasing attenuation, which was found to be between 50 and ∼100 Hz, was inverted above ∼100 Hz. We suggest that this change is due to the transition of the parenchymal model from open to closed cell. These results indicate that acoustic propagation characteristics are a function of the density of the transmission media and, hence, may be used to locate collapsed lung tissue noninvasively.
Catecholamine responses to α-adrenergic blockade during exercise in women acutely exposed to altitude
Authors: Mazzeo Robert S. , Carroll Joy D. , Butterfield Gail. E. , Braun Barry , Rock Paul B. , Wolfel Eugene E. , Zamudio Stacy , Moore Lorna G.
Published: December 2017

We have previously documented the importance of the sympathetic nervous system in acclimatizing to high altitude in men. The purpose of this investigation was to determine the extent to which α-adrenergic blockade affects the sympathoadrenal responses to exercise during acute high-altitude exposure in women. Twelve eumenorrheic women (24.7 ± 1.3 yr, 70.6 ± 2.6 kg) were studied at sea level and on day 2 of high-altitude exposure (4,300-m hypobaric chamber) in either their follicular or luteal phase. Subjects performed two graded-exercise tests at sea level (on separate days) on a bicycle ergometer after 3 days of taking either a placebo or an α-blocker (3 mg/day prazosin). Subjects also performed two similar exercise tests while at altitude. Effectiveness of blockade was determined by phenylephrine challenge. At sea level, plasma norepinephrine levels during exercise were 48% greater when subjects were α-blocked compared with their placebo trial. This difference was only 25% when subjects were studied at altitude. Plasma norepinephrine values were significantly elevated at altitude compared with sea level but to a greater extent for the placebo (↑59%) vs. blocked (↑35%) trial. A more dramatic effect of both altitude (↑104% placebo vs. 95% blocked) and blockade (↑50% sea level vs. 44% altitude) was observed for plasma epinephrine levels during exercise. No phase differences were observed across any condition studied. It was concluded that α-adrenergic blockade 1) resulted in a compensatory sympathoadrenal response during exercise at sea level and altitude, and 2) this effect was more pronounced for plasma epinephrine.
Influence of head-down and lateral decubitus neck flexion on heart rate variability
Authors: Lee C. Matthew , Wood Robert H. , Welsch Michael A.
Published: December 2017

The purpose of this study was to examine the response of heart rate variability (HRV), a noninvasive index of autonomic control, to head-down neck flexion (HDNF), which engages both otoliths and neck muscle afferents, and to lateral decubitus neck flexion (LNF), in which neck afferents are activated, whereas otolith afferent input is not. HRV and forearm blood flow were evaluated in participants lying prone, during HDNF, lying in the lateral decubitus position, and during LNF. Compared with the prone position, HDNF resulted in lower high-frequency (46.9 ± 7.1 vs. 62.3 ± 6.2) and higher low-frequency (53.1 ± 7.1 vs. 37.7 ± 6.2) power, expressed as normalized units, along with higher low-frequency-to-high-frequency ratio (1.65 ± 0.3 vs. 0.78 ± 0.2), whereas LNF resulted in no alterations in HRV indexes. Furthermore, there were no significant differences in forearm blood flow or vascular resistance among any of the positions. Our data suggest that otolith organs influence autonomic modulation of the heart, supporting previous studies reporting that HDNF elicits increased sympathetic outflow. These data further suggest that HDNF results in a parasympathetic withdrawal from the heart in addition to sympathetic activation.
Alterations in enzymes involved in fat metabolism after acute and chronic altitude exposure
Authors: Kennedy Sarah L. , Stanley William C. , Panchal Ashish R. , Mazzeo Robert S.
Published: December 2017

The purpose of this study was to examine the effect of acute (24 h) and chronic (5 wk) hypobaric hypoxic exposure equivalent to a simulated altitude of 4,300 m (446 mmHg) on the enzymes of fat metabolism. Heart, liver, and skeletal muscle were taken from 32 male Sprague-Dawley rats. Altitude exposure did not affect the activity of citrate synthase in any of the tissues, suggesting that mitochondrial content was unchanged. Carnitine palmitoyltransferase-I (CPT-I) activity was significantly reduced in the heart by both acute and chronic high altitude exposure compared with controls. A similar reduction was found for CPT-I activity in extensor digitorum longus after acute and chronic exposure compared with control animals. CPT-I activity was not affected by altitude exposure in the soleus muscle or the liver. 3-Hydroxyacyl-CoA dehydrogenase (β-HAD) activity was significantly depressed in the hearts of chronically exposed animals compared with controls. No difference between acute and control animals was found in the heart for β-HAD activity. Liver β-HAD activity was also significantly decreased in the acclimatized as well as in the acute animals compared with the control group. Quadriceps β-HAD activity was reduced for the chronic animals only compared with controls. These data suggest that acclimatization to high altitude selectively decreases key enzymes in fat utilization and oxidation in the heart, liver, and select skeletal muscles.
Exercise attenuates α-adrenergic-receptor responsiveness in skeletal muscle vasculature
Authors: Buckwalter John B. , Naik Jay S. , Valic Zoran , Clifford Philip S.
Published: December 2017

Attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during dynamic exercise is controversial. A potential mechanism is a reduction in α-adrenergic-receptor responsiveness. The purpose of this study was to examine α1- and α2-adrenergic-receptor-mediated vasoconstriction in resting and exercising skeletal muscle using intra-arterial infusions of selective agonists. Thirteen mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective α1-adrenergic agonist (phenylephrine) or the selective α2-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of 76 ± 4, 71 ± 5, and 31 ± 2% at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by 81 ± 5, 49 ± 4, and 14 ± 2%, respectively. The response to intra-arterial infusion of clonidine was unaffected by surgical sympathetic denervation. Agonist infusion did not affect either systemic blood pressure, heart rate, or blood flow in the contralateral iliac artery. α1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, α2-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. These results suggest that the mechanism of exercise sympatholysis may involve reductions in postsynaptic α-adrenergic-receptor responsiveness.
Effects of long-term spaceflight on mechanical properties of muscles in humans
Authors: Lambertz Daniel , Pérot Chantal , Kaspranski Rustem , Goubel Francis
Published: December 2017

The effects of long-term spaceflight (90–180 days) on the contractile and elastic characteristics of the human plantarflexor muscles were studied in 14 cosmonauts before and 2–3 days after landing. Despite countermeasures practiced aboard, spaceflight was found to induce a decrease in maximal isometric torque (17%), whereas an index of maximal shortening velocity was found to increase (31%). In addition, maximal muscle activation evaluated during isokinetic tests decreased by 39%. Changes in musculotendinous stiffness and whole joint stiffness were characterized by means of quick-release movements and sinusoidal perturbations. Musculotendinous stiffness was found to be increased by 25%. Whole joint stiffness decreased under passive conditions (21%), whereas whole joint stiffness under active conditions remained unchanged after spaceflight (−1%). This invariance suggests an adaptive mechanism to counterbalance the decrease in stiffness of passive structures by an increased active stiffness. Changes in neural drive could participate in this equilibrium.
Parasympathetic innervation of canine tracheal smooth muscle
Authors: Valic Zoran , Vidruk Edward H. , Ruble Stephen B. , Buckwalter John B. , Clifford Philip S.
Published: December 2017

To investigate whether efferent parasympathetic fibers to the tracheal smooth muscle course through the pararecurrent nerve rather than the recurrent or the superior laryngeal nerve, we stimulated all three nerves in anesthetized dogs. We also recorded the pararecurrent nerve activity response to bronchoconstrictor stimuli and compared it with pressure changes inside a saline-filled cuff of an endotracheal tube. Electrical stimulation (30 s, 100 Hz, 0.1 ms, 10 mA) increased tracheal cuff pressure by 21.0 ± 3.2 and 1.3 ± 0.7 cmH2O for the pararecurrent and the recurrent laryngeal nerve, respectively. Stimulation of the superior laryngeal nerve increased tracheal cuff pressure before, but not after, sectioning of the ramus anastomoticus, which connects it to the pararecurrent nerve. Intravenous administration of sodium cyanide increased pararecurrent nerve activity by 208 ± 51% and tracheal cuff pressure by 14.4 ± 3.5 cmH2O. Elevation of end-tidal Pco 2 to 50 Torr increased pararecurrent nerve activity by 49 ± 19% and tracheal cuff pressure by 8.4 ± 3.6 cmH2O. Further elevation to 60 Torr increased pararecurrent nerve activity by 101 ± 33% and tracheal cuff pressure by 11.3 ± 2.9 cmH2O. These results lead us to the conclusion that parasympathetic efferent fibers reach the smooth muscle of the canine trachea via the pararecurrent nerve.
Selected Contribution: Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle
Authors: Gordon Joe W. , Rungi Arne A. , Inagaki Hidetoshi , Hood David A.
Published: December 2017

Mitochondrial transcription factor A (Tfam) is a nuclear-encoded gene product that is imported into mitochondria and is required for the transcription of mitochondrial DNA (mtDNA). We hypothesized that conditions known to produce mitochondrial biogenesis in skeletal muscle would be preceded by an increase in Tfam expression. Therefore, rat muscle was stimulated (10 Hz, 3 h/day). Tfam mRNA levels were significantly elevated (by 55%) at 4 days and returned to control levels at 14 days. Tfam import into intermyofibrillar (IMF) mitochondria was increased by 52 and 61% ( P < 0.05) at 5 and 7 days, respectively. This corresponded to an increase in the level of import machinery components. Immunoblotting data indicated that IMF Tfam protein content was increased by 63% ( P < 0.05) at 7 days of stimulation. This was associated with a 49% ( P < 0.05) increase in complex formation at the mtDNA promoter and a 65% ( P< 0.05) increase in the levels of a mitochondrial transcript, cytochrome- c oxidase (COX) subunit III. Similarly, COX enzyme activity was elevated by 71% ( P < 0.05) after 7 days of contractile activity. These results indicate that early events in mitochondrial biogenesis include increases in Tfam mRNA, followed by accelerations in mitochondrial import and increased Tfam content, which correspond with increased binding to the mtDNA promoter region. This was accompanied by increased mitochondrial transcript levels and elevated COX activity. These data support the role of Tfam as a regulatory protein involved in contractile activity-induced mitochondrial biogenesis.
Orthostatic intolerance and motion sickness after parabolic flight
Authors: Schlegel Todd T. , Brown Troy E. , Wood Scott J. , Benavides Edgar W. , Bondar Roberta L. , Stein Flo , Moradshahi Peyman , Harm Deborah L. , Fritsch-Yelle Janice M. , Low Phillip A.
Published: December 2017

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.
Maximal instantaneous muscular power after prolonged bed rest in humans
Authors: Ferretti Guido , Berg Hans E. , Minetti Alberto E. , Moia Christian , Rampichini Susanna , Narici Marco V.
Published: December 2017

A reduction in lower limb cross-sectional area (CSA) occurs after bed rest (BR). This should lead to an equivalent reduction in maximal instantaneous muscular power (W˙p) if the body segments' lengths remain unchanged. W˙p was determined during maximal jumps off both feet on a force platform before and on days 2, 6, 10, 32, and 48 after a 42-day duration BR. CSA of thigh muscles was measured by magnetic resonance imaging before and on day 5 after BR. Before BR, W˙p was 3.63 ± 0.43 kW or 48.6 ± 3.3 W/kg. On days 2 and 6 after BR, W˙p was reduced by 23.7 ± 6.9 and 22.7 ± 5.4% ( P < 0.01), respectively. Thigh extensors CSA (CSAext) was 16.7 ± 4.7% ( P < 0.01) lower than before. When normalized per CSAext, W˙p was reduced by only 4.8 ± 4.5% ( P < 0.05). By day 48 of recovery,W˙p had returned to baseline values. Therefore, ifW˙p is appropriately normalized for CSA of the extensor muscles, the reduction in CSAext explains most of the decrease in W˙p decrease after BR. Other factors such as a deficit in neural activation or a decrease in fiber-specific tension may account for only 5% of theW˙p loss after BR.
Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats
Authors: Osman Abdullah A. , Hancock Joe , Hunt Desmond G. , Ivy John L. , Mandarino Lawrence J.
Published: December 2017

Acute exercise and training increase insulin action in skeletal muscle, but the mechanism responsible for this effect is unknown. Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways. Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise. It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway. The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance. To accomplish this, obese Zucker rats were studied by using the hindlimb perfusion method with or without 7 wk of treadmill training. Activation of the MAPK pathway was determined in gastrocnemius muscles exposed in situ to insulin. Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2). Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity. This effect was maintained for at least 96 h in the case of ERK2. The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity. Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity. The increase in basal ERK2 activity may be related to the response of muscle to training.
CO2-controlled sampling of alveolar gas in mechanically ventilated patients
Authors: Schubert Jochen K. , Spittler Karl-Heinz , Braun Guenther , Geiger Klaus , Guttmann Josef
Published: December 2017

A newly designed gas-sampling device using end-tidal CO2to separate dead space gas from alveolar gas was evaluated in 12 mechanically ventilated patients. For that purpose, CO2-controlled sampling was compared with mixed expiratory sampling. Alveolar sampling valves were easily controlled via CO2concentration. Concentrations of four volatile substances were determined in the expired and inspired gas. Isoflurane and isoprene, which did not occur in the inspired air, had ratios of end-tidal to mixed expired concentrations of 1.75 and 1.81, respectively. Acetone and pentane, found in both the inspired and expired air, showed ratios of 0.96 and 1.0, respectively. Precision of concentration measurements was between 2.4% (isoprene) and 11.2% (isoflurane); reproducibility (as coefficient of variation) was 5%. Because the only possible source of isoflurane and isoprene in this setting was patients' blood, selective enrichment of alveolar gas was demonstrated. By using the new sampling technique, sensitivity of breath analysis was nearly doubled.
Steady-state measurement of NO and CO lung diffusing capacity on moderate exercise in men
Authors: Borland Colin , Mist Bryan , Zammit Mariella , Vuylsteke Alain
Published: December 2017

Using a rapidly responding nitric oxide (NO) analyzer, we measured the steady-state NO diffusing capacity (DlNO) from end-tidal NO. The diffusing capacity of the alveolar capillary membrane and pulmonary capillary blood volume were calculated from the steady-state diffusing capacity for CO (measured simultaneously) and the specific transfer conductance of blood per milliliter for NO and for CO. Nine men were studied bicycling at an average O2consumption of 1.3 ± 0.2 l/min (mean ± SD). DlNOwas 202.7 ± 71.2 ml · min−1· Torr−1and steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO2, mixed expired CO2, and mixed expired CO, was 46.9 ± 12.8 ml · min−1· Torr−1. NO dead space = (Vt × FeNO− Vt × FaNO)/(FiNO− FaNO) = 209 ± 88 ml, where Vt is tidal volume and FeNO, FiNO, and FaNOare mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO2dead space from mixed exhaled and end-tidal (assumed alveolar) CO2= 430 ± 136 ml. Predicted anatomic dead space = 199 ± 22 ml. Membrane diffusing capacity was 333 and 166 ml · min−1· Torr−1for NO and CO, respectively, and pulmonary capillary blood volume was 140 ml. Inhalation of repeated breaths of NO over 80 s did not alter DlNOat the concentrations used.
Dual assessment of airway area profile and respiratory input impedance from a single transient wave
Authors: Louis Bruno , Fodil Redouane , Jaber Samir , Pigeot Jérôme , Jarreau Pierre-Henri , Lofaso Frédéric , Isabey Daniel
Published: December 2017

This report concerns the inference of geometric and mechanical airway characteristics based on information derived from a single transient planar wave recorded at the airway opening. We describe a new method to simultaneously measure upper airway area and respiratory input impedance by performing dual analysis of a single pressure wave. The algorithms required to reconstruct airway dimensions and mechanical characteristics were developed, implemented, and tested with reference to known physical models. Our method appears suitable to estimate, even under severe intensive care unit conditions, the respiratory system frequency response (above 10 Hz) in intubated patients and the patency of the endotracheal tube used to connect the patients to the ventilator.
Chronic tobacco smoke exposure increases airway sensitivity to capsaicin in awake guinea pigs
Authors: Bergren Dale R.
Published: December 2017

Tobacco smoke (TS) exposure induces airway hyperreactivity, particularly in sensitive individuals with asthma. However, the mechanism of this airway hyperreactivity is not well understood. To investigate the relative susceptibility of atopic and nonatopic individuals to TS-induced airway hyperreactivity, we exposed ovalbumin (OA)-sensitized and nonsensitized guinea pigs to TS exposure (5 mg/l air, 30-min exposure, 7 days/wk for 120–156 days). Two similar groups exposed to compressed air served as controls. Airway reactivity was assessed as an increase in enhanced pause (Penh) units using a plethysmograph that allowed free movement of the animals. After 90 days of exposure, airway reactivity increased in OA-TS guinea pigs challenged with capsaicin, bradykinin, and neurokinin A fragment 4–10 aerosols. In addition, substance P content increased in lung perfusate of OA-TS guinea pigs in response to acute TS challenge compared with that of the other groups. Airway hyperirritability was not enhanced by phosphoramidon but was attenuated by a cocktail of neurokinin antagonists, nor was airway hyperreactivity observed after either methacholine or histamine challenge in OA-TS guinea pigs. Chronic TS exposure enhanced neither airway reactivity to histamine or methacholine nor contractility of isolated tracheal rings. In conclusion, chronic TS exposure increased airway reactivity to capsaicin and bradykinin aerosol challenge, and OA-TS guinea pigs were most susceptible to airway dysfunction as the result of exposure to TS compared with the other groups. Increased airway reactivity to capsaicin suggests a mechanism involving neurogenic inflammation, such as increased activation of lung C fibers.
Methods for averaging irregular respiratory flow profiles in awake humans
Authors: Sato Jiro , Robbins Peter A.
Published: December 2017

Respiratory flow profiles have been of interest as an output of the respiratory controller. In determining average flow profiles, however, previous methods that align individual breaths in the time domain are susceptible to distortions caused by the great variability, both between breaths and within breaths. We aimed to develop a method for determining typical flow profiles that circumvents such distortions. Our method aligns different breaths by phase of respiratory cycle, which is defined as the angle associated with the point on the normalized flow-volume diagram (a phase-plane plot). Over a number of breaths, median values for flow, volume, and elapsed time from the start of the breath at each phase angle are determined. Because these estimates are mutually semi-independent and in general violate the laws of mass balance, an adjustment was performed such that the volume was precisely the time integral of the flow. The method produced typical flow profiles with characteristics that were significantly closer to the mean values obtained from the individual cycles than those obtained by the technique of Benchetrit and co-workers (Benchetrit G, Shea SA, Dinh TP, Bodocco S, Baconnier P, and Guz A, Respir Physiol 75: 199–210, 1989), which reconstructs the typical flow profile from Fourier coefficients.
Selected Contribution: Plasticity of airway smooth muscle stiffness and extensibility: role of length-adaptive mechanisms
Authors: Gunst Susan J. , Wu Ming-Fang
Published: December 2017

Airway smooth muscle exhibits the property of length adaptation, which enables it to optimize its contractility to the mechanical conditions under which it is activated. Length adaptation has been proposed to result from a dynamic modulation of contractile and cytoskeletal filament organization, in which the cell structure adapts to changes in cell shape at different muscle lengths. Changes in filament organization would be predicted to alter muscle stiffness and extensibility. We analyzed the effects of tracheal muscle length at the time of contractile activation on the stiffness and extensibility of the muscle during subsequent stretch over a constant range of muscle lengths. Muscle strips were significantly stiffer and less extensible after contractile activation at a short length than after activation at a long length, consistent with the prediction of a shorter, thicker array of the cytoskeletal filaments at a short muscle length. Stretch beyond the length of contractile activation resulted in a persistent reduction in stiffness, suggesting a stretch-induced structural rearrangement. Our results support a model in which the filament organization of airway smooth muscle cells is plastic and can be acutely remodeled to adapt to the changes in the external physical environment.
Substrate utilization during exercise in formerly morbidly obese women
Authors: Guesbeck Nicole R. , Hickey Matthew S. , MacDonald Kenneth G. , Pories Walter J. , Harper Inge , Ravussin Eric , Dohm G. Lynis , Houmard Joseph A.
Published: December 2017

The purpose of this study was to compare substrate utilization during fasting and submaximal exercise in morbidly obese women after weight loss (WL) with that in weight-matched controls (C). WL were studied in the weight-stable condition ∼24 mo after gastric bypass surgery. Energy intake (self-reported) and expenditure (2H2 18O) were also compared. The respiratory exchange ratio during exercise at the same absolute (15 W) workload was significantly ( P ≤ 0.05) elevated in WL vs. C (0.90 ± 0.02 vs. 0.83 ± 0.03); this was reflected as lower fat utilization in WL (29.7 ± 4.8 vs. 53.2 ± 9.7% of energy from fat). Respiratory exchange ratio during exercise at the same relative (65% of maximal O2 uptake) intensity was also significantly ( P < 0.05) elevated in WL (0.96 ± 0.01 vs. 0.89 ± 0.02), and fat use was concomitantly depressed (12.4 ± 3.0 vs. 34.3 ± 9.9% of energy from fat). Resting substrate utilization, daily energy expenditure, and self-reported relative macronutrient intake did not differ between groups. These data suggest that lipid oxidation is depressed during physical activity in WL. This defect may, at least in part, contribute to a propensity for the development of morbid obesity.