bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased brain capillaries in chronic hypoxia
Authors: Boero Jaime A. , Ascher Jonathan , Arregui Alberto , Rovainen Carl , Woolsey Thomas A.
Published: December 2017

The effect of chronic hypobaric hypoxia (28 days, 455 Torr) on the organization of brain vessels was studied in Balb/c mice. In comparison to age-matched controls kept at sea level, emulsion-perfused capillaries in hypoxic mice showed marked dilation in all brain areas studied. Capillary length per unit volume of tissue ( L v) was increased in the cerebellar granular layer, the caudate nucleus, the globus pallidus, the substantia nigra, the superior colliculus, and the dentate gyrus. There was a selective increase of L v in the hippocampus (CA1 strata pyramidale and lacunosum and CA3 strata pyramidale and oriens) and in somatosensory cortex layers V and VI, motor cortex layers II, III, V, and VI, and auditory cortex layers II and III. An increase in capillary surface area per unit volume of tissue was also determined in several brain areas, including layer IV of somatosensory cortex, where L v was not significantly increased. The O2diffusion conductance and [Formula: see text] in the tissues were estimated with a mathematical model. The remodeling of capillary diameter and length during chronic hypoxia accounts for the significant increase of O2conductance to neural tissues. Also the estimated tissue[Formula: see text] in chronic brain hypoxia is markedly increased in the caudate nucleus and the substantia nigra compared with acute hypoxia. These results suggest that formation of new capillaries is an important mechanism to restore the O2 deficit in chronic brain hypoxia and that local rates of energy utilization may influence angiogenesis in different areas of the brain.
High aerobic capacities in the skeletal muscles of pinnipeds: adaptations to diving hypoxia
Authors: Kanatous Shane B. , DiMichele Leonard V. , Cowan Daniel F. , Davis Randall W.
Published: December 2017

The objective was to assess the aerobic capacity of skeletal muscles in pinnipeds. Samples of swimming and nonswimming muscles were collected from Steller sea lions ( Eumetopias jubatus, n = 27), Northern fur seals ( Callorhinus ursinus, n = 5), and harbor seals ( Phoca vitulina, n = 37) by using a needle biopsy technique. Samples were either immediately fixed in 2% glutaraldehyde or frozen in liquid nitrogen. The volume density of mitochondria, myoglobin concentration, citrate synthase activity, and β-hydroxyacyl-CoA dehydrogenase was determined for all samples. The swimming muscles of seals had an average total mitochondrial volume density per volume of fiber of 9.7%. The swimming muscles of sea lions and fur seals had average mitochondrial volume densities of 6.2 and 8.8%, respectively. These values were 1.7- to 2.0-fold greater than in the nonswimming muscles. Myoglobin concentration, citrate synthase activity, and β-hydroxyacyl-CoA dehydrogenase were 1.1- to 2.3-fold greater in the swimming vs. nonswimming muscles. The swimming muscles of pinnipeds appear to be adapted for aerobic lipid metabolism under the hypoxic conditions that occur during diving.
Expiratory time determined by individual anxiety levels in humans
Authors: Masaoka Yuri , Homma Ikuo
Published: December 2017

We have previously found that individual anxiety levels influence respiratory rates in physical load and mental stress (Y. Masaoka and I. Homma. Int. J. Psychophysiol. 27: 153–159, 1997). On the basis of that study, in the present study we investigated the metabolic outputs during tests and analyzed the respiratory timing relationship between inspiration and expiration, taking into account individual anxiety levels. Disregarding anxiety levels, there were correlations between O2 consumption (V˙o 2) and minute ventilation (V˙e) and betweenV˙o 2 and tidal volume in the physical load test, but no correlations were observed in the noxious audio stimulation test. There was a volume-based increase in respiratory patterns in physical load; however,V˙e increased not only for the adjustment of metabolic needs but also for individual mental factors; anxiety participated in this increase. In the high-anxiety group, theV˙e-to-V˙o 2ratio, indicating ventilatory efficiency, increased in both tests. In the high-anxiety group, increases in respiratory rate contributed to aV˙e increase, and there were negative correlations between expiratory time and anxiety scores in both tests. In an awake state, the higher neural structure may dominantly affect the mechanism of respiratory rhythm generation. We focus on the relationship between expiratory time and anxiety and show diagrams of respiratory output, allowing for individual personality.
V˙co 2 andV˙e kinetics during moderate- and heavyintensity exercise after acetazolamide administration
Authors: Scheuermann Barry W. , Kowalchuk John M. , Paterson Donald H. , Cunningham David A.
Published: December 2017

The effect of carbonic anhydrase inhibition with acetazolamide (Acz) on CO2 output (V˙co 2) and ventilation (V˙e) kinetics was examined during moderate- and heavy-intensity exercise. Seven men [24 ± 1 (SE) yr] performed cycling exercise during control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject performed step transitions (6 min) in work rate from 0 to 100 W [below ventilatory threshold (V˙eT)].V˙e and gas exchange were measured breath by breath. The time constant (τ) was determined for exercise V˙eT by using a three-component model (fit from the start of exercise).V˙co 2 kinetics were slower in Acz (V˙eT, MRT = 75 ± 10 s) than Con (V˙eT, MRT = 54 ± 7 s). During V˙eT kinetics were faster in Acz (MRT = 85 ± 17 s) than Con (MRT = 106 ± 16 s). Carbonic anhydrase inhibition slowedV˙co 2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise. The slowedV˙e kinetics in Acz during exercise <V˙eT is consistent with a mechanism coupling V˙e kinetics with the flow of CO2 to the lungs.
Relative contribution of core and cutaneous temperatures to thermal comfort and autonomic responses in humans
Authors: Frank Steven M. , Raja Srinivasa N. , Bulcao Christian F. , Goldstein David S.
Published: December 2017

Subjective thermal comfort plays a critical role in body temperature regulation since this represents the primary stimulus for behavioral thermoregulation. Although both core (Tc) and skin-surface (Tsk) temperatures are known afferent inputs to the thermoregulatory system, the relative contributions of Tc and Tsk to thermal comfort are unknown. We independently altered Tc and Tsk in human subjects while measuring thermal comfort, vasomotor changes, metabolic heat production, and systemic catecholaminergic responses. Multiple linear regression was used to determine the relative Tc/Tskcontribution to thermal comfort and the autonomic thermoregulatory responses, by using the ratio of regression coefficients for Tc and Tsk. The Tc/Tskcontribution ratio was relatively lower for thermal comfort (1:1) than for vasomotor changes (3:1; P = 0.008), metabolic heat production (3.6:1; P = 0.001), norepinephrine (1.8:1; P = 0.03), and epinephrine (3:1; P = 0.006) responses. Thus Tc and Tsk contribute about equally toward thermal comfort, whereas Tcpredominates in regulation of the autonomic and metabolic responses.
Assessments of flow by transcranial Doppler ultrasound in the middle cerebral artery during exercise in humans
Authors: Poulin Marc J. , Syed Rebecca J. , Robbins Peter A.
Published: December 2017

This study examined the consistency between three indexes of cerebral blood flow (CBF) obtained by using transcranial Doppler ultrasound in eight human volunteers. Each subject undertook three sessions of graded exercise, consisting of 6 min of rest, 6 min at 20% of maximal oxygen uptake (V˙o 2 max), 6 min at 40% V˙o 2 max, and 6 min of recovery. Values were obtained every 10 ms for the velocity associated with the maximal frequency of the Doppler shift ( V P), the intensity-weighted mean velocity ( V IWM), and total signal power ( P). Beat-by-beat averages for three indexes ([Formula: see text] P,[Formula: see text] IWM,[Formula: see text]provided significantly different results for the percent changes in CBF with exercise. At 20% ofV˙o 2 max,[Formula: see text] P and[Formula: see text] IWM showed significant ( P < 0.05) increases of 8 and 6%, respectively, whereas[Formula: see text]showed a nonsignificant increase of 3%. At 40% ofV˙o 2 max,[Formula: see text] P and[Formula: see text] IWM showed significant ( P < 0.05) increases of 14 and 8%, respectively, whereas[Formula: see text]showed a nonsignificant increase of 4%. Our results suggest that the increase in CBF with exercise that has been reported with transcranial Doppler ultrasound needs to be treated with caution, as much of the response could arise as an artifact from the increase in amplitude and frequency of the arterial pressure waveform.
Detection of changes in lung tissue properties with multiple-indicator dilution
Authors: Roerig D. L. , Audi S. H. , Linehan J. H. , Krenz G. S. , Ahlf S. B. , Lin W. , Dawson C. A.
Published: December 2017

We evaluated the potential utility of a group of indicators, each of which targets a particular tissue property, as indicators in the multiple-indicator dilution method to detect and to identify abnormalities in lung tissue properties resulting from lung injury models. We measured the pulmonary venous outflow concentration vs. time curves of [14C]diazepam, 3HOH, [14C]phenylethylamine, and a vascular reference indicator following their bolus injection into the pulmonary artery of isolated perfused rabbit lungs under different experimental conditions, resulting in changes in the lung tissue composition. The conditions included granulomatous inflammation, induced by the intravenous injection of complete Freund’s adjuvant (CFA), and intratracheal fluid instillation, each of which resulted in similar increases in lung wet weight. Each of these conditions resulted in a unique pattern among the concentration vs. time outflow curves of the indicators studied. The patterns were quantified by using mathematical models describing the pulmonary disposition of each of the indicators studied. A unique model parameter vector was obtained for each condition, demonstrating the ability to detect and to identify changes in lung tissue properties by using the appropriate group of indicators in the multiple-indicator dilution method. One change that was particularly interesting was a CFA-induced change in the disposition of diazepam, suggestive of a substantial increase in peripheral-type benzodiazepine receptors in the inflamed lungs.
Skeletal muscle phosphocreatine recovery in exercise-trained humans is dependent on O2availability
Authors: Haseler Luke J. , Hogan Michael C. , Richardson Russell S.
Published: December 2017

In skeletal muscle, phosphocreatine (PCr) recovery from submaximal exercise has become a reliable and accepted measure of muscle oxidative capacity. During exercise, O2availability plays a role in determining maximal oxidative metabolism, but the relationship between O2availability and oxidative metabolism measured by31P-magnetic resonance spectroscopy (MRS) during recovery from exercise has never been studied. We used31P-MRS to study exercising human gastrocnemius muscle under conditions of varied fractions of inspired O2[Formula: see text]) to test the hypothesis that varied O2availability modulates PCr recovery from submaximal exercise. Six male subjects performed three bouts of 5-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery in a 1.5-T magnet while breathing three different[Formula: see text] concentrations (0.10, 0.21, and 1.00). Under each[Formula: see text] treatment, the PCr recovery time constants were significantly different, being longer in hypoxia [33.5 ± 4.1 s (SE)] and shorter in hyperoxia (20.0 ± 1.8 s) than in normoxia (25.0 ± 2.7 s) ( P ≤ 0.05). End-exercise pH was not significantly different among the three treatments (7.08 ± 0.01 for 0.10, 7.04 ± 0.01 for 0.21, and 7.04 ± 0.02 for 1.00). These results demonstrate that PCr recovery is significantly altered by[Formula: see text] and suggest that, after submaximal exercise, PCr recovery, under normoxic conditions, is limited by O2availability.
Effect of aging on response to exercise training in humans: skeletal muscle GLUT-4 and insulin sensitivity
Authors: Cox Julie H. , Cortright Ronald N. , Dohm G. Lynis , Houmard Joseph A.
Published: December 2017

The purpose of this study was to compare the effects of short-term exercise training on insulin-responsive glucose transporter (GLUT-4) concentration and insulin sensitivity in young and older individuals. Young and older women [22.4 ± 0.8 (SE) yr, n = 9; and 60.9 ± 1.0 yr, n = 10] and men (20.9 ± 0.9, n = 9; 56.5 ± 1.9 yr, n = 8), respectively, were studied before and after 7 consecutive days of exercise training (1 h/day, ≈75% maximal oxygen uptake). The older groups had more adipose tissue, increased central adiposity, and a lower maximal oxygen uptake. Despite these differences, increases in whole body insulin action (insulin sensitivity index, determined with an intravenous glucose tolerance test and minimal-model analysis) with training were similar regardless of age, in both the women and men (mean increase of 2.2 ± 0.3-fold). This was accompanied by similar relative increases in muscle (vastus lateralis) GLUT-4 protein concentration, irrespective of age (mean increase of 3.1 ± 0.7-fold). Body mass did not change with training in any of the groups. These data suggest that older human skeletal muscle retains the ability to rapidly increase muscle GLUT-4 and improve insulin action with endurance training.
Alveolar epithelial surface area-volume relationship in isolated rat lungs
Authors: Tschumperlin Daniel J. , Margulies Susan S.
Published: December 2017

In vitro studies of the alveolar epithelial response to deformation require knowledge of the in situ mechanical environment of these cells. Because of the presence of tissue folding and crumpling, previous measurements of the alveolar surface area available for gas exchange are not equivalent to the epithelial surface area. To identify epithelial deformations in uniformly inflated lungs representative of the in vivo condition, we studied isolated Sprague-Dawley rat lungs ( n = 31) fixed by perfusion with glutaraldehyde on deflation after cycling three times at high lung volume (10–25 cmH2O). The epithelial basement membrane in 45 electron micrographs (×12,000)/rat was traced, digitally scanned, and analyzed. Epithelial basement membrane surface area (EBMSA) was computed from a morphometric relationship. EBMSA was found to increase 5, 16, 12, and 40% relative to EBMSA at 24% total lung capacity at lung volumes of 42, 60, 82, and 100% total lung capacity, respectively. The increases in EBMSA suggest that epithelial cells undergo significant deformations with large inflations and that alveolar basement membrane deformation may contribute to lung recoil at high lung pressures.
Dexamethasone in resting and exercising men. I. Effects on bioenergetics, minerals, and related hormones
Authors: Marquet P. , Lac G. , Chassain A. P. , Habrioux G. , Galen F. X.
Published: December 2017

A placebo and a low and a high dose of dexamethasone (Dex) were administered for 4.5 days, at 3-wk intervals, to 24 healthy men, following a double-blind, random-order, crossover procedure. After the last dose the subjects performed a maximal cycling exercise, during which respiratory exchanges, electrocardiogram, and blood pressures were monitored. Blood was sampled just before and after each exercise bout. Dex showed no significant effect on fitness, sleep, exhaustion during exercise, maximal O2 consumption, ventilatory threshold, maximal blood lactate, or rest and exercise blood pressures. On the contrary, both doses of Dex significantly decreased heart rate at rest and during maximal exercise. Blood glucose at rest was higher after both doses of Dex than after placebo; the opposite was found during exercise. Blood levels of ACTH, β-endorphin, cortisol, and cortisol-binding globulin were lowered by Dex at rest and after exercise. Dex stimulated the increase in atrial natriuretic factor during exercise and lowered rest and postexercise aldosterone. Finally, no difference between “fit or trained” and “less fit or untrained” subjects could be found with respect to Dex effects.
Training-induced elevation in FABPPMis associated with increased palmitate use in contracting muscle
Authors: Turcotte Lorraine P. , Swenberger Jason R. , Tucker Michelle Z. , Yee Alice J.
Published: December 2017

To evaluate the effects of endurance training in rats on fatty acid metabolism, we measured the uptake and oxidation of palmitate in isolated rat hindquarters as well as the content of fatty acid-binding proteins in the plasma membranes (FABPPM) of red and white muscles from 16 trained (T) and 18 untrained (UT) rats. Hindquarters were perfused with 6 mM glucose, 1,800 μM palmitate, and [1-14C]palmitate at rest and during electrical stimulation (ES) for 25 min. FABPPMcontent was 43–226% higher in red than in white muscles and was increased by 55% in red muscles after training. A positive correlation was found to exist between succinate dehydrogenase activity and FABPPMcontent in muscle. Palmitate uptake increased by 64–73% from rest to ES in both T and UT and was 48–57% higher in T than UT both at rest (39.8 ± 3.5 vs. 26.9 ± 4.4 nmol ⋅ min−1⋅ g−1, T and UT, respectively) and during ES (69.0 ± 6.1 vs. 43.9 ± 4.4 nmol ⋅ min−1⋅ g−1, T and UT, respectively). While the rats were resting, palmitate oxidation was not affected by training; palmitate oxidation during ES was higher in T than UT rats (14.8 ± 1.3 vs. 9.3 ± 1.9 nmol ⋅ min−1⋅ g−1, T and UT, respectively). In conclusion, endurance training increases 1) plasma free fatty acid (FFA) uptake in resting and contracting perfused muscle, 2) plasma FFA oxidation in contracting perfused muscle, and 3) FABPPMcontent in red muscles. These results suggest that an increased number of these putative plasma membrane fatty acid transporters may be available in the trained muscle and may be implicated in the regulation of plasma FFA metabolism in skeletal muscle.
Low doses of melatonin and diurnal effects on thermoregulation and tolerance to uncompensable heat stress
Authors: McLellan Tom M. , Gannon Greg A. , Zamecnik Jiri , Gil Valerie , Brown Greg M.
Published: December 2017

This study examined whether the reported hypothermic effect of melatonin ingestion increased tolerance to exercise at 40°C, for trials conducted either in the morning or afternoon, while subjects were wearing protective clothing. Nine men performed four randomly ordered trials; two each in the morning (0930) and afternoon (1330) after the double-blind ingestion of either two placebo capsules or two 1-mg capsules of melatonin. Despite significant elevations in plasma melatonin to over 1,000 ng/ml 1 h after the ingestion of the first 1-mg dose, rectal temperature (Tre) was unchanged before or during the heat-stress exposure. Also, all other indexes of temperature regulation and the heart rate response during the uncompensable heat stress were unaffected by the ingestion of melatonin. Initial Tre was increased during the afternoon (37.1 ± 0.2°C), compared with the morning (36.8 ± 0.2°C) exposures, and these differences remained throughout the uncompensable heat stress, such that final Tre was also increased for the afternoon (39.2 ± 0.2°C) vs. the morning (39.0 ± 0.3°C) trials. Tolerance times and heat storage were not different among the exposures at ∼110 min and 16 kJ/kg, respectively. It was concluded that this low dose of melatonin had no impact on tolerance to uncompensable heat stress and that trials conducted in the early afternoon were associated with an increased Tre tolerated at exhaustion that offset the circadian influence on resting Tre and thus maintained tolerance times similar to those of trials conducted in the morning.
Changes in respiratory timing induced by hypercapnia in maturing rats
Authors: Abu-Shaweesh Jalal M. , Dreshaj Ismail A. , Thomas Agnes J. , Haxhiu Musa A. , Strohl Kingman P. , Martin Richard J.
Published: December 2017

Premature infants respond to hypercapnia by an attenuated ventilatory response that is characterized by a decrease in respiratory frequency. We hypothesized that this impaired hypercapnic ventilatory response is of central origin and is mediated via γ-aminobutyric acid-ergic (GABAergic) pathways. We therefore studied two groups of maturing Sprague-Dawley rats: unrestrained rats in a whole body plethysmograph at four postnatal ages (5, 16–17, 22–23, and 41–42 days); and ventilated, decerebrate, vagotomized, paralyzed rats in which phrenic nerve responses to hypercapnia were measured at 4–6 and 37–39 days of age. In the unrestrained group, the increase in minute ventilation induced by hypercapnia was significantly lower at 5 days vs. beyond 16 days. Although there was an increase in tidal volume at all ages, frequency decreased significantly from baseline at 5 days, whereas it increased significantly at 16–17, 22–23, and 41–42 days. The decrease in frequency at 5 days of age was mainly due to a significant prolongation in expiratory duration (Te). In the ventilated group, hypercapnia also caused prolongation in Te at 4–6 days but not at 37–39 days of age. Intravenous administration of bicuculline (GABAA-receptor blocker) abolished the prolongation of Te in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO2expressed as a centrally mediated prolongation of Te that appears to be mediated by GABAergic mechanisms.
Relationship between magnitude estimation of resistive loads, inspiratory pressures, and the RREP P1 peak
Authors: Knafelc Marie , Davenport Paul W.
Published: December 2017

This study investigated the relationship among resistive load magnitude (ΔR), the cortical evoked potential P1peak amplitude of the respiratory-related evoked potential (RREP), mouth pressure (Pm), esophageal pressure (Pes), transdiaphragmatic pressure (Pdi), and resistive load magnitude estimation (ME) in human subjects. The RREP, Pdi, Pes, Pm, and ME were recorded in response to three ΔR values. The RREP was recorded from C3 and C4, referenced to the vertex CZ. The group means of the Pdi, Pm, ME, and RREP P1 amplitude increased with increases in the ΔR. A log-log plot of the P1 amplitudes showed a relationship with ME as did Pes, Pdi, and Pm. There were linear log-log relationships between CZ-C3P1 amplitude, CZ-C4P1 amplitude, and Pdi to ME. Pdi had a linear log-log relationship with CZ-C3and CZ-C4. These results support the hypothesis that the estimated magnitude of the respiratory load is related to the P1 amplitude of the RREP. Pm, Pes, and Pdi are mechanically related and correlated with the P1 peak amplitude, suggesting that the mechanoreceptors mediating the P1 peak of the RREP are activated by changes in mechanical forces related to the inspiratory pump.
Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation
Authors: Brusasco Vito , Crimi Emanuele , Barisione Giovanni , Spanevello Antonio , Rodarte Joseph R. , Pellegrino Riccardo
Published: December 2017

We determined the dose-response curves to inhaled methacholine (MCh) in 16 asthmatic and 8 healthy subjects with prohibition of deep inhalations (DIs) and with 5 DIs taken after each MCh dose. Flow was measured on partial expiratory flow-volume curves at an absolute lung volume (plethysmographically determined) equal to 25% of control forced vital capacity (FVC). Airway inflammation was assessed in asthmatic subjects by analysis of induced sputum. Even when DIs were prohibited, the dose of MCh causing a 50% decrease in forced partial flow at 25% of control FVC (PD50MCh) was lower in asthmatic than in healthy subjects ( P < 0.0001). In healthy but not in asthmatic subjects, repeated DIs significantly decreased the maximum response to MCh [from 90 ± 4 to 62 ± 8 (SD) % of control, P < 0.001], increased PD50MCh ( P < 0.005), without affecting the dose causing 50% of maximal response. In asthmatic subjects, neither PD50MCh when DIs were prohibited nor changes in PD50MCh induced by DIs were significantly correlated with inflammatory cell numbers or percentages in sputum. We conclude that 1) even when DIs are prohibited, the responsiveness to MCh is greater in asthmatic than in healthy subjects; 2) repeated DIs reduce airway responsiveness in healthy but not in asthmatic subjects; and 3) neither airway hyperresponsiveness nor the inability of DIs to relax constricted airways in asthmatic subjects is related to the presence of inflammatory cells in the airways.
Dexamethasone attenuates acute macromolecular efflux increase evoked by smokeless tobacco extract
Authors: Gao Xiao-Pei , Akhter Syed R. , Ikezaki Hiroyuki , Hong Dennis , Rubinstein Israel
Published: December 2017

The purpose of this study was to determine whether dexamethasone attenuates the acute increase in macromolecular efflux from the oral mucosa elicited by an aqueous extract of smokeless tobacco (STE) in vivo, and, if so, whether this response is specific. Using intravital microscopy, we found that 20-min suffusion of STE elicited significant, concentration-related leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated the bradykinin-induced leaky site formation and the increase in clearance of FITC-dextran from the cheek pouch. However, it had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on baseline arteriolar diameter and on bradykinin-induced vasodilation in the cheek pouch. Collectively, these data indicate that dexamethasone attenuates, in a specific fashion, the acute increase in macromolecular efflux from the in situ oral mucosa evoked by short-term suffusion of STE. We suggest that corticosteroids mitigate acute oral mucosa inflammation elicited by smokeless tobacco.
TRH microdialysis into the RTN of the conscious rat increases breathing, metabolism, and temperature
Authors: Cream Carlos , Nattie Eugene , Li Aihua
Published: December 2017

Thyrotropin-releasing hormone (TRH) injected into the retrotrapezoid nucleus (RTN) of anesthetized rats produces a large, prolonged stimulation of ventilatory output (C. L. Cream, A. Li, and E. E. Nattie. J. Appl. Physiol. 83: 792–799, 1997). Here we inject or dialyze TRH into the RTN of conscious rats. In 6 of 17 injections (200 nl, 3.1 ± 1.7 mM), ventilation (V˙e) increased 31% by 10 min, with recovery by 60 min. With dialysis, each animal of one group ( n = 5) received, in random order, 10 mM TRH, 10 mM TRHOH (a metabolite of TRH), and artificial cerebrospinal fluid (aCSF); each animal of a second group ( n = 5) received aCSF and 1 mM TRH. TRHOH and aCSF had no sustained effects. TRH (1 mM) increasedV˙e (32%, P < 0.02, by 10 min, with recovery by 60 min), O2 consumption (V˙o 2; 19%, P < 0.03), and body (rectal) temperature (Tre; 0.5°C, P < 0.09). TRH (10 mM) increasedV˙e (78%, P < 0.01, by 10 min, with no recovery at 60 min), V˙o 2(48%, P < 0.01), and Tre (1.0°C, P < 0.01). TRH also induced arousal. The tissue volume affected in dialysis, estimated by spread of dialyzed fluorescein (332.3 mol wt, mol wt of TRH = 362.4), was 1,580 ± 256 nl for 10 mM ( n = 5) and 590 ± 128 nl for 1 mM ( n = 5). We conclude that 1) the RTN is involved in the integration ofV˙e,V˙o 2, Tre, and arousal and 2) TRH may establish the responsiveness of RTN neurons.
Contribution of exertional hyperthermia to sympathoadrenal-mediated lymphocyte subset redistribution
Authors: Rhind Shawn G. , Gannon Greg A. , Shek Pang N. , Brenner Ingrid K. M. , Severs Yvonne , Zamecnik Jiri , Buguet Alain , Natale Valéria M. , Shephard Roy J. , Radomski Manny W.
Published: December 2017

The contribution of hyperthermia to the differential leukocytosis of exercise remains obscure. This study examined changes in circulating sympathoadrenal hormone concentrations and patterns of leukocyte and lymphocyte subset (CD3+, CD4+, CD8+, CD19+, CD3−16+/56+) redistribution during exercise, with and without a significant rise of rectal temperature (Tre). Ten healthy men [age 26.9 ± 5.7 (SD) yr, body mass 76.0 ± 10.9 kg, body fat 13.9 ± 4.6%, peak O2consumption: 48.0 ± 12.4 ml ⋅ kg−1⋅ min−1] exercised for 40 min (65% peak O2consumption) during water immersion at 39 or 18°C. Treincreased from 37.2 to 39.3°C ( P < 0.0001) after 40 min of exercise in 39°C water but was held constant to an increment of 0.5°C during exercise in 18°C water. Application of this thermal clamp reduced exercise-associated increments of plasma epinephrine (Epi) and norepinephrine (NE) by >50% ( P < 0.05) and abolished the postexercise increase in cortisol. Thermal clamping also reduced the exercise-induced leukocytosis and lymphocytosis. Multiple regression demonstrated that Trehad no direct association with lymphocyte subset mobilization but was significantly ( P < 0.0001) correlated with hormone levels. Epi was an important determinant of total leukocytes, lymphocytes, and CD3+, CD4+, CD8+, and CD3−CD16+/56+subset redistribution. The relationship between NE and lymphocyte subsets was weaker than that with Epi, with the exception of CD3−CD16+/56+counts, which were positively ( P < 0.0001) related to NE. Cortisol was negatively associated with leukocytes, CD14+monocytes, and CD19+B- and CD4+T-cell subsets but was positively related to granulocytes. We conclude that hyperthermia mediates exercise-induced immune cell redistribution to the extent that it causes sympathoadrenal activation, with alterations in circulating Epi, NE, and cortisol.
Venous hydrostatic indifference point as a marker of postnatal adaptation to orthostasis in swine
Authors: Buckner Phillip S. , Quail Anthony W. , Cottee David B. F. , White Saxon W.
Published: December 2017

The postulate that venous adaptation assists postural baroreflex regulation by shifting the hydrostatic indifference point (HIP) toward the heart was investigated in eight midazolam-sedated newborn piglets. Whole body head-up (+15, +30, and +45°) and head-down (−15 and −30°) tilt provided a physiological range of orthostatic strain. HIP for all positive tilts shifted toward the heart ( P < 0.05), +45° HIP shifted most [6.7 ± 0.3, 5.9 ± 0.5, and 3.6 ± 0.3 (SE) cm caudal to right atrium on days 1, 3, and 6, respectively]. HIP for negative tilts (3.0 ± 0.2 cm caudal to right atrium) did not shift with postnatal age. Euthanasia on day 6 caused 2.1 ± 0.3-cm caudal displacement of HIP for positive and negative tilts ( P < 0.05). HIP proximity to right atrium was not altered by α-, β-adrenoceptor and cholinoceptor blockade on day 5. It is concluded that early HIP migration reflects enhancement of venous pressure control to head-up orthostatic strain. The effect is independent of baroreflex-mediated adrenoceptor and cholinoceptor mechanisms.
Modeling the influence of body size onV˙o2 peak: effects of model choice and body composition
Authors: Batterham Alan M. , Vanderburgh Paul M. , Mahar Matthew T. , Jackson Andrew S.
Published: December 2017

This study examined the bivariate relationship between peak oxygen uptake (V˙o2 peak; l/min) and body size in adult men ( n = 1,314, age 17–66 yr), using both “simple” and “full” iterative nonlinear allometric models. The simple model was described byV˙o2 peak= Mb(or FFMb) exp( c SR-PA) exp( a + d age) ε (where M is body mass in kg; FFM is fat-free mass in kg; SR-PA is self-reported physical activity; ε is a multiplicative error term; and exp indicates natural antilogarithms). The full model was described byV˙o2 peak= Mb(or FFMb) exp( c SR-PA) exp( a + d age) + e (ε), where e is a permitted Y-intercept term. The M exponent obtained from simple allometry was 0.65 [95% confidence interval (CI), 0.59–0.71], suggestive of a curvilinear relationship constrained to pass through the origin. This “zero Y-intercept” assumption was examined via the full allometric model, which revealed an M exponent of 1.00 (95% CI, 0.7–1.31), together with a positive Y-intercept term ( e) of 1.13 (95% CI, 0.54–1.73). The FFM exponents were not significantly different from unity in either the simple or full allometric models. It appears that the curvilinearity of the simple allometric model (using total M) is fictitious and is due to the inappropriate forcing of the regression line through the origin. Utilizing FFM as the body-size variable revealed a linear relationship between body size andV˙o2 peak, irrespective of model choice. We conclude that the population mass exponent forV˙o2 peakis close to unity.
Dissociation of peak vascular conductance andV˙o 2 max among highly trained athletes
Authors: Hepple Russell T. , Babits Thomas L. , Plyley Michael J. , Goodman Jack M.
Published: December 2017

Previously, a strong relationship has been found between whole body maximal aerobic power (V˙o 2 max) and peak vascular conductance in the calf muscle (J. L. Reading, J. M. Goodman, M. J. Plyley, J. S. Floras, P. P. Liu, P. R. McLaughlin, and R. J. Shephard. J. Appl. Physiol. 74: 567–573, 1993; P. G. Snell, W. H. Martin, J. C. Buckley, and C. G. Blomqvist. J. Appl. Physiol. 62: 606–610, 1987), suggesting a matching between maximal exercise capacity and peripheral vasodilatory reserve across a broad range of aerobic power. In contrast, long-term training could alter this relationship because of the unique demands for muscle blood flow and cardiac output imposed by different types of training. In particular, the high local blood flows but relatively low cardiac output demand imposed by the type of resistance training used by bodybuilders may cause a relatively greater development in peripheral vascular reserve than in aerobic power. To examine this possibility, we studied the relationship between treadmillV˙o 2 max and vascular conductance in the calf by using strain-gauge plethysmography after maximal ischemic plantar flexion exercise in 8 healthy sedentary subjects (HS) and 28 athletes. The athletes were further divided into three groups: 10 elite middle-distance runners (ER), 11 power athletes (PA), and 7 bodybuilders (BB). We found that both BB and ER deviate from the previously demonstrated relationship betweenV˙o 2 max and vascular conductance. Specifically, for a given vascular conductance, BB had a lower V˙o 2 max, whereas ER had a higherV˙o 2 max than did HS and PA. We conclude that the relationship between peak vascular conductance and aerobic power is altered in BB and ER because of training-specific effects on central vs. peripheral cardiovascular adaptation to local skeletal muscle metabolic demand.
Effect of training status on fuel selection during submaximal exercise with glucose ingestion
Authors: van Loon Luc J. C. , Jeukendrup Asker E. , Saris Wim H. M. , Wagenmakers Anton J. M.
Published: December 2017

In this study, an oral glucose load was enriched with a [U-13C]glucose tracer to determine differences in substrate utilization between endurance-trained (T) and untrained (UT) subjects during submaximal exercise at the same relative and absolute workload when glucose is ingested. Six highly trained cyclists/triathletes [maximal workload (Wmax), 400 ± 9 W] and seven UT subjects (Wmax, 296 ± 8 W) were studied during 120 min of cycling exercise at 50% Wmax (∼55% maximal O2 consumption). The T subjects performed a second trial at the mean workload of the UT group (148 ± 4 W). Before exercise, 8.0 ml/kg of a13C-enriched glucose solution (80 g/l) was ingested. During exercise, boluses of 2.0 ml/kg of the same solution were administered every 15 min. Measurements were made in the 90- to 120-min period when a steady state was present in breath13CO2and plasma glucose 13C enrichment. Energy expenditure was higher in T than in UT subjects (58 vs. 47 kJ/min, respectively; P < 0.001) at the same relative intensity. This was completely accounted for by an increased fat oxidation (0.57 vs. 0.40 g/min; P < 0.01). At the same absolute intensity, fat oxidation contributed more to energy expenditure in the T compared with the UT group (44 vs. 33%, respectively; P < 0.01). The reduction in carbohydrate oxidation in the T group was explained by a diminished oxidation rate of muscle glycogen (indirectly assessed by using tracer methodology at 0.72 ± 0.1 and 1.03 ± 0.1 g/min, respectively; P < 0.01) and liver-derived glucose (0.15 ± 0.03 and 0.22 ± 0.02 g/min, respectively; P < 0.05). Exogenous glucose oxidation rates were similar during all trials (±0.70 g/min).
Mechanical contribution of expiratory muscles to pressure generation during spinal cord stimulation
Authors: DiMarco A. F. , Romaniuk J. R. , Kowalski K. E. , Supinski G.
Published: December 2017

Lower thoracic spinal cord stimulation (SCS) results in the generation of large positive airway pressures (Paw) and may be a useful method of restoring cough in patients with spinal cord injury. The purpose of the present study was to assess the mechanical contribution of individual respiratory muscles to pressure generation during SCS. In anesthetized dogs, SCS was applied at different spinal cord levels by using a 15-lead multicontact electrode before and after sequential ablation of the external and internal obliques, transversus abdominis (TA), rectus abdominis, and internal intercostal muscles. Paw was monitored after tracheal occlusion. SCS at the T9 spinal cord level resulted in maximal changes in Paw (60 ± 3 cmH2O). Section of the oblique muscles resulted in a fall in Paw to 29 ± 2 cmH2O. After subsequent section of the rectus abdominis and TA, Paw fell to 25 ± 2 and 12 ± 1 cmH2O respectively. There was a small remaining Paw (4 ± 1 cmH2O) after section of the internal intercostal nerves. Stimulation with a two-electrode lead system (T9 + T13) resulted in significantly greater pressure generation compared with a single-electrode lead due to increased contributions from the obliques and transversus muscles. In a separate group of animals, Paw generation was monitored after section of the abdominal muscles and again after section of the external intercostal and levator costae muscles. These studies demonstrated that inspiratory intercostal muscle stimulation resulted in only a small opposing inspiratory action (≤3 cmH2O). We conclude that, during SCS, 1) contraction of the obliques and TA muscles makes the largest contribution to changes in Paw, and 2) stimulation with a two-electrode lead system results in more complete abdominal muscle activation and enhanced mechanical actions of the obliques and transversus muscles.
Fetal diuretic responses to maternal hyponatremia: contribution of placental sodium gradient
Authors: Roberts Todd J. , Nijland Mark J. M. , Williams Leslee , Ross Michael G.
Published: December 2017

Maternal hyponatremia induces fetal hyponatremia and increased fetal urine flow. We sought to examine the relative contributions of the placental Na+gradient vs. the absolute decrease in fetal plasma Na+ in the fetal diuretic response to hyponatremia. Seven ewes with singleton fetuses (130 ± 2 days) were prepared. Ewes received intravenous 1-desamino-8-d-arginine vasopressin (20 μg) and warm tap water (2 liters). Maternal plasma Na+ was decreased to achieve two levels of maternal hyponatremia. Maternal and fetal blood volume were measured with radiolabeled red blood cells. In response to the first decrease in maternal plasma Na+, fetal plasma Na+ did not change initially. Subsequently, fetal plasma Na+ decreased, normalizing the gradient. The second decrease in maternal plasma Na+ similarly induced a reduced and normalized placental gradient at lower fetal plasma Na+ values. Fetal urine flow increased in direct proportion to the degree of fetal hyponatremia (13, 38, 63, 100%, respectively). Maternal, although not fetal, blood volume significantly increased in response to hyponatremia. These results suggest that chronic fetal hyponatremia will result in a persistent diuresis, despite placental equilibration.
Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass
Authors: Visser Marjolein , Fuerst Thomas , Lang Thomas , Salamone Loran , Harris Tamara B. , Health For The , Absorptiometry Aging,body Composition Study Dual-E , Group Body Composition Working
Published: December 2017

The aim of the study was to examine the accuracy of fan-beam dual-energy X-ray absorptiometry (DEXA) for measuring total body fat-free mass (FFM) and leg muscle mass (MM) in elderly persons. Participants were 60 men and women aged 70–79 yr and with a body mass index of 17.5–39.8 kg/m2. FFM and MM at four leg regions were measured by using DEXA (Hologic 4500A, v8.21). A four-compartment body composition model (4C) and multislice computed tomography (CT) of the legs were used as the criterion methods for FFM and MM, respectively. FFM by DEXA was positively associated with FFM by 4C ( R 2 = 0.98, SE of estimate = 1.6 kg). FFM by DEXA was higher [53.5 ± 12.0 (SD) kg] than FFM by 4C (51.6 ± 11.9 kg; P < 0.001). No association was observed between the difference and the mean of the two methods. MM by DEXA was positively associated with CT at all four leg regions ( R 2 = 0.86–0.96). MM by DEXA was higher than by CT in three regions. The results of this study suggest that fan-beam DEXA offers considerable promise for the measurement of total body FFM and leg MM in elderly persons.
Does β3-adrenoreceptor blockade attenuate acute exercise-induced reductions in leptin mRNA?
Authors: Bramlett S. Brooke , Zhou Jun , Harris Ruth B. S. , Hendry Stephen L. , Witt Trudy L. , Zachwieja Jeffrey J.
Published: December 2017

We investigated the effect of a single bout of exercise on leptin mRNA levels in rat white adipose tissue. Male Sprague-Dawley rats were randomly assigned to an exercise or control group. Acute exercise was performed on a rodent treadmill and was carried out to exhaustion, lasting an average of 85.5 ± 1.5 min. At the end of exercise, soleus muscle and liver glycogen were reduced by 88% ( P < 0.001). Acutely exercised animals had lower ( P< 0.05) leptin mRNA levels in retroperitoneal but not epididymal fat, and this was independent of fat pad weight. To test the hypothesis that β3-adrenergic-receptor stimulation was involved in the downregulation of leptin mRNA in retroperitoneal fat, a second experiment was performed in which rats were randomized into one of four groups: control, control + β3-antagonist, exercise, and exercise + β3-antagonist. A highly selective β3-antagonist (SR-59230A) or vehicle was given by gavage 30 min before exercise or control experiment. Exercise consisted of 55 min of treadmill running, sufficient to reduce liver and muscle glycogen by 70 and 80%, respectively (both P < 0.0001). Again, acute exercise reduced leptin mRNA in retroperitoneal fat (exercise vs. control; P < 0.05), but β3-antagonism blocked this effect (exercise + β3-antagonist vs. control + β3-antagonist; P = 0.42). Unexpectedly, exercise increased serum leptin. This would be consistent with the idea that there are releasable, preformed pools of leptin within adipocytes. We conclude that β3-receptor stimulation is a mechanism by which acute exercise downregulates retroperitoneal adipose tissue leptin mRNA in vivo.
Rapid vasodilation in response to a brief tetanic muscle contraction
Authors: Naik Jay S. , Valic Zoran , Buckwalter John B. , Clifford Philip S.
Published: December 2017

To test the hypothesis that vasodilation occurs because of the release of a vasoactive substance after a brief muscle contraction and to determine whether acetylcholine spillover from the motor nerve is involved in contraction-induced hyperemia, tetanic muscle contractions were produced by sciatic nerve stimulation in anesthetized dogs ( n = 16), instrumented with flow probes on both external iliac arteries. A 1-s stimulation of the sciatic nerve at 1.5, 3, and 10 times motor threshold increased blood flow above baseline ( P < 0.01) for 20, 25, and 30 s, respectively. Blood flow was significantly greater 1 s after the contraction ended for 3 and 10 × motor threshold ( P < 0.01) and did not peak until 6–7 s after the contraction. The elevations in blood flow to a 1-s stimulation of the sciatic nerve and a 30-s train of stimulations were abolished by neuromuscular blockade (vecuronium). The delayed peak blood flow response and the prolonged hyperemia suggest that a vasoactive substance is rapidly released from the contracting skeletal muscle and can affect blood flow with removal of the mechanical constraint imposed by the contraction. In addition, acetylcholine spillover from the motor nerve is not responsible for the increase in blood flow in response to muscle contraction.
Assessment of methods for improving tracer estimation of non-steady-state rate of appearance
Authors: Gastaldelli A. , Coggan A. R. , Wolfe R. R.
Published: December 2017

The most common approach for estimating substrate rate of appearance (Ra) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. ( Am. J. Physiol. 187: 15–24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215–224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng ⋅ kg−1 ⋅ min−1) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of Raobtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating Ra for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR1/TTR2approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose Ra can be obtained with the constant-infusion technique if V = 145 ml/kg.
Effects of prior exercise on muscle metabolism during sprint exercise in horses
Authors: McCutcheon L. J. , Geor R. J. , Hinchcliff K. W.
Published: December 2017

The effect of warm-up exercise on energy metabolism and muscle glycogenolysis during sprint exercise (Spr) was examined in six fit Standardbred horses exercised at 115% of maximal O2consumption (V˙o2 max) until fatigued, 5 min after each of three protocols: 1) no warm-up (NWU); 2) 10 min at 50% ofV˙o2 max[low-intensity warm-up (LWU)]; and 3) 7 min at 50%V˙o2 maxfollowed by 45-s intervals at 80, 90, and 100%V˙o2 max[high-intensity warm-up (HWU)]. Warm-up increased ( P < 0.0001) muscle temperature (Tm) at the onset of Spr in LWU (38.3 ± 0.2°C) and HWU (40.0 ± 0.3°C) compared with NWU (36.6 ± 0.2°C), and the rate of rise in Tmduring Spr was greater in NWU than in LWU and HWU ( P < 0.01). PeakV˙o2was higher and O2deficit lower ( P < 0.05) when Spr was preceded by warm-up. Rates of muscle glycogenolysis were lower ( P < 0.05) in LWU, and rates of blood and muscle lactate accumulation and anaerobic ATP provision during Spr were lower in LWU and HWU compared with NWU. Mean runtime (s) in LWU (173 ± 10 s) was greater than HWU (142 ± 11 s) and NWU (124 ± 4 s) ( P < 0.01). Warm-up was associated with augmentation of aerobic energy contribution to total energy expenditure, decreased glycogenolysis, and longer run time to fatigue during subsequent sprint exercise, with no additional benefit from HWU vs. LWU.