bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke volume decline during prolonged exercise is influenced by the increase in heart rate
Authors: Fritzsche Ricardo G. , Switzer Thomas W. , Hodgkinson Bradley J. , Coyle Edward F.
Published: December 2017

This study determined whether the decline in stroke volume (SV) during prolonged exercise is related to an increase in heart rate (HR) and/or an increase in cutaneous blood flow (CBF). Seven active men cycled for 60 min at ∼57% peak O2 uptake in a neutral environment (i.e., 27°C, <40% relative humidity). They received a placebo control (CON) or a small oral dose (i.e., ∼7 mg) of the β1-adrenoceptor blocker atenolol (BB) at the onset of exercise. At 15 min, HR and SV were similar during CON and BB. From 15 to 55 min during CON, a 13% decline in SV was associated with an 11% increase in HR and not with an increase in CBF. CBF increased mainly from 5 to 15 min and remained stable from 20 to 60 min of exercise in both treatments. However, from 15 to 55 min during BB, when the increase in HR was prevented by atenolol, the decline in SV was also prevented, despite a normal CBF response (i.e., similar to CON). Cardiac output was similar in both treatments and stable throughout the exercise bouts. We conclude that during prolonged exercise in a neutral environment the decline in SV is related to the increase in HR and is not affected by CBF.
Pulmonary capillary perfusion: intra-alveolar fractal patterns and interalveolar independence
Authors: Wagner Wiltz W. , Todoran Thomas M. , Tanabe Nobuhiro , Wagner Teresa M. , Tanner Judith A. , Glenny Robb W. , Presson Robert G.
Published: December 2017

Pulmonary capillary perfusion was analyzed from videomicroscopic recordings to determine flow switching characteristics among capillary segments in isolated, blood-perfused canine lungs. Within each alveolus, the rapid switching pattern was repetitive and was, therefore, nonrandom (fractal dimensions near 1.0). This self-similarity over time was unexpected in a network widely considered to be passive. Among adjacent alveoli, the relationship among the switching patterns was even more surprising, for there was virtually no relationship between the perfusion patterns (coefficients of determination approaching zero). These findings demonstrated that the perfusion patterns in individual alveolar walls were independent of their next-door neighbors. The lack of dependence among neighboring networks suggests an interesting characteristic: the failure of one alveolar-capillary bed would leave its neighbors relatively unaffected, a feature of a robust design.
Hormone-related, muscle-specific changes in protein metabolism and fiber type profile after faba bean intake
Authors: Frühbeck Gema , Villaro A. Cristina , Monreal Ignacio , Santidrián Santiago
Published: December 2017

Male growing Wistar rats were fed, over 15 days, isoenergetic (16.72 ± 0.49 MJ) and isoproteic (11%) diets containing either lactalbumin or raw Vicia faba L. (Vf) as the sole source of protein. Compared with pair-fed controls (PF), soleus muscles of Vf-fed rats showed increased ( P < 0.05) synthesis and breakdown rates. In addition, the soleus of Vf-fed rats displayed a decrease ( P < 0.05) in type I and an increase ( P < 0.01) in type IIc fibers compared with that of PF animals. On the contrary, extensor digitorum longus muscles of both Vf-fed and PF rats showed an increase ( P < 0.01) in type I and a reduction ( P < 0.05) in type IIb fibers together with a decrease ( P < 0.05) in the cross-sectional area of the latter fibers. Vf-fed rats exhibited a significant decrease in serum insulin ( P < 0.05) and thyrotropin ( P < 0.01) levels, together with an increase in plasma glucagon ( P < 0.05) and 3,5,3′-triiodothyronine ( P < 0.01) concentrations, compared with the PF group. Both Vf-fed and PF rats experienced an increase in corticosterone concentrations ( P < 0.01 vs. control; P < 0.05 vs. PF). The muscle-specific changes in both protein metabolism and fiber type composition may partly depend on the hormonal changes that were observed after Vf intake.
Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise
Authors: Parkin J. M. , Carey M. F. , Zhao S. , Febbraio M. A.
Published: December 2017

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3°C (CT), 20°C (NT), and 40°C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher ( P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 ± 8 vs. 60 ± 11 vs. 30 ± 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher ( P < 0.05) when HT was compared with NT, which in turn was higher ( P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 ± 33 vs. 153 ± 27 and 116 ± 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher ( P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase ( P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.
Intestinal reperfusion injury is mediated by IgM and complement
Authors: Williams Julian P. , Pechet Taine T. V. , Weiser Martin R. , Reid Russell , Kobzik Les , Moore Francis D. , Carroll Michael C. , Hechtman Herbert B.
Published: December 2017

Intestinal ischemia-reperfusion injury is dependent on complement. This study examines the role of the alternative and classic pathways of complement and IgM in a murine model of intestinal ischemia-reperfusion. Wild-type animals, mice deficient in complement factor 4 (C4), C3, or Ig, or wild-type mice treated with soluble complement receptor 1 were subjected to 40 min of jejunal ischemia and 3 h of reperfusion. Compared with wild types, knockout and treated mice had significantly reduced intestinal injury, indicated by lowered permeability to radiolabeled albumin. When animals deficient in Ig were reconstituted with IgM, the degree of injury was restored to wild-type levels. Immunohistological staining of intestine for C3 and IgM showed colocalization in the mucosa of wild-type controls and minimal staining for both in the intestine of Ig-deficient and C4-deficient mice. We conclude that intestinal ischemia-reperfusion injury is dependent on the classic complement pathway and IgM.
Myogenic and vasoconstrictor responsiveness of skeletal muscle arterioles is diminished by hindlimb unloading
Authors: Delp Michael D.
Published: December 2017

The purpose of the present study was to determine whether hindlimb unloading of rats alters vasoconstrictor and myogenic responsiveness of skeletal muscle arterioles. After either 2 wk of hindlimb unloading (HU) or cage control (C), second-order arterioles were isolated from the white portion of gastrocnemius (WG; C: n = 9, HU: n = 10) or soleus (Sol; C: n = 9, HU: n = 10) muscles and cannulated with two micropipettes connected to reservoir systems for in vitro study. Intraluminal pressure was set at 60 cmH2O. The arterioles were exposed to step changes in intraluminal pressure ranging from 20 to 140 cmH2O to determine myogenic responsiveness and to KCl (10–100 mM) and norepinephrine (10−9–10−4M) to determine vasoconstrictor responsiveness. Although maximal diameter of WG arterioles was not different between C (185 ± 12 μm) and HU (191 ± 14 μm) rats, WG arterioles from HU rats developed less spontaneous tone (C: 33 ± 5%, HU 20 ±3%), were unable to maintain myogenic tone at pressures from 140 to 100 cmH2O, and were less sensitive to the vasoconstrictor effects of KCl and norepinephrine (as indicated by a higher agonist concentration that produced 50% of maximal vasoconstrictor response). In contrast, maximal diameter of Sol arterioles from HU rats (117 ± 12 μm) was smaller than that in C rats (148 ± 14 μm). However, the development of spontaneous tone (C: 30 ± 4%, HU: 36 ± 5%), myogenic activity, and the responsiveness to vasoconstrictor agonists were not different between Sol arterioles from C and HU rats. These results indicate that hindlimb unloading diminishes the myogenic autoregulatory and contractile responsiveness of arterioles from muscle composed of type IIB fibers and suggest that the compromised ability to elevate vascular resistance after exposure to microgravity may be related to these vascular alterations. In addition, hindlimb unloading appears to induce vascular remodeling of arterioles from muscle composed of type I fibers, as indicated by the decrease in maximal diameter of arterioles from Sol muscle.
Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs
Authors: Chen Ling , Sica Anthony L. , Scharf Steven M.
Published: December 2017

This study was designed to evaluate the importance of sympathoadrenal activation in the acute cardiovascular response to apneas and the role of hypoxemia in this response. In addition, we evaluated the contribution of the vagus nerve to apnea responses after chemical sympathectomy. In six pigs preinstrumented with an electromagnetic flow probe and five nonpreinstrumented pigs, effects of periodic nonobstructive apneas were tested under the following six conditions: room air breathing, 100% O2 supplementation, both repeated after administration of hexamethonium (Hex), and both repeated again after bilateral vagotomy in addition to Hex. With room air apneas, during the apnea cycle, there were increases in mean arterial pressure (MAP; from baseline of 108 ± 4 to 124 ± 6 Torr, P < 0.01), plasma norepinephrine (from 681 ± 99 to 1,825 ± 578 pg/ml, P < 0.05), and epinephrine (from 191 ± 67 to 1,245 ± 685 pg/ml, P < 0.05) but decreases in cardiac output (CO; from 3.3 ± 0.6 to 2.4 ± 0.3 l/min, P < 0.01) and cervical sympathetic nerve activity. With O2supplementation relative to baseline, apneas were associated with small increases in MAP (from 112 ± 4 to 118 ± 3 Torr, P < 0.01) and norepinephrine (from 675 ± 97 to 861 ± 170 pg/ml, P< 0.05). After Hex, apneas with room air were associated with small increases in MAP (from 103 ± 6 to 109 ± 6 Torr, P < 0.05) and epinephrine (from 136 ± 45 to 666 ± 467 pg/ml, P < 0.05) and decreases in CO (from 3.6 ± 0.4 to 3.2 ± 0.5 l/min, P < 0.05). After Hex, apneas with O2 supplementation were associated with decreased MAP (from 107 ± 5 to 100 ± 5 Torr, P < 0.05) and no other changes. After vagotomy + Hex, with room air and O2 supplementation, apneas were associated with decreased MAP (from 98 ± 6 to 76 ± 7 and from 103 ± 7 to 95 ± 6 Torr, respectively, both P < 0.01) but increased CO [from 2.7 ± 0.3 to 3.2 ± 0.4 l/min ( P < 0.05) and from 2.4 ± 0.2 to 2.7 ± 0.2 l/min ( P < 0.01), respectively]. We conclude that sympathoadrenal activation is the major pressor mechanism during apneas. Cervical sympathetic nerve activity does not reflect overall sympathoadrenal activity during apneas. Hypoxemia is an important but not the sole trigger factor for sympathoadrenal activation. There is an important vagally mediated reflex that contributes to the pressor response to apneas.
Transport of colloidal particles in lymphatics and vasculature after subcutaneous injection
Authors: Higuchi Makoto , Fokin Alexander , Masters Thomas N. , Robicsek Francis , Schmid-Schönbein Geert W.
Published: December 2017

This study was designed to determine the transport of subcutaneously injected viral-size colloid particles into the lymph and the vascular system in the hind leg of the dog. Transport of two colloid particles, with average size ∼1 and 0.41 μm, respectively, and with and without leg rotation, was tested. Leg rotation serves to enhance the lymph flow rates. The right femoral vein, lymph vessel, and left femoral artery were cannulated while the animal was under anesthesia, and samples were collected at regular intervals after subcutaneous injection of the particles at the right knee level. The number of particles in the samples were counted under fluorescence microscopy by using a hemocytometer. With and without leg rotation, both particle sets were rapidly taken up into the venous blood and into the lymph fluid. The number of particles carried away from the injection site within the first 5 min was <5% of the injected pool. Particles were also seen in arterial blood samples; this suggests reflow and a prolonged residence time in the blood. These results show that particles the size of viruses are rapidly taken up into the lymphatics and blood vessels after subcutaneous deposition.
Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo
Authors: Akhter Syed R. , Ikezaki Hiroyuki , Gao Xiao-Pei , Rubinstein Israel
Published: December 2017

The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-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 substance P-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch but had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on arteriolar diameter in the cheek pouch. On balance, these data indicate that dexamethasone attenuates grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.
Aerobic training and cutaneous vasodilation in young and older men
Authors: Thomas Carla M. , Pierzga Jane M. , Kenney W. Larry
Published: December 2017

To determine the effect and underlying mechanisms of exercise training and the influence of age on the skin blood flow (SkBF) response to exercise in a hot environment, 22 young (Y; 18–30 yr) and 21 older (O; 61–78 yr) men were assigned to 16 wk of aerobic (A; YA, n = 8; OA, n = 11), resistance (R; YR, n = 7; OR, n = 3), or no training (C; YC, n = 7; OC, n = 7). Before and after treatment, subjects exercised at 60% of maximum oxygen consumption (V˙o 2 max) on a cycle ergometer for 60 min at 36°C. Cutaneous vascular conductance, defined as SkBF divided by mean arterial pressure, was monitored at control (vasoconstriction intact) and bretylium-treated (vasoconstriction blocked) sites on the forearm using laser-Doppler flowmetry. Forearm vascular conductance was calculated as forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure. Esophageal and skin temperatures were recorded. Only aerobic training (functionally defined a priori as a 5% or greater increase inV˙o 2 max) produced a decrease in the mean body temperature threshold for increasing forearm vascular conductance (36.89 ± 0.08 to 36.63 ± 0.08°C, P < 0.003) and cutaneous vascular conductance (36.91 ± 0.08 to 36.65 ± 0.08°C, P < 0.004). Similar thresholds between control and bretylium-treated sites indicated that the decrease was mediated through the active vasodilator system. This shift was more pronounced in the older men who presented greater training-induced increases in V˙o 2 maxthan did the young men (22 and 9%, respectively). In summary, older men improved their SkBF response to exercise-heat stress through the effect of aerobic training on the cutaneous vasodilator system.
Downregulation of Na+-K+-ATPase pumps in skeletal muscle with training in normobaric hypoxia
Authors: Green H. , MacDougall J. , Tarnopolsky M. , Melissa N. L.
Published: December 2017

To investigate the effects of training in normoxia vs. training in normobaric hypoxia (fraction of inspired O2 = 20.9 vs. 13.5%, respectively) on the regulation of Na+-K+-ATPase pump concentration in skeletal muscle (vastus lateralis), 9 untrained men, ranging in age from 19 to 25 yr, underwent 8 wk of cycle training. The training consisted of both prolonged and intermittent single leg exercise for both normoxia (N) and hypoxia (H) during a single session (a similar work output for each leg) and was performed 3 times/wk. Na+-K+-ATPase concentration was 326 ± 17 (SE) pmol/g wet wt before training (Control), increased by 14% with N (371 ± 18 pmol/g wet wt; P < 0.05), and decreased by 14% with H (282 ± 20 pmol/g wet wt; P < 0.05). The maximal activity of citrate synthase, selected as a measure of mitochondrial potential, showed greater increases ( P < 0.05) with H (1.22 ± 0.10 mmol ⋅ h−1 ⋅ g wet wt−1; 70%; P < 0.05) than with N (0.99 ± 0.10 mmol ⋅ h−1 ⋅ g wet wt−1; 51%; P < 0.05) compared with pretraining (0.658 ± 0.09 mmol ⋅ h−1 ⋅ g wet wt−1). These results demonstrate that normobaric hypoxia induced during exercise training represents a potent stimulus for the upregulation in mitochondrial potential while at the same time promoting a downregulation in Na+-K+-ATPase pump expression. In contrast, normoxic training stimulates increases in both mitochondrial potential and Na+-K+-ATPase concentration.
Effects of experimental cortical seizures on respiratory motor nerve activities in piglets
Authors: Terndrup Thomas E. , Darnall Robert , Knuth Susan L. , Bartlett Donald
Published: December 2017

Airway obstruction at the level of the larynx causes respiratory insufficiency during experimental seizures in spontaneously breathing, anesthetized piglets (T. E. Terndrup and W. E. Fordyce, Pediatr. Res., 38: 61–66, 1995). To investigate further the neural mechanisms of this obstruction, the activities of the phrenic nerve (PH) and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 11 anesthetized, vagotomized, paralyzed, and ventilated piglets. After a control recording period, seizures were induced by subcortical penicillin G injections. Compared with baseline conditions, nerve activities became irregular during seizures. Extraneous TA bursts during PH activation were evident in all piglets during seizures. During ictal phases of seizures, the peak integrated activities of the PH and the expiratory component of the PCA, but not TA or inspiratory PCA activities, were significantly decreased compared with interictal phases. During seizures, a significant delay in the onset of the inspiratory component of PCA activation with respect to the onset of the PH was observed. This study helps to explain respiratory impairment during cortical seizures by providing evidence of impaired timing of activation of laryngeal dilator mechanisms and coordination with those activating the diaphragm. Cyclical PH inhibition during high-intensity cortical discharges may provide a secondary mechanism producing respiratory insufficiency during seizures.
Fat mass deposition during pregnancy using a four-component model
Authors: Kopp-Hoolihan L. E. , van Loan M. D. , Wong W. W. , King J. C.
Published: December 2017

Estimates of body fat mass gained during human pregnancy are necessary to assess the composition of gestational weight gained and in studying energy requirements of reproduction. However, commonly used methods of measuring body composition are not valid during pregnancy. We used measurements of total body water (TBW), body density, and bone mineral content (BMC) to apply a four-component model to measure body fat gained in nine pregnant women. Measurements were made longitudinally from before conception; at 8–10, 24–26, and 34–36 wk gestation; and at 4–6 wk postpartum. TBW was measured by deuterium dilution, body density by hydrodensitometry, and BMC by dual-energy X-ray absorptiometry. Body protein was estimated by subtracting TBW and BMC from fat-free mass. By 36 wk of gestation, body weight increased 11.2 ± 4.4 kg, TBW increased 5.6 ± 3.3 kg, fat-free mass increased 6.5 ± 3.4 kg, and fat mass increased 4.1 ± 3.5 kg. The estimated energy cost of fat mass gained averaged 44,608 kcal (95% confidence interval, −31,552–120,768 kcal). The large variability in the composition of gestational weight gained among the women was not explained by prepregnancy body composition or by energy intake. This variability makes it impossible to derive a single value for the energy cost of fat deposition to use in estimating the energy requirement of pregnancy.
Distribution of lung density after strenuous, prolonged exercise
Authors: Manier Gérard , Duclos Martine , Arsac Laurent , Moinard Jean , Laurent François
Published: December 2017

The postexercise alteration in pulmonary gas exchange in high-aerobically trained subjects depends on both the intensity and the duration of exercise (G. Manier, J. Moinard, and H. Stoı̈cheff. J. Appl. Physiol. 75: 2580–2585, 1993; G. Manier, J. Moinard, P. Techoueyres, N. Varène, and H. Guénard. Respir. Physiol. 83: 143–154, 1991). In a recent study that used lung computerized tomography (CT), evidence was found for accumulation of water within the lungs after exercise (C. Caillaud, O. Serre-Cousine, F. Anselme, X. Capdevilla, and C. Prefaut. J. Appl. Physiol. 79: 1226–1232, 1995). On representative slices of the lungs, mean lung density increased by 0.040 ± 0.007 g/cm3(19%, P < 0.001) in athletes after a triathlon. To verify and quantify the mechanism, we determined the change in pulmonary density and mass after strenuous and prolonged exercise using another exercise protocol and methodology for CT scanning. Nine trained runners (age 30–46 yr) volunteered to participate in the study. Each subject ran for 2 h on a treadmill at a rate corresponding to 75% of maximum O2consumption. CT measurements were made before and immediately after the exercise test with the subject supine and holding his breath at a point close to functional residual capacity. The lungs were scanned from the apex to the diaphragm and reconstructed in 8-mm-thick slices. Attenuation values of X-rays in each part of the lung were expressed in Hounsfield units (HU), which are related to density (D): D = 1 + HU/1,000. No significant alteration in pulmonary density (0.37 ± 0.04 vs. 0.35 ± 0.03, not significant) was observed after the 2-h run test. Although lung volume slightly increased (change of 166 ± 205 ml, P < 0.05), lung mass remained stable because of a change in density distribution. We failed to detect any changes in postexercise lung mass, suggesting that other mechanisms need to be considered to explain the observed alterations in pulmonary gas exchange after prolonged strenuous exercise.
Nitric oxide donors can increase heart rate independent of autonomic activation
Authors: Hogan Niall , Casadei Barbara , Paterson David J.
Published: December 2017

Administration of nitric oxide (NO) donors in vivo is accompanied by a baroreflex-mediated increase in heart rate (HR). In vitro, however, NO donors can increase HR directly by stimulating a pathway that involves NO, cGMP, and the hyperpolarization-activated current ( I f). The aim of this study was to assess the functional significance of this pathway in vivo by testing whether NO donors can increase HR in the anesthetized rabbit independent of the autonomic nervous system. New Zealand White rabbits were vagotomized, cardiac sympathectomized, and treated with propranolol (0.3 mg/kg iv). The NO donor molsidomine (0.2 mg/kg iv) caused a progressive increase (Δ) in HR (ΔHR, 14 ± 3 beats/min; P < 0.01). This effect was significantly reduced by the I f blocker ZD-7288 (0.2 mg/kg iv; ΔHR, 2 ± 3 beats/min; P = not significant). Similar results were seen with sodium nitroprusside. The positive chronotropic effect of sodium nitroprusside (50 μM) was confirmed in the isolated working rabbit heart preparation (ΔHR, 17 ± 3 beats/min; P < 0.01). In conclusion, NO donors exert a small, but significant, positive chronotropic effect in vivo that is independent of the autonomic nervous system. These results are also consistent with data in sinoatrial node cells that show that NO donors increase HR by stimulating I f.
Equivalent radius of paracellular “pores” of the mesothelium
Authors: Agostoni Emilio , Bodega Francesca , Zocchi Luciano
Published: December 2017

Diffusional permeability ( P) to water ( Pw), Cl−([Formula: see text]), and mannitol ( Pman) was determined in specimens of rabbit parietal pericardium without and with phospholipids added on the luminal side, as previously done with sucrose and Na+. P to the above-mentioned molecules and to Na+([Formula: see text]) was also determined after mesothelium was scraped away from specimens. Pw,[Formula: see text],[Formula: see text], and Pmanof connective tissue were the following (×10−5cm/s): 73.1 ± 7.3 (SE), 59.5 ± 4.5, 41.7 ± 3.4, and 23.4 ± 2.4, respectively. From these and corresponding data on integer pericardium, Pw,[Formula: see text],[Formula: see text], and Pmanof mesothelium were computed. They were the following: 206, 17.9, 9.52, and 3.93, and 90.2, 14.4, 4.34, and 1.75 × 10−5cm/s without and with phospholipids, respectively. As previously found for P to sucrose, P to solutes is smaller in mesothelium than in connective tissue, although the latter is ∼35-fold thicker; instead, Pwis higher in mesothelium, suggesting marked water diffusion through cell membrane. Equivalent radius of paracellular “pores” of mesothelium was computed with two approaches, disregarding Pw. The former, a graphical analysis on a P-molecular radius diagram, yielded 6.0 and 1.7 nm without and with phospholipids, respectively. The latter, on the basis of Pman, P to sucrose, and function for restricted diffusion, yielded 7.8 and 1.1 nm, respectively.
Apocynin improves diaphragmatic function after endotoxin administration
Authors: Supinski G. , Stofan D. , Nethery D. , Szweda L. , DiMarco A.
Published: December 2017

Free radicals are known to play an important role in modulating the development of respiratory muscle dysfunction during sepsis. Moreover, neutrophil numbers increase in the diaphragm after endotoxin administration. Whether or not superoxide derived from infiltrating white blood cells contributes to muscle dysfunction during sepsis is, however, unknown. The purpose of the present study was to examine the effect of apocynin, an inhibitor of the superoxide-generating neutrophil NADPH complex, on endotoxin-induced diaphragmatic dysfunction. We studied groups of rats given saline, endotoxin, apocynin, or both endotoxin and apocynin. Animals were killed 18 h after injection, a portion of the diaphragm was used to assess force generation, and the remaining diaphragm was used for determination of 4-hydroxynonenal (a marker of lipid peroxidation) and nitrotyrosine levels (a marker of free radical-mediated protein modification). We found that endotoxin reduced diaphragm force generation and that apocynin partially prevented this decrease [e.g., force in response to 20 Hz was 23 ± 1 (SE), 12 ± 2, 23 ± 1, and 19 ± 1 N/cm2, respectively, for saline, endotoxin, apocynin, and endotoxin/apocynin groups; P < 0.001]. Apocynin also prevented endotoxin-mediated increases in diaphragm 4-hydroxynonenal and nitrotyrosine levels ( P < 0.01). These data suggest that neutrophil-derived free radicals contribute to diaphragmatic dysfunction during sepsis.
Formation of reactive oxygen species by the contracting diaphragm is PLA2dependent
Authors: Nethery D. , Stofan D. , Callahan L. , DiMarco A. , Supinski G.
Published: December 2017

Recent work indicates that respiratory muscles generate superoxide radicals during contraction (M. B. Reid, K. E. Haack, K. M. Francik, P. A. Volberg, L. Kabzik, and M. S. West. J. Appl. Physiol. 73: 1797–1804, 1992). The intracellular pathways involved in this process are, however, unknown. The purpose of the present study was to test the hypothesis that contraction-related formation of reactive oxygen species (ROS) by skeletal muscle is linked to activation of the 14-kDa isoform of phospholipase A2(PLA2). Studies were performed by using an in vitro hemidiaphragm preparation submerged in an organ bath, and formation of ROS in muscles was assessed by using a recently described fluorescent indicator technique. We examined ROS formation in resting and contracting muscle preparations and then determined whether contraction-related ROS generation could be altered by administration of various PLA2inhibitors: manoalide and aristolochic acid, both inhibitors of 14-kDa PLA2; arachidonyltrifluoromethyl ketone (AACOCF3), an inhibitor of 85-kDa PLA2; and haloenol lactone suicide substrate (HELSS), an inhibitor of calcium-independent PLA2. We found 1) little ROS formation [2.0 ± 0.8 (SE) ng/mg] in noncontracting control diaphragms, 2) a high level of ROS (20.0 ± 2.0 ng/mg) in electrically stimulated contracting diaphragms (trains of 20-Hz stimuli for 10 min, train rate 0.25 s−1), 3) near-complete suppression of ROS generation in manoalide (3.0 ± 0.5 ng/mg, P < 0.001)- and aristolochic acid-treated contracting diaphragms (4.0 ± 1.0 ng/mg, P < 0.001), and 4) no effect of AACOCF3or HELSS on ROS formation in contracting diaphragm. During in vitro studies examining fluorescent measurement of ROS formation in response to a hypoxanthine/xanthine oxidase superoxide-generating solution, manoalide, aristolochic acid, AACOCF3, and HELSS had no effect on signal intensity. These data indicate that ROS formation by contracting diaphragm muscle can be suppressed by the administration of inhibitors of the 14-kDa isoform of PLA2and suggest that this enzyme plays a critical role in modulating ROS formation during muscle contraction.
A metabolic limit on the ability to make up for lost time in endurance events
Authors: Fukuba Yoshiyuki , Whipp Brian J.
Published: December 2017

It has been repeatedly demonstrated that the tolerable duration ( t) of high-intensity cycling is well characterized as a hyperbolic function of power ( P) with an asymptote that has been termed the “fatigue threshold” and with a curvature constant. This hyperbolic P- trelationship has also been confirmed in running and swimming, when speed ( V) is used instead of P; that is, ( V − V F) ⋅ t= D′, where V F is the V at the fatigue threshold, and D′ is the curvature constant. Therefore, we theoretically analyzed herein the consequences of an athlete performing the initial part of an endurance event at a V different from the constant rate that would allow the performance time to be determined by the hyperbolic V- trelationship. We considered not only the V- tconstraints that limit the athlete’s ability to make up the time lost by too slow an early pace but also the consequences of a more rapid early pace. Our analysis demonstrates that both the V F and D′ parameters of the athlete’s V- tcurve play an important role in the pace allocation strategy of the athlete. That is, 1) when the running V during any part of the whole running distance is below V F, the athlete can never attain the goal of achieving the time equivalent to that of running the entire race at constant maximal V (i.e., that determined by one’s own best V- tcurve); and 2) the “endurance parameter ratio” D′/ V F is especially important in determining the flexibility of the race pace that the athlete was able to choose intentionally.
Exercise attenuates nuclear protein binding to gene regulatory sequences of hepatic fatty acid synthase
Authors: Fiebig Russel , Gore Mitchell T. , Ji Li Li
Published: December 2017

The effect of an acute bout of exhaustive exercise on hepatic fatty acid synthase (FAS) gene expression was examined in rats. Female Sprague-Dawley rats (age 8 wk) were fasted for 48 h (F, n = 6), or fasted, refed a high-fructose diet for 6 h, and killed at rest (R, n = 6) or killed after running on a treadmill at 27 m/min and 5% grade for 88 ± 7 min (E, n = 6). Gel mobility shift assay indicated that R rats had twofold higher liver nuclear protein binding to oligonucleotides corresponding to the insulin responsive sequence (−71/−50) and carbohydrate response element (+283/+303) on the FAS promoter, compared with F rats. Exercise severely attenuated this binding in liver nuclear extracts to the levels seen in F rats. Competition and supershift experiments revealed that the bound protein complexes contained the upstream stimulatory factors. Nuclear run-on experiment revealed a 49-fold increase in transcription rate of the FAS gene in R vs. F rats, whereas exercise suppressed the transcription rate. FAS mRNA abundance and FAS enzyme activity were dramatically increased with refeeding but were unaltered by exercise. The results reveal that dietary induction of hepatic FAS is stimulated by increased nuclear protein binding to insulin responsive sequence and carbohydrate response element, whereas exhaustive exercise attenuates the binding, which may precede downregulation of FAS mRNA and enzyme synthesis reported in our previous work (M. A. Griffiths, R. Fiebig, M. T. Gore, D. H. Baker, K. Esser, L. Oscai, and L. L. Ji. J. Nutr. 126, 1959–1971, 1996).
Pontine cholinergic mechanisms enhance trigeminally evoked respiratory suppression in the anesthetized rat
Authors: Dutschmann Mathias , Herbert Horst
Published: December 2017

In the present study, we investigated in anesthetized rats the influences of the pontine rapid-eye-movement (REM) sleep center on trigeminally induced respiratory responses. We evoked the nasotrigeminal reflex by electrical stimulation of the ethmoidal nerve (EN5) and analyzed the EN5-evoked respiratory suppression before and after injections into the pontine reticular nuclei of the cholinergic agonist carbachol. After injections of 80–100 nl of carbachol (20 mM), we observed a decrease in respiratory rate, respiratory minute volume, and blood pressure but an increase in tidal volume. In those cases in which carbachol injections alone caused these REM sleep-like autonomic responses, we also observed that the EN5-evoked respiratory suppression was significantly potentiated. Unfortunately, carbachol injections failed to depress genioglossus electromyogram (EMG) effectively, because the EMG activity was already strongly depressed by the anesthetic α-chloralose. We assume that pontine carbachol injections in our anesthetized rats cause autonomic effects that largely resemble REM sleep-like respiratory and vascular responses. We therefore conclude that the observed potentiation of EN5-evoked respiratory suppression after carbachol might be due to REM sleep-associated neuronal mechanisms. We speculate that activation of sensory trigeminal afferents during REM sleep might contribute to pathological REM sleep-associated respiratory failures.
Increase in blood bradykinin concentration after eccentric weight-training exercise in men
Authors: Blais Charles , Adam Albert , Massicotte Denis , Péronnet François
Published: December 2017

The purpose of this study was to verify the possible appearance in the blood of bradykinin (BK) and des-Arg9-bradykinin (des-Arg9-BK) after eccentric exercise in 13 male subjects. Eccentric exercise (5 × 10 leg presses at 120% maximal voluntary concentric contraction) resulted in muscle damage and inflammation, as suggested by the significant increase in serum creatine kinase activity (from 204 ± 41 to 322 ± 63 U/l 12 h postexercise) and by severe lasting pain, which also peaked at 12 h postexercise. Blood BK and des-Arg9-BK concentrations were measured by competitive enzyme immunoassays using highly specific polyclonal rabbit IgG. Des-Arg9-BK concentration was not modified (preexercise: 44 ± 14 pmol/l; pooled postexercise: 47 ± 4 pmol/l). In contrast, BK concentration significantly increased immediately after the exercise session (68 ± 9 vs. 42 ± 3 pmol/l preexercise) and returned to basal values at 12, 24, and 48 h (pooled value: 40 ± 4 pmol/l). This observation suggests that the inflammatory process due to eccentric exercise-induced muscle damage could be mediated in part by BK.
In vivo characterization of the transitional bronchioles by aerosol-derived airway morphometry
Authors: Zeman Kirby L. , Scheuch Gerhard , Sommerer Knut , Brown James S. , Bennett William D.
Published: December 2017

Effective airway dimensions (EADs) were determined in vivo by aerosol-derived airway morphometry as a function of volumetric lung depth (VLD) to identify and characterize, noninvasively, the caliber of the transitional bronchiole region of the human lung and to compare the EADs by age, gender, and disease. By logarithmically plotting EAD vs. VLD, two distinct regions of the lung emerged that were identified by characteristic line slopes. The intersection of proximal and distal segments was defined as VLDtransand associated EADtrans. In our normal subjects ( n = 20), VLDtrans [345 ± 83 (SD) ml] correlated significantly with anatomic dead space (224 ± 34 ml) and end of phase II of single-breath nitrogen washout (360 ± 53 ml). The corresponding EADtranswas 0.42 ± 0.07 mm, in agreement with other ex vivo measurements of the transitional bronchioles. VLDtrans was smaller (216 ± 64 ml) and EADtrans was larger (0.83 ± 0.04 mm) in our patients with chronic obstructive pulmonary disease ( n = 13). VLDtrans increased with age for children (age 8–18 yr; P = 0.006, n = 26) and with total lung capacity for age 8–81 yr ( P < 0.001, n = 61). This study extends the usefulness of aerosol-derived airway morphometry to in vivo measurements of the transitional bronchioles.
Chest wall kinematics and respiratory muscle action in walking healthy humans
Authors: Sanna A. , Bertoli F. , Misuri G. , Gigliotti F. , Iandelli I. , Mancini M. , Duranti R. , Ambrosino N. , Scano G.
Published: December 2017

We studied chest wall kinematics and respiratory muscle action in five untrained healthy men walking on a motor-driven treadmill at 2 and 4 miles/h with constant grade (0%). The chest wall volume (Vcw), assessed by using the ELITE system, was modeled as the sum of the volumes of the lung-apposed rib cage (Vrc,p), diaphragm-apposed rib cage (Vrc,a), and abdomen (Vab). Esophageal and gastric pressures were measured simultaneously. Velocity of shortening ( V di) and power [W˙di = diaphragm pressure (Pdi) × V di] of the diaphragm were also calculated. During walking, the progressive increase in end-inspiratory Vcw ( P < 0.05) resulted from an increase in end-inspiratory Vrc,p and Vrc,a ( P < 0.01). The progressive decrease ( P < 0.05) in end-expiratory Vcw was entirely due to the decrease in end-expiratory Vab ( P < 0.01). The increase in Vrc,a was proportionally slightly greater than the increase in Vrc,p, consistent with minimal rib cage distortion (2.5 ± 0.2% at 4 miles/h). The Vcw end-inspiratory increase and end-expiratory decrease were accounted for by inspiratory rib cage (RCM,i) and abdominal (ABM) muscle action, respectively. The pressure developed by RCM,i and ABM and Pdi progressively increased ( P < 0.05) from rest to the highest workload. The increase in V di, more than the increase in the change in Pdi, accounted for the increase inW˙di. In conclusion, we found that, in walking healthy humans, the increase in ventilatory demand was met by the recruitment of the inspiratory and expiratory reserve volume. ABM action accounted for the expiratory reserve volume recruitment. We have also shown that the diaphragm acts mainly as a flow generator. The rib cage distortion, although measurable, is minimized by the coordinated action of respiratory muscles.
Lactate transport activity in rat skeletal muscle sarcolemmal vesicles after acute exhaustive exercise
Authors: Dubouchaud H. , Eydoux N. , Granier P. , Préfaut C. , Mercier J.
Published: December 2017

The effect of a single bout of exhaustive exercise on muscle lactate transport capacity was studied in rat skeletal muscle sarcolemmal (SL) vesicles. Rats were assigned to a control (C) group ( n = 14) or an acutely exercised (E) group ( n = 20). Exercise consisted of treadmill running (25 m/min, 10% grade) to exhaustion. SL vesicles purified from C and E rats were sealed because of sensitivity to osmotic forces. The time course of 1 mM lactate uptake in zero- trans conditions showed that the equilibrium level in the E group was significantly lower than in the C group ( P < 0.05). The initial rate of 1 mM lactate uptake decreased significantly from 2.44 ± 0.22 to 1.03 ± 0.08 nmol ⋅ min−1 ⋅ mg protein−1( P < 0.05) after exercise, whereas that of 50 mM lactate uptake did not differ significantly between the two groups. For 100 mM external lactate concentration ([lactate]), exhaustive exercise increased initial rates of lactate uptake (219.6 ± 36.3 to 465.4 ± 80.2 nmol ⋅ min−1 ⋅ mg protein−1, P < 0.05). Although saturation kinetics were observed in the C group with a maximal transport velocity of 233 nmol ⋅ min−1 ⋅ mg protein−1 and a Michealis-Menten constant of 24.5 mM, saturation properties were not seen after exhaustive exercise in the E group, because initial rates of lactate uptake increased linearly with external [lactate]. We conclude that a single bout of exhaustive exercise significantly modified SL lactate transport activity, resulting in a decrease in 1 mM lactate uptake and was associated with alterations in the saturable properties at [lactate] above 50 mM. These results suggest that changes in sarcolemmal lactate transport activity may alter lactate and proton exchanges after exhaustive exercise.
Static respiratory muscle work during immersion with positive and negative respiratory loading
Authors: Taylor Nigel A. S. , Morrison James B.
Published: December 2017

Upright immersion imposes a pressure imbalance across the thorax. This study examined the effects of air-delivery pressure on inspiratory muscle work during upright immersion. Eight subjects performed respiratory pressure-volume relaxation maneuvers while seated in air (control) and during immersion. Hydrostatic, respiratory elastic (lung and chest wall), and resultant static respiratory muscle work components were computed. During immersion, the effects of four air-delivery pressures were evaluated: mouth pressure (uncompensated); the pressure at the lung centroid (Pl,c); and at Pl,c ±0.98 kPa. When breathing at pressures less than the Pl,c, subjects generally defended an expiratory reserve volume (ERV) greater than the immersed relaxation volume, minus residual volume, resulting in additional inspiratory muscle work. The resultant static inspiratory muscle work, computed over a 1-liter tidal volume above the ERV, increased from 0.23 J ⋅ l−1, when subjects were breathing at Pl,c, to 0.83 J ⋅ l−1at Pl,c −0.98 kPa ( P < 0.05), and to 1.79 J ⋅ l−1at mouth pressure ( P < 0.05). Under the control state, and during the above experimental conditions, static expiratory work was minimal. When breathing at Pl,c +0.98 kPa, subjects adopted an ERV less than the immersed relaxation volume, minus residual volume, resulting in 0.36 J ⋅ l−1of expiratory muscle work. Thus static inspiratory muscle work varied with respiratory loading, whereas Pl,c air supply minimized this work during upright immersion, restoring lung-tissue, chest-wall, and static muscle work to levels obtained in the control state.
Lung elastic recoil during breathing at increased lung volume
Authors: Rodarte Joseph R. , Noredin Gassan , Miller Charles , Brusasco Vito , Pellegrino Riccardo ,   (With the Technical Assistance of Todd M. Officer)
Published: December 2017

During dynamic hyperinflation with induced bronchoconstriction, there is a reduction in lung elastic recoil at constant lung volume (R. Pellegrino, O. Wilson, G. Jenouri, and J. R. Rodarte. J. Appl. Physiol. 81: 964–975, 1996). In the present study, lung elastic recoil at control end inspiration was measured in normal subjects in a volume displacement plethysmograph before and after voluntary increases in mean lung volume, which were achieved by one tidal volume increase in functional residual capacity (FRC) with constant tidal volume and by doubling tidal volume with constant FRC. Lung elastic recoil at control end inspiration was significantly decreased by ∼10% within four breaths of increasing FRC. When tidal volume was doubled, the decrease in computed lung recoil at control end inspiration was not significant. Because voluntary increases of lung volume should not produce airway closure, we conclude that stress relaxation was responsible for the decrease in lung recoil.
Interrupter airway and tissue resistance: errors caused by valve properties and respiratory system compliance
Authors: Kessler Volker , Mols Georg , Bernhard Holger , Haberthür Christoph , Guttmann Josef
Published: December 2017

The interrupter technique is used to determine airway and tissue resistance. Their accuracy is influenced by the technical properties of the interrupter device and the compliance of the respiratory system. We investigated the influence of valve characteristics and respiratory system compliance on the accuracy of determining airway and tissue resistance by means of a computer simulation. With decreasing compliance we found increasing errors in both airway and tissue resistance determination of up to 34 and 71%, respectively. On this basis we developed a new occlusion valve, with special emphasis on rapid closing time and tightness in the closed state to improve the accuracy of resistance determination. The newly developed occlusion device greatly improves the accuracy of airway and tissue resistance determination. We conclude that respiratory system compliance is a limiting factor for the accuracy of the interrupter technique. To apply the interrupter technique in patients with extremely low respiratory system compliances, we need sophisticated technical devices.
Modulation of the corticospinal control of ventilation by changes in reflex respiratory drive
Authors: Corfield D. R. , Roberts C. A. , Guz A. , Murphy K. , Adams L.
Published: December 2017

We have determined whether changes in [Formula: see text]above and below eucapnia modulate the precision of the voluntary control of breathing. Twelve trained subjects performed a compensatory tracking task in which they had to maintain the position of a cursor (perturbed by a variable triangular forcing function) on a fixed target by breathing in and out of a spirometer (ventilatory tracking; at 10 l/min). Before each task, subjects hyperventilated for 5 min, and the end-tidal [Formula: see text]([Formula: see text]) was controlled; tracking was then performed separately at hypocapnia, eucapnia, and hypercapnia ([Formula: see text] ∼25, 37, and 43 Torr, respectively). Ventilatory tracking error was unchanged during hypocapnia ( P > 0.05) but was significantly worse during hypercapnia ( P < 0.003), compared with eucapnia; arm tracking error, performed as a control, was not significantly affected by[Formula: see text]( P > 0.05). In conclusion, ventilatory tracking performance is unaffected by the eucapnic[Formula: see text]. From this, we suggest that resting breathing in awake humans may be independent of chemical drives and of the prevailing [Formula: see text].