bluuebunny/crossref_metadata_2025 huggingface dataset:
The V˙o2slow component for severe exercise depends on type of exercise and is not correlated with time to fatigue
Authors: Billat Veronique L. , Richard Ruddy , Binsse Valerie M. , Koralsztein Jean P. , Haouzi Philippe
Published: December 2017

The purpose of this study was to examine the influence of the type of exercise (running vs. cycling) on the O2uptake (V˙o2) slow component. Ten triathletes performed exhaustive exercise on a treadmill and on a cycloergometer at a work rate corresponding to 90% of maximalV˙o2(90% work rate maximalV˙o2). The duration of the tests before exhaustion was superimposable for both type of exercises (10 min 37 s ± 4 min 11 s vs. 10 min 54 s ± 4 min 47 s for running and cycling, respectively). TheV˙o2slow component (difference between V˙o2at the last minute and minute 3 of exercise) was significantly lower during running compared with cycling (20.9 ± 2 vs. 268.8 ± 24 ml/min). Consequently, there was no relationship between the magnitude of theV˙o2slow component and the time to fatigue. Finally, because blood lactate levels at the end of the tests were similar for both running (7.2 ± 1.9 mmol/l) and cycling (7.3 ± 2.4 mmol/l), there was a clear dissociation between blood lactate and the V˙o2slow component during running. These data demonstrate that 1) theV˙o2slow component depends on the type of exercise in a group of triathletes and 2) the time to fatigue is independent of the magnitude of theV˙o2slow component and blood lactate concentration. It is speculated that the difference in muscular contraction regimen between running and cycling could account for the difference in theV˙o2slow component.
Bronchial vascular contribution to lung lymph flow
Authors: Wagner Elizabeth M. , Blosser Sandralee , Mitzner Wayne
Published: December 2017

The lymphatic vessels of the lung provide an important route for clearance of interstitial edema fluid filtered from pulmonary blood vessels. However, the importance of lung lymphatics for the removal of airway liquid filtered from the systemic circulation of the lung has not been demonstrated. We studied the contribution of the bronchial vasculature to lung lymph flow in anesthetized, ventilated sheep ( n = 35). With the bronchial artery cannulated and perfused (control flow = 0.6 ml ⋅ min−1⋅ kg−1), lymph flow from the efferent duct of the caudal mediastinal lymph node was measured 1) during increased bronchial vascular perfusion (300% of control flow); 2) with a hydrated interstitium induced by a 1-h period of left atrial hypertension and subsequent recovery, both with and without bronchial perfusion; and 3) during infusion (directly into the bronchial artery) of bradykinin, an inflammatory mediator known to cause changes in bronchial vascular permeability. Increased bronchial perfusion for 90 min resulted in an average 35% increase in lung lymph flow. During left atrial hypertension, the increase in lung lymph flow was significantly greater with bronchial perfusion (339% increase over baseline) than without bronchial perfusion (138% increase). Furthermore, recovery after left atrial hypertension was more complete after 90 min without bronchial perfusion (91%) than with bronchial perfusion (63%). Infusion of bradykinin into the bronchial artery resulted in a prompt and prolonged 107% increase in lung lymph flow. This was not seen if the same dose was infused into the pulmonary artery. Thus bronchial vascular transudate contributes significantly to lymph flow from the efferent duct of the caudal mediastinal lymph node. These results demonstrate that lymph vessels clear excess fluid from the airway wall and should be considered when evaluating the effect of vascular leak in airway obstruction.
Human skeletal muscle HSP70 response to training in highly trained rowers
Authors: Liu Yuefei , Mayr Sabine , Opitz-Gress Alexandra , Zeller Claudia , Lormes Werner , Baur Susanne , Lehmann Manfred , Steinacker Jürgen M.
Published: December 2017

Previous studies have demonstrated exercise-induced heat shock protein 70 (HSP70) in animals. The purpose of this study was to investigate human skeletal muscle HSP70 response to rowing training. Ten male rowers trained for 4 wk with different forms, durations, and intensities of exercise. Biopsy was performed in the right musculus vastus lateralis before training and at the end of each week. HSP70 in 5 μg of total protein from the muscle sample was determined by using Western blot and immunodetection with chemiluminescence technique, by means of laser densitometer referring to a series of known standard HSP70. Compared with pretraining (100%), HSP70 increased during training (181, 405, 456, and 363% from the first to fourth training week, respectively) with the maximum HSP70 production at the end of second training week. Thus HSP70 is induced in highly trained human muscle by long-term training.
Evidence that neuroepithelial endocrine cells control the spontaneous tone in guinea pig tracheal preparations
Authors: Skogvall Staffan , Korsgren Magnus , Grampp Wolfgang
Published: December 2017

The hypothesis that neuroepithelial endocrine (NEE) cells control spontaneous tone in isolated guinea pig tracheal preparations was examined. Epithelium-denuded preparations were unable to develop a normal oscillating tone in 12% oxygen (corresponding to systemic arterial oxygen levels) and, instead, developed a strong, smooth tone, similar to the “classic” tone in 94% oxygen. Inhibition of the hydrogen peroxide-producing NADPH oxidase in the NEE cells by 20 μM diphenyleneiodonium chloride transformed, in intact preparations in 94% oxygen, the tone from a strong, smooth type to an oscillating tone of considerably less force. Similar experiments in denuded preparations showed no change of tone and no oscillations. After pretreatment with the catalase inhibitor 3-amino-1,2,4-triazole (1 mM), addition of 2 mM hydrogen peroxide to intact preparations displaying the oscillating tone caused a transformation to a strong, smooth type. These findings support the hypothesis that the spontaneous tone in this preparation is largely controlled by the oxygen-sensing NEE cells. For the first time, previous findings on isolated cells can be linked to effects in intact tissue preparations. The results also suggest that the regulation by the NEE cells involves the release of powerful relaxing and contracting factors from the epithelium.
Efficacy of recombinant human Hb by31P-NMR during isovolemic total exchange transfusion
Authors: Sillerud Laurel O. , Caprihan Arvind , Berton Nancy , Rosenthal Gary J.
Published: December 2017

The ability of recombinant human Hb (rHb1.1), which is being developed as an oxygen therapeutic, to support metabolism was measured by in vivo31P-NMR surface coil spectroscopy of the rat abdomen in control animals and in animals subjected to isovolemic exchange transfusion to hematocrit of <3% with human serum albumin or 5 g/dl rHb1.1. No significant changes in metabolite levels were observed in control animals for up to 6 h. The albumin-exchange experiments, however, resulted in a more than eightfold increase in Pi and a 50% drop in phosphocreatine and ATP within 40 min. The tissue pH dropped from 7.4 to 6.8. The decrease in high-energy phosphates obeyed Michaelis-Menten kinetics, with a Michaelis-Menten constant of 3% as the hematocrit at which a 50% drop in high-energy phosphates was observed. Exchange transfusion with rHb1.1 resulted in no significant drop in high-energy phosphates, no rise in Pi, and no change in tissue pH from 7.35 ± 0.15 for up to 5 h after exchange. By these criteria, rHb1.1 at a plasma Hb concentration of ∼5 g/dl after total exchange transfusion was able to sustain energy metabolism of gut tissue at levels indistinguishable from control rats with a threefold higher total Hb level in erythrocytes.
Alterations in diaphragm contractility after nandrolone administration: an analysis of potential mechanisms
Authors: Lewis Michael I. , Fournier Mario , Yeh Amelia Y. , Micevych Paul E. , Sieck Gary C.
Published: December 2017

The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg ⋅ kg−1 ⋅ day−1; with weight gain, final dose: 2.7 mg ⋅ kg−1 ⋅ day−1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening ( V o) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as V o, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26–47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC2B with Nan. Ca2+-activated myosin ATPase activity was increased 35–39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of cross-bridge turnover and thus increased V o. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.
Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia
Authors: Grimm David R. , Arias Ercilia , Lesser Marvin , Bauman William A. , Almenoff Peter L.
Published: December 2017

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4–7) and six with paraplegia (T9–L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 ± 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 ± 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.
Reduced reflex sensitivity persists several days after long-lasting stretch-shortening cycle exercise
Authors: Avela Janne , Kyröläinen Heikki , Komi Paavo V. , Rama Daniel
Published: December 2017

The mechanisms related to the acute and delayed secondary impairment of the stretch reflex function were investigated after long-lasting stretch-shortening cycle exercise. The results demonstrated a clear deterioration in muscle function immediately after fatigue, which was accompanied by a clear reduction in active and passive reflex sensitivity. For active and passive stretch reflexes, this reduction was biphasic ( P < 0.05 to P < 0.001). However, for the ratio of the electrically induced maximal Hoffmann reflex to the maximal mass compound action potential, only one significant reduction was seen immediately after fatigue (71.2%, P < 0.01). A similar significant ( P < 0.01) decrease in the stretch-resisting force of the muscle was also detected. Clear increases were found in the indirect markers of muscle damage (serum creatine kinese activity and skeletal troponin I), which could imply the occurrence of ultrastructural muscle damage. It is suggested that the acute reduction in reflex sensitivity is of reflex origin and due to two active mechanisms, disfacilitation and presynaptic inhibition. However, the delayed second decline in the sensitivity of some reflex parameters may be attributable to the secondary injury, because of some inflammatory response to the muscle damage. This might emphasize the role of presynaptic inhibition via group III and IV muscle afferents.
Modeling the effects of proteins on pH in plasma
Authors: Watson Philip D.
Published: December 2017

Stewart’s model of plasma acid-base balance ( Can. J. Physiol. Pharmacol. 61: 1444–1461, 1983) has three weaknesses in the treatment of weak acids: 1) the combination of all weak acids into one entity, 2) inappropriate chemistry for the protein combination with H+, and 3) undocumented values for the dissociation parameters. The present study models serum albumin acid-base properties by fixed negative charges and the association of H+with the imidazole side chain of histidine. This model has three parameters: 1) the net negative fixed charge (21 eq/mol), 2) the number of histidine residues (16/mol), and 3) the association constant for the imidazole side chain (1.77 × 10−7eq/l), all determined from published values. The model was compared with that of Figge, Mydosh, and Fencl ( J. Lab. Clin. Med.120: 713–719, 1992) and with the pH data of Figge, Rossing, and Fencl ( J. Lab. Clin. Med. 117: 453–467, 1991). The predictions of pH were excellent, comparable to those found by Figge, Mydosh, and Fencl. The model has the advantages that its structure and parameter values are supported by the literature and that the acid-base effects of factors modifying protein can be investigated.
Perfluorocarbon emulsion improves oxygenation of the cat primary visual cortex
Authors: Padnick Lissa B. , Linsenmeier Robert A. , Goldstick Thomas K.
Published: December 2017

Tissue[Formula: see text] was measured in the primary visual cortex of anesthetized, artificially ventilated, normovolemic cats to evaluate the effect of small doses [1 g perfluorocarbon (PFC)/kg] of a PFC emulsion (1 g PFC/1.1 ml emulsion; Alliance Pharmaceutical, San Diego, CA) on brain oxygenation. The change in tissue [Formula: see text]([Formula: see text]), resulting from briefly changing the respiratory gas from room air to 100% oxygen, was measured before and after intravenous infusion of the emulsion. Before emulsion, [Formula: see text] was 51.1 ± 45.6 Torr ( n = 8 cats). Increases in [Formula: see text] of 34.0 ± 26.1 (SD) % ( n = 8) and 16.3 ± 8.4% ( n = 6) were observed after the first and second emulsion infusions, respectively. The further increase in [Formula: see text] after the third dose (7.9 ± 10.5%; n = 7) was not statistically significant. The observed increases in tissue oxygenation as a result of the PFC infusions appear to be the result of enhanced oxygen transport to the tissue.
Dilation of rat diaphragmatic arterioles by flow and hypoxia: roles of nitric oxide and prostaglandins
Authors: Ward Michael E.
Published: December 2017

The in vitro responses to ACh, flow, and hypoxia were studied in arterioles isolated from the diaphragms of rats. The endothelium was removed in some vessels by low-pressure air perfusion. In endothelium-intact arterioles, pressurized to 70 mmHg in the absence of luminal flow, ACh (10−5 M) elicited dilation (from 103 ± 10 to 156 ± 13 μm). The response to ACh was eliminated by endothelial ablation and by the nitric oxide synthase antagonists N G-nitro-l-arginine (l-NNA; 10−5 M) and N G-nitro-l-arginine methyl ester (l-NAME, 10−5 M) but not by indomethacin (10−5 M). Increases in luminal flow (5–35 μl/min in 5 μl/min steps) at constant distending pressure (70 mmHg) elicited dilation (from 98 ± 8 to 159 ± 12 μm) in endothelium-intact arterioles. The response to flow was partially inhibited byl-NNA,l-NAME, and indomethacin and eliminated by endothelial ablation and by concurrent treatment withl-NAME and indomethacin. The response to hypoxia was determined by reducing the periarteriolar[Formula: see text] from 100 to 25–30 Torr by changing the composition of the gas used to bubble the superfusing solution. Hypoxia elicited dilation (from 110 ± 9 to 165 ± 12 μm) in endothelium-intact arterioles but not in arterioles from which the endothelium had been removed. Hypoxic vasodilation was eliminated by treatment with indomethacin and was not affected byl-NAME orl-NNA. In rat diaphragmatic arterioles, the response to ACh is dependent on endothelial nitric oxide release, whereas the response to hypoxia is mediated by endothelium-derived prostaglandins. Flow-dilation requires that both nitric oxide and cyclooxygenase pathways be intact.
Hyperoxia-induced changes in antioxidant capacity and the effect of dietary antioxidants
Authors: Cao Guohua , Shukitt-Hale Barbara , Bickford Paula C. , Joseph James A. , McEwen John , Prior Ronald L.
Published: December 2017

We investigated, by measuring oxygen radical absorbance capacity (ORAC), whether hyperoxia causes alterations in antioxidant status and whether these alterations could be modulated by dietary antioxidants. Rats were fed for 8 wk a control diet or a control diet supplemented with vitamin E (500 IU/kg) or with aqueous extracts (ORAC: 1.36 mmol Trolox equivalents/kg) from blueberries or spinach and then were exposed to air or >99% O2for 48 h. Although the constituents of the extracts were not extensively characterized, HPLC indicated that blueberry extract was particularly rich in anthocyanins, and the spinach extract did not contain any anthocyanins. The ORAC was determined in samples without proteins [serum treated with perchloric acid (PCA); ORACPCA] and with proteins (ORACtot). Hyperoxia induced a decrease in serum protein concentration, an increase in serum ORACPCA, decreases in lung ORACPCAand ORACtot, and an equilibration of proteins and ORACPCAbetween serum and pleural effusion. These alterations suggested a redistribution of antioxidants between tissues and an increase in capillary permeability during hyperoxia. Only the blueberry extract was effective in alleviating the hyperoxia-induced redistribution of antioxidants between tissues.
Effects of vagotomy on cardiovascular response to periodic apneas in sedated pigs
Authors: Slamowitz D. , Chen L. , Scharf S. M.
Published: December 2017

There are few studies investigating the influence of vagally mediated reflexes on the cardiovascular response to apneas. In 12 sedated preinstrumented pigs, we studied the effects of vagotomy during apneas, controlling for apnea periodicity and thoracic mechanical effects. Nonobstructive apneas were produced by paralyzing and mechanically ventilating the animals, then turning the ventilator off and on every 30 s. Before vagotomy, relative to baseline, apnea caused increased mean arterial pressure (MAP; +19 ± 25%, P < 0.05), systemic vascular resistance (SVR; +33 ± 16%, P < 0.0005), and heart rate (HR; +5 ± 6%, P < 0.05) and decreased cardiac output (CO) and stroke volume (SV; −16 ± 10% P < 0.001). After vagotomy, no significant change occurred in MAP, SVR, and SV during apneas, but CO and HR increased relative to baseline. HR was always greater (∼14%, P < 0.01) during the interapneic interval compared with during apnea. We conclude that vagally mediated reflexes are important mediators of the apneic pressor response. HR increases after apnea termination are related, at least in part, to nonvagally mediated reflexes.
Thermoregulatory responses to cold water at different times of day
Authors: Castellani John W. , Young Andrew J. , Kain James E. , Sawka Michael N.
Published: December 2017

This study examined how time of day affects thermoregulation during cold-water immersion (CWI). It was hypothesized that the shivering and vasoconstrictor responses to CWI would differ at 0700 vs. 1500 because of lower initial core temperatures (Tcore) at 0700. Nine men were immersed (20°C, 2 h) at 0700 and 1500 on 2 days. No differences ( P > 0.05) between times were observed for metabolic heat production (M˙, 150 W ⋅ m−2), heat flow (250 W ⋅ m−2), mean skin temperature (T sk, 21°C), and the mean body temperature-change in M˙(ΔM˙) relationship. Rectal temperature (Tre) was higher ( P < 0.05) before (Δ = 0.4°C) and throughout CWI during 1500. The change in Tre was greater ( P < 0.05) at 1500 (−1.4°C) vs. 0700 (−1.2°C), likely because of the higher Tre-T skgradient (0.3°C) at 1500. These data indicate that shivering and vasoconstriction are not affected by time of day. These observations raise the possibility that CWI may increase the risk of hypothermia in the early morning because of a lower initial Tcore.
Anatomic localization of 24- and 96-h particle retention in canine airways
Authors: Kreyling W. G. , Blanchard J. D. , Godleski J. J. , Haeussermann S. , Heyder J. , Hutzler P. , Schulz H. , Sweeney T. D. , Takenaka S. , Ziesenis A.
Published: December 2017

Long-term retention of particles in airways is controversial. However, precise anatomic localization of the particles is not possible in people. In this study the anatomic location of retained particles after shallow bolus inhalation was determined in anesthetized, ventilated beagle dogs. Fifty 30-cm3 boluses containing monodisperse 2.5-μm polystyrene particles (PSL) were delivered to a shallow lung depth of 81–129 cm3. At 96 h before euthanasia, red fluorescent PSL were used; at 24 h, green fluorescent PSL and99mTc-labeled PSL were used. Clearance of 99mTc-PSL was measured during the next 24 h. Sites of particle retention were determined in systematic, volume-weighted random samples of microwave-fixed lung tissue. Precise particle localization and distribution was analyzed by using gamma counting, conventional fluorescence microscopy, and confocal microscopy. Within 24 h after shallow bolus inhalation, 50–95% of the deposited99mTc-PSL were cleared, but the remaining fraction was cleared slowly in all dogs, similar to previous human results. The three-dimensional deposition patterns showed particles across the entire cross-sectional plane of the lungs at the level of the carina. In these locations, 33 ± 9.9% of the retained particles were found in small, nonrespiratory airways (0.3- to 1-mm diameter) and 49 ± 10% of the particles in alveoli; the remaining fraction was found in larger airways. After 96 h, a similar pattern was found. These findings suggest that long-term retention in airways is at the bronchiolar level.
Fatigability of rat hindlimb muscles after acute irreversible acetylcholinesterase inhibition
Authors: Panenic Robert , Gisiger Victor , Gardiner Phillip F.
Published: December 2017

The purpose of this study was to investigate the functional impact of acute irreversible inhibition of acetylcholinesterase (AChE) on the fatigability of medial gastrocnemius and plantaris muscles of Sprague-Dawley rats. After treatment with methanesulfonyl fluoride (a lipid-soluble anticholinesterase), which reduced their AChE activity by >90%, these muscles were subjected to an in situ indirect stimulation protocol, including a series of isolated twitch and tetanic contractions preceding a 3-min fatigue regimen (100-ms trains at 75 Hz applied every 1.5 s). During the first minute of the fatigue regimen, the effects of AChE inhibition were already near maximal, including marked reductions in peak tension and the force-time integral (area), as well as a decrement of compound muscle action potential amplitudes within a stimulus train. Neuromuscular transmission failure was the major contributor of the force decreases in the AChE-inhibited muscles. However, despite this neuromuscular transmission failure, muscles of which all AChE molecular forms were nearly completely inhibited were still able to function, although abnormally, during 3 min of intermittent high-frequency nerve stimulation.
Developmental change in magnesium sulfate-induced relaxation of rabbit pulmonary arteries
Authors: Tolsa Jean-Francois , Gao Yuansheng , Raj J. Usha
Published: December 2017

Magnesium causes a variety of vascular smooth muscle to relax. The present study was designed to determine whether there is a developmental change in the magnesium-induced response of pulmonary vasculature. Isolated pulmonary arteries (PA) of newborn (1- to 3-day-old) and juvenile (4- to 6-wk-old) rabbits were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2, 37.0°C), and their isometric tension was recorded. In arteries preconstricted with endothelin-1 to a similar tension level, MgSO4 caused greater relaxation of juvenile rabbit PA than that of the newborn rabbit PA. Verapamil, a voltage-dependent Ca2+ channel blocker, attenuated magnesium-induced relaxation in juvenile rabbit PA but not in newborn PA. The uptake of Ca2+ of juvenile rabbit PA was inhibited by MgSO4, and the inhibition was attenuated by verapamil. The uptake of Ca2+ of newborn rabbit PA was smaller than that of the juvenile PA and was not significantly affected by MgSO4 and verapamil. These results demonstrate that there is a developmental increase in the dilator effect of MgSO4 in rabbit PA. In newborn rabbit PA, an incomplete maturation of the voltage-dependent Ca2+ channels may contribute to the smaller vasodilation induced by MgSO4.
Force depression in human quadriceps femoris following voluntary shortening contractions
Authors: Lee Hae-Dong , Suter Esther , Herzog Walter
Published: December 2017

The purpose of this study was to investigate whether the isometric muscle force, redeveloped following maximal-effort voluntary shortening contractions in human skeletal muscle, is smaller than the purely isometric muscle force at the corresponding length. Isometric knee extensor moments, surface electromyographic (EMG) signals of quadriceps femoris, and interpolated twitch moments (ITMs) were measured while 10 subjects performed purely isometric knee extensor contractions at a 60° knee angle and isometric knee extensor contractions at a 60° knee angle preceded by maximal-effort voluntary shortening of the quadriceps muscles. It was found that the knee extensor moments were significantly decreased for the isometric-shortening-isometric contractions compared with the isometric contractions for the group as a whole, whereas the corresponding EMG and ITM values were the same. This study is the first to demonstrate force depression following muscle shortening for voluntary contractions. We concluded that force depression following muscle shortening is an actual property of skeletal muscle rather than a stimulation artifact and that force depression during voluntary contraction is not accompanied by systematic changes in muscle activation as evaluated by EMG and ITM.
Tidal volume amplitude affects the degree of induced bronchoconstriction in dogs
Authors: Salerno Francesco G. , Shinozuka Norihiro , Fredberg Jeffrey J. , Ludwig Mara S.
Published: December 2017

When isolated constricted airway smooth muscle is oscillated, muscle tone decreases. We investigated whether changing tidal volume (Vt) would affect induced bronchoconstriction in an in vivo canine model. Open-chest dogs were intubated with a double-lumen endotracheal tube, which isolated each main bronchus, and mechanically ventilated with a dual-cylinder ventilator. Bronchial pressure (Pbr) and flow were measured separately in each lung. Resistance and elastance were calculated by fitting the changes in Pbr, flow, and volume to the equation of motion. After baseline measurements at the same Vt (150 ml), the two lungs were ventilated with different Vt (50 vs. 250 ml) at a constant positive end-expiratory pressure. A continuous infusion of methacholine was begun, and measurements were repeated. The two lungs were then ventilated with the same Vt (250 ml), and measurements were again repeated. A similar protocol was performed in a second group of dogs in which mean Pbr was kept constant. Bronchoconstriction was more severe in the lung ventilated with lower Vt in both protocols. When Vt was reset to the same amplitude in the two lungs, the difference in bronchoconstriction was abrogated. These results demonstrate that large Vt inhibits airway smooth muscle contraction, regardless of mean Pbr.
Pulmonary and bronchial circulatory responses to segmental lung injury
Authors: Lakshminarayan S. , Bernard S. , Polissar N. L. , Glenny R. W.
Published: December 2017

In regional lung injury, pulmonary blood flow decreases to the injured regions, and anastomotic bronchial blood flow and total bronchial blood flow increase. However, the pattern of redistribution of the two blood flows to the injured and noninjured areas is not known. In six anesthetized sheep, pulmonary and bronchial blood flows were measured with 15-μm fluorescent microspheres by using the reference flow method. Blood flows were measured in the control state and 1 h after instilling 1 ml/kg of 0.1 N hydrochloric acid into a dependent segment of the left lung. The lungs were then removed, dried, and cubed into ∼2-cm cubes while spatial coordinates were noted. Blood flow to each piece was calculated. Mean pulmonary blood flow to the noninjured pieces went from 730 ± 246 to 574 ± 347 ml/min ( P = 0.22), whereas in the injured pieces the pulmonary blood flow decreased from 246 ± 143 to 56 ± 46 ml/min ( P < 0.01). In contrast, bronchial blood flow to the injured pieces increased from 0.51 ± 0.1 to 1.43 ± 0.85 ml/min ( P = 0.005). We measured the change in flow as it related to the distance from the center of the injured area. Pulmonary blood flow decreased most at the center of the injury, whereas bronchial blood flow doubled at the center of injury and decreased with the distance away from the injury. The absolute increase in bronchial blood flow was substantially less than the decrease in pulmonary blood flow in the injured pieces. We also partitioned the observed variation in pulmonary and bronchial blood flow into that attributable to structure and that due to lung injury and found that 48% of the variation in pulmonary blood flow could be attributed to structure, whereas in the bronchial circulation 70% was attributable to structure. The reasons for these differences are not known and may reflect the intrinsic properties of the systemic and pulmonary circulations.
Spatial distribution of venous gas emboli in the lungs
Authors: Souders Jennifer E. , Doshier Jeffrey B. , Polissar Nayak L. , Hlastala Michael P.
Published: December 2017

The distribution of gaseous pulmonary emboli is presumed to be determined by their buoyancy. We hypothesized that regional pulmonary blood flow may also influence their distribution. Therefore, pulmonary blood flow was measured in supine, anesthetized dogs with use of 15-μm fluorescent microspheres at baseline and during N2 embolism. The animals were killed, and the lungs were excised, air-dried, and diced into ∼2-cm3 pieces with weights and spatial coordinates recorded. Embolism was defined as a >10% flow decrease relative to baseline. Vertically, the incidence of embolism increased substantially by 6 ± 1% per additional centimeter in height compared with baseline ( P = 0.0003). Embolism also increased radially by 3 ± 1%/cm from the hilum ( P = 0.002). There was a weaker but statistically significant increase in embolism to pieces with greater baseline flow, 9 ± 2% for every 1.0 increase in relative baseline flow ( P = 0.008). We conclude that the distribution of gaseous emboli is influenced by buoyancy and flow dynamics within the pulmonary vasculature.
Validation of fluorescent-labeled microspheres for measurement of relative blood flow in severely injured lungs
Authors: Hübler Matthias , Souders Jennifer E. , Shade Erin D. , Hlastala Michael P. , Polissar Nayak L. , Glenny Robb W.
Published: December 2017

The aim of the study was to validate a nonradioactive method for relative blood flow measurements in severely injured lungs that avoids labor-intensive tissue processing. The use of fluorescent-labeled microspheres was compared with the standard radiolabeled-microsphere method. In seven sheep, lung injury was established by using oleic acid. Five pairs of radio- and fluorescent-labeled microspheres were injected before and after established lung injury. Across all animals, 175 pieces were selected randomly. The radioactivity of each piece was determined by using a scintillation counter. The fluorescent dye was extracted from each piece with a solvent without digestion or filtering. The fluorescence was determined with an automated fluorescent spectrophotometer. Perfusion was calculated for each piece from both the radioactivity and fluorescence and volume normalized. Correlations between flow determined by the two methods were in the range from 0.987 ± 0.007 (SD) to 0.991 ± 0.002 (SD) after 9 days of soaking. Thus the fluorescent microsphere technique is a valuable tool for investigating regional perfusion in severely injured lungs and can replace radioactivity.
Versatile, high-speed force transducer using a laser diode beam as an optical lever
Authors: Barb Matthew D. , Morris Andrew B. , Maass-Moreno Roberto , Ragozzino Joseph , Ford Lincoln E.
Published: December 2017

A force transducer with variable sensitivity and speed is described. Its moving element is a cantilever beam that projects vertically into a muscle bath. A brace constrains bending of the beam to a short, proximal “hinge.” Rotation of the beam about the hinge is amplified 30-fold by an optical lever consisting of a laser diode beam reflected from a mirror on the cantilever to a photodiode pair. This design places the electrical components at a distance from the damp environment of the muscle bath. Large changes in sensitivity and speed can be obtained by substituting different cantilevers. Smaller changes can be made by varying the length of the hinge. A transducer with a 6-mm cantilever optimized for the study of single, skinned skeletal muscle fibers is described in detail. This device had a resonant frequency of 22 kHz and sensitivity such that the total root-mean-square noise in the circuit was more than 500-fold smaller than the expected maximum force. Variations of this device with orders of magnitude different sensitivities are also described.
Twitch transdiaphragmatic pressure depends critically on thoracoabdominal configuration
Authors: Chen Rongchang , Kayser Bengt , Yan Sheng , Macklem Peter T.
Published: December 2017

We measured the effect of thoracoabdominal configuration on twitch transdiaphragmatic pressure (Pdi, t) in response to supramaximal, transcutaneous, bilateral phrenic nerve shocks in three thin normal men. Pdi, t was measured as a function of lung volume (Vl) in the relaxation configuration, at functional residual capacity (FRC), and at the same end-tidal Vl 1) during relaxation; 2) with the abdomen (Ab) expanded and the rib cage (RC) in its relaxed FRC configuration; 3) with RC expanded and Ab in its relaxed FRC configuration; and 4) in configuration 3 with an active transdiaphragmatic pressure similar to that required to produce configuration 2. In increasing Vl from FRC to configuration 1, Pdi, t decreased by 3.6 cmH2O; to configuration 2 by 14.8 cmH2O; to configuration 3 by 3.7 cmH2O; and to configuration 4 by 2.7 cmH2O. We argue that changes in velocity of shortening and radius of curvature are unlikely to account for these effects and suggest that changes in diaphragmatic fiber length ( L di) are primarily responsible. If so, equivolume displacements of Ab and RC change L di in a ratio of ∼4:1. We conclude that Pdi, t is exquisitely sensitive to abdominal displacements that must be rigorously controlled if Pdi, t is to be used to assess diaphragmatic contractility.
Stretch-activated ion channels contribute to membrane depolarization after eccentric contractions
Authors: McBride Todd A. , Stockert Bradley W. , Gorin Fredric A. , Carlsen Richard C.
Published: December 2017

We tested the hypothesis that eccentric contractions activate mechanosensitive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance. Resting membrane potentials and contractile function were measured in rat tibialis anterior muscles after single or multiple exposures to a series of eccentric contractions. Each exposure produced a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers. The magnitude and duration of the depolarization were related to the number of contractions. Membrane depolarization was due primarily to an increase in Na+ influx, because the estimated Na+-to-K+ permeability ratio was increased in exercised muscles and resting membrane potentials could be partially repolarized by substituting an impermeant cation for extracellular Na+ concentration. Neither the Na+/H+ antiport inhibitor amiloride nor the fast Na+ channel blocker TTX had a significant effect on the depolarization. In contrast, addition of either of two nonselective SAC inhibitors, streptomycin or Gd3+, produced significant membrane repolarization. The results suggest that muscle fibers experience prolonged depolarization after eccentric contractions due, principally, to the activation of Na+-selective SAC.
Effects of atropine and l-NAME on cutaneous blood flow during body heating in humans
Authors: Shastry Shubha , Minson Christopher T. , Wilson Shurea A. , Dietz Niki M. , Joyner Michael J.
Published: December 2017

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1.0 ± 0.1°C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereasl-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion ofl-NAME resulted in a significant decrease in CVC (37 ± 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.
Airway narrowing and internal structural constraints
Authors: Seow Chun Y. , Wang Lu , Paré Peter D.
Published: December 2017

A computer model has been developed to simulate the movement restriction in the lamina propria-submucosa (L-S) layer (sandwiched by the basement membrane and the muscle layer) in a cartilage-free airway due to constriction of the smooth muscle layer. It is assumed that the basement membrane is inextensible; therefore, in the two-dimensional simulation, the perimeter outlining the membrane is a constant whether the airway is constricted or dilated. The cross-sectional area of the L-S layer is also assumed to be constant during the simulated airway narrowing. Folding of the mucosal membrane in constricted airways is assumed to be a consequence of the L-S area conservation and also due to tethering between the basement membrane and the muscle layer. The number of tethers determines the number of folds. The simulation indicates that the pressure in the L-S layer resulting from movement restriction can be a major force opposing muscle contraction and that the maximum shortening of the muscle layer is inversely proportional to the number of tethers (or folds) and the L-S layer thickness.
Genomics, genes, and environmental interaction: the role of exercise
Authors: Bray Molly S.
Published: December 2017

Regular exercise has been shown to improve control of lipid abnormalities, diabetes mellitus, hypertension, and obesity, with the greatest benefits realized by sedentary individuals who begin to exercise. Responses to exercise interventions are often highly variable among individuals, however, and research has indicated that response to exercise may be mediated in large part by variation in genes. As we strive to unravel the complex etiology of diseases like obesity, diabetes, and cardiovascular disease through the use of molecular and genetic tools now available, understanding the interaction and influence of environmental factors, such as exercise, on gene expression and function has taken on increasing importance. This review briefly summarizes strategies presently being used to elucidate genes and genetic effects that may be mediated or influenced by exercise and serves to illustrate the importance of considering the effect of exercise when investigating genes related to health or other physiological outcomes.
Protective and defensive airway reflexes evoked by nasal exposure to wood smoke in anesthetized rats
Authors: Ho C.-Y. , Kou Y. R.
Published: December 2017

We investigated the airway responses evoked by nasal wood smoke in anesthetized Sprague-Dawley rats. Wood smoke (5 ml, 1.4 ml/s) was delivered into an isolated nasal cavity while animals breathed spontaneously. In study 1, nasal wood smoke triggered either an apneic response ( n = 26) or a sniff-like response ( n = 16) within 1 s after smoke exposure in 42 normal rats. Both airway responses were abolished by trigeminal nerve denervation and by nasal application of a local anesthetic or a hydroxyl radical scavenger, but they were not significantly affected by removal of smoke particulates or nasal application of a saline vehicle. In study 2, nasal wood smoke only triggered a mild apneic response in two rats neonatally treated with capsaicin and had no effect on breathing in the other six; the treatment is known to chronically ablate C fibers and some Aδ fibers. In contrast, nasal wood smoke evoked an apneic response in six rats neonatally treated with the vehicle of capsaicin and elicited a sniff-like response in the other two. These results suggest that the apneic and sniff-like responses evoked by nasal wood smoke result from the stimulation of trigeminal nasal C-fiber and Aδ-fiber afferents by the gas-phase smoke and that hydroxyl radical is the triggering chemical factor.
Effects of spaceflight and thyroid deficiency on rat hindlimb development. II. Expression of MHC isoforms
Authors: Adams G. R. , Haddad F. , McCue S. A. , Bodell P. W. , Zeng M. , Qin L. , Qin A. X. , Baldwin K. M.
Published: December 2017

Both slow-twitch and fast-twitch muscles are undifferentiated after birth as to their contractile protein phenotype. Thus we examined the separate and combined effects of spaceflight (SF) and thyroid deficiency (TD) on myosin heavy chain (MHC) gene expression (protein and mRNA) in muscles of neonatal rats (7 and 14 days of age at launch) exposed to SF for 16 days. Spaceflight markedly reduced expression of the slow, type I MHC gene by ∼55%, whereas it augmented expression of the fast IIx and IIb MHCs in antigravity skeletal muscles. In fast muscles, SF caused subtle increases in the fast IIb MHC relative to the other adult MHCs. In contrast, TD prevented the normal expression of the fast MHC phenotype, particularly the IIb MHC, whereas TD maintained expression of the embryonic/neonatal MHC isoforms; this response occurred independently of gravity. Collectively, these results suggest that normal expression of the type I MHC gene requires signals associated with weight-bearing activity, whereas normal expression of the IIb MHC requires an intact thyroid state acting independently of the weight-bearing activities typically encountered during neonatal development of laboratory rodents. Finally, MHC expression in developing muscles is chiefly regulated by pretranslational processes based on the tight relationship between the MHC protein and mRNA data.
V˙o 2 kinetics and the O2 deficit in heavy exercise
Authors: Bearden S. E. , Moffatt R. J.
Published: December 2017

The purpose of this study was to examine a new method for calculating the O2 deficit that considered the O2 uptake (V˙o 2) kinetics during exercise as two separate phases in light of previous research in which it was shown that the traditional O2 deficit calculation overestimated the recovery O2 consumption (ROC). Eight subjects completed exercise transitions between unloaded cycling and 25% (heavy, H) or 50% (very heavy, VH) of the difference between the lactic acid threshold (LAT) and peakV˙o 2 for 8 min. The O2 deficit, calculated in the traditional manner, was significantly greater than the measured ROC for both above-LAT exercises: 4.03 ± 1.01 vs. 2.63 ± 0.80 (SD) liters for VH and 2.36 ± 0.91 vs. 1.74 ± 0.63 liters for H for the O2deficit vs. ROC ( P < 0.05). When the kinetics were viewed as two separate components with independent onsets, the calculated O2 deficit (2.89 ± 0.79 and 1.71 ± 0.70 liters for VH and H, respectively) was not different from the measured ROC ( P < 0.05). Subjects also performed the same work rate for only 3 min. These data, from bouts terminated before the slow component could contribute appreciably to the overallV˙o 2 response, show that the O2 requirement during the transition is less than the final steady state for the work rate, as evidenced by symmetry between the O2 deficit and ROC. This new method of calculating the O2 deficit more closely reflects the expected O2 deficit-ROC relationship (i.e., ROC ≥ O2deficit). Therefore, estimation of the O2 deficit during heavy exercise transitions should consider the slow component ofV˙o 2 as an additional deficit component with delayed onset.
A new ventilator for monitoring lung mechanics in small animals
Authors: Volgyesi G. A. , Tremblay L. N. , Webster P. , Zamel N. , Slutsky A. S.
Published: December 2017

Researchers investigating the genetic component of various disease states rely increasingly on murine models. We have developed a ventilator to simplify respiratory research in small animals down to murine size. The new ventilator provides constant-flow inflation and tidal volume delivery independent of respiratory parameter changes. The inclusion of end-inspiratory and end-expiratory pauses simplifies the measurement of airway resistance and compliance and allows the detection of dynamic hyperinflation (auto-positive end-expiratory pressure). After bench testing, we performed intravenous methacholine challenge on two strains of mice (A/J and C57bl/bj) known to differ in their responses by using the new ventilator. Dynamic hyperinflation and a decrease in compliance developed during methacholine challenge whenever respiratory rates of 60–120 breaths/min were employed. In contrast, if dynamic hyperinflation was prevented by lengthening expiratory time, (respiratory rate = 20 breaths/min), static compliance remained constant. More importantly, the coefficient of variation of the results decreased when lung volume shifts were prevented. In conclusion, airway challenge studies have greater precision when dynamic hyperinflation is prevented.