bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis
Authors: Rosser D. M. , Stidwill R. P. , Jacobson D. , Singer M.
Published: December 2017

The effect of endotoxin on tissue oxygen tension measured at the bladder epithelium was assessed in spontaneously breathing Sprague-Dawley rats anesthetized with halothane. Hyperdynamic (high cardiac output, group A, n = 6) and hypodynamic (low cardiac output, group B, n = 6) circulatory responses were achieved by intravenous administration of Escherichia coli lipopolysaccharide, 10 mg/kg over 30 min or 20 mg/kg over 1 min, respectively. Comparison was made against sham-operated control rats (group C, n = 6). Aortic and renal blood flows increased in group A and fell in group B (P < 0.001). However, in both groups, bladder epithelial oxygen tension rose significantly compared with control (P < 0.01), despite an increasing metabolic acidosis. This is in contradistinction to previous studies of nonseptic insults where bladder epithelial oxygen tension fell in line with an increasing arterial base deficit. If a raised tissue oxygen tension could be demonstrated in other organ beds, this would suggest that decreased utilization of oxygen rather than reduced tissue oxygen availability is responsible for the apparent anaerobic respiration seen in sepsis.
Retention of insoluble particles after local intrabronchial deposition in dogs
Authors: Lay J. C. , Berry C. R. , Kim C. S. , Bennett W. D.
Published: December 2017

Recent studies have challenged the generally accepted hypothesis that bronchial particle clearance is complete within 24–48 h postdeposition. We studied bronchial retention of inert particles using a bronchoscope and microspray nozzle to localize deposition in a bronchus while avoiding alveolar deposition. Six-microliter aliquots (444 kBq) of submicrometer (number mean diameter = 0.22 microns, geometric standard deviation = 1.75) technetium-99m-labeled (99mTc) sulfur colloid (SC) particles (n = 6) or the unbound radiolabel 99mTc-pertechnetate (99mTcO4-; n = 3) were sprayed onto a 5-mm-diam bronchus in halothane-anesthetized dogs. Radioactivity at the deposition site and clearance pathway was monitored externally with a gamma camera beginning immediately postspray. Bronchial retention of SC was 8.5 +/- 2.4 and 1.5 +/- 0.7% at 3 and 24 h postspray, respectively. Tracheal mucus velocity was measured at 10.4 +/- 2.2 mm/min. For comparison, clearance of inhaled submicrometer SC particles was also measured in the same dogs. Retention of inhaled aerosolized SC (peripheral lung deposition) was 98.1 +/- 1.1 and 76.3 +/- 1.8% at 3 and 24 h, respectively. 99mTcO4- cleared from the bronchi slightly more rapidly than did SC. Radioactivity was readily detected in the blood after deposition of 99mTcO4- but not of SC. Thus SC cleared by mucociliary transport, whereas 99mTcO4- cleared predominantly by transepithelial absorption. We conclude that clearance of submicrometer particles from a 5-mm conducting airway is very nearly complete by 24 h, with approximately 92% of the clearance occurring within the first 3 h postdeposition.
Thermal artifacts in plethysmographic airway resistance measurements
Authors: Peslin R. , Duvivier C. , Vassiliou M. , Gallina C.
Published: December 2017

Measurements of airway resistance (Raw) by body plethysmography during unconditioned air breathing are implicitly based on the assumption that the warming and humidification of air in the airways are instantaneous. Simulation with a simple model suggests that Raw may be frequency dependent and substantially underestimated at most breathing frequencies if the time constant of gas conditioning (theta) is between 0.01 and 0.3 s. We measured the frequency dependence of the real (Re) and imaginary parts of the relationship between the plethysmographic signal and airway flow from 0.5 to 3 Hz in six healthy subjects in several situations. During breathing of unconditioned air through a heated pneumotachograph, Re increased by 47 +/- 70% between 2 and 3 Hz; the data were consistent with a theta of 0.087 +/- 0.023 s. Additional dead spaces moderately increased theta: 0.105 +/- 0.031 and 0.120 +/- 0.027 s with 50-cm-long polyvinyl chloride and copper tubes, respectively. During breathing of saturated air conditioned at 34, 36, 38, and 40 degrees C, Re exhibited a much smaller positive frequency dependence, most of which was probably due to a flow dependence of Raw. We conclude that unless the inspired gas is conditioned, plethysmographic Raw is likely to be substantially underestimated, particularly when measured during spontaneous breathing.
Strength of the Breuer-Hering inflation reflex in term and preterm infants
Authors: De Winter J. P. , Merth I. T. , Berkenbosch A. , Brand R. , Quanjer P. H.
Published: December 2017

The effect of the presence of the respiratory distress syndrome (RDS) or related factors (static compliance of the respiratory system and transcutaneous blood gases) and gestational age on the strength of the Breuer-Hering inflation reflex (BHIR) was studied in three groups of infants. Twenty-six ventilated preterm infants with and without RDS were studied 6 h after birth (group 1). In 24 preterm infants, we followed the development of reflex strength during the first year of life (group 2). Twenty-one healthy nonintubated term infants were studied within the first week of life (group 3). The BHIR was initiated by end-inspiratory occlusions, and the strength was characterized by the ratio of expiratory time after and without preceding airway occlusion. The static compliance of the respiratory system in ventilated infants was assessed by the multiple-occlusion technique. In group 1, reflex strength declined with increasing gestational age; in the presence of RDS or low respiratory compliance, the decline was less. Transcutaneous blood gases did not affect reflex strength. At term age, reflex strength was similar in spontaneously breathing preterm (group 2) and term infants (group 3). The BHIR decreased in strength during the first year after preterm birth. We conclude that 1) the strength of the BHIR decreases with increasing gestational and postnatal ages and 2) RDS, due to changes in respiratory system mechanics, causes an increase in reflex strength.
Nonlinear relationship between heat production and force during voluntary contractions in humans
Authors: Saugen E. , Vollestad N. K.
Published: December 2017

The rate of temperature rise (dT/dt) in the vastus lateralis muscle of seven subjects was measured at four to five locations in each muscle during voluntary isometric contractions ranging from 10 to 90% of maximal voluntary contraction (MVC) force. dT/dt increased from 3.1 +/- 1.1 mK/s at 10% MVC to 14.5 +/- 1.3 mK/s at 90% MVC. In the typical subject, the increase in dT/dt with force was markedly higher between 30 and 70% MVC than in the upper and lower force ranges. The estimated ratio between heat rate in active muscle and force was six times higher at 10% MVC than at 90% MVC, indicating a markedly increasing economy of contraction with increasing force. The lower contraction economy at low forces may be explained by an increased rate of energy turnover associated with force generation and relaxation when motor units are contracting at low firing rates. Hence, we argue that recruitment and rate coding may have a profound effect on the economy of contraction at different force levels.
Diaphragm microvascular plasma PO2 measured in vivo
Authors: Poole D. C. , Wagner P. D. , Wilson D. F.
Published: December 2017

Phosphorescence quenching techniques measure microvascular PO2 without direct surgical manipulation of the tissue. At a given arterial PO2, microvascular PO2 reflects the local O2 uptake-to-O2 delivery ratio, i.e., VO2/QO2. We evaluated the potential of phosphorescence quenching to determine microvascular PO2 in the rat costal diaphragm (PdiaO2). PdiaO2 and arterial blood gases were monitored across transient changes of inspired O2 among 21, 10, and 100% and also during hypotensive states evoked by progressive phlebotomy. After a transit delay, PdiaO2 responded rapidly to alterations of inspired and thus arterial PO2, with half times of the response averaging 5–7 s for switches to a lower inspired O2 (i.e., from 21 to 10%, from 100 to 21%, and from 100 to 10%) and also from 10 to 21%. By comparison, half times of the 10 to 100% and 21 to 100% switches were longer [11 s (P = 0.085) and 21 s (P < 0.05), respectively]. Below a mean arterial blood pressure (BP) of 120–130 mmHg, PdiaO2 decreased as a linear function of BP, with these variables being significantly correlated in each instance (n = 5, r = 0.851–0.937, P < 0.01 for all animals). From these results, it appears feasible to measure PdiaO2 in the spontaneously breathing rat in vivo under steady-state and transient conditions. Also, during progressive hypotension, the fall in PdiaO2 is significantly related to falling BP, likely as a consequence of an increased metabolic demand (increased ventilation and diaphragm VO2) concomitant with decreased blood flow. We conclude that phosphorescence quenching techniques offer a powerful tool for assessing diaphragm physiology and pathophysiology.
Glycerol hyperhydration: hormonal, renal, and vascular fluid responses
Authors: Freund B. J. , Montain S. J. , Young A. J. , Sawka M. N. , DeLuca J. P. , Pandolf K. B. , Valeri C. R.
Published: December 2017

Glycerol ingestion has been shown to mediate hyperhydration; however, the mechanism(s) responsible for this improved fluid retention is not well understood. This study examined the hormonal, renal, and vascular fluid responses to glycerol hyperhydration in 11 resting male volunteers who ingested one of two experimental solutions and then a water bolus. The volume of fluid ingested was determined from the subjects' measured total body water (TBW; total volume = 37 ml/l TBW, 1,765 +/- 162 ml). Experimental solutions (5.0 ml/l TBW) were matched for color and taste and differed only in that one contained 1.5 g glycerol/l TBW (total osmolar load = 777 +/- 24 mosmol). Nine of the 11 subjects also completed a control trial during which no fluid was ingested. Glycerol ingestion (GI) resulted in greater fluid retention than the ingestion of water alone (WI; 60 vs. 32% 3-h posthyperhydration, P < 0.01). This improved fluid retention with GI resulted from lower urine flow rates (peak 6.2 vs. 10.5 ml/min, P < 0.01) associated with lower free water clearance rates (peak = 1.2 vs. 8.2 ml/min, P < 0.01). Hyperhydration had no effect on plasma atrial natriuretic peptide concentrations. Changes in plasma aldosterone were unrelated to differences in fluid retention. Antidiuretic hormone concentrations (ADH) were significantly reduced from prehyperhydration levels during both hyperhydration trials but tended (P = 0.07) to rise during GI compared with WI at the very time urine flow and free water clearance differences were also evident. This suggests that ADH may, in part, be responsible for glycerol's effectiveness, although differences in ADH concentrations were small and near the assay's sensitivity limits. Alternatively, glycerol's effectiveness may result from its directly increasing the kidneys' medullary concentration gradient and, hence, water reabsorption.
Quantitation of progressive muscle fatigue during dynamic leg exercise in humans
Authors: Fulco C. S. , Lewis S. F. , Frykman P. N. , Boushel R. , Smith S. , Harman E. A. , Cymerman A. , Pandolf K. B.
Published: December 2017

There is virtually no published information on muscle fatigue, defined as a gradual decline in force-generating capacity, during conventional dynamic (D) leg exercise. To quantitate progression of fatigue, we developed 1) a model featuring integration of maximal voluntary static contraction (MVC) of knee extension (KE) muscles with ongoing DKE and 2) a device that allows frequent rapid transfer between DKE isolated to the quadriceps femoris muscles and measurement of KE MVC. Eight healthy men performed graded and submaximal constant work rate one-leg DKE to exhaustion while seated. Work rate, a product of a contraction rate (1 Hz), force measured at the ankle, and distance of ankle movement from 90 degrees to 150 degrees of KE, was precisely controlled. Lack of rise in myoelectric activity in biceps femoris of the active leg during DKE and MVC was consistent with restriction of muscle action to quadriceps femoris. The slope of the linear relationship between O2 uptake and work rate was 13.7 ml O2/W (r = 0.93). This slope and the increase of heart rate relative to increasing work intensity agreed with published values for D leg exercise. Test-retest values for O2 uptake were similar (P > 0.05) for matched DKE work rates. To track fatigue, MVC (90 degrees knee angle) was performed every 2 min of DKE. After 4 min of DKE at work rates corresponding to (mean +/- SE) 66 +/- 2, 78 +/- 2, and 100% of peak DKE O2 uptake, MVC fell to 95 +/- 3, 90 +/- 5, and 65 +/- 7%* of MVC of rested muscle, respectively (*P < 0.01 from previous work rates). Virtually identical declines in MVC were observed by the end of graded work rate DKE and submaximal constant work rate DKE tests. Quantitation of progressive muscle fatigue during D leg exercise provides a framework to study the effects of a variety of interventions on the fatigue process and may permit unique insights into the involved mechanisms.
Reflectance spectroscopy of pancreatic microcirculation
Authors: Knoefel W. T. , Kollias N. , Rattner D. W. , Nishioka N. S. , Warshaw A. L.
Published: December 2017

A technique employing diffuse reflectance spectroscopy (DRS) is described to assess and mirror dynamic changes of pancreatic tissue perfusion. An especially designed reflectance spectrophotometer was initially used to derive the quantitative relation between hemoglobin concentration ([Hb]) and reflectance measurements in vitro. Over a wide range of scattering related to the medium in which the measurements were made (scattering coefficient: 6.5-13 cm-1), a close, direct correlation existed with a slope of 0.376 +/- 0.012. In Sprague-Dawley rats under general anesthesia, the pancreas was isolated in situ and perfused with graded infusions of hemoglobin solutions. A correlation, comparable to the in vitro setting, was found between a [Hb] of 0 and 14 g/dl in the perfusate with slopes of 0.0037 and 0.0035. Changes in perfusion induced by adrenergic drugs produced changes in hemoglobin oxygen saturation and [Hb] that correspond with measured alterations of systemic arterial pressure and aortic blood flow. We conclude that diffuse reflectance spectroscopy reliably provides data on intrapancreatic hemoglobin oxygen saturation and [Hb] that can be a valuable tool for minimally invasive on-line evaluation of these aspects of pancreatic perfusion in the rat. This newly designed device is superior to previously used ones in that it analyzes the entire spectrum and therefore can account for changes in scattering that are very likely to occur with pathophysiological alterations such as edema formation.
Intratracheal administration of DBcAMP attenuates edema formation in phosgene-induced acute lung injury
Authors: Sciuto A. M. , Strickland P. T. , Kennedy T. P. , Guo Y. L. , Gurtner G. H.
Published: December 2017

Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-threatening latent noncardiogenic pulmonary edema. Mechanisms related to its toxicity appear to involve lipoxygenase mediators of arachidonic acid (AA) and can be inhibited by pretreatment with drugs that increase adenosine 3′,5′-cyclic monophosphate (cAMP). In the present study, we used the isolated buffer-perfused rabbit lung model to investigate the mechanisms by which cAMP protects against phosgene-induced lung injury. Posttreatment with dibutyryl cAMP (DBcAMP) was given 60-85 min after exposure by an intravascular or intratracheal route. Lung weight gain (LWG) was measured continuously. AA metabolites leukotriene (LT) C4, LTD4, and LTE4 and 6-ketoprostaglandin F1 alpha were measured in the perfusate at 70, 90, 110, 130, and 150 min after exposure. Tissue malondialdehyde and reduced and oxidized glutathione were analyzed 150 min postexposure. Compared with measurements in the lungs of rabbits exposed to phosgene alone, posttreatment with DBcAMP significantly reduced LWG, pulmonary arterial pressure, and inhibited the release of LTC4, LTD4, and LTE4. Intratracheal administration of DBcAMP was more effective than intravascular administration in reducing LWG. Posttreatment also decreased MDA and protected against glutathione oxidation observed with phosgene exposure. We conclude that phosgene causes marked glutathione oxidation, lipid peroxidation, release of AA mediators, and increases LWG. Posttreatment with DBcAMP attenuates these effects, not only by previously described inhibition of pulmonary endothelial or epithelial cell contraction but also by inhibition of AA-mediator production and a novel antioxidant effect.
Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats
Authors: Aaron E. A. , Forster H. V. , Lowry T. F. , Korducki M. J. , Ohtake P. J.
Published: December 2017

To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml/h iv) during 5 h of normoxia and hypoxia. Arterial PCO2 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA (from 111.8 to 42.0 Torr) infusions. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33.5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P = 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.
Effect of fluid ingestion on muscle metabolism during prolonged exercise
Authors: Hargreaves M. , Dillo P. , Angus D. , Febbraio M.
Published: December 2017

Five trained men were studied during 2 h of cycling exercise at 67% peak oxygen uptake at 20-22 degrees C to examine the effect of fluid ingestion on muscle metabolism. On one occasion, the subjects completed this exercise without fluid ingestion (NF) while on the other they ingested a volume of distilled deionized water that prevented loss of body mass (FR). No differences in oxygen uptake during exercise were observed between the two trials. Heart rate was lower (P < 0.01) throughout exercise when fluid was ingested, and rectal temperature after 2 h of exercise was lower (38.0 +/- 0.2 and 38.6 +/- 0.2 degrees C for FR and NF, respectively; P < 0.01), as was muscle (vastus lateralis) temperature (38.5 +/- 0.4 and 39.1 +/- 0.5 degrees C for FR and NF, respectively; P < 0.05). Resting muscle ATP, creatine phosphate, creatine, glycogen, and lactate levels were similar in the two trials, as were the postexercise ATP, creatine phosphate, and creatine levels. In contrast, muscle glycogen was higher (P < 0.05) and muscle lactate was lower (P < 0.05) after 2 h of exercise in FR compared with NF. Net muscle glycogen utilization during exercise was reduced by 16% when fluid was ingested (318 +/- 46 and 380 +/- 53 mmol/kg dry weight for FR and NF, respectively; P < 0.05). These results indicate that fluid ingestion reduces muscle glycogen use during prolonged exercise, which may account, in part, for the improved performance previously observed with fluid ingestion.
Nonuniform expansion of constricted dog lungs
Authors: Hubmayr R. D. , Hill M. J. , Wilson T. A.
Published: December 2017

The parenchymal marker technique was used to measure regional tidal volumes of samples of lung parenchyma in four open-chest supine dogs. Radiopaque markers that had been implanted in the lower lobe were tracked by biplane video fluoroscopy during sinusoidal volume oscillations at tidal volumes of approximately 20% of total lung capacity and frequencies of 1-40 breaths/min before and after methacholine was administered by aerosol. The volumes of tetrahedrons with apexes at four markers were computed, and sine waves were fit to the data for volume vs. time for each tetrahedron. The ratio of mean regional volume to mean airway pressure decreased by 10-45% after exposure to methacholine. Dynamic lung elastance and resistance of the constricted lungs were larger than control, and both were frequency dependent. Regional elastance and resistance varied considerably among tetrahedrons, and these were also frequency dependent. The data were fit by a model in which tissue elastance was uniform and nearly equal to elastance in the control state, but small-airway resistance was high and variable. We conclude that the lung contracts under bronchoconstriction but that the increased dynamic elastance and resistance of the constricted lung may be primarily the result of nonuniform increased airway resistance at the level of the terminal bronchioles.
Measurement of PO2 in liver using EPR oximetry
Authors: Jiang J. , Nakashima T. , Liu K. J. , Goda F. , Shima T. , Swartz H. M.
Published: December 2017

With the use of India ink and lithium phthalocyanine (LiPc) as electron paramagnetic resonance (EPR) oximetry probes, the PO2 of the liver was investigated in mice. Because India ink was taken up by the Kupffer cells of the liver, the EPR signal of the India ink reflected the average PO2 in phagocytic vesicles of these cells. The mean value of PO2 in the Kupffer cells measured by India ink was 15.3 +/- 4.4 Torr in unanesthetized animals. LiPc was administered as a macroscopic crystal and therefore reflected the PO2 of the overall liver. The PO2 measured by LiPc was 23.4 +/- 4.4 Torr, which is consistent with the median value of 23.5 Torr reported previously with the use of an oxygen electrode. Anesthesia (injection of 60 mg/kg ip pentobarbital sodium) decreased the average PO2 in both Kupffer cells and the overall liver. The effects of perturbing the blood flow were studied by reversible blockage of the portal vein and hepatic artery in anesthetized mice; the PO2 in both Kupffer cells (measured with India ink) and in overall liver (measured with LiPc) decreased with obstruction of the blood flow and returned toward normal with reperfusion. These results indicate that the PO2 in different locations in the liver can be significantly different under both normal conditions and after perturbation by either anesthesia or ischemia. These results also demonstrate that EPR oximetry can provide sensitive measurements of PO2 in the liver in vivo under various conditions.
Beneficial effects of voluntary wheel running on the properties of dystrophic mouse muscle
Authors: Hayes A. , Williams D. A.
Published: December 2017

Effects of voluntary exercise on the isometric contractile, fatigue, and histochemical properties of hindlimb dystrophic (mdx and 129ReJ dy/dy) skeletal muscles were investigated. Mice were allowed free access to a voluntary running wheel at 4 wk of age for a duration of 16 (mdx) or 5 (dy/dy) wk. Running performance of mdx mice (approximately 4 km/day at 1.6 km/h) was inferior to normal mice (approximately 6.5 km/day at 2.1 km/h). However, exercise improved the force output (approximately 15%) and the fatigue resistance of both C57BL/10 and mdx soleus muscles. These changes coincided with increased proportions of smaller type I fibers and decreased proportions of larger type IIa fibers in the mdx soleus. The extensor digitorum longus of mdx, but not of normal, mice also exhibited improved resistance to fatigue and conversion towards oxidative fiber types. The dy/dy animals were capable of exercising, yet ran significantly less than normal animals (approximately 0.5 km/day). Despite this, running increased the force output of the plantaris muscle (approximately 50%). Taken together, the results showed that exercise can have beneficial effects on dystrophic skeletal muscles.
Echinocytic transformation and aggregation of red cells in uremic patients
Authors: Agroyannis B. , Dalamangas A. , Tzanatos H. , Fourtounas C. , Kopelias I. , Koutsikos D.
Published: December 2017

Isolated rabbit lungs were perfused with washed and resuspended human red blood cells (RBCs) in the presence of drugs known to change the shape and deformability of RBCs. With sodium salicylate (0.5-2 g/l), which causes echinocytosis and increases RBC deformability, lung diffusing capacity for O2 (DLO2) increased by 21%. When chlorpromazine, which induces stomatocytosis and stiffens RBCs, was given (50 mg/l), DLO2 decreased by 18% under chlorpromazine. Comparative experiments with hemoglobin solutions did not reveal any effect of those two drugs either on DLO2 or on pulmonary arterial pressure, which indicates that the effects of sodium salicylate and chlorpromazine were due to changes in RBC shape and deformability. It is concluded that RBC shape and deformability affect pulmonary artery pressure and oxygen diffusing capacity, which may have an influence on oxygen transfer to tissue and hence be of clinical relevance.
T.H. Ravenhill and his contributions to mountain sickness
Authors: West J. B.
Published: December 2017

Thomas Holmes Ravenhill (1881-1952) was an important pioneer in high-altitude medicine but almost nothing has been published about him. He wrote a landmark paper in 1913 that included the classification of high-altitude sickness that is still in use, and it also contained the first accurate descriptions of high-altitude pulmonary edema and high-altitude cerebral edema, although he used different terms. The work was done while he was medical officer at the Collahuasi and Poderosa mines in northern Chile at altitudes he gave as 4,690-4,940 m. Remarkably, the paper was then forgotten until it was rediscovered over 50 yr later, but it is now cited in any comprehensive study of high-altitude illness. Ravenhill graduated in medicine from the University of Birmingham, Birmingham, UK, in 1905 and 4 yr later went to the mines where he spent 2 yr. Subsequently, he served in the Royal Army Medical Corps in the 1914-1918 war and was awarded the Military Cross. He returned to general practice but after a few years gave up medicine altogether. He then made important contributions to archeology and spent the last third of his life in London as a painter, mainly in watercolors. It is unclear to what extent his war experiences brought about his dramatic career change.
Adaptive responses to muscle lengthening and shortening in humans
Authors: Hortobagyi T. , Hill J. P. , Houmard J. A. , Fraser D. D. , Lambert N. J. , Israel R. G.
Published: December 2017

We tested the hypothesis that exercise training with maximal eccentric (lengthening) muscle actions results in greater gains in muscle strength and size than training with concentric (shortening) actions. Changes in muscle strength, muscle fiber size, and surface electromyographic (EMG) activity of the quadriceps muscle were compared after 36 sessions of isokinetic concentric (n = 8) or eccentric (n = 7) exercise training over 12 wk with use of a one-leg model. Eccentric training increased eccentric strength 3.5 times more (pre/post 46%, P < 0.05) than concentric training increased concentric strength (pre/post 13%). Eccentric training increased concentric strength and concentric training increased eccentric strength by about the same magnitude (5 and 10%, respectively, P = 0.05). Eccentric training increased EMG activity seven times more during eccentric testing (pre/post 86%, P < 0.05) than concentric training increased EMG activity during concentric testing (pre/post 12%). Eccentric training increased the EMG activity measured during concentric tests and concentric training increased the EMG activity measured during eccentric tests by about the same magnitude (8 and 11%, respectively, P = 0.05). Type I muscle fiber percentages did not change significantly, but type IIa fibers increased and type IIb fibers decreased significantly (P < 0.05) in both training groups. Type I fiber areas did not change significantly (P = 0.05), but type II fiber area increased approximately 10 times more (P < 0.05) in the eccentric than in the concentric group. It is concluded that adaptations to training with maximal eccentric contractions are specific to eccentric muscle actions that are associated with greater neural adaptation and muscle hypertrophy than concentric exercise.
Interaction between clenbuterol and run training: effects on exercise performance and MLC isoform content
Authors: Ingalls C. P. , Barnes W. S. , Smith S. B.
Published: December 2017

The purpose of this study was to determine the separate and combined effects of clenbuterol (CB) administration and interval training on running performance and myosin light-chain (MLC) isoform expression in mouse skeletal muscle. Mice were randomly assigned to one of four treatment groups: 1) control (Con), 2) exercise (Ex), 3) drug (CB), or 4) exercise + drug (Ex + CB). CB and Ex + CB mice were given CB (1.6 mg/kg) orally 4 days/wk. Ex and Ex + CB mice were trained 4 days/wk on a motorized treadmill (3 sets of 3 min, 36-40 m/min, 10-17% grade, 30-s recovery). After 8 wk of treatment, exercise conditioning increased total work performed 58% in the Ex group during a run-to-exhaustion treadmill test, whereas CB decreased total work by 25% in the CB group; in combination with exercise training, CB treatment eliminated the Ex-induced increase in work. Polyacrylamide gel electrophoresis indicated that run training, CB treatment, or a combination did not (P = 0.01) promote changes in fast and slow MLC isoforms in the soleus, gastrocnemius, or tibialis anterior muscles. Although not different from each other after 8 wk, CB and Ex + CB treatments produced significantly greater values than Con and Ex for the following variables: muscle mass (17-46%), total protein (22-50%), and myofibrillar protein (19-53%). It was concluded that CB decreases exercise performance and that the combination of Ex and CB have antagonistic effects on running performance; the two treatments do not interact to diminish the anabolic effects of CB on skeletal muscle and do not alter MLC isoform profiles.
Microgravity decreases heart rate and arterial pressure in humans
Authors: Fritsch-Yelle J. M. , Charles J. B. , Jones M. M. , Wood M. L.
Published: December 2017

Spaceflight causes adaptive changes in cardiovascular physiology, such as postflight orthostatic intolerance, that can have deleterious effects on astronauts. In-flight cardiovascular data are difficult to obtain, and results have been inconsistent. To determine normative in-flight changes in Shuttle astronauts, we measured heart rate, arterial pressure, and cardiac rhythm disturbances for 24-h periods before, during, and after spaceflight on Shuttle astronauts performing their normal routines. We found that heart rate, diastolic pressure, variability of heart rate and diastolic pressure, and premature ventricular contractions all were significantly reduced in flight. Systolic pressure and premature atrial contractions also tended to be reduced in flight. These data constitute the first systematic evaluation of in-flight changes in basic cardiovascular variables in Shuttle astronauts and suggest that a microgravity environment itself does not present a chronic stress to the cardiovascular system.
Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury
Authors: Lewis J. F. , Goffin J. , Yue P. , McCaig L. A. , Bjarneson D. , Veldhuizen R. A.
Published: December 2017

Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.
Acute histamine-induced flux of airway liquid: role of neuropeptides
Authors: Yager D. , Martins M. A. , Feldman H. , Kamm R. D. , Drazen J. M.
Published: December 2017

The role of capsaicin-sensitive neuropeptides in the accumulation of airway wall liquid observed 30 s after histamine infusion was investigated in guinea pigs. Two groups were studied: normal animals and animals in which endogenous neuropeptides had been depleted by capsaicin pretreatment. A rapid intravenous infusion of saline or histamine (11 micrograms/kg resulted in marked but similar changes in pulmonary mechanics in normal and capsaicin-pretreated animals. To assess liquid accumulation in airway wall compartments, the lungs were frozen 30 s after histamine infusion; airways from these lungs, 0.15-2.44 mm in internal perimeter, were imaged by low-temperature scanning electron microscopy. There was no difference in average airway surface liquid thickness (hASL) in normal or capsaicin-pretreated airways in response to saline. In capsaicin-pretreated animals, histamine infusion was associated with a significantly decreased hASL (hASL, cap11/hASL,cap0 = 0.58, P < 0.04). Capsaicin pretreatment, without histamine exposure, caused significant increases in epithelial and submucosal areas (Aepi,cap0/Aepi,norm0 = 1.23, P < 0.06; Asub,cap0/Asub,norm0 = 1.40, P < 0.01). The notation cap0 and cap11 indicates capsaicin-pretreated airways given 0 or 11 micrograms/kg histamine, respectively; similarly, norm0 and norm11 indicate normal airways given 0 and 11 micrograms/kg histamine, respectively. Histamine infusion in capsaicin-pretreated animals was associated with liquid shifts from epithelium to lamina propria and from submucosa to adventitia; however, the total wall area was similar to, if not smaller than, that in capsaicin-pretreated animals without histamine treatment. In contrast, histamine infusion in normal animals resulted in significant increases in the areas of the epithelial and lamina propria compartments (Aepi,norm11/Aepi,norm0 = 1.25, P < 0.05; Alp,norm11/Alp,norm0 = 2.19, P < 0.001) as well as a substantial increase in adventitial area, which was significantly attenuated by capsaicin pretreatment (Aadv,cap11/Aadv,norm11 = 0.40, P < 0.001). The resulting total wall area was more than twice that in normal animals without histamine treatment. Our data indicate that histamine-induced accumulation of liquid in the epithelium, lamina propria, and adventitia of normal airways is rapid in onset, most likely derives from a leaky bronchial microvasculature, and is mediated by the secondary release of neurokinins.
Expiratory muscle endurance performance after exhaustive submaximal exercise
Authors: Fuller D. , Sullivan J. , Fregosi R. F.
Published: December 2017

The aim of our study was to describe the endurance capacity of the expiratory muscles and to determine whether it is altered after exhaustive cycling exercise. Subjects performed repeated maximal expiratory efforts against a closed breathing valve, with and without prior exercise performed at a work rate that elicited 75% of the maximum ventilation rate. Each expiratory effort lasted 6 s, was separated by 10 s of rest, and was initiated from the end-expiratory lung volume. Endurance performance was assessed by measuring the decline in area under the pressure*time curve over 39 contractions. Prior exhaustive exercise attenuated the ability to generate and sustain maximal expiratory pressure (P = 0.013) and resulted in significant declines in the integrated electromyogram of the rectus abdominis (P = 0.005) and external oblique (P = 0.036) abdominal muscles. Each subject also performed a handgrip endurance task before and after exhaustive exercise on a separate day. Prior exercise had no effect on handgrip endurance performance, suggesting that the decline in expiratory muscle performance after exercise was not the result of reduced motivation. We conclude that the ability to maximally activate the abdominal expiratory muscles and to generate maximum expiratory pressure is impaired after exhaustive exercise. Declines in the surface integrated electromyogram despite maximal effort is consistent with findings in limb muscles and is thought to be due to a slowing of motoneuron firing rates or to neuromuscular transmission failure.
Control of nasal dilator muscle activities during exercise: role of nasopharyngeal afferents
Authors: Sullivan J. , Fuller D. , Fregosi R. F.
Published: December 2017

Our primary aim was to determine whether reducing the activity of nasal airway receptors would influence drive to the nasal dilator muscles (NDMs) during exercise. We used lidocaine (2%) or nasal splints to diminish afferent airway receptor activity and measured the electromyogram (EMG) activity of the NDMs during incremental bicycle exercise in subjects who breathed nasally. NDM EMG activities increased as a function of exercise intensity but were not changed by lidocaine and were only slightly reduced by splinting. Similarly, neither intervention altered the normal decrease in NDM EMG activity associated with reductions in airway resistance evoked by He-O2 breathing. We also compared the NDM EMG response to exercise with that evoked by CO2 rebreathing at rest to determine whether the nature of the ventilatory stimulus influences drive to the NDMs; comparisons were made at constant levels of nasal inspired ventilation and, therefore, constant total ventilatory output. The increase in EMG activity was much higher during exercise compared with hyperoxic hypercapnia. In conclusion, 1) desensitizing the nasal airway does not alter NDM activity significantly during exercise and 2) exercise results in much greater increases in NDM activity compared with hypercapnia, indicating that different ventilatory stimuli can evoke more or less activation of upper airway motoneurons, even when comparisons are made at constant levels of total ventilatory output.
Smoking increases conversion of lactate to glucose during submaximal exercise
Authors: Huie M. J. , Casazza G. A. , Horning M. A. , Brooks G. A.
Published: December 2017

We examined the hypotheses that 1) smoking acutely before exercise (AS) results in a higher rate of lactate production during exercise compared with chronic smoking with preexercise abstinence (CS) and 2) smokers have a higher rate of lactate conversion to glucose during exercise compared with nonsmokers (NS). To test our hypotheses, seven male smokers and seven nonsmokers were studied by using a primed continuous infusion of [3-13C]lactate during 90 min of rest and 60 min of exercise on a cycle ergometer at 50% peak O2 consumption; smokers were studied twice: once after an overnight smoking abstinence and once after smoking three cigarettes before exercise. The rates of lactate appearance and conversion to glucose were increased markedly with exercise compared with rest in all groups (P < 0.05); the rate of lactate appearance for AS was significantly greater (7.87 +/- 0.77 mg.kg-1.min-1) than for both CS (4.64 +/- 0.33 mg.kg-1.min-1) and NS (5.57 +/- 0.60 mg.kg-1.min-1) (P < 0.05). The rate of lactate conversion to glucose was similar between CS and AS (6.49 +/- 1.82 and 6.30 +/- 1.69 mg.kg-1.min-1, respectively) during exercise; NS had a significantly lower rate (3.31 +/- 0.90 mg.kg-1.min-1) compared with CS and AS (P < 0.05). In summary, acute smoking increases lactate flux during exercise; in addition, smokers have a higher rate of lactate to glucose conversion during exercise compared with nonsmokers, which may indicate an increased glucose dependency.
Effects of ovariectomy and exercise training on muscle GLUT-4 content and glucose metabolism in rats
Authors: Hansen P. A. , McCarthy T. J. , Pasia E. N. , Spina R. J. , Gulve E. A.
Published: December 2017

The present study examined the effects of 6 wk of ovarian endocrine deficiency on skeletal muscle GLUT-4 glucose transporter protein and glucose transport activity in sedentary and endurance-trained rats. Female Wistar rats (10 wk old) underwent bilateral ovariectomy (OVX) or sham surgery followed by a 5-wk swim-training protocol. OVX resulted in no significant changes in glycogen or GLUT-4 glucose transporter concentration in the soleus, epitrochlearis, or flexor digitorum brevis (FDB) muscles or in basal and maximally insulin-stimulated 2-deoxy-D-[1,2-3H]glucose (2-[3H]DG) transport in the soleus or epitrochlearis, suggesting that moderate-duration ovarian hormone deficiency does not significantly impair insulin action in skeletal muscle. In contrast, OVX decreased the maximal activation of 2-[3H]DG transport in the FDB by in vitro electrical stimulation. OVX had no significant effect on the training-induced changes in oxidative enzyme activities, GLUT-4 protein expression, glycogen content, or insulin-stimulated 2-[3H]DG transport in the soleus or epitrochlearis. These findings provide the first evidence that ovarian hormone deficiency decreases contraction-stimulated glucose transport in skeletal muscle.
Alteration of human cutaneous afferent discharges as the result of long-lasting vibration
Authors: Ribot-Ciscar E. , Roll J. P. , Tardy-Gervet M. F. , Harlay F.
Published: December 2017

The unitary activities of slowly (15 SAI) and fast-adapting type I (12 FAI) skin mechanoreceptive afferent units innervating the anterior part of the human leg and foot were recorded by using the microneurographic method. The recordings were performed both at rest and on application of cutaneous stimuli of various intensities before and after exposure of the corresponding receptive fields to vibration (0.5 mm peak to peak, 100 pulses/s, 10 min). The results show that 11% of the units tested, which were previously silent, developed a bursting pattern of postvibratory activity, which lasted 12 min on average. This induced resting activity may account for the tingling sensations usually perceived after exposure to vibration. Furthermore, application of vibration to the cutaneous receptive fields impaired the response properties of the corresponding cutaneous fibers much more markedly in the case of the SAI than in the FAI units. More specifically, less than one-half of the FAI fibers tested showed a postvibratory depressed sensitivity to skin stroking applied at various velocities that persisted for only a few minutes, whereas the responses of all the SAI units to suprathreshold maintained skin indentations applied with increasing amplitudes decreased significantly for 20 min. These fairly durable changes in the transductive properties of the mechanoreceptive afferent units probably lead to an impairment of perceptual and sensorimotor processes and consequently may at least partly account for the alterations in sensorimotor performance that have been reported to occur in humans after exposure to vibration.
Effect of N-methyl-D-aspartate-receptor blockade on hypoxic ventilatory response in unanesthetized piglets
Authors: Lin J. , Suguihara C. , Huang J. , Hehre D. , Devia C. , Bancalari E.
Published: December 2017

The central excitatory amino acid (EAA) neurotransmitter glutamate has been shown to mediate the ventilatory response to hypoxia through N-methyl-D-aspartate (NMDA) receptors in anesthetized adult animals. To determine the role of the EAA glutamate in the neonatal ventilatory response to hypoxia, 19 unanesthetized chronically instrumented piglets were studied. Minute ventilation (VE), oxygen consumption (VO2), arterial blood pressure (ABP), heart rate (HR), and blood gases were measured in room air (RA) and after 1, 5, and 10 min of hypoxia (inspired oxygen fraction = 0.10) before and after an infusion of saline or CGS-19755, a competitive NMDA-receptor blocker (10 mg/kg i.v.). Nine control piglets [age 6 +/- 1 (SD) days; weight 2.02 +/- 0.40 kg] and 10 CGS-19755-treated animals (age 6 +/- 1 days; weight 1.90 +/- 0.66 kg) were studied during quiet sleep and in a thermoneutral environment. There was a marked decrease in the VE response to hypoxia after the administration of CGS-19755. The ventilatory response to hypoxia was not modified by saline infusion. Changes in ABP and arterial PO2 during hypoxia were similar between groups, whereas the decrease in arterial PCO2 was significantly less after CGS-19755 administration. The increase in HR with hypoxia was eliminated by the NMDA-receptor blocker administration. VO2 decreased with hypoxia in both groups, but this decrease was more marked after the NMDA-receptor blockade. These results suggest that the central EAA glutamate mediates, at least in part, the hypoxic hyperventilation in unanesthetized newborn piglets.
Scalp topography of the short-latency components of the respiratory-related evoked potential in children
Authors: Davenport P. W. , Colrain I. M. , Hill P. M.
Published: December 2017

Respiratory-related evoked potentials (RREPs) have been elicited by inspiratory occlusion and recorded at electroencephalographic (EEG) sites overlying the somatosensory cortex in adults. The present study was the first to be conducted in normal children and was designed to identify the scalp distribution of the early RREP components. EEG responses to occlusion were recorded from CZ-C3, CZ-C4, and 17 sites referenced to the linked earlobes. The RREP was observed in all subjects in the CZ-C3 and CZ-C4 electrode pairs. The earlobe-referenced recordings revealed two RREP patterns. The P1 and N1 peaks were found in C3, C4, P3, P4, T3, and T4. The RREPs recorded from the F3, F4, F7, and F8 electrodes did not exhibit either the P1 or N1 peaks. A negative peak (NF) occurred approximately 13 ms after the P1 peak. The results show that the RREPs to inspiratory occlusions were present bilaterally but diminished greatly over midline sites. Furthermore, consistent with mechanically and electrically elicited somatosensory evoked potentials, the RREP displayed a polarity inversion over the central sulcus in the early component latency range.