bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of varied extracellular P O 2 on muscle performance inXenopussingle skeletal muscle fibers
Authors: Stary Creed M. , Hogan Michael C.
Published: December 2017

The purpose of this study was to examine the development of fatigue in isolated, single skeletal muscle fibers when O2availability was reduced but not to levels considered rate limiting to mitochondrial respiration. Tetanic force was measured in single living muscle fibers ( n = 6) from Xenopus laevis while being stimulated at increasing contraction rates (0.25, 0.33, 0.5, and 1 Hz) in a sequential manner, with each stimulation frequency lasting 2 min. Muscle fatigue (determined as 75% of initial maximum force) was measured during three separate work bouts (with 45 min of rest between) as the perfusate [Formula: see text] was switched between values of 30 ± 1.9, 76 ± 3.0, or 159 Torr in a blocked-order design. No significant differences were found in the initial peak tensions between the high-, intermediate-, and low-[Formula: see text] treatments (323 ± 22, 298 ± 27, and 331 ± 24 kPa, respectively). The time to fatigue was reached significantly sooner ( P < 0.05) during the 30-Torr treatment (233 ± 39 s) compared with the 76- (385 ± 62 s) or 159-Torr (416 ± 65 s) treatments. The calculated critical extracellular [Formula: see text]necessary to develop an anoxic core within these fibers was 13 ± 1 Torr, indicating that the extracellular[Formula: see text] of 30 Torr should not have been rate limiting to mitochondrial respiration. The magnitude of an unstirred layer (243 ± 64 μm) or an intracellular O2diffusion coefficient (0.45 ± 0.04 × 10−5cm2/s) necessary to develop an anoxic core under the conditions of the study was unlikely. The earlier initiation of fatigue during the lowest extracellular[Formula: see text] condition, at physiologically high intracellular [Formula: see text] levels, suggests that muscle performance may be O2dependent even when mitochondrial respiration is not necessarily compromised.
Sodium-free fluid ingestion decreases plasma sodium during exercise in the heat
Authors: Vrijens D. M. J. , Rehrer N. J.
Published: December 2017

This study assessed whether replacing sweat losses with sodium-free fluid can lower the plasma sodium concentration and thereby precipitate the development of hyponatremia. Ten male endurance athletes participated in one 1-h exercise pretrial to estimate fluid needs and two 3-h experimental trials on a cycle ergometer at 55% of maximum O2 consumption at 34°C and 65% relative humidity. In the experimental trials, fluid loss was replaced by distilled water (W) or a sodium-containing (18 mmol/l) sports drink, Gatorade (G). Six subjects did not complete 3 h in trial W, and four did not complete 3 h in trial G. The rate of change in plasma sodium concentration in all subjects, regardless of exercise time completed, was greater with W than with G (−2.48 ± 2.25 vs. −0.86 ± 1.61 mmol ⋅ l−1 ⋅ h−1, P = 0.0198). One subject developed hyponatremia (plasma sodium 128 mmol/l) at exhaustion (2.5 h) in the W trial. A decrease in sodium concentration was correlated with decreased exercise time ( R = 0.674; P = 0.022). A lower rate of urine production correlated with a greater rate of sodium decrease ( R = −0.478; P = 0.0447). Sweat production was not significantly correlated with plasma sodium reduction. The results show that decreased plasma sodium concentration can result from replacement of sweat losses with plain W, when sweat losses are large, and can precipitate the development of hyponatremia, particularly in individuals who have a decreased urine production during exercise. Exercise performance is also reduced with a decrease in plasma sodium concentration. We, therefore, recommend consumption of a sodium-containing beverage to compensate for large sweat losses incurred during exercise.
A muscle-powered energy delivery system and means for chronic in vivo testing
Authors: Trumble Dennis R. , Magovern James A.
Published: December 2017

Electrically stimulated skeletal muscle represents a potentially unlimited source of energy for the actuation of motor prostheses. Devices to harvest and deliver contractile power have proven mechanically feasible, but long-term efficacy has not been demonstrated. This report describes recent refinements in muscle energy converter (MEC) design and details the development of an implantable afterload chamber (IAC) designed to facilitate implant testing. The IAC comprises a fluid-filled bladder housed within a titanium cylinder that connects directly to the MEC. A vascular access port allows percutaneous measurement and adjustment of air pressure within the housing and provides a means both to monitor MEC function and to control hydraulic loading conditions. Data from in vitro tests show that IAC pressure mirrors changes in MEC-piston displacement over a wide range of actuation speeds and stroke lengths. Stroke lengths and actuation forces calculated from IAC pressure readings were typically found to be within 5% of measured values. This testing scheme may yield important information in regard to the ability to harness energy from in situ muscle over prolonged periods.
Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study
Authors: Smith Sinclair A. , Montain Scott J. , Matott Ralph P. , Zientara Gary P. , Jolesz Ferenc A. , Fielding Roger A.
Published: December 2017

Five women and 3 men (29.8 ± 1.4 yr) performed dynamic knee-extension exercise inside a magnetic resonance system (means ± SE). Two trials were performed 7–14 days apart, consisting of a 4- to 5-min exhaustive exercise bout. To determine quadriceps cost of contraction, brief static and dynamic contractions were performed pre- and postexercise.31P spectra were used to determine pH and relative concentrations of Pi, phosphocreatine (PCr), and βATP. Subjects consumed 0.3 g ⋅ kg−1 ⋅ day−1of a placebo ( trial 1) or creatine ( trial 2) for 5 days before each trial. After creatine supplementation, resting ΔPCr increased from 40.7 ± 1.8 to 46.6 ± 1.1 mmol/kg ( P = 0.04) and PCr during exercise declined from −29.6 ± 2.4 to −34.1 ± 2.8 mmol/kg ( P = 0.02). Muscle static (ΔATP/N) and dynamic (ΔATP/J) costs of contraction were unaffected by creatine supplementation as well as were ATP, Pi, pH, PCr resynthesis rate, and muscle strength and endurance. ΔATP/J and ΔATP/N were greatest at the onset of the exercise protocol ( P< 0.01). In summary, creatine supplementation increased muscle PCr concentration, which did not affect muscle ATP cost of contraction.
Kinetics of oxygen uptake during supine and upright heavy exercise
Authors: Koga Shunsaku , Shiojiri Tomoyuki , Shibasaki Manabu , Kondo Narihiko , Fukuba Yoshiyuki , Barstow Thomas J.
Published: December 2017

It is presently unclear how the fast and slow components of pulmonary oxygen uptake (V˙o 2) kinetics would be altered by body posture during heavy exercise [i.e., above the lactate threshold (LT)]. Nine subjects performed transitions from unloaded cycling to work rates representing moderate (below the estimated LT) and heavy exercise (V˙o 2 equal to 50% of the difference between LT and peakV˙o 2) under conditions of upright and supine positions. During moderate exercise, the steady-state increase in V˙o 2was similar in the two positions, butV˙o 2 kinetics were slower in the supine position. During heavy exercise, the rate of adjustment ofV˙o 2 to the 6-min value was also slower in the supine position but was characterized by a significant reduction in the amplitude of the fast component ofV˙o 2, without a significant slowing of the phase 2 time constant. However, the amplitude of the slow component was significantly increased, such that the end-exerciseV˙o 2 was the same in the two positions. The changes inV˙o 2 kinetics for the supine vs. upright position were paralleled by a blunted response of heart rate at 2 min into exercise during supine compared with upright heavy exercise. Thus the supine position was associated with not only a greater amplitude of the slow component forV˙o 2 but also, concomitantly, with a reduced amplitude of the fast component; this latter effect may be due, at least in part, to an attenuated early rise in heart rate in the supine position.
Effect of pressure on hydraulic conductivity of endothelial monolayers: role of endothelial cleft shear stress
Authors: Tarbell John M. , Demaio Lucas , Zaw Mark M.
Published: December 2017

Significant changes in transvascular pressure occur in pulmonary hypertension, microgravity, and many other physiological and pathophysiological circumstances. Using bovine aortic endothelial cells grown on porous, rigid supports, we demonstrate that step changes in transmural pressure of 10, 20, and 30 cmH2O induce significant elevations in endothelial hydraulic conductivity ( L p) that require 5 h to reach new steady-state levels. The increases in L p can be reversed by addition of a stable cAMP analog (dibutyryl cAMP), and the increases in L pin response to pressure can be inhibited significantly with nitric oxide synthase inhibitors ( N G-monomethyl-l-arginine and nitro-l-arginine methyl ester). The increase in L p was not due to pressure-induced stretch because the endothelial cell (EC) support was rigid. It is unlikely that the increase in L p was due to a direct effect of pressure because exposure of the cells to elevated pressure (25 cmH2O) for 4 h had no effect on the volume flux driven by a transmural pressure of 10 cmH2O. We hypothesize that elevated endothelial cleft shear stress induced by elevated transmural flow in response to elevated pressure stimulates the increase in L p through a nitric oxide-cAMP-dependent mechanism. This is consistent with recent studies of the effects of shear stress on the luminal surface of ECs. We provide simple estimates of endothelial cleft shear stress, which suggest magnitudes comparable to those imposed by blood flow on the luminal surface of ECs.
Inhaled NO preadministration modulates local and remote ischemia-reperfusion organ injury in a rat model
Authors: Guery Benoit , Neviere Remy , Viget Nathalie , Foucher Claude , Fialdes Patrice , Wattel Francis , Beaucaire Gilles
Published: December 2017

Inhaled nitric oxide (iNO) has been shown to have a protective effect in lung ischemia-reperfusion (I/R)-induced injuries. We studied the role of iNO (10 parts/million for 4 h) administered before I/R. In an isolated perfused lung preparation, iNO decreased the extravascular albumin accumulation from 2,059 ± 522 to 615 ± 105 μl and prevented the increase in lung wet-to-dry weight ratio. To study the mechanisms of this prevention, we evaluated the role of nitric oxide (NO) transport and lung exposure with matched experiments by using either lungs or blood of animals exposed to iNO and blood or lungs of naive animals. iNO-exposed blood with naive lungs did not limit the extravascular albumin accumulation (2,561 ± 397 μl), but iNO-exposed lungs showed a leak not significantly different from the group in which both lungs and blood were iNO exposed (855 ± 224 vs. 615 ± 105 μl). An improvement in heart I/R left ventricular developed pressure in the animals exposed to iNO showed that blood-transported NO was, however, sufficient to trigger remote organ endothelium and reduce the consequences of a delayed injury. In conclusion, preventive iNO reduces the consequences of lung I/R injuries by a mechanism based on tissue or endothelium triggering.
Developmental changes in response to subatmospheric pressure loading of the upper airway
Authors: Marcus Carole L. , Lutz Janita , Hamer Audrey , Smith Philip L. , Schwartz Alan
Published: December 2017

Children snore less than adults and have fewer obstructive apneas, suggesting a less collapsible upper airway. We therefore hypothesized that the compensatory upper airway responses to subatmospheric pressure loading decrease with age because of changes in upper airway structure and ventilatory drive. We measured upper airway upstream pressure-flow relationships during sleep in 20 nonsnoring, nonobese children and adults. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. The slope of the upstream pressure-flow curve ( SPF) was used to characterize upper airway function. We found that SPFwas flatter in children than in adults (8 ± 5 vs. 30 ± 18 ml ⋅ s−1⋅ cmH2O−1, P < 0.002) and that SPFcorrelated with age ( r = 0.62, P < 0.01) and body mass index ( r = 0.63, P < 0.01). The occlusion pressure in 100 ms during sleep was measured in six children and two adults; it correlated inversely with SPF( r = −0.80, P < 0.02). We conclude that the upper airway compensatory responses to subatmospheric pressure loading decrease with age. This is associated with increased body mass index, even in nonsnoring, nonobese subjects. Ventilatory drive during sleep plays a role in modulating upper airway responses.
Modulation of myonuclear number in functionally overloaded and exercised rat plantaris fibers
Authors: Roy Roland R. , Monke Steven R. , Allen David L. , Edgerton V. Reggie
Published: December 2017

The effects of 10 wk of functional overload (FO), with and without daily treadmill endurance training, on the cross-sectional area, myonuclear number, and myonuclear domain size of mechanically isolated single fiber segments of the adult rat plantaris were determined. The fibers were typed on the basis of high-resolution gel electrophoresis for separation of specific myosin heavy chain (MHC) isoforms and grouped as type I+(containing some type I MHC with or without any combination of fast MHCs), type IIa+(containing some type IIa with or without some type IIx and/or IIb but no type I MHC), and type IIx/b (containing only type IIx and/or IIb MHCs). Type I+fibers had a higher myonuclear number than did both fast types of fibers in the control and FO, but not in the FO and treadmill trained, rats. All fiber types in both FO groups had a significantly larger (36–90%) cross-sectional area and a significantly higher (61–109%) myonuclear number than did control. The average myonuclear domain size of each fiber type was similar among the three groups, except for a smaller domain size in the type IIx/b fibers of the FO compared with control. In general, these data indicate that during hypertrophy the number of myonuclei increase proportionally to the increase in fiber volume. The maintenance of myonuclear domain size near control values suggests that regulatory mechanisms exist that ensure a tight coupling between the quantity of genetic machinery and the protein requirements of a fiber.
Rhythmic sympathetic nerve discharges in an in vitro neonatal rat brain stem-spinal cord preparation
Authors: Su Chun-Kuei
Published: December 2017

To understand the origination of sympathetic nerve discharge (SND), I developed an in vitro brain stem-spinal cord preparation from neonatal rats. Ascorbic acid (3 mM) was added into the bath solution to increase the viability of preparations. At 24°C, rhythmic SND (recorded from the splanchnic nerve) was consistently observed, but it became quiescent at <16°C. Respiratory-related SND (rSND) was discernible and was well correlated with C4 root activity. Power spectral analysis of SND revealed a dominant 2-Hz oscillation. In most preparations (86%), such oscillation was persistent, whereas it only slightly reduced its magnitude after isolation from the brain stem. The removal of neural structures rostral to the superior cerebellar artery (equivalent to the level of facial nuclei) reduced rSND, increased tonic SND, but did not affect the temporal coupling between SND and C4 root activity. Our data suggest a prominent contribution of SND from the neural mechanisms confined within the neonatal rat spinal cord. This ascorbic acid-enhanced in vitro preparation is a very useful model to study neural mechanisms underlying sympathorespiratory integration.
Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing
Authors: Supinski G. , Nethery D. , Stofan D. , Szweda L. , DiMarco A.
Published: December 2017

The purpose of the present study was to determine whether it is possible to alter the development of fatigue and ablate free radical-mediated lipid peroxidation of the diaphragm during loaded breathing by administering oxypurinol, a xanthine oxidase inhibitor. We studied 1) room-air-breathing decerebrate, unanesthetized rats given either saline or oxypurinol (50 mg/kg) and loaded with a large inspiratory resistance until airway pressure had fallen by 50% and 2) unloaded saline- and oxypurinol-treated room-air-breathing control animals. Additional sets of studies were performed with animals breathing 100% oxygen. Animals were killed at the conclusion of loading, and diaphragmatic samples were obtained for determination of thiobarbituric acid-reactive substances and assessment of in vitro force generation. We found that loading of saline-treated animals resulted in significant diaphragmatic fatigue and thiobarbituric acid-reactive substances formation ( P < 0.01). Oxypurinol administration, however, failed to increase load trial time, reduce fatigue development, or prevent lipid peroxidation in either room-air-breathing or oxygen-breathing animals. These data suggest that xanthine oxidase-dependent pathways do not generate physiologically significant levels of free radicals during the type of inspiratory resistive loading examined in this study.
Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia
Authors: Remsburg Stacia , Launois Sandrine H. , Weiss J. Woodrow
Published: December 2017

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations ([Formula: see text]) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% [Formula: see text]: OSA patients, 9 ± 11 mmHg; controls, 12 ± 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change −37 ± 19% at [Formula: see text]80%) but not in patients (mean change −4 ± 16% at 80%[Formula: see text]). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline −85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.
Regional skeletal muscle measurement: evaluation of new dual-energy X-ray absorptiometry model
Authors: Wang Wei , Wang Zimian , Faith Myles S. , Kotler Donald , Shih Rick , Heymsfield Steven B.
Published: December 2017

Although there is growing interest in studying muscle distribution, regional skeletal muscle (SM) mass measurement methods remain limited. The aim of the present study was to develop a new dual-energy X-ray absorptiometry (DEXA) model for estimating regional adipose tissue-free skeletal muscle mass (AT-free SM). Relationships were derived from Reference Man data between tissue-system- level components (i.e., AT-free SM, AT, skeleton, and skin) and molecular-level components including fat-free soft tissue, fat, and bone mineral. The proposed DEXA-SM model was evaluated by multiscan computerized axial tomography (CT). Twenty-seven male subjects [age, 36 ± 12 (SD) yr; body mass, 73.2 ± 12.4 kg; 20 were healthy, and 7 had acquired immunodeficiency syndrome] completed DEXA and CT studies. Identical landmarks for DEXA and CT measurements were selected in three regions, including calves, thighs, and forearms. There was a strong correlation for AT-free SM estimates between the new DEXA and CT methods (e.g., sum of three regions, r= 0.86, P < 0.001). Regional AT-free SM measured in the 27 subjects by DEXA and CT, respectively, were 3.44 ± 0.60 and 3.47 ± 0.55 kg (difference 0.9%, P > 0.05) for calves, 10.49 ± 1.77 and 10.05 ± 1.79 kg (difference 4.4%, P < 0.05) for thighs, 1.36 ± 0.49 and 1.20 ± 0.41 kg (difference 13.3%, P < 0.01) for forearms, and 15.29 ± 2.33 and 14.72 ± 2.33 kg (difference 3.9%, P < 0.05) for the sum all three regions. Although the suggested DEXA-SM model needs minor refinements, this is a promising in vivo approach for measurement of regional SM, because DEXA is widely available, relatively inexpensive, and radiation exposure is low.
Metabolic and performance responses to constant-load vs. variable-intensity exercise in trained cyclists
Authors: Palmer Garry S. , Borghouts Lars B. , Noakes Timothy D. , Hawley John A.
Published: December 2017

We studied glucose oxidation (Gluox) and glycogen degradation during 140 min of constant-load [steady-state (SS)] and variable-intensity (VI) cycling of the same average power output, immediately followed by a 20-km performance ride [time trial (TT)]. Six trained cyclists each performed four trials: two experimental bouts (SS and VI) in which muscle biopsies were taken before and after 140 min of exercise for determination of glycogen and periodic acid-Schiff’s staining; and two similar trials without biopsies but incorporating the TT. During two of the experimental rides, subjects ingested a 5 g/100 ml [U-14C]glucose solution to determine rates of Gluox. Values were similar between SS and VI trials: O2 consumption (3.08 ± 0.02 vs. 3.15 ± 0.03 l/min), energy expenditure (901 ± 40 vs. 904 ± 58 J ⋅ kg−1 ⋅ min−1), heart rate (156 ± 1 vs. 160 ± 1 beats/min), and rating of perceived exertion (12.6 ± 0.6 vs. 12.7 ± 0.7). However, the area under the curve for plasma lactate concentration vs. time was significantly greater during VI than SS (29.1 ± 3.9 vs. 24.6 ± 3.7 mM/140 min; P = 0.03). VI resulted in a 49% reduction in total muscle glycogen utilization vs. 65% for SS, while total Gluoxwas higher (99.2 ± 5.3 vs. 83.9 ± 5.2 g/140 min; P < 0.05). The number of glycogen-depleted type I muscle fibers at the end of 140 min was 98% after SS but only 59% after VI. Conversely, the number of type II fibers that showed reduced periodic acid-Schiff’s staining was 1% after SS vs. 10% after VI. Despite these metabolic differences, subsequent TT performance was similar (29.14 ± 0.9 vs. 30.5 ± 0.9 min for SS vs. VI). These results indicate that whole body metabolic and cardiovascular responses to 140 min of either SS or VI exercise at the same average intensity are similar, despite differences in skeletal muscle carbohydrate metabolism and recruitment.
Serial segmental bronchoalveolar lavage in individual rats
Authors: Varner Arthur E. , Sorkness Ronald L. , Kumar Aparna , Kaplan Michael R. , Lemanske Robert F.
Published: December 2017

Bronchoalveolar lavage (BAL) is a well-characterized technique for analysis of cellular constituents of the airways and air spaces, but whole lung lavage requires that the animal be euthanized. We describe a technique of segmental BAL in rats that allows serial measurements of inflammation. A tracheal tube was placed, under direct visualization, in lightly anesthetized animals, and a catheter was passed through the tracheal tube and advanced to a wedge position. Five 0.1-ml volumes of buffer solution were instilled and then withdrawn with gentle suction. In normal rats, the percentages of neutrophils, eosinophils, and mononuclear cells had a high level of agreement in the segmental samples compared with those obtained subsequently by whole lung lavage. In rats with acute pulmonary inflammation, the differential leukocyte counts from segmental samples exhibited patterns of change that differed from those of whole lung lavage; however, most segmental samples were obtained from the left lung base so that regional variability could be minimized in serial studies. Lung mechanics and airway inflammation were not affected by repeated segmental BALs done 2 wk apart.
Arterial pressure in humans during weightlessness induced by parabolic flights
Authors: Pump Bettina , Videbæk Regitze , Gabrielsen Anders , Norsk Peter
Published: December 2017

Results from our laboratory have indicated that, compared with those of the 1-G supine (Sup) position, left atrial diameter (LAD) and transmural central venous pressure increase in humans during weightlessness (0 G) induced by parabolic flights (R. Videbæk and P. Norsk. J. Appl. Physiol. 83: 1862–1866, 1997). Therefore, because cardiopulmonary low-pressure receptors are stimulated during 0 G, the hypothesis was tested that mean arterial pressure (MAP) in humans decreases during 0 G to values below those of the 1-G Sup condition. When the subjects were Sup, 0 G induced a decrease in MAP from 93 ± 4 to 88 ± 4 mmHg ( P< 0.001), and LAD increased from 30 ± 1 to 33 ± 1 mm ( P < 0.001). In the seated position, MAP also decreased from 93 ± 6 to 87 ± 5 mmHg ( P < 0.01) and LAD increased from 28 ± 1 to 32 ± 1 mm ( P < 0.001). During 1-G conditions with subjects in the horizontal left lateral position, LAD increased compared with that of Sup ( P < 0.001) with no further effects of 0 G. In conclusion, MAP decreases during short-term weightlessness to below that of 1-G Sup simultaneously with an increase in LAD. Therefore, distension of the heart and associated central vessels during 0 G might induce the hypotensive effects through peripheral vasodilatation. Furthermore, the left lateral position in humans could constitute a simulation model of weightlessness.
Hering-Breuer reflex in conscious newborn rats: effects of changes in ambient temperature during hypoxia
Authors: Merazzi Daniele , Mortola Jacopo P.
Published: December 2017

In a previous study in conscious normoxic newborn rats, we found that the strength of the Hering-Breuer reflex (HB reflex) was greater (188%) at high (36°C) than at low (24°C) ambient temperature (Ta; D. Merazzi and J. P. Mortola. Pediatr. Res. 45: 370–376, 1999). We now asked what the effect would be of changes in Ta during hypoxia. Rat pups at 3–4 days of age were studied in a double-chamber airflow plethysmograph. The HB reflex was induced by negative body surface pressures of 5 or 10 cmH2O and quantified from the inhibition of breathing during maintained lung inflation. Rats were first studied at Ta = 32°C in normoxia, followed by hypoxia (10% O2breathing). During hypoxia, oxygen consumption (V˙o 2) averaged 47%, and HB reflex 115%, of the corresponding normoxic values, confirming that in the newborn, differently from the adult, hypoxia does not decrease the strength of the HB reflex. As hypoxia was maintained, lowering Ta to 24°C or increasing it to 36°C, on average, had no significant effects onV˙o 2 and the HB reflex. However, with 5-cmH2O inflations, the HB reflex during the combined hypoxia and hyperthermia was significantly stronger than in normoxia. We conclude that in conscious newborn rats during normoxia the Ta sensitivity of the HB reflex is largely mediated by the effects of Ta on thermogenesis andV˙o 2; in hypoxia, because thermogenesis is depressed andV˙o 2 varies little with Ta, the HB reflex is Ta independent. The observation that the reflex response to lung inflations during hypoxic hyperthermia can be greater than in normoxia may be of importance in the pathophysiology of apneas during the neonatal period.
Pulmonary inflammation alters the lung  disposition of lipophilic amine indicators
Authors: Audi Said H. , Roerig David L. , Ahlf Susan B. , Lin Win , Dawson Christopher A.
Published: December 2017

Many lipophilic amine compounds are rapidly extracted from the blood on passage through the pulmonary circulation. The extent of their extraction in normal lungs depends on their physical-chemical properties, which affect their degree of ionization, lipophilicity, and propensity for interacting with blood and tissue constituents. The hypothesis of the present study was that changes in the tissue composition that occur during pulmonary inflammation would have a differential effect on the pulmonary extraction of lipophilic amines having different properties. If so, measurement of the extraction patterns for a group of lipophilic amines, having different physical-chemical properties, might provide a means for detecting and identifying lung tissue abnormalities. To evaluate this hypothesis, we measured the pulmonary extraction patterns for four lipophilic amines, [14C]diazepam, [3H]alfentanil, [14C]lidocaine, and [14C]codeine, along with two hydrophilic compounds,3HOH and [14C]phenylethylamine, after the bolus injection of these indicators into the pulmonary artery of isolated lungs from normal rabbits and from rabbits with pulmonary inflammation induced by an intravenous injection of complete Freund's adjuvant. The pulmonary extraction patterns, parameterized using a previously developed mathematical model, were, in fact, differentially altered by the inflammatory response. For example, the tissue sequestration rate, k seq (ml/s), per unit3HOH accessible extravascular lung water volume significantly increased for diazepam and lidocaine, but not for codeine and alfentanil. The results are consistent with the above hypothesis and suggest the potential for using lipophilic amines as indicators for detection and quantification of changes in lung tissue composition associated with lung injury and disease.
Equine sweating responses to submaximal exercise during 21 days of heat acclimation
Authors: McCutcheon Laura Jill , Geor Raymond J. , Ecker Gayle L. , Lindinger Michael I.
Published: December 2017

This study examined sweating responses in six exercise-trained horses during 21 consecutive days (4 h/day) of exposure to, and daily exercise in, hot humid conditions (32–34°C, 80–85% relative humidity). On days 0, 3, 7, 14, and 21, horses completed a standardized exercise test on a treadmill (6° incline) at a speed eliciting 50% of maximal O2uptake until a pulmonary artery temperature of 41.5°C was attained. Sweat was collected at rest, every 5 min during exercise, and during 1 h of standing recovery for measurement of ion composition (Na+, K+, and Cl−) and sweating rate (SR). There was no change in the mean time to reach a pulmonary artery temperature of 41.5°C (range 19.09 ± 1.41 min on day 0 to 20.92 ± 1.98 min on day 3). Peak SR during exercise (ml ⋅ m−2⋅ min−1) increased on day 7 (57.5 ± 5.0) but was not different on day 21 (48.0 ± 4.7) compared with day 0 (52.0 ± 3.4). Heat acclimation resulted in a 17% decline in SR during recovery and decreases in body mass and sweat fluid losses during the standardized exercise test of 25 and 22%, respectively, by day 21. By day 21, there was also a 10% decrease in mean sweat Na+concentration for a given SR during exercise and recovery; this contributed to an ∼26% decrease in calculated total sweat ion losses (3,112 ± 114 mmol on day 0 vs. 2,295 ± 107 mmol on day 21). By day 21, there was a decrease in sweating threshold (∼1°C) but no change in sweat sensitivity. It is concluded that horses responded to 21 days of acclimation to, and exercise in, hot humid conditions with a reduction in sweat ion losses attributed to decreases in sweat Na+concentration and SR during recovery.
Alveolar epithelial fluid transport can be simultaneously upregulated by both KGF and β-agonist therapy
Authors: Wang Yibing , Folkesson Hans G. , Jayr Christian , Ware Lorraine B. , Matthay Michael A.
Published: December 2017

Although keratinocyte growth factor (KGF) protects against experimental acute lung injury, the mechanisms for the protective effect are incompletely understood. Therefore, the time-dependent effects of KGF on alveolar epithelial fluid transport were studied in rats 48–240 h after intratracheal administration of KGF (5 mg/kg). There was a marked proliferative response to KGF, measured both by in vivo bromodeoxyuridine staining and by staining with an antibody to a type II cell antigen. In controls, alveolar liquid clearance (ALC) was 23 ± 3%/h. After KGF pretreatment, ALC was significantly increased to 30 ± 2%/h at 48 h, to 39 ± 2%/h at 72 h, and to 36 ± 3%/h at 120 h compared with controls ( P < 0.05). By 240 h, ALC had returned to near-control levels (26 ± 2%/h). The increase in ALC was explained primarily by the proliferation of alveolar type II cells, since there was a good correlation between the number of alveolar type II cells and the increase in ALC ( r = 0.92, P = 0.02). The fraction of ALC inhibited by amiloride was similar in control rats (33%) as in 72-h KGF-pretreated rats (38%), indicating that there was probably no major change in the apical pathways for Na uptake in the KGF-pretreated rats at this time point. However, more rapid ALC at 120 h, compared with 48 h after KGF treatment, may be explained by greater maturation of α-epithelial Na channel, since its expression was greater at 120 than at 48 h, whereas the number of type II cells was the same at these two time points. β-Adrenergic stimulation with terbutaline 72 h after KGF pretreatment further increased ALC to 50 ± 7%/h ( P < 0.5). In summary, KGF induced a sustained increase over 120 h in the fluid transport capacity of the alveolar epithelium. This impressive upregulation in fluid transport was further enhanced with β-adrenergic agonist therapy, thus providing evidence that two different treatments can simultaneously increase the fluid transport capacity of the alveolar epithelium.
A computer model of human thermoregulation for a wide range of environmental conditions: the passive system
Authors: Fiala Dusan , Lomas Kevin J. , Stohrer Martin
Published: December 2017

A dynamic model predicting human thermal responses in cold, cool, neutral, warm, and hot environments is presented in a two-part study. This, the first paper, is concerned with aspects of the passive system: 1) modeling the human body, 2) modeling heat-transport mechanisms within the body and at its periphery, and 3) the numerical procedure. A paper in preparation will describe the active system and compare the model predictions with experimental data and the predictions by other models. Here, emphasis is given to a detailed modeling of the heat exchange with the environment: local variations of surface convection, directional radiation exchange, evaporation and moisture collection at the skin, and the nonuniformity of clothing ensembles. Other thermal effects are also modeled: the impact of activity level on work efficacy and the change of the effective radiant body area with posture. A stable and accurate hybrid numerical scheme was used to solve the set of differential equations. Predictions of the passive system model are compared with available analytic solutions for cylinders and spheres and show good agreement and stable numerical behavior even for large time steps.
Modeling expiratory flow from excised tracheal tube laws
Authors: Aljuri Nikolai , Freitag Lutz , Venegas José G.
Published: December 2017

Flow limitation during forced exhalation and gas trapping during high-frequency ventilation are affected by upstream viscous losses and by the relationship between transmural pressure (Ptm) and cross-sectional area ( A tr) of the airways, i.e., tube law (TL). Our objective was to test the validity of a simple lumped-parameter model of expiratory flow limitation, including the measured TL, static pressure recovery, and upstream viscous losses. To accomplish this objective, we assessed the TLs of various excised animal tracheae in controlled conditions of quasi-static (no flow) and steady forced expiratory flow. A tr was measured from digitized images of inner tracheal walls delineated by transillumination at an axial location defining the minimal area during forced expiratory flow. Tracheal TLs followed closely the exponential form proposed by Shapiro (A. H. Shapiro. J. Biomech. Eng. 99: 126–147, 1977) for elastic tubes: Ptm = K p[( A tr/ A tr0)− n − 1], where A tr0 is A tr at Ptm = 0 and K p is a parametric factor related to the stiffness of the tube wall. Using these TLs, we found that the simple model of expiratory flow limitation described well the experimental data. Independent of upstream resistance, all tracheae with an exponent n < 2 experienced flow limitation, whereas a trachea with n > 2 did not. Upstream viscous losses, as expected, reduced maximal expiratory flow. The TL measured under steady-flow conditions was stiffer than that measured under expiratory no-flow conditions, only if a significant static pressure recovery from the choke point to atmosphere was assumed in the measurement.
Early events in stretch-induced muscle damage
Authors: Morgan D. L. , Allen D. G.
Published: December 2017

Unaccustomed exercise involving stretch of active muscle at long length causes an immediate loss of tension-generating capacity, a shift of optimum length, and changes in excitation-contraction coupling. Eventually, fiber damage may be observed, resulting in pain and tenderness. The subject of this review is the early stage in this process, particularly the cause of the immediate drop in tension. There is strong evidence pointing to sarcomere length instabilities and nonuniformities as important contributors to these changes. The evidence includes the influence of initial length, electron microscopy of rapidly fixed active fibers, the shift in optimum length in single fibers, and the effects of training on sacomere numbers. Experiments using Ca2+-sensitive dyes clearly show changes in excitiation-contraction coupling, but cross-species comparisons indicate that these are not always able to explain the consequences seen. We conclude that sarcomere length instabilities provide the most comprehensive explanation of the early consequences of eccentric exercise.
Changes in viscoelastic properties of rat lung parenchymal strips with maturation
Authors: Tanaka R. , Ludwig M. S.
Published: December 2017

The lung extracellular matrix changes rapidly with maturation. To further our understanding of the mechanisms underlying lung tissue mechanics, we studied age-related changes in mechanical properties in lung parenchymal strips from baby (10–15 days old), young (∼3 wk old), and adult (∼8 wk old) rats. Subpleural strips were cut and suspended in a fluid-filled organ bath. One end of the strip was attached to a force transducer and the other to a servo-controlled lever arm. Measurements of force (F) and length ( L) were recorded during sinusoidal oscillations of various amplitudes and frequencies. Resistance modulus (R) and elastance modulus (E) were estimated by fitting the equation of motion to changes in stress (T) and stretch ratio (λ). Hysteresivity (η) was calculated as follows: η = (R/E)2π f, where f is frequency. Slow-cycling T-λ curves were measured by applying a constant slow length change. Finally, quasi-static T-λ curves were measured as stress was increased from 0 to 6 kPa and back to 0 kPa in stepwise increments. Our results showed that lung tissue from immature rats was stiffer and less hysteretic than tissue from more mature animals. In addition, tissue from baby animals behaved in a manner compatible with an increased vulnerability to plastic change.
Pixel T2 distribution in functional magnetic resonance images of muscle
Authors: Prior Barry M. , Foley Jeanne M. , Jayaraman Roop C. , Meyer Ronald A.
Published: December 2017

Increases in skeletal muscle1H-NMR transverse relaxation time (T2) observed by magnetic resonance imaging have been used to map whole muscle activity during exercise. Some studies further suggest that intramuscular variations in T2 after exercise can be used to map activity on a pixel-by-pixel basis by defining an active T2 threshold and counting pixels that exceed the threshold as “active muscle.” This implies that motor units are nonrandomly distributed across the muscle and, therefore, that the distribution of pixel T2 values ought to be substantially broader after moderate exercise than at rest or after more intense exercise, since moderate-intensity exercise should recruit some motor units, and hence some pixels, but not others. This study examined the distribution of pixel T2 values in three muscles (quadriceps, anterior tibialis, and biceps/brachialis) of healthy subjects (5 men and 2 women, 18–46 yr old) at rest, after exercise to fatigue (50% 1 repetition maximum at 20/min to failure = Max), and at ½Max (25% 1 repetition maximum, same number of repetitions as Max). Although for each muscle there was a linear relationship between exercise intensity and mean pixel T2, there was no significant difference in the variance of pixel T2 between ½Max and Max exercise. There was a modest (10–43%) increase in variance of pixel T2 after both exercises compared with rest, but this was consistent with a Monte Carlo simulation of muscle activity that assumed a random distribution of motor unit territories across the muscle and a random distribution of muscle cells within each motor unit's territory. In addition, 40% of the pixel-to-pixel muscle T2 variations were shown to be due to imaging noise. The results indicate that magnetic resonance imaging T2 cannot reliably map active muscle on a pixel-by-pixel basis in normal subjects.
Oxygen-conserving effects of apnea in exercising men
Authors: Lindholm Peter , Sundblad Patrik , Linnarsson Dag
Published: December 2017

We sought to determine whether apnea-induced cardiovascular responses resulted in a biologically significant temporary O2 conservation during exercise. Nine healthy men performing steady-state leg exercise carried out repeated apnea (A) and rebreathing (R) maneuvers starting with residual volume +3.5 liters of air. Heart rate (HR), mean arterial pressure (MAP), and arterial O2 saturation (SaO2 ; pulse oximetry) were recorded continuously. Responses (ΔHR, ΔMAP) were determined as differences between HR and MAP at baseline before the maneuver and the average of values recorded between 25 and 30 s into each maneuver. The rate of O2 desaturation (ΔSaO2 /Δ t) was determined during the same time interval. During apnea, ΔSaO2/Δ t had a significant negative correlation to the amplitudes of ΔHR and ΔMAP ( r 2 = 0.88, P < 0.001); i.e., individuals with the most prominent cardiovascular responses had the slowest ΔSaO2 /Δ t. ΔHR and ΔMAP were much larger during A (−44 ± 8 beats/min, +49 ± 4 mmHg, respectively) than during R maneuver (+3 ± 3 beats/min, +30 ± 5 mmHg, respectively). ΔSaO2 /Δ t during A and R maneuvers was −1.1 ± 0.1 and −2.2 ± 0.2% units/s, respectively, and nadir SaO2 values were 58 ± 4 and 42 ± 3% units, respectively. We conclude that bradycardia and hypertension during apnea are associated with a significant temporary O2 conservation and that respiratory arrest, rather than the associated hypoxia, is essential for these responses.
A three-dimensional model of the human airway tree
Authors: Kitaoka Hiroko , Takaki Ryuji , Suki Béla
Published: December 2017

A three-dimensional (3D) model of the human airway tree is proposed using a deterministic algorithm that can generate a branching duct system in an organ. The algorithm is based on two principles: 1) the amount of fluid delivery through a branch is proportional to the volume of the region it supplies; and 2) the terminal branches are arranged homogeneously within the organ. These principles define the basic process of branching: generation of the dimensions and directionality of two daughter branches is governed by the properties of the parent branch and the region the parent supplies. The algorithm is composed of nine basic rules and four complementary rules. When the contour of an organ and the position of the trunk are specified, branches are successively generated by the algorithm. Applied to the human lung, the algorithm generates an airway tree that consists of ∼54,000 branches. Its morphometric characteristics are in good agreement with those reported in the literature. The algorithm and the 3D airway model are useful for studying the structure-function relationship in the lung.
Adenosine contributes to hypoxia-induced forearm vasodilation in humans
Authors: Leuenberger Urs A. , Gray Kris , Herr Michael D.
Published: December 2017

In humans, hypoxia leads to increased sympathetic neural outflow to skeletal muscle. However, blood flow increases in the forearm. The mechanism of hypoxia-induced vasodilation is unknown. To test whether hypoxia-induced vasodilation is cholinergically mediated or is due to local release of adenosine, normal subjects were studied before and during acute hypoxia (inspired O210.5%; ∼20 min). In experiment I, aminophylline (50–200 μg ⋅ min−1 ⋅ 100 ml forearm tissue−1) was infused into the brachial artery to block adenosine receptors ( n = 9). In experiment II, cholinergic vasodilation was blocked by atropine (0.4 mg over 4 min) infused into the brachial artery ( n = 8). The responses of forearm blood flow (plethysmography) and forearm vascular resistance to hypoxia in the infused and opposite (control) forearms were compared. During hypoxia (arterial O2 saturation 77 ± 2%), minute ventilation and heart rate increased while arterial pressure remained unchanged; forearm blood flow rose by 35 ± 6% in the control forearm but only by 5 ± 8% in the aminophylline-treated forearm ( P < 0.02). Accordingly, forearm vascular resistance decreased by 29 ± 5% in the control forearm but only by 9 ± 6% in the aminophylline-treated forearm ( P < 0.02). Atropine did not attenuate forearm vasodilation during hypoxia. These data suggest that adenosine contributes to hypoxia-induced vasodilation, whereas cholinergic vasodilation does not play a role.
Rapid force recovery in contracting skeletal muscle after brief ischemia is dependent on O2 availability
Authors: Hogan Michael C. , Kohin Suzanne , Stary Creed M. , Hepple Russell T.
Published: December 2017

We tested the hypothesis that contracting skeletal muscle can rapidly restore force development during reperfusion after brief total ischemia and that this rapid recovery depends on O2 availability and not an alternate factor related to blood flow. Isolated canine gastrocnemius muscle ( n = 5) was stimulated to contract tetanically (isometric contraction elicited by 8 V, 0.2-ms duration, 200-ms trains, at 50-Hz stimulation) every 2 s until steady-state conditions of muscle blood flow (controlled by pump perfusion) and developed force were attained (3 min). While maintaining the same stimulation pattern, muscle blood flow was then reduced to zero (complete ischemia) for 2 min. Normal blood flow was then restored to the contracting muscle; however, two distinct conditions of oxygenation (at the same blood flow) were sequentially imposed: deoxygenated blood (30 s), blood with normal arterial O2content (30 s), a return to deoxygenated blood (30 s), and finally a return to normal arterial O2 content (90 s). During the ischemic period, force development fell to 39 ± 6 (SE)% of normal (from 460 ± 40 to 170 ± 20 N/100 g). When muscle blood flow was restored to normal by perfusion with deoxygenated blood, developed force continued to decline to 140 ± 20 N/100 g. Muscle force rapidly recovered to 310 ± 30 N/100 g ( P < 0.05) during the 30 s in which the contracting muscle was perfused with oxygenated blood and then fell again to 180 ± 30 N/100 g when perfused with blood with low[Formula: see text]. These findings demonstrate that contracting skeletal muscle has the capacity for rapid recovery of force development during reperfusion after a short period of complete ischemia and that this recovery depends on O2availability and not an alternate factor related to blood flow restoration.