bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of concentration on albumin diffusion in lung interstitium
Authors: Qiu Xiao L. , Brown Laura V. , Parameswaran Sandhya , Ibbott Geoffrey S. , Lai-Fook Stephen J.
Published: December 2017

The transport of macromolecules through the lung interstitium depends on both bulk transport of fluid and diffusion. In the present study, we studied the diffusion of albumin. Isolated rabbit lungs were inflated with silicon rubber via airways and blood vessels, and two chambers were bonded to the sides of a 0.5-cm-thick slab that enclosed a vessel with an intersititial cuff. One chamber was filled with either albumin solution (2 or 5 g/dl) containing tracer125I-albumin or with tracer125I-albumin alone; the other was filled with Ringer solution. Unbound125I was removed from the tracer by dialysis before use. The chamber with Ringer solution was placed in the well of a NaI(Tl) scintillation detector. Diffusion of tracer through the interstitium was measured continuously for 60 h. Tracer mass ( M) showed a time ( t) delay followed by an increase to a steady-state flow (d M/d tconstant). Albumin diffusion coefficient ( D) was given by L 2/(6 T), where T was the time intercept of the steady-state M- tline at zero M, and L was interstitial length. Interstitial cuff thickness-to-vessel radius ratio ( Th 0/ R) was estimated by using Fick’s law for steady-state diffusion. Both D and Th 0/ Rwere independent of albumin concentration. D averaged 6.6 × 10−7cm2/s, similar to the free D for albumin. Values of Th 0/ Raveraged 0.047 ± 0.024 (SD), near the values measured histologically. Thus pulmonary interstitial constituents offered no restriction to the diffusion of albumin.
Effects of surfactant distribution and ventilation strategies on efficacy of exogenous surfactant
Authors: Kerr Carolyn L. , Ito Yushi , Manwell Stuart E. E. , Veldhuizen Ruud A. W. , Yao Li-Juan , McCaig Lynda A. , Lewis James F.
Published: December 2017

The effects of both surfactant distribution patterns and ventilation strategies utilized after surfactant administration were assessed in lung-injured adult rabbits. Animals received 50 mg/kg surfactant via intratracheal instillation in volumes of either 4 or 2 ml/kg. A subset of animals from each treatment group was euthanized for evaluation of the exogenous surfactant distribution. The remaining animals were randomized into one of three ventilatory groups: group 1 [tidal volume (Vt) of 10 ml/kg with 5 cmH2O positive end-expiratory pressure (PEEP)]; group 2(Vt of 5 ml/kg with 5 cmH2O PEEP); or group 3(Vt of 5 ml/kg with 9 cmH2O PEEP). Animals were ventilated and monitored for 3 h. Distribution of the surfactant was more uniform when it was delivered in the 4 ml/kg volume. When the distribution of surfactant was less uniform, arterial[Formula: see text] values were greater in groups 2 and 3 compared with group 1. Oxygenation differences among the different ventilation strategies were less marked in animals with the more uniform distribution pattern of surfactant (4 ml/kg). In both surfactant treatment groups, a high mortality was observed with the ventilation strategy used for group 3. We conclude that the distribution of exogenous surfactant affects the response to different ventilatory strategies in this model of acute lung injury.
Concurrent resistance and endurance training influence basal metabolic rate in nondieting individuals
Authors: Dolezal Brett A. , Potteiger Jeffrey A.
Published: December 2017

Thirty physically active healthy men (20.1 ± 1.6 yr) were randomly assigned to participate for 10 wk in one of the following training groups: endurance trained (ET; 3 days/wk jogging and/or running), resistance trained (RT; 3 days/wk resistance training), or combined endurance and resistance trained (CT). Before and after training, basal metabolic rate (BMR), percent body fat (BF), maximal aerobic power, and one-repetition maximum for bench press and parallel squat were determined for each subject. Urinary urea nitrogen was determined pre-, mid-, and posttraining. BMR increased significantly from pre- to posttraining for RT (7,613 ± 968 to 8,090 ± 951 kJ/day) and CT (7,455 ± 964 to 7,802 ± 981 kJ/day) but not for ET (7,231 ± 554 to 7,029 ± 666 kJ/day). BF for CT (12.2 ± 3.5 to 8.7 ± 1.7%) was significantly reduced compared with RT (15.4 ± 2.7 to 14.0 ± 2.7%) and ET (11.8 ± 2.9 to 9.5 ± 1.7%). Maximal aerobic power increased significantly for ET (13%) but not RT (−0.2%) or CT (7%), whereas the improvements in one-repetition maximum bench press and parallel squat were greater in RT (24 and 23%, respectively) compared with CT (19 and 12%, respectively). Urinary urea nitrogen loss was greater in ET (14.6 ± 0.9 g/24 h) than in RT (11.7 ± 1.0 g/24 h) and CT (11.5 ± 1.0 g/24 h) at the end of 10 wk of training. These data indicate that, although RT alone will increase BMR and muscular strength, and ET alone will increase aerobic power and decrease BF, CT will provide all of these benefits but to a lesser magnitude than RT and ET after 10 wk of training.
Angiogenic growth factor mRNA responses to passive and contraction-induced hyperperfusion in skeletal muscle
Authors: Roca Josep , Gavin Timothy P. , Jordan Maria , Siafakas Nikos , Wagner Harrieth , Benoit Henri , Breen Ellen , Wagner Peter D.
Published: December 2017

It has been proposed that, in skeletal muscle, the angiogenic response to exercise may be signaled by the increase in muscle blood flow, via biomechanical changes in the microcirculation (increased shear stress and/or wall tension). To examine this hypothesis, we compared the change in abundance of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-β1(TGF-β1) mRNA in skeletal muscles of the canine leg after 1 h of pump-controlled high blood flow alone (passive hyperperfusion; protocol A) and electrical stimulation of the femoral and sciatic nerves producing muscle contraction ( protocol B). The increase in leg blood flow (5.4- and 5.9-fold change from resting values, respectively) was similar in both groups. Passive hyperperfusion alone did not increase message abundance for VEGF (ratio of mRNA to 18S signals after vs. before hyperperfusion, 0.94 ± 0.08) or bFGF (1.08 ± 0.05) but slightly increased that of TGF-β1 (1.14 ± 0.07; P < 0.03). In contrast, as previously found in the rat, electrical stimulation provoked more than a threefold increase in VEGF mRNA abundance (3.40 ± 1.45; P < 0.02). However, electrical stimulation produced no significant changes in either bFGF (1.16 ± 0.13) or TGF-β1 (1.31 ± 0.27). These results suggest that the increased muscle blood flow of exercise does not account for the increased abundance of these angiogenic growth factor mRNA levels in response to acute exercise. We speculate that other factors, such as local hypoxia, metabolite concentration changes, or mechanical effects of contraction per se, may be responsible for the effects of exercise.
Letters to the Editor
Authors: Gourgoulianis K. I. , Molyvdas P. A.
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter:

Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol.83(6):1907–1916, 1997.—We investigated ventilation inhomogeneity during provocation with inhaled histamine in 20 asymptomatic nonsmoking subjects. We used N2 multiple-breath washout (MBW) to derive parameters S cond and S acin as a measurement of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV1) was used to distinguish responders from nonresponders. In the responder group, average FEV1decreased by 26%, whereas S cond increased by 390% with no significant change in S acin. In the nonresponder group, FEV1 decreased by 11%, whereas S cond increased by 198% with no significant S acin change. Despite the absence of change in S acin during provocation, baseline S acin was significantly larger in the responder vs. the nonresponder group. The main findings of our study are that during provocation large ventilation inhomogeneities occur, that the small airways affected by the provocation process are situated proximal to the acinar zone where the diffusion front stands, and that, in addition to overall decrease in airway caliber, there is inhomogeneous narrowing of parallel airways.
Pulse pressure response to the strain of the Valsalva maneuver in humans with preserved systolic function
Authors: Hébert Jean-Louis , Coirault Catherine , Zamani Karen , Fontaine Guy , Lecarpentier Yves , Chemla Denis
Published: December 2017

Arterial pulse pressure response during the strain phase of the Valsalva maneuver has been proposed as a clinical tool for the diagnosis of left heart failure, whereas responses of subjects with preserved systolic function have been poorly documented. We studied the relationship between the aortic pulse amplitude ratio (i.e., minimum/maximum pulse pressure) during the strain phase of the Valsalva maneuver and cardiac hemodynamics at baseline in 20 adults (42 ± 14 yr) undergoing routine right and left heart catheterization. They were normal subjects ( n = 5) and patients with various forms of cardiac diseases ( n = 15), and all had a left ventricular ejection fraction ≥40%. High-fidelity pressures were recorded in the right atrium and the left ventricle at baseline and at the aortic root throughout the Valsalva maneuver. Aortic pulse amplitude ratio 1) did not correlate with baseline left ventricular end-diastolic pressure, cardiac index (thermodilution), or left ventricular ejection fraction (cineangiography) and 2) was positively related to total arterial compliance (area method) ( r = 0.59) and to basal mean right atrial pressure ( r = 0.57) (each P < 0.01). Aortic pulse pressure responses to the strain were not related to heart rate responses during the maneuver. In subjects with preserved systolic function, the aortic pulse amplitude ratio during the strain phase of the Valsalva maneuver relates to baseline total arterial compliance and right heart filling pressures but not to left ventricular function.
Apneic threshold for CO2 in the anesthetized rat: fundamental properties under steady-state conditions
Authors: Boden A. G. , Harris M. C. , Parkes M. J.
Published: December 2017

Experiments were performed to measure the apneic threshold for CO2 and its fundamental properties in anesthetized rats under steady-state conditions. Breathing was detected from diaphragmatic electromyogram activity. Mechanical hyperventilation resulted in apnea once arterial[Formula: see text]([Formula: see text]) had fallen far enough. Apnea was not a reflex response to lung inflation because it did not occur immediately, was not prevented by vagotomy, and was reversed by raising [Formula: see text]without changing mechanical hyperventilation. The apneic threshold was measured by hyperventilating rats mechanically with O2 until apnea had occurred and then raising [Formula: see text] at constant hyperventilation until breathing reappeared. The mean[Formula: see text] level of the apneic threshold in 42 rats was 32.8 ± 0.4 Torr. The level of the threshold did not depend on the volume at which the lungs were inflated. The level of the threshold, under steady-state conditions, was the same when approached from hypocapnia as from eupnea. The level of the threshold could be raised by 9 Torr by chronic elevation of the eupneic [Formula: see text] level by 18 Torr.
Creatine supplementation and age influence muscle metabolism during exercise
Authors: Smith Sinclair A. , Montain Scott J. , Matott Ralph P. , Zientara Gary P. , Jolesz Ferenc A. , Fielding Roger A.
Published: December 2017

Young [ n = 5, 30 ± 5 (SD) yr] and middle-aged ( n = 4, 58 ± 4 yr) men and women performed single-leg knee-extension exercise inside a whole body magnetic resonance system. Two trials were performed 7 days apart and consisted of two 2-min bouts and a third bout continued to exhaustion, all separated by 3 min of recovery.31P spectra were used to determine pH and relative concentrations of Pi, phosphocreatine (PCr), and β-ATP every 10 s. The subjects consumed 0.3 g ⋅ kg−1 ⋅ day−1of a placebo ( trial 1) or creatine ( trial 2) for 5 days before each trial. During the placebo trial, the middle-aged group had a lower resting PCr compared with the young group (35.0 ± 5.2 vs. 39.5 ± 5.1 mmol/kg, P < 0.05) and a lower mean initial PCr resynthesis rate (18.1 ± 3.5 vs. 23.2 ± 6.0 mmol ⋅ kg−1 ⋅ min−1, P < 0.05). After creatine supplementation, resting PCr increased 15% ( P < 0.05) in the young group and 30% ( P < 0.05) in the middle-aged group to 45.7 ± 7.5 vs. 45.7 ± 5.5 mmol/kg, respectively. Mean initial PCr resynthesis rate also increased in the middle-aged group ( P < 0.05) to a level not different from the young group (24.3 ± 3.8 vs. 24.2 ± 3.2 mmol ⋅ kg−1 ⋅ min−1). Time to exhaustion was increased in both groups combined after creatine supplementation (118 ± 34 vs. 154 ± 70 s, P < 0.05). In conclusion, creatine supplementation has a greater effect on PCr availability and resynthesis rate in middle-aged compared with younger persons.
Leg mass and lower body negative pressure tolerance in men and women
Authors: Lawler Lori A. , Halliwill John R. , Summer Jolene M. , Joyner Michael J. , Mulvagh Sharon L.
Published: December 2017

To explore the hypothesis that lower body muscle mass correlates with orthostatic tolerance, 18 healthy volunteers (age 18–48 yr; 10 men, 8 women) underwent a graded lower body negative pressure (LBNP) protocol consisting of six, 5-min stages of suction up to 60 mmHg in 10-mmHg increments. Forearm blood flow, heart rate, and blood pressure were measured, and forearm vascular resistance was calculated. Leg muscle mass was assessed by dual-energy X-ray absorptiometry. All subjects received standard intravenous hydration for at least 8 h before the study. Six men and four women completed all stages of LBNP. Four men and four women developed presyncopal symptoms, including marked bradycardia and/or hypotension, at LBNP levels of 30 mmHg ( n = 2; 1 man, 1 woman), 40 mmHg ( n = 2; 1 man, 1 woman), and 50 mmHg ( n = 4; 2 men, 2 women). The presyncopal subjects had leg muscle masses ranging from 19.5 to 25.2 kg in men and from 11.7 to 16.6 kg in women. In subjects who completed all stages of LBNP, leg muscle mass ranged from 17.5 to 24.1 kg in men and from 10.4 to 18.0 kg in women. Leg muscle mass did not differ between presyncopal subjects and those who completed the protocol. Furthermore, there were no differences in the hemodynamic responses to LBNP between subjects with low vs. high leg mass. These data suggest that leg muscle mass is not a critical determinant of LBNP tolerance in otherwise healthy men and women.
Hormonal responses to consecutive days of heavy-resistance exercise with or without nutritional supplementation
Authors: Kraemer William J. , Volek Jeff S. , Bush Jill A. , Putukian Margot , Sebastianelli Wayne J.
Published: December 2017

Nine resistance-trained men consumed either a protein-carbohydrate supplement or placebo for 1 wk in a crossover design separated by 7 days. The last 3 days of each treatment, subjects performed resistance exercise. The supplement was consumed 2 h before and immediately after the workout, and blood was obtained before and after exercise (0, 15, 30, 45, and 60 min postexercise). Lactate, growth hormone, and testosterone were significantly ( P ≤ 0.05) elevated immediately postexercise. The lactate response was significantly lower during supplementation on days 2 and 3. Growth hormone and prolactin responses on day 1 were significantly higher during supplementation. After exercise, testosterone declined below resting values during supplementation. Cortisol decreased immediately postexercise on day 1; the response was diminished on days 2 and 3. Glucose and insulin were significantly elevated by 30 min during supplementation and remained stable during placebo. Insulin-like growth factor-I was higher during supplementatiom on days 2 and 3. These data indicate that protein-carbohydrate supplementation before and after training can alter the metabolic and hormonal responses to consecutive days of heavy-resistance exercise.
Multichannel EEG analysis of respiratory evoked-potential components during wakefulness and NREM sleep
Authors: Webster Kate E. , Colrain Ian M.
Published: December 2017

Airway occlusion in awake humans produces a somatosensory evoked response called the respiratory-related evoked potential (RREP). In the present study, 29 channel evoked-potential recordings were obtained from seven men who were exposed to 250-ms inspiratory airway occlusions during wakefulness, stage 1, stage 2, and slow-wave sleep. The RREP recorded during wakefulness was similar to previous reports, with the unique observation of an additional short-latency positive peak with a mean latency of 25 ms. Short-latency RREP components were maintained in non-rapid-eye-movement (NREM) sleep. The clearly seen N1 vertex and late positive complex components during wakefulness were markedly attenuated during NREM sleep, and two large negative components (N300 and N550) dominated the sleep RREP. These findings indicate the maintenance of central nervous system monitoring of respiratory afferent information during NREM sleep, presumably to facilitate protective arousal responses to pathophysiological respiratory phenomena.
Magnetic resonance imaging of total body fat
Authors: Thomas E. Louise , Saeed Nadeem , Hajnal Joseph V. , Brynes Audrey , Goldstone Anthony P. , Frost Gary , Bell Jimmy D.
Published: December 2017

In this study we assessed different magnetic resonance imaging (MRI) scanning regimes and examined some of the assumptions commonly made for measuring body fat content by MRI. Whole body MRI was used to quantify and study different body fat depots in 67 women. The whole body MRI results showed that there was a significant variation in the percentage of total internal, as well as visceral, adipose tissue across a range of adiposity, which could not be predicted from total body fat and/or subcutaneous fat. Furthermore, variation in the amount of total, subcutaneous, and visceral adipose tissue was not related to standard anthropometric measurements such as skinfold measurements, body mass index, and waist-to-hip ratio. Finally, we show for the first time subjects with a percent body fat close to the theoretical maximum (68%). This study demonstrates that the large variation in individual internal fat content cannot be predicted from either indirect methods or direct imaging techniques, such as MRI or computed tomography, on the basis of a single-slice sampling strategy.
Effects of airway inflammation on cough response in the guinea pig
Authors: Xiang Anbo , Uchida Yoshiyuki , Nomura Akihiro , Iijima Hiroaki , Dong Fang , Zhang Min-Jie , Hasegawa Shizuo
Published: December 2017

We have developed a guinea pig model for cough related to allergic airway inflammation. Unanesthetized animals were exposed to capsaicin aerosols for 10 min, and cough frequency was counted during this period. The cough evaluation was performed by the following three methods: visual observation, acoustic analysis, and monitoring of pressure changes in the body chamber. These analyses clearly differentiated a cough from a sneeze. To elucidate the relationship between cough response and airway inflammation, animals were immunosensitized and multiple challenged. Sensitized guinea pigs presented no specific changes microscopically, but multiple-challenged animals showed an increased infiltration of inflammatory cells into the airway. Cough number in response to capsaicin increased significantly from 4.7 ± 1.4 coughs/10 min in normal animals to 10.6 ± 2.0 coughs/10 min in sensitized animals and further to 22.8 ± 1.3 coughs/10 min in multiple-challenged animals. This augmented cough frequency was significantly inhibited by the inhalation of tachykinin-receptor antagonists and by oral ingestion, but not inhalation, of codeine phosphate. The results suggest that airway inflammation potentiates an elevation of cough sensitivity in this model.
Human ventilatory response to CO2 after 8 h of isocapnic or poikilocapnic hypoxia
Authors: Fatemian Marzieh , Robbins Peter A.
Published: December 2017

During ventilatory acclimatization to hypoxia (VAH), the relationship between ventilation (V˙e) and end-tidal[Formula: see text]([Formula: see text]) changes. This study was designed to determine 1) whether these changes can be seen early in VAH and 2) if these changes are present, whether the responses differ between isocapnic and poikilocapnic exposures. Ten healthy volunteers were studied by using three 8-h exposures: 1) isocapnic hypoxia (IH), end-tidal [Formula: see text]([Formula: see text]) = 55 Torr and[Formula: see text] held at the subject’s normal prehypoxic value; 2) poikilocapnic hypoxia (PH),[Formula: see text] = 55 Torr; and 3) control (C), air breathing. TheV˙e-[Formula: see text]relationship was determined in hyperoxia ([Formula: see text] = 200 Torr) before and after the exposures. We found a significant increase in the slopes ofV˙e-[Formula: see text]relationship after both hypoxic exposures compared with control (IH vs. C, P < 0.01; PH vs. C, P < 0.001; analysis of covariance with pairwise comparisons). This increase was not significantly different between protocols IH and PH. No significant changes in the intercept were detected. We conclude that 8 h of hypoxia, whether isocapnic or poikilocapnic, increases the sensitivity of the hyperoxic chemoreflex response to CO2.
Effect of beverage osmolality on intestinal fluid absorption during exercise
Authors: Gisolfi C. V. , Summers R. W. , Lambert G. P. , Xia T.
Published: December 2017

To determine how osmolality of an orally ingested fluid-replacement beverage would alter intestinal fluid absorption from the duodenum and/or jejunum during 85 min of cycle exercise (63.3 ± 0.9% peak O2 uptake) in a cool environment (22°C), seven subjects (5 men, 2 women, peak O2 uptake = 54.5 ± 3.8 ml ⋅ kg−1 ⋅ min−1) participated in four experiments separated by 1 wk in which they ingested a water placebo (WP) or one of three 6% carbohydrate (CHO) beverages formulated to give mean osmolalities of 197, 295, or 414 mosmol/kgH2O. CHO solutions also contained 17–18 meq Na+ and 3.2 meq K+. Nasogastric and multilumen tubes were fluoroscopically positioned in the gastric antrum and duodenojejunum, respectively. Subjects ingested a total of 23 ml/kg body mass of the test solution, 20% (370 ± 9 ml) of this volume 5 min before exercise and 10% (185 ± 4 ml) every 10 min thereafter. By using the rate of gastric emptying as the rate of intestinal perfusion (G. P. Lambert, R. T. Chang, D. Joensen, X. Shi, R. W. Summers, H. P. Schedl, and C. V. Gisolfi. Int. J. Sports Med. 17: 48–55, 1996), intestinal absorption was determined by segmental perfusion from the duodenum (0–25 cm) and jejunum (25–50 cm). There were no differences ( P > 0.05) in gastric emptying (mean 18.1 ± 1.3 ml/min) or total fluid absorption (802 ± 109, 650 ± 52, 674 ± 62, and 633 ± 74 ml ⋅ 50 cm−1 ⋅ h−1for WP, hypo-, iso-, and hypertonic solutions, respectively) among beverages; but WP was absorbed faster ( P < 0.05) from the duodenum than in the jejunum. Of the total volume of fluid ingested, 82 ± 14, 74 ± 6, 76 ± 5, and 68 ± 7% were absorbed for WP, hypo-, iso-, and hypertonic beverages, respectively. There were no differences in urine production or percent change in plasma volume among solutions. We conclude that total fluid absorption of 6% CHO-electrolyte beverages from the duodenojejunum during exercise, within the osmotic range studied, is not different from WP.
Women at altitude: changes in carbohydrate metabolism at 4,300-m elevation and across the menstrual cycle
Authors: Braun Barry , Butterfield Gail E. , Dominick Shannon B. , Zamudio Stacy , McCullough Rosann G. , Rock Paul B. , Moore Lorna G.
Published: December 2017

We hypothesized that, in women, the blood glucose response to a meal (BGR) would be lower after exposure to 4,300 m compared with sea level (SL) and that BGR would be reduced in the presence of estrogen plus progesterone (E+P) relative to estrogen alone (E). Sixteen women were studied in both the E and E+P conditions at SL and in either the E or E+P condition at 4,300 m. On day 9 in each condition, blood was sampled before, and every 30 min for 2 h after, the subjects ate a high-carbohydrate meal. At 4,300 m, BGR peaked at a lower value (5.73 ± 0.94 mM) than at SL (6.44 ± 1.45 mM) and returned to baseline more slowly ( P < 0.05). Plasma insulin values were the same but C peptide was slightly higher at 4,300 m ( P < 0.05). At SL, BGR returned to baseline more slowly in E+P condition (5.13 ± 0.89 and 5.21 ± 0.91 mM at 60 and 90 min, respectively) relative to E condition (4.51 ± 0.52 and 4.69 ± 0.88 mM, respectively) ( P < 0.05). Insulin and C peptide were not different between E and E+P conditions. The data indicate that BGR is lower in women at high altitude compared with the SL, possibly due to greater suppression of hepatic glucose production or stimulation of peripheral glucose uptake by insulin. BGR was lower in E condition relative to E+P condition at SL and possibly at 4,300 m, but the relative concentrations of ovarian hormones do not appear to alter the magnitude of the change in BGR when women are exposed to high altitude.
Voluntary activation of the human diaphragm in health and disease
Authors: Sinderby Christer , Beck Jennifer , Spahija Jadranka , Weinberg Jan , Grassino Alex
Published: December 2017

Intersubject comparison of the crural diaphragm electromyogram, as measured by an esophageal electrode, requires a reliable means for normalizing the signal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high and reproducible diaphragm electromyogram root-mean-square (RMS) values and 2) to determine the relative diaphragm activation and mechanical and ventilatory outputs during breathing at rest in healthy subjects ( n = 5), in patients with severe chronic obstructive pulmonary disease (COPD, n = 5), and in restrictive patients with prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher during inspiration to total lung capacity than during sniff inhalation through the nose ( P = 0.035, ANOVA). The RMS (percentage of voluntary maximal RMS) during quiet breathing was 8% in healthy subjects, 43% in COPD patients, and 45% in PPI patients. Despite the large difference in relative RMS ( P = 0.012), there were no differences in mean transdiaphragmatic pressure ( P= 0.977) and tidal volumes ( P = 0.426). We conclude that voluntary maximal RMS is reliably obtained during an inspiration to total lung capacity but a sniff inhalation could be a useful complementary maneuver. Severe COPD and PPI patients breathing at rest are characterized by increased diaphragm activation with no change in diaphragm pressure generation.
Leptin attenuates respiratory complications associated with the obese phenotype
Authors: Tankersley C. G. , O’Donnell C. , Daood M. J. , Watchko J. F. , Mitzner W. , Schwartz A. , Smith P.
Published: December 2017

A profile of respiratory complications has been associated with the onset and development of obesity in humans. Similar phenotypes have been routinely demonstrated in genetic animal models of obesity such as the ob mouse (C57BL/6J- Lepob). The objective of the present study was to test the hypothesis that a constellation of respiratory complications are attenuated with leptin (i.e., protein product of the ob gene) replacement. Daily leptin administration during a 6-wk period was conducted to control body weight of mutant ob mice similar to genotypic control groups. During the treatment period, repeated baseline ventilatory measurements were assessed by using whole body plethysmography while quasistatic pressure-volume curves were performed to further explore the role of leptin in improving lung mechanics. Diaphragmatic myosin heavy chain (MHC) isoform phenotype was examined to determine proportional changes in MHC composition. In room air, breathing frequency and minute ventilation were significantly ( P < 0.01) different among ob treatment groups, suggesting that leptin opposed the development of a rapid breathing pattern observed in vehicle-treated ob mice. Quasistatic deflation curves indicated that the lung volume of leptin-treated ob mice was significantly ( P < 0.05) greater relative to vehicle-treated ob mice at airway pressures between 0 and 30 cmH2O. Diaphragm MHC composition of leptin-treated ob mice was restored significantly ( P < 0.05) to resemble the control phenotype. In this genetic mouse model of obesity, the results suggested that respiratory complications associated with the obese phenotype, including rapid breathing pattern at baseline, diminished lung compliance, and abnormal respiratory muscle adaptations, are attenuated with prolonged leptin treatment.
α1-Adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise
Authors: Buckwalter John B. , Mueller Patrick J. , Clifford Philip S.
Published: December 2017

Attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during dynamic exercise is controversial. One potential mechanism is a reduction in α1-adrenergic-receptor responsiveness. The purpose of this study was to examine α1-adrenergic-receptor-mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective agonist. Seven mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. A selective α1-adrenergic-receptor agonist (phenylephrine) was infused as a bolus into the femoral artery catheter at rest and during exercise. All dogs ran on a motorized treadmill at two exercise intensities (3 and 6 miles/h). Intra-arterial infusions of the same effective concentration of phenylephrine elicited reductions in vascular conductance of 76 ± 4, 76 ± 6, and 67 ± 5% ( P > 0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic blood pressure and blood flow in the contralateral iliac artery were unaffected by phenylephrine. These results do not demonstrate an attenuation of vasoconstriction to a selective α1-agonist during exercise and do not support the concept of sympatholysis.
Nitric oxide production and absorption in trachea, bronchi, bronchioles, and respiratory bronchioles of humans
Authors: DuBois Arthur B. , Kelley Patrick M. , Douglas James S. , Mohsenin Vahid
Published: December 2017

Different volumes of dead-space gas were collected and analyzed for nitric oxide (NO) content, either immediately after inspiration or after a period of breath holding on clean air or NO mixtures. This allowed calculation of NO equilibrium, NO production, and NO absorption. In seven young, healthy, adult nonsmokers, the mean NO equilibrium values in parts per billion (ppb) were 56 ± 11 (SE) in the trachea, 37 ± 6 in the bronchi, 21 ± 3 in the bronchioles, and 16 ± 2 in the respiratory bronchioles. At any given NO concentration, the NO absorption rate (in nl/min) equaled the NO concentration (in ppb) times A (the absorption coefficient in l/min). A values (in l/min) were 0.11 ± 0.01 in the trachea, 0.17 ± 0.04 in the bronchi, 0.66 ± 0.09 in the bronchioles, and 1.35 ± 0.32 in the respiratory bronchioles. NO equilibrium concentrations and production rates in one 74-yr-old subject were three to five times as high as those found in the young subjects. Mouth equilibrium NO concentrations were 3 and 6 parts per million in two subjects who had oral production rates of 6 and 23 nl/min, respectively. In conclusion, production and absorption of NO occur throughout the first 450 ml of the airways.
Splenic contraction-induced reversible increase in hemoglobin concentration in intermittent hypoxia
Authors: Kuwahira Ichiro , Kamiya Uguri , Iwamoto Tokuzen , Moue Yoshihiro , Urano Tetsuya , Ohta Yasuyo , Gonzalez Norberto C.
Published: December 2017

The effect of intermittent hypoxia (IHx) on blood hemoglobin concentration ([Hb]) and the underlying mechanisms were studied in rats exposed to 10% O2, 1 h/day, for up to 5 wk. IHx protocols with longer daily hypoxic exposure show persistent polycythemia; however, it is unknown whether [Hb] increases transiently during hypoxia in protocols without polycythemia. Hypoxia produced a reversible [Hb] increase after 4 days of IHx but not in normoxic controls (NxC) or after shorter period of IHx. Splenectomy abolished the phenomenon. Plasma epinephrine and norepinephrine levels during hypoxia were comparable in IHx and NxC groups, but the epinephrine-induced [Hb] increase was larger in IHx. The α1- and α2-adrenoreceptor blockade (phentolamine) and α2-blockade (yohimbine) abolished the [Hb] increase of IHx rats. Conversely, α2-receptor stimulation (oxymetazoline) increased [Hb] during normoxia in IHx but not in NxC. In conclusion, this IHx protocol results in reversible [Hb] increases during hypoxia via splenic contraction mediated by increased α2-adrenoreceptor response. This may protect O2supply during hypoxia without the cardiovascular burden of polycythemia during normoxia.
Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women
Authors: Stephenson Lou A. , Kolka Margaret A. ,   (With the Technical Assistance of Jane De Luca)
Published: December 2017

The purpose of this study was to test the hypothesis that regulated body temperature is decreased in the preovulatory phase in eumenorrheic women. Six women were studied in both the preovulatory phase (Preov-2; days 9–12), which was 1–2 days before predicted ovulation when 17β-estradiol (E2) was estimated to peak, and in the follicular phase (F; days 2–6). The subjects walked on a treadmill (∼225 W ⋅ m−2) in a warm chamber (ambient temperature = 30°C; dew-point temperature = 11.5°C) while heavily clothed. E2, esophageal temperature (Tes), local skin temperatures, and local sweating rate were measured. The estimate of when the E2 surge would occur was correct for four of six subjects. In these four subjects, E2 increased ( P ≤ 0.05) from 42.0 ± 24.5 pg/ml during F to 123.2 ± 31.3 pg/ml during Preov-2. Resting Tes was 37.02 ± 0.20°C during F and 36.76 ± 0.28°C during Preov-2 ( P ≤ 0.05). The Tes threshold for sweating was decreased ( P ≤ 0.05) from 36.88 ± 0.27°C during F to 36.64 ± 0.35°C during Preov-2. Both mean skin and mean body temperatures were decreased during rest in Preov-2 group. The hypothesis that regulated body temperature is decreased during the preovulatory phase is supported.
Ozone-induced pulmonary inflammation and epithelial proliferation are partially mediated by PAF
Authors: Longphre M. , Zhang L.-Y. , Harkema J. R. , Kleeberger S. R.
Published: December 2017

Ozone (O3) exposure stimulates airway inflammation and epithelial sloughing in a number of species, including mice. Platelet-activating factor (PAF) is a lipid mediator released by activated mast cells, macrophages, and epithelial cells and causes pulmonary inflammation and hyperpermeability. We hypothesized that the activation of PAF receptors is central to the development of inflammation and epithelial injury induced by acute O3exposure in mice. To test this hypothesis, O3-susceptible C57BL/6J mice were treated with a PAF-receptor antagonist, UK-74505, or vehicle either before or immediately after 3-h exposure to O3(2 parts/million) or filtered air. Bronchoalveolar lavage (BAL) fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage were used as indicators of inflammation in the airways. O3-induced epithelial injury was assessed by light microscopy, and DNA synthesis in epithelium of terminal bronchioles was estimated by using a bromodeoxyuridine-labeling index. Intercellular adhesion molecule 1 (ICAM-1) expression was also examined in the lung by immunohistochemical localization. O3caused significant increases in polymorphonuclear leukocytes and protein in the BAL fluid, increased pulmonary epithelial proliferation, and increased epithelial expression of ICAM-1 compared with air-exposed, vehicle-treated control mice. Relative to O3-exposed, vehicle-treated control mice, UK-74505 before exposure significantly ( P < 0.05) decreased BAL protein, polymorphonuclear leukocytes, and epithelial cells. O3-induced inflammation was similarly attenuated in mice treated with UK-74505 after exposure. These experiments thus support the hypothesis that O3-induced airways inflammation and epithelial damage in mice are partially mediated by activation of PAF receptors, possibly through modulation of ICAM-1 expression.
Rat hindlimb muscle blood flow during level and downhill locomotion
Authors: Delp Michael D. , Duan Changping , Ray Chester A. , Armstrong R. B.
Published: December 2017

During eccentrically biased exercise (e.g., downhill locomotion), whole body oxygen consumption and blood lactate concentrations are lower than during level locomotion. These general systemic measurements indicate that muscle metabolism is lower during downhill exercise. This study was designed to test the hypothesis that hindlimb muscle blood flow is correspondingly lower during downhill vs. level exercise. Muscle blood flow (determined by using radioactive microspheres) was measured in rats after 15 min of treadmill exercise at 15 m/min on the level (L, 0°) or downhill (D, −17°). Blood flow to ankle extensor muscles was either lower (e.g., white gastrocnemius muscle: D, 9 ± 2; L, 15 ± 1 ml ⋅ min−1⋅ 100 g−1) or not different (e.g., soleus muscle: D, 250 ± 35; L, 230 ± 21 ml ⋅ min−1⋅ 100 g−1) in downhill vs. level exercise. In contrast, blood flow to ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 ± 5; L, 31 ± 6 ml ⋅ min−1⋅ 100 g−1) during downhill vs. level exercise. When individual extensor and flexor muscle flows were summed, total flow to the leg was lower during downhill exercise (D, 3.24 ± 0.08; L, 3.47 ± 0.05 ml/min). These data indicate that muscle blood flow and metabolism are lower during eccentrically biased exercise but are not uniformly reduced in all active muscles; i.e., flows are equivalent in several ankle extensor muscles and higher in ankle flexor muscles.
Expiratory flow limitation during exercise in competition cyclists
Authors: Mota Susana , Casan Pere , Drobnic Franchek , Giner Jordi , Ruiz Olga , Sanchis Joaquín , Milic-Emili Joseph
Published: December 2017

In some trained athletes, maximal exercise ventilation is believed to be constrained by expiratory flow limitation (FL). Using the negative expiratory pressure method, we assessed whether FL was reached during a progressive maximal exercise test in 10 male competition cyclists. The cyclists reached an average maximal O2 consumption of 72 ml ⋅ kg−1 ⋅ min−1(range: 67–82 ml ⋅ kg−1 ⋅ min−1) and ventilation of 147 l/min (range: 122–180 l/min) (88% of preexercise maximal voluntary ventilation in 15 s). In nine subjects, FL was absent at all levels of exercise (i.e., expiratory flow increased with negative expiratory pressure over the entire tidal volume range). One subject, the oldest in the group, exhibited FL during peak exercise. The group end-expiratory lung volume (EELV) decreased during light-to-moderate exercise by 13% (range: 5–33%) of forced vital capacity but increased as maximal exercise was approached. EELV at peak exercise and at rest were not significantly different. The end-inspiratory lung volume increased progressively throughout the exercise test. The conclusions reached are as follows: 1) most well-trained young cyclists do not reach FL even during maximal exercise, and, hence, mechanical ventilatory constraint does not limit their aerobic exercise capacity, and 2) in absence of FL, EELV decreases initially but increases during heavy exercise.
Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats
Authors: Risby Terence H. , Jiang Long , Stoll Sigfried , Ingram Donald , Spangler Edward , Heim Jane , Cutler Richard , Roth George S. , Rifkind Joseph M.
Published: December 2017

Breath ethane, O2consumption, and CO2 production were analyzed in 24-mo-old female Fischer 344 rats that had been fed continuously ad libitum (AL) or restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a glass chamber that was first flushed with air, then with a gas mixture containing 12% O2. After equilibration, a sample of the outflow was collected in gas sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels were also directly monitored in the outflow of the chamber. O2 consumption and CO2 production increased for DR rats. Hypoxia decreased O2consumption and CO2 production for the AL-fed and DR rats. These changes reflect changes in metabolic rate due to diet and [Formula: see text]. A significant decrease in ethane generation was found in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of ethane generation increased, resulting in a DR-associated decrease in ethane from 2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR reduces the level of oxidative stress.
Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure in the isolated heart
Authors: Slovut David P. , Wenstrom John C. , Moeckel Richard B. , Salerno Christopher T. , Park Soon J. , Osborn John W.
Published: December 2017

A goal of clinicians caring for heart transplant recipients has been to use heart rate variability as a noninvasive means of diagnosing graft rejection. The determinants of beat-to-beat variability in the surgically denervated heart have yet to be elucidated. We used an isolated, blood buffer-perfused porcine heart preparation to quantitatively assess the relationship between coronary perfusion and sinus node automaticity. Hearts ( n = 9) were suspended in a Langendorff preparation, and heart rate (HR) fluctuations were quantified while perfusion pressure was modulated between 70/50, 80/60, 90/70, and 100/80 mmHg at 0.067 Hz. In 32 of 32 recordings, the cross spectrum of perfusion pressure vs. HR showed the largest peak centered at 0.067 Hz. In eight of nine experiments during nonpulsatile perfusion, HR accelerated as perfusion pressure was increased from 40 to 110 mmHg (mean increase 24.2 ± 3.0 beats/min). HR increased 0.34 beats/min per mmHg increase in perfusion pressure (least squares linear regression y = −25.8 mmHg + 0.34 x; r = 0.88, P < 0.0001). Administration of low- and high-dose nitroglycerin (Ntg) resulted in a modest increase in flow but produced a significant decrease in HR and blunted the response of HR to changes in perfusion pressure (HR increase 0.26 beats ⋅ min−1 ⋅ mmHg−1, r = 0.87, P < 0.0001 after low-dose Ntg; 0.25 beats ⋅ min−1 ⋅ mmHg−1, r = 0.78, P < 0.0001 after high-dose Ntg). These experiments suggest that sinus node discharge in the isolated perfused heart is mechanically coupled to perfusion pressure on a beat-to-beat basis.
Phosphorescence quenching method for measurement of intracellular P O 2 in isolated skeletal muscle fibers
Authors: Hogan Michael C.
Published: December 2017

Values of skeletal muscle intracellular[Formula: see text] during conditions ranging from rest to maximal metabolic rates have been difficult to quantify. A method for measurement of intracellular[Formula: see text] in isolated single skeletal muscle fibers by using O2-dependent quenching of a phosphorescent-O2probe is described. Intact single skeletal muscle fibers from Xenopus laevis were dissected from the lumbrical muscle and mounted in a glass chamber containing Ringer solution at 20°C. The chamber was placed on the stage of an inverted microscope configured for epi-illumination. A solution containing palladium- meso-tetra (4-carboxyphenyl) porphine bound to bovine serum albumin was injected into single fibers by micropipette pressure injection. Phosphorescence-decay curves (average of 10 rapid flashes) were recorded every 7 s from single cells ( n = 24) in which respiration had been eliminated with NaCN, while the [Formula: see text]of the Ringer solution surrounding the cell was varied from 0 to 159 Torr. For each measurement, the phosphorescence lifetime was calculated at the varied extracellular [Formula: see text] by obtaining a best-fit estimate by using a monoexponential function. The phosphorescence lifetime varied from 40 to 70 μs at an extracellular[Formula: see text] of 159 Torr to 650–700 μs at 0 Torr. The phosphorescent lifetimes for the varied[Formula: see text] were used to calculate, by using the Stern-Volmer relationship, the phosphorescence-quenching constant (100 Torr−1⋅ s−1), and the phosphorescence lifetime in a zero-O2environment (690 μs) for the phosphor within the intracellular environment. This technique demonstrates a novel method for determining intracellular[Formula: see text] in isolated single skeletal muscle fibers.
Influence of central antitussive drugs on the cough motor pattern
Authors: Bolser Donald C. , Hey John A. , Chapman Richard W.
Published: December 2017

The present study was conducted to determine the effects of administration of centrally active antitussive drugs on the cough motor pattern. Electromyograms of diaphragm and rectus abdominis muscles were recorded in anesthetized, spontaneously breathing cats. Cough was produced by mechanical stimulation of the intrathoracic trachea. Centrally acting drugs administered included codeine, morphine, dextromethorphan, baclofen, CP-99,994, and SR-48,968. Intravertebral artery administration of all drugs reduced cough number (number of coughs per stimulus trial) and rectus abdominis burst amplitude in a dose-dependent manner. Codeine, dextromethorphan, CP-99,994, SR-48,968, and baclofen had no effect on cough cycle timing (CTtot) or diaphragm amplitude during cough, even at doses that inhibited cough number by 80–90%. Morphine lengthened CTtotand inhibited diaphragm amplitude during cough, but these effects were not dose dependent. Only CP-99,994 altered the eupneic respiratory pattern. Central antitussive drugs primarily suppress cough by inhibition of expiratory motor drive and cough number. CTtotand inspiratory motor drive are relatively insensitive to the effects of these drugs. CTtotcan be controlled independently from cough number.
Breathing responses to small inspiratory threshold loads in humans
Authors: Yan Sheng , Bates Jason H. T.
Published: December 2017

To investiage the effect of inspiratory threshold load (ITL) on breathing, all previous work studied loads that were much greater than would be encountered under pathophysiological conditions. We hypothesized that mild ITL from 2.5 to 20 cmH2O is sufficient to modify control and sensation of breathing. The study was performed in healthy subjects. The results demonstrated that with mild ITL 1) inspiratory difficulty sensation could be perceived at an ITL of 2.5 cmH2O; 2) tidal volume increased without change in breathing frequency, resulting in hyperpnea; and 3) although additional time was required for inspiratory pressure to attain the threshold before inspiratory flow was initiated, the total inspiratory muscle contraction time remained constant. This resulted in shortening of the available time for inspiratory flow, so that the tidal volume was maintained or increased by significant increase in mean inspiratory flow. On the basis of computer simulation, we conclude that the mild ITL is sufficient to increase breathing sensation and alter breathing control, presumably aiming at maintaining a certain level of ventilation but minimizing the energy consumption of the inspiratory muscles.