bluuebunny/crossref_metadata_2025 huggingface dataset:
New in situ mouse model to quantify alveolar epithelial fluid clearance
Authors: Garat Chrystelle , Carter Ethan P. , Matthay Michael A.
Published: December 2017

Because the availability of transgenic mice makes it possible to examine the contribution of single genes to in vivo function, we developed a simple in situ mouse model that can be used to quantify isosmolar alveolar epithelial fluid clearance (AFC). Mice were killed, a tracheostomy was done, and then a test solution of a 5% isosmolar albumin solution with 0.1 μCi of125I-labeled albumin was instilled via the trachea into the distal air spaces of both lungs. After instillation, the lungs were inflated to 7 cmH2O with 100% O2 and maintained at 37°C by placing the animals under an infrared lamp. AFC was measured by the progressive increase in concentration of labeled and unlabeled protein over 1 h. The results indicated the following. 1) Basal, unstimulated AFC in mouse lungs was significantly faster than in ex vivo rat lungs (27 ± 5% in in situ mice vs. 11 ± 3% in ex vivo rat lungs; P < 0.05). 2) Comparison of equivalent doses (10−4 M) of β-adrenergic agonist (isoproterenol) and β2-adrenergic agonists (terbutaline and salmeterol) indicated that stimulated clearance occurred only in presence of isoproterenol. 3) Because atenolol, a specific β1-antagonist, abolished the effect of isoproterenol, the β-adrenergic stimulation appears to be mediated by β1-receptors. The rate of AFC in nonperfused mouse lungs was significantly faster than in prior studies of nonperfused lungs in rats and sheep. Interestingly, the stimulated clearance rate in mice was similar to the fast rates of AFC that we recently reported in patients recovering from hydrostatic pulmonary edema. This in situ model is a unique experimental preparation that can be readily used to quantify isosmolar epithelial fluid clearance in mice.
Regional deposition of inhaled particles in human lungs: comparison between men and women
Authors: Kim Chong S. , Hu S. C.
Published: December 2017

We measured detailed regional deposition patterns of inhaled particles in healthy adult male ( n = 11; 25 ± 4 yr of age) and female ( n = 11; 25 ± 3 yr of age) subjects by means of a serial bolus aerosol delivery technique for monodisperse fine [particle diameter ( D p) = 1 μm] and coarse aerosols ( D p = 3 and 5 μm). The bolus aerosol (40 ml half-width) was delivered to a specific volumetric depth (Vp) of the lung ranging from 100 to 500 ml with a 50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp, showing characteristic unimodal curves with respect to particle size and flow rate. However, the unevenness was more pronounced in women. LDF tended to be greater in all regions of the lung in women than in men for D p = 1 μm. For D p = 3 and 5 μm, LDF showed a marked enhancement in the shallow region of Vp ≤ 200 ml in women compared with men ( P < 0.05). LDF in women was comparable to or smaller than those of men in deep lung regions of Vp > 200 ml. Total lung deposition was comparable between men and women for fine particles but was consistently greater in women than men for coarse particles regardless of flow rates used: the difference ranged from 9 to 31% and was greater with higher flow rates ( P < 0.05). The results indicate that 1) particle deposition characteristics differ between healthy men and women under controlled breathing conditions and 2) deposition in women is greater than that in men.
Effect of continuous negative-pressure breathing on skin blood flow during exercise in a hot environment
Authors: Nagashima Kei , Nose Hiroshi , Takamata Akira , Morimoto Taketoshi
Published: December 2017

To assess the impact of continuous negative-pressure breathing (CNPB) on the regulation of skin blood flow, we measured forearm blood flow (FBF) by venous-occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest during exercise in a hot environment (ambient temperature = 30°C, relative humidity = ∼30%). Seven male subjects exercised in the upright position at an intensity of 60% peak oxygen consumption rate for 40 min with and without CNPB after 20 min of exercise. The esophageal temperature (Tes) in both conditions increased to 38.1°C by the end of exercise, without any significant differences between the two trials. Mean arterial pressure (MAP) increased by ∼15 mmHg by 8 min of exercise, without any significant difference between the two trials before CNPB. However, CNPB reduced MAP by ∼10 mmHg after 24 min of exercise ( P < 0.05). The increase in FBF and LDF in the control condition leveled off after 18 min of exercise above a Tes of 37.7°C, whereas in the CNPB trial the increase continued, with a rise in Tes despite the decrease in MAP. These results suggest that CNPB enhances vasodilation of skin above a Tes of ∼38°C by stretching intrathoracic baroreceptors such as cardiopulmonary baroreceptors.
Arousal and ventilatory responses during sleep in children with obstructive sleep apnea
Authors: Marcus Carole L. , Lutz Janita , Carroll John L. , Bamford Owen
Published: December 2017

Abnormal central regulation of upper airway muscles may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). We hypothesized that this was secondary to global abnormalities of ventilatory control during sleep. We therefore compared the response to chemical stimuli during sleep between prepubertal children with OSAS and controls. Patients with OSAS aroused at a higher[Formula: see text] (58 ± 2 vs. 60 ± 5 Torr, P < 0.05); those with the highest apnea index had the highest arousal threshold ( r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was a poor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responses were similar between patients with OSAS and controls; however, the sample size was small. We conclude that children with OSAS have slightly blunted arousal responses to hypercapnia. However, the overall ventilatory and arousal responses are normal in children with OSAS, indicating that a global deficit in respiratory drive is not a major factor in the etiology of childhood OSAS. Nevertheless, subtle abnormalities in ventilatory control may exist.
Alternate activity in the synergistic muscles during prolonged low-level contractions
Authors: Tamaki H. , Kitada K. , Akamine T. , Murata F. , Sakou T. , Kurata H.
Published: December 2017

The purpose of this study was to investigate the functional interrelationship between synergistic muscle activities during low-level fatiguing contractions. Six human subjects performed static and dynamic contractions at an ankle joint angle of 110° plantar flexion and within the range of 90–110° (anatomic position = 90°) under constant load (10% maximal voluntary contraction) for 210 min. Surface electromyogram records from lateral gastrocnemius (LG), medial gastrocnemius (MG), and soleus (Sol) muscles showed high and silent activities alternately in the three muscles and a complementary and alternate activity between muscles in the time course. In the second half of all exercise times, the number of changes in activity increased significantly ( P < 0.05) in each muscle. The ratios of active to silent periods of electromyogram activity were significantly higher ( P< 0.05) in MG (4.5 ± 2.2) and Sol (4.3 ± 2.8) than in the LG (0.4 ± 0.1), but no significant differences were observed between MG and Sol. These results suggest that the relative activation of synergistic motor pools are not constant during a low-level fatiguing task.
Antioxidants protect rat diaphragmatic muscle function under hypoxic conditions
Authors: Mohanraj Priya , Merola A. John , Wright Valerie P. , Clanton Thomas L.
Published: December 2017

In hypoxia, mitochondrial respiration is decreased, thereby leading to a buildup of reducing equivalents that cannot be transferred to O2at the cytochrome oxidase. This condition, called reductive stress, can paradoxically lead to enhanced formation of reactive O2species, or a decrease in the ability of the cell to defend against an oxidative stress. We hypothesized that antioxidants would protect tissues under conditions of hypoxia. Rat diaphragm strips were incubated in tissue baths containing one of four antioxidants: N-acetyl-l-cysteine, dimethyl sulfoxide, superoxide dismutase, or Tiron. The strips were directly stimulated in an electrical field. Force-frequency relationships were studied under baseline oxygenation (95% O2-5% CO2), after 30 min of hypoxia (95% N2-5% CO2), and 30 min after reoxygenation. In all tissues, antioxidants markedly attenuated the loss of contractile function during hypoxia ( P < 0.01) and also significantly improved recovery on reoxygenation ( P < 0.05). We conclude that both intracellular and extracellular antioxidants improve skeletal muscle contractile function in hypoxia and facilitate recovery during reoxygenation in an in vitro system. The strong influence of antioxidants during hypoxic exposure suggests that they can be as effective in protecting cell function in a reducing environment as they have been in oxidizing environments.
Cellular adaptations of skeletal muscles to cyclosporine
Authors: Biring Manmohan S. , Fournier Mario , Ross David J. , Lewis Michael I.
Published: December 2017

The aim of this study was to evaluate the cellular response of the diaphragm, extensor digitorum longus (EDL), and soleus (Sol) muscles to clinically relevant doses of cyclosporine administered to male rats over 4 wk. Control rats were provided with vehicle only. Muscle fiber types, cross-sectional areas, indexes of capillarity, and succinate dehydrogenase (SDH) activity were determined by quantitative histochemistry. Myosin heavy chain isoforms were identified by SDS-PAGE, and their proportions were measured by scanning densitometry. Serum cyclosporine level, 20–24 h after the last dose of cyclosporine, was 145 ± 81 ng/ml. Final body weight and muscle mass were similar between the cyclosporine and control groups. In the diaphragm, EDL, and Sol, no differences were observed between the groups with regard to fiber type proportions, fiber cross-sectional areas, and proportions of myosin heavy chain isoforms. In the EDL, reductions, both in SDH activity in type I, IIx, and IIb fibers (−26 to −37%) and in indexes of capillarity (−18 to −37%), were noted. In the Sol, SDH activity and capillarity were similar between the groups. In the diaphragm of cyclosporine-treated rats, there was significant reduction in the number of capillaries around individual fibers (−5%), whereas levels of SDH activity tended to be lower. This suggests that activation history may in part determine muscle-specific responses to cyclosporine. We speculate that reduced oxidative activity and capillarity of some limb muscles contribute to reduced exercise capacity and the “deconditioned state” observed in patients receiving cyclosporine after successful solid-organ transplantation.
Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic circulation in septic sheep
Authors: Bone Hans G. , Schenarts Paul J. , Fischer Stefanie R. , McGuire Roy , Traber Lillian D. , Traber Daniel L.
Published: December 2017

We investigated the effects of modified hemoglobin on regional blood flow and function of different organs during hyperdynamic sepsis. Fourteen sheep were surgically prepared for the study. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa bacteria was begun and maintained for 48 h. At 24 h, after a hyperdynamic circulation had developed, the animals were randomly assigned to two groups: 1) a treatment group ( n = 7) that received an infusion with 100 mg/kg pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) over 30 min and 2) a control group ( n = 7) that received only the vehicle. PHP infusion increased mean arterial pressure from 86 ± 2.8 to 101.8 ± 3.5 mmHg ( P < 0.05) and systemic vascular resistance index from 769 ± 42.1 to 1,087 ± 56.8 dyn ⋅ s ⋅ m2⋅ cm−5( P < 0.05). PHP infusion did not decrease regional blood flow, measured with fluorescent microspheres, below the baseline values in any of the analyzed tissues. None of the investigated blood chemistry variables showed any changes indicative of impaired organ function after PHP infusion. In our model of ovine sepsis we found no side effects after PHP infusion that would limit the use of PHP as a nitric oxide scavenger in sepsis.
Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs
Authors: Heller H. , Schuster K.-D.
Published: December 2017

The contribution of reaction resistance to overall resistance to pulmonary carbon monoxide (CO) uptake [DlCO/(ΘCO⋅ Vc), where DlCOis lung CO diffusing capacity, ΘCOis CO uptake conductance of erythrocytes, and Vc is pulmonary capillary blood volume] was determined in 10 anesthetized, paralyzed, and artificially ventilated rabbits. On the basis of the classical double-reciprocal equation of F. G. W. Roughton and R. E. Forster ( J. Appl. Physiol. 11: 290–302, 1957), DlCO/(ΘCO⋅ Vc) was obtained by solving the relation DlCO/(ΘCO⋅ Vc) = 1 − 2/(DlNO/DlCO), where DlNO/DlCOrepresents the ratio between the respective single-breath diffusing capacities (Dl) of nitric oxide (NO) and CO pulmonary capillary blood. The lungs of eight rabbits were inflated, starting from residual volume, by using 55 ml of indicator gas mixture (0.2% CO and 0.05% NO in nitrogen). Dl values were calculated by taking the end-tidal partial pressures of CO and NO as analyzed by using a respiratory mass spectrometer. The overall value was DlCO/(ΘCO⋅ Vc) = 0.4 ± 0.025 (mean ± SD). Because of the use of O2-free indicator gas mixtures, the end-tidal O2partial pressures were ∼21 Torr. In one other rabbit, the application of 0.2% CO and 0.001% NO yielded DlCO/(ΘCO⋅ Vc) = 0.39; in the tenth rabbit, however, inspiratory volume was varied, and an identical value was found at functional residual capacity. We conclude that the contribution of reaction resistance to overall resistance to pulmonary CO uptake is independent of the inspiratory NO concentration used, including, with respect to the pertinent literature, the conclusion that in rabbits, dogs, and humans this contribution amounts to 40% when determined at functional residual capacity.
Regional measurements of pulmonary edema by using magnetic resonance imaging
Authors: Caruthers S. D. , Paschal C. B. , Pou N. A. , Roselli R. J. , Harris T. R.
Published: December 2017

A three-dimensional magnetic resonance imaging (MRI) method to measure pulmonary edema and lung microvascular barrier permeability was developed and compared with conventional methods in nine mongrel dogs. MRIs were obtained covering the entire lungs. Injury was induced by injection of oleic acid (0.021–0.048 ml/kg) into a jugular catheter. Imaging followed for 0.75–2 h. Extravascular lung water and permeability-related parameters were measured from multiple-indicator dilution curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR). Postinjury wet-to-dry lung weight ratio was 5.30 ± 0.38 ( n = 9). Extravascular lung water increased from 2.03 ± 1.11 to 3.00 ± 1.45 ml/g ( n = 9, P < 0.01). Indicator dilution studies yielded parameters characterizing capillary exchange of urea and butanediol: the product of the square root of equivalent diffusivity of escape from the capillary and capillary surface area ( D 1/2 S) and the capillary permeability-surface area product ( PS). The ratio of D 1/2 Sfor urea to D 1/2 Sfor butanediol increased from 0.583 ± 0.027 to 0.852 ± 0.154 ( n = 9, P < 0.05). Whole lung SNR at baseline, before injury, correlated with D 1/2 Sand PS ratios (both P < 0.02). By using rate of SNR change, the mismatch of transcapillary filtration flow and lymph clearance was estimated to be 0.2–1.8 ml/min. The filtration coefficient was estimated from these values. Results indicate that pulmonary edema formation during oleic acid injury can be imaged regionally and quantified globally, and the results suggest possible regional quantification by using three-dimensional MRI.
Predictors of age-associated decline in maximal aerobic capacity: a comparison of four statistical models
Authors: Rosen Mitchell J. , Sorkin John D. , Goldberg Andrew P. , Hagberg James M. , Katzel Leslie I.
Published: December 2017

Studies assessing changes in maximal aerobic capacity (V˙o2 max) associated with aging have traditionally employed the ratio ofV˙o2 maxto body weight. Log-linear, ordinary least-squares, and weighted least-squares models may avoid some of the inherent weaknesses associated with the use of ratios. In this study we used four different methods to examine the age-associated decline inV˙o2 maxin a cross-sectional sample of 276 healthy men, aged 45–80 yr. Sixty-one of the men were aerobically trained athletes, and the remainder were sedentary. The model that accounted for the largest proportion of variance was a weighted least-squares model that included age, fat-free mass, and an indicator variable denoting exercise training status. The model accounted for 66% of the variance inV˙o2 maxand satisfied all the important general linear model assumptions. The other approaches failed to satisfy one or more of these assumptions. The results indicated thatV˙o2 maxdeclines at the same rate in athletic and sedentary men (0.24 l/min or 9%/decade) and that 35% of this decline (0.08 l ⋅ min−1⋅ decade−1) is due to the age-associated loss of fat-free mass.
Letters to the Editor
Authors: Mitzner Wayne , Wagner Elizabeth
Published: December 2017

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

Yuan, Huichin, Edward P. Ingenito, and Béla Suki. Dynamic properties of lung parenchyma: mechanical contributions of fiber network and interstitial cells. J. Appl. Physiol. 83(5): 1420–1431, 1997.—We investigated the contributions of the connective tissue fiber network and interstitial cells to parenchymal mechanics in a surfactant-free system. In eight strips of uniform dimension from guinea pig lung, we assessed the storage (G′) and loss (G") moduli by using pseudo-random length oscillations containing a specially designed set of seven frequencies from 0.07 to 2.4 Hz at baseline, during methacholine (MCh) challenge, and after death of the interstitial cells. Measurements were made at mean forces of 0.5 and 1 g and strain amplitudes of 5, 10, and 15% and were repeated 12 h later in the same, but nonviable samples. The results were interpreted using a linear viscoelastic model incorporating both tissue damping (G) and stiffness (H). The G′ and G" increased linearly with the logarithm of frequency, and both G and H showed negative strain amplitude and positive mean force dependence. After MCh challenge, the G′ and G" spectra were elevated uniformly, and G and H increased by <15%. Tissue stiffness, strain amplitude, and mean force dependence were virtually identical in the viable and nonviable samples. The G and hence energy dissipation were ∼10% smaller in the nonviable samples due to absence of actin-myosin cross-bridge cycling. We conclude that the connective tissue network may also dominate parenchymal mechanics in the intact lung, which can be influenced by the tone or contraction of interstitial cells.
Glycogen supercompensation masks the effect of a traininginduced increase in GLUT-4 on muscle glucose transport
Authors: Host Helen H. , Hansen Polly A. , Nolte Lorraine A. , Chen May M. , Holloszy John O.
Published: December 2017

Endurance exercise training induces a rapid increase in the GLUT-4 isoform of the glucose transporter in muscle. In fasted rats, insulin-stimulated muscle glucose transport is increased in proportion to the increase in GLUT-4. There is evidence that high muscle glycogen may decrease insulin-stimulated glucose transport. This study was undertaken to determine whether glycogen supercompensation interferes with the increase in glucose transport associated with an exercise-induced increase in GLUT-4. Rats were trained by means of swimming for 6 h/day for 2 days. Rats fasted overnight after the last exercise bout had an approximately twofold increase in epitrochlearis muscle GLUT-4 and an associated approximately twofold increase in maximally insulin-stimulated glucose transport activity. Epitrochlearis muscles of rats fed rodent chow after exercise were glycogen supercompensated (86.4 ± 4.8 μmol/g wet wt) and showed no significant increase in maximally insulin-stimulated glucose transport above the sedentary control value despite an approximately twofold increase in GLUT-4. Fasting resulted in higher basal muscle glucose transport rates in both sedentary and trained rats but did not significantly increase maximally insulin-stimulated transport in the sedentary group. We conclude that carbohydrate feeding that results in muscle glycogen supercompensation prevents the increase in maximally insulin-stimulated glucose transport associated with an exercise training-induced increase in muscle GLUT-4.
Exercise training enhances adrenergic constriction and dilation in the rat spinotrapezius muscle
Authors: Lash Julia M.
Published: December 2017

Treadmill training increases functional vasodilation in the rat spinotrapezius muscle, although there is no acute increase in blood flow and no increase in oxidative capacity. To assess concurrent changes in vascular reactivity, we measured arterial diameters in the spinotrapezius muscle of sedentary (Sed) and treadmill-trained (Tr; 9–10 wk; terminal intensity 30 m/min, 1.5° incline, for 90 min) rats during iontophoretic application of norepinephrine, epinephrine (Epi), and H+ (HCl) and during superfusion with adenosine. Terminal-feed arteries and first-order arterioles in Tr rats constricted more than those in Sed rats at the higher current doses of norepinephrine and Epi. In contrast, at low-current doses of Epi, first- and second-order arterioles dilated in Tr but not in Sed rats. The vascular responses to HCl were highly variable, but second-order arterioles of Tr rats constricted more than those of Sed rats at intermediate-current doses. There were no significant differences between Sed and Tr rats in the vascular responses to adenosine. Both adrenergic vasodilation and vasoconstriction were enhanced in the spinotrapezius muscle of Tr rats, and enhanced adrenergic vasodilation may contribute to increased functional vasodilation. These observations further demonstrate vascular adaptations in “nontrained” skeletal muscle tissues.
Thermoregulatory reflexes and cutaneous active vasodilation during heat stress in hypertensive humans
Authors: Kellogg D. L. , Morris S. R. , Rodriguez S. B. , Liu Y. , Grossmann M. , Stagni G. , Shepherd A. M. M.
Published: December 2017

During dynamic exercise in the heat, increases in skin blood flow are attenuated in hypertensive subjects when compared with normotensive subjects. We studied responses to passive heat stress (water-perfused suits) in eight hypertensive and eight normotensive subjects. Forearm blood flow was measured by venous-occlusion plethysmography, mean arterial pressure (MAP) was measured by Finapres, and forearm vascular conductance (FVC) was calculated. Bretylium tosylate (BT) iontophoresis was used to block active vasoconstriction in a small area of skin. Skin blood flow was indexed by laser-Doppler flowmetry at BT-treated and untreated sites, and cutaneous vascular conductance was calculated. In normothermia, FVC was lower in hypertensive than in normotensive subjects ( P < 0.01). During heat stress, FVC rose to similar levels in both groups ( P > 0.80); concurrent cutaneous vascular conductance increases were unaffected by BT treatment ( P > 0.60). MAP was greater in hypertensive than in normotensive subjects during normothermia ( P < 0.05, hypertensive vs. normotensive subjects). During hyperthermia, MAP fell in hypertensive subjects but showed no statistically significant change in normotensive subjects ( P < 0.05, hypertensive vs. normotensive subjects). The internal temperature at which vasodilation began did not differ between groups ( P> 0.80). FVC is reduced during normothermia in unmedicated hypertensive subjects; however, they respond to passive heat stress in a fashion no different from normotensive subjects.
IGF-I and/or growth hormone preserve diaphragm fiber size with moderate malnutrition
Authors: Lewis Michael I. , Feinberg Andrea T. , Fournier Mario
Published: December 2017

Resistance to the anabolic effects of growth hormone (GH) occurs with severe caloric deficit. This study examined whether moderate caloric deficit (50% of daily intake for 7 days) in the adolescent rat exceeds a critical threshold for GH action and whether a combination of GH and insulin-like growth factor I (IGF-I) would have enhanced anabolic effects on the diaphragm (Dia). Five groups of rats (4 wk old) were studied: 1) control (Ctl), 2) nutritionally deprived (ND), 3) ND + GH, 4) ND + IGF-I, and 5) ND + GH + IGF-I. IGF-I was given by continuous infusion (200 μg/day). GH was injected subcutaneously (250 μg every 12 h). Contractile and fatigue properties of the Dia were determined in vitro. Quantitative histochemical methods were used to determine Dia fiber type proportions, cross-sectional areas, and succinate dehydrogenase activities. The body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas that of ND rats receiving growth factors was intermediate. Serum IGF-I levels were reduced 54% in ND animals and maintained with the provision of growth factors. Dia fatigue resistance was improved in ND animals receiving growth factors. There were no differences in Dia contractile properties, fiber type proportions, or succinate dehydrogenase activities across groups. ND resulted in atrophy/growth arrest of all Dia fibers (20–32%) compared with Ctl. Administration of IGF-I and/or GH completely prevented atrophy/growth arrest of all Dia fibers. No additive or synergistic effects were noted. We propose that these growth factors may provide useful short-term adjunctive nutritional support in circumstances in which the provision of optimal nutrition may be delayed or inadequate.
Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects
Authors: Dirksen Asger , Holstein-Rathlou Niels-Henrik , Madsen Flemming , Skovgaard Lene T. , Ulrik Charlotte S. , Heckscher Thomas , Kok-Jensen Axel
Published: December 2017

In obstructive lung disease the annual change in lung function is usually estimated from serial measurements of forced expiratory volume in 1 s (FEV1). Frequent measurements in each patient may not improve this estimate because data are not statistically independent; i.e., the measurements are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe α1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self-administered spirometry. FEV1measurements fulfilling standard criteria were detrended, and the autocorrelation profile and the power spectrum were calculated. On average the subjects were followed for >3 yr and performed >1,000 acceptable spirometries. The autocorrelation of FEV1 measurements in the emphysematous patients was ∼0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of −0.1 at ∼8 mo and then increased toward zero over the following 12 mo. The autocorrelation function in the two normal subjects showed a similar pattern, but with a faster decay toward zero. In the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/ f pattern, where f is frequency, with a slope of −0.88 at lower frequencies. We conclude that serial spirometric measurements show long-range correlations. The practical implication is that FEV1 need not be measured more often than once every 3 mo in studies of the long-term trends in lung function.
Repetitive prenatal glucocorticoid therapy reduces oxidative stress in the lungs of preterm lambs
Authors: Walther Frans J. , Jobe Alan H. , Ikegami Machiko
Published: December 2017

Repetitive courses of maternal prenatal glucocorticoids are often used in high-risk pregnancies with threatening preterm labor to induce lung maturation, but the effects on the cellular oxidant-antioxidant balance in the fetal lung have not been evaluated. We investigated the effect of repetitive treatment with glucocorticoids, beginning early in gestation, on oxidative stress in the preterm ovine lung. Pregnant ewes were randomized to receive one, two, three, or four doses of 0.5 mg/kg betamethasone or saline placebo at 7-day intervals on 104, 111, 118, and 124 days gestation ( n = 11 for each group). All lambs were delivered preterm at 125 days gestation, and lung tissue was assayed for antioxidant enzymes, lipid hydroperoxides, and carbonyl proteins. Lung manganese superoxide dismutase, catalase, and glutathione peroxidase activity increased after 1 dose of betamethasone given at 104 days gestation, whereas copper-zinc superoxide dismutase activity increased after 2 doses given at 104 and 111 days gestation. The activity of all four antioxidant enzymes further increased with additional doses and was maximal after four doses of betamethasone. Lung lipid hydroperoxide levels and carbonyl protein content decreased stepwise after each dose of betamethasone and were lowest after four doses. Repetitive prenatal glucocorticoid therapy increases antioxidant enzyme activity and reduces oxidative stress in the lungs of preterm lambs, and these effects begin early in gestation and persist for 2–3 wk.
Alae nasi activation decreases nasal resistance during hyperoxic hypercapnia
Authors: Shi Yong-Xin , Seto-Poon Margaret , Wheatley John R.
Published: December 2017

It has been proposed that decreases in nasal resistance (Rn) during hypercapnia are entirely due to vasoconstriction in the nasal cavity. We hypothesized that alae nasi (AN) muscle activity dilates the nasal vestibule and contributes to the decrease in Rn during hypercapnia. Nine normal subjects were studied during hyperoxic hypercapnia (HH). Rn and vestibular resistance (Rvest) for one nasal passage were measured simultaneously with the AN electromyogram before and after nasal decongestion. HH decreased Rvest from 1.6 ± 0.6 to 0.8 ± 0.9 cmH2O ⋅ l−1 ⋅ s (predecongestant) and from 1.3 ± 0.8 to 0.6 ± 0.7 cmH2O ⋅ l−1 ⋅ s (postdecongestant; both P < 0.01). Nasal decongestant decreased Rn but not Rvest. Significant inverse linear relationships between Rvest and AN electromyogram were demonstrated for all subjects. We conclude that in normal subjects during HH 1) decreases in Rvest are predominantly due to increases in AN activity; and 2) decreases in Rn are due to a combination of mucosal vasoconstriction and AN activation.
Impaired reactivity of rat aorta to phenylephrine and KCl after prolonged hypoxia: role of the endothelium
Authors: Auer Grant , Ward Michael E.
Published: December 2017

The hemodynamic response to reductions in systemic oxygen availability serves to redistribute blood flow and maintain vital organ function. The efficacy of this response depends on the degree to which hypoxia alters the function of the vascular tissues themselves. In this study we have evaluated these effects in rats exposed to 10% oxygen for 0 (control), 12, and 48 h and for 48 h followed by 12 h of normoxic recovery. In aortic segments from each group, the cumulative concentration response relationships were constructed for phenylephrine and KCl. Maximum tension generated during activation by these agents was reduced after both 12 and 48 h of hypoxic exposure. After 48 h of hypoxia, the maximum tension during activation by phenylephrine was 0.46 ± 0.04 vs. 1.31 ± 0.09 g/mg dry wt for the control group ( P< 0.05 for difference). The maximum tension during activation by KCl was similarly affected (0.32 ± 0.02 vs. 0.98 ± 0.06 g/mg dry wt, 48 h of hypoxia vs. control, respectively; P < 0.05 for difference). Exposure to hypoxia did not alter the EC50 for either agent. Twelve hours of normoxic recovery did not fully restore contractility after 48 h of hypoxia. In aortic rings from control rats, endothelial removal enhanced contraction, whereas, in rings from rats exposed to hypoxia, removal of the endothelium was associated with a decrease in maximum tension. Prolonged exposure to hypoxia results in impairment of systemic arterial smooth muscle contractility. This is partly compensated by the release of vasoconstricting substances from the endothelium.
Metabolic and performance responses during endurance exercise after high-fat and high-carbohydrate meals
Authors: Whitley Helena A. , Humphreys S. M. , Campbell I. T. , Keegan M. A. , Jayanetti T. D. , Sperry D. A. , MacLaren D. P. , Reilly T. , Frayn K. N.
Published: December 2017

We studied the effects of preexercise meal composition on metabolic and performance-related variables during endurance exercise. Eight well-trained cyclists (maximal oxygen uptake 65.0 to 83.5 ml ⋅ kg−1⋅ min−1) were studied on three occasions after an overnight fast. They were given isoenergetic meals containing carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body wt): high-carbohydrate meal, 215 CHO, 26 P, 3 F; high-fat meal, 50 CHO, 14 P, 80 F. On the third occasion subjects were studied after an overnight fast. Four hours after consumption of the meal, subjects started exercise for 90 min at 70% of their maximal oxygen uptake, followed by a 10-km time trial. The high-carbohydrate meal compared with the high-fat meal resulted in significant decreases ( P < 0.05) in blood glucose, plasma nonesterified fatty acids, plasma glycerol, plasma chylomicron-triacylglycerol, and plasma 3-hydroxybutyrate concentrations during exercise. This was accompanied by an increase in plasma insulin ( P < 0.01 vs. no meal), plasma epinephrine, and plasma growth hormone concentrations (each P < 0.05 vs. either of the other conditions) during exercise. Despite these large differences in substrate and hormone concentrations in plasma, substrate oxidation during the 90-min exercise period was similar in the three trials, and there were no differences in performance on the time trial. These results suggest that, although the availability of fatty acids and other substrates in plasma can be markedly altered by dietary means, the pattern of substrate oxidation during endurance exercise is remarkably resistant to alteration.
Effects of CO2-induced acidification on the fatigue resistance of single mouse muscle fibers at 28°C
Authors: Bruton Joseph D. , Lännergren Jan , Westerblad Håkan
Published: December 2017

The role of reduced muscle pH in the development of skeletal muscle fatigue is unclear. This study investigated the effects of lowering skeletal muscle intracellular pH by exposure to 30% CO2on the number of isometric tetani needed to induce significant fatigue. Isolated single mouse muscle fibers were stimulated repetitively at intervals of 4–2.5 s by using 80-Hz, 400-ms tetani at 28°C in Tyrode solution bubbled with either 5 or 30% CO2. Stimulation continued until tetanic force had fallen to 40% of the initial value. Exposure to 30% CO2caused a significant fall in intracellular pH of ∼0.3 pH unit but did not cause any significant changes in initial peak tetanic force. During the course of repetitive stimulation, intracellular pH fell by ∼0.3 pH unit in both normal and acidified fibers. The number of tetani needed to reduce force to 40% of the initial value was not significantly different in 5 and 30% CO2Tyrode. The sole effect of acidosis was to reduce the rate of relaxation of force, especially in fatigued fibers. It is concluded that, at 28°C, acidosis per se does not accelerate the development of fatigue during repeated tetanic stimulation of isolated mouse skeletal muscle fibers.
Regional differences in endothelial function in horse lungs: possible role in blood flow distribution?
Authors: Pelletier Nicolas , Robinson N. Edward , Kaiser Lana , Derksen Frederik J.
Published: December 2017

We investigated regional differences of in vitro responses of pulmonary arteries (6-mm OD) from the dorsocaudal (top) and cranioventral (bottom) lung regions to endothelium-dependent vasodilators (methacholine, bradykinin, and calcium ionophore A-23187). Methacholine relaxed endothelium-intact top vessels; however, in bottom vessels, a small relaxation preceded a profound contraction. In top vessels, removal of endothelial cells converted relaxation to contraction, and in bottom vessels it abolished relaxation and enhanced contraction. Bradykinin and A-23187 were more potent and caused greater endothelium-mediated relaxation in top than in bottom arteries. The endothelium-independent vasodilator sodium nitroprusside caused similar relaxations in all rings. Nω-nitro-l-arginine and NG-monomethyl-l-arginine and methylene blue abolished relaxation of top and bottom arteries to methacholine; meclofenamate had little effect. We conclude that regional differences in endothelium-mediated relaxation are caused by differences in the magnitude of the endothelial release of nitric oxide. Similar differences in endothelium-dependent flow-mediated vasodilation and endothelial nitric oxide release may result in preferential perfusion of caudodorsal lung regions.
Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space
Authors: Bennett William D. , Scheuch Gerhard , Zeman Kirby L. , Brown James S. , Kim Chong , Heyder Joachim , Stahlhofen Willi
Published: December 2017

The fractional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the relative volume and size of an individual’s airways. To evaluate the effect of variable anatomic dead space (ADS) on aerosol bolus delivery we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5 μm mean mondispersed aerosol diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at a lung volume of 70% total lung capacity end inhalation. By using filter techniques, aerosol photometry, and gamma camera analysis, we estimated the fraction of the inhaled boluses deposited in intrathoracic airways (IDF). ADS by single-breath N2 washout was also measured from 70% total lung capacity. Results showed that among all subjects IDF was variable (range = 0.04–0.43, coefficient of variation = 0.54) and increased with decreasing ADS ( r = −0.76, P = 0.001, n = 16). We found significantly greater deposition in the left (L) vs. right (R) lungs; mean L/R (ratio of deposition in L lung to R lung, normalized to ratio of L-to-R lung volume) was 1.58 ± 0.42 (SD; P < 0.001 for comparison with 1.0). Retention of deposited particles at 2 h was independent of ADS or IDF. There was significant retention of particles at 24 h postdeposition (0.27 ± 0.05) and slow clearance of these particles continued through 48 h postdeposition. Finally, analysis of central-to-peripheral ratios of initial deposition and 24-h-retention gamma-camera images suggest significant retention of insoluble particles in large bronchial airways at 24 h postdeposition (i.e., 24 h central-to-peripheral ratio = 1.40 ± 0.44 and 1.82 ± 0.54 in the R and L lung, respectively; P < 0.02 for comparison with 1.0). These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.
Effects of microgravity and bone morphogenetic protein II on GFAP in rat brain
Authors: Day J. R. , Frank A. T. , O’Callaghan J. P. , DeHart B. W.
Published: December 2017

This study evaluated effects of bone morphogenetic protein II (BMP) on glial fibrillary acidic protein (GFAP) in the brain of female Fischer 344 rats during 14 days of spaceflight. GFAP mRNA decreased in vehicle-implanted rats flown on the space shuttle by 53 and 48% in the stratum moleculare and stratum lacunosum moleculare hippocampal subregions, respectively. GFAP mRNA was not significantly affected by BMP implantation during spaceflight. Rats returning from space exhibited a 56% increase in serum corticosterone. BMP treatment did not additively increase corticosterone elevations in microgravity but appeared to increase serum corticosterone and reduce GFAP mRNA in the stratum moleculare in control rats. These data suggest that exposure to microgravity reduces GFAP expression in hippocampal astrocytes.
Development of a model of complete heart block in rats
Authors: Lee Randall J. , Sievers Richard E. , Gallinghouse G. Joseph , Ursell Philip C.
Published: December 2017

Atrioventricular (AV) block is a useful substrate for the study of cardiac physiology. The objective of this investigation was to develop a straightforward and reproducible model of permanent AV block in rats. Working through a sternotomy, we used an epicardial fat pad between the aortic root and the right atrial wall of the rat as a landmark for the site for injection of 70% ethanol (5–10 μl) into the myocardium 3 mm below the epicardial surface. Stable, complete heart block was produced in 23 of 28 rats (82%) with a success rate of 100% in the last 16 rats of the series. Saline injection produced no heart block in 15 rats. A separate group of 14 animals was allowed to recover. Chronic heart block was achieved in all ethanol-injected animals for up to 7 days before death. The survival rate in the recovered rats was 90% in the ethanol-injected group and 100% in the saline-injected control group. Acute hemodynamic changes following the production of heart block consisted of an increase in central venous pressure, a decrease in systolic blood pressure, a decrease in left ventricular pressure, and a decrease in change in pressure over time. Chronic hemodynamic changes demonstrated a return to baseline of the central venous pressure, a persistent decrease in systolic blood pressure, and a decrease in left ventricular pressure. After the rats were killed and the hearts were dissected, discrete areas of myocardial damage were identified histologically in the atrial septum near the AV conduction axis tissue in the ethanol-injected hearts. Complete heart block was associated only with lesions extending into the specialized muscle of the AV node or His bundle. Focal mild hemorrhage, inflammation, and damaged myocardial fibers were observed in the acute stage, whereas healing lesions were characterized by granulation tissue and fibrosis replacing conduction tissue. The simple technique described provides a reproducible model for permanent, complete heart block and the study of cardiac function.
Blood-gas measurements adjusted for temperature at three sites during incremental exercise in the horse
Authors: Taylor L. E. , Kronfeld D. S. , Ferrante P. L. , Wilson J. A. , Tiegs W.
Published: December 2017

Rectal temperature (Tre) is often used to adjust measurements of blood gases, but these adjusted measurements may not approximate temperatures during intense exercise at main sites of gas exchange: muscle and lung. To evaluate differences in blood gases between sites, temperatures (T) were measured with thermocouples in the rectum (re), in mixed venous blood (v), in gluteal muscle (mu), and on the skin (sk) in seven Arabian horses as they underwent an incremental exercise test on a treadmill. Blood samples were drawn from the carotid artery and pulmonary artery (mixed venous) 30 s before each increase in speed and during recovery. Blood gases and pH were measured at 37°C, and all variables were adjusted to Tre,[Formula: see text], and Tmu. Adjusted variables during exercise and recovery were significantly different from each other at the three sites. Linear and polynomial equations described the time course of venous temperature and[Formula: see text] from Treand Tskduring exercise and from Tskduring recovery. Interpretation of changes in muscle metabolism and gas exchanges based on blood-gas measurements is improved if they are adjusted appropriately to Tmuor[Formula: see text], which may be predicted from Tskin addition to Treduring strenuous exercise and from Tskduring recovery.
Regulation of the endogenous NO pathway by prolonged inhaled NO in rats
Authors: Frank Deborah U. , Horstman Damian J. , Morris Geoffrey N. , Johns Roger A. , Rich George F.
Published: December 2017

Nitric oxide (NO) modulates the endogenous NO-cGMP pathway. We determined whether prolonged inhaled NO downregulates the NO-cGMP pathway, which may explain clinically observed rebound pulmonary hypertension. Rats were placed in a normoxic (N; 21% O2) or hypoxic (H; 10% O2) environment with and without inhaled NO (20 parts/million) for 1 or 3 wk. Subsequently, nitric oxide synthase (NOS) and soluble guanylate cyclase (GC) activity and endothelial NOS (eNOS) protein levels were measured. Perfusate cGMP levels and endothelium-dependent and -independent vasodilation were determined in isolated lungs. eNOS protein levels and NOS activity were not altered by inhaled NO in N or H rats. GC activity was decreased by 60 ± 10 and 55 ± 11% in N and H rats, respectively, after 1 wk of inhaled NO but was not affected after 3 wk. Inhaled NO had no effect on perfusate cGMP in N lungs. Inhaled NO attenuated the increase in cGMP levels caused by 3 wk of H by 57 ± 11%, but there was no rebound in cGMP after 24 h of recovery. Endothelium-dependent vasodilation was not altered, and endothelium-independent vasodilation was not altered (N) or slightly increased (H, 10 ± 3%) by prolonged inhaled NO. In conclusion, inhaled NO did not alter the endogenous NO-cGMP pathway as determined by eNOS protein levels, NOS activity, or endothelium-dependent vasodilation under N and H conditions. GC activity was decreased after 1 wk; however, GC activity was not altered by 3 wk of inhaled NO and endothelium-independent vasodilation was not decreased.
Heavy snoring with upper airway resistance syndrome may induce intrinsic positive end-expiratory pressure
Authors: Lofaso Frédéric , Lorino Anne Marie , Fodil Redouane , D’Ortho Marie Pia , Isabey Daniel , Lorino Hubert , Goldenberg Françoise , Harf Alain
Published: December 2017

We studied eight heavy snorers with upper airway resistance syndrome to investigate potential effects of sleep on expiratory airway and lung resistance, intrinsic positive end-expiratory pressure, hyperinflation, and elastic inspiratory work of breathing (WOB). Wakefulness and non-rapid-eye-movement sleep with high- and with low-resistance inspiratory effort (H-RIE and L-RIE, respectively) were compared. No differences in breathing pattern were seen across the three conditions. In contrast, we found increases in expiratory airway and lung resistance during H-RIE compared with L-RIE and wakefulness (56 ± 24, 16 ± 4, and 11 ± 4 cmH2O ⋅ l−1 ⋅ s, respectively), with attendant increases in intrinsic positive end-expiratory pressure (5.4 ± 1.8, 1.4 ± 0.5, and 1.3 ± 1.3 cmH2O, respectively) and elastic WOB (6.1 ± 2.2, 3.7 ± 1.2, and 3.4 ± 0.7 J/min, respectively). The increase in WOB during H-RIE is partly caused by the effects of dynamic pulmonary hyperinflation produced by the increased expiratory resistance. Contrary to the Starling model, a multiple-element compliance model that takes into account the heterogeneity of the pharynx may explain flow limitation during expiration.