bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaled furosemide attenuates hyperpnea-induced obstruction and intra-airway thermal gradients
Authors: Gilbert I. A. , Lenner K. A. , Nelson J. A. , Wolin A. D. , Fouke J. M.
Published: December 2017

Inhaled furosemide attenuates exercise- and isocapnic hyperventilation-induced asthma; however, the mechanism for this phenomenon is unknown. Because the magnitude of the intra-airway thermal gradient that develops between the cooling of hyperpnea and the rewarming that occurs once hyperventilation ceases is directly related to the severity of thermally induced obstruction in humans, we wondered if furosemide blunted these temperature changes. To explore this issue, eight asthmatic subjects had tracheobronchial airstream temperature measures as they performed isocapnic hyperventilation with frigid air alone (HV) or with pretreatment with inhaled saline (S + HV) or 45 +/- 3 (SE) mg of furosemide (F + HV). HV and S + HV resulted in similar degrees of obstruction, whereas the mechanical decrements after F + HV were significantly less. In concert with this protective effect, F + HV resulted in less airstream cooling during hyperventilation and slower rewarming in the recovery period. Because the major source of heat to the airways is provided by its microcirculation, inhaled furosemide may be acting as a topical vasodilator serving to enhance heat availability and thus reducing the effective thermal burden of hyperpnea.
Pulmonary inflammatory cell response to sustained endotoxin administration
Authors: Wang C. Z. , Herndon D. N. , Traber L. D. , Yang S. F. , Cox R. A. , Nakazawa H. , Barrow R. E. , Traber D. L.
Published: December 2017

We have developed a model of human sepsis in sheep. Twenty-four hours after continuous infusion of Escherichia coli endotoxin (lipopolysaccharide) (10 ng.kg-1.min-1) was begun, pulmonary transvascular fluid flux was almost five times the baseline values, cardiac output was nearly doubled, and mean arterial pressure was reduced by approximately 20 mmHg. At this time, the animals were killed and their lungs were fixed by endotracheal installation of 2.5% glutaraldehyde at 25 cmH2O pressure. Morphometry was performed by point counting, and data were expressed as relative volume density. Pulmonary edema and congestion were observed in sheep receiving lipopolysaccharide, whereas sham controls appeared normal. There was an increase in interstitial volume density. There was a significant increase (P < 0.01) in volume density of the pulmonary intravasculature (180%), interstitial macrophages (270%), and mast cells (240%). The volume densities of intravascular and interstitial polymorphonuclear neutrophils also showed a small insignificant increase.
Effects of interleukin-2 on the pulmonary microvasculature in anesthetized sheep
Authors: Lei D. , Jerome E. H. , Douguet D. , Jesmok G. J. , Schuster D. P. , Johnson C. W. , Staub N. C.
Published: December 2017

Interleukin-2 (IL-2) is reputed to cause pulmonary microvascular injury. We studied the pulmonary and splanchnic microcirculation of anesthetized sheep after one dose (1.8 x 10(6) IU/kg) of IL-2 (n = 9) and after six doses (1.8 x 10(6) IU.kg-1.dose-1) of IL-2 over 3 days (n = 9). Seven control sheep received only 5% dextrose diluent. We measured hemodynamics and lymph dynamics in anesthetized sheep after the final dose of IL-2 or diluent. After one dose of IL-2, caudal mediastinal node (mainly pulmonary) lymph flow was stable, whereas thoracic duct lymph flow increased from a baseline of 54 +/- 6 to 124 +/- 22 ml/h. After 3 days of IL-2, the caudal mediastinal node lymph flow increased from 7.7 +/- 5.5 to 19.0 +/- 14.8 ml/h 5–6 h after the final dose of IL-2, and thoracic duct lymph flow increased from 84 +/- 43 to 143 +/- 42 ml/h. The lymph-to-plasma protein concentration ratio increased after IL-2 for thoracic duct but not for caudal mediastinal node lymph. The equilibration rate of 125I-albumin from plasma to caudal mediastinal node lymph did not change, whereas plasma-to-thoracic duct lymph equilibration was faster after both one dose and 3 days of IL-2. Positron emission tomography showed no increase in the pulmonary transcapillary escape rate for 68Ga-labeled transferrin or in extravascular lung water (n = 4). We conclude that IL-2 at doses two to three times those used clinically does not significantly injure the pulmonary microcirculation of sheep.
Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor function
Authors: Schultheis A. H. , Bassett D. J. , Fryer A. D.
Published: December 2017

The effect of acute ozone exposure on the function of efferent parasympathetic nerves, M3 muscarinic receptors on airway smooth muscle, and inhibitory M2 muscarinic receptors on the parasympathetic nerves was studied. Immediately after exposure to 2.0 ppm ozone for 4 h, guinea pigs became hyperresponsive to electrical stimulation of the vagus nerves. The normal airway response to intravenous cholinergic agonists at this time demonstrates normal M3 receptor function. M2 muscarinic receptors on the nerves, which normally inhibit release of acetylcholine, were dysfunctional after ozone exposure, as demonstrated by the failure of the muscarinic agonist pilocarpine to inhibit, and the failure of the M2 antagonist gallamine to potentiate, vagally mediated bronchoconstriction. Thus, loss of inhibitory M2 muscarinic receptor function after ozone exposure potentiates release of acetylcholine from the vagus nerves, increasing vagally mediated bronchoconstriction. By 14 days, postozone responses to vagal nerve stimulation were not different from those of air-exposed animals and the function of the neuronal M2 muscarinic receptor was normal, confirming that ozone-induced hyperresponsiveness is reversible.
Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture
Authors: Abraini J. H. , Gardette-Chauffour M. C. , Martinez E. , Rostain J. C. , Lemaire C.
Published: December 2017

Six commercial divers were investigated for neurological and psychosensorimotor responses during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture containing 49% hydrogen. Results showed only moderate neurological symptoms of high-pressure nervous syndrome, whereas the narcotic effect of hydrogen was detectable, as investigated by psychosensorimotor tests. Nevertheless, the divers successfully carried out the main purpose of the operational dive, which was to prove the feasability of such diving methods by connecting specific elements of an offshore oil installation. Finally, these data support the hypothesis that hydrogen can alleviate some of the symptoms of the high-pressure nervous syndrome and can constitute a useful gas for commercial diving, as it decreases the density of the breathing mixture and therefore improves the living conditions, work, and comfort of the divers. Nevertheless, the present results underscore the relevance of research on individual susceptibility to pressure environment regardless of the composition of the breathing mixture.
Clinical tests explain blunted cortisol responsiveness but not mild hypercortisolism in amenorrheic runners
Authors: De Souza M. J. , Luciano A. A. , Arce J. C. , Demers L. M. , Loucks A. B.
Published: December 2017

To investigate mechanisms of blunted adrenocortical responsiveness to exercise and mild hypercortisolism in amenorrheic runners, adrenocorticotropic hormone [ACTH-(1–24) 0.25 mg Cortrosyn] stimulation tests were performed in the presence and absence of overnight dexamethasone (1 mg) suppression (DX and NDX condition, respectively) in six eumenorrheic sedentary women (ES), nine eumenorrheic runners (ER), and nine amenorrheic runners (AR). Before the NDX stimulation test, plasma cortisol was higher (P < 0.001) in AR than in ER and ES. The cortisol response to the NDX stimulation test was blunted (P < 0.001) in AR but reached similar (P > 0.7) peak levels in all groups. Dexamethasone suppressed (P < 0.001) cortisol to similar (P > 0.5) levels (approximately 20 nmol/l) in all groups. In AR, cortisol responses to the DX test were larger (P < 0.03) than to the NDX test and similar (P > 0.6) in the three groups, again reaching comparable (P > 0.8) peak levels. The blunted cortisol response to stimulation in AR in the presence of their mild hypercortisolism appears to be due to a normal limitation in maximal adrenal secretory capacity. Extrapituitary modulators of adrenal responsiveness to ACTH may explain the mild hypercortisolism observed in AR, but limitations of these tests prevent a central negative-feedback defect or an intrinsic adrenal abnormality from being excluded until results of additional studies with even lower doses of dexamethasone and submaximal doses of ACTH-(1-24) are available.
Natural surfactant and hyperoxic lung injury in primates. I. Physiology and biochemistry
Authors: Huang Y. C. , Caminiti S. P. , Fawcett T. A. , Moon R. E. , Fracica P. J. , Miller F. J. , Young S. L. , Piantadosi C. A.
Published: December 2017

Surfactant dysfunction contributes to the pathophysiology of adult respiratory distress syndrome (ARDS), and we hypothesized that surfactant treatment would improve experimental ARDS produced by continuous exposure to hyperoxia. Twelve healthy male baboons (10–15 kg) were anesthetized, paralyzed, and mechanically ventilated with 2.5 cmH2O positive end-expiratory pressure (PEEP) for 96 h. Baboons were divided into three groups: 1) the O2 group (n = 5) received 100% O2, 2) the surfactant group (n = 5) received 100% O2 and aerosolized porcine surfactant, and 3) a control group (n = 2) was ventilated at fractional concentration of inspired O2 of 0.21 for 96 h to control for effects of anesthesia and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion (VA/Q) distribution was measured daily by multiple inert gas elimination technique. PEEP was increased once or twice daily to 10 cmH2O for 30 min to study its effects on measurements of VA/Q. At the end of experiments, lungs were obtained for biochemical analysis. Prolonged hyperoxia resulted in progressive worsening in VA/Q, hemodynamic deterioration, severe lung edema, and altered surfactant metabolism. Surfactant administration increased disaturated phosphatidylcholine in lavage fluid but did not improve lung edema or gas exchange. In the surfactant group, however, the addition of 10 cmH2O PEEP resulted in a greater degree of shunt reduction than did 2.5 cmH2O PEEP (47 vs. 31% in the O2 group, P < 0.05). We conclude that aerosolized porcine surfactant did not prevent pulmonary O2 injury in baboons, but it potentiated the shunt-reducing effect of PEEP.
Ventilatory responses to hypoxia in rats pretreated with nonpeptide NK1 receptor antagonist CP-96,345
Authors: De Sanctis G. T. , Green F. H. , Jiang X. , King M. , Remmers J. E.
Published: December 2017

This study reports experiments designed to evaluate the role of neurokinin-1 (NK1) receptors for substance P (SP) in the ventilatory response to acute hypoxia. Ventilation was measured by indirect plethysmography in eight unanesthetized unrestrained adult rats before and after bolus injection of 1, 5, or 10 mg/kg (ip) of CP-96,345 (Pfizer), a potent nonpeptide competitive antagonist of the SP NK1 receptor. Ventilation was measured while the rats breathed air or 8% O2–92% N2 with and without administration of SP antagonist. Pretreatment with CP-96,345 decreased the magnitude of the hypoxic response in a dose-dependent fashion. Minute ventilation in rats pretreated with CP-96,345 was reduced by 22.1% (P < 0.05) at the highest dose (10 mg/kg), largely because of an attenuation of the frequency component. Although both control and treated rats responded to hypoxia with a decrease in duration of inspiration and expiration rats pretreated with CP-96,345 displayed a smaller decrease in inspiration and expiration than control rats (P < 0.05). We have recently shown that neuropeptide-containing fibers are important for mediating the tachypnic response during acute isocapnic hypoxia in rats. The attenuation in minute ventilation at the highest dose (10 mg/kg) is comparable in magnitude to the attenuation observed with neonatal capsaicin treatment, which permanently ablates neuropeptide-containing unmyelinated fibers. Accordingly, this previously reported role of capsaicin-sensitive nerves in the hypoxic ventilatory response of rats is probably attributable to released SP acting at NK1 receptors. One of the likely sites of action of SP antagonists is the carotid body.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharyngeal myopathy of loaded upper airway in dogs with sleep apnea
Authors: Petrof B. J. , Pack A. I. , Kelly A. M. , Eby J. , Hendricks J. C.
Published: December 2017

Recent work indicates that upper airway dilator muscles of individuals with obstructive sleep apnea syndrome (OSAS) demonstrate an increased level of activity during wakefulness compared with normal subjects. In addition, massive bursts of pharyngeal dilator activity are associated with the termination of upper airway occlusive events during sleep. This complex pattern of altered pharyngeal dilator activation is also observed in the English bulldog, an animal model of OSAS. In the present study, it was hypothesized that such alterations in activity level might lead to changes in the structure of pharyngeal muscles in the bulldog. Full-thickness biopsies were obtained from two pharyngeal dilator muscles, the sternohyoid (SH) and geniohyoid, as well as a limb muscle, the anterior tibialis, in bulldogs (n = 5) and control dogs (n = 7). Immunohistochemical analysis of myosin heavy chain expression revealed an increased contribution of fast type II myosin heavy-chain fibers to SH in bulldogs. The bulldog SH also demonstrated increased connective tissue content compared with control dogs, consistent with the presence of fibrosis. Both pharyngeal dilators in the bulldog exhibited an elevated proportion of morphologically abnormal fibers indicative of ongoing or prior injury. No differences in any of the above parameters were seen between bulldogs and control dogs in the anterior tibialis limb muscle. We conclude that the chronic load and altered pattern of usage imposed on the upper airway dilators in OSAS lead to myopathic changes that may ultimately impair the ability of these muscles to maintain pharyngeal patency.
Endurance training fails to inhibit skeletal muscle glucose uptake during exercise
Authors: Sumida K. D. , Donovan C. M.
Published: December 2017

The effects of endurance training (running 30 m/min, 10% grade for 90 min, 5 days/wk for 12 wk) on skeletal muscle glucose uptake during steady-state exercise (running 20 m/min) were studied in fed rats. A bolus injection of 2-[1,2–3H]deoxyglucose was administered to assess the glucose metabolic index (R′g), an indicator of glucose uptake, in individual tissues of the animal. After 55 min of rest or moderate exercise, various tissues were analyzed for accumulation of phosphorylated 2-[1,2–3H]-deoxyglucose and/or glycogen content. No differences were observed between groups in the resting glycogen content for any of the muscle samples examined. Resting plasma glucose concentrations were not significantly different between groups. Furthermore, no significant differences were observed in R′g between groups for any of the muscle examined (tibialis anterior, extensor digitorum longus, soleus, white gastrocnemius, red gastrocnemius). During exercise, plasma glucose concentrations were not significantly different between groups. Exercise significantly elevated R′g above resting values in the tibialis anterior (5-fold), soleus (3-fold), and red gastrocnemius (7.5-fold). Despite an elevated R′g for specific muscles during exercise, no significant differences were observed in glucose uptake between groups for any tissue examined. Concomitantly, trained animals exhibited significantly less muscle glycogen depletion during exercise compared with control animals. Liver glycogen levels were also significantly higher post-exercise in trained vs. control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Spectral analysis of hemodynamics during infusions of epinephrine and norepinephrine in men
Authors: Tulen J. H. , Man in ′t Veld A. J. , Van Roon A. M. , Moleman P. , Van Steenis H. G. , Blankestijn P. J. , Boomsma F.
Published: December 2017

Spectral analysis of fluctuations in heart rate (HR) and arterial blood pressure (BP) during a 6-h infusion of epinephrine (15 ng.kg-1.min-1) or norepinephrine (30 ng.kg-1.min-1) in 10 normotensive males was used to analyze effects of peripheral sympathetic nervous system activity and adrenal medullary discharge on cardiovascular variability. Power spectra were calculated for each 5-min period for HR, systolic BP, and diastolic BP to yield power values for three frequency bands: low (0.02–0.06 Hz), mid (0.07–0.14 Hz), and high (0.15–0.40 Hz). Infusion of epinephrine and norepinephrine induced plasma concentrations of epinephrine and norepinephrine, respectively, within the high physiological range. Spectral analysis showed that low-frequency fluctuations of BP during infusions of epinephrine and midfrequency fluctuations of BP during infusion of norepinephrine changed in opposite directions. These fluctuations may represent different components of short-term cardiovascular control mechanisms during situations that mimic increased sympathoadrenal activity. No changes were observed in HR fluctuations or high-frequency fluctuations of BP after either catecholamine. Our data imply that changes in concentrations of circulating catecholamines cannot be unequivocally labeled as indexes of an altered sympathoadrenal involvement in short-term cardiovascular control.
Frequency dependence of pulmonary and chest wall mechanics in young and adult cats
Authors: Shardonofsky F. R. , Sato J. , Eidelman D. H.
Published: December 2017

The frequency (f) dependence of pulmonary and chest wall mechanics was assessed in nine kittens and four cats. Kittens and cats were anesthetized, paralyzed, and mechanically ventilated at various f between 0.13 and 1.6 Hz and 0.09 and 0.79 Hz, respectively. Resistance and dynamic compliance pertaining to the respiratory system (Rrs and Cdyn,rs), lungs (RL and Cdyn,L), and chest wall (RW and Cdyn,W) were estimated by fitting a single-compartment model to data obtained from regular ventilation. Static lung and chest wall compliances (Cst,L and Cst,W) were computed from quasi-static pressure-volume data. Lung tissue resistance (Rti) was estimated with alveolar capsules in open-chest animals. The f dependence of the two-compartment viscoelastic model of the respiratory system was assessed by computing the effective resistance [Rmod,rs(omega)] and compliance [Cmod,rs(omega)] from data obtained at the lowest experimental f. Both Cdyn,L and Cdyn,W decreased with increasing f in all animals. Cdyn,L/Cst,L and Cdyn,W/Cst,W were lower in kittens than in cats. RL and RW decreased markedly with f in all animals. Rti/RL showed a marked f dependence, its values being similar in both young and adult cats at their respective resting f. CstW/Cst,L ratio was higher in kittens than in cats. A better agreement was found between Cmod,rs(omega) and Cdyn,rs than between Rmod,rs(omega) and Rrs.
Epinephrine-induced in vivo muscle glycogen depletion enhances insulin sensitivity of glucose transport
Authors: Nolte L. A. , Gulve E. A. , Holloszy J. O.
Published: December 2017

Muscle glycogen depletion by means of exercise is associated with increased insulin-stimulated glucose transport activity. To determine whether reduction in muscle glycogen content independent of muscle contractions would increase glucose transport activity, rats were injected with epinephrine (20 micrograms/100 g body wt) or saline. Two hours later, epitrochlearis muscles were removed, washed thoroughly to remove epinephrine, and assayed for glucose transport activity with 3-O-methyl-D-glucose (3-MG). Muscle adenosine 3′,5′-cyclic monophosphate concentration was elevated 441% in muscles frozen immediately after removal from epinephrine-injected rats but had returned to control levels by the time 3-MG transport was measured. Prior exposure to epinephrine resulted in depletion of muscle glycogen [from 18.6 +/- 1.4 to 11.0 +/- 0.1 (SE) mumol glucose units/g wet wt] and a small increase in basal glucose transport activity (from 0.13 +/- 0.02 to 0.24 +/- 0.04 mumol 3-MG.ml-1 x 10 min-1, P < 0.05). A submaximally effective insulin concentration (30 microU/ml) induced a 70% greater increase in 3-MG transport in epinephrine-treated muscles than in controls (0.57 +/- 0.09 and 0.34 +/- 0.04 mumol.ml-1 x 10 min-1, respectively, P < 0.001). Response to a maximally effective concentration of insulin was unaltered by prior exposure to epinephrine. When epinephrine-induced glycogen depletion was prevented by prior injection with the beta-adrenergic antagonist propranolol, glucose transport activity was no longer enhanced by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of exercise on macrophage activation for antitumor cytotoxicity
Authors: Woods J. A. , Davis J. M. , Mayer E. P. , Ghaffar A. , Pate R. R.
Published: December 2017

Recent evidence suggests that exercise affects macrophage functions and that amount of exercise may be important. We determined effects of moderate (MOD) and exhaustive treadmill running (EXH) on 1) ability of macrophages to become activated for antitumor cytotoxicity after injection of heat-inactivated Propionibacterium acnes in vivo, 2) macrophage responsiveness to activating agents lipopolysaccharide and interferon-gamma, and 3) role of glucocorticoids and various macrophage metabolic products in modulating cytotoxicity in exercised animals. Male C3H/HeN mice were randomly assigned to MOD (18 m/min, 5% grade, 30 min/day) or EXH (18–35 m/min, 5%, 2–4 h) on a motor-driven treadmill. Control animals were kept in simulated treadmill lanes located directly over the runners. In general, both MOD and EXH increased cytotoxicity (42 and 22%, respectively, across all experiments; P < 0.05). Enhanced cytotoxicity was not due to altered macrophage adherence, tumor necrosis factor-alpha, interleukin-1 beta, or reactive oxygen species. Reactive nitrogen species were responsible for enhanced toxicity in EXH only. Macrophage cytotoxicity was further increased by lipopolysaccharide and interferon-gamma to a similar maximal level that was the same in all groups. Plasma corticosterone was elevated two- and fourfold in MOD and EXH, respectively, but there was no correlation between plasma corticosterone and macrophage cytotoxicity when compared across all groups even though cells were sensitive to steroid-mediated suppression in vitro. However, consistent with a corticosterone effect, EXH reduced the number of peritoneal macrophages elicited during P. acnes inflammation and abolished the typical exercise-induced increase in cytotoxicity of activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Differing effects of anesthetics on splanchnic arterial blood flow during hemorrhagic shock
Authors: Myers S. I. , Hernandez R. , Miller T. A.
Published: December 2017

The effect of anesthesia on splanchnic blood flow was examined during hemorrhagic shock and resuscitation. Sprague-Dawley rats were anesthetized with the inhalation anesthetic, methoxyflurane, or pentobarbital (65 mg/kg). Transonic Doppler flow probes were placed around the superior mesenteric artery (SMA) and the abdominal aorta, and the animals were subjected to acute hemorrhage (or sham) to 30 mmHg for 90 min followed by 30 min of resuscitation with shed blood (n = 6/group). At 90, 105, and 120 min, sham animals in both anesthetic groups showed comparable blood pressures with a 50% decrease in SMA and aortic blood flow. Acute hemorrhage decreased SMA blood flow by 94.5 +/- 0.01 and 86.0 +/- 2.8%, respectively, in the pentobarbital and methoxyflurane groups, with similar changes occurring in aortic blood flow. During resuscitation, arterial pressure remained significantly depressed and SMA blood flow decreased by 65% in the pentobarbital group, whereas blood pressure returned to control levels and SMA blood flow increased to 56% of control values (P < 0.001) in the methoxyflurane group. The findings indicate that the choice of anesthetic agent may significantly impact splanchnic blood flow and needs to be taken into account when designing experiments examining effects of hemorrhagic shock.
Effect of high blood flow on pulmonary vascular permeability to protein
Authors: Ehrhart I. C. , McCloud L. L. , Orfanos S. E. , Catravas J. D. , Hofman W. F.
Published: December 2017

The elevated cardiac output associated with exercise increases lung lymph flow and may increase extravascular lung water. However, it is not known if extremely elevated cardiac output alters pulmonary vascular permeability. The hematocrit-protein method was used to determine the solvent drag reflection coefficient, an index of vascular permeability to proteins, in the isolated blood-perfused canine lung lobe. Microvascular pressure was obtained by double vascular occlusion. Lobes filtered fluid during perfusion at normal flow, 0.451 +/- 0.005 l/min (LF; n = 8), or high flow, 2.319 +/- 0.080 l/min (HF; n = 7). In the LF, venous pressure was elevated to 19.0 +/- 0.5 Torr to induce filtration, whereas Pv was 3.3 +/- 0.1 Torr in the HF. In HF vs. LF, respectively, arterial pressure was 61.4 +/- 7.1 vs. 28.0 +/- 1.0 Torr (P < 0.05), microvascular pressure was 31.9 +/- 3.0 vs. 22.2 +/- 0.9 Torr (P < 0.05), and sigma was 0.52 +/- 0.07 vs. 0.51 +/- 0.02 (P > 0.05). The fivefold increase in blood flow did not alter pulmonary vascular permeability to proteins; however, the capillary filtration coefficient was fivefold greater in the HF vs. LF group (0.328 +/- 0.059 vs. 0.067 +/- 0.007; P < 0.002). These data are compatible with enzyme activity measures indicating a direct linear relationship between blood flow rate and perfused pulmonary microvascular surface area. Although the data do not rule out the possibility of increased pulmonary vascular permeability to water during very elevated blood flow rates, the greater filtration rate during elevated flow is more likely related to increases in both microvascular pressure and surface area.
Cortical blood flow and +Gz acceleration in conscious rabbits
Authors: Florence G. , Roucher P. , Vallet R. , Lemenn M. , Charbonne R. , Seylaz J.
Published: December 2017

We examined whether superficial cortical blood flow (CBF) of nonanesthetized rabbits (n = 11) is affected by gravitational (G) stress. Blood flow was measured by laser-Doppler flowmetry through a chronic Plexiglas window implanted over the parietal cortex. Mean arterial blood pressure (MABP) was recorded via an aortic catheter with the pressure transducer situated at the level of the head. The electrocorticogram (ECoG) was also studied in seven rabbits. The animals were exposed to tail-to-head acceleration [6, 10, 15, and 20 G acceleration (Gz) for 1 min]. MABP fell with increasing acceleration (regression line equation: MABP = -7.0 Gz + 129.1; P < 0.001, r = 0.85), whereas CBF was statistically either not different from or greater than control. In one rabbit exposed to 20 Gz, high voltage and slow waves were observed on the ECoG and these changes were preceded by a decrease in CBF to 66% of control. We conclude that the stress and the siphon effect may account for the maintenance of elevated CBF despite low or negative MABP until the occurrence of vascular collapse that induces loss of consciousness.
Oxidative stress after human exercise: effect of N-acetylcysteine supplementation
Authors: Sen C. K. , Rankinen T. , Vaisanen S. , Rauramaa R.
Published: December 2017

The association between exercise intensity and related oxidative stress was investigated in nine men who exercised for 30 min at their aerobic (AeT) and anaerobic (AnaeT) thresholds. We also tested the effect of oral N-acetylcysteine (NAC) on exercise-associated rapid blood glutathione (GSH) oxidation in subjects performing two identical maximal bicycle ergometer exercise (Max) tests. Before the second test (Max with NAC supplementation [Max(NAC)]), the men took 200 x 4 mg/day of NAC tablets for 2 days and an additional 800 mg on the test morning. Blood samples were drawn before, immediately after, and 24 h after the tests. Total and oxidized GSH levels in blood were determined. Plasma thiobarbituric acid-reactive substances and net peroxyl radical scavenging capacity (PSC) were assayed. Exercise-associated damage in leukocyte DNA was estimated by fluorometric analysis of DNA unwinding. A single bout of exercise at Max, AeT, and AnaeT resulted in a significant increase in blood GSH oxidation but did not influence net PSC of plasma. Although an association between a single bout of exercise and leukocyte DNA damage was apparent, this study suggests that the parameter may not serve as a sensitive index to assess the role of exercise intensity in the extent of exercise-associated oxidative stress. Plasma thiobarbituric acid-reactive substances did not change after either Max or Max(NAC) tests. NAC supplementation resulted in an increase in preexercise PSC, indicating a higher net antioxidant capacity of the plasma, but did not affect blood GSH.(ABSTRACT TRUNCATED AT 250 WORDS)
Tensile stiffness of ovine tracheal wall
Authors: Codd S. L. , Lambert R. K. , Alley M. R. , Pack R. J.
Published: December 2017

The epithelial folding that occurs during bronchoconstriction requires that the pressure on the muscle side of the folding membrane be greater than that on the lumen side. The pressure required for a given level of folding depends on the elastic properties of the tissue and on the geometry of the folding. To quantify the elastic properties, uniaxial tensile stiffness of the tracheal inner wall of nine sheep was measured in two directions: parallel to the tracheal axis and circumferentially. The tissue showed anisotropic behavior, being approximately three times stiffer longitudinally than circumferentially. Histological examination showed that collagen in the lamina propria was randomly arranged, whereas there were straight elastin fibers aligned with the tracheal axis. This observation could explain the observed elastic anisotropy. Mechanical removal of the epithelium had no effect on tensile stiffness. It was also found that the tissue was under tension in situ. When a strip was excised, its length decreased by > or = 30%. After allowing for the systematic errors inherent in this experiment, the in situ circumferential tensile stiffness is estimated to be > or = 20 kPa. If the equivalent tissue in the bronchioles has the same tensile stiffness as that in the trachea, the forces required to fold the membrane are significant at small transbronchial pressure differences and increase in the presence of membrane thickening such as that seen in asthma.
Aerobic muscle contraction impaired by serotonin-mediated vasoconstriction
Authors: Dora K. A. , Rattigan S. , Colquhoun E. Q. , Clark M. G.
Published: December 2017

Vasoconstriction mediated by serotonin (5-HT) inhibits muscle metabolism in resting constant-flow-perfused rat hindlimb and may do so by vascular shunting. In the present study, the effects of 5-HT on tension development and contraction-induced oxygen uptake by the sciatic nerve-stimulated gastrocnemius-plantaris-soleus muscle group of the perfused rat hindlimb and tension development by electrically stimulated isolated incubated soleus and extensor digitorum longus muscles were examined. In both erythrocyte and erythrocyte-free perfusions, 0.25 microM 5-HT increased perfusion pressure and markedly decreased contraction-induced tension, oxygen uptake, and lactate release. The release of metabolic vasodilators from exercising skeletal muscle did not appear to affect 5-HT-mediated vasoconstriction; rather, vascular resistance increased during the period of muscle contraction. In contrast, vasoconstriction during muscle contraction mediated by alpha-adrenoceptor stimulation did not impair tension and was partially overcome by metabolic vasodilators. In addition, contraction of isolated incubated soleus and extensor digitorum longus muscles was not affected by 5-HT addition to the incubation medium. We conclude that 5-HT impairs contractility of working muscle during the aerobic phase by limiting oxygen delivery through redistributing perfusate flow. The results are consistent with a vasoconstrictor action of 5-HT on larger vessels, perhaps at feed arteries external to the working muscle. When constricted by 5-HT, these vessels are apparently insensitive to metabolic vasodilatation.
Adaptation of rat soleus muscles to 4 wk of intermittent strain
Authors: Stauber W. T. , Miller G. R. , Grimmett J. G. , Knack K. K.
Published: December 2017

The effect of repeated strains on rat soleus muscles was investigated by stretching active muscles 3 times/wk for 4 wk with two different methods of stretching. The adaptation of myofibers and noncontractile tissue was followed by histochemical techniques and computer-assisted image analysis. Muscle hypertrophy was seen in the slow-stretched muscles, which increased in mass by 13% and increased in myofiber cross-sectional area by 30%. In the fast-stretched muscle, mass increased by 10% but myofiber cross-sectional area actually decreased. This decrease in mean fiber area was the result of a population of very small fibers (population A) that coexisted with slightly smaller normal-sized fibers (population B). Fibers in population A did not have the distribution expected from atrophy compared with atrophic fibers from unloaded muscles; they were much smaller. In addition, there was a 44% increase in noncontractile tissue in the fast-stretched muscles. Thus, soleus muscles subjected to repeated strains respond differently to slow and fast stretching. Slow stretching results in typical muscle hypertrophy, whereas fast stretching produces somewhat larger muscles but with a mixture of small and normal-sized myofibers accompanied by a marked proliferation of noncontractile tissue.
Pressure transmission across the respiratory system at raised lung volumes in infants
Authors: Turner D. J. , Lanteri C. J. , LeSouef P. N. , Sly P. D.
Published: December 2017

Forced expiratory flow-volume (FEFV) curves can be generated from end-tidal inspiration in infants with use of an inflatable jacket. We have developed a technique to raise lung volume in the infant before generation of FEFV curves. Measurements of pressure transmission to the airway opening by use of static maneuvers have shown no change with increasing lung volume above end-tidal inspiration. The aim of this study was to determine, under dynamic conditions (i.e., during rapid thoracic compression), whether the efficiency of pressure transmission across the chest wall is altered by raising lung volume above the tidal range. Dynamic pressure transmission (Ptx,dyn) was measured in five infants (age 6–17 mo). Jacket pressure (Pj), esophageal pressure, and volume were measured throughout passive and FEFV curves at lung volumes set by 10, 15, and 20 cmH2O preset pressure. The group mean Ptx,dyn was 37 +/- 6% (SE) of Pj at end-tidal inspiration, and no change was seen with further increases in lung volume. However, a mean decrease in Ptx,dyn of 42% was evident throughout the tidal volume range (i.e., from end-tidal inspiration to end expiration). Isovolume static pressure transmission (Ptx,st) was measured in three of the five infants by inflation of the jacket in a stepwise manner with the airway closed. Measurements were made at end-tidal inspiration and lung volumes at 10, 15, and 20 cmH2O preset pressure. Resulting changes in Pj, esophageal pressure, and airway opening pressure were compared using linear regressions to determine Ptx,st.(ABSTRACT TRUNCATED AT 250 WORDS)
Nitric oxide-independent response to acetylcholine by terminal arterioles in rat cremaster muscle
Authors: Vicaut E. , Baudry N. , Hou X.
Published: December 2017

The aim of the present study was to establish whether, in terminal arterioles from the rat cremaster, acetylcholine (ACh) elicits nitric oxide (NO)-independent dilation corresponding to the transient ACh-induced endothelium-dependent hyperpolarization described in arteries. For this purpose, the responses of terminal arterioles [mean diam 15.0 +/- 0.4 (SE) microns] were studied by intravital microscopy in rat cremaster muscle. During 15 min of superfusion by 10(-5) M ACh, the response was characterized by an initial maximal dilation (peak time < 3 min) followed by a more sustained dilation that slightly decreased with time. Inhibition of NO synthesis by 2 x 10(-4) M N omega-nitro-L-arginine (L-NNA) significantly reduced, but did not eliminate, both the peak and sustained responses. Simultaneous administration of 2 x 10(-4) M L-NNA and 2 x 10(-5) M mefenamic acid, an inhibitor of prostaglandin synthesis, did not induce a significantly different response from that observed with L-NNA alone. Procaine (10(-3) M), which is known to inhibit completely ACh-induced hyperpolarization in carotid artery, drastically reduced the initial part of the ACh-induced dilation but not the sustained response. Simultaneous administration of procaine and L-NNA almost completely inhibited the peak response to ACh. Similar results were obtained when L-NNA was combined with a superfusion bath containing 20 mM KCl, a concentration known to reduce hyperpolarization in arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of strength training on total and regional body composition in older men
Authors: Treuth M. S. , Ryan A. S. , Pratley R. E. , Rubin M. A. , Miller J. P. , Nicklas B. J. , Sorkin J. , Harman S. M. , Goldberg A. P. , Hurley B. F.
Published: December 2017

The effects of a 16-wk strength-training program on total and regional body composition were assessed by dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), and hydrodensitometry in 13 untrained healthy men [60 +/- 4 (SD) yr]. Nine additional men (62 +/- 6 yr) served as inactive controls. The strength-training program resulted in substantial increases in both upper (39 +/- 8%; P < 0.001) and lower (42 +/- 14%; P < 0.001) body strength. Total fat-free mass (FFM) increased by 2 kg (62.0 +/- 7.1 to 64.0 +/- 7.2 kg; P < 0.001), and total fat mass decreased by the same amount (23.8 +/- 6.7 to 21.8 +/- 6.0 kg; P < 0.001) when measured by DEXA. When measured by hydrodensitometry, similar increases in FFM (61.3 +/- 7.8 to 63.0 +/- 7.6 kg; P < 0.01) and decreases in fat mass (23.8 +/- 7.9 to 22.1 +/- 7.7 kg; P < 0.001) were observed. When measured by DEXA, FFM was increased in the arms (6.045 +/- 0.860 to 6.418 +/- 0.803 kg; P < 0.01), legs (19.416 +/- 2.228 to 20.131 +/- 2.303 kg; P < 0.001), and trunk (29.229 +/- 4.108 to 30.134 +/- 4.184 kg; P < 0.01), whereas fat mass was reduced in the arms (2.383 +/- 0.830 to 2.128 +/- 0.714 kg; P < 0.01), legs (7.583 +/- 1.675 to 6.945 +/- 1.551 kg; P < 0.001), and trunk (12.216 +/- 4.143 to 11.281 +/- 3.653 kg; P < 0.01) as a result of training.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration
Authors: Van Baak M. A. , Mooij J. M.
Published: December 2017

To investigate the effect of glucose (Glc) infusion on endurance performance after beta-adrenoceptor blockade, eight healthy male volunteers performed four endurance cycle ergometer tests at 67% of maximal work load after 80 mg of propranolol (Pr) or placebo (Pl) were administered orally in combination with a continuous infusion of Glc (0.5 g/min) or saline (Sal). The order of the tests was randomized. Endurance times were 53 +/- 6 (SE), 64 +/- 7, 26 +/- 5, and 31 +/- 6 min after Pl+Sal, Pl+Glc, Pr+Sal, and Pr+Glc, respectively (P < 0.001). Glc infusion increased endurance after Pl (P < 0.05) but not after Pr. Glc infusion resulted in significantly higher plasma Glc concentrations during exercise compared with Sal infusion (P < 0.001). Glc infusion had no effect on cardiorespiratory or other metabolic variables. Plasma ammonia concentration was increased during the Pr tests (P < 0.001) but reached similar values at exhaustion in all tests and was not affected by Glc infusion. The maintenance of plasma Glc concentration during endurance exercise at or above preexercise levels did not improve the reduction of endurance performance after Pr, indicating that the availability of blood Glc is not a limiting factor in this process.
Bronchial and reverse pulmonary venous blood flow protect the lung from ischemia-reperfusion injury
Authors: Hamvas A. , Schuster D. P.
Published: December 2017

We used an intact in vivo canine model of pulmonary ischemia-reperfusion injury to evaluate whether the bronchial circulation or reverse pulmonary venous blood flow would protect the lung from injury during 2 h of unilateral pulmonary arterial (PA) occlusion and lung deflation. Serial measurements of regional extravascular density and transcapillary protein flux were made after reperfusion by using the quantitative imaging technique of positron emission tomography. Twenty-one animals were divided into four experimental groups. In all experimental groups, the left PA was clamped and the left lung was allowed to collapse and remain unventilated for a period of 2 h. In addition, in group I (n = 5) the left bronchial circulation was disrupted and the left pulmonary veins were clamped, in group II (n = 5) the bronchial circulation and the pulmonary veins were left intact, in group III (n = 6) the bronchial circulation was left intact but the pulmonary veins were clamped, and in group IV (n = 5) the bronchial circulation was disrupted but the pulmonary veins remained patent. The rate of protein flux in the left lung was increased only in group I (complete ischemia with lung deflation) [mean 195 x 10(-4) min-1 (range 85–453 x 10(-4) min-1) at 0.25 h and 114 x 10(-4) min-1 (range 22–200 x 10(-4) min-1) at 3 h] after reventilation and PA reperfusion (normal = 49 +/- 31 x 10(-4) min-1). Extravascular density increased significantly from 0.25 to 3 h only in group I.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of transferrin saturated with iron with lung surfactant in respiratory failure
Authors: Hallman M. , Sarnesto A. , Bry K.
Published: December 2017

Proteins that decrease the surface activity of surfactant accumulate in epithelial lining fluid in respiratory failure. The aim of this study was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). This inhibitor was identified as being transferrin (TF). Unlike serum TF, TF recovered in respiratory failure was saturated with iron (Fe(3+)-TF). Fe(3+)-TF decreased the surface activity of normal surfactant in vitro, whereas iron-free TF had no effect. In the presence of H2O2 and a reducing agent, Fe(+3)-TF inactivated the surfactant complex: the surface absorption rate was decreased, immunoreactive surfactant protein A was decreased, and malondialdehyde was formed. The acute effects of Fe(3+)-TF and iron-free TF applied to the airways were studied in animal models. In respiratory failure induced by BAL, Fe(3+)-TF deteriorated respiratory failure, whereas iron-free TF had no effect. In respiratory failure induced by hyperoxia for 48 h, administration of iron-free TF ameliorated the respiratory failure and improved the surface activity in BAL. We propose that Fe(3+)-TF accumulating in epithelial lining fluid during lung damage contributes to surfactant inhibition and promotes the formation of free radicals that inactivate the surfactant system.
Catecholamine responses to short-term high-intensity resistance exercise overtraining
Authors: Fry A. C. , Kraemer W. J. , Van Borselen F. , Lynch J. M. , Triplett N. T. , Koziris L. P. , Fleck S. J.
Published: December 2017

Seventeen weight-trained males were divided into an overtraining group [OT; n = 11; age = 22.0 +/- 0.9 (SE) yr] that weight trained their legs daily for 2 wk with 100% 1 repetition maximum relative intensity on a squat machine and a control group (n = 6; age = 23.7 +/- 2.4 yr) that exercised 1 day/wk with low relative intensity (50% 1 repetition maximum). Test batteries including strength assessments and resting and exercise-induced concentrations of epinephrine and norepinephrine were conducted at the beginning, middle, and end (tests 1–3, respectively) of the study. Strength capabilities decreased by test 3 for the OT group (P < 0.05). Resting catecholamine concentrations did not change for either group during the study, whereas exercise-induced concentrations of both epinephrine (test 1 = 3,407.9 +/- 666.6 pmol/l, test 2 = 7,563.7 +/- 1,210.6 pmol/l, test 3 = 6,931.6 +/- 919.3 pmol/l) and norepinephrine (test 1 = 42.9 +/- 7.4 nmol/l, test 2 = 70.0 +/- 8.8 nmol/l, test 3 = 85.2 +/- 14.5 nmol/l) significantly increased by tests 2 and 3 for only the OT group. Correlation coefficients suggested decreased responsitivity of skeletal muscle to sympathetic nervous system activity. It appears that altered exercise-induced sympathetic nervous system activity accompanies high relative intensity resistance exercise overtraining and may be among the initial responses to the onset of the previously theoretical sympathetic overtraining syndrome.
Surface activity of lipid extract surfactant in relation to film area compression and collapse
Authors: Schurch S. , Schurch D. , Curstedt T. , Robertson B.
Published: December 2017

The physical properties of modified porcine surfactant (Curosurf), isolated from minced lungs by extraction with chloroform-methanol and further purified by liquid-gel chromatography, were investigated with the captive bubble technique. Bubble size, and thus the surface tension of an insoluble film at the bubble surface, is altered by changing the pressure within the closed bubble chamber. The film surface tension and area are determined from the shape (height and diameter) of the bubble. Adsorption of fresh Curosurf is characterized by stepwise decreases in surface tension, which can easily be observed by sudden quick movements of the bubble apex. These “adsorption clicks” imply a cooperative movement of large collective units of molecules, approximately 10(14) (corresponding to approximately 120 ng of phospholipid) or approximately 10(18) molecules/m2, into the interface during adsorption. Films formed in this manner are already highly enriched in dipalmitoyl phosphatidylcholine, as seen by the extremely low compressibility, close to that of dipalmitoyl phosphatidylcholine. Near-zero minimum tensions are obtained, even at phospholipid concentrations as low as 50 micrograms/ml. During dynamic cycling (20–50 cycles/min), low minimum surface tensions, good film stability, low compressibility, and maximum surface tensions between 30 and 40 mN/m are possible only if the films are not overcompressed near zero surface tension; i.e., the overall film area compression should not substantially exceed 30%.
Endothelins and pulmonary diseases
Authors: Barnes P. J.
Published: December 2017

Endothelins (ETs) are expressed in several types of cell in human lung, including airway epithelial cells, pulmonary vascular endothelial cells, submucosal glands, and type II pneumocytes. There is evidence for increased expression of ET-1 in several pulmonary diseases, including asthma, fibrosing alveolitis, and pulmonary hypertension, suggesting that ET-1 may play a pathophysiological role. ET binding sites are widely distributed and are localized to airway and pulmonary vascular smooth muscle, fibroblasts, submucosal glands, and airway nerves, indicating that ETs may have widespread effects. ET-1 and ET-3 are potent constrictors of human airway smooth muscle via a direct effect on ET receptors in airway smooth muscle; these receptors are probably ETB receptors. ETs may have other effects on airway function, including constriction of bronchial vessels, increased plasma exudation, increased mucus secretion, airway smooth muscle hyperplasia, and possibly increased fibrogenesis; these effects may be mediated via ETA receptors. ET-1 is a potent constrictor of human pulmonary vessels, whereas ET-3 is less effective, suggesting a predominance of ETA receptors. Similarly, chemotaxis and mitogenesis of pulmonary vascular fibroblasts and smooth muscle are mediated via ETA receptors. These findings implicate ETs in various pulmonary diseases and suggest that ET antagonists may be useful in their treatment.