bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of airway and left atrial pressures on microvascular and interstitial pressures in adult lungs
Authors: Fike C. D. , Kaplowitz M. R.
Published: December 2017

The purpose of this study was to determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 80-microns-diam arterioles and venules in isolated perfused lungs of adult rabbits. We used the micropuncture technique and measured microvascular or interstitial pressures at constant airway pressures of 5 and 15 cmH2O with left atrial pressure adjusted above (zone 3 conditions) or below (zone 2 conditions) airway pressure. Only in lungs inflated to the higher airway pressure did a reduction in left atrial pressure below airway pressure result in concomitant reductions in venular pressure. This suggests that the site of flow limitation in zone 2 shifted from venules > 80 microns diam toward vessels <20 microns diam with inflation from 5 to 15 cmH2O. With the lungs under zone 3 conditions, both transarteriolar and transvenular gradients (microvascular-interstitial pressures) were greater at the higher compared with the lower airway pressure. In contrast, transarteriolar and transvenular gradients changed in opposite directions when compared at the two inflation pressures under zone 2 conditions. Counteracting changes in transmicrovascular gradients make it difficult to predict the effect on fluid filtration from lung inflation under zone 2 conditions. When zone 3 conditions are maintained during inflation, the tendency for edema formation should increase.
Near-infrared spectrophotometric device to measure fluid exchange in blood-perfused organs
Authors: Oppenheimer L. , Huebert D.
Published: December 2017

We describe an on-line spectrophotometric device designed to estimate the volume of transvascular fluid exchange (VE) continuously in isolated organ preparations. The device is interposed in the perfusion circuit, and VE is continuously estimated from changes in light transmission proportional to changes in perfusate hematocrit. In our perfusing circuit, hemolysis was negligible. Using hourly determinations of free hemoglobin, we estimated errors in VE due to hemolysis to be on the order of 1 ml for every hour of perfusion (expt I). When logarithms of on-line spectrophotometric signals were plotted against measured hematocrits (expt II), there was always an excellent linear correlation over a wide range of hematocrits (from 0.247 to 0.583). Finally, there was also an excellent correlation between spectrophotometric [QF(Spectr)] and gravimetric [QF(wt)] estimates of constant rates of transvascular fluid exchange in five isolated excised canine left lower pulmonary lobes, where QF(Spectr) = delta VE/delta t and QF(wt) = delta wt/delta t (expt III). QF(Spectr) = 1.035QF(wt) - 0.038 (r2 = 0.9772).
Functional and structural adaptation of the yak pulmonary circulation to residence at high altitude
Authors: Durmowicz A. G. , Hofmeister S. , Kadyraliev T. K. , Aldashev A. A. , Stenmark K. R.
Published: December 2017

The high-altitude (HA) native yak (Bos grunniens) has successfully adapted to chronic hypoxia (CH) despite being in the same genus as domestic cows, which are known for their great hypoxic pulmonary vasoconstrictor responses (HPVRs), muscular pulmonary arteries, and development of severe pulmonary hypertension on exposure to CH. To determine possible mechanisms by which the pulmonary circulation may adapt to CH, yak pulmonary vascular reactivity to both vasoconstrictor and vasodilator stimuli and yak pulmonary artery structure were assessed. Hypoxia caused a small but significant HPVR, and norepinephrine infusion caused a greater rise in pulmonary arterial pressure (Ppa) than did hypoxia. Acetylcholine, an endothelium-dependent vasodilator, had no effect on Ppa but lowered pulmonary resistance (Rp) by causing an increase in cardiac output. Sodium nitroprusside, an endothelium-independent vasodilator, decreased both Ppa and Rp significantly. Yak small pulmonary arteries had a 4.1 +/- 0.1% medial thickness, with vessels < or = 100 microns devoid of smooth muscle. Yak pulmonary artery endothelial cells were much longer, wider, and rounder in appearance than those of domestic cows. Thus the yak has successfully adapted to HA conditions by maintaining both a blunted HPVR and thin-walled pulmonary vessels. Differences in both endothelial cell morphology and response to acetylcholine between the yak and those reported in the domestic cow suggest the adaptation to HA may include changes not only in the amount of pulmonary vascular smooth muscle but in endothelial cell function and structure as well.
Electrochemical detection of catecholamine release from rat carotid body in vitro
Authors: Donnelly D. F.
Published: December 2017

Neurotransmitter secretion from carotid body glomus cells is hypothesized to be an essential element of chemotransduction. To address one aspect of this hypothesis, catecholamine release in response to hypoxic hypoxia and histotoxic hypoxia was examined using electrically treated carbon-fiber microelectrodes placed in rat carotid bodies in vitro. Carotid bodies of mature rats were removed, along with a portion of the sinus nerve, and suspended in oxygenated (95% O2–5% CO2) Ringer saline at 35 degrees C. The microelectrode differential current after a 50-mV step was recorded over the potential range of -300 to +500 mV. In some preparations, a suction electrode applied to the sinus nerve recorded single-fiber chemoreceptor afferent activity. Stimulation by severe hypoxia (Po2 approximately 0–10 Torr for 3 min, n = 10) and cyanide (2 mM for 2 min) caused an increase in sinus nerve activity and an increase in the carbon-fiber electrode current at a potential corresponding to the oxidation potential of dopamine. As measured in the amperometric mode (constant voltage), tissue catecholamine was 0.35 +/- 0.05 microM (n = 6) and increased to 1.64 +/- 0.43 microM by 1 min of severe hypoxia or to 1.06 +/- 0.17 microM at 2 min of moderate hypoxia (Po2 approximately 50 Torr). Exposure to calcium-free Ringer saline before hypoxia ablated the increase in electrode current, and the response was restored after reperfusion with calcium-containing saline. Repeated exposures to hypoxia (3-min duration) every 15 min resulted in significantly smaller nerve and catecholamine responses. By the third hypoxia exposure, nerve and catecholamine responses were diminished by 30–50%.
Contribution of vagal afferents to respiratory reflexes evoked by acute inhalation of ozone in dogs
Authors: Schelegle E. S. , Carl M. L. , Coleridge H. M. , Coleridge J. C. , Green J. F.
Published: December 2017

Acute inhalation of ozone induces vagally mediated rapid shallow breathing and bronchoconstriction. In spontaneously breathing anesthetized dogs, we attempted to determine whether afferent vagal C-fibers in the lower airways contributed to these responses. Dogs inhaled 3 ppm ozone for 40–70 min into the lower trachea while cervical vagal temperature was maintained successively at 37, 7, and 0 degrees C. At 37 degrees C, addition of ozone to the inspired air decreased tidal volume and dynamic lung compliance and increased breathing frequency, total lung resistance, and tracheal smooth muscle tension. Ozone still evoked significant effects when conduction in myelinated vagal axons was blocked selectively by cooling the nerves to 7 degrees C. Ozone-induced effects were largely abolished when nonmyelinated vagal axons were blocked by cooling to 0 degree C, breathing during ozone inhalation at 0 degree C being generally similar to that during air breathing at 0 degree C, except that minute volume and inspiratory flow were higher. We conclude that afferent vagal C-fibers in the lower airways make a major contribution to the acute respiratory effects of ozone and that nonvagal afferents contribute to the effects that survive vagal blockade.
Acute inhalation of ozone stimulates bronchial C-fibers and rapidly adapting receptors in dogs
Authors: Coleridge J. C. , Coleridge H. M. , Schelegle E. S. , Green J. F.
Published: December 2017

To identify the afferents responsible for initiating the vagally mediated respiratory changes evoked by acute exposure to ozone, we recorded vagal impulses in anesthetized, open-chest, artificially ventilated dogs and examined the pulmonary afferent response to ozone (2–3 ppm in air) delivered to the lower trachea for 20–60 min. Bronchial C-fibers (BrCs) were the lung afferents most susceptible to ozone, the activity of 10 of 11 BrCs increasing from 0.2 +/- 0.2 to 4.6 +/- 1.3 impulses/s within 1–7 min of ozone exposure. Ten of 15 rapidly adapting receptors (RARs) were stimulated by ozone, their activity increasing from 1.5 +/- 0.4 to 4.7 +/- 0.7 impulses/s. Stimulation of RARs (but not of BrCs) appeared secondary to the ozone-induced reduction of lung compliance because it was abolished by hyperinflation of the lungs. Ozone had little effect on pulmonary C-fibers or slowly adapting pulmonary stretch receptors. Our results suggest that both BrCs and RARs contribute to the tachypnea and bronchoconstriction evoked by acute exposure to ozone when vagal conduction is intact and that BrCs alone are responsible for the vagally mediated tachypnea that survives vagal cooling to 7 degrees C.
Techniques for measuring respiratory mechanics: an analytic approach with a viscoelastic model
Authors: Lorino A. M. , Harf A.
Published: December 2017

A homogeneous model with stress relaxation that is described by a pure viscoelastic component was recently proposed to describe the mechanical behavior of the respiratory system during mechanical ventilation (Bates et al. J. Appl. Physiol. 67: 2276–2285, 1989). With the use of this model, analytic expressions of the pressure in response to typical volume inputs are developed, and the recently published studies relating to the influence of the ventilatory pattern on respiratory mechanics are reviewed and analyzed. The analytic expression of pressure responses to rapid airway occlusion following constant-flow inflation and to sinusoidal volume oscillations allows prediction of most of the reported results. The theoretical analysis suggests that in normal subjects the observed flow and volume dependencies of respiratory mechanics are, in fact, illustrations of the dependence of the viscoelastic resistance on inspiratory time and respiratory frequency. Thus the homogeneous viscoelastic model appears suitable to describe respiratory system mechanical behavior under mechanical ventilation.
Respiratory epithelium modulates the responses of canine bronchi to cooling
Authors: Gao Y. , Vanhoutte P. M.
Published: December 2017

The present study was designed to investigate the effect of cooling on the modulatory role of the respiratory epithelium on the underlying smooth muscle. Canine bronchial rings and segments (with or without epithelium) were suspended in organ chambers and perfused with modified Krebs-Ringer bicarbonate solution, respectively. Isometric force was recorded. Cooling did not affect the resting tension of the bronchi. During contractions to carbachol, cooling evoked contractions in bronchi with epithelium but relaxations in those without epithelium. In the presence of indomethacin, cooling induced contractions in both preparations with and without epithelium. The contractions in bronchi with epithelium were significantly larger than those in bronchi without epithelium. After treatment with indomethacin, exogenous arachidonic acid potentiated the cooling-induced contractions in preparations with epithelium but not in those without epithelium. This potentiation was not affected by nordihydroguaiaretic acid. SKF 525-A and metyrapone, inhibitors of cytochrome P-450 monooxygenases, converted the cooling-induced contractions of preparations with epithelium to relaxations and had no significant effects on the responses of preparations without epithelium. These observations suggest that cooling induces from the epithelium the release of a cytochrome P-450-derived eicosanoid that potentiates contractions of the underlying airway smooth muscle to carbachol.
A specific endothelin-1 antagonist blocks inhaled endothelin-1-induced bronchoconstriction in sheep
Authors: Abraham W. M. , Ahmed A. , Cortes A. , Spinella M. J. , Malik A. B. , Andersen T. T.
Published: December 2017

In this study we used conscious sheep to compare the relative potencies of inhaled endothelin- (ET) 1 and ET-3 and to determine whether a newly described selective ET-1 receptor antagonist, [diaminopropionic acid1-Asp15]ET-1 ([Dpr1-Asp15]ET-1), when given as an aerosol blocks ET-1-induced bronchoconstriction. Partial concentration-response curves to ET-1 and ET-3 were obtained by measuring the change in pulmonary airflow resistance (RL) after aerosol challenge. Both ET-1 (n = 6) and ET-3 (n = 4) caused concentration-dependent (10(-10)-10(-7) bronchoconstriction, but ET-3 was 400-fold less potent than ET-1. Pretreatment (30 min) with 25 breaths of 5 x 10(-8) M [Dpr1-Asp15]ET-1 caused a 100-fold rightward shift of the ET-1 concentration-response curve. The activity of the ET-1 antagonist (25 breaths of 5 x 10(-8) M) was compared with that of various control peptides (25 breaths of 10(-8) M). ET-1 (50 breaths of 10(-7) M) caused an increase in RL of 133 +/- 33% (SE) over baseline. [Dpr1-Asp15]ET-1 significantly inhibited this response by 54%. No protection was seen with a monocyclic control peptide or a thrombin receptor peptide. There was, however, a small protective effect (38%, P < 0.05) seen with [Dpr1-Asp15]ET-3, a structurally homologous ET-3 antagonist. [Dpr1-Asp15]ET-1 had no effect on carbachol (n = 3) or leukotriene D4-induced bronchoconstriction. Thus inhaled ET-1 and, to a lesser extent, ET-3 cause concentration-dependent bronchoconstriction in conscious sheep.
Spine and total body bone mineral density in amenorrheic endurance athletes
Authors: Rutherford O. M.
Published: December 2017

Lumbar spine, total body, and regional bone mineral densities (BMDs) were measured in eumenorrheic and amenorrheic runners and triathletes by using dual-energy X-ray absorptiometry (Lunar DPX). Values were also compared with age- and weight-matched reference data from the Lunar British database. The amenorrheic group had significantly lower lumbar spine (P = 0.003), arm (P = 0.018), trunk (P = 0.014), and total spine (P < 0.0001) BMDs compared with the eumenorrheic group and significantly lower lumbar (P = 0.002) and total spine (P < 0.001) values compared with the reference controls. Leg (P = 0.009) and arm (P < 0.001) densities were significantly higher than controls. All regions, apart from the lumbar spine, were significantly higher in the eumenorrheic group compared with the reference group. There were no within-group differences for the runners and triathletes. Compared with the eumenorrheic athletes, the amenorrheic women had significantly later age of menarche (P = 0.0032). The type of physical activity undertaken by these athletes can compensate for the loss of menses at the majority of skeletal sites with the exception of the spine.
Fetal respiratory neuronal activity during REM and NREM sleep
Authors: Ioffe S. , Jansen A. H. , Chernick V.
Published: December 2017

Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 +/- 0.01 vs. 0.45 +/- 0.02), right ventricular systolic pressures (25 +/- 2 vs. 29 +/- 2 mmHg), and lung dry weight-to-body weight ratios (0.48 +/- 0.03 vs. 0.57 +/- 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 +/- 1.4 vs. 17.4 +/- 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.
Increased afterload intensifies asynchronous wall motion and impairs ventricular relaxation
Authors: Miura T. , Bhargava V. , Guth B. D. , Sunnerhagen K. S. , Miyazaki S. , Indolfi C. , Peterson K. L.
Published: December 2017

To clarify whether impaired left ventricular relaxation elicited by increased afterload is attributable to regional dyssynchrony, we analyzed in dogs simultaneous left ventricular contrast ventriculography and pressure before and during angiotensin II infusion. Regional shortening was measured by a centerline method and a video-intensity method that served to define asynchronous motion. During angiotensin II, peak left ventricular pressure increased 35 +/- 6 mmHg, and the isovolumic pressure time constant (tau) was prolonged from 32.7 +/- 4.1 to 39.2 +/- 7.6 ms (P < 0.01). During increased afterload, early diastolic asynchrony, confined to the apical (5 of 7) and inferior regions (2 of 7), was detected in all dogs. Early systolic asynchrony was detected in the apical (5 of 7) and inferior (1 of 7) regions in six dogs. At control, systolic excursion was lower in the anteroapical than in the anterobasal region (P < 0.05). During angiotensin II, excursion of all regions was reduced, with the apical region lower than other regions (P < 0.01). In the normal dog heart, impaired relaxation with augmented afterload is coincident with asynchronous wall motion, especially in the apical-inferior region. Temporal dispersion of regional contraction may explain delayed left ventricular relaxation associated with increased afterload.
Role of thermal factors on aerobic capacity improvements with endurance training
Authors: Young A. J. , Sawka M. N. , Quigley M. D. , Cadarette B. S. , Neufer P. D. , Dennis R. C. , Valeri C. R.
Published: December 2017

This investigation studied the importance of the rise in body temperature during exercise for aerobic capacity adaptations produced by endurance training. The approach used was to compare training effects produced by subjects exercising in hot (35 degrees C) water vs. cold (20 degrees C) water. Hot water was used to potentiate, and cold water to blunt, the rise in body temperature during exercise. Eighteen young men trained by cycle-ergometer exercise at 60% of maximal oxygen uptake (VO2max) while immersed to the neck in either hot (HWT, n = 9) or cold (CWT, n = 9) water for 60 min, 5 days/wk, for 8 wk. Before and after training, VO2max, erythrocyte volume, plasma volume, and vastus lateralis citrate synthase activity were measured. Training increased (P < 0.01) VO2max by 13%, with no difference between HWT and CWT in the magnitude of the effect. Erythrocyte volume increased 4% (P < 0.01) with training, with no difference between HWT and CWT in the magnitude of the effect. Plasma volume remained unchanged by training in both the HWT and CWT groups. Last, vastus lateralis citrate synthase activity increased by 38% with training, but there was no difference between HWT and CWT in the training effect. Thus, exercise-induced body temperature elevations are not an important stimulus for the aerobic adaptations to moderate-intensity endurance training.
Reflex control of diaphragm activation by thoracic afferents
Authors: Romaniuk J. R. , Supinski G. S. , DiMarco A. F.
Published: December 2017

Recent studies suggest that chest wall reflexes may have a role in modulating diaphragm activation. The purpose of this study was to more closely examine this issue by assessing the diaphragmatic motor response to airway occlusion. Studies were performed in vagotomized mongrel dogs anesthetized with pentobarbital sodium. Diaphragmatic electromyogram (EMG) and phrenic neurogram (ENG) responses to airway occlusion were evaluated at different precontractile respiratory muscle lengths, achieved by passive inflation and deflation with a volume syringe during the preceding expiration. Lung volume was expressed as the corresponding change in airway pressure. At functional residual capacity, deflation (-5 cmH2O), and large inflation (+25 cmH2O), phrenic ENG during occlusion was 90 +/- 2 (SE), 84 +/- 5, and 86 +/- 3% of the preceding control breaths, respectively (n = 9). Qualitatively similar, but somewhat more pronounced, responses were observed on diaphragmatic EMG. With small lung inflations, the degree of reduction of phrenic ENG with airway occlusion was less. Consequently, the relationship between airway pressure and degree of inhibition was best described as a reverse parabola with the maximum at approximately +10–15 cmH2O. Responses were not significantly affected by bilateral cervical phrenicotomy. Complete section of the spinal cord at the high thoracic level (T1-T2) abolished the observed reduction in phrenic ENG in response to airway occlusion. Our results demonstrate 1) the existence of nonvagal nonphrenic reflex control of diaphragm activation most likely secondary to activation of intercostal afferents and 2) that the magnitude of this reflex is highly dependent on factors related to lung volume.
NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha
Authors: Johnson D. , Hurst T. , Wilson T. , Murphy F. , Saxema A. , To T. , Mayers I.
Published: December 2017

Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha.
Human muscle metabolism during intermittent maximal exercise
Authors: Gaitanos G. C. , Williams C. , Boobis L. H. , Brooks S.
Published: December 2017

Eight male subjects volunteered to take part in this study. The exercise protocol consisted of ten 6-s maximal sprints with 30 s of recovery between each sprint on a cycle ergometer. Needle biopsy samples were taken from the vastus lateralis muscle before and after the first sprint and 10 s before and immediately after the tenth sprint. The energy required to sustain the high mean power output (MPO) that was generated over the first 6-s sprint (870.0 +/- 159.2 W) was provided by an equal contribution from phosphocreatine (PCr) degradation and anaerobic glycolysis. Indeed, within the first 6-s bout of maximal exercise PCr concentration had fallen by 57% and muscle lactate concentration had increased to 28.6 mmol/kg dry wt, confirming significant glycolytic activity. However, in the tenth sprint there was no change in muscle lactate concentration even though MPO was reduced only to 73% of that generated in the first sprint. This reduced glycogenolysis occurred despite the high plasma epinephrine concentration of 5.1 +/- 1.5 nmol/l after sprint 9. In face of a considerable reduction in the contribution of anaerobic glycogenolysis to ATP production, it was suggested that, during the last sprint, power output was supported by energy that was mainly derived from PCr degradation and an increased aerobic metabolism.
Tracheobronchial dilation during isocapnic hypoxia in conscious humans
Authors: Julia-Serda G. , Molfino N. A. , Furlott H. G. , McClean P. A. , Rebuck A. S. , Hoffstein V. , Slutsky A. S. , Zamel N. , Chapman K. R.
Published: December 2017

To assess the effects of isocapnic hypoxia on the pharynx, glottis, extrathoracic trachea (ET), intrathoracic trachea (IT), and main bronchi (MB), we measured the cross-sectional areas of these airways by acoustic reflection technique in 15 healthy volunteers. Measurements were made during tidal volume breathing while subjects were normoxic [arterial O2 saturation (SaO2) > 95%] or were made hypoxic by a rebreathing procedure. Under hypoxemic conditions, airway cross-sectional areas increased significantly at ET, IT, and MB levels (P < 0.001). The magnitude of this dilation was similar for both levels of hypoxemia studied (SaO2 80#x2013;85% and 70#x2013;75%); at the milder of the two hypoxemic conditions, ET cross-sectional area increased by 12.4 +/- 4.2% (SE), IT by 10.2 +/- 5.9%, and MB by 19.1 +/- 3.2%. No significant changes were found in the pharyngeal or glottic areas. Dilation was not produced by normoxic isocapnic hyperventilation, and the use of hypoxic airway gas mixtures did not artifactually alter acoustic reflection measurements in a mechanical model. Vagal airway tone, as reflected by airway constriction during pauses in tidal breathing, was unaffected by isocapnic hypoxia. We conclude that isocapnic hypoxia produces dilation of the trachea and major bronchi, an effect unaccounted for by an alteration in the ventilatory pattern.
Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure
Authors: Hampl V. , Archer S. L. , Nelson D. P. , Weir E. K.
Published: December 2017

It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.
Effects of age, adiposity, and fitness level on plasma catecholamine responses to standing and exercise
Authors: Kohrt W. M. , Spina R. J. , Ehsani A. A. , Cryer P. E. , Holloszy J. O.
Published: December 2017

The plasma norepinephrine (NE) and epinephrine (E) responses to a variety of stressors are influenced by age, adiposity, and exercise training status. The objectives of this study were to 1) compare basal levels as well as posture- and exercise-induced changes in plasma NE and E concentrations in young [25 +/- 1 (SE) yr; n = 24] and older (64 +/- 1 yr; n = 106) people and examine the associations of the responses with adiposity and maximal O2 uptake (VO2max) and 2) determine the extent to which the NE and E responses are altered by exercise training in older people. We found no significant differences in basal NE and E levels between young and older subjects. However, the NE response to standing was exaggerated in older people (696 +/- 39 vs. 512 +/- 61 pg/ml; P < 0.05), whereas NE and E responses to exercise requiring approximately 78% of VO2max were attenuated in older people (NE: 1,444 +/- 74 vs. 1,983 +/- 222 pg/ml; E: 109 +/- 10 vs. 228 +/- 29 pg/ml; both P < 0.01). Increments in NE and E during exercise were more closely associated with age (NE: r = -0.38; E: r = -0.46; both P < 0.05) and VO2max (NE: r = 0.43; E: r = 0.52; both P < 0.05) than with adiposity (NE: r = -0.29; E: r = -0.25; both P < 0.05). In 48 older subjects who completed 9 mo of exercise training, the increases in NE and E during exercise at the same absolute intensity were 39 and 57% lower, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Relevance of classification by size to topographical differences in bronchial smooth muscle response
Authors: Chitano P. , Sigurdsson S. B. , Halayko A. J. , Stephens N. L.
Published: December 2017

To investigate heterogeneity of airway smooth muscle response, we studied strips of large and small branches from third- to sixth-generation bronchi obtained from ragweed antigen-sensitized and control dogs. The response to electrical field stimulation and carbamylcholine chloride was greater in strips from larger branches of the same generation when expressed as "tissue stress" (force per unit cross-sectional area of the whole tissue), whereas no difference emerged with use of the more appropriate "smooth muscle stress" (force per unit cross-sectional area of the muscle tissue). The response to histamine was significantly higher in small branches than in large ones, and histamine sensitivity [mean effective concentration (EC50)] was 7.79 x 10(-6) [geometric standard error of the mean (GSEM) 1.20] and 1.49 x 10(-5) M (GSEM 1.14), respectively (P < 0.01). Strips from control and sensitized animals at each site and strips from different generations did not show any significant difference. When we clustered our preparations according to dimensions, the response to histamine was significantly higher in small bronchi than in large ones and histamine EC50 was 8.95 x 10(-6) (GSEM 1.17) and 1.57 x 10(-5) M (GSEM 1.18), respectively (P < 0.05). We conclude that evaluation of muscle response in different tissues requires appropriate normalization. Furthermore, classification into generations is inadequate to study bronchial responsiveness, inasmuch as major differences originate from airway size.
Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar epithelial type II cells
Authors: Wallaert B. , Aerts C. , Gressier B. , Gosset P. , Voisin C.
Published: December 2017

The aim of this work was to evaluate the ability of guinea pig alveolar epithelial type II cells to generate significant amounts of reactive oxygen species to inactivate alpha 1-proteinase inhibitor (alpha 1-PI). Inactivation of alpha 1-PI was evaluated by its inhibitory activity against porcine pancreatic elastase and was expressed as a percentage. The same experiments were performed in parallel with alveolar macrophages (AM) obtained from the same animals and with MRC-5 fibroblasts. Both type II cells and AM released significant amounts of hydrogen peroxide and superoxide, whereas the fibroblasts did not. Unstimulated type II cells (0.5 +/- 2%), AM (1.2 +/- 1.5%), and fibroblasts (0.5 +/- 0.5%) were unable to inactivate alpha 1-PI. Addition of phorbol myristate acetate did not increase their ability to inactivate alpha 1-PI. In contrast, type II cells (79.7 +/- 7%) and AM (80.1 +/- 8%) dramatically inactivated alpha 1-PI in the presence of myeloperoxidase (25 mU/ml), whereas fibroblasts did not. Addition of catalase to the reaction significantly prevented the inactivation of alpha 1-PI. Western blot analysis of alpha 1-PI did not reveal a significant proteolysis of alpha 1-PI, which supports the hypothesis that, in the presence of neutrophil-derived myeloperoxidase, type II cells may oxidatively inactivate alpha 1-PI.
Dynamics of soluble gas exchange in the airways. III. Single-exhalation breathing maneuver
Authors: George S. C. , Babb A. L. , Hlastala M. P.
Published: December 2017

The exchange characteristics of a highly soluble gas with the pulmonary airways during a single-exhalation maneuver were analyzed using a mathematical model previously described by our group (M. E. Tsu et al. Ann. Biomed. Eng. 16: 547–571, 1988). The model integrates the simultaneous exchange of water, heat, and a soluble gas with the pulmonary airways. The purpose of this paper is to provide experimental data for model validation. Exhaled ethyl alcohol concentration profiles of human subjects were measured with an Intoxilyzer 5000 and were plotted against exhaled volume measured with a wedge spirometer. Each subject performed a series of breathing maneuvers in which exhalation flow rate was the only variable. Phase III has a positive slope (0.047 +/- 0.0089 mol alcohol in air.mol alcohol in alveolus-1.l-1) that is statistically independent (P > 0.05) of flow rate. Reducing the molecular diffusion coefficient of alcohol in the nonperfused tissue layer improves the fit of the model to the experimental data. The optimal diffusion coefficient of alcohol for all subjects was 12 +/- 5.3 (SD) x 10(-7) cm2/s, which is 8% of the diffusion coefficient of alcohol in water (1.6 x 10(-5) cm2/s). We concluded that the experimental data showing a positive slope of the exhaled alcohol profile are consistent with a reduced diffusivity of alcohol in the respiratory mucosa. The reduced diffusion coefficient enhances reabsorption of alcohol by the airways on exhalation and creates a positive phase III slope.
Increased muscle perfusion reduces muscle sympathetic nerve activity during handgripping
Authors: Joyner M. J. , Wieling W.
Published: December 2017

This study sought to determine whether increasing blood flow to active muscles can blunt the normal rise in muscle sympathetic nerve activity (MSNA) during heavy rhythmic forearm exercise in humans. Subjects performed 5- to 6-min exercise bouts of handgripping (30/min) at 40–50% of maximum voluntary contraction (MVC). Blood flow was increased by application of suction (50 mmHg) around the forearm. Suction increased deep venous oxygen saturation in blood draining the forearm from 34 +/- 4 to 45 +/- 4%, indicating that muscle blood flow had risen by approximately 20%. Suction had no impact on the heart rate, perceived exertion, or electromyographic responses to the handgripping. During 6 min of exercise at 50% of MVC, MSNA rose from 376 +/- 67 to 970 +/- 125 units during the control trial vs. 396 +/- 69 to 729 +/- 94 units during the suction trial, and the difference was maintained during 2 min of postexercise ischemia (P < 0.05; suction < control). Mean arterial pressure (MAP) rose from 99 +/- 4 to 129 +/- 6 mmHg during control vs. 99 +/- 4 to 126 +/- 6 mmHg during the suction trial, and these responses were only different (P < 0.05; suction < control) during the final minute of the exercise bouts. During postexercise ichemia, MAP was 122 +/- 6 mmHg after the control trial but was only 112 +/- 4 mmHg after the suction trial. These results indicate that forearm suction augmented muscle blood flow, limited the activation of chemosensitive muscle afferents, and blunted the rise in MSNA during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Low-frequency respiratory mechanics using ventilator-driven forced oscillations
Authors: Lutchen K. R. , Kaczka D. W. , Suki B. , Barnas G. , Cevenini G. , Barbini P.
Published: December 2017

We evaluated the potential for using a fast Fourier transform (FFT) analysis applied to a standard ventilator waveform to estimate (< 2 Hz) frequency dependence of respiratory or lung resistance (R) and elastance (E). In four healthy humans we measured pressure and flow at the airway opening while applying sine wave forcing from 0.2 to 0.6 Hz at two tidal volumes (VT; 250 and 500 ml). We then applied a step inspiratory ventilator flow wave with relaxed expiration at the same VT and only 0.2 Hz. Step waveform data were also acquired from nine mechanically ventilated patients under intensive care unit conditions. Finally, we simultaneously measured total respiratory (rs), lung (L), and chest wall (cw) impedance data from two dogs (0.156–2 Hz) before and after severe pulmonary edema. Rrs and Ers were estimated by the FFT approach. Humans displayed a small frequency dependence in Rrs and Ers from 0.2 to 0.6 Hz, and both Rrs and Ers decreased at the higher VT. The spectral estimates of Rrs and Ers with the step ventilator wave were often qualitatively comparable to sine wave results below 0.6 Hz but became extremely erratic above the third harmonic. Conversely, in dogs the step wave produced reliable and stable estimates up to 2 Hz in all conditions. Nevertheless, Ecw and Ers still displayed clear and correlated oscillations with increasing frequency, whereas EL showed none. This suggests that nonlinear processes, most likely at the chest wall, contribute to periodic-like fluctuations in respiratory mechanical properties when estimated by applying FFT to a step ventilator wave. Moreover, in humans, but not dogs, a ventilator flow cycle contains insufficient signal energy beyond the third harmonic. We show that the amount of energy available at higher frequencies is largely governed by the mechanical time constant contributing to passive expiratory flow. In dogs the shorter time constant contributes to increased energy. In essence, the frequency content of the flow is subject dependent, and this is not a desirable situation for controlling the quality of the impedance spectra available from a standard ventilator wave.
Heart rate variability and fractal dimension during orthostatic challenges
Authors: Butler G. C. , Yamamoto Y. , Xing H. C. , Northey D. R. , Hughson R. L.
Published: December 2017

Heart rate variability (HRV) spectral analysis has been used as a tool for short-term assessment of parasympathetic (PNS) and sympathetic nervous system (SNS) control of heart rate. However, it has been suggested that the PNS and SNS indicators are superimposed on a broad-band noise spectrum in which the power spectral densities are inversely proportional to their frequency (1/f beta). In this study, we have used coarse-graining spectral analysis to extract the harmonic components for calculation of PNS and SNS indicators and to obtain the slope (beta) of the 1/f beta component to estimate fractal dimension (DF) of a trail of HRV. DF was regarded as an indicator of cardiovascular system complexity. Ten healthy young subjects (6 women and 4 men) were studied in supine rest and with sequential applications of four levels of lower body negative pressure (LBNP; -10, -20, -30, and -50 mmHg) and head-up tilt (HUT; 10, 20, 30, and 70 degrees). In the 20 tests, there were six occurrences of presyncopal symptoms that required the test to be terminated before the planned end point. At low levels of LBNP or HUT, arterial pulse pressure (PP) was not changed from rest, and calculated DF was very high (beta approximately 1.00). At the higher levels of LBNP and HUT, PP decreased. Coincident with this reduction in PP, PNS activity decreased, SNS activity increased, and DF was reduced, each with a significant linear relationship to the change in PP (PNS: r = 0.56; SNS: r = 0.57; DF: r = 0.70, P < 0.01). Each occurrence of presyncope was associated a low PNS indicator as well as DF < 2.50 (beta > or = 1.80). These data indicate that the cardiovascular system is operating at a reduced level of complexity and further suggest that reduced complexity might not be compatible with cardiovascular homeostasis.
Skeletal unloading causes organ-specific changes in immune cell responses
Authors: Armstrong J. W. , Nelson K. A. , Simske S. J. , Luttges M. W. , Iandolo J. J. , Chapes S. K.
Published: December 2017

The effects of skeletal unloading using antiorthostatic tail suspension on the mouse immune system are tissue specific. This phenomenon was demonstrated by analyzing cells from the lymph nodes, spleen, and bone marrow. Phytohemagglutinin-induced T-cell proliferation was depressed in lymph nodes after 11 days of antiorthostatic suspension. In contrast, splenic T-cell proliferation in response to phytohemagglutinin was enhanced. Splenic natural killer cell cytotoxicity was unchanged after suspension, which demonstrated the organ- and cell-specific effects of skeletal unloading. Whereas antiorthostatic suspension induced minimal changes in bone, there was a significant depression in the number of macrophage precursors in the bone marrow. Overall, skeletally unloaded animals had slightly higher blood corticosterone levels than did control animals; however, it did not appear to be responsible for the observed changes. In conclusion, skeletal unloading produces organ- and cell-specific changes in the murine immune system rather than a generalized immunosuppression.
Effects of adrenalectomy or RU-486 on rat muscle fibers during hindlimb suspension
Authors: Aboudrar S. , Sempore B. , Koubi H. , Dechaud H. , Desplanches D.
Published: December 2017

The purpose of this study was to investigate the effects of a glucocorticoid antagonist, RU-486, and of adrenalectomy (ADX) on rat skeletal muscle structural properties after 3, 7, and 14 days of hindlimb suspension (H). After H, a significant loss in muscle weight was observed as early as 3 days in soleus (SOL; -10%) and adductor longus (AL; -14%) muscles. In SOL, after only 7 days, a reduction (-14%) in type I fiber percent distribution occurred, accompanied by an increase (+129%) in intermediate type I fibers. Fiber type changes increased depending on the duration of H. In AL muscle, no change occurred after H in the fiber type composition despite a similar degree of muscle atrophy. Treatment with RU-486 or ADX significantly reduced the loss of SOL weight observed after 14 days (-42 and -44%, respectively, vs. -50% for H rats), delayed the SOL atrophy (from 3 to 7 days), and normalized the shift in fiber type distribution induced by H. In SOL, administration of RU-486 (but not ADX) partly prevented the reduction in size induced by H of all the fibers. In AL, neither treatment affected the extent of muscle atrophy, even though the reduction in type IIa fiber size was prevented by RU-486 but not by ADX after 14 days of suspension. ADX or RU-486 administration did not prevent the extensor digitorum longus weight loss observed after 14 days of suspension but allowed a recovery of its normal fiber type composition.(ABSTRACT TRUNCATED AT 250 WORDS)
High-sucrose diet inhibits basal secretion of intradentinal dye penetration-stimulating parotid hormone in pigs
Authors: Tieche J. M. , Leonora J. , Steinman R. R.
Published: December 2017

Earlier studies indicated that feeding rats a high-sucrose diet for 1 wk decreases the intrinsic rate of intradentinal dye penetration in molar teeth. Because intradentinal dye penetration appears to be controlled by a parotid hormone, we investigated the chronic effect of a high-sucrose diet on basal parotid hormone secretion in pigs. In fasted pigs, the plasma immunoreactive parotid hormone titer decreased significantly after substitution of a high-sucrose diet for standard chow and remained at a level 72% lower for 40 days until the diet was reverted to standard chow. Within 3 days of diet reversion, the basal hormone titer returned to its original value. The results indicate that a high-sucrose diet can significantly alter the basal secretion of parotid hormone. The possibility exists that inhibition of intradentinal dye penetration after ingestion of a high-sucrose diet could be the result of depressed parotid hormone secretion.
Role of the bronchial circulation in ischemia-reperfusion lung injury
Authors: Pearse D. B. , Wagner E. M.
Published: December 2017

Bronchial arterial (BA) perfusion could modify pulmonary arterial (PA) ischemia-reperfusion (IR) injury by promoting clearance of peribronchial edema or limiting edema formation through maintenance of pulmonary vessel integrity via bronchopulmonary anastomotic or pulmonary vasa vasorum flow. The purpose of this study was to determine the effect of BA perfusion on IR injury in isolated sheep lungs. In 12 lungs (BA++) the BA was perfused throughout 30 min of PA ischemia and 180 min of reperfusion. In 12 lungs (BA-+) BA perfusion was begun with PA reperfusion, and in 15 lungs (BA--) the BA was never perfused. After 180 min, extravascular lung water was less (P < 0.05) in BA++ and B-+ lungs [4.70 +/- 0.16 and 4.57 +/- 0.18 g/g blood-free dry lung (bfdl)] than in BA-- lungs (5.23 +/- 0.19 g/g bfdl). The reflection coefficient for albumin was greater (P < 0.05) in BA++ and BA-+ (0.57 +/- 0.06 and 0.75 +/- 0.03) than in BA-- lungs (0.44 +/- 0.04). The filtration coefficient in BA++ and BA-+ lungs (0.016 +/- 0.006 and 0.015 +/- 0.006 g.min-1 x mmHg-1 x kg-1) was not different from that in BA-- lungs (0.025 +/- 0.006 g.min-1 x mmHg-1 x kg-1). These results suggest that BA perfusion decreased reperfusion edema by attenuating the increase in pulmonary vascular permeability caused by IR injury. Moreover the result in BA-+ lungs suggests that the protective effect was mediated by BA perfusion of PA vasa vasorum rather than bronchopulmonary anastomotic flow, which was trivial compared with PA blood flow.
Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study
Authors: Kuebler W. M. , Kuhnle G. E. , Groh J. , Goetz A. E.
Published: December 2017

To determine the site of sequestration of leukocytes in the lung, we investigated the kinetics of fluorescently labeled erythrocytes and leukocytes in pulmonary arterioles, venules, and alveolar capillaries in vivo by using fluorescence videomicroscopy. The subpleural pulmonary microcirculation of the ventilated rabbit lung was visualized via a transparent window implanted into the right thoracic wall. Fluorescein isothiocyanate-labeled erythrocytes were administered intravenously, whereas leukocytes were labeled in vivo by intravenous injection of rhodamine 6G. Rolling and adherence of leukocytes on the surface of the vessel walls were observed in arterioles as well as in venules. The median velocity of nonadherent leukocytes was significantly higher in arterioles than in venules (84 +/- 12 vs. 15 +/- 3% of erythrocyte velocity, respectively). In alveolar capillaries the majority of leukocytes were retained at distinct sites for periods of 0.1 to > 5 s (median 0.61 s). The relative velocity of leukocytes moving in capillaries was comparable to that determined in arterioles (80 +/- 9% of erythrocyte velocity). These measurements indicate that leukocyte sequestration in the lung is governed by the retention of leukocytes in capillaries and by the interaction of leukocytes with microvascular endothelium of arterioles and venules. We propose that the kinetics of these phenomena determine the equilibrium between circulating and sequestered leukocytes.