bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)
Authors: Gelfand R. , Lambertsen C. J. , Clark J. M. , Hopkin E.
Published: December 2017

Gelfand, R., C. J. Lambertsen, J. M. Clark, and E. Hopkin.Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI). J. Appl. Physiol. 84(1): 292–302, 1998.—Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.
Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres
Authors: Buchwalder Lynn F. , Lin Michelle , McDonald Thomas J. , Nathanielsz Peter W.
Published: December 2017

Buchwalder, Lynn F., Michelle Lin, Thomas J. McDonald, and Peter W. Nathanielsz. Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres. J. Appl. Physiol. 84(1): 82–89, 1998.—Adrenal gland blood flow (ABF) increases during hypoxemia in fetal sheep, but regulation of ABF is poorly understood. The purpose of this study was to determine the effects of splanchnic nerve section on fetal ABF responses to hypoxemia using the fluorescent microsphere (FM) technique. At 125 days of gestation, 14 unanesthetized fetal sheep [bilateral splanchnicotomy (Splx, n = 6) and control (Cont, n = 8)] were injected with FM before and at 60 min of N2-induced hypoxemia (∼40% decrease in fetal arterial [Formula: see text]). Adrenal tissue and reference blood samples were digested and filtered, and FM dye was extracted for spectrometer analysis. Baseline whole, medullary, and cortical ABF for the Cont group were similar to published values using radioactive microspheres and did not differ from Splx values. Hypoxemia increased whole, medullary, and cortical ABF (mean ± SE) from baseline for the Cont group by 281 ± 35, 258 ± 31, and 496 ± 81% ( P < 0.05). The increase for the Splx group was attenuated compared with the Cont group ( P < 0.05) for whole and medullary ABF (139 ± 27 and 43 ± 27%) but not cortical ABF (326 ± 91%). We conclude that 1) the FM technique is valid for measuring fetal ABF and 2) in fetal sheep the splanchnic nerve is not necessary to maintain basal ABF but plays an important role in regulating the hypoxemia-induced increase in ABF through the medullary, but not cortical, ABF response.
Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography
Authors: Peslin R. , Duvivier C.
Published: December 2017

Peslin, R., and C. Duvivier. Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography. J. Appl. Physiol. 84(2): 553–561, 1998.—We have tested the feasibility of separating the airway (Zaw) and tissue (Zti) components of total respiratory input impedance (Zrs,in) in healthy subjects by measuring alveolar gas compression by body plethysmography (Vpl) during pressure oscillations at the airway opening. The forced oscillation setup was placed inside a body plethysmograph, and the subjects rebreathedbtps gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zaw and Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gas volume. The data were in good agreement with previous observations: airway and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 ± 0.003 hPa ⋅ s2 ⋅ l−1and tissue reactance with an elastance of 36 ± 8 hPa/l. The changes seen with varying lung volume, during elastic loading of the chest and during bronchoconstriction, were mostly in agreement with the expected effects. The data, as well as computer simulation, suggest that the partitioning is unaffected by mechanical inhomogeneity and only moderately affected by airway wall shunting.
Age and gender dependency of baroreflex sensitivity in healthy subjects
Authors: Laitinen Tomi , Hartikainen Juha , Vanninen Esko , Niskanen Leo , Geelen Ghislaine , Länsimies Esko
Published: December 2017

Laitinen, Tomi, Juha Hartikainen, Esko Vanninen, Leo Niskanen, Ghislaine Geelen, and Esko Länsimies. Age and gender dependency of baroreflex sensitivity in healthy subjects. J. Appl. Physiol. 84(2): 576–583, 1998.—We evaluated the correlates of baroreflex sensitivity (BRS) in healthy subjects. The study consisted of 117 healthy, normal-weight, nonsmoking male and female subjects aged 23–77 yr. Baroreflex control of heart rate was measured by using the phenylephrine bolus-injection technique. Frequency- and time-domain analysis of heart rate variability and an exercise test were performed. Plasma norepinephrine, epinephrine, insulin, and arginine vasopressin concentrations and plasma renin activity were measured. In the univariate analysis, BRS correlated with age ( r = −0.65, P < 0.001), diastolic blood pressure ( r = −0.47, P < 0.001), exercise capacity ( r = 0.60, P < 0.001), and the high-frequency component of heart rate variability ( r= 0.64, P < 0.001). There was also a significant correlation between BRS and plasma norepinephrine concentration ( r = −0.22, P < 0.05) and plasma renin activity ( r = 0.32, P < 0.001). According to the multivariate analysis, age and gender were the most important physiological correlates of BRS. They accounted for 52% of interindividual BRS variation. In addition, diastolic blood pressure and high-frequency component of heart rate variability were significant independent correlates of BRS. BRS was significantly higher in men than in women (15.0 ± 1.2 vs. 10.2 ± 1.1 ms/mmHg, respectively; P < 0.01). Twenty-four percent of women >40 yr old and 18% of men >60 yr old had markedly depressed BRS (<3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthy subjects. In addition, we demonstrate that BRS values that have been proposed to be useful in identifying postinfarction patients at high risk of sudden death are frequently found in healthy subjects.
Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity
Authors: Lauzon Anne-Marie , Elliott Ann R. , Paiva Manuel , West John B. , Prisk G. Kim
Published: December 2017

Lauzon, Anne-Marie, Ann R. Elliott, Manuel Paiva, John B. West, and G. Kim Prisk. Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity. J. Appl. Physiol. 84(2): 661–668, 1998.—We studied the phase relationships of the cardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (μG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balance O2, preceded at residual volume by a 150-ml Ar bolus. Pairs of gas signals, all of which still showed cardiogenic oscillations, were cross-correlated, and their phase difference was expressed as an angle. Phase relationships between inspired gases (e.g., He) and resident gas (N2) showed no change from 1 G (211 ± 9°) to μG (163 ± 7°). Ar bolus and He were unaltered between 1 G (173 ± 15°) and μG (211 ± 25°), showing that airway closure in μG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast, CO2 reversed phase with He between 1 G (332 ± 6°) and μG (263 ± 27°), strongly suggesting that, in μG, areas of high ventilation are associated with high ventilation-perfusion ratio (V˙a/Q˙). This widening of the range ofV˙a/Q˙in μG may explain previous measurements (G. K. Prisk, A. R. Elliott, H. J. B. Guy, J. M. Kosonen, and J. B. West. J. Appl. Physiol. 79: 1290–1298, 1995) of an overall unaltered range ofV˙a/Q˙in μG, despite more homogeneous distributions of both ventilation and perfusion.
Kinetics of CO2excretion and intravascular pH disequilibria during carbonic anhydrase inhibition
Authors: Cardenas Victor , Heming Thomas A. , Bidani Akhil
Published: December 2017

Cardenas, Victor, Jr., Thomas A. Heming, and Akhil Bidani.Kinetics of CO2excretion and intravascular pH disequilibria during carbonic anhydrase inhibition. J. Appl. Physiol. 84(2): 683–694, 1998.—Inhibition of carbonic anhydrase (CA) activity (activity in red blood cells and activity available on capillary endothelium) results in decrements in CO2excretion (V˙co2) and plasma-erythrocyte CO2-[Formula: see text]-H+disequilibrium as blood travels around the circulation. To investigate the kinetics of changes in blood [Formula: see text]and pH during progressive CA inhibition, we used our previously detailed mathematical model of capillary gas exchange to analyze experimental data of V˙co2and blood-gas/pH parameters obtained from anesthetized, paralyzed, and mechanically ventilated dogs after treatment with acetazolamide (Actz, 0–100 mg/kg iv). Arterial and mixed venous blood samples were collected via indwelling femoral and pulmonary arterial catheters, respectively. Cardiac output was measured by thermodilution. End-tidal[Formula: see text], as a measure of alveolar[Formula: see text], was obtained from continuous records of airway [Formula: see text] above the carina. Experimental results were analyzed with the aid of a mathematical model of lung and tissue-gas exchange. Progressive CA inhibition was associated with stepwise increments in the equilibrated mixed venous-alveolar [Formula: see text] gradient (9, 19, and 26 Torr at 5, 20, and 100 mg/kg Actz, respectively). The maximum decrements in V˙co2were 10, 24, and 26% with 5, 20, and 100 mg/kg Actz, respectively, without full recovery ofV˙co2at 1 h postinfusion. Equilibrated arterial [Formula: see text]overestimated alveolar [Formula: see text], and tissue [Formula: see text] was underestimated by the measured equilibrated mixed venous blood[Formula: see text]. Mathematical model computations predicted hysteresis loops of the instantaneous CO2-[Formula: see text]-H+relationship and in vivo blood[Formula: see text]-pH relationship due to the finite reaction times for CO2-[Formula: see text]-H+reactions. The shape of the hysteresis loops was affected by the extent of Actz inhibition of CA in red blood cells and plasma.
Controlled dissolution from wax-coated aerosol particles in canine lungs
Authors: Pillai Raviraj S. , Yeates Donovan B. , Miller Irving F. , Hickey Anthony J.
Published: December 2017

Pillai, Raviraj S., Donovan B. Yeates, Irving F. Miller, and Anthony J. Hickey. Controlled dissolution from wax-coated aerosol particles in canine lungs. J. Appl. Physiol. 84(2): 717–725, 1998.—Treatment of pulmonary and systemic diseases may be improved and toxicity reduced by pulmonary deposition of drug-containing aerosols exhibiting delayed dissolution. Aqueous disodium fluorescein and pentamidine aerosols were dried, concentrated, and condensation coated with paraffin wax. The apparent mass median aerodynamic diameters of the coated fluorescein particles were 2.8–4.0 μm. Wax-to-fluorescein ratios were 0.38–1.05. The dissolution half times determined using a single-pass flow system were 1.5 min for uncoated fluorescein and 0.8 min for uncoated pentamidine. These increased over threefold when the aerosols were coated with paraffin wax to maxima of 5.3 and 2.6 min, respectively. Wax-coated aerosols generated from fluorescein mixed with99mTc-labeled iron oxide colloid delivered to the canine lungs demonstrated a 3.4-fold increase in the absorption half time of disodium fluorescein compared with uncoated fluorescein (11.2 vs. 38.4 min). The absence of changes in pulmonary function on inhalation of these wax-coated aerosols, together with a high drug load and delayed release, establishes a foundation for future therapeutic applications.
Electrical impedance tomography can monitor dynamic hyperinflation in dogs
Authors: Adler Andy , Shinozuka Norihiro , Berthiaume Yves , Guardo Robert , Bates Jason H. T.
Published: December 2017

Adler, Andy, Norihiro Shinozuka, Yves Berthiaume, Robert Guardo, and Jason H. T. Bates. Electrical impedance tomography can monitor dynamic hyperinflation in dogs. J. Appl. Physiol. 84(2): 726–732, 1998.—We assessed in eight dogs the accuracy with which electrical impedance tomography (EIT) can monitor changes in lung volume by comparing the changes in mean lung conductivity obtained with EIT to changes in esophageal pressure (Pes) and to airway opening pressure (Pao) measured after airway occlusion. The average volume measurement errors were determined: 26 ml for EIT; 35 ml for Pao; and 54 ml for Pes. Subsequently, lung inflation due to applied positive end-expiratory pressure was measured by EIT (ΔVEIT) and Pao (ΔVPao) under both inflation and deflation conditions. Whereas ΔVPaowas equal under both conditions, ΔVEITwas 28 ml greater during deflation than inflation, indicating that EIT is sensitive to lung volume history. The average inflation ΔVEITwas 67.7 ± 78 ml greater than ΔVPao, for an average volume increase of 418 ml. Lung inflation due to external expiratory resistance was measured during ventilation by EIT (ΔVEIT,vent) and Pes (ΔVPes,vent) and at occlusion by EIT (ΔVEIT,occl), Pes, and Pao. The average differences between EIT estimates and ΔVEIT,occlwere 5.8 ± 44 ml for ΔVEIT,ventand 49.5 ± 34 ml for ΔVEIT,occl. The average volume increase for all dogs was 442.2 ml. These results show that EIT can provide usefully accurate estimates of changes in lung volume over an extended time period and that the technique has promise as a means of conveniently and noninvasively monitoring lung hyperinflation.
Acoustic reflections during rhinometry: spatial resolution and sound loss
Authors: Hilberg Ole , Lyholm Benny , Michelsen Axel , Pedersen Ole F. , Jacobsen Oluf
Published: December 2017

The accuracy of the acoustic reflections method for the evaluation of human nasal airway geometry is determined by the physical limitations of the technique and also by the in vivo deviations from the assumptions of the technique. The present study 1) examines the sound loss caused by nonrigidity of the nasal mucosa and viscous loss caused by complex geometry and its influence on the estimation of the acoustic area-distance function; 2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathing He-O2during the measurements on accuracy. Measurements made in eight plastic models, with cavities exactly identical to the “living” nasal cavities, revealed only minor effects of nonrigidity of the nasal mucosa. This was confirmed by an electrical analog model, based on laser vibrometry admittance measurements of the nasal mucosa, which indicated that the error in the acoustic measurements caused by wall motion is insignificant. The complex geometry of the nasal cavity per se (i.e., departure from circular) showed no significant effects on the measurements. Low-pass filtering of the signal is necessary to cut off cross modes arising in the nasal cavity. Computer simulations and measurements in models showed that the sampling frequency should be approximately four times the low-pass filtering frequency (i.e., twice the Nyquist frequency) to avoid influence on the result. No advantage was found for the the use of He-O2vs. air in the nasal cavity.
Probabilistic models of the role of oxygen in human decompression sickness
Authors: Parker E. C. , Survanshi S. S. , Massell P. B. , Weathersby P. K.
Published: December 2017

Probabilistic models of human decompression sickness (DCS) have been successful in describing DCS risk observed across a wide variety of N2-O2dives but have failed to account for the observed DCS incidence in dives with high [Formula: see text] during decompression. Our most successful previous model, calibrated with 3,322 N2-O2dives, predicts only 40% of the observed incidence in dives with 100% O2 breathing during decompression. We added 1,013 O2 decompression dives to the calibration data. Fitting the prior model to this expanded data set resulted in only a modest improvement in DCS prediction of O2 data. Therefore, two O2-specific modifications were proposed: [Formula: see text]-based alteration of inert gas kinetics ( model 1) and[Formula: see text] contribution to total inert gas ( model 2). Both modifications statistically significantly improved the fit, and each predicts 90% of the observed DCS incidence in O2dives. The success of models 1 and 2 in improving prediction of DCS occurrence suggests that elevated [Formula: see text]levels contribute to DCS risk, although less than the equivalent amount of N2. Both models allow rational optimization of O2 use in accelerating decompression procedures.
Appropriate background correction for DTPA aerosol clearance
Authors: Mason G. R. , Peters A. M. , Myers M. J. , Hughes J. M. B.
Published: December 2017

Measurement of the clearance rate of inhaled aerosols of99mTc-diethylenetriamine pentaacetic acid (DTPA) from distal airway to pulmonary capillary is a sensitive technique for the detection of lung injury. As the solute diffuses across the blood-gas barrier, the concentration in circulating blood increases, giving rise to a background signal superimposed on the signal from residual DTPA in the airway. Background subtraction is conventionally based on the thigh, but this tissue has the disadvantage in that its composition, in terms of the relative volumes of its extracellular extravascular and intravascular compartments (a ratio of ∼4:1), is quite different from that of the lung (<1:6). With comparison to the thigh, we examined alternative regions for background, liver, and cranium, which have extravascular-to-intravascular compartment ratios much closer to these for the lung, to determine the most appropriate background for correction of the pulmonary signal. From 1 min after intravenous injection of 99mTc-DTPA, the time-activity curves recorded by a gamma camera over the liver and lung in a group of otherwise normal cigarette smokers decreased up to 30 min after injection, with time courses that could essentially be superimposed on each other; the curve recorded over the thigh with a separate scintillation probe continued to increase. The curve recorded over the cranium had a time course similar to that for the liver and lung. Following aerosol inhalation, the lung clearance rates over the initial 7 min when background subtraction was used, based on the liver, cranium, and thigh were, respectively, 4.9 ± 2.9, 4.7 ± 2.6, and 5.4 ± 3.4 (SD) %/min, compared with 4.1 ± 2.2%/min without subtraction. The corresponding values based on 30 min of data were 3.3 ± 1.4, 3.4 ± 1.4, 4.2 ± 2.3, and 2.8 ± 1.0%/min. When the liver was used for background, the lung clearance curves were clearly multiexponential, whereas thigh correction tended to give curves that were monoexponential or even convex upward on semilogarithmic axes. With an appropriate region for background, the true shape of a lung curve can be identified, which permits the study of an intervention on the clearance while it is in progress. The intravenous DTPA, required for calibrating the background regions, can be given before inhalation of the tracer.
Mitochondrial redox state as a potential detector of liver dysoxia in vivo
Authors: Dishart Michael K. , Schlichtig Robert , Tønnessen Tor Inge , Rozenfeld Ranna A. , Simplaceanu Elena , Williams Donald , Gayowski Timothy J. P.
Published: December 2017

Dysoxia can be defined as ATP flux decreasing in proportion to O2availability with preserved ATP demand. Hepatic venous β-hydroxybutyrate-to-acetoacetate ratio (β-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detect the onset of dysoxia. During partial dysoxia (as opposed to anoxia), however, flow may be adequate in some liver regions, diluting effluent from dysoxic regions, thereby rendering venous β-OHB/AcAc unreliable. To address this concern, we estimated tissue ATP while gradually reducing liver blood flow of swine to zero in a nuclear magnetic resonance spectrometer. ATP flux decreasing with O2availability was taken as O2uptake (V˙o2) decreasing in proportion to O2delivery (Q˙o2); and preserved ATP demand was taken as increasing Pi/ATP.V˙o2, tissue Pi/ATP, and venous β-OHB/AcAc were plotted againstQ˙o2to identify critical inflection points. Tissue dysoxia required meanQ˙o2for the group to be critical for bothV˙o2and for Pi/ATP. CriticalQ˙o2values forV˙o2and Pi/ATP of 4.07 ± 1.07 and 2.39 ± 1.18 (SE) ml ⋅ 100 g−1⋅ min−1, respectively, were not statistically significantly different but not clearly the same, suggesting the possibility that dysoxia might have commenced after V˙o2began decreasing, i.e., that there could have been “O2conformity.” CriticalQ˙o2for venous β-OHB/AcAc was 2.44 ± 0.46 ml ⋅ 100 g−1⋅ min−1( P = NS), nearly the same as that for Pi/ATP, supporting venous β-OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver.
Effect of reactive oxygen species on K+ contractures in the rat diaphragm
Authors: Lawler John M. , Hu Z. , Barnes W. S.
Published: December 2017

Reactive oxygen species (ROS) are postulated to alter low-frequency contractility of the unfatigued and fatigued diaphragm. It has been proposed that ROS affect contractility through changes in membrane excitability and excitation-contraction coupling. If this hypothesis is true, then ROS should alter depolarization-dependent K+contractures. Xanthine oxidase (0.01 U/ml) + hypoxanthine (1 mM) were used as a source of superoxide anion eliciting oxidative stress on diaphragm fiber bundles in vitro. Diaphragm fiber bundles from 4-mo-old Fischer 344 rats were extracted and immediately placed in Krebs solution bubbled with 95% O2-5% CO2. After 10 min of equilibration, a K+ contracture (Pre; 135 mM KCl) was induced. Fiber bundles were assigned to the following treatment groups: normal Krebs-Ringer (KR; Con) and the xanthine oxidase system (XO) in KR solution. After 15 min of treatment exposure, a second (Post) K+contracture was elicited. Mean time-to-peak tension for contractures was significantly decreased in Post vs. Pre (16.0 ± 0.7 vs. 19.8 ± 1.0 s) with XO; no change was noted with Con. Furthermore, peak contracture tension was significantly higher (31.5%) in the XO group Post compared with Pre; again, no significant change was found with KR. The relaxation phase was also altered with XO but not with KR. Additional experiments were conducted with application of 1 mM hypoxanthine, with results similar to the Con group. We conclude that the application of ROS altered the dynamics of K+ contractures in the rat diaphragm, indicating changes in voltage-dependent excitation-contraction coupling.
Sustained submaximal exercise does not alter the integrity of the lung blood-gas barrier in elite athletes
Authors: Hopkins Susan R. , Schoene Robert B. , Henderson William R. , Spragg Roger G. , West John B.
Published: December 2017

The extreme thinness of the pulmonary blood-gas barrier results in high mechanical stresses in the capillary wall when the capillary pressure rises during exercise. We have previously shown that, in elite cyclists, 6–8 min of maximal exercise increase blood-gas barrier permeability and result in higher concentrations of red blood cells, total protein, and leukotriene B4 in bronchoalveolar lavage (BAL) fluid compared with results in sedentary controls. To test the hypothesis that stress failure of the barrier only occurs at the highest level of exercise, we performed BAL in six healthy athletes after 1 h of exercise at 77% of maximal O2 consumption. Controls were eight normal nonathletes who did not exercise before BAL. In contrast with our previous study, we did not find higher concentrations of red blood cells, total protein, and leukotriene B4 in the exercising athletes compared with control subjects. However, higher concentrations of surfactant apoprotein A and a higher surfactant apoprotein A-to-phospholipid ratio were observed in the athletes performing prolonged exercise, compared with both the controls and the athletes from our previous study. These results suggest that, in elite athletes, the integrity of the blood-gas barrier is altered only at extreme levels of exercise.
Production and absorption of nitric oxide gas in the nose
Authors: Dubois Arthur B. , Douglas James S. , Stitt John T. , Mohsenin Vahid
Published: December 2017

Some nitric oxide gas (NO) produced in the sinuses and nasal cavity is absorbed before leaving the nose. To measure production and absorption, we introduced NO at different concentrations into one nostril while sampling the NO leaving the opposite nostril with the soft palate closed. The quantity of NO gas produced in six normal subjects (amount leaving plus the amount absorbed) averaged 352 nl/min and was the same at gas flows ranging from 8 to 347 ml/min and at 10 l/min. An absorption coefficient A was calculated by dividing the amount of NO absorbed by the concentration leaving the nose. A ranged from 17 ml/min at a nasal gas flow of 8 ml/min to an A of 24 ml/min at a nasal gas flow of 347 ml/min. The calculated rates of production and absorption did not change when gas flow rate was increased, suggesting diffusion equilibrium. The amount of uptake of NO in the nasal mucosa can be explained by its solubility coupled with tissue and blood reactivity.
Exercise training increases K+-channel contribution to regulation of coronary arterial tone
Authors: Bowles D. K. , Laughlin M. H. , Sturek M.
Published: December 2017

The present study examined whether regulation of coronary tone in conduit arteries (>1.0 mm ID) is altered by exercise training. Yucatan miniature swine were treadmill trained for 16–20 wk (Ex) and compared with sedentary counterparts (Sed). Endothelium-denuded arterial rings were stretched to optimal length and allowed to equilibrate for 60 min. Inhibition of either Ca2+-activated channels [1 mM tetraethylammonium (TEA) or 10 nM iberiotoxin (IBTX)] or voltage-dependent K+channels [1 mM 4-aminopyridine (4-AP)] significantly increased resting tension in both groups; however, the effect of all K+-channel blockers was greater in Ex. Addition of 1 mM sodium nitroprusside reduced resting tension in both groups, confirming the presence of active basal tone; however, sodium nitroprusside-sensitive tone was increased approximately twofold in Ex compared with Sed group. Perforated patch-clamp experiments on isolated smooth muscle cells demonstrated no effect of exercise training on whole cell TEA-sensitive, 4-AP-sensitive, or basal K+current. Similarly, whereas TEA, 4-AP, and IBTX all decreased resting membrane potential, there was no difference in depolarization between groups. The greater effect of TEA on resting tension in Ex could be mimicked in Sed by addition of the Ca2+-channel agonist BAY K 8644. In conclusion, the greater response to K+-channel blockers after exercise training is consistent with an increased contribution of K+channels to regulation of basal tone in conduit coronary arteries. The lack of an effect of training on K+current characteristics or membrane potential responses in isolated cells suggests that a requisite factor for enhanced K+-channel activation in arteries from Ex, possibly stretch, is absent in isolated cells.
Diet-induced insulin resistance precedes other aspects of the metabolic syndrome
Authors: Barnard R. James , Roberts Christian K. , Varon Shira M. , Berger Joshua J.
Published: December 2017

This study was designed to examine the effects of a high-fat refined-sugar (HFS) or a low-fat complex-carbohydrate (LFCC) diet on insulin-stimulated skeletal muscle glucose transport, plasma insulin, blood pressure, plasma triglycerides, plasma glycerol, body weight, and body fat in female Fischer rats. Insulin-stimulated glucose transport was significantly reduced in the HFS group at 2 wk, 2 mo, and 2 yr, whereas serum insulin was significantly elevated at all time points. Blood pressure was not significantly elevated in the HFS group until 12 mo, and all HFS animals were hypertensive by 18 mo. Glycerol, triglycerides, and abdominal fat cell size were not significantly different at 2 wk but were significantly elevated in the HFS rats at 2 and 6 mo. Body weight was similar in both groups until 20 wk on the diet, when the HFS rats started to gain more weight. These results demonstrate that insulin resistance and hyperinsulinemia occur before the other manifestations of the metabolic syndrome and that diet, not obesity, is the underlying cause.
Effect on airway caliber of stimulation of the hypothalamic locomotor region
Authors: Beyaert Christian A. , Hill Janeen M. , Lewis Brock K. , Kaufman Marc P.
Published: December 2017

Airway dilation is one of the many autonomic responses to exercise. Two neural mechanisms are believed to evoke these responses: central command and the muscle reflex. Previously, we found that activation of central command, evoked by electrical and chemical stimulation of the mesencephalic locomotor region, constricted the airways rather than dilated them. In the present study we examined in decerebrate paralyzed cats the role played by the hypothalamic locomotor region, the activation of which also evokes central command, in causing the airway dilator response to exercise. We found that activation of the hypothalamic locomotor region by electrical and chemical stimuli evoked fictive locomotion and, for the most part, airway constriction. Fictive locomotion also occurred spontaneously, and this too, for the most part, was accompanied by airway constriction. We conclude that central command plays a minor role in the airway dilator response to exercise.
Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure
Authors: Silber David H. , Sutliff Greg , Yang Qing X. , Smith Michael B. , Sinoway Lawrence I. , Leuenberger Urs A.
Published: December 2017

In congestive heart failure (CHF), the mechanisms of exercise-induced sympathoexcitation are poorly defined. We compared the responses of sympathetic nerve activity directed to muscle (MSNA) and to skin (SSNA, peroneal microneurography) during rhythmic handgrip (RHG) at 25% of maximal voluntary contraction and during posthandgrip circulatory arrest (PHG-CA) in CHF patients with those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similar in both groups (CHF patients, n = 12; controls, n = 10). However, during PHG-CA, in the controls MSNA returned to baseline, whereas it remained elevated in CHF patients ( P < 0.05). Similarly, at end exercise, the increase in SSNA was comparable in both groups (CHF patients, n = 11; controls, n = 12), whereas SSNA remained elevated during PHG-CA in CHF patients but not in the controls ( P < 0.05). In a separate control group ( n = 6), even high-intensity static handgrip was not accompanied by sustained elevation of SSNA during PHG-CA.31P-nuclear magnetic resonance spectroscopy during RHG demonstrated significant muscle acidosis and accumulation of inorganic phosphate in CHF patients ( n = 7) but not in controls ( n = 9). We conclude that in CHF patients rhythmic forearm exercise leads to premature fatigue and accumulation of muscle metabolites. The prominent PHG-CA response of MSNA and SSNA in CHF patients suggests activation of the muscle metaboreflex. Because, in contrast to controls, in CHF patients both MSNA and SSNA appear to be under muscle metaboreflex control, the mechanisms and distribution of sympathetic outflow during exercise appear to be different from normal.
Nicotine impairs histamine-induced increases in macromolecular efflux: role of oxygen radicals
Authors: Mayhan William G. , Sharpe Glenda M.
Published: December 2017

Nicotine, a major component of cigarettes and smokeless tobacco, has toxic effects on endothelium and impairs reactivity of resistance arterioles in response to agonists that stimulate the synthesis and/or release of nitric oxide. However, the effect of nicotine on nitric oxide synthase-dependent increases in macromolecular transport is not known. Thus our first goal was to determine the effect of nicotine on histamine-induced increases in macromolecular efflux. We used intravital microscopy and FITC dextran (mol wt 70,000) (FITC-dextran-70K) to examine macromolecular extravasation from postcapillary venules in response to histamine before and after intravenous infusion of vehicle or nicotine. Extravasation of macromolecules was quantitated by counting venular leaky sites and calculating clearance (ml/s × 10−6) of FITC-dextran-70K. Histamine elicited reproducible increases in venular leaky sites and clearance in hamsters infused with vehicle. In contrast, nicotine infusion inhibited histamine-induced increases in macromolecular efflux. Histamine (1.0 and 5.0 μM) elicited 19 ± 2 and 34 ± 4 vs. 3 ± 1 and 11 ± 5 leaky sites per 0.11 cm2, before vs. after nicotine infusion, respectively ( P < 0.05). Histamine-induced clearance of FITC-dextran-70K was also impaired after infusion of nicotine. Our second goal was to examine whether alterations in histamine-induced increases in macromolecular efflux by nicotine may be related to the production of oxygen radicals. Application of superoxide dismutase (150 U/ml) to the hamster cheek pouch restored histamine-induced increases in venular leaky sites and clearance of FITC-dextran-70K during infusion of nicotine. Thus nicotine alters agonist-induced increases in microvascular permeability, via the formation of oxygen radicals, to presumably inactivate nitric oxide.
Gravity effects on upper airway area and lung volumes during parabolic flight
Authors: Beaumont Maurice , Fodil Redouane , Isabey Daniel , Lofaso Frédéric , Touchard Dominique , Harf Alain , Louis Bruno
Published: December 2017

We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity (∼0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1.8 +Gzwas associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (−0.6 liter) and from microgravity to hypergravity (−0.5 liter). Laryngeal narrowing also occurred in both positions (about −15%) when gravity increased from 0 to 1.8 +Gz. We concluded that variation in lung volume is insufficient to explain all upper airway caliber variation but that direct gravity effects on tissues surrounding the upper airway should be taken into account.
Regulation of glucose transporters GLUT-4 and GLUT-1 gene transcription in denervated skeletal muscle
Authors: Jones Jared P. , Tapscott Edward B. , Olson Ann Louise , Pessin Jeffrey E. , Dohm G. Lynis
Published: December 2017

Because GLUT-4 expression is decreased whereas GLUT-1 expression is increased in denervated skeletal muscle, we examined the effects of denervation on GLUT-4 and GLUT-1 gene transcription. The right hindlimb skeletal muscle of male transgenic mice containing sequential truncations (2,400, 1,639, 1,154, and 730 bp) of the human GLUT-4 promoter linked to the chloramphenacol acyl transferase (CAT) gene was denervated, and the contralateral hindlimb was sham operated. RNase protection analysis revealed that after 72 h denervation decreased CAT mRNA and GLUT-4 mRNA levels 64–85%, respectively ( P < 0.05), in the gastrocnemius muscles. In contrast, denervation of the right hindlimb of male rats increased GLUT-1 gene transcription and GLUT-1 mRNA levels by 94 and 213%, respectively ( P < 0.05). In conclusion, GLUT-4 transcription is decreased but GLUT-1 transcription is increased in denervated skeletal muscle, suggesting that the effects of denervation on GLUT-4 and GLUT-1 expression are, in part, transcriptionally mediated. Furthermore, these data indicate that a DNA sequence regulated by denervation is located within 730 bp of the 5′-flanking promoter region of the human GLUT-4 gene.
Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle
Authors: Galassetti Pietro , Gibbons Fiona K. , Hamilton Katherine S. , Lacy D. Brooks , Cherrington Alan D. , Wasserman David H.
Published: December 2017

The hypothesis that glucose ingestion in the postexercise state enhances the synthesis of glutamine and alanine in the skeletal muscle was tested. Glucose was infused intraduodenally for 150 min (44.5 μmol ⋅ kg−1⋅ min−1) beginning 30 min after a 150-min period of exercise ( n = 7) or an equivalent duration sedentary period ( n = 10) in 18-h-fasted dogs. Prior exercise caused a twofold greater increase in limb glucose uptake during the intraduodenal glucose infusion compared with uptake in sedentary dogs. Arterial glutamine levels fell gradually with the glucose load in both groups. Net hindlimb glutamine efflux increased in response to intraduodenal glucose in exercised but not sedentary dogs ( P < 0.05–0.01). Arterial alanine levels, depleted by 50% with exercise, rose with intraduodenal glucose in exercised but not sedentary dogs ( P < 0.05–0.01). Net hindlimb alanine efflux also rose in exercised dogs in response to intraduodenal glucose ( P < 0.05–0.01), whereas it was not different from baseline in sedentary controls for the first 90 min of glucose infusion. Beyond this point, it, too, rose significantly. We conclude that oral glucose may facilitate recovery of muscle from prolonged exercise by enhancing the removal of nitrogen in the form of glutamine and alanine.
Load compensation as a function of state during sleep onset
Authors: Gora John , Kay Amanda , Colrain Ian M. , Kleiman Jan , Trinder John
Published: December 2017

Ventilation decreases and airway resistance increases with the loss of electroencephalogram alpha activity at sleep onset. The aim of this study was to determine whether reflexive load compensation is lost immediately on the loss of alpha activity. Six healthy male subjects were studied under two conditions (load and control-no load), in three states (continuous alpha, continuous theta, and immediately after a transition from alpha to theta), and in two phases (early and late sleep onset). Ventilation and respiratory timing were measured. A comparison of loaded with control conditions indicated that loading had no effect on inspiratory minute ventilation during continuous alpha (differential effect of 0.00 l/min) and only a small, nonsignificant effect in theta immediately after phase 2 transitions (0.31 l/min), indicating a preservation of load compensation at these times. However, there were significant decreases in inspiratory minute ventilation on loaded trials during continuous theta in phase 2 (0.77 l/min) and phase 3 (1.15 l/min) and during theta immediately after a transition in phase 3 (0.87 l/min), indicating a lack of reflexive load compensation. The results indicate that, because reflex load compensation is state dependent, state-related changes in airway resistance contribute to state-related changes in ventilation during sleep onset. However, this effect was slightly delayed with transitions into theta early in sleep.
Meniscus formation during tracheal instillation of surfactant
Authors: Espinosa F. F. , Kamm R. D.
Published: December 2017

The method of surfactant instillation into the lungs for treatment of neonatal respiratory distress syndrome is an important attribute of delivery, and it may determine the overall efficacy of treatment. Previous studies primarily focused on the rate at which the bolus is instilled. These findings show that rapid injections lead to a more homogenous distribution, whereas slow infusions drain into the dependent lung with respect to gravity, resulting in a heterogeneous deposition. These results suggest that it is beneficial to form a meniscus, from which a more homogenous dispersal can proceed. The objective of the present study was to develop a functional criterion for meniscus formation during bolus injection. An in vitro experiment was used to examine the clinical setting of surfactant instillation. The physical variables examined were the bolus viscosity (μ) and density (ρ), gravity ( g), injection rate (Q), orientation of the trachea with respect to gravity (θ), tracheal size ( D), surface tension (γ), and catheter size ( d). All quantities were varied, except gravity and catheter size. Experimental results show that a meniscus will form when NSt> 0.004Re2/3, where NStis Stokes number and Re is Reynolds number, NSt= μQ/ D4ρ gsinθ, a ratio of viscous effects to gravitational effects, and Re = ρQ D/ d2μ, a ratio of inertial effects to viscous effects. Rapid injections, high viscosity, and small inclination with respect to gravity promote meniscus formation. These results can be used to refine the guidelines for administration of surfactant replacement therapy.
Lack of effect of spaceflight on bone mass and bone formation in group-housed rats
Authors: Wronski T. J. , Li M. , Shen Y. , Miller S. C. , Bowman B. M. , Kostenuik P. , Halloran B. P.
Published: December 2017

As part of an experiment to study the role of corticosteroids in bone changes during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs) aboard the space shuttle Columbia (STS-78). Control rats were group housed in a similar manner in ground-based AEMs or standard vivarium cages. Adrenal hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed a lack of significant changes in bone mass and bone formation in these animals. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were nearly the same in flight and ground-based rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation rate was found to be identical in flight and ground-based rats. The results indicate that, under conditions of group housing in AEMs, spaceflight has minimal effects on bone mass and bone formation in rapidly growing rats. These findings emphasize the need to investigate the importance of rat age, strain, and especially housing conditions for studies of the skeletal effects of spaceflight.
Hysteresis of the nasal pressure-flow relationship during hyperpnea in normal subjects
Authors: Shi Yong-Xin , Seto-Poon Margaret , Wheatley John R.
Published: December 2017

Hysteresis of the nasal airway pressure-flow relationship (PFR) is seen during hyperpnea, with lower nasal resistance during increasing inspiratory flow than during decreasing flow. We hypothesized that the nasal PFR hysteresis arose in the nasal vestibule airway because of progressive collapse during the inspiration. We measured the inspiratory transnasal and transvestibular PFR for one nasal passage in five normal subjects breathing via a nasal mask during voluntary hyperventilation, both with voluntary nostril flaring and without flaring. The inspiratory hysteresis (IH) was quantified as the ratio of the areas under the descending and ascending pressure-flow curves. Flaring reduced the vestibular IH from 1.96 ± 0.06 to 1.15 ± 0.06 and the nasal IH from 2.05 ± 0.13 to 1.28 ± 0.06 (both P < 0.01). Our results demonstrate that hysteresis arises in the compliant vestibule segment of the nasal airway, likely because of progressive collapse of the nasal vestibule during inspiration. The findings suggest that hysteresis is prevented by voluntary nostril flaring maintained throughout inspiration.
Assessment of cutaneous blood flow by using topographical perfusion mapping techniques
Authors: Mack Gary W.
Published: December 2017

The ability of laser Doppler scanning to reproduce the spatial pattern of cutaneous vascular conductance (CVC) in a 6.25-cm2 area of skin was evaluated at supine rest (28°C), during thermal stress (cold and heat), and during baroreceptor unloading with −40-mmHg lower body negative pressure (LBNP). The spatial pattern of resting CVC was similar on 3 different days, varying by 6 ± 3%. During cold stress, 89 ± 2% of the skin area showed a decrease in skin blood flow (37 ± 2%), whereas heat stress increased CVC in 94 ± 5% of the skin area. During LBNP, the pattern of CVC response was not uniform, and frequency analysis indicated that 47 ± 5% of the pixels showed a reduction in CVC (>1 SE), 28 ± 2% of the skin area were unaffected, and the remaining 26 ± 5% of the pixels showed some increase in CVC. These data indicate the ability of topographical perfusion mapping to provide quantitative and reproducible information about the spatial distribution of CVC. In addition, the site-to-site variability in reflex control of skin blood flow during LBNP is intriguing and requires more rigorous evaluation.
Recent advances in pulmonary drug delivery using large, porous inhaled particles
Authors: Edwards David A. , Ben-Jebria Abdelaziz , Langer Robert
Published: December 2017

The ability to deliver proteins and peptides to the systemic circulation by inhalation has contributed to a rise in the number of inhalation therapies under investigation. For most of these therapies, aerosols are designed to comprise small spherical droplets or particles of mass density near 1 g/cm3 and mean geometric diameter between ∼1 and 3 μm, suitable for particle penetration into the airways or lung periphery. Studies performed primarily with liquid aerosols have shown that these characteristics of inhaled aerosols lead to optimal therapeutic effect, both for local and systemic therapeutic delivery. Inefficient drug delivery can still arise, owing to excessive particle aggregation in an inhaler, deposition in the mouth and throat, and overly rapid particle removal from the lungs by mucocilliary or phagocytic clearance mechanisms. To address these problems, particle surface chemistry and surface roughness are traditionally manipulated. Recent data indicate that major improvements in aerosol particle performance may also be achieved by lowering particle mass density and increasing particle size, since large, porous particles display less tendency to agglomerate than (conventional) small and nonporous particles. Also, large, porous particles inhaled into the lungs can potentially release therapeutic substances for long periods of time by escaping phagocytic clearance from the lung periphery, thus enabling therapeutic action for periods ranging from hours to many days.