bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of NG-substituted arginines on coronary vascular function after endotoxin
Authors: Winn M. J. , Vallet B. , Asante N. K. , Curtis S. E. , Cain S. M.
Published: December 2017

We investigated the responses of canine coronary rings to endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg). EDRF-NO-dependent relaxation to thrombin [control maximum response produced after administration of thrombin (Emax) was -85.2 +/- 7.0% of the constrictor response produced by the thromboxane analogue U-46619], acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax -80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%; Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%). Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings (-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However, neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA; 8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/- 23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was present, and the increases were no greater in LPS-treated groups than in controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of methacholine on low-frequency mechanics of canine airways and lung tissue
Authors: Sato J. , Suki B. , Davey B. L. , Bates J. H.
Published: December 2017

We measured tracheal flow, tracheal pressure, and alveolar capsule pressure in four anesthetized paralyzed tracheostomized open-chest dogs. Lung impedance between 0.12 and 4.88 Hz was measured with a forced volume oscillation technique before and after the intravenous administration of methacholine (MCh). Before MCh administration, lung impedance was well described by a model featuring a single airway leading to an alveolar region surrounded by tissue with a continuous distribution of viscoelastic time constants as used by Hantos et al. (J. Appl. Physiol. 68: 849–860, 1990). After MCh, however, this model gave a poor fit to the impedances. The impedances were well accounted for, however, when the model was enhanced to include an extra time constant term, which we suspect is required to account for the uneven ventilation distribution produced by MCh. Airway impedance before MCh administration was well described by a simple resistance-inertance model, but a model incorporating serial inhomogeneity of ventilation was again required after MCh. Our results support those of previous studies indicating that the impedance of the normal dog lung is well described by a homogeneously ventilated viscoelastic tissue model. In contrast, our results after MCh administration show strong evidence of marked regional ventilation inhomogeneity in addition to the rheological properties of the tissues.
Lack of importance of the superior laryngeal nerves in citric acid cough in humans
Authors: Stockwell M. , Lang S. , Yip R. , Zintel T. , White C. , Gallagher C. G.
Published: December 2017

The relative importance of laryngeal afferents in the cough reflex in humans is unknown. This study was designed to investigate the importance of superior laryngeal nerve afferents in the cough reflex induced by inhaled nebulized citric acid in awake humans. Nine healthy volunteers had their cough thresholds to inhaled nebulized citric acid measured after superior laryngeal nerve conduction blockade and after a sham nerve block. Of the nine subjects, four showed no change in cough threshold after superior laryngeal nerve anesthesia, three showed increased cough threshold after nerve block compared with no block, and two showed decreased cough threshold after nerve block. The geometric means of the cough thresholds for the nerve block vs. sham block tests were 16 +/- 13 (SD) and 15 +/- 8% citric acid, respectively. There was no statistically significant difference (Wilcoxon signed-rank test) between the cough thresholds with and without superior laryngeal nerve block (P > 0.05). We conclude that, in the awake human, superior laryngeal nerve afferents do not play a necessary role in initiation of citric acid-induced cough.
Relationship between arterial and portal vein immunoreactive glucagon during exercise
Authors: Wasserman D. H. , Lacy D. B. , Bracy D. P.
Published: December 2017

The importance of changes in glucagon in the regulation of hepatic glucose production (Ra) during exercise has been questioned, as an increase in arterial immunoreactive glucagon (IRG) is not always detectable. However, IRG in the portal vein (PV) and not in the artery is most relevant, as flow through PV is approximately 80% of liver blood flow. To assess the extent that arterial IRG reflects the levels the liver is exposed to in PV, dogs (n = 5) were implanted with catheters in a carotid artery, hepatic vein (HV), and PV. Dogs were studied > or = 16 days later during rest and 150 min of moderate treadmill exercise, with indocyanine green and [3–3H]glucose infused to assess hepatic plasma flow (HPF) and hepatic Ra. IRG was 66 +/- 7, 73 +/- 8, and 81 +/- 7 pg/ml in the artery, HV, and PV at rest; it rose at 10 and 150 min of exercise to 89 +/- 9 and 127 +/- 13 pg/ml in the artery, 106 +/- 17 and 186 +/- 21 pg/ml in HV, and, by considerably more, to 153 +/- 20 and 261 +/- 25 pg/ml in PV. HPF fell by approximately 30% with exercise. The fall in HPF accounted for < 11% of the increased arterial-to-PV IRG gradient during exercise, with increased splanchnic IRG release comprising the remainder. Ra was linearly related to IRG levels in the three vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of continuous negative airway pressure-related lung deflation on upper airway collapsibility
Authors: Series F. , Marc I.
Published: December 2017

Continuous negative airway pressure (CNAP) causes a decrease in lung volume, which is known to increase upper airway resistance by itself. We studied how this lung volume change could modify upper airway collapsibility with five normal awake subjects. In a first trial, pressure in a nasal mask (Pm) was progressively decreased in 3- to 5-cmH2O steps (CNAP). In a second trial, changes in lung volumes resulting from CNAP were prevented by applying simultaneously an equivalent level of negative extrathoracic pressure into a poncho-type respirator [isovolumetric CNAP (CNAPisovol)]. For each trial, we examined the relationship between the maximal inspiratory airflow of each flow-limited inspiratory cycle and the corresponding Pm by least-squares linear regression analysis and determined the critical pressure. We also determined the Pm threshold corresponding to the first Pm value below which flow limitation occurred. Flow limitation was observed in each subject with CNAP but in only two subjects with CNAPisovol. In these two subjects, the Pm threshold values were -20 and -9 cmH2O with CNAP and -39 and -16 cmH2O with CNAPisovol, respectively. Critical pressures for the same two subjects were -161 and -96 cmH2O with CNAP and -202 and -197 cmH2O with CNAPisovol, respectively. We conclude that CNAP-induced decreases in lung volume increase upper airway collapsibility.
Tissue gas stores of the body and head-out immersion in humans
Authors: Liner M. H.
Published: December 2017

Breath-by-breath gas exchange was studied in 10 subjects during and after transitions between dry conditions and head-out immersion in thermoneutral conditions. Cardiac index (CI) was estimated by means of impedance cardiography. Previous largely qualitative models of changes in tissue gas stores after blood volume shifts could be confirmed and extended to include a quantitative analysis of O2 and CO2 tissue stores. An increase in CI by 47.0% during immersion was associated with an increase in the tissue O2 stores by 122 ml/m2 and a decrease in the tissue CO2 stores by 148 ml/m2. The time constants for the recovery of O2 uptake (tau O2) and CO2 elimination after initial increases after the dry-to-immersion transition were 32.4 and 79.3 s, respectively. The decrease in CI on return to the dry conditions was associated with a drop in tissue O2 stores and a tau O2 of 144 s. The increase in tissue O2 stores during immersion as well as the difference in tau O2 between the two transitions were larger than could be explained by the change in CI only. This was attributed to changes in the distributions of peripheral blood flow and venous blood volume. Compared with the O2 stores, the decrease in CO2 stores was better predicted by the change in CI. The present results emphasize that the changes in pulmonary and tissue gas exchange imposed by head-out immersion transients mainly reflect movement of gas in and out of body stores.
Effect of lung volume maintenance during sleep in nocturnal asthma
Authors: Martin R. J. , Pak J. , Irvin C. G.
Published: December 2017

Previous studies have shown that lung volume decreases and airway resistance increases during sleep in patients with nocturnal asthma. To determine whether the fall in lung volume per se causes the overnight decrement in forced expiratory volume in 1 s (FEV1) and/or increase in bronchial responsiveness, we investigated the effect of preventing this nocturnal decrease in lung volume. The mean volume change on a baseline night was -16.3 +/- 1.6% from presleep values and on the volume maintenance night +7.1 +/- 3.0% (P = 0.0001). However, this maintenance of lung volume did not alter the overnight decrement in FEV1 (-29.6 +/- 5.2% baseline vs. -30.2 +/- 5.8% volume maintenance). Similarly, the increase in bronchial responsiveness was also unaltered from baseline to volume maintenance nights, with presleep provocative concentrations of methacholine producing a 20% decrement in FEV1 of 0.28 +/- 0.15 vs. 0.22 +/- 0.7 mg/ml, respectively, and postsleep values of 0.07 +/- 0.03 vs. 0.04 +/- 0.02 mg/ml, respectively. Thus the fall in lung volume during sleep in the nocturnal asthmatic patient is a result, not a cause, of the overnight worsening of lung function.
High muscle blood flow in man: is maximal O2 extraction compromised?
Authors: Richardson R. S. , Poole D. C. , Knight D. R. , Kurdak S. S. , Hogan M. C. , Grassi B. , Johnson E. C. , Kendrick K. F. , Erickson B. K. , Wagner P. D.
Published: December 2017

During conventional cycle ergometry, as work rate (WR) is increased toward maximum, O2 extraction increases hyperbolically, typically achieving values of 80–90% at peak O2 uptake (VO2). In contrast, studies using isolated knee-extensor exercise report much higher mass-specific blood flows (Q) and lower maximal O2 extractions (approximately 70%), which have been interpreted as transit time limitation to O2 movement out of the muscle capillary. However, maximal achievable WR levels during conventional cycle ergometry are generally reached (over 10–15 min) after rapid increases in WR, whereas the reported knee-extensor studies have used only more lengthy protocols (45 min). The duration of these protocols may have prevented the attainment of high WR levels and thus high O2 extraction ratios. Accordingly, this investigation examined leg Q and O2 extraction responses during single-leg knee-extensor exercise incremented rapidly (steps of 15–25 W per 2- to 3-min interval), which produced fatigue in 13–15 min. Q and muscle VO2 increased linearly with WR to fatigue with Q-WR and VO2-WR slopes similar to those reported in previous knee-extensor studies. However, with the use of this protocol, very high maximal achievable WR [99 +/- 6 (SE) W] and muscle Q (385 +/- 26 ml.min-1 x 100 g-1) levels were attained, some 80% greater than previously reported. An O2 extraction of 84.6 +/- 2.1% was reached, giving a maximal VO2 of 60.2 +/- 5.8 ml.min-1 x 100 g-1. We conclude that, even under the high Q conditions of single-leg knee-extensor exercise, O2 extraction does not reach a plateau on the basis of short transit times and that previous conclusions to the contrary reflect failure to attain sufficiently high WR levels. Maximal VO2, Q, and O2 extraction in this model have yet to be defined.
Effects of respiratory afferent stimulation on phrenic neurogram during hypoxic gasping in the cat
Authors: Melton J. E. , Chae L. O. , Edelman N. H.
Published: December 2017

Previous studies suggested that phrenic motor output is largely refractory to afferent stimuli during gasping. We tested this concept by electrically stimulating the carotid sinus nerve (CSN) or the superior laryngeal nerve (SLN) of anesthetized peripherally chemodenervated vagotomized ventilated cats during eupnea or gasping induced by hypoxia. During eupnea, phrenic neurogram amplitude (PNA) increased by 110% during 30 s of supramaximal CSN stimulation, but burst frequency did not change. Progressive hypoxia caused gasping after arterial O2 content was reduced by 75%. During gasping, CSN stimulation caused premature onset of gasp in 12 of 13 trials, shortened intergasp interval [6.3 +/- 0.9 vs. 14.8 +/- 2.5 (SE) s], and resulted in a small (20%) but significant increase in PNA. Intensity of SLN stimulation was adjusted to abolish phrenic activity during the 30-s eupneic stimulation period. During gasping, SLN stimulation of the same intensity tended to delay onset of the next gasp, increased intergasp interval (16.9 +/- 1.9 vs. 13.3 +/- 1.2 s), and reduced PNA by 32%. Thus the respiratory burst pattern formation circuitry responds to afferent stimuli during gasping, albeit in a manner different from the eupneic response. These observations suggest that gasping is the output of a modified eupneic burst pattern formation circuit.
Influence of body position on diaphragmatic and scalene activation during hypoxic rebreathing
Authors: Xie A. , Takasaki Y. , Bradley T. D.
Published: December 2017

We measured electromyographic activity of the diaphragm (EMGdi) and scalene (EMGsc) during isocapnic progressive hypoxic ventilatory responses in five normal males in the supine and upright seated positions. The slope of the regression line relating EMGdi expressed as a percentage of maximum to percent fall in arterial oxyhemoglobin saturation was 93% steeper upright than supine (P < 0.005), whereas the slope of EMGdi activity to minute volume of ventilation was 73% higher upright than supine (P < 0.05). In addition, the slope of EMGsc activity relative to percent fall in arterial oxyhemoglobin saturation and minute ventilation was greater upright than supine (151%, P < 0.001 and 61%, P = 0.056, respectively). Greater EMGsc activity upright than supine was similar to findings during hypercapnic rebreathing. However, the greater EMGdi activity upright than supine stands in contrast to hypercapnic rebreathing where it was previously shown that EMGdi activity was not affected by a change in body position. We conclude that during hypoxic ventilatory responses both EMGdi and EMGsc activities are more pronounced upright than supine. Diaphragmatic activation during progressive hypoxia in response to a change in body position is different from that seen during progressive hypercapnia.
Density of decompression bubbles and competition for gas among bubbles, tissue, and blood
Authors: Van Liew H. D. , Burkard M. E.
Published: December 2017

We used numerical solutions of a system of equations to simulate gas exchanges of bubbles after a decompression, with particular attention to the effect of number of bubble formation sites per unit of tissue. If many bubbles grow, they deplete the excess dissolved gas in the tissue. The consequences are as follows: 1) the many individual bubbles do not become as large as they would if fewer were competing for gas; 2) more gas is evolved when there are many sites; 3) the bubbles are absorbed sooner than the bigger bubbles that grow with few sites; 4) after diffusion into many bubbles causes N2 partial pressure in the tissue to fall immediately to a low level, N2 partial pressure in the tissue and the exiting blood remain "clamped" to this low level because dissolved N2 removed by blood is replenished by diffusion out of the bubbles; and 5) as long as many bubbles persist, the long-term removal of inert gas from the total system (tissue plus bubbles) follows a straight-line time course rather than an exponential course.
Role of nitric oxide in effects of tumor necrosis factor-alpha on microcirculation in rat
Authors: Baudry N. , Vicaut E.
Published: December 2017

The involvement of nitric oxide (NO) in the effects of tumor necrosis factor-alpha (TNF-alpha) on the microcirculation was studied by in vivo microscopy in rat cremaster muscle. We examined second-, third-, and fourth-order arterioles with mean diameters under control conditions of 62.2, 37.4, and 16.9 microns, respectively. The vasodilation observed after topical administration of 100 ng/ml recombinant TNF-alpha (rTNF-alpha) was partly but significantly inhibited when NO synthesis was inhibited by 2 x 10(-4) M N omega-nitro-L-arginine (L-NNA). Almost complete inhibition of the acute vasodilatory effect of rTNF-alpha was found when both NO and prostaglandin synthesis were blocked by simultaneous administration of L-NNA and mefanamic acid. The effect of rTNF-alpha on vasoconstriction in response to norepinephrine (NE) was a dramatic reduction after 2 h of exposure to 1 ng/ml rTNF-alpha. Concomitant administration of 2 x 10(-4) M L-NNA prevented this hyporeactivity for second- and third-order, but not for fourth-order, arterioles. However, at 2 x 10(-3) M, L-NNA totally prevented the hyporeactivity to NE for all arteriolar orders. No changes in vasoconstriction to 70 mM KCl were observed either immediately after rTNF-alpha administration or after 2 h of exposure. We conclude that 1) the direct acute vasodilatory effect of rTNF-alpha on the microcirculation is mediated by both prostaglandins and NO, 2) long exposure to rTNF-alpha diminishes the response of the arterioles to NE but not to KCl, and 3) this effect is mediated by NO.
Role of eicosanoids in hyperpnea-induced airway responses in guinea pigs
Authors: Garland A. , Jordan J. E. , Ray D. W. , Spaethe S. M. , Alger L. , Solway J.
Published: December 2017

Guinea pigs mechanically hyperventilated with dry gas exhibit hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH). Tachykinins released from airway C-fiber neurons are the central mediators of guinea pig HIB but play only a contributory role in HIBVH. Recent studies suggest that eicosanoid mediators can provoke bronchoconstriction and bronchovascular hyperpermeability, are released by dry gas hyperpnea, and can themselves elicit or modulate tachykinin release. We therefore hypothesized that eicosanoids may participate in HIB and/or HIBVH. To test these hypotheses, we analyzed respiratory system resistance changes and Evans blue-labeled albumin extravasation into the airways of 60 tracheostomized and mechanically ventilated guinea pigs. Animals were subjected to 10 min of isocapnic dry gas hyperpnea or to quiet breathing of humidified gas and received as pretreatment either piroxicam, a cyclooxygenase (CO) inhibitor; A-63162, a 5-lipoxygenase (5-LO) inhibitor; BW-755c, a combined CO and 5-LO inhibitor; ICI-198,615, a leukotriene D4 receptor antagonist; or no drug. HIB was substantially (50–80%) reduced by each of the four eicosanoid-modulating drugs. In contrast, HIBVH was reduced only by BW-755c, and this effect occurred only within the extrapulmonary airways (42% reduction). These data indicate that both CO and 5-LO products, including leukotriene D4, participate in the pathogenesis of HIB but that, like tachykinins, they play only a small contributory role in HIBVH. Together with our previous demonstration that sensory neuropeptide release is critical for the occurrence of HIB, we conclude that the roles of eicosanoids and tachykinins in guinea pig HIB are interdependent.
Exercise training does not compensate for age-related decrease in myocardial GLUT-4 content
Authors: Hall J. L. , Mazzeo R. S. , Podolin D. A. , Cartee G. D. , Stanley W. C.
Published: December 2017

We assessed the effects of age and endurance exercise training (treadmill running at 75% maximal running capacity, 1 h/day, 5 days/wk for 10 wk) on the total concentration of insulin-regulatable glucose transporters (GLUT-4) and GLUT-4 mRNA levels in the myocardium of male Fischer 344 rats aged 7, 15, and 25 mo. Myocardial GLUT-4 concentration was quantified with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting and detected with a polyclonal antibody to the GLUT-4 transporter. Myocardial GLUT-4 mRNA levels were quantified with slot-blot analysis and a cDNA probe for GLUT-4. Myocardial GLUT-4 concentration in the 25-mo group decreased 27 and 20% compared with the 7- and 15-mo group, respectively (P < 0.0001 and P < 0.003). GLUT-4 mRNA also decreased significantly in the 25-mo group compared with the 7-mo group (20% in the trained and 11% in the untrained group, P < 0.05). Endurance training did not significantly affect myocardial GLUT-4 concentrations in any age group despite a significant increase in GLUT-4 mRNA in the 7- and 25-mo trained groups. In conclusion, myocardial GLUT-4 protein levels in the rat are significantly decreased with age but are unaffected by 10 wk of treadmill running.
Reversal of persistent postbronchiolitis airway abnormalities with dexamethasone in rats
Authors: Sheth K. K. , Sorkness R. L. , Clough J. J. , McAllister P. K. , Castleman W. L. , Lemanske R. F.
Published: December 2017

Viral bronchiolitis is a common disease that may result in persistent airway abnormalities. Previous studies of neonatal bronchiolitis in rats revealed chronic sequelae, including airway obstruction, airway hyperresponsiveness, increased production of airway eicosanoids, and increased numbers of bronchiolar mast cells. To address the hypothesis that postbronchiolitis airway obstruction is caused in part by reversible processes, we tested whether obstruction could be reversed by a brief course of high-dose corticosteroids. Neonatal Brown Norway rats (5 days of age) were inoculated with parainfluenza type 1 virus or sterile vehicle. At 8 wk of age, rats were treated with dexamethasone (1.4 mg.kg-1 x day-1 sc) or saline for 3 days and were evaluated for lung mechanics, gas exchange, and lung inflammatory cells 1 day after the last injection. Dexamethasone normalized the chronic virus-induced airway obstruction and reduced the numbers of bronchiolar mast cells and other inflammatory cells. Resistance and dynamic compliance correlated significantly with bronchiolar mast cells but not with other airway inflammatory cell infiltrates. We conclude that the airway abnormalities that persist in rats after recovery from neonatal bronchiolitis are associated with increased numbers of bronchiolar mast cells and are largely due to corticosteroid-sensitive mechanisms.
Daily exercise improved blood pressure homeostasis of rats subjected to surgical stress
Authors: Scislo T. J. , DiCarlo S. E. , Jarjoura D. G.
Published: December 2017

The effect of daily spontaneous running on blood pressure homeostasis (BPH) was evaluated in 19 male and 13 female control rats and 7 male and 13 female daily spontaneous running rats subjected to surgery and subsequent repetitive hemodynamic disturbances. BPH was operationally defined as the ability to maintain mean arterial pressure above 60 mmHg during the experimental protocol. The length of time the rats maintained BPH was compared across males and females and trained and control groups. Significant sex (P = 0.01) and training (P = 0.05) effects were found. Females maintained homeostasis longer than males and trained longer than controls. Sex effects were not due to differences in the body mass. The mechanisms responsible for the higher resistance to deterioration of homeostasis merit further investigation.
Effect of acid-base balance on the growth hormone response to acute high-intensity cycle exercise
Authors: Gordon S. E. , Kraemer W. J. , Vos N. H. , Lynch J. M. , Knuttgen H. G.
Published: December 2017

To investigate the effect of acid-base balance on serum human growth hormone (hGH) concentration after an acute high-intensity anaerobic exercise bout, 10 untrained but normally active men [age, 24.6 +/- 1.5 (SE) yr] participated in a randomized double-blind counterbalanced experiment. Each subject reported in a fasted state at the same time of day for two experimental sessions separated by 1 wk. For each session, subjects were administered a decaffeinated tea solution containing either 0.3 g NaHCO3/kg body wt [alkalosis (ALK)] or 0.04 g NaCl/kg body wt [control (CTRL)] over a 45-min ingestion period. Venous blood samples were obtained before [baseline (BL)] and 75 min after the ingestion period, as well as postexercise at 0, 5, 10, 15, 20, and 30 min. The exercise task immediately followed the preexercise blood draw and consisted of 90 s of maximal-effort cycle ergometry against an opposing force of 0.49 N (0.05 kg)/kg body wt. There were no differences between the ALK and CTRL conditions in mean or peak power output or total work during the exercise task. Whole blood pH was significantly (P < or = 0.05) elevated in ALK above CTRL at all time points except BL. Postexercise serum hGH concentration significantly increased above BL at 10, 15, 20, and 30 min in CTRL and at 20 and 30 min in ALK. The hGH concentration was significantly lower in ALK than in CTRL at 15, 20, and 30 min postexercise. These data indicate that an increase in blood hydrogen ion concentration may be partly responsible for the hGH response to acute high-intensity anaerobic exercise.
Analyzing 13NN lung washout curves in the presence of intraregional nonuniformities
Authors: Simon B. A. , Venegas J. G.
Published: December 2017

The use of 13NN and positron imaging provides a powerful noninvasive means of assessing regional pulmonary function. Current techniques for analyzing lung washout curves, however, are subject to error due to intraregional nonuniformities, particularly in the presence of areas with very long time constants or gas trapping. This paper presents a simple “hybrid” method for analyzing 13NN-washout studies that addresses the problems of regions of air trapping and long time constants within a region of interest. This method assumes an exponential washout form for the slow regions, estimates their fractional volume, and subtracts their contribution from the overall washout curve. The modified Stewart-Hamilton method is then applied to the remaining washout curve to calculate its ventilation. The over-all specific ventilation of the region is calculated as the volume-weighted average of the specific ventilations of the two compartments. The performance of the hybrid method is compared with other currently used correction techniques by using a simulated two-compartment lung washout in which there is a variable amount of gas trapping. The analysis techniques are also applied to washout data with intraregional nonuniformities obtained during experimentally created unilateral bronchial obstruction. This new approach has the advantages of automatically correcting for washout truncation, estimating the relative size of the trapped or slow region while eliminating its bias on the regional ventilation, and yet retaining the unrestricted and robust nature of the Stewart-Hamilton method in the analysis of the well-ventilated regions.
Small-amplitude pressure oscillations do not modify respiratory mechanics in rabbits
Authors: Peslin R. , Saunier C. , Gallina C. , Duvivier C.
Published: December 2017

Changes in respiratory mechanics have occasionally been observed during high-frequency ventilation. In this study we investigated whether small pressure oscillations such as those used for respiratory impedance measurements modified total respiratory resistance (Rrs) and total respiratory elastance (Ers). The latter were measured in six paralyzed artificially ventilated rabbits with and without superimposed pressure oscillations at the airway opening. Rrs and Ers were obtained by least square fitting of low-pass filtered tracheal pressure and flow to the usual first-order model. Pressure oscillations of 2–4 hPa peak-to-peak at 10, 20, and 30 Hz applied for periods of 10 min had virtually no effect on Ers (changes ranging from -2.5 to 2.6%) and Rrs (0-8.2%). Analysis of variance did not show a significant difference on the pooled data. Pressure oscillations were also applied every other minute after a histamine aerosol. Ers and Rrs were similarly unchanged. We conclude that the small pressure oscillations used in respiratory impedance measurements do not modify lung mechanical properties and lung response to bronchomotor agents.
Effect of beta-receptor blockade on splanchnic and muscle metabolism during prolonged exercise in men
Authors: Ahlborg G. , Juhlin-Dannfelt A.
Published: December 2017

The importance of beta-receptor stimulation for the metabolism and circulation in the liver and exercising muscle was studied in six men during 3 h of leg exercise at 50% of maximum oxygen uptake. At 160 min of exercise, 0.15 mg propranolol/kg body wt was given intravenously. The results were compared with a previously studied control group examined in the same way but without beta-receptor blockade. The data show that beta-blockade during prolonged leg exercise, compared with exercising controls, results in 1) reduced splanchnic and leg blood flows (P < 0.005–0.01); 2) higher epinephrine and norepinephrine levels (P < 0.001); 3) unchanged respiratory exchange values, indicating unchanged carbohydrate oxidation; 4) a less marked drop in leg glucose uptake, suggesting reduced muscle glycogenolysis; 5) a higher splanchnic glucose output (P < 0.05) but lower splanchnic uptakes of lactate and glycerol after propranolol (P < 0.025–0.01), i.e., diminished uptake of gluconeogenic precursors, indicating accelerated hepatic glycogenolysis; and 6) unchanged glycerol levels with a lower splanchnic glycerol uptake, indicating reduced lipolysis. The data imply that, despite lower glycogen stores during prolonged exercise, liver glycogenolysis, as opposed to exercising muscle glycogenolysis, may be accelerated during beta-receptor blockade.
Beta-carotene and CNS oxygen toxicity in rats
Authors: Bitterman N. , Melamed Y. , Ben-Amotz A.
Published: December 2017

Beta-carotenes are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Oxygen free radicals that are produced in excess during exposure to oxygen at high pressures and overwhelm the body's normal antioxidant defense systems seem to mediate the hyperoxic insult. We decided to test the possible protective effect against central nervous system oxygen toxicity of a natural beta-carotene composed of equal amounts of the all-trans and 9-cis isomers obtained from the unicellular halotolerant alga Dunaliella bardawil. Rats implanted with chronic cortical electrodes for continuous electroencephalogram monitoring were fed on ground commercial food enriched with natural beta-carotene (1 g/kg diet). On completion of 1 wk of the diet, the rats were exposed to 0.5 MPa oxygen and then their livers were removed for beta-carotene and vitamin A analysis. A significant increase was noted in the latent period preceding oxygen seizures in the group of rats in which the diet was supplemented by natural beta-carotene compared with rats given a normal diet (38.5 +/- 3.4 vs. 16.8 +/- 1.8 min; P < 0.05). Further experiments are required to evaluate the potential benefit of supplementing the diet of divers and patients exposed to high pressures of oxygen with the beta-carotene-rich D. bardawil.
Contribution of potassium channels to active hyperemia of the canine diaphragm
Authors: Vanelli G. , Chang H. Y. , Gatensby A. G. , Hussain S. N.
Published: December 2017

Glibenclamide, iberiotoxin, and apamin (blockers of ATP-sensitive, large-conductance, and small-conductance Ca(2+)-activated K+ channels, respectively) were infused into the diaphragmatic vasculature of anesthetized indomethacin-treated dogs to assess the contribution of K+ channels to active hyperemia. Diaphragmatic blood flow (Qphr) and O2 uptake (VO2di) were measured at rest and during 2 min of continuous left phrenic nerve stimulation at 0.5, 1, 2, and 4 Hz. These measurements were repeated before (control) and after the infusion of a selective K+ channel blocker in three groups of animals. Glibenclamide at 10(-5) M significantly attenuated Qphr at rest and in response to all stimulation frequencies. Whereas resting VO2di remained unchanged, glibenclamide infusion significantly reduced VO2di in response to all stimulation frequencies. The slope of the linear relationship between Qphr and VO2di, however, was not affected by glibenclamide. By comparison, infusion of iberiotoxin (10(-7) M) in a second group reduced Qphr at rest and in response to 0.5- and 1-Hz stimulation, whereas Qphr measured in response to 2- and 4-Hz stimulation remained similar to control values. Apamin (10(-6) M) infusion in a third group reduced only resting Qphr with no effect on active hyperemia during phrenic nerve stimulation. Neither iberiotoxin nor apamin influenced resting or stimulated VO2di. In all groups diaphragmatic tension measured after the infusion of K+ channel blockers remained similar to control values. These results indicate that K+ channels, especially those sensitive to glibenclamide, modulate the increase in Qphr and VO2di in response to moderate augmentation of metabolic demands.
Effect of simple carbohydrates, casein hydrolysate, and a lipid test meal on ethane exhalation rate
Authors: Mooradian A. D. , Habib M. P. , Dickerson F.
Published: December 2017

To determine the potential differences in the effect of various nutrients on lipid peroxidation, the ethane exhalation (EE) rate, an index of lipid peroxidation, was measured in rats at 4 (young), 18 (intermediate age), and 24 (aged) mo of age at fasting conditions and after acute ingestion of various test meals. The EE rate (means +/- SD) after a 15-h fast was significantly reduced in 24-mo-old rats (2.45 +/- 0.44 pmol.min-1.100 g body wt-1) and 18-mo-old rats (3.51 +/- 0.55 pmol.min-1.100 g body wt-1) compared with 4-mo-old rats (4.44 +/- 0.66 pmol.min-1.100 g body wt-1; P < 0.01). The EE rate significantly increased in 4-mo-old rats after ingestion of 50% (wt/vol) dextrose (8.59 +/- 2.9 pmol.min-1.100 g body wt-1), 50% casein hydrolysate (6.77 +/- 1.23 pmol.min-1.100 g body wt-1), and 20% neutral lipid emulsion (7.33 +/- 1.96 pmol.min-1.100 g body wt-1; P < 0.01). The response of aged rats to these nutrients compared with young rats was reduced by approximately 50%. A 25% dextrose solution or a 50% solution of sucrose, fructose, maltose, or galactose did not significantly alter EE rate. It is concluded that various macronutrients have a diverse potential of inducing lipid peroxidation. The responsiveness of aged rats to meal-induced enhancement of EE and presumably lipid peroxidation is significantly reduced.
Elimination of glutathione-induced protection from hyperbaric hyperoxia by acivicin
Authors: Peacock M. D. , Schenk D. A. , Lawrence R. A. , Morgan J. A. , Jenkinson S. G.
Published: December 2017

Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of hypercapnia on metabolism, temperature, and ventilation during heat and fever
Authors: Sachdeva U. , Jennings D. B.
Published: December 2017

We wished to determine whether 1) acute hypercapnia in cats changes metabolic heat production to affect temperature regulation and 2) heat exposure and fever affect the normal response. The effects of breathing 4% CO2 on O2 consumption (VO2), rectal temperature (Tre), and ventilation (V) were measured in five conscious resting cats. Cats were exposed to a normal (24–27 degrees C) chamber temperature (Ta) and a warm (33–34 degrees C) chamber Ta. Fever was produced by intravenous injection of Escherichia coli endotoxin (0.02 microgram/kg) at a normal Ta. In normothermic cats, hypercapnia decreased VO2 by approximately 40%, despite an increased V (approximately 100%), but Tre decreased only transiently and slightly compared with studies in which air was breathed throughout. During heat studies, average V was elevated but VO2 was markedly lower than at the normal Ta; Tre gradually increased. Hypercapnia combined with heat did not cause additional increases in VO2, nor did it cause a decrease in VO2, as at a normal Ta; however, the rate of rise of Tre during heat was slowed by hypercapnia. During febrigenesis, hypercapnia prevented the transient increase in VO2 observed when air was breathed and delayed the rate of rise in Tre. As Tre was falling in fever, hypercapnia depressed VO2 but did not affect Tre compared with fever studies in which air was breathed. Unlike heat exposure, hypercapnia had a further additive stimulatory effect on the increase in V at the onset of fever, and it increased V during the falling phase of fever when V had returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Nucleus tractus solitarius and excitatory amino acids in afferent-evoked inspiratory termination
Authors: Karius D. R. , Ling L. , Speck D. F.
Published: December 2017

This study tested the hypothesis that excitatory amino acid (EAA) neurotransmission at non-N-methyl-D-aspartate (non-NMDA), but not NMDA, receptors within medial regions of the nucleus tractus solitarius (NTS) is required in the inspiratory termination elicited by vagal or intercostal nerve (ICN) stimulation. Adult cats were anesthetized, decerebrated, vagotomized, and ventilated. After control responses to stimulation of the superior laryngeal nerve (SLN), vagus, and ICN were obtained, EAA receptor antagonists were injected into the medial aspects of the NTS. Injections of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 6,7-dinitro-quinoxaline-2,3-dione (DNQX), EAA receptor antagonists; (+/-)-2-amino-5-phosphonopentanoic acid (AP5), an NMDA antagonist; or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), a non-NMDA antagonist, ipsilateral to the vagus abolished the termination response. The SLN-elicited response persisted after AP5 injection but was abolished by NBQX injections. The ICN-elicited response persisted after bilateral injections of CNQX/DNQX or procaine. We conclude that the inspiratory termination elicited by ICN stimulation is independent of the regions medial to the NTS. Inspiratory termination elicited by vagal or SLN stimulation requires non-NMDA-mediated EAA neurotransmission within medial aspects of the NTS, but the vagally elicited response also requires NMDA receptors.
Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury
Authors: Kavanagh B. P. , Mouchawar A. , Goldsmith J. , Pearl R. G.
Published: December 2017

Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90–120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.
Hemodynamics in the abdominal aorta: a comparison of in vitro and in vivo measurements
Authors: Moore J. E. , Maier S. E. , Ku D. N. , Boesiger P.
Published: December 2017

In vivo measurements of blood velocity profiles are difficult to obtain and interpret, since the parameters that govern the normally highly complex flow situation may not be fully quantified or understood at the time of measurement. In vitro flow models have been used often to better understand vascular hemodynamics. The assumptions made in the design of these models limit the applicability of the results. In this study, in vitro flow measurements made in a carefully designed model of the abdominal aorta were compared with in vivo measurements obtained with magnetic resonance imaging. In the suprarenal aorta, the velocity profiles were mostly forward and axisymmetric in both the in vitro and in vivo cases. In the infrarenal aorta, there was extensive flow reversal noted near the posterior wall in both cases. In the aortic bifurcation, two peaks of flow reversal were noted near the lateral posterior walls, and M-shaped velocity profiles were observed in late diastole. The in vitro and in vivo measurements exhibited good qualitative agreement. The in vitro model was accurate in modeling the in vivo hemodynamics of the abdominal aorta. The complex phenomena observed in vivo were explained on the basis of knowledge gained from the in vitro study.
Nicotine and acetylcholine induce release of calcitonin gene-related peptide from rat trachea
Authors: Jinno S. , Hua X. Y. , Yaksh T. L.
Published: December 2017

In the present study, we observed that nicotine, the nicotinic analogue cytisine, and acetylcholine (ACh) evoked a concentration-dependent (5 x 10(-6)-5 x 10(-5) M) release of calcitonin gene-related peptide (CGRP) from the rat trachea. After a prolonged exposure to capsaicin, nicotine-induced CGRP release was absent, suggesting that the release of CGRP by nicotine is derived from capsaicin-sensitive afferent terminals. Nicotine- and cytisine-induced release displayed a significant degree of tachyphylaxis after sequential exposures. The release of CGRP evoked by capsaicin was also reduced after nicotine and cytisine desensitization. This indicates that similar mechanisms may mediate the tachyphylactic effect of capsaicin and nicotine. Hexamethonium and mecamylamine blocked the effect of nicotine but not that of ACh, whereas atropine significantly attenuated the release of CGRP outflow induced by ACh. Physostigmine and neostigmine did not alter resting release of CGRP from rat trachea, although exogenous (10(-5) M) ACh-induced CGRP release was enhanced in the presence of neostigmine, suggesting minimal tonic cholinergic activity in this model. We conclude that activation of nicotinic and muscarinic receptors in the rat trachea can induce local release of CGRP. These observations indicate that cholinergically induced airway responses may be mediated in part by activation of the peripheral terminals of primary afferent sensory neurons and subsequent release of local neuropeptides.
Depression of hypercapnic ventilatory drive by testosterone in the sleeping infant primate
Authors: Emery M. J. , Hlastala M. P. , Matsumoto A. M.
Published: December 2017

In postnatal infants, there is similarity between the time course of transient gonadal steroid secretion and the age-related incidence of sudden infant death syndrome (SIDS). The cause of death in SIDS is generally thought to be a ventilatory arrest, but the mechanism responsible for such an event remains unknown. Testosterone has been demonstrated to depress ventilatory drive and increase sleep apnea in adult men. We tested the hypothesis that the gonadal steroid testosterone depresses infant ventilatory drive during sleep. Three newborn male infant primates were gonadectomized after birth. Ventilation was observed and quantified for each animal during completely natural unencumbered sleep by plethysmography for an average of 16 wk. Ventilatory patterns were recorded, and ventilatory drive was challenged with hypercapnia and hypoxia during quiet sleep on the night before and the night after testosterone administration. Hypercapnic ventilatory drive during sleep was significantly depressed by an average of 33.6% on the night after compared with the night before testosterone administration. Depression of the response to hypercapnia after testosterone was not accompanied by any change in resting minute ventilation measured during quiet sleep. Hypoxic ventilatory drive, incidence of apneic events, and length of apnea were not different after testosterone. The effects of injecting a placebo on ventilatory patterns and drive were tested by giving the placebo to all animals on several test weeks. Placebo injections produced no significant change in any measured parameters. These results support the hypothesis that testosterone depresses hypercapnic ventilatory drive during sleep in the infant primate.(ABSTRACT TRUNCATED AT 250 WORDS)