bluuebunny/crossref_metadata_2025 huggingface dataset:
Central and spinal effects of sodium cyanide on respiratory activity
Authors: Haxhiu M. A. , Erokwu B. , van Lunteren E. , Cherniack N. S. , Strohl K. P.
Published: December 2017

The pharmacological actions of cyanide on respiratory activity have been known for some time and are attributed mainly to effects on peripheral chemoreceptors. In the studies reported here, we have examined the acute central effects of cyanide when applied topically to the ventral surface of the medulla (VMS) and when administered into the spinal intrathecal space at the C5-T3 level on activities of the phrenic nerve, diaphragm, parasternal intercostal, triangularis sterni, and transversus abdominis muscles. Topical application of 10–100 micrograms (10 microliters of 1–10 mg/ml) cyanide to the intermediate area of the VMS decreased respiratory activity by > 50%, and expiratory muscles were more sensitive to inhibition than inspiratory muscles. The onset of depression of phrenic nerve or respiratory muscle activity occurred within 20 s of administration, and the effects reversed after washout. In contrast, intrathecal administration of cyanide in doses of 10–100 micrograms (100 microliters of 0.1–1 mg/ml) increased electrical activity of the respiratory muscles. Diaphragm activity changed from 17 +/- 2 to 42 +/- 8 (SE) units (P < 0.01), parasternal intercostal activity increased from 18 +/- 3 to 46 +/- 9 units (P < 0.01), and expiratory activity of the chest wall and abdominal muscles increased from 9 +/- 2 to 39 +/- 10 units (P < 0.05). Both topical application on the VMS and intrathecal administration of cyanide caused an increase in arterial blood pressure and a slight insignificant acceleration of heart rate. These data suggest that cyanide acting on the VMS causes respiratory depression and enhancement of sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)
Oxygen radicals in bronchoconstriction of guinea pigs elicited by isocapnic hyperpnea
Authors: Fang Z. X. , Lai Y. L.
Published: December 2017

The role of oxygen radicals in isocapnic hyperpnea-induced bronchoconstriction (HIB) of guinea pigs was investigated using scavengers of the radicals. In series 1, 50 young guinea pigs were randomly divided into seven groups: control 1, control 2, chlorisondamine, tetrodotoxin (TTX), acute dimethylthiourea (DMTU), tachykinin depletion, and 5% CO2 in air. Animals of the control 2 group received vehicle (saline) infusion while those of the control 1 group did not. Chlorisondamine was used to block ganglionic transmission, TTX to interrupt nerve conduction, DMTU to scavenge hydroxyl radicals, and chronic capsaicin pretreatment to deplete tachykinins. The animals in the last group were ventilated with dry 5% CO2 in air during hyperpnea. In series 2, 13 additional animals were used to test the effects of intratracheal administration of superoxide dismutase and catalase (SOD + CAT) on HIB. Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and mechanically ventilated. During the baseline period, each animal was ventilated normally with humidified air. Then it was hyperventilated 15 min with a dry gas mixture of 95% O2–5% CO2, except animals in the last group of series 1. Subsequently, all animals returned to normal ventilation with humidified air for 45 min (recovery period). The maximal expiratory flow and dynamic compliance were obtained periodically during the recovery period. The isocapnic hyperpnea using 95% O2–5% CO2, but not 5% CO2 in air, caused bronchoconstriction that was significantly blocked by acute DMTU, acute SOD + CAT, and tachykinin depletion. In an additional group of six animals, acute DMTU did not significantly alter acetylcholine-induced airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Is nitric oxide released in oleic acid lung injury?
Authors: Leeman M. , De Beyl V. Z. , Gilbert E. , Melot C. , Naeije R.
Published: December 2017

Inhibitors of endothelium-derived nitric oxide synthesis or activity have been reported to enhance hypoxic vasoconstriction in isolated lung preparations. We hypothesized that methylene blue, a guanylate cyclase inhibitor, and N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, would increase pulmonary vascular tone and improve gas exchange in anesthetized and ventilated (inspired O2 fraction 0.4) dogs with oleic acid (OA) lung injury. Mean pulmonary arterial pressure-(Ppa) flow (Q) relationships (generated by a manipulation of venous return, which was increased by opening a femoral arteriovenous bypass or decreased by inflating an inferior vena cava balloon) and gas exchange (evaluated by arterial blood gases and SF6 intrapulmonary shunt determinations) were investigated before and after OA (0.06 ml/kg i.v.) and again after solvent (n = 8), methylene blue (8 mg/kg i.v., n = 10), or N omega-nitro-L-arginine (40 mg/kg i.v., n = 8) in a randomized order. OA administration induced pulmonary hypertension, decreased arterial PO2, and increased intrapulmonary shunt. After OA, solvent had no effect on pulmonary hemodynamics and gas exchange. Both methylene blue and N omega-nitro-L-arginine further increased Ppa at all levels of Q. Only methylene blue, however, improved gas exchange after OA (arterial PO2 from 71 +/- 6 to 89 +/- 12 Torr and intrapulmonary shunt from 44 +/- 6 to 34 +/- 6%, both P < 0.02). These results suggest that nitric oxide is released during OA lung injury and modulates pulmonary hypertension. Whether nitric oxide impairs the regulation of gas exchange in OA lung injury remains uncertain, however.
Training cessation does not alter GLUT-4 protein levels in human skeletal muscle
Authors: Houmard J. A. , Hortobagyi T. , Neufer P. D. , Johns R. A. , Fraser D. D. , Israel R. G. , Dohm G. L.
Published: December 2017

The purpose of this study was to determine whether short-term training cessation resulted in reduced GLUT-4 protein levels. Endurance- (n = 12, ET) and strength-trained (n = 12) individuals (ST) were examined before and after 14 days of training withdrawal. GLUT-4 content was determined from muscle biopsy samples of the gastrocnemius in ET and the vastus lateralis in ST. Insulin sensitivity (oral glucose tolerance test) was significantly (P < 0.05) reduced in ET and ST with training cessation. GLUT-4 content was unaltered (P > 0.05) in both groups (92 and 100% of trained values for ET and ST, respectively). In ET, citrate synthase activity decreased significantly (P < 0.05) with training withdrawal (41.0 +/- 3.6 vs. 30.6 +/- 2.8 mumol.g-1.min-1); in ST no change was evident. The decrement in insulin sensitivity with the cessation of endurance- or resistance-oriented activity is therefore not associated with a reduction in GLUT-4 protein content. Muscle oxidative capacity and GLUT-4 content do not coincide with the removal of endurance training.
Ventilatory work and oxygen consumption during exercise and hyperventilation
Authors: Coast J. R. , Rasmussen S. A. , Krause K. M. , O'Kroy J. A. , Loy R. A. , Rhodes J.
Published: December 2017

The work of breathing (WB), and thus the energy requirement of the respiratory muscles, is increased any time minute ventilation (VE) is elevated, by either exercise or voluntary hyperventilation. Respiratory muscle O2 consumption (VRMO2) in humans has generally been estimated by having subjects breathe at a level comparable to that during exercise while the change in O2 consumption (VO2) is measured. The difference between VO2 at rest and during hyperventilation is attributed to the respiratory muscles and is assumed to be similar to VRMO2 during exercise at the same VE. However, it has been suggested that WB differs between exercise and hyperventilation and that WB during exercise is lower than during hyperventilation at the same VE. In this study we measured WB during exercise and hyperventilation and from these measurements estimated VRMO2. WB, VE, and VO2 were measured in five male subjects during rest and during exercise or hyperventilation at levels of VE ranging from 30 to 130 l/min. VE/WB relationship was determined for both hyperventilation and exercise. Multiple regression analysis showed that the shape of the two curves was different (P < 0.0001), with WB at high levels of VE being < or = 25% higher in hyperventilation than in exercise. In a second study in which frequency, tidal volume, and duty cycle were controlled as well as VE, there was no difference in WB between exercise and hyperventilation. VO2 was significantly correlated with WB, and the estimated VRMO2 did not increase as a fraction of total VO2 as exercise intensity rose.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo quantitation of carbonic anhydrase and band 3 protein contributions to pulmonary gas exchange
Authors: Swenson E. R. , Gronlund J. , Ohlsson J. , Hlastala M. P.
Published: December 2017

The contributions to pulmonary gas exchange of red blood cell (RBC) membrane band 3 protein HCO3(-)-Cl- exchange and carbonic anhydrase- (CA) catalyzed HCO3- dehydration have never been determined directly in the whole animal. We utilized an experimental and model approach to measure these by analysis of phase III exhaled CO2 and O2 profiles in anesthetized dogs. In this method, we inhibit RBC membrane band 3 protein and cytoplasmic CA in RBCs passing the pulmonary capillaries and lung vascular luminal membrane-bound CA during a single ventilatory cycle. This is achieved with appropriately timed right atrial infusions of 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS) to inhibit band 3 protein, ethoxzolamide (a lipophilic CA inhibitor with rapid membrane penetrance) to inhibit RBC and lung tissue CA, and benzolamide (an extremely hydrophilic CA inhibitor with virtually no penetrance into RBC cytoplasm) to inhibit only lung vascular luminal membrane CA. DNDS caused a 15% reduction in CO2 production (VCO2) without any change in O2 consumption (VO2). The addition of benzolamide to DNDS did not cause any further decrease in VCO2. Inhibition of RBC CA by ethoxzolamide caused a 67% reduction in VCO2 and a 11.5% reduction in VO2. Inhibition of lung vascular CA by benzolamide alone caused no statistically significant changes in either VCO2 or VO2. These results are in general agreement with in vitro data and model calculations. The only exceptions are the higher than predicted effect of RBC CA inhibition on VO2 (Bohr effect) and the lack of any contribution to CO2 transfer in the dog by lung vascular CA with access to plasma as a possible consequence of an endogenous plasma CA inhibitor.
Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling
Authors: Zhao L. , Crawley D. E. , Hughes J. M. , Evans T. W. , Winter R. J.
Published: December 2017

We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood-perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2–5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Centrally driven slow oscillating potential of extrathoracic trachea
Authors: Kondo T. , Kobayashi I. , Hirokawa Y. , Ohta Y. , Yamabayashi H. , Arita H.
Published: December 2017

Spontaneous electrical activity of extrathoracic trachea was recorded along with force developed by tracheal smooth muscle and phrenic nerve activity in decerebrated, paralyzed, and artificially ventilated dogs with pneumothorax. The tracheal electrical activity exhibited slow oscillating potentials that were coupled with spontaneous phasic contraction of trachea. Both rhythmic changes were synchronous with central respiratory rhythm represented by phrenic burst, independent of the respirator's rhythm. The dominant component of the slow oscillating potentials consisted of sinusoidal waves with large amplitude that occurred shortly after cessation of phrenic burst, i.e., in the postinspiratory phase. The concomitant small change in the slow oscillating potentials began in the late inspiratory phase just before the initiation of the tracheal contraction. This phase relationship was preserved after removal of intrathoracic vagal afferents from lungs. Such slow oscillating potentials were also observed during lung collapse produced by disconnecting the tube attached to the respirator. Transection of recurrent laryngeal nerves abolished the slow oscillating potentials. These results indicate that the slow oscillating potentials of the extrathoracic trachea are generated by a physiological process associated with the central respiratory rhythm. The dominant component of the slow oscillating potentials occurs in the postinspiratory phase.
Breathing periodicity in intact and carotid body-denervated ponies during normoxia and chronic hypoxia
Authors: Brown D. R. , Forster H. V. , Greene A. S. , Lowry T. F.
Published: December 2017

Periodic oscillations in pulmonary ventilation (VI), tidal volume (VT), and inspiratory and expiratory times (TI and TE) were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40–50 Torr) in awake intact (n = 8) and carotid body-denervated (CBD; n = 8) ponies. Periodic oscillations were identified by fast-Fourier transformation of breath-by-breath data and quantitated by determining the power ratio of significant periodic oscillations to total power of data sequence. Periodic oscillations of 0.063–0.500 cycles/breath were observed in all parameters during both normoxia and hypoxia. During normoxia, CBD accentuated periodicity of VT (P < 0.02) and VI (P < 0.01) but did not change TI or TE periodicity (P > 0.05). These findings suggest that carotid chemoreceptors serve to stabilize breathing (i.e., decrease periodicity) during normoxia, conceivably because of their shorter response time compared with that of central chemoreceptors. During certain periods of hypoxia, periodicity of VT and VI was significantly (P < 0.05) increased in intact ponies. The response to hypoxia in CBD ponies was variable, with VI periodicity significantly (P < 0.05) increasing, decreasing, or unchanging. Because some CBD ponies significantly changed their periodicity during hypoxia compared with normoxia, we conclude that carotid chemoreceptors are not requisite for hypoxia-induced changes in periodic breathing. In addition, our observations in both groups of ponies during normoxia and hypoxia suggest that multiple mechanisms may lead to periodic oscillations in breathing.
Effect of pulmonary blood flow on measurements of respiratory mechanics using the interrupter technique
Authors: Freezer N. J. , Lanteri C. J. , Sly P. D.
Published: December 2017

The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary arterial pressure, and left atrial pressure is unclear. Conventional methods for the measurement of respiratory mechanics model the respiratory system as a single compartment, which may not adequately represent the respiratory system in a diseased state. The interrupter technique models the respiratory system as two compartments, with the "flow resistance" of the conducting airways and chest wall (Raw) considered separately from Pdif, a measure of the viscoelastic properties of the lung and chest wall, together with any pendelluft present. The respiratory mechanics of 15 infants in the first year of life were studied during cardiac catheterization with the use of conventional methods and the interrupter technique. The infants had a PBF-to-systemic blood flow ratio ranging from 0.6 to 4.0:1. The specific dynamic compliance of the respiratory system was not related to the PBF; however, there was a significant relationship between PBF and the total resistance of the respiratory system (Rrs) [analysis of variance (ANOVA) F = 5.69, P < 0.05], Raw (ANOVA, F = 12.30, P < 0.01), and Pdif (ANOVA, F = 3.79, P < 0.05). Rrs increased significantly with an increase in mean left atrial pressure (ANOVA, F = 6.92, P < 0.05); however, dynamic compliance, Raw, and Pdif did not. These results suggest that the relationship between Rrs and PBF is due an increase in the resistive properties of the conducting airways and tissue components.
Effect of inspiratory muscle unloading on arousal responses to CO2 and hypoxia in sleeping dogs
Authors: Kimoff R. J. , Kozar L. F. , Yasuma F. , Bradley T. D. , Phillipson E. A.
Published: December 2017

Chemical respiratory stimuli can induce arousal from sleep, but the specific mechanisms involved have not been established. Therefore, we tested the hypothesis that mechanoreceptor stimuli arising in the ventilatory apparatus have a role in the arousal responses to progressive hypercapnia and hypoxia by comparing arousal responses during spontaneous ventilation with those obtained when the inspiratory muscles were unloaded by mechanical ventilatory assistance. Studies were performed in three trained dogs in which the adequacy of inspiratory muscle unloading was verified by diaphragmatic electromyographic (EMG) recordings. In rapid-eye-movement (REM) sleep the arousal threshold during progressive hypercapnia increased from 68.4 +/- 0.5 (SE) mmHg during spontaneous runs to 72.3 +/- 0.8 mmHg during mechanically assisted runs (P < 0.01). In contrast there were no changes in arousal responses to hypercapnia during non-REM (NREM) sleep or to hypoxia in either NREM or REM sleep. However, during the assisted hypoxic runs, EMG activity of the transversus abdominis muscle was increased compared with the unassisted runs; therefore, the effects on arousal threshold of unloading the inspiratory muscles may have been offset by increased loading of the expiratory muscles. The findings indicate that even in the absence of added mechanical loads, mechanoreceptor stimuli probably arising in the respiratory muscles contribute to the arousal response to hypercapnia during REM sleep.
Inhaled FMLP increases microvascular permeability in the rabbit trachea
Authors: Bell S. C. , Rynell A. C. , Matheson M. J. , Finnimore A. J. , Berend N.
Published: December 2017

This study was designed to determine the effect of inhaled N-formyl-methionyl-leucyl-phenylalanine (FMLP) on microvascular permeability in the rabbit trachea and to determine if the effect could be modified by cholinergic antagonism, neutral endopeptidase (NEP) inhibition, opioid receptor antagonism, or an opioid agonist. New Zealand White rabbits were anesthetized and pretreated intravenously with one of the following: saline, dimethyl sulfoxide (DMSO) (both controls), thiorphan, phosphoramidon (both NEP inhibitors), thiorphan and naloxone, morphine, or atropine. All rabbits were then given intravenous Evans blue before inhalation of nebulized DMSO (control) or FMLP. Extravascular tracheal Evans blue concentration was subsequently determined spectrophotometrically. FMLP caused a highly significant increase in microvascular permeability (92.6 +/- 7.1 micrograms/g of trachea, control 20.4' +/- 3.4). The effect of FMLP was significantly modified by cholinergic blockade (61.1 +/- 6.9) and by NEP inhibition (thiorphan 38.8 +/- 5.6, phosphoramidon 52.6 +/- 4.2). This effect of NEP inhibition could be reversed by concurrent treatment with the opioid receptor antagonist naloxone (95.9 +/- 34.6). Morphine had no significant effect. We concluded that FMLP increases microvascular permeability, which may in part explain the effect of FMLP on airway resistance in the rabbit. Inhibiting NEP decreases the response possibly through an effect on endogenous opioids. The response appears to be partially vagally mediated.
Muscle metabolism during lactate infusion in human phosphofructokinase deficiency
Authors: Bertocci L. A. , Haller R. G. , Lewis S. F.
Published: December 2017

We studied the effect of intravenous infusion of sodium lactate (La) on muscle high-energy phosphate metabolism, pH, and venous effluent [NH3] in three patients with muscle phosphofructokinase (PFK) deficiency and three healthy subjects during maximal-effort rhythmic handgrip exercise (5 s of contraction alternated with 5 s of rest) performed for 3 min. Healthy subjects were matched to PFK-deficient patients for gender and maximal handgrip strength. Force production was recorded and during lactate infusion was matched to that without lactate. 31P-magnetic resonance spectroscopy was used to measure intracellular phosphocreatine (PCr), orthophosphate (Pi), ATP, and pH in the flexor digitorum profundus of the exercising forearm. La infusion had no effect on healthy subjects or patients during rest. In healthy subjects, La infusion had no effect on depletion of PCr; accumulation of Pi, ADP, or venous effluent NH3; or decline in pH in exercising muscle. In contrast, during exercise in PFK-deficient patients, [PCr] was higher (17.9 +/- 1.9 vs. 13.1 +/- 1.4 mmol/kg) and [phosphomonoester] (11.4 +/- 1.3 vs. 6.5 +/- 1.4 mmol/kg), [Pi] (9.2 +/- 1.8 vs. 5.0 +/- 0.7 mmol/kg), [ADP] (60.4 +/- 7.0 vs. 37.9 +/- 9.9 mumol/kg), and venous effluent [NH3] (335 +/- 136 vs. 176 +/- 61 mM) were lower (P < 0.05) during La infusion than in control conditions. The effects of La infusion on intracellular [PCr], [Pi], [phosphomonoester], [ADP], and [NH3] in PFK-deficient patients are consistent with the hypothesis that exogenous La augments the rate of oxidative phosphorylation in active muscle by bypassing the enzymatic block at PFK.
Role of tendon properties on the dynamic performance of different isometric muscles
Authors: Roeleveld K. , Baratta R. V. , Solomonow M. , van Soest A. G. , Huijing P. A.
Published: December 2017

The effect of the tendon's viscoelastic stiffness on the dynamic performance of muscles with different architecture was determined using the cat's medial gastrocnemius and extensor digitorum longus. Dynamic response models were derived under sinusoidal contraction-relaxation in the range of 0.4 (556.0 Hz and between 20 and 80% of the muscles' maximal isometric tension, manipulated by orderly recruitment-derecruitment of motor units together with firing rate increase-decrease. It was shown that, for isometric contractions at the muscle's optimum length, the dynamic response of the muscles was not significantly different before and after dissection of the tendon. Therefore the conclusion that under these conditions the tendon acts like a stiff force transmitter without significantly modifying the muscle's performance was confirmed and extended to muscles with different architecture.
Skeletal muscle calcium-activated neutral protease (calpain) with exercise
Authors: Belcastro A. N.
Published: December 2017

The purpose of this study was to investigate whether exercise could induce calpain activation by altering the Ca2+ required for half-maximal activity (pCa50) and/or susceptibility of digestible muscle protein substrates. Rats (225 g) were assigned to control, exercise (25 m/min, 0% grade), and 24-h recovery groups. Exercise resulted in a generalized 48 +/- 18% loss of muscle glycogen and a twofold increase in plasma creatine kinase levels (P < or = 0.05). Exercise increased total caseinolysis of diethylaminoethyl Sepharose-prepared low (u) and high (m) Ca2+ calpain isoforms by 22 and 30%, respectively (P < or = 0.05). The pCa50 of u- and m-calpain with exercise increased from 5.98 +/- 0.12 to 6.20 +/- 0.15 (P > or = 0.05) and from 3.63 +/- 0.10 to 3.90 +/- 0.16 (P > or = 0.05), respectively. In vitro, calpain-mediated degradation/disappearance rates (i.e., percentage of protein degraded in 10 min) for control tropomyosin and alpha-actinin were 69 and 30% compared with 92 and 61% after exercise (P < or = 0.05). The results of this study confirm that level running increases total nonlysosomal Ca2+ specific protease activity, which may promote exercise-induced muscle damage or fatigue.
Adenosine decreases permeability of in vitro endothelial monolayers
Authors: Haselton F. R. , Alexander J. S. , Mueller S. N.
Published: December 2017

The addition of adenosine to perfusates flowing through an in vitro cell-column model of the vasculature decreases the permeability of cell column fetal bovine aortic endothelial monolayers. At 10(-4) M adenosine, cell monolayer permeability to the paracellular tracers polyethylene glycol (mol wt 900) and cyanocobalamin (mol wt 1,355) is significantly decreased within 15 min. In continuous treatments with adenosine for up to 30 min, the permeability reduction is maintained, and removal of adenosine returns permeability to baseline levels within 15 min. The effect of adenosine is concentration dependent, with a 5% reduction in permeability with 10(-6) M adenosine, a 21% reduction with 10(-5) M adenosine, and a 37% reduction with 10(-4) M adenosine. The effects of adenosine are not blocked by the adenosine transport inhibitor dipyridamole. Permeability is significantly reduced by the A2-specific adenosine analogue 5′-(N-cyclopropyl)-carboxamidoadenosine but not by the A1-specific adenosine analogue N6-(L-2-phenylisopropyl)adenosine. In addition, the permeability decrease is blocked by the A2-receptor antagonist 8-phenyltheophylline (10(-5)M). We conclude that adenosine decreases the permeability of bovine fetal aortic endothelial monolayers via endothelial A2-purinoceptors.
Modulation of maximal inspiratory airflow by neuromuscular activity: effect of CO2
Authors: Schwartz A. R. , Thut D. C. , Brower R. G. , Gauda E. B. , Roach D. , Permutt S. , Smith P. L.
Published: December 2017

To determine how maximal inspiratory airflow (VImax) is modulated by changes in airway neuromuscular activity, we analyzed pressure-flow relationships obtained during inspiration and expiration in isolated upper airways of anesthetized hyperoxic dogs at different levels of CO2. Inspiratory airflow (VI), hypopharyngeal pressure (Php), pharyngeal pressure at the flow-limiting site (FLS), and alae nasi (AN) and genioglossus (GG) electromyographic (EMG) activity were recorded while VI limitation was produced by rapidly lowering Php until VI plateaued at VImax. VImax and its mechanical determinants, pharyngeal critical pressure (Pcrit) and nasal resistance (Rn) upstream to the FLS, were measured. During hypercapnia (high CO2), VImax increased significantly during inspiration (217.3) and expiration (184.1%). These increases were associated with significant increases in phasic but not tonic AN and GG activity. They were also associated with decreases in Pcrit from -6.2 +/- 1.6 (SE) at hypocapnia to -9.3 +/- 3.0 and -11.8 +/- 3.4 cmH2O at high CO2 during expiration and inspiration, respectively. No significant changes in Rn occurred. When phasic neuromuscular activity was abolished by complete neuromuscular blockade in three dogs, these increases in VImax and decreases in Pcrit at high CO2 were eliminated. When phasic EMG activity was accentuated in four vagotomized dogs, significant increases in VImax and decreases in Pcrit were demonstrated during inspiration vs. expiration at high CO2. These findings indicate that upper airway neuromuscular activity increases VImax in the isolated upper airway by decreasing collapsibility (Pcrit) at the FLS site when neuromuscular activity is stimulated by hypercapnia.
Computer simulation of neutrophil transit through the pulmonary capillary bed
Authors: Hanger C. C. , Wagner W. W. , Janke S. J. , Lloyd T. C. , Capen R. L.
Published: December 2017

One-half of the neutrophils that enter the pulmonary circulation become temporarily trapped in capillaries. The neutrophils that are impeded make complete stops between free-flowing movements. These observations, based on in vivo microscopy, suggest that pulmonary margination is caused by neutrophils being impeded at focal sites in the capillary bed. To investigate the frequency with which impeding sites had to occur in the pulmonary capillaries to trap one-half of the circulating neutrophils, we developed a computer model to simulate neutrophils encountering discrete obstructions in a capillary-like network. Surprisingly, if only 1% of the capillaries in the network acted as traps, one-half of the neutrophils stopped at least once. The trapping ability of a given percentage of obstructions was independent both of the geometry of the network was whether the obstructions occurred in the segments or junctions. To simulate neutrophil transit more realistically, both neutrophil and capillary diameters were randomly selected from published diameter distributions. Every neutrophil was trapped multiple times by this model, suggesting that cell deformation contributes importantly to neutrophil passage through the pulmonary capillary bed.
Determination of maximal power output at neuromuscular fatigue threshold
Authors: Moritani T. , Takaishi T. , Matsumoto T.
Published: December 2017

The purpose of this study was to determine the maximal power output at the neuromuscular fatigue threshold (EMGFT), as estimated from electromyographic (EMG) data from representative leg muscles during cycling. The rate of rise in integrated EMG activity as a function of time (iEMG slope) was calculated at each of four constant-power-output ergometer bouts for 20 subjects. The iEMG slopes were plotted against work rates that were well described as linear functions (0.84 < R2 < 0.99). This iEMG slope vs. work rate relationship was extrapolated to zero slope to give an intercept on the power axis that was interpreted as the highest work rate sustainable without EMG evidence of neuromuscular fatigue (EMGFT). Each individual EMGFT was then expressed in terms of an O2 output (VO2) equivalent on the basis of the individual delta efficiency calculated during a linearly increasing maximal exercise test on the same bicycle ergometer. Results indicated a highly significant correlation (r = 0.92, P < 0.01) between EMGFT VO2 and anaerobic threshold VO2, as determined by conventional gas exchange criteria. The mean EMGFT VO2 (1.84 +/- 0.55 l/min) was, however, significantly greater (P < 0.01) than the anaerobic threshold VO2 (1.72 +/- 0.54 l/min). It was suggested that the EMGFT may provide an attractive alternative to the measurement of the highest work rate that can be sustained without evidence of neuromuscular fatigue.
Autonomic mechanisms of muscle metaboreflex control of heart rate
Authors: O'Leary D. S.
Published: December 2017

Ischemia in active skeletal muscle induces reflex increases in systemic arterial pressure (SAP) and heart rate (HR), termed the muscle metaboreflex. When metaboreflex activation is maintained during postexercise muscle ischemia, SAP remains elevated; however, HR decreases. Why the HR responses differ with metaboreflex activation during exercise vs. during postexercise ischemia while the SAP responses are similar in each setting remains unclear. Two hypotheses were tested: 1) the increase in HR with muscle ischemia occurs predominantly via an increase in sympathetic activity, and 2) sympathetic activity to the heart remains elevated during post-exercise ischemia; however, HR decreases because of an increase in parasympathetic outflow. The muscle metaboreflex was activated in conscious dogs during treadmill exercise (3.2 kph, 0% grade) by progressively decreasing perfusion to the hindlimbs. Experiments were performed before and after muscarinic (atropine) or beta- (atenolol or propranolol) receptor blockade. In control experiments, once beyond the threshold for the reflex, the HR sensitivity of the muscle metaboreflex averaged -2.4 +/- 0.3 beats.min-1.mmHg-1 and the reflex open-loop gain averaged -3.2 +/- 0.3 (calculated as the ratio of the increase in HR or SAP to the decrease in hindlimb perfusion pressure beyond threshold). Atropine had no effect on either HR sensitivity (-2.7 +/- 0.4 beats.min-1.mmHg-1) or open-loop gain (-3.3 +/- 0.5, both P > 0.05 vs. control). However, pretreatment with beta-receptor antagonist significantly decreased both HR sensitivity (-0.7 +/- 0.1 beats.min-1.mmHg-1, P < 0.001) and open-loop gain (-1.9 +/- 0.3, P < 0.01). During postexercise ischemia, HR decreased while SAP remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of blood flow in the perfused tracheae of sheep: a search for arteriovenous anastomoses
Authors: Corfield D. R. , Webber S. E. , Widdicombe J. G.
Published: December 2017

The possible existence of arteriovenous anastomoses (AVAs) in the tracheobronchial circulation has been largely ignored; however, their presence would have many implications. Here we have searched for AVAs in the tracheal circulation of seven anesthetized sheep that were ventilated through a low cervical tracheostomy. Arteries to the midcervical trachea were isolated and perfused in situ at systemic blood pressure; blood flow was measured with an electromagnetic flow probe. A vein draining the perfused segment was cannulated. Radiolabeled microspheres (16 microns diam) injected into the arterial inflow of the perfusion indicated the distribution of blood flow (cervical trachea, 69.9 +/- 4.55% (SE); esophagus, 15.1 +/- 3.9%; connective tissue and blood vessels near trachea, 9.5 +/- 1.8%; lymph nodes, 4.0 +/- 2.2%; skeletal muscle, 0.17 +/- 0.07%; trachea below intubation, 0.00%; larynx, 0.00%; other tissues 0.81 +/- 0.32%). Less than 0.6% of the activity was detected in the tracheal venous blood and lungs, indicating little shunting via AVAs. Within the trachea, blood flow (per wet weight of tissue) to the mucosa overlying smooth muscle was approximately 25% of that to the mucosa overlying cartilage. Intra-arterial infusion of methacholine doubled perfusion blood flow without altering the proportion of shunted blood. Within the trachea, blood flow increased most to the mucosa overlying smooth muscle and to smooth muscle. In conclusion the contribution of AVAs to total blood flow in the cervical trachea is < 1%.
Blood flow distribution to upper airway muscles
Authors: Brancatisano A. , Kelly W. T. , Baile E. M. , Pare P. , Engel L. A.
Published: December 2017

Radiolabeled (15-microns) microspheres were used to measure blood flow to upper airway muscles [alae nasi (AN), intrinsic laryngeal, tongue, cervical strap, and hyoid musculature], diaphragm (DI), and parasternals (PS) during spontaneous breathing in 24 anesthetized tracheotomized supine dogs. Six dogs were also studied while -28 +/- 3 (SE) cmH2O tracheal airway pressure was generated against an inspiratory resistance (IR) (upper airway bypassed). Blood flow to posterior cricoarytenoid muscle (PCA) [24.0 +/- 2.1 (SE) ml.min-1.100 g-1] was greater than that to DI (18.0 +/- 2.3 ml.min-1.100 g-1) and comparable to that to PS (21.4 +/- 2.9 ml.min-1.100 g-1). Blood flow per unit weight did not differ between AN, tongue muscles, laryngeal adductors, cervical strap muscles, and cricothyroid (CT). Average blood flow to these muscles was only 8.0 +/- 0.8 ml.min-1.100 g-1. With the exception of CT, blood flow to these upper airway muscles was less than that to DI and PCA. Relative to blood flow during spontaneous breathing, IR loading increased blood flow to AN by a factor of 7.5, to PCA by 3.4, to DI by 3.2 and to PS by 1.9. There was no change in blood flow in the other muscles during loading. Our results show that at rest blood flow to main glottic dilator (PCA) is similar to that to main inspiratory muscles. Furthermore, in response to an IR load, blood flow to PCA and AN increased by an equivalent or greater amount than that to DI.(ABSTRACT TRUNCATED AT 250 WORDS)
A distensible vessel model applied to hypoxic pulmonary vasoconstriction in the neonatal pig
Authors: Nelin L. D. , Krenz G. S. , Rickaby D. A. , Linehan J. H. , Dawson C. A.
Published: December 2017

Recently, we presented a simple two-parameter distensible vessel model as a potential tool for characterizing pulmonary vascular pressure vs. flow curves under zone 3 conditions (Linehan et al. J. Appl. Physiol. 73: 987–994, 1992). One parameter, alpha, represents the distensibility of the resistance vessels as the fractional change in vessel diameter per Torr change in pressure, and the other parameter, R0, represents the vascular resistance that would exist if the resistance vessels were at their respective diameters obtained if the vascular pressure were zero. The objective of the present study was to determine whether this distensible vessel model was capable of describing the pressure vs. flow data obtained during hypoxia vasoconstriction and under control conditions in isolated lungs from neonatal pigs. The piglet lungs were perfused with autologous blood, and the pulmonary arterial pressure was measured over a range of flow rates from 15 to 250 ml.min-1 x kg-1 at constant left atrial (3 Torr) pressure. The model provided a reasonable fit to the data under both conditions. Hypoxia resulted in a significant increase in R0, from 0.39 +/- 0.10 Torr.ml-1 x min.kg during control conditions to 1.41 +/- 0.46 Torr.ml-1 x min.kg during hypoxia. alpha was 2.4 +/- 0.4%/Torr under control conditions and 2.0 +/- 0.4%/Torr during hypoxia, but this difference was not statistically significant. The results suggest that the distensible vessel model may be useful for interpreting pressure-flow data in terms of changes in geometry and distensibility of the resistance vessels in response to a vasoconstrictor stimulus such as hypoxia.
Effects of acute hypoxia on intracranial dynamics in unanesthetized goats
Authors: Yang Y. B. , Sun B. , Yang Z. , Wang J. , Pong Y.
Published: December 2017

The effects of acute hypoxia on intracranial dynamics were studied in six unanesthetized goats that were subjected to hypobaric hypoxia at a simulated 4,000-m high altitude for 2 h. Another six nonhypoxic goats served as control group for cerebral water content (CWC). In this study, we measured cerebral blood flow (CBF) by electromagnetic flowmeter, intracranial pressure (ICP) through an intraventricular catheter, and CWC by a wet-to-dry weight technique for a given volume of brain tissue. Intracranial compliance was calculated from a pressure-volume index derived from the change in intraventricular pressure after a subarachnoid injection of saline. During acute hypoxia CBF increased from 146.0 +/- 10.60 to 185.3 +/- 7.83 ml x min-1.100 g-1, ICP increased from 15.4 +/- 1.82 to 27.4 +/- 3.84 cmH2O, and CWC increased from 78.7 +/- 0.30 to 79.5 +/- 0.16%, but intracranial compliance decreased from 0.65 +/- 0.28 to 0.36 +/- 0.19 ml/cmH2O. The data suggest that acute hypoxia results in a significant disturbance of intracranial dynamics, which may be one of the important pathophysiological mechanisms of high-altitude cerebral edema and acute mountain sickness.
Involvement of inhibitory dopamine-2 receptors in resting bradycardia in exercise-conditioned rats
Authors: Slavik K. J. , LaPointe J.
Published: December 2017

The purpose of this investigation was to examine the underlying cause for the resting bradycardia and lower resting blood pressure demonstrated in conscious rats that performed 12 wk of treadmill exercise conditioning. The influence of inhibitory dopamine (DA2) receptors and alpha 2-adrenoceptors, which are known to mediate bradycardia and hypotension, was assessed in exercise-conditioned (EC) and nonexercised conditioned (NC) rats. To accomplish this, preferential DA2 and alpha 2-agonists and antagonists were administered at rest to conscious rats after they participated in an exercise conditioning program. The results obtained with the DA2 antagonist metoclopramide (15 mg/kg ip) alone suggest that there is physiological activation of cardiovascular DA2 receptors in EC rats but not in NC rats. Furthermore, the results obtained with the DA2 agonist bromocriptine (1.5 mg/kg ip) suggest that the DA2 receptor-mediated bradycardia and hypotension are greater in EC rats than in NC rats. In addition, heart rate and blood pressure responses to the alpha 2-agonist clonidine (0.1 mg/kg ip) and antagonist yohimbine (1 mg/kg ip) were not different between EC and NC rats. These data suggest that enhanced DA2 receptor influence accounts, in part, for the resting bradycardia and lower resting blood pressure demonstrated in EC rats after 12 wk of exercise conditioning.
Effect of dynamic exercise on renal sympathetic nerve activity in conscious rabbits
Authors: O'Hagan K. P. , Bell L. B. , Mittelstadt S. W. , Clifford P. S.
Published: December 2017

Renal sympathetic nerve activity (RSNA) increases abruptly at the onset of treadmill exercise in conscious rabbits. This study investigated whether the rise in RSNA is related to the intensity of the exercise and whether an elevated level of RSNA is maintained during submaximal exercise. RSNA, arterial blood pressure (BP), and heart rate (HR) were recorded in 10 New Zealand White rabbits during two treadmill exercise protocols at 0% grade: 7 m/min for 5 min and 12 m/min for 2 min. Peak levels of RSNA were observed in the first 10 s of exercise at 7 and 12 m/min. Through 2 min of exercise, the rise in RSNA was greater (P < 0.05) at 12 m/min (delta 83 +/- 22%) compared with 7 m/min (delta 49 +/- 8%). At 7 m/min, HR and BP reached steady-state levels during the 2nd min of exercise. RSNA remained elevated at delta 43 +/- 10 to delta 54 +/- 13% over resting levels as exercise continued from the 2nd through the 5th min of exercise (P < 0.05). These data demonstrate that the RSNA response to exercise is intensity related and suggest that RSNA remains elevated and thus may contribute to the control of renal blood flow during submaximal dynamic exercise.
Contribution of tissue lipid to long xenon residence times in muscle
Authors: Novotny J. A. , Parker E. C. , Survanshi S. S. , Albin G. W. , Homer L. D.
Published: December 2017

Experiments demonstrate that the mean residence time of an inert gas in tissue is longer than that predicted by a single-compartment model of gas exchange. Also the relative dispersion (RD, the standard deviation of residence times divided by the mean) is 1 according to this model, but RDs in real tissues are closer to 2, suggesting that a multiple-compartment model might be more accurate. The residence time of a gas is proportional to its solubility in the tissue. Although the noble gases in particular are 10 times more soluble in lipid than in nonlipid tissues, models of gas exchange generally do not incorporate measurements of the lipid in tissue, which may lead to error in the predicted gas residence times. Could a multiple-compartment model that accounts for the lipid in tissue more accurately predict the mean and RD of gas residence times? In this study, we determined the mean and RD of Xe residence times in intact and surgically isolated muscles in a canine model. We then determined the lipid content and the perfusion heterogeneity in each tissue, and we used these measurements with a multiple-compartment model of gas exchange to predict the longest physiologically plausible Xe residence times. Even so, we found the observed Xe mean residence times to be twice as long as those predicted by the model. However, the predicted RDs were considerably larger than the observed RDs. We conclude that lipid alone cannot account for the residence times of Xe in tissue and that a multiple-compartment model is not an accurate representation of inert gas exchange in tissue.
Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury
Authors: Davis J. M. , Rosenfeld W. N. , Sanders R. J. , Gonenne A.
Published: December 2017

To determine if recombinant human Cu-Zn superoxide dismutase (rhSOD) would prevent acute lung injury caused by hyperoxia and barotrauma, 26 newborn piglets were studied. Ten piglets were hyperventilated (arterial PCO2 15–20 Torr) with 100% O2 for 48 h. A second group received identical treatment for 4 h (n = 2) or 48 h (n = 8) but was given 5 mg/kg of rhSOD intratracheally at time 0. Six piglets were normally ventilated (arterial PCO2 40–45 Torr) for 48 h with 21% O2. Pulmonary function and tracheal aspirates were examined at time 0 and at 24 and 48 h, and bronchoalveolar lavage was performed at 48 h. In piglets treated with hyperoxia and hyperventilation, lung compliance decreased 42%, and tracheal aspirates showed an increase in neutrophil chemotactic activity (32%), total cell counts (135%), elastase activity (93%), and albumin concentration (339%) over 48 h (P < 0.05). All variables were significantly lower in rhSOD-treated piglets and comparable to normoxic control values. Surfactant remained active in all groups. Immunohistochemistry demonstrated that at 48 h significant rhSOD was distributed homogeneously in terminal airways. Adding rhSOD to tracheal aspirates of hyperoxic hyperventilated piglets did not alter neutrophil chemotaxis, suggesting that rhSOD protected the lung by reducing the production of chemotactic mediators. Results indicate that acute lung injury caused by 48 h of hyperoxia and hyperventilation is significantly ameliorated by prophylactic intratracheal administration of rhSOD.
Effect of adrenodemedullation on decline in muscle malonyl-CoA during exercise
Authors: Winder W. W. , Braiden R. W. , Cartmill D. C. , Hutber C. A. , Jones J. P.
Published: December 2017

Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase, a rate-limiting enzyme of fatty acid oxidation. Previous studies have indicated that muscle malonyl-CoA declines in rats during treadmill running. This decrease may be important for allowing an increased rate of fatty acid oxidation during prolonged exercise. This study was designed to determine whether epinephrine is essential for inducing the decline in muscle malonyl-CoA during exercise. Male Sprague-Dawley rats underwent adrenodemedullation (ADM) or sham operation. After allowing 3 wk for recovery, rats were killed (pentobarbital anesthesia) at rest or after running at 21 m/min up a 15% grade for 60 min. Red quadriceps malonyl-CoA decreased from 2.6 +/- 0.3 to 0.8 +/- 0.07 nmol/g in sham-operated rats and from 2.2 +/- 0.3 to 0.8 +/- 0.1 nmol/g in ADM rats. White quadriceps malonyl-CoA decreased to similar levels during exercise in both sham-operated and ADM rats. A second experiment on 24-h fasted rats also showed no impairment in the exercise-induced decline in red quadriceps malonyl-CoA as a result of adrenodemedullation. The hormones of the adrenal medulla are therefore unessential for inducing the decline in malonyl-CoA during exercise.