bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of IgG1 and its fragments on resting membrane potential of isolated tracheal myocytes
Authors: Souhrada M. , Souhrada J. F.
Published: December 2017

We enzymatically isolated airway smooth muscle cells from the trachea of guinea pigs (400–600 g body wt). After removal of connective tissue, strips of trachealis muscle were cleaned under a dissecting microscope and incubated with collagenase (type I, 1 mg/ml) and elastase (type I, 15 U/ml) for 20 min. Cells were resuspended in Dulbecco's modified Eagle's medium and seeded on 1.5% gelatin-coated Petri dishes (35 mm). The viability of cells was assessed by trypan blue exclusion. Individual myocytes were impaled with glass microelectrodes (input resistance 90–100 M omega). Resting membrane potential (Em) was determined before and after administration of 1) immune serum, 2) highly purified specific immunoglobulin G1 (IgG1), and 3) enzymatically prepared fragments of IgG1-F(ab')2 and Fc. We found that 1) Em of isolated tracheal myocytes is -60.5 +/- 0.5 mV; 2) some myocytes exhibit spontaneous electrical rhythm with mean frequency of 16.9 +/- 12 min-1 and mean amplitude of 3.7 +/- 0.6 mV; 3) immune serum, IgG1, and Fc fragments induced a biphasic change in Em: the initial mean depolarization (-51.5 +/- 0.8 mV) was followed by a steady-state hyperpolarization (-68.3 +/- 0.6 mV); and 4) pretreatment of myocytes with amiloride (10(-5) M) or exposure of myocytes to a low-sodium environment prevented changes in Em induced by the passive in vitro sensitization. It is likely that airway smooth muscle cells have a low-affinity Fc receptor, the occupancy of which leads to activation of amiloride-sensitive sodium influx.
Phrenic and sympathetic nerve responses to glutamergic blockade during normoxia and hypoxia
Authors: Chae L. O. , Melton J. E. , Neubauer J. A. , Edelman N. H.
Published: December 2017

Because hypoxia increases brain extracellular glutamate levels, we hypothesized that gasping and increased sympathetic activity during severe hypoxia result from glutamergic excitation. To test this hypothesis, we exposed anesthetized paralyzed vagotomized glomectomized cats to hypoxia before and after N-methyl-D-aspartate (NMDA) glutamergic blockade (MK-801, 1 mg/kg iv) or non-NMDA blockade (NBQX, 3 mg/kg iv) while monitoring phrenic neurogram (PN) and inspiratory-synchronous (ISSN) and tonic (TSN) activity in cervical sympathetic neurogram (SN). Before hypoxia, MK-801 caused apneusis and reduced PN and ISSN amplitude by 38 and 84%, respectively, but TSN activity was unaffected. During hypoxia, MK-801 had no effect on PN gasping or TSN activity but reduced ISSN amplitude during gasping. Before hypoxia, NBQX reduced PN and ISSN amplitude by 54 and 60%, respectively but did not affect inspiratory timing or TSN activity. Gasping activity in PN and ISSN and TSN activity during hypoxia were unaffected by NBQX. We conclude that 1) ionotropic glutamergic receptor activation is important for eupneic phrenic patterning but is not involved in genesis of gasping, 2) NMDA receptor activation is involved in integration of respiratory and sympathetic activity, and 3) changes in TSN activity are independent of ionotropic glutamergic receptor activation.
Inherent coupling of elastic and dissipative behavior of the lung through a viscoelastic time constant
Authors: Nicolai T. , Lanteri C. J. , Sly P. D.
Published: December 2017

The simple model best able to describe the viscoelastic behavior of lung tissues contains a Kelvin body. Some facets of the viscoelastic behavior of the model can be characterized by a time constant. We have performed a series of experiments to demonstrate this viscoelastic time constant in open-chest mechanically ventilated puppies by recording the stress recovery after midexpiratory flow interruption. In 19 8- to 10-wk-old puppies, the mean time constant was 0.64 +/- 0.01 (SE) s. This time constant remained unchanged after inhalation challenge with histamine, methacholine, or hypertonic saline, despite marked changes in tissue mechanics (resistance and elastance) and in hysteresivity. The constancy of the viscoelastic time constant demonstrates a tight coupling of the parameters of the Kelvin body model, effectively reducing the viscoelastic parameters to a single degree of freedom, and may explain the coupling between the dynamic elastic and resistive properties of the lung tissues previously demonstrated.
TNF-alpha and cyclooxygenase metabolites do not modulate C. albicans septic shock with disseminated candidiasis
Authors: Matuschak G. M. , Klein C. A. , Tredway T. L. , Schilly D. R. , Lechner A. J.
Published: December 2017

We analyzed differences in host regulation of tumor necrosis factor-alpha (TNF-alpha) production and pathophysiological responses in conscious rats after infection with two strains of pathogenic Candida albicans spp. (CA-1 and CA-2) compared with Escherichia coli serotype 055:B5 (EC). The hypothesis was tested that, in contrast to EC, hypotension, organ injury, and mortality after candidemia are not obligatorily dependent on TNF-alpha or TNF-alpha-induced cyclooxygenase pathway metabolites. Dose, viability, and strain-specific dependencies were established after intravenous 10(6) or 10(9) viable CA, as well as heat-killed (HK) or Formalin-inactivated (FI) CA blastospores, compared with live EC at the 24-h LD25 [10(9) colony-forming units (CFU)] and LD100 (10(10) CFU). Shock without endotoxemia developed 4–8 h after 10(9) live CA-1 or CA-2 (LD100 at 24 h) with disseminated yeast-mycelial transformation and increased microvascular permeability in multiple organs but not after HK or FI CA-1. Peak serum TNF-alpha after an LD100 of CA-1 or CA-2 was < 3% of LD25 EC values and was < 1% of peak values during lethal bacteremia. Similar pathogen-specific differences were found in liver- and lung-associated TNF. Production of functionally inactive TNF-alpha during candidemia was excluded by enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blotting. Passive immunization against TNF-alpha 2 h before microbial challenge was not protective against CA but prevented otherwise lethal EC sepsis. Cyclooxygenase inhibition also failed to attenuate candidemic shock. We conclude that the magnitude and kinetics of TNF-alpha production and TNF-alpha-dependent immunophysiological responses are differentially regulated after lethal fungal vs. gram-negative bacterial infection. Thus TNF-alpha is not a pivotal mediator of the acute Candida septic shock syndrome with disseminated candidiasis.
NK1 receptors mediate neurogenic inflammatory increase in blood flow in rat airways
Authors: Piedimonte G. , Hoffman J. I. , Husseini W. K. , Snider R. M. , Desai M. C. , Nadel J. A.
Published: December 2017

We studied the effect of neurogenic inflammation on airway blood flow in anesthetized F-344 rats. Three successive determinations of blood flow were made by injecting radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. A selective agonist of the tachykinin receptor neurokinin 1 (NK1) increased airway blood flow, but NK2- and NK3-selective agonists were without effect. The natural agonist of NK1 receptors, substance P (1 micrograms/kg), increased airway blood flow, an effect that was abolished by the selective NK1 receptor antagonist CP-99,994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] but not by the (2R,3R)-enantiomer CP-100,263. Capsaicin (25 micrograms/kg), a drug that releases tachykinins and calcitonin gene-related peptide from sensory nerves, increased airway blood flow, and again this effect was abolished by CP-99,994. We also studied the effect of a selective inhibitor (captopril, 2.5 mg/kg) of the tachykinin-degrading enzyme kininase II [or angiotensin-converting enzyme (ACE)] on substance P-induced airway vasodilation. Captopril potentiated and prolonged the vasodilator effect of substance P. We conclude that neurogenic vasodilation in rat airways is due to the release of substance P, acts via NK1 receptors, and may be modulated by ACE.
Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training
Authors: Hellsten-Westing Y. , Norman B. , Balsom P. D. , Sjodin B.
Published: December 2017

The effect of high-intensity intermittent training on the adenine nucleotide content of skeletal muscle was studied. Eleven male subjects (group A) performed high-intensity intermittent training on a cycle ergometer three times per week for 6 wk, followed by 1 wk of the same kind of training with two sessions per day. Nine males (group B) exclusively performed 1 wk of training with two sessions per day. In group A, skeletal muscle total adenine nucleotide (TAN) levels decreased from 25.1 +/- 0.7 (SE) to 22.0 +/- 0.6 mmol/kg dry wt over the 6-wk period (P < 0.01). The subsequent intensive week did not further alter TAN levels. In group B, the intensive week of training reduced TAN levels from 25.1 +/- 0.5 to 19.4 +/- 0.6 mmol/kg dry wt (P < 0.001). The decrease was sustained 72 h after training (P < 0.001). During the intensive week, there was no change in plasma creatine kinase activity in either group A or group B. The plasma activity was, however, higher in group B than in group A on days 4 and 7 of the intensive week (P < 0.05). The results from this study indicate that high-intensity intermittent exercise causes a decrease in resting levels of skeletal muscle adenine nucleotide without a concomitant indication of muscle damage. A training-induced adaptation appears to occur with training by which a further loss of adenine nucleotides is prevented despite an increased training dose.
Noninvasive cardiac output measurement by arterial pulse analysis compared with inert gas rebreathing
Authors: Stok W. J. , Baisch F. , Hillebrecht A. , Schulz H. , Meyer M. , Karemaker J. M.
Published: December 2017

Noninvasive cardiac output (CO) measured by arterial pulse analysis was compared with that measured by inert gas rebreathing in six healthy male volunteers. Pulse contour analysis was applied to the pressure wave output of a Finapres, which noninvasively measures continuous arterial pressure in a finger. Data were collected before, during, and after a 10-day 6 degrees head-down tilt experiment. Intravenous saline loading and lower body negative pressure stimuli varied CO over 2.8–9.6 l/min, as measured by the rebreathing technique. Because pulse contour provides only relative changes in CO, to obtain absolute values it must be calibrated against another measurement. Pulse contour data were calibrated every measurement day against the mean of two to four control rebreathing CO measurements before the lower body negative pressure or intravenous saline loading stimuli. Using one averaged calibration factor per subject for a total of 27 days, we compared the results of both methods. The linear regression between pulse contour (Pc CO) and rebreathing CO (Rebr CO) was Pc CO = 0.15 + 0.98(Rebr CO) (r = 0.96). The standard deviation of the difference of the two methods was 0.5 l/min (n = 205), excluding data used for calibration. By monitoring pulse contour CO before and during rebreathing, the rebreathing maneuver itself was shown to produce a substantial increase in CO that was mainly related to an increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of theophylline on brain tissue oxygenation during normoxia and hypoxia in humans
Authors: Nishimura M. , Yoshioka A. , Yamamoto M. , Akiyama Y. , Miyamoto K. , Kawakami Y.
Published: December 2017

Although theophylline, an adenosine receptor antagonist, is known to reduce cerebral blood flow, little clinical attention has been paid to this adverse effect. This study was designed to examine the effect of theophylline on brain tissue oxygenation for a wide range of arterial PO2 in healthy volunteers. Partial gas pressures and O2 saturation in an artery (SaO2) and the internal jugular vein (SjO2) were simultaneously measured while subjects (n = 6) were breathing room air and then exposed to two levels of isocapnic hypoxia (arterial PO2 = 60 and 45 Torr) before and after infusion of theophylline (6 mg/kg of aminophylline). For the same levels of arterial oxygenation, jugular vein PO2 markedly dropped, by 3–5 Torr, after theophylline infusion, as did SjO2, by as much as 6–10%, under the arterial PCO2, which was slightly lower by 1–2 Torr in the theophylline study. By use of the linear regression lines obtained from the relationship between SaO2 and SjO2 in each study, it was calculated that the SjO2 with theophylline, while SaO2 was 95, 90, and 80%, was comparable to that without theophylline when SaO2 was 81, 78, and 73%, respectively. On the basis of the assumption that partial gas pressures and SjO2 reflect brain tissue oxygenation, these data suggest that the effect of theophylline on brain tissue oxygenation should not be ignored in some clinical settings. The effects of chronic administration remain to be studied.
Transcapillary fluid responses to lower body negative pressure
Authors: Aratow M. , Fortney S. M. , Watenpaugh D. E. , Crenshaw A. G. , Hargens A. R.
Published: December 2017

The effect of lower body negative pressure (LBNP) on transcapillary fluid balance is unknown. Therefore, our objective was to assess leg interstitial fluid pressures (IFP), leg circumference, plasma volume (PV), and net whole body transcapillary fluid transport (TFT) during and after supine LBNP and to evaluate the addition of oral saline ingestion on transcapillary exchange. Six healthy men 23–41 yr old underwent 4 h of 30 mmHg LBNP, followed by 50 min of supine recovery on two separate occasions, once with and once without ingestion of 1 liter of isotonic saline. IFP was measured continuously in subcutis as well as superficial and deep regions of the tibialis anterior muscle by slit catheters. TFT was calculated by subtracting urine production and calculated insensible fluid loss from changes in PV. During exposure to LBNP, IFP decreased in parallel with chamber pressure, foot venous pressure did not change, leg circumference increased by 3 +/- 0.35% (SE) (P < 0.05), and PV decreased by 14 +/- 2.3%. IFP returned to near control levels after LBNP. At the end of minute 50 of recovery, PV remained decreased (by 7.5 +/- 5.2%) and leg circumference remained elevated (by 1 +/- 0.37%). LBNP alone produced significant movement of fluid into the lower body but no net TFT (-7 +/- 12 ml/h). During LBNP with saline ingestion, 72 +/- 4% of the ingested fluid volume filtered out of the vascular space (TFT = 145 +/- 10 ml/h), and PV decreased by 6 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
Construction and uses of a concentric catheter for gas sampling in lung airways
Authors: Gavriely N. , Solway J. , Elad D. , Shabtai-Musih Y. , Gaver D. P. , Grotberg J. B. , Drazen J. M.
Published: December 2017

A catheter for intra-airway sampling of gas concentrations was constructed from concentric polyethylene tubes. The internal tube (0.58 mm ID, 0.91 mm OD) was connected to a gas analyzer while the external tube (1.20 mm ID, 1.75 mm OD) was constantly flushed by air or a calibration gas, except during sampling. Injection and sampling dead spaces were 0.35 and 0.28 ml, respectively. Delay at 4-ml/min sampling rate was 4.0 +/- 0.2 s. The 0–90% step response to a sudden change in gas composition was 0.24 s when connected to a mass spectrometer. This catheter was used to assess tracer gas dispersion during oscillatory flow (1–20 Hz) in a straight long tube. Local concentrations measured through the catheter, after a small bolus of tracer gas was injected through the external tube, compared favorably with direct measurements through needles inserted via the tube wall and with theoretical predictions. The catheter was also used to measure intra-airway gas concentrations in dog airways during spontaneous breathing, conventional mechanical ventilation, high-frequency ventilation, high-frequency vibration ventilation, and constant-flow ventilation. It ws placed by a fiber-optic bronchoscope and used to measure local quasi-steady concentrations of CO2 and local dispersion with the bolus method. The occurrence of catheter clogging with secretions was substantially reduced with flow through the external tube. Transmitting a calibration gas through the external tube facilitated in situ recalibration of the gas analyzer without removing the catheter. The use of this catheter improved the efficiency and accuracy of measurements of gas concentrations inside lung airways.
Functional evidence for different endothelin receptors in the lung
Authors: Lippton H. L. , Hauth T. A. , Cohen G. A. , Hyman A. L.
Published: December 2017

The present study was undertaken to compare and contrast the characteristics of the pulmonary and systemic vascular responses to endothelin (ET) isoforms in the intact spontaneously breathing cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone (PVT) was actively increased by intralobar infusion of U-46619, intralobar arterial bolus injections of 1 microgram ET-1, 1 microgram ET-2, or 3 micrograms ET-3 markedly decreased lobar arterial pressure, systemic arterial pressure, and systemic vascular resistance. After seven repeated injections of ET-1 or ET-2 to separate groups of cats, pulmonary and systemic responses were largely reversed from vasodilation to vasoconstriction. In contrast, the pulmonary vasodilator response to ET-3 remained intact after multiple ET-3 injections, whereas its systemic vasodilator response was lost. Repeated intralobar arterial bolus injections of ET-1, ET-2, or ET-3 also caused the loss of pulmonary vasodilation to subsequent doses of ET-1, ET-2, or sarafotoxin 6b but not to ET-3. The present data suggest that the pulmonary and systemic vasodilator responses to ET-1 and ET-2 undergo tachyphylaxis and cross-tachyphylaxis. In contrast, the pulmonary vasodilator response to ET-3, unlike its systemic vasodilator response, is resistant to tachyphylaxis and cross-tachyphylaxis. The present data provide a functional correlate for the existence of at least two ET receptor subtypes, ETA-like and ETC-like receptors, in the adult pulmonary vascular bed.
Effects of muscle contraction on cytochrome a,a3 redox state
Authors: Duhaylongsod F. G. , Griebel J. A. , Bacon D. S. , Wolfe W. G. , Piantadosi C. A.
Published: December 2017

The relationships among mitochondrial O2 availability, O2 delivery, and lactate formation in exercising skeletal muscle remain unclear. Some data suggest that muscle O2 provision is sufficient at maximal O2 consumption (VO2max) to challenge the concept of a mitochondrial O2 limitation at VO2max. The relationships among VO2, mitochondrial O2 availability, and net lactate production were studied over a wide range of exercise intensities. Using near-infrared spectroscopy, the oxidation-reduction state of cytochrome a,a3 was monitored in the canine gracilis in vivo. Twenty adult dogs were anesthetized with alpha-chloralose, intubated, and mechanically ventilated on room air. Five-minute stimulation periods at rates of 2, 3, 4, 5, 7, 8, 10, or 12 stimuli/s were performed. VO2max generally was achieved at a stimulation rate of 8 stimuli/s; mean VO2max was 0.12 +/- 0.09 (SE) ml.min-1 x g-1. The concentration of oxidized mitochondrial cytochrome a,a3 decreased at all work loads relative to resting state and demonstrated a near-linear relationship with muscle VO2 (r2 = 0.99). Muscle lactate efflux and the lactate-pyruvate ratio also were correlated positively with cytochrome a,a3 reduction, suggesting a common regulatory mechanism coupling the processes of aerobic glycolysis and oxidative phosphorylation. At VO2max, the corresponding cytochrome oxidation was not significantly different from that observed at death. Thus, in the gracilis maximal exercise leads to near-complete reduction of cytochrome a,a3 secondary to deficient O2 provision. We conclude that VO2max is limited primarily by O2 delivery to this muscle and not by other factors limiting mitochondrial ATP production or substrate oxidation.
Respiratory muscle fatigue resistance relates to myosin phenotype and SDH activity during development
Authors: Watchko J. F. , Sieck G. C.
Published: December 2017

We correlated the fatigue resistance (FR) of the costal diaphragm (DIA) and external abdominal oblique (EAO) of the rat during postnatal development with their respective 1) myosin heavy chain (MHC) phenotypes and 2) oxidative capacities [indexed by quantitative measurements of succinic dehydrogenase (SDH) enzyme activity]. FR was measured in vitro during isometric contractions with the use of the Burke fatigue test. FR of the DIA and EAO was high in newborns and declined during postnatal development. SDH activity was uniformly low in neonatal DIA and EAO and increased during early postnatal development before declining to adult levels. FR did not significantly correlate with SDH activity (r2 = 0.01) but did relate to the MHC phenotype as indexed by the ratio of adult MHC isoform content (slow + IIa + IIx + IIb) to developmental MHC isoform content (slow + neonatal; r2 = 0.88, P < 0.01). Stepwise regression revealed that neonatal MHC expression alone accounted for 60% of the developmental variance in FR. The correlation between FR and MHC phenotype was improved if SDH was also considered, i.e., the ratio of SDH to MHC phenotype (r2 = 0.99, P < 0.01). We conclude that FR of respiratory muscle during development relates to a balance between the energetic demands of the muscle contractile proteins as reflected by MHC isoform composition and its oxidative capacity with MHC phenotype alone exerting a strong predictive effect on FR.
Hypoglossal and phrenic nerve responses to carotid baroreceptor stimulation
Authors: Wasicko M. J. , Giering R. W. , Knuth S. L. , Leiter J. C.
Published: December 2017

We examined the relationship between hypoglossal and phrenic nerve activities and carotid sinus pressure. In 12 adult cats that were decerebrate, vagotomized, paralyzed, and mechanically ventilated, we isolated the left carotid sinus for perfusion and denervated the right carotid sinus. Mean arterial blood pressure was maintained at 90–100 mmHg using a low resistance-reservoir containing saline and connected to the abdominal aorta. Constant pressure was applied to the carotid sinus region. We found that increased carotid sinus pressure immediately inhibited inspiratory-synchronous (phasic) hypoglossal nerve activity and that there was a direct inverse relationship between phasic hypoglossal activity and carotid sinus pressure up to a carotid pressure of 285 mmHg. Increased carotid sinus pressure had no effect on tonic hypoglossal nerve activity and only slightly inhibited phrenic nerve activity. Cutting the left carotid sinus nerve abolished this response. We also applied pressure pulses to the carotid sinus at discrete times during the phrenic cycle. We found that baroreceptor inhibition of phasic hypoglossal nerve activity was gated during the phrenic cycle: maximum inhibition occurred when the pulse was applied in late expiration. We conclude that carotid baroreceptor stimulation preferentially inhibits inspiratory synchronous hypoglossal nerve activity and that this afferent information traveling in the carotid sinus nerve is gated by the respiratory control center.
Model of pleural fluid turnover
Authors: Miserocchi G. , Venturoli D. , Negrini D. , Del Fabbro M.
Published: December 2017

A model of pleural fluid turnover, based on mass conservation law, was developed from experimental evidence that 1) pleural fluid filters through the parietal pleura and is drained by parietal lymphatics and 2) lymph flow increases after an increase in pleural liquid volume, attaining a maximum value 10 times greater than control. From the differential equation describing the time evolution of pleural liquid pressure, we obtained the equation for the steady-state condition ("set point") of pleural liquid pressure: Pss = (KfPi*+KlPzf)/Kf+Kl), where Kf is parietal pleura filtration coefficient, Kl is initial lymphatic conductance, Pzf is lymphatic potential absorption pressure, and Pi* is a factor accounting for the protein reflection coefficient of parietal mesothelium and hydraulic and colloid osmotic pressure of parietal interstitium and pleural liquid. Lymphatics act as a passive negative-feedback control tending to offset increases in pleural liquid volume. Some features of this control are summarized here: 1) lymphatics exert a tight control on pleural liquid volume or pressure so that the set point is maintained close to the potential absorption pressure of lymphatics; 2) a 10-fold increase in Kf would cause only a 2- and 5-fold increase in pleural liquid volume with normal (1.8 g/dl) and increased (3.4 g/dl) protein concentration of the pleural fluid, respectively; and 3) the reduction in maximum lymph flow greatly reduces the range of operation of the control with increased filtration and/or protein concentration of pleural fluid.
Interactive effect of inhaled bradykinin with histamine and PGD2 in bronchial asthma
Authors: Rajakulasingam K. , Gnanakumaran G. , Church M. K. , Howarth P. H. , Holgate S. T.
Published: December 2017

Interaction among mediators such as bradykinin (BK), histamine (H), and prostaglandin (PG) D2 may contribute to reduction in airway caliber in asthma. Ten stable asthmatic subjects took part in a study to investigate possible mediator interaction. The provocative concentration of mediator required to reduce forced expiratory volume in 1 s (FEV1) by 12.5% from the starting baseline value (PC12.5) and that required to reduce the fall in FEV1 from 12.5 to 25% (PC25–12.5) of H, BK, and PGD2 were determined. On three subsequent occasions, subjects inhaled either the vehicle plus BK PC12.5 or the vehicle plus H or PGD2 PC25–12.5, and FEV1 was measured at regular time intervals up to 40 min. Predicted time course curves were calculated from these results. On two additional occasions, interactive time course studies were undertaken when the subject inhaled BK PC12.5 followed by H or PGD2 PC25–12.5. On a further three visits, the time courses of individual mediators were studied. When BK was combined with H and PGD2, the maximum fall in FEV1 and the rate of recovery after inhalation of the second mediator were not significantly different from those values of predicted time course responses for the same combination of mediator. Thus, by employing pharmacologically active concentrations of inhaled BK, H, and PGD2, which act through separate receptor mechanisms, we were unable to demonstrate any pharmacological interaction on airway caliber in asthma.
Cerebral blood flow and evoked potentials during reoxygenation with 21 or 100% O2 in newborn pigs
Authors: Rootwelt T. , Odden J. P. , Hall C. , Ganes T. , Saugstad O. D.
Published: December 2017

The effects of resuscitation with 21 or 100% O2 on cerebral blood flow (CBF) and somatosensory evoked potentials (SEPs) were studied in 19 newborn pigs anesthetized with pentobarbital sodium. They were ventilated with 8% O2 until base excess reached -20 mmol/l and then were randomly reoxygenated with 21% O2 (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2. Mean duration of hypoxemia in the two groups was 57 +/- 6 (SE) and 59 +/- 6 min, respectively. CBF determined by radioactive microspheres was significantly increased in all areas in both groups after 5 and 20 min of reoxygenation. At 5 min of reoxygenation forebrain O2 uptake (CMRo2) had increased significantly compared with baseline values in the 21% O2 group (2.5 +/- 0.1 to 3.2 +/- 0.2 ml.100 g-1.min-1) but not in the 100% O2 group. There were, however, no significant differences between the two groups in CBF or CMRo2 at any time, and by 60 min of reoxygenation both had returned to baseline levels. SEPs were not significantly different in the two groups. We conclude that, as judged by CBF, CMRo2, and SEP, 21% O2 is not inferior to 100% O2 when hypoxemic newborn pigs are reoxygenated.
Effects of age and acclimation on responses to passive heat exposure
Authors: Armstrong C. G. , Kenney W. L.
Published: December 2017

To examine the effect of chronological age on thermoregulation during passive heat exposure, six older (O, 61 +/- 1 yr) and six young (Y, 26 +/- 2 yr) men sat at rest during a 30-min baseline period (dry-bulb temperature = 28 degrees C), a 60-min thermal transient (28–46 degrees C by 2 degrees C steps every 5 min), and 30 min at 46 degrees C dry-bulb temperature. Subjects were matched for maximal O2 consumption, anthropometry, and body composition. Testing was repeated after a 9-day active heat acclimation protocol. There were no age differences in rectal (Tre), mean skin (Tsk), or mean body temperature (Tb = 0.8Tre + 0.2Tsk) before or after acclimation, but heart rate was lower (P < 0.01) in the O group in both acclimation states. Heat acclimation resulted in a significantly lower baseline Tre and Tb in both groups, which remained lower throughout the passive heat stress (P < 0.05). To examine the effects of age and acclimation on thermoregulatory effector function, forearm blood flow (by venous occlusion plethysmography) and chest sweating rate (SRch, by dew-point hygrometry) were plotted against Tb. The slope of the forearm blood flow-Tb relationship was significantly (P < 0.05) lower in the O group before and after acclimation. A lower maximal SRch (P < 0.05) was achieved by the O group, but neither the slope of SRch-Tb relationship nor the Tb threshold for sweating was affected by age. Predictably, acclimation resulted in a lower Tb threshold for the onset of sweating and skin vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Velocity profiles measured for airflow through a large-scale model of the human nasal cavity
Authors: Hahn I. , Scherer P. W. , Mozell M. M.
Published: December 2017

An anatomically accurate, x20 enlarged scale model of a healthy right human adult nasal cavity was constructed from computerized axial tomography scans for the study of nasal airflow patterns. Detailed velocity profiles for inspiratory and expiratory flow through the model and turbulence intensity were measured with a hot-film anemometer probe with 1 mm spatial resolution. Steady flow rates equivalent to 1,100, 560, and 180 ml/s through one side of the real human nose were studied. Airflows were determined to be moderately turbulent, but changes in the velocity profiles between the highest and lowest flow rates suggest that for normal breathing laminar flow may be present in much of the nasal cavity. The velocity measurements closest to the model wall were estimated to be inside the laminar sublayer, such that the slopes of the velocity profiles are reasonably good estimates of the velocity gradients at the walls. The overall longitudinal pressure drop inside the nasal cavity for the three inspiratory flow rates was estimated from the average total shear stress measured at the central nasal wall and showed good agreement with literature values measured in human subjects.
Effects of hyperoxia on maximal leg O2 supply and utilization in men
Authors: Knight D. R. , Schaffartzik W. , Poole D. C. , Hogan M. C. , Bebout D. E. , Wagner P. D.
Published: December 2017

We studied O2 transport in the leg to determine if hyperoxia will increase the maximal rate of O2 uptake (VO2max) in exercising muscle. An increase in inspired O2 fraction (FIO2) from 0.21 to 1.00 was postulated to have the following effects: 1) increase the leg VO2max by approximately 5–10%, 2) increase the maximal O2 delivery [arterial O2 concentration.flow (CaO2.Q] by approximately 10%, and 3) raise the leg VO2max in proportion to both the femoral venous PO2 and mean leg capillary PO2. To test these hypotheses, 11 men performed cycle exercise to the highest work rates (WRmax) they could achieve while breathing 100% O2 (hyperoxia), 21% O2 (normoxia), and 12% O2 (hypoxia). Leg VO2 was derived from duplicate measurements of femoral venous blood flow and CaO2 and femoral venous blood O2 concentrations (CVO2) at 20, 35, 50, 92, and 100% WRmax in each FIO2. Femoral venous leg Q (Qleg) was measured by the constant-infusion thermodilution technique, and leg O2 uptake (VO2) was determined by the Fick principle [VO2 = Qleg(CaO2-CVO2)]. Leg VO2max was the mean of duplicate values of VO2 at 100% WRmax for each FIO2. Hyperoxia increased leg VO2max by 8.1% (P = 0.016) and maximal O2 delivery by 10.9% (P = 0.05) without changing Qleg. There was a significant increase in femoral venous PO2 (P < 0.001) that was proportionally greater than the increase in leg VO2max. The results support our first and second hypotheses, providing direct evidence that in normal subjects leg VO2max is limited by O2 supply during normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Limitations of a pulsed Doppler velocimeter for blood flow measurement in small vessels
Authors: Quail A. W. , Cottee D. B. , White S. W.
Published: December 2017

The performance of a new and simplified flow probe construction and the Iowa 545C-4 pulsed Doppler velocimeter was evaluated for measurement of blood flow over several months in small arteries of awake animals. Calibrations were performed over a wide range of intraluminal pressures and physiological flow velocities. Pressure-dependent differences in slope of the Doppler shift-volume flow relationship were detected in some probes. Signal strength was maintained at hematocrits > 10%. Distortion of pulsed Doppler signal peaks occurred in the conscious rabbit at peak aortic velocities, at which Reynold's number for turbulence was exceeded and the Doppler shift surpassed the Nyquist limit of 31.25 kHz for the velocimeter. Although the Doppler shift-volume flow relationship is linear at < 5 kHz, in some cases at higher Doppler shifts and blood flow velocities the relationship may become nonlinear, thus causing the volume flow rate to be underestimated by up to 38%. The cause of this phenomenon may be "aliasing" and/or the consequence of the range control capability of the velocimeter selectively sampling changing velocity profiles and flow disturbances in the central stream at higher velocities.
31P-NMR spectroscopy, rsEMG, and histochemical fiber types of human wrist flexor muscles
Authors: Mizuno M. , Secher N. H. , Quistorff B.
Published: December 2017

The metabolic response to graded rhythmic forearm exercise determined by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy was evaluated with respect to recruitment pattern of muscles and to fiber type composition of the nondominant arm in 14 untrained subjects. Rectified smoothed surface electromyography (rsEMG) over finger and wrist flexor muscles increased similarly and progressively at 30, 45, and 60% of maximal exercise intensity. On the basis of the 31P-NMR response pattern during exercise, subjects were separated into three groups: H group (n = 4), with a single high-pH P(i) peak; M group (n = 7), with two P(i) peaks reflecting two pH components; and L group (n = 3), with a single low-pH P(i) peak. The H group demonstrated a faster recovery of P(i) and phosphocreatine than the L group (P < 0.05). The M group displayed both types of P(i) recovery and an intermediate resynthesis rate of phosphocreatine. The M group had an even distribution of slow- and fast-twitch fibers in the flexor carpi radialis muscle, whereas subjects in the H and L groups possessed a predominance of slow- and fast-twitch fibers, respectively. The results suggest that during rhythmic forearm exercise the interindividual NMR variation in energy metabolism is related closely to fiber type composition of the muscle.
Pulmonary removal and production of endothelin in the anesthetized dog
Authors: Dupuis J. , Goresky C. A. , Stewart D. J.
Published: December 2017

The single-bolus multiple-indicator-dilution technique was used to evaluate pulmonary removal of tracer 125I-labeled endothelin-1 in seven anesthetized dogs. Simultaneously, pulmonary arterial and aortic blood samples were obtained and assayed to determine the levels of immunoreactive endothelin-1. When 125I-endothelin-1 was compared with a plasma vascular reference (Evans blue dye), there was a single passage mean extraction of 31 +/- 8%. In contrast, there was no significant difference between immunoreactive endothelin-1 levels measured in blood samples from the pulmonary artery and the aorta (1.26 +/- 0.58 and 1.37 +/- 0.50 pg/ml, respectively; P = 0.47). The absence of an arteriovenous difference for bulk endothelin-1 across the lungs in the presence of tracer data indicating a substantial uptake implies that an amount of endothelin-1 quantitatively more or less equal to that removed is produced by the lung. The shapes of the dilution curves suggest that the tracer endothelin uptake by the lung is a one-way process without vascular reentry of tracer. We conclude that the dog lung is an important site for both uptake and release of endothelin-1.
Endogenous vasodilators modulate pulmonary vascular anaphylaxis
Authors: Kelly L. J. , Undem B. J. , Adams G. K.
Published: December 2017

We examined the role of endothelium-derived nitric oxide during antigen-induced contraction in pulmonary arteries isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml)-induced contraction was not sustained, and tension returned to baseline within 15 min. Pretreatment with methylene blue (10(-5) M) increased both the amplitude and the duration of the contractile response in these tissues. At 15 min, tension remained elevated and was > 70% of the peak amplitude. Removal of the endothelium with saponin (200 micrograms/ml) increased the magnitude of the contraction by > 125%; however, the duration of the response was unaffected. After pretreatment with saponin, methylene blue no longer increased the amplitude of antigen-induced contraction but its effect on the duration was unchanged. Pretreatment with nitro-L-arginine methyl ester significantly increased the magnitude of the contraction in each of the tissues. These results suggest that the response of guinea pig pulmonary arteries to antigen is modulated by two types of endogenous vasodilators, endothelium-derived nitric oxide that inhibits the initial phase of the response and an endothelium-independent relaxing factor that is guanosine 3′,5′-cyclic monophosphate dependent and attenuates the duration of anaphylactic contraction.
Selectivity for Echo Spectral Interference and Delay in the Auditory Cortex of the Big Brown Bat Eptesicus fuscus
Authors: Sanderson Mark I. , Simmons James A.
Published: December 2017

The acoustic environment for an echolocating bat can contain multiple objects that reflect echoes so closely separated in time that they are almost completely overlapping. This results in a single echo with a spectrum characterized by deep notches due to interference. The object of this study was to document the possible selectivity, or lack thereof, of auditory neurons to the temporal separation of biosonar signals on a coarse (ms) and fine (μs) temporal scale. We recorded single-unit activity from the auditory cortex of big brown bats while presenting four protocol designs using wideband FM signals. The protocols simulated a pair of partially overlapping echoes where the separation between the first and second echo varied between 0 and 72 μs, a pulse followed by a single echo at varying delay from 0 to 30 ms, a pulse followed at a fixed delay by a pair of partially overlapping echoes that had a varying temporal separation of 0–72 μs, and a pulse followed, with a varying delay between 0 and 30 ms, by a pair of echoes that themselves had a fixed temporal separation on a microsecond time scale. About half of the cortical units showed increased spike counts to pairs of partially overlapping echoes at particular separations (6–72 μs) compared with a baseline stimulus at 0-μs separation. For many neurons tested with a pulse followed by two overlapping echoes, we observed a sensitivity to the coarse delay between the pulse and pair of overlapping echoes and to the separation between the two echoes themselves. The sensitivity to the partial overlap between the two echoes was not tuned to a single temporal separation. For bats, this means that the absolute range to the closest reflector and range between reflectors may be jointly encoded across a small population of single units. There are several possible neuronal mechanisms for encoding the separation between two nearby echoes based on the sensitivity to spectral notches.
Gating of Local Network Signals Appears as Stimulus-Dependent Activity Envelopes in Striate Cortex
Authors: Schiff N. D. , Purpura K. P. , Victor J. D.
Published: December 2017

Neuronal activity often is treated as a composition of a stimulus-driven component and a second component that corrupts the signal, adding or deleting spikes at random. Standard quantitative methods such as peristimulus histograms and Fourier analysis use stimulus-locked averaging to enhance detection of the driven component of neuronal responses and de-emphasize the “noise.” However, neural activity also includes bursts, oscillations, and other episodic events that standard averaging methods overlook. If this activity is stimulus independent, it can be characterized by standard power spectral analysis (or autocorrelation). But activity that is excited by (but not temporally locked to) the visual stimulus cannot be characterized by averaging or standard spectral analysis. Phase-locked spectral analysis (PLSA) is a new method that examines this “residual” activity—the difference between the individual responses to each cycle of a periodic stimulus and their average. With PLSA, residual activity is characterized in terms of temporal envelopes and their carriers. Previously, PLSA demonstrated broadband interactions between periodic visual stimuli and fluctuations in the local field potential of macaque V1. In the present study, single-unit responses (SUA) from parafoveal V1 in anesthetized macaque monkey are examined with this technique. Recordings were made from 21 neurons, 6 of which were recorded in pairs along with multiunit activity (MUA) from separate electrodes and 8 of which were recorded along with MUA from the same electrode. PLSA was applied to responses to preferred (orientation, direction, and spatial frequency) and nonpreferred drifting gratings. For preferred stimuli, all cells demonstrated broadband (1–10 Hz and higher) residual activity that waxed and waned with the stimulus cycle, suggesting that changes in the residual activity are introduced routinely by visual stimulation. Moreover, some reconstructed envelopes indicate that the residual activity was sharply gated by the stimulus cycle. Oscillations occasionally were seen in the power spectrum of single units. Phase-locked cross-spectra were determined for 3 SUA/SUA pairs and 11 SUA/MUA pairs. Residual activity in the cross-spectra was generally much less than the residual activity determined separately from each neuron. The reduction in the residual activity in the cross-spectra suggests that nearby neurons may gate inputs from distinct and relatively independent neuronal subpopulations that together generate the background rhythms of striate cortex.
Compensation for Interaction Torques During Single- and Multijoint Limb Movement
Authors: Gribble Paul L. , Ostry David J.
Published: December 2017

During multijoint limb movements such as reaching, rotational forces arise at one joint due to the motions of limb segments about other joints. We report the results of three experiments in which we assessed the extent to which control signals to muscles are adjusted to counteract these “interaction torques.” Human subjects performed single- and multijoint pointing movements involving shoulder and elbow motion, and movement parameters related to the magnitude and direction of interaction torques were manipulated systematically. We examined electromyographic (EMG) activity of shoulder and elbow muscles and, specifically, the relationship between EMG activity and joint interaction torque. A first set of experiments examined single-joint movements. During both single-joint elbow ( experiment 1) and shoulder ( experiment 2) movements, phasic EMG activity was observed in muscles spanning the stationary joint (shoulder muscles in experiment 1 and elbow muscles in experiment 2). This muscle activity preceded movement and varied in amplitude with the magnitude of upcoming interaction torque (the load resulting from motion of the nonstationary limb segment). In a third experiment, subjects performed multijoint movements involving simultaneous motion at the shoulder and elbow. Movement amplitude and velocity at one joint were held constant, while the direction of movement about the other joint was varied. When the direction of elbow motion was varied (flexion vs. extension) and shoulder kinematics were held constant, EMG activity in shoulder muscles varied depending on the direction of elbow motion (and hence the sign of the interaction torque arising at the shoulder). Similarly, EMG activity in elbow muscles varied depending on the direction of shoulder motion for movements in which elbow kinematics were held constant. The results from all three experiments support the idea that central control signals to muscles are adjusted, in a predictive manner, to compensate for interaction torques—loads arising at one joint that depend on motion about other joints.
Altered Taste Responses in Adult NST After Neonatal Chorda Tympani Denervation
Authors: Dinkins Mark E. , Travers Susan P.
Published: December 2017

Anatomic and behavioral changes have been observed in the taste system after peripheral deafferentation, but their physiological consequences remain unknown. Interestingly, a recent behavioral study suggested that peripheral denervation could induce central plasticity. After neonatal chorda tympani (CT) transection, adult rats demonstrated a marked preference for a normally avoided salt, NH4Cl. In the present study, taste responses were recorded from the nucleus of the solitary tract (NST) in similarly CT-denervated rats to investigate a physiological basis for this behavioral phenomenon. We hypothesized that alterations in functional connectivity of remaining afferent nerves might underlie the behavioral change. Specifically, if NST neurons formerly activated by sodium-selective CT fibers were instead driven by more broadly tuned glossopharyngeal (GL) afferents, neural coding of salt responses would be altered. Such a change should be accompanied by a shift in orotopic representation and increased NH4Cl responses. This hypothesis was not supported. After CT denervation, orotopy was unaltered, NH4Cl responsiveness declined, and no other changes occurred that could simply explain the behavioral effects. Indeed, the most pronounced consequence of CT denervation was a 68% reduction in NaCl responses, supporting previous evidence for a critical role of this nerve in coding sodium salts. In addition, we found “reorganizational” changes similar to, albeit smaller than, those observed in other sensory systems after deafferentation. There was a trend for increased responses elicited by stimulation of receptor subpopulations innervated by the GL and greater superficial petrosal nerves. In addition, the spontaneous rate of nasoincisor duct-responsive cells increased significantly. This effect on spontaneous rate is opposite to that produced by CT anesthesia, suggesting that acute versus chronic denervation may affect central taste neurons differently. In conclusion, the taste system at the medullary level seems more resistant to large-scale plasticity than other sensory systems, but nevertheless reacts to lost afferent input. Because the most robust plastic changes have been documented at cortical levels in other sensory pathways, the substrate for the behavioral effect of neonatal CT transection may be located more centrally in the gustatory system.