bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory-related control of palatoglossus and levator palatini muscle activity
Authors: Tangel D. J. , Mezzanotte W. S. , White D. P.
Published: December 2017

Route of respiration [nasal (NR) vs. oral (OR)] is determined by the position of the soft palate. Despite this, little is known about the respiratory-related activity of palatal muscles. We investigated the activity of two palatal muscles: palatoglossus (PG) and levator palatini (LP). Eight normal male subjects were studied during wakefulness with intramuscular electrodes placed in the PG and LP. The electromyograms (EMGs) of the PG and LP were measured during both NR and OR under 1) quiet basal respiration, 2) inspiratory resistive loading (25 cmH2O.l–1.s), and 3) progressive hypercapnia. The PG consistently demonstrated inspiratory phasic activity during NR with greater inspiratory and expiratory EMGs (P < 0.05) during basal NR compared with basal OR [3.3 +/- 0.2 (SE), 1.1 +/- 0.1, 2.3 +/- 0.4, and 1.0 +/- 0.2 arbitrary units for PG nasal inspiratory, PG oral inspiratory, PG nasal expiratory, and PG oral expiratory, respectively]. During OR, the LP was inspiratory phasic in 4 subjects and expiratory phasic in 4 subjects, with greater inspiratory and expiratory EMGs during basal OR compared with basal NR (5.5 +/- 1.1, 2.1 +/- 0.4, 6.8 +/- 1.5, and 1.8 +/- 0.4 arbitrary units for LP oral inspiratory, LP nasal inspiratory, PG oral expiratory, and PG nasal expiratory, respectively). Both muscles demonstrated significantly increased activity during both inspiratory resistive loading and hypercapnia. However, their route-specific activation pattern continued during such stimulated breathing. We conclude that 1) the route of respiration is influenced by the complex interaction of the PG and LP and 2) the response of these muscles to respiratory stimuli is dependent on the route of respiration.
Influences of NREM sleep on activity of palatoglossus and levator palatini muscles in normal men
Authors: Tangel D. J. , Mezzanotte W. S. , White D. P.
Published: December 2017

Most evidence indicates that palatal position has an important influence on respiration during sleep. We have previously demonstrated during wakefulness that the levator palatini (LP) and the palatoglossus (PG) muscles function in an integrated manner in determining the route of respiration. In this study we first determined the effect of non-rapid-eye-movement (NREM) sleep on LP and PG electromyograms (EMGs) and then assessed if subjects could switch from nasal (NR) to oral (OR) respiration during NREM sleep without arousal. Six normal males subjects were studied using intramuscular EMG recording electrodes (LP and PG) and a divided mask to separate NR and OR. Peak inspiratory and end-expiratory EMGs of the LP fell significantly during NREM sleep [3.7 +/- 0.4 (SE), 1.9 +/- 0.4, and 2.4 +/- 0.7 arbitrary units for LP peak inspiratory awake, stage 2, and stage 3/4, respectively; 2.7 +/- 0.2, 1.5 +/- 0.2, and 1.8 +/- 0.5 arbitrary units for LP end-expiratory awake, stage 2, and stage 3/4, respectively; P < 0.05]. In a similar manner, the peak inspiratory EMG of the PG fell from wakefulness to stage 2 NREM sleep [5.1 +/- 0.5 and 3.9 +/- 0.5 arbitrary units for PG peak inspiratory awake and stage 2, respectively]. On the other hand, the PG peak inspiratory activity returned to near waking levels during stage 3/4 sleep, with the PG end-expiratory activity never falling during sleep. A total of 14 nasal occlusions were performed during NREM sleep. In all cases except one, an arousal was required to institute a change to OR.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in human skeletal muscle ultrastructure and force production after acute resistance exercise
Authors: Gibala M. J. , MacDougall J. D. , Tarnopolsky M. A. , Stauber W. T. , Elorriaga A.
Published: December 2017

Muscle ultrastructure and contractile properties were examined before and after a single bout of resistance exercise (8 sets of 8 repetitions at 80% of 1 repetition maximum). Eight untrained males performed the concentric (Con) phase of arm-curl exercise with one arm and the eccentric (Ecc) phase with the other arm. Needle biopsies were obtained from biceps brachii before exercise (Base), immediately postexercise from each arm (post-Con and post-Ecc), and 48 h postexercise from each arm (48 h-Con and 48 h-Ecc). Electron microscopy was used to quantify the presence of disrupted fibers in each sample. Analysis of variance revealed a greater (P < or = 0.05) proportion of disrupted fibers in post-Con, post-Ecc, 48 h-Con, and 48 h-Ecc samples compared with Base. Significantly more fibers were disrupted in post-Ecc (82%) and 48 h-Ecc (80%) samples compared with post-Con (33%) and 48 h-Con (37%), respectively. Voluntary and evoked strength measurements recovered to Base values within 24 h in the Con arm but remained depressed (P < or = 0.05) for 72–96 h in the Ecc arm. These data indicate that both the raising and lowering phases of weightlifting produced myofibrillar disruption, with the greatest disruption occurring during the lowering phase.
Fluid changes during pregnancy: use of bioimpedance spectroscopy
Authors: Van Loan M. D. , Kopp L. E. , King J. C. , Wong W. W. , Mayclin P. L.
Published: December 2017

The increase in body water during pregnancy is responsible for the largest portion of weight gain and is of interest of clinical practitioners. However, assessing changes in body fluids is not easily accomplished during pregnancy. The purpose of this study was to examine the accuracy of bioelectrical impedance spectroscopy for estimating fluid volumes before, during, and after pregnancy. Ten healthy adult women were recruited for the study. Total body water (TBW) and extracellular fluid (ECF) volume were measured at baseline (preconception); 8–10, 24–26, and 34–36 wk of gestation; and 4–6 wk postpartum by deuterium oxide and NaBr dilution, respectively. Estimates of TBW and ECF were also obtained by bioimpedance spectroscopy (BIS). At baseline, mean values for dilution and BIS estimates of TBW and ECF were 33.2 +/- 4.6 (SD) vs. 31.6 +/- 6.2 liters and 15.2 +/- 1.3 vs. 16.9 +/- 2.3 liters, respectively. TBW and ECF estimated by BIS were not significantly different from the dilution values at any time point. These results suggest that BIS may be useful in estimating volumes of ECF and TBW during pregnancy.
Alterations in respiratory control during 8 h of isocapnic and poikilocapnic hypoxia in humans
Authors: Howard L. S. , Robbins P. A.
Published: December 2017

In the preceding companion paper (L. S. G. E. Howard and P.A. Robbins, J. Appl. Physiol. 78: 1092–1097, 1995), we showed that ventilation rises during 8 h of isocapnic hypoxia. In the present study we report the changes that occur in the ventilatory response to acute hypoxia (AHVR) over 8 h of both isocapnic and poikilocapnic hypoxia. Ten subjects completed the study. Each was seated inside a chamber in which the inspired gas could be controlled so as to maintain the desired end-tidal gases (sampled via nasal catheter) constant. Three 8-h protocols were compared: 1) isocapnic hypoxia, at an end-tidal PO2 of 55 Torr with the end-tidal PCO2 held at the subject's resting value; 2) poikilocapnic hypoxia, at the same end-tidal PO2; and 3) control, where the inspired gas was air. AHVR was measured before and at 20 min and 4 and 8 h after the start of the experiment. A sequence of hypoxic square waves and sawtooth inputs was imposed by an end-tidal forcing system, with the subject breathing through a mouthpiece. End-tidal PCO2 was held constant at 1–1.5 Torr above resting. Values for hypoxic sensitivity (Gp; 1.min-1.%-1) and hypoxia-independent ventilation (Vc; l/min) were calculated for each test of AHVR. Both Gp and Vc increased significantly during both hypoxic exposures in relation to control (P < 0.001, analysis of variance). Over the 8-h period, increases in Gp were 87% in isocapnic hypoxia and 44% in poikilocapnic hypoxia, and increases in Vc were 89% in isocapnic hypoxia and 84% in poikilocapnic hypoxia. There were no significant differences between the isocapnic and poikilocapnic exposures. We conclude that Gp and Vc rise mainly as result of hypoxia per se and not the associated alkalosis.
Acute lung injury in endotoxemic pigs: role of leukotriene B4
Authors: VanderMeer T. J. , Menconi M. J. , O'Sullivan B. P. , Larkin V. A. , Wang H. , Sofia M. , Fink M. P.
Published: December 2017

The role of leukotriene B4 (LTB4) in the pathogenesis of acute lung injury was examined in endotoxemic pigs. In a preliminary study, the activity and specificity of an LTB4-receptor antagonist, LY-306669, were evaluated. In vitro, LY-306669 completely blocked the functional upregulation of phagocyte opsonin receptors induced by LTB4 but had a much smaller effect on opsonin receptor upregulation induced by platelet-activating factor. In pigs treatment with LY-306669 prevented leukopenia induced by injection of authentic LTB4 but had no effect on the hematologic or hemodynamic effects of PAF or U-48816, a thromboxane-A2 mimetic. In a second study, pigs received an intravenous priming dose of lipopolysaccharide (LPS) at time (t) = -18 h and were randomized to receive 1) no further treatment (n = 5), 2) LPS (250 micrograms/kg over 1 h beginning at t = 0 h) and LY-306669 (10 mg/kg bolus and 3 mg.kg-1.h-1 infusion beginning at t = -15 min) (n = 7), or 3) LPS and vehicle (n = 6). Treatment with LY-306669 significantly ameliorated LPS-induced hypoxemia, pulmonary edema, and alveolitis. These data suggest that LTB4 is an important mediator of pulmonary dysfunction and transendothelial migration of neutrophils in LPS-induced acute lung injury.
In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. II. Implementation and application
Authors: Schuster D. P. , McCarthy T. J. , Welch M. J. , Holmberg S. , Sandiford P. , Markham J.
Published: December 2017

We measured pulmonary angiotensin-converting enzyme (ACE) kinetics with fluorine-18 captopril and positron emission tomographic (PET) imaging in five control dogs and in five dogs after 20–30 min of left caudal lobe (LCL) hypoxic ventilation. Time-activity data obtained with PET were interpreted with a compartmental receptor model relating changes in tissue and blood activity to one another within the region. In control dogs, the mean ratio of regional blood flow (measured by PET) between left and right dorsal lung regions was 0.90 +/- 0.16 (SD) vs. 0.54 +/- 0.24 (P < 0.05) in LCL hypoxic dogs. In control dogs, the amount of perfused unbound enzyme normalized to regional extravascular water concentration (Bmax/EVLW) averaged 13.3 +/- 8.9 x 10(-6) mmol ACE/ml EVLW; the ratio of regional values between the left and right sides was 1.02 +/- 0.18. In the LCL hypoxic dogs, Bmax/EVLW was 9.7 +/- 11.3 x 10(-6) mmol/ml hypoxic lung region and the ratio was 0.47 +/- 0.31 (P < 0.05). In control dogs, the coefficient of variation for Bmax/EVLW among regions was only 19 +/- 10%, although the between-dog variation was greater (64 +/- 4%). We conclude that this completely noninvasive method appears to be a promising approach for evaluating the expression of pulmonary ACE in vivo.
Sympathetic nervous system activity, body fatness, and body fat distribution in younger and older males
Authors: Poehlman E. T. , Gardner A. W. , Goran M. I. , Arciero P. J. , Toth M. J. , Ades P. A. , Calles-Escandon J.
Published: December 2017

It was hypothesized that an increase in total and central body fatness is related to higher sympathetic nervous system activity (SNSA) in older men. Resting SNSA was measured from norepinephrine (NE) kinetics in 69 younger (18–36 yr) and 69 healthy older men (55–80 yr). Body fat distribution was estimated from the waist circumference, body composition from underwater weighing, peak oxygen consumption from a treadmill test to exhaustion, and dietary intake from food diaries. Plasma NE concentrations were 41% higher (P < 0.001) in older men due to a 27% increase (P < 0.001) in NE appearance rate and a tendency for a lower NE clearance rate (P = 0.08). NE appearance rate was higher in individuals of both age groups who exhibited a greater waist circumference and body fatness (range of r values 0.49–0.69; P < 0.01). The waist circumference, and not age, was the strongest predictor of the increase in NE appearance rate in older men. Statistically controlling for the waist circumference or body fatness diminished age-related differences in NE concentrations and in NE appearance rate. These findings suggest that an accumulation of total and central body fat is associated with higher levels of SNSA in older males.
The effects of rM-CSF and rIL-6 therapy on immunosuppressed antiorthostatically suspended mice
Authors: Armstrong J. W. , Kirby-Dobbels K. , Chapes S. K.
Published: December 2017

Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of antiorthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors.
Substance P-induced histamine release in tracheally perfused guinea pig lungs
Authors: Lilly C. M. , Hall A. E. , Rodger I. W. , Kobzik L. , Haley K. J. , Drazen J. M.
Published: December 2017

The capacity of substance P (SP) and endogenously released tachykinins to liberate histamine was examined in isolated tracheally perfused guinea pig lungs. Increasing doses of tracheally injected SP were associated with the recovery of increasing amounts of histamine from lung effluent. The mechanism of SP-induced histamine liberation was explored in studies with neurokinin-(NK) receptor agonists and antagonists. Tracheal injection of either the NK1 agonist [Sar9,Met(O2)11]SP or the NK2 agonist [beta-Ala8]-neurokinin A-(4–10) was associated with a significant increase in histamine recovery from lung effluent. In addition, both the NK1 antagonist CP-99994 and the NK2 antagonist SR-48968 significantly inhibited SP-induced histamine release. These findings support the hypothesis that SP can liberate histamine from guinea pigs lungs by a mechanism that depends predominantly on NK1- and NK2-receptor activation. The liberation of endogenous tachykinins by acute tracheal injection of capsaicin was also associated with augmented histamine recovery, which was inhibited by combined NK1- and NK2-receptor blockade. Tracheal injection of SP was associated with an increase in the percentage of airway mast cells exhibiting histological evidence of degranulation. This study demonstrates that exogenous SP, as well as endogenous tachykinins released from capsaicin-sensitive neurons, can liberate histamine, most likely from airway mast cells, by a mechanism that depends predominantly on the activation of NK1 and NK2 receptors.
Prolonged pulmonary vasodilator action of inhaled nitric oxide by Zaprinast in awake lambs
Authors: Ichinose F. , Adrie C. , Hurford W. E. , Zapol W. M.
Published: December 2017

Inhaled nitric oxide (NO) has been shown to selectively dilate the pulmonary vasculature. Zaprinast, an inhibitor of guanosine 3′,5′-cyclic monophosphate-specific phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators. The present study was designed to determine whether intravenous administration of Zaprinast potentiates the vasodilating effects or prolongs the duration of action of intermittent NO inhalation. Eight awake lambs with U-46619-induced pulmonary hypertension breathed three concentrations of NO (5, 10, and 20 ppm) in a random order before and during an intravenous Zaprinast infusion (0.1 mg.kg-1.min-1). Inhaled NO decreased pulmonary arterial pressure (PAP) in a dose-dependent fashion, with mean PAP reduction at 5, 10, and 20 ppm NO inhalation of 6 +/- 1, 7 +/- 1, and 9 +/- 1 (SE) mmHg, respectively. Although the Zaprinast infusion did not change the magnitude of mean PAP reduction, it caused a statistically significant reduction of pulmonary vascular resistance and prolonged the duration of action of inhaled NO (half-times of vasodilator response to 5, 10, and 20 ppm NO inhalation: 1.9 +/- 0.1, 2.1 +/- 0.2, and 2.1 +/- 0.2 min, respectively; half-times of NO inhalation with Zaprinast: 9.7 +/- 1.7, 11.5 +/- 2.2, and 12.3 +/- 2.0, respectively). Plasma concentrations as well as the transpulmonary differences of guanosine 3′,5′-cyclic monophosphate were increased by the Zaprinast infusion during NO inhalation. A stable level of pulmonary vasodilation was demonstrated in four additional lambs by combining intermittent NO breathing with an intravenous infusion of Zaprinast.
Persistent small-airways dysfunction after exposure to hyperoxia
Authors: Thorsen E. , Kambestad B. K.
Published: December 2017

To assess the contribution of hyperoxia to reduced pulmonary function after a deep saturation dive, a shallow saturation dive to a pressure of 0.25 MPa with the same profile of hyperoxic exposure as in a deep saturation dive to 3.7 MPa was conducted. The PO2 was 40 kPa, with periods of 75 kPa for 2 h every 2nd day during the first 14 days, 50 kPa the next 12 days, and a gradual fall to 21 kPa over the last 2 days in decompression. Seven submariners and one professional diver aged 22–27 yr participated. Pulmonary function, including static and dynamic lung volumes and flows and transfer factor for carbon monoxide (TLCO), were measured twice before, immediately after, 1 mo after, and 1 and 3 yr after the dive. As reported previously, there was a significant reduction in TLCO and in maximal expiratory flow rates at low lung volumes immediately after the dive. At the follow-up examinations 1 and 3 yr after, there was no recovery of the maximal expiratory flow rates. Forced midexpiratory flow rate was still reduced by 8.7 +/- 5.6% (P < 0.05) and 9.3 +/- 7.1% (P < 0.01), respectively. Forced expired volume in 1 s and forced vital capacity were not significantly reduced. There was a complete recovery of the TLCO. The findings are consistent with the studies indicating development of airway obstruction in divers, and the findings indicate that exposure to hyperoxia contributes to this effect.
Effects of cortisone and testosterone on diaphragmatic function and biochemistry in the rabbit
Authors: Ferguson G. T.
Published: December 2017

The effects of cortisone and testosterone on in vivo diaphragmatic function and biochemistry were assessed in rabbits to determine whether androgens can prevent the effects of corticosteroids on diaphragmatic function and biochemistry and what mechanisms of muscle function may be altered. Cortisone altered respiratory muscle endurance and diaphragmatic glycogen and lactate levels but had little effect on diaphragmatic strength. Testosterone had no significant impact on diaphragmatic strength, endurance, or biochemistry. However, concomitant administration of testosterone with cortisone blunted the effect of cortisone on respiratory muscle endurance, even though it failed to block the effects of cortisone on diaphragmatic glycogen and lactate levels. Alterations in respiratory muscle endurance were not due to low- or high-frequency contractile fatigue of the diaphragm or diaphragmatic glycogen depletion or lactate accumulation in any of the treatment conditions. On the other hand, alterations in central drive played a dominant role, as evidenced by alterations in inspiratory duty cycle and a falloff in the intensity of central drive during loading. Although the exact mechanisms underlying the alterations in central drive remain unknown, concomitant administration of androgens with corticosteroids blunted the impact of corticosteroids on respiratory muscle function.
Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs
Authors: Grimminger F. , Spriestersbach R. , Weissmann N. , Walmrath D. , Seeger W.
Published: December 2017

Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs. J. Appl. Physiol. 78(4): 1509–1515, 1995.--We investigated the role of nitric oxide (NO) generation in hypoxic pulmonary vasoconstriction in buffer-perfused rabbit lungs. Exhaled NO was detected by chemiluminescence, and intravascular NO release was quantified as perfusate accumulation of nitrite, peroxynitrite, and nitrate (NOx). Under baseline conditions, exhaled NO was 45.3 +/- 4.1 parts per billion (1.8 +/- 0.2 nmol/min), and lung NOx release into the perfusate was 4.1 +/- 0.4 nmol/min. Alveolar hypoxia (alveolar PO2 of approximately 23 Torr) induced readily reproducible pressor responses preceded by a sharp drop in exhaled NO concentration. In contrast, perfusate NOx accumulation was not affected. Vasoconstrictor responses to U-46619 and angiotensin II were not accompanied by a decrease in NO exhalation. NG-monomethyl-L-arginine dose-dependently suppressed NO exhalation and amplified pressor responses to hypoxia > U-46619 and angiotensin II. In conclusion, portions of baseline NO generation originating from sites with ready access to the gaseous space sharply decrease in response to alveolar hypoxia, whereas the intravascular release of NO is unchanged. Such differential regulation of lung NO synthesis in response to hypoxia may suggest a complex role in the regulation or modulation of hypoxic pulmonary vasoconstriction.
Aortic-cardiac reflex during dynamic exercise
Authors: Shi X. , Potts J. T. , Raven P. B. , Foresman B. H.
Published: December 2017

We investigated the aortic-cardiac reflex during low-intensity cycling in 10 healthy volunteers. Baroreflex function was assessed by the ratio of change in heart rate to mean arterial pressure (delta HR/delta MAP) during phenylephrine (PE) infusion. The ratio obtained during PE combined with low-level lower body negative pressure (LBNP) and calculated neck pressure (NP) was assessed as the gain of the aortic-cardiac reflex. Exercise (approximately 25% maximal O2 uptake or 25 +/- 2 W) significantly increased HR from 64 +/- 2 to 98 +/- 2 beats/min, MAP from 90 +/- 3 to 98 +/- 3 mmHg, cardiac output from 6.6 +/- 0.5 to 12.0 +/- 1.4 l/min, and O2 uptake from 3.8 +/- 0.2 to 10.4 +/- 0.6 ml.min-1.kg-1. However, delta MAP (+11.8 +/- 0.4 vs. + 11.3 +/- 0.8 mmHg), delta HR (-12.7 +/- 2 vs. -12.9 +/- 2 beats/min), and delta HR/delta MAP (1.10 +/- 0.19 vs. 1.15 +/- 0.15 beats.min-1.mmHg-1) were not statistically different between rest and exercise during PE. Although PE significantly increased central venous pressure in both supine rest (from 6.7 +/- 0.7 to 10.4 +/- 0.7 mmHg) and exercise (5.8 +/- 0.8 to 8.6 +/- 0.9 mmHg) conditions, when LBNP (-15 +/- 2 vs. -16 +/- 1 Torr for rest vs. exercise) was applied, both rest and exercise central venous pressures were returned to the preinfusion baseline values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
O2 dependence of pregnenolone and aldosterone synthesis in mitochondria from bovine zona glomerulosa cells
Authors: Raff H. , Jankowski B.
Published: December 2017

Hypoxia in vivo results in a decrease in aldosterone not accounted for by extra-adrenal controllers. We have demonstrated that aldosteronogenesis but not cortisol synthesis in the whole cell is O2 sensitive. In the intact glomerulosa cell, this sensitivity is located in the late pathway step catalyzed by conversion of corticosterone to aldosterone (P-450aldo), whereas the early pathway catalyzed by conversion of cholesterol to pregnenolone (P-450scc) is not inhibited until PO2 is very low. Because P-450aldo and P-450scc are mitochondrial enzymes that depend on the same NADPH-specific electron transport proteins, we hypothesized that O2 sensitivity would be independent of energy production and expressed in isolated mitochondria. We measured the conversion of exogenous 25(OH)-cholesterol to pregnenolone and of exogenous corticosterone to aldosterone in the presence of cyanoketone in mitochondria isolated from bovine zona glomerulosa cells and exposed to an experimental gas (1–100% O2) vs. a room air control. Pregnenolone production was not affected until PO2 was < 35 Torr and decreased to almost nil when PO2 was < 30 Torr. In contrast, aldosterone production increased under hyperoxia and decreased under moderate decreases in O2. The conversion of corticosterone to aldosterone was maintained at approximately 50% of control, even when PO2 was < 20 Torr. The sensitivity of the aldosterone pathway to changes in O2 within the physiological range appears to reside in the mitochondrial late pathway (i.e., P-450aldo) and is not significantly influenced by cytosolic regulators of steroidogenesis or by limitation of reducing equivalents.
Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung
Authors: Rimar S. , Gillis C. N.
Published: December 2017

To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 microM indomethacin. Inhaled NO (120 ppm for 3 min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5–1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 +/- 51 (SE) vs. 1,545 +/- 109 mmHg.l–1.min; P < 0.01]. Acetylcholine infusion (ACh; 2–5 nmol/min) and nitroglycerin (NTG; 0.35 mumol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well.
Effects of isoproterenol on the cardiovascular system of fetal sheep exposed to long-term high-altitude hypoxemia
Authors: Kamitomo M. , Ohtsuka T. , Gilbert R. D.
Published: December 2017

We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days gestation, when we measured fetal heart rate, right and left ventricular outputs with electromagnetic flow probes, and arterial blood pressure during an isoproterenol dose-response infusion. We also measured the distribution of cardiac output with radiolabeled microspheres during the maximal isoproterenol dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest dose. Heart rate was the same in both groups and did not differ during isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in right ventricular output. During the isoproterenol infusion, right ventricular output increased to the same extent in both hypoxemic and normoxic fetuses (approximately 35%); however, left ventricular output increased only approximately 15% in the hypoxemic group compared with approximately 40% in the normoxic group. The percent change in individual organ blood flows during isoproterenol infusion in the hypoxemic groups was not significantly different from the normoxic group. All of the mechanisms that might be responsible for the differential response of the fetal left and right ventricles to long-term hypoxia are not understood and need further exploration.
Lung tissue and airway impedances during pulmonary edema in normal range of breathing
Authors: Barnas G. M. , Sprung J. , Kahn R. , Delaney P. A. , Agarwal M.
Published: December 2017

How pulmonary edema affects lung tissue and airway properties is not clear. From measurements of airway pressure and flow, we measured lung elastance (EL) and resistance (RL) in 5 anesthetized-paralyzed open-chested dogs during sinusoidal forcing in the frequency (f) and tidal volume (VT) ranges of normal breathing. RL was divided into its tissue (Rti) and airway (Raw) components from measurements of alveolar pressure through capsules glued to the lung surface. After induction of severe pulmonary edema by injection of oleic acid into the right atrium, forcing was repeated at the same mean airway pressure (Paw) as in control animals (11 cmH2O) and at a higher Paw (14 cmH2O), as would occur in closed-chested dogs during edema (G. M. Barnas, D. Stamenovic, and K. R. Lutchen. J. Appl. Physiol. 73: 1040–1046, 1992). Edema increased EL, and this increase was greater at Paw = 14 cmH2O (P < 0.05). The f dependences of EL and Rti were increased by edema (P < 0.05), and there was a large negative dependence of EL on VT at Paw = 14 cmH2O. Edema increased RL (P < 0.05), but this increase depended on f, VT, and Paw. The increase in RL was due largely to increases in Rti at Paw = 14 cmH2O and to increases in Raw at Paw = 11 cmH2O. We conclude that the functional effects of oleic acid-induced pulmonary edema on RL are due mostly to changes in lung tissue.
Mechanisms of airway protection after pharyngeal fluid infusion in healthy sleeping piglets
Authors: Page M. , Jeffery H. E. , Marks V. , Post E. J. , Wood A. K.
Published: December 2017

The airway protective mechanisms evoked after infusion of fluids into the pharynx were examined in the intact and healthy newborn piglet during sleep. Thirteen healthy normothermic piglets (3–6 days of age) were examined on 4 consecutive days during sleep. The fluids infused (0.05–1.5 ml) were 0.9% saline, distilled water, and HCl (pH 3 and pH 2). Respiratory rate, heart rate, oxygen saturation (SaO2), swallowing, and arousal were compared pre- and postinfusion during active (AS) and quiet sleep (QS) for each test fluid. The most common response in AS and QS was swallowing (90%) and then arousal (24%); however, no apnea occurred, and respiratory rate and SaO2 were always maintained. A significant difference occurred between HCl infusions of pH 2 and pH 3; at pH 2, the frequency of swallows and latency to the first swallow were reduced (P < 0.05) and the frequency of arousal was reduced in AS compared with that in QS (P < 0.01). Airway protection after pharyngeal fluid stimulation is achieved primarily by swallowing and arousal, without any effect on respiratory rate and SaO2. Attenuation of protective mechanisms occurred, however, when the infusate was at pH 2.
State of airway surface liquid on guinea pig trachea
Authors: Rahmoune H. , Shephard K. L.
Published: December 2017

Two preparations of the guinea pig trachea have been examined: an isolated preparation and a preparation in vivo, both exposed to air on the mucosal surface. Ion-selective microelectrodes have been used to measure Na (alpha Na) and K activities (alpha K) in airway surface liquid (ASL) while airflows tending either to evaporate or to condense water were applied. Other variables measured included ASL depth and transepithelial potential difference (TEPD). In isolated preparations, condensation did not progressively alter depth, alpha Na, or TEPD but caused a slight increase in alpha K. Evaporation decreased depth; increased alpha Na, alpha K, and osmotic pressure; and changed TEPD. Measurements on preparations in vivo broadly supported these observations. In addition, the depth of ASL developed on isolated preparations was related to the humidity of the air to which animals had been previously exposed. We conclude that condensation and evaporation at the ASL-air interface in isolated preparations and in preparations in vivo do significantly modify key ASL variables as does the relative humidity of the air to which animals are exposed before experimentation.
Changes in regional vascular resistance and blood volume after hemorrhage in fed and fasted awake rats
Authors: Darlington D. N. , Jones R. O. , Marzella L. , Gann D. S.
Published: December 2017

To determine whether fasting alters the response of blood flow to hemorrhage, blood flow was measured by radiolabeled microspheres before and after a 20 ml.kg-1.3 min-1 hemorrhage in fed and fasted chronically cannulated male Sprague-Dawley rats. Restitution of blood volume, as determined by dilution of hematocrit, was attenuated in fasted rats, although the responses of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance were not significantly different. Fasting only affected resting blood flow in the bronchial artery and fat and had no effect on resting vascular resistance in any organ studied. In both fed and fasted rats, hemorrhage led to a significant fall in blood flow to the stomach, small intestine, cecum, colon, spleen, pancreas, kidney, bronchial artery, thymus, and muscle and a rise in blood flow to the adrenals. However, fasting did not significantly alter the response of flow or vascular resistance to these organs. Fasting did alter the blood flow response to hemorrhage in bone, fat, and the hepatic artery. These results demonstrate that 24 h of fasting does not affect the responses of blood flow and vascular resistance to hemorrhage in most organs, even though restitution of blood volume is attenuated.
Peroxide-cyclooxygenase interactions in postasphyxial changes in retinal and choroidal hemodynamics
Authors: Chemtob S. , Hardy P. , Abran D. , Li D. Y. , Peri K. , Cuzzani O. , Varma D. R.
Published: December 2017

To test the role of reactive oxygen species and cyclooxygenase products in the retinal hemodynamic changes induced by asphyxia, we measured retinal (RBF) and choroidal blood flows (ChBF), malondialdehyde (MDA), prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) in 1- to 3-day-old pigs treated with saline, the free radical scavengers U-74389F or high-dose allopurinol, the cyclooxygenase inhibitors ibuprofen or indomethacin, or the thromboxane synthase blocker CGS-13080 before and 5 and 60 min after a 5-min period of asphyxia. In saline-treated animals, RBF and ChBF increased 5 min after asphyxia and decreased at 60 min. The increases in RBF and ChBF at 5 min postasphyxia were slightly attenuated by cyclooxygenase blockers and free radical scavengers but not by thromboxane synthase inhibition, whereas all drugs prevented the decreases at 60 min. MDA, TxB2, PGE2, and 6-keto-PGF1 alpha increased 5 min after asphyxia; at 60 min, PGE2 and 6-keto-PGF1 alpha returned to nearly preasphyxial levels, but MDA and TxB2 continued to increase. Cyclooxygenase inhibition prevented the asphyxia-induced rise in MDA, and the free radical scavengers prevented that of prostanoids. In isolated eyecup preparations, H2O2 and cumene hydroperoxide constricted retinal arteries; this effect was blocked by cyclooxygenase and thromboxane synthase inhibitors. The data suggest that during oxidative stresses reactive oxygen species are generated from the cyclooxygenase pathway and, in turn, also activate the synthesis of thromboxane; the latter mediates the oxidative stress-induced ocular vasoconstriction that might trigger the neovascularization of retinopathy of prematurity.
Immediate effects of arousal from sleep on cardiac autonomic outflow in the absence of breathing in dogs
Authors: Horner R. L. , Brooks D. , Kozar L. F. , Tse S. , Phillipson E. A.
Published: December 2017

To determine the immediate effects of arousal from non-rapid-eye-movement (non-REM) sleep on cardiac sympathetic and parasympathetic activities, six dogs were studied breathing through an endotracheal tube inserted into a chronic tracheostomy. Mean heart rates (HRs) during non-REM sleep were compared with 1) awake periods immediately after spontaneous arousals (ARs) and 2) later periods of stable relaxed wakefulness (RW). During spontaneous breathing, HR increased after AR (mean = 31.0%; P < 0.001) and in RW (mean = 7.6%; P < 0.001). To avoid the confounding influence of changes in breathing pattern, lung volume, and blood gases accompanying AR on HR, further studies were performed during constant mechanical hyperventilation that eliminated spontaneous breathing. In this condition, HR still increased after AR (mean = 29.9%; P < 0.001) and in RW (mean = 5.7%; P < 0.001), suggesting that the HR increases could be mediated by an effect of the state change per se on autonomic activity. This interpretation was confirmed when the HR increases were essentially abolished by combined cardiac sympathetic and parasympathetic block. In contrast, parasympathetic block alone did not prevent the HR increases after AR (mean = 12.2%; P < 0.001) or in RW (mean = 12.3%; P < 0.001), whereas sympathetic block alone almost abolished the HR increases in RW (mean = 3.6%) but did not prevent the HR increases during AR (mean = 30.2%; P < 0.001). The results show that, compared with non-REM sleep, AR is associated with acute cardiac sympathetic activation and parasympathetic withdrawal, whereas stable RW is associated mainly with sympathetic activation. These effects may have clinical relevance to the cardiovascular sequelae of breathing disorders that cause repetitive arousals from sleep.
Fiber type-specific effects of clenbuterol and exercise training on insulin-resistant muscle
Authors: Torgan C. E. , Etgen G. J. , Kang H. Y. , Ivy J. L.
Published: December 2017

The interrelationships among glucose uptake, GLUT-4 protein, and citrate synthase activity in insulin-resistant skeletal muscle were investigated. Female obese (fa/fa) Zucker rats were randomly assigned to treadmill training, ingestion of the selective beta 2-adrenergic agonist clenbuterol, or sedentary control groups. After 7–8 wk of treatment, hindlimbs were perfused to determine maximal insulin-stimulated (10 mU/ml) 2-[3H]deoxy-D-glucose (2-DG) uptake. Exercise training significantly enhanced 2-DG uptake and GLUT-4 protein in red gastrocnemius and plantaris. Alternatively, 2-DG uptake was not altered in soleus after exercise training despite a 52% increase in GLUT-4 protein. The increases in GLUT-4 protein in red gastrocnemius, plantaris, and soleus of the trained rats were accompanied by increases in citrate synthase activity. In contrast to exercise training, clenbuterol administration decreased citrate synthase activity in red and white gastrocnemius, yet had no effect on GLUT-4 protein levels or maximal insulin-stimulated 2-DG uptake. Clenbuterol treatment did, however, increase citrate synthase activity and GLUT-4 protein in soleus. These findings indicate that total GLUT-4 protein largely determines the maximal rate of insulin-stimulated glucose uptake in fast-twitch muscle, whereas in slow-twitch muscle it does not. In addition, the results demonstrate that coordination of proteins governing glucose uptake and disposal may be disrupted in a fiber type-specific manner. Overall, the findings raise important questions as to whether regulation of proteins governing glucose uptake and disposal differs significantly among fiber types.
Effects of nasal positive-pressure hyperventilation on the glottis in normal awake subjects
Authors: Jounieaux V. , Aubert G. , Dury M. , Delguste P. , Rodenstein D. O.
Published: December 2017

We have recently observed obstructive apneas during nasal intermittent positive-pressure ventilation (nIPPV) and suggested that they were due to hypocapnia-induced glottic closure. To confirm this hypothesis, we studied seven healthy subjects and submitted them to nIPPV while their glottis was continuously monitored through a fiber-optic bronchoscope. During wakefulness, we measured breath by breath the widest inspiratory angle formed by the vocal cords at the anterior commissure along with several other indexes. Mechanical ventilation was progressively increased up to 30 l/min. In the absence of diaphragmatic activity, increases in delivered minute ventilation resulted in progressive narrowing of the vocal cords, with an increase in inspiratory resistance and a progressive reduction in the percentage of the delivered tidal volume effectively reaching the lungs. Adding CO2 to the inspired gas led to partial widening of the glottis in two of three subjects. Moreover, activation of the diaphragmatic muscle was always associated with a significant inspiratory abduction of the vocal cords. Sporadically, complete adduction of the vocal cords was directly responsible for obstructive laryngeal apneas and cyclic changes in the glottic aperture resulted in waxing and waning of tidal volume. We conclude that in awake humans passive ventilation with nIPPV results in vocal cord adduction that depends partly on hypocapnia, but our results suggest that other factors may also influence glottic width.
Combined hypoxia and hypercapnia evokes long-lasting sympathetic activation in humans
Authors: Morgan B. J. , Crabtree D. C. , Palta M. , Skatrud J. B.
Published: December 2017

We studied ventilatory and neurocirculatory responses to combined hypoxia (arterial O2 saturation 80%) and hypercapnia (end-tidal CO2 + 5 Torr) in awake humans. This asphyxic stimulus produced a substantial increase in minute ventilation (6.9 +/- 0.4 to 20.0 +/- 1.5 l/min) that promptly subsided on return to room air breathing. During asphyxia, muscle sympathetic nerve activity (intraneural microelectrodes) increased to 220 +/- 28% of the room air baseline. Approximately two-thirds of this sympathetic activation persisted after return to room air breathing for the duration of our measurements (20 min in 8 subjects, 1 h in 2 subjects). In contrast, neither ventilation nor sympathetic outflow changed during time control experiments. A 20-min exposure to hyperoxic hypercapnia also caused a sustained increase in sympathetic activity, but, unlike the aftereffect of asphyxia, this effect was short lived and coincident with continued hyperpnea. In summary, relatively brief periods of asphyxic stimulation cause substantial increases in sympathetic vasomotor outflow that outlast the chemical stimuli. These findings provide a potential explanation for the chronically elevated sympathetic nervous system activity that accompanies sleep apnea syndrome.
Pulmonary vascular adaptations to augmented polycythemia during chronic hypoxia
Authors: Petit R. D. , Warburton R. R. , Ou L. C. , Hill N. S.
Published: December 2017

We previously found that augmentation of polycythemia by exogenous human recombinant erythropoietin (EPO) failed to worsen the severity of hypoxic pulmonary hypertension in rats. We asked whether this unexpected finding was related to reductions in cardiac output, left ventricular end-diastolic pressure, pulmonary vascular resistance, or some combination of these factors. Four groups of Sprague-Dawley rats were studied over a 3-wk period: hypoxic (0.5 ATM) and normoxic animals each injected with EPO (500 U/kg sc thrice weekly) or saline (control animals). As observed previously, we found that pulmonary arterial (PA) pressures and right ventricular hypertrophy were not increased in EPO-treated rats despite significant increases in hematocrit and blood viscosity. Cardiac outputs, blood volumes, and left ventricular end-diastolic pressures were similar in EPO-treated and control rats. Acute PA pressure responses to acute normoxia in hypoxic rats and to acute hypoxia in normoxic rats were similar, suggesting no differences in vasoreactivity. However, lungs isolated from EPO-treated hypoxic rats had lower pulmonary vascular resistance than saline-treated hypoxic rats when perfused with blood from normocythemic donor rats. PA medial thickness and the percentage of muscularized small PAs were significantly lower in EPO-treated hypoxic rats. These results indicate that augmented polycythemia fails to worsen hypoxic pulmonary hypertension in rats because of a decrease in the severity of structural remodeling.
Vascular adaptations in rat hindlimb skeletal muscle after voluntary running-wheel exercise
Authors: Sexton W. L.
Published: December 2017

To test the hypothesis that voluntary running-wheel exercise would elicit vascular adaptations in rat skeletal muscle, male Sprague-Dawley rats (202 +/- 5 g) were cage confined (C, n = 11) or housed in cages with free access to running wheels (R, n = 13) for 12 wk. Vascular transport capacity was determined in maximally vasodilated (papaverine) hindquarters of C and R rats with measurements of total and regional (radiolabeled microspheres) flow capacity and capillary filtration coefficient. R rats voluntarily ran 29 +/- 4 km/wk over the 12-wk period; however, performance of individual rats varied greatly (range 4–74 km/wk). Citrate synthase activity was increased in the medial head (81%, P < 0.001) and the red long head (88%, P < 0.001) of the triceps brachii muscle in R rats but not in the white long head (25%, P = 0.06). Capillary filtration coefficient was 27% greater in R compared with C rats (0.040 +/- 0.003 vs. 0.031 +/- 0.002 ml.min-1.100 g-1.mmHg-1, respectively, P < 0.001) suggesting that there was an increase in microvascular surface area available for fluid exchange. Total hindquarters flow was increased in R rats (P < 0.05) at all perfusion pressures examined, indicative of an increased flow capacity. Regional flows revealed that skin flow was unchanged in R rats and that the increase in total flow was due to increased skeletal muscle flow capacity. These results indicate that voluntary running-wheel exercise elicits adaptive increases in skeletal muscle vascular transport capacity and oxidative capacity comparable to those seen in treadmill-trained rats and support the use of voluntary running-wheel exercise as a less stressful training modality in exercise studies using rats.
Early adaptations in collateral and microvascular resistances after ligation of the rat femoral artery
Authors: Unthank J. L. , Nixon J. C. , Lash J. M.
Published: December 2017

Collateral and microvascular (including feed artery) resistances in the rat hindlimb were determined immediately or 1 wk after ligation of the femoral artery. Collateral-to-microvascular resistance ratios were determined from in vivo pressure measurements proximal and distal to the ligation. Microvascular resistance was 32 +/- 2.5 and 41 +/- 1.5% of the total collateral-dependent vasculature in acutely and chronically ligated limbs, respectively, and decreased 20% in both groups during reactive hyperemia. Minimum resistances of collateral vessels and the microcirculation arising from arterial branches proximal and distal to the ligation were determined by using a modification of the standard hindquarter perfusion technique for determining maximum vascular conductance. One week postligation, minimum total hindquarter resistance was decreased by a reduction in the resistance of the collaterals (approximately 50%) and microcirculation (approximately 33%) proximal to the ligation. The results suggest that the microvasculature distal to the occlusion is able to increase flow by dilation both initially and at 1 wk postligation but that collateral adaptations are primarily responsible for decreases in the minimum total resistance of the collateral-dependent region.