bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental changes in effects of histamine on segmental pulmonary vascular resistances
Authors: Gordon J. B. , Clement de Clety S. , Chu K.
Published: December 2017

In mature animals histamine infusion typically causes an H1-mediated increase and H2-mediated decrease in pulmonary vascular resistance (PVR). Moreover, low histamine concentrations can cause H1-mediated relaxation of vascular strips in mature animals, and in newborn animals histamine infusion causes only H1-mediated decreases in PVR. The mechanisms responsible for the different H1-mediated responses are unknown. We used an inflow-outflow occlusion technique to identify the sites of H1- and H2-mediated responses in lungs of developing lambs. Histamine was infused at 1.0 and 10.0 micrograms.kg-1.min-1 in control and H1- and H2-blocked lungs of newborn and juvenile lambs under “normoxic” and hypoxic conditions and in hypoxic H2-blocked lungs of mature sheep. In newborns histamine caused significant H1-mediated decreases in resistance across the arterial (delta Pa) and middle (delta Pm) segments of the circuit during both normoxia and hypoxia. In normoxic juveniles low-dose histamine caused H1-mediated decreases in the resistance across delta Pa and delta Pm, but the resistances across delta Pm rose above baseline at the higher dose. The venous segment exhibited only a high-dose increase in resistance. During hypoxia, the high-dose H1-mediated pressor response of delta Pm was attenuated compared with that during normoxia; however, the increase in venous resistance was unaffected. In hypoxic mature sheep, no low dose H1-mediated decrease in segmental resistances was seen, but at the higher dose an increase in all resistances occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Pressure-induced striatal dopamine release correlates hyperlocomotor activity in rats exposed to high pressure
Authors: Abraini J. H. , Rostain J. C.
Published: December 2017

Free-moving rats chronically implanted in the striatum with multifiber carbon electrodes selective to dopamine were compressed in a helium-oxygen mixture to 80 bars. Extracellular dopamine level and behavioral symptoms of high-pressure neurological syndrome were simultaneously recorded. Under these conditions, the extracellular level of dopamine monitored by differential pulse voltammetry was found to be pressure dependent, and hyperlocomotor activity, a behavioral symptom of high-pressure neurological syndrome, was found to be linked to these pressure-induced changes in dopamine release.
Prevention of H2O2 generation by monoamine oxidase protects against CNS O2 toxicity
Authors: Zhang J. , Piantadosi C. A.
Published: December 2017

Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between regional generation of hydrogen peroxide (H2O2) in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ), and protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline. At 6 ATA of oxygen, pargyline significantly protected rats from CNS O2 toxicity whereas ATZ enhanced O2 toxicity. In animals pretreated with ATZ, HBO inactivated 21–40% more catalase than air exposure in the six brain regions studied. Because ATZ-mediated inactivation of catalase was H2O2 dependent, the decrease in catalase activity during hyperoxia was proportional to the intracellular production of H2O2. Pargyline, administered 30 min before HBO, inhibited MAO by greater than 90%, prevented ATZ inhibition of catalase activity during HBO, and reversed the augmentation of CNS O2 toxicity by ATZ. These findings indicate that H2O2 generated by MAO during hyperoxia is important to the pathogenesis of CNS O2 toxicity in rats.
Pulmonary vascular smooth muscle: biochemical and mechanical developmental changes
Authors: Belik J. , Halayko A. , Rao K. , Stephens N.
Published: December 2017

To evaluate the developmental changes in pulmonary vascular smooth muscle contractile protein content, mechanical properties, and their contribution to the high resistance characteristic of the fetal and immediate neonatal period, we studied pulmonary vessels of fetal, newborn, and adult sheep, as well as newborn and adult pigs. Strips of the second- through fifth-generation vessels were dissected, and their content of tissue total smooth muscle cell protein, myosin, and actin-to-myosin ratio were measured; the mechanical properties of the second-generation vascular strips were also studied. For all ages the smooth muscle protein and myosin content of the second-generation vessels were significantly greater than for the lower pulmonary vascular orders (P less than 0.05). The myosin content in fetal sheep (0.77 +/- 0.03 micrograms/mg wet tissue) was similar to that of the newborn (0.79 +/- 0.04) and adult (0.86 +/- 0.05). However, the smooth muscle protein content (7.94 +/- 0.21 micrograms/mg wet tissue) and the actin-to-myosin ratio of the pulmonary vascular tissue of the fetus (1.00 +/- 0.04) were lower (P less than 0.01) in the fetal than in the newborn (9.16 +/- 0.26 and 1.60 +/- 0.12) and adult (9.38 +/- 0.3 and 1.60 +/- 0.11, respectively). No differences were observed for these parameters between the newborn and adult pig. Stress (16.5 +/- 1.7 mN/mm2) and the maximum shortening capacity (13.0 +/- 1.5% of optimal length) in the newborn pulmonary vascular strips were significantly greater than for the fetus (6.8 +/- 1.4 and 5.9 +/- 1.0, respectively) but similar to those of the adult sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytochrome c protein synthesis rate in rat skeletal muscle
Authors: Booth F. W.
Published: December 2017

Endurance training is associated with increases in mitochondrial density, of which cytochrome c protein is an index. Increases in the synthesis rates of cytochrome c protein in skeletal muscle during endurance training have been inferred (Biochem. Biophys. Res. Commun. 66: 173, 1975; J. Biol. Chem. 252: 416, 1977). One purpose of the present study was to test these indirect approximations with direct measurements of the synthesis rates of cytochrome c protein in skeletal muscles postexercise. No change in the fractional synthesis rate of cytochrome c was detected in the red quadriceps muscle of rats either 2–7 h after a 104-min run on a motor-driven treadmill or 17–22 h after the final bout of 4 days of running 100 min/day. If the 16% increase in cytochrome c protein concentration in the red quadriceps muscle on the 5th day of training is used to calculate the nanomoles of cytochrome c synthesized per gram of wet muscle weight, the normalized rate of cytochrome c protein synthesis is increased 29% on the 5th day of training. The observation of no significant alteration in cytochrome c mRNA in the red quadriceps muscle of rats during the 1st wk of training implies that the initial increase in the synthesis rate of cytochrome c protein normalized per unit of muscle mass during treadmill training is likely to occur at a translational or posttranslational step. These results suggest that the control of increased cytochrome c expression in skeletal muscle during exercise training involves a complex mechanism.
Linear and nonlinear characteristics of oxygen uptake kinetics during heavy exercise
Authors: Barstow T. J. , Mole P. A.
Published: December 2017

We assessed the linearity of oxygen uptake (VO2) kinetics for several work intensities in four trained cyclists. VO2 was measured breath by breath during transitions from 33 W (baseline) to work rates requiring 38, 54, 85, and 100% of maximal aerobic capacity (VO2max). Each subject repeated each work rate four times over 8 test days. In every case, three phases (phases 1, 2, and 3) of the VO2 response could be identified. VO2 during phase 2 was fit by one of two models: model 1, a double exponential where both terms begin together close to the start of phase 2, and model 2, a double exponential where each of the exponential terms begins independently with separate time delays. VO2 rose linearly for the two lower work rates (slope 11 ml.min-1 W-1) but increased to a greater asymptote for the two heavier work rates. In all four subjects, for the two lighter work rates the double-exponential regression reduced to a single value for the time constant (average across subjects 16.1 +/- 7.7 s), indicating a truly monoexponential response. In addition, one of the responses to the heaviest work rate was monoexponential. For the remaining seven biexponential responses to the two heaviest work rates, model 2 produced a significantly better fit to the responses (P less than 0.05), with a mean time delay for the slow component of 105 +/- 46 s.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates
Authors: Wolfson M. R. , Greenspan J. S. , Deoras K. S. , Rubenstein S. D. , Shaffer T. H.
Published: December 2017

To differentiate the effects of gas and liquid ventilation on cardiopulmonary function during early development, we compared the clinical, physiological, and histological profiles of gas- and liquid-ventilated preterm lambs (n = 16; 108–116 days gestation). Immediately after cesarean section delivery, ventilation commenced using gas delivered by a volume ventilator (n = 9) or liquid perfluorochemical (n = 7) delivered by a mechanically assisted liquid ventilation system. Pulmonary gas exchange, acid-base status, vital signs, and respiratory compliance were assessed during the 3-h protocol; sections of the lungs were obtained for histological analyses when the animals were killed. Six of nine gas-ventilated lambs expired from respiratory failure before 3 h, with the remaining animals experiencing severe respiratory insufficiency, pneumothoraces, and cardiovascular deterioration. Six of seven liquid-ventilated lambs survived with good gas exchange and cardiovascular stability and without fluorothorax; one experienced ventricular fibrillation before 1 h and expired despite pulmonary stability. Respiratory compliance was significantly greater in the liquid- than in the gas-ventilated lambs. Histological analyses of gas-ventilated lungs demonstrated nonhomogeneous lung expansion, with thick-walled gas exchange spaces containing proteinaceous exudate, hemorrhage, and hyaline membranes. In contrast, liquid-ventilated lungs appeared clear, with thin-walled and uniformly expanded gas exchange spaces that were free of hyaline membranes and luminal debris. Morphometric analyses demonstrated that surface area and gas exchange index were greater in the liquid- than in the gas-ventilated lambs. These results indicate that elimination of surface active forces by liquid ventilation during early development provides more effective gas exchange with less barotrauma compared with gas ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Development of mucociliary transport in the postnatal ferret trachea
Authors: Voter K. Z. , Leigh M. W. , Boat T. F. , Carson J. L. , Wood R. E.
Published: December 2017

Little is known of the developmental aspects of mucociliary transport. Previous studies have documented that newborn ferret trachea has very few ciliated cells but numerous immature secretory cells in the epithelium and only rudimentary submucosal glands. Rapid and complete maturation occurs in the first postnatal month. This study examines mucociliary transport during this period of rapid maturation. We made direct observations of particle movement across the epithelium of ferret tracheas. No mucus transport could be demonstrated on the first day of life. Transport was discernible, although sporadic and slow, by 7 days and reached adult levels (10.7 +/- 3.7 mm/min) by 28 postnatal days. The emergence of transport capability correlated well with previously described developmental changes in ciliation, mucus secretion, and ion permeability and transport. Threshold mucus transport occurred at 1 wk of age when 20–25% of the surface cells are ciliated. The neonatal ferret appears to be a useful model for assessing integrated epithelial structure-function relationships that are important not only during early development but also during repair after airway injury involving deciliation.
Longitudinal distribution of ozone absorption in the lung: quiet respiration in healthy subjects
Authors: Hu S. C. , Ben-Jebria A. , Ultman J. S.
Published: December 2017

The objective of this research was to develop a bolus-response method for the noninvasive determination of O3 distribution in the human lung. A previously developed O3 analyzer and bolus generator were incorporated in a computer-controlled inhalation system, and measurements of O3 absorption from inhaled 10-ml boluses with a peak O3 concentration of 4 ppm were carried out on nine previously unexposed healthy male subjects engaged in quiet oral breathing. The fraction of O3 absorbed during a single breath was measured over a range of airway penetrations from 20 to 200 ml, with inspiratory and expiratory flows fixed at a nominal value of 250 ml/s. The resulting data indicated that 50% of the inhaled O3 was absorbed at a penetration of 70 ml, which roughly corresponds to the upper airways, and essentially complete absorption occurred at a penetration of 180 ml, which roughly corresponds to the 16th airway generation, the beginning of the proximal alveolar region. This compares favorably with the results of direct-sampling methods, which indicated that 40.4% of continuously inhaled O3 is removed by the extrathoracic airways (Gerrity et al. J. Appl. Physiol. 65: 393–400, 1988). The computation of an absorption rate constant, Ka, revealed that the efficiency of O3 uptake increased with longitudinal position throughout most of the conducting airways but began to fall off at a penetration of 160 ml.
Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro
Authors: Reid M. B. , Haack K. E. , Franchek K. M. , Valberg P. A. , Kobzik L. , West M. S.
Published: December 2017

We hypothesized that muscle fiber bundles produce reactive oxygen intermediates and that reactive oxidant species contribute to muscular fatigue in vitro. Fiber bundles from rat diaphragm were mounted in chambers containing Krebs-Ringer solution. In studies of intracellular oxidant kinetics, bundles were loaded with 2′,7′-dichlorofluorescin, a fluorochrome that emits at 520 nm when oxidized; emissions were quantified using a fluorescence microscope. Emissions from unstimulated muscles increased over time (P < 0.001). Accumulation of fluorescence was slowed by addition of catalase (P < 0.001) or superoxide dismutase (P < 0.001) and was accelerated by repetitive muscular contraction (P < 0.05). To determine effects of reactive oxygen intermediates on fatigue, curarized bundles were stimulated to contract isometrically; force was measured. Catalase, superoxide dismutase, and dimethyl sulfoxide were screened for effects on low- and high-frequency fatigue. Antioxidants inhibited low-frequency fatigue [after 5 min of repetitive contractions, force at 30 Hz was 20% greater than control (P < 0.015)] and increased the variability of fatigue at 30 Hz (P < 0.03). Antioxidants did not alter high-frequency (200-Hz) fatigue. We conclude that 1) diaphragm fiber bundles produce reactive oxygen intermediates, including O2-. and H2O2; 2) muscular contraction increases intracellular oxidant levels; and 3) reactive oxygen intermediates promote low-frequency fatigue in this preparation.
Energy expenditure climbing Mt. Everest
Authors: Westerterp K. R. , Kayser B. , Brouns F. , Herry J. P. , Saris W. H.
Published: December 2017

Weight loss is a well-known phenomenon at high altitude. It is not clear whether the negative energy balance is due to anorexia only or an increased energy expenditure as well. The objective of this study was to gain insight into this matter by measuring simultaneously energy intake, energy expenditure, and body composition during an expedition to Mt. Everest. Subjects were two women and three men between 31 and 42 yr of age. Two subjects were observed during preparation at high altitude, including a 4-day stay in the Alps (4,260 m), and subsequently during four daytime stays in a hypobaric chamber (5,600–7,000 m). Observations at high altitude on Mt. Everest covered a 7- to 10-day interval just before the summit was reached in three subjects and included the summit (8,872 m) in a fourth. Energy intake (EI) was measured with a dietary record, average daily metabolic rate (ADMR) with doubly labeled water, and resting metabolic rate (RMR) with respiratory gas analysis. Body composition was measured before and after the interval from body mass, skinfold thickness, and total body water. Subjects were in negative energy balance (-5.7 +/- 1.9 MJ/day) in both situations, during the preparation in the Alps and on Mt. Everest. The loss of fat mass over the observation intervals was 1.4 +/- 0.7 kg, on average two-thirds of the weight loss (2.2 +/- 1.5 kg), and was significantly correlated with the energy deficit (r = 0.84, P < 0.05). EI on Mt. Everest was 9–13% lower than during the preparation in the Alps.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal water absorption from select carbohydrate solutions in humans
Authors: Gisolfi C. V. , Summers R. W. , Schedl H. P. , Bleiler T. L.
Published: December 2017

Eight men positioned a triple-lumen tube in the duodenojejunum. By use of segmental perfusion, 2, 4, 6, or 8% solutions of glucose (111–444 mM), sucrose (55–233 mM), a maltodextrin [17–67 mM, avg. chain length = 7 glucose units (7G)], or a corn syrup solid [40–160 mM, avg. chain length = 3 glucose units (3G)] were perfused at 15 ml/min for 70 min after a 30-min equilibration period. All solutions were made isotonic with NaCl, except 6 and 8% glucose solutions, which were hypertonic. An isotonic NaCl solution was perfused as control. Water absorption (range: 9–15 ml.h-1.cm-1) did not differ for the 2, 4, and 6% CHO solutions but was greater (P < 0.05) than absorption from control (3.0 +/- 2.2 ml.h-1.cm-1). The 8% glucose and 3G solutions reduced (P < 0.05) net water flux compared with their 2, 4, and 6% solutions, but 8% sucrose and 8% 7G solutions promoted water absorption equivalent to lower CHO concentrations. Water absorption was independent of [Na+] in the original solution. In the test segment, 1) Na+ flux correlated with net water flux (r = 0.72, P < 0.01), K+ (r = 0.78, P < 0.01), and [Na+] (r = 0.68, P < 0.001); 2) Na+ absorption occurred at luminal [Na+] as low as 50 mM; 3) glucose transport increased linearly over the luminal concentration range of 40–180 mM; and 4) net water flux was similar over a range of glucose-to-Na+ concentration ratios of 0.4:1 to 3.5:1.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle
Authors: Dodd S. L. , Powers S. K. , Brooks E. , Crawford M. P.
Published: December 2017

This investigation was designed to describe alterations in O2 uptake (VO2) and tension development in a contracting in situ gastrocnemious-plantaris muscle preparation during three conditions of reduced O2 delivery [arterial O2 concentration X blood flow (Q)]. The three conditions, hypoxemia (H), ischemia (I), and anemia (A), were matched for O2 delivery. A normoxic normal flow condition was also utilized for comparison. H was produced by respiring the animals with 9% O2 in N2; I was produced by lowering Q, and A was produced by hemodilution with 6% dextran. The stimulation pattern for the isometric tetanic contractions used was 1 train/s, and each train was 200 ms, 70 Hz, and 6 V. The muscle was maximally contracted during each of the experimental conditions, and the conditions were administered in random order. In each bout the contractions continued for 5 min with 30 min of rest between bouts. Samples of arterial and muscle venous blood were obtained during the last 30 s of each bout. VO2 during I (125 ml.kg-1.min-1) was less than during N (145 ml.kg-1.min-1; P < 0.05) and greater than during H or A (104 and 101 ml.kg-1.min-1, respectively; P < 0.05). Venous PO2 (PVO2) was significantly lower during H (17.1 Torr) compared with the other conditions; no differences existed between N, I, and A (26.8, 26.0, and 28.1 Torr, respectively). Tension development was reduced by the reduction of O2 delivery during I, H, and A compared with N. Tension developed among the reduced O2 delivery groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Interactions between Hb, Mg, DPG, ATP, and Cl determine the change in Hb-O2 affinity at high altitude
Authors: Mairbaurl H. , Oelz O. , Bartsch P.
Published: December 2017

Ascent to high altitude (HA) causes an increase in erythrocyte 2,3-diphsophoglycerate (DPG) and standard PO2 at 50% O2 saturation, PCO2 40 Torr, and blood pH 7.4 (P50,st). We studied the early phase of acclimatization to HA of mountaineers without and with a history of HA pulmonary edema. Tests were performed before ascent and after arrival at HA (4,559 m), approximately 22 h after the departure from low altitude (HA1) and on the following 3 days at HA (HA2-HA4). We investigated the relation between changes in DPG and P50,st, since at moderate altitude P50,st increases more rapidly than DPG, indicating that other factors may contribute to the change in P50,st. Combined effects of interaction between allosteric effectors of hemoglobin (Hb) (DPG, ATP, Cl) and Mg, which competes with Hb for DPG and ATP binding, might explain that phenomenon. Therefore concentrations of liganded Hb species were calculated from the total erythrocyte concentrations of the ligands by use of published binding constants and were related to changes in Hb-O2 affinity. P50,st increased at HA by approximately 4.5 Torr; the concentration of total DPG and ATP increased by 28 and 19%, respectively. Whereas P50,st reached a plateau already at HA1, the concentration of DPG reached its highest value at HA4. The erythrocyte Cl concentration decreased, whereas cellular Hb and Mg concentrations increased slightly. The sum of concentrations of all liganded Hb species increased, reaching 79% of its total change within 22 h after ascent; this can mainly be attributed to the change in the concentration of Hb[DPG] (+77% of total increase).(ABSTRACT TRUNCATED AT 250 WORDS)
Seven-day validation of doubly labeled water method using indirect room calorimetry
Authors: Seale J. L. , Conway J. M. , Canary J. J.
Published: December 2017

Carbon dioxide production, water production, and energy expenditure (EE) determined with 2H2(18)O were validated using a room calorimeter. Nine human subjects (5 males, 4 females) resided in the calorimeter for five to seven consecutive 23.5-h days. Daily carbon dioxide and water production and EE were averaged from calorimeter data and compared with 2H2(18)O results for the same period and for the following week. Isotope concentrations were measured by isotope ratio mass spectroscopy (18O) and infrared spectrophotometry (2H). Isotope clearance rates and pool sizes were determined by two multipoint methods and the two-point method. No significant differences were measured between calorimetry and 2H2(18)O results for the period within the chamber [multipoint A.M. urine 1.55% +/- 2.57 (SD) %, multipoint A.M. + P.M. urine 0.98% +/- 8.19%, two-point 1.59% +/- 4.50%]. Free-living EE was 13% +/- 7% greater. The results indicate that the 2H2(18)O method as applied is a valid technique for measuring EE, that multipoint calculation methods can be as precise as the two-point method, and that EE was greater in free-living than in calorimeter-confined conditions.
Influence of in vivo hypobaric hypoxia on function of lymphocytes, neutrocytes, natural killer cells, and cytokines
Authors: Klokker M. , Kharazmi A. , Galbo H. , Bygbjerg I. , Pedersen B. K.
Published: December 2017

We have investigated the effects of short-term hypoxia in vivo on the human cellular immune system. Seven young healthy volunteers were placed in a decompression chamber (380 Torr) for 20 min with or without supplemental O2. The leukocyte concentration increased during hypobaric conditions because of an increased concentration of lymphocytes. The absolute and relative concentration of CD16+ natural killer (NK) cells increased markedly during hypoxia and returned to pretest values after 2 h of recovery. The NK cell activity of blood mononuclear cells (BMNC, %lysis/fixed no. of BMNC) boosted with interferon-alpha, interleukin-2 (IL-2), and indomethacin rose in parallel with unboosted NK cell activity during hypoxia. The percentage of CD4+ and CD8+ cells declined during hypoxia, whereas the absolute concentration of both CD8+ cells and CD14+ monocytes increased. Although the BMNC composition varied, the proliferative responses of BMNC after stimulation with phytohemagglutinin, purified derivative of tuberculin, and IL-2 did not change significantly. The in vitro production of interleukin-1 beta and IL-2 in supernatants obtained after stimulation of BMNC with phytohemagglutinin or lipopolysaccharide was not affected. The chemiluminescence response of neutrocytes increased 2 h after hypoxia. It was concluded that acute hypoxia induced marked alterations in the immune system and that the NK cells are especially sensitive to the hypoxic stimulus.
Airway occlusion pressure
Authors: Whitelaw W. A. , Derenne J. P.
Published: December 2017

Airway occlusion pressure has been used in the past two decades for assessing output of the respiratory controller. It gives a measurement of a weighted sum of the effect of all respiratory muscles active at a given time and, unlike ventilation or tidal volume, does not depend on the resistance or compliance of the respiratory system. In anesthetized subjects or animals, it gives a tracing of the time course of respiratory neuromuscular output through the respiratory cycle, modified by elimination of most phasic vagal stretch receptor feedback and perhaps slightly by activation of some chest wall reflexes. The original postulate that an occluded inspiration would be isometric and the measured pressure free from losses due to force-length and force-velocity has been shown to be incorrect. The volume at which occlusion takes effect, distortions of the chest wall during the maneuver, tonic vagal input, and strength of the muscles must be taken into account when the data are interpreted. Brief occlusions [pressure at 0.1 s (P0.1)] are useful in measuring output in the very first part of inspiration in conscious subjects but must be treated with a great deal of caution. They are most reliable when end-expiratory volume remains constant and there are no important phase lags between flow and pressure. Allowance may be necessary for damping of the pressure signal on its passing through the compliant upper airway. Changes in P0.1 may often be due to changes in the shape of the driving pressure wave without a proportionate change in overall output. The technique remains useful when its limitations are recognized. Because of its simplicity, it can be easily and usefully applied to a range of clinical investigations.
Dynamic imaging of the upper airway during respiration in normal subjects
Authors: Schwab R. J. , Gefter W. B. , Pack A. I. , Hoffman E. A.
Published: December 2017

The present study was conducted to determine the effects of quiet respiration on upper airway caliber in 15 normal subjects by using cine computed tomography. The cine computed tomography (Imatron) scanner was programmed to obtain 8-mm-thick axial slices every 0.4 s during inspiration and expiration at four anatomic levels, from the nasopharynx to the retroglossal region. Airflow (pneumotachograph) was measured, and tidal volume was obtained by integration. Upper airway area, determined by an objective edge detection algorithm, was plotted as a function of tidal volume to generate a loop describing upper airway area changes at each level during a respiratory cycle. The results demonstrate a 17% change in airway size across all anatomic levels during respiration. The maximum upper airway cross-sectional area at all four anatomic levels was significantly greater during expiration than during inspiration. Other major findings include 1) upper airway cross-sectional area decreases slightly during early inspiration, enlarges toward end inspiration, and is larger at end inspiration than at the beginning of inspiration; 2) upper airway cross-sectional area enlarges from end inspiration to the first point in expiration; the airway enlarges further, reaching its maximum early in expiration, and then narrows toward end expiration; and 3) the changes in upper airway dimensions during resting tidal breathing are greater in the lateral than in the anteroposterior direction. The data suggest that during inspiration, the action of negative intraluminal pressure may be largely balanced by the action of the upper airway dilator muscles, whereas during expiration, positive intraluminal pressure produces expansion of the upper airway.
Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation
Authors: Tokyay R. , Zeigler S. T. , Traber D. L. , Stothert J. C. , Loick H. M. , Heggers J. P. , Herndon D. N.
Published: December 2017

Splanchnic ischemia has been associated with bacterial translocation and increased endotoxin absorption from the gut. To study the effects of major burn on splanchnic circulation, minipigs were randomized to receive 40% flame burn and Parkland resuscitation or sham burn and maintenance fluids. Total and fractionated blood flow, O2 delivery and consumption, mucosal pH of the intestine, and endotoxin levels in the superior mesenteric vein were measured for 48 h, and then abdominal organs were harvested for bacteriological culture and histopathological analysis. Total mesenteric blood flow and fractionated blood flow to the mucosa-submucosa of the jejunum, cecum, and colon decreased 2 and 4 h postburn. Although mesenteric O2 consumption was unchanged, mesenteric O2 delivery and intestinal mucosal pH were decreased during the early postburn period. Concomitantly, endotoxin levels in the superior mesenteric vein were significantly elevated during the first 8 h postburn. The bacteriological cultures of the systemic tissue samples showed increased bacterial translocation in the burn group. After major burns, there is a transient selective splanchnic vasoconstriction, which is associated with intestinal mucosal acidosis and increased incidence of bacterial translocation and endotoxin absorption from the gut.
Attenuation of acute lung injury and oxygen radical production by the 21-aminosteroid, U-78518F
Authors: Tanigaki T. , Suzuki Y. , Heimer D. , Sussman H. H. , Ross W. G. , Raffin T. A.
Published: December 2017

Oxygen radicals play an important role in the mechanism of acute lung injury. The 21-aminosteroid lazaroid, U-78518F, is a potent antioxidant. We examined the effect of intravenous U-78518F on acute lung injury in septic guinea pigs over 8 h. The experimental groups (n = 6) were 1) saline control, 2) Escherichia coli (2 x 10(9)/kg i.v.), 3) pretreatment (U-78518F 5 mg/kg bolus + 1 mg.kg-1 x h-1, 15 min before E. coli injection), and 4) posttreatment (U-78518F 30 min after E. coli injection). We measured wet-to-dry weight ratio (W/D) as an index of pulmonary edema and concentration ratios of 125I-labeled albumin in lung tissue and bronchoalveolar lavage fluid compared with plasma (L/P and BAL/P, respectively) as indexes of lung protein fluxes. In septic guinea pigs, pretreatment with U-78518F attenuated W/D, L/P, and BAL/P and posttreatment attenuated W/D and BAL/P (P < 0.05 for each). Furthermore, we studied the effect of U-78518F on human neutrophil oxygen radical production (ORP) by using flow cytometry to assess intracellular ORP and lucigenin-dependent chemiluminescence to assess extracellular ORP. Neutrophils (5 x 10(5) were stimulated with 0.5 micrograms/ml of phorbol myristate acetate. With flow cytometry, we measured intracellular ORP, cross-sectional cell area, and degranulation in neutrophils. U-78518F (minimum concn 1.0 microM) decreased intracellular ORP (n = 4; P < 0.05) when the dihydrorhodamine 123 assay was used. U-78518F (minimum concn 1.0 microM) inhibited phorbol myristate acetate-induced neutrophil chemiluminescence (n = 4; P < 0.05).
Spaceflight on STS-48 and earth-based unweighting produce similar effects on skeletal muscle of young rats
Authors: Tischler M. E. , Henriksen E. J. , Munoz K. A. , Stump C. S. , Woodman C. R. , Kirby C. R.
Published: December 2017

Our knowledge of the effects of unweighting on skeletal muscle of juvenile rapidly growing rats has been obtained entirely by using hindlimb-suspension models. No spaceflight data on juvenile animals are available to validate these models of simulated weightlessness. Therefore, eight 26-day-old female Sprague-Dawley albino rats were exposed to 5.4 days of weightlessness aboard the space shuttle Discovery (mission STS-48, September 1991). An asynchronous ground control experiment mimicked the flight cage condition, ambient shuttle temperatures, and mission duration for a second group of rats. A third group of animals underwent hindlimb suspension for 5.4 days at ambient temperatures. Although all groups consumed food at a similar rate, flight animals gained a greater percentage of body mass per day (P < 0.05). Mass and protein data showed weight-bearing hindlimb muscles were most affected, with atrophy of the soleus and reduced growth of the plantaris and gastrocnemius in both the flight and suspended animals. In contrast, the non-weight-bearing extensor digitorum longus and tibialis anterior muscles grew normally. Earlier suspension studies showed that the soleus develops an increased sensitivity to insulin during unweighting atrophy, particularly for the uptake of 2-[1,2–3H]deoxyglucose. Therefore, this characteristic was studied in isolated muscles within 2 h after cessation of spaceflight or suspension. Insulin increased uptake 2.5- and 2.7-fold in soleus of flight and suspended animals, respectively, whereas it increased only 1.6-fold in control animals. In contrast, the effect of insulin was similar among the three groups for the extensor digitorum longus, which provides a control for potential systemic differences in the animals.
Collateral ventilation and pulmonary arterial smooth muscle in the coati
Authors: Hanson W. L. , Boggs D. F. , Kay J. M. , Hofmeister S. E. , Wagner W. W.
Published: December 2017

Collateral ventilation can participate in ventilation-perfusion regulation by shifting normoxic gas into hypoxic lung regions. In species lacking collateral pathways, such as cattle and swine, ventilation-perfusion balance must rely heavily on hypoxic vasoconstriction, which may explain why their muscular pulmonary arteries are much thicker than those of other animal species. The presence of these unusually muscular vessels in turn may account for the vigorous pressor response to acute hypoxia in these species. The only other species known to lack collateral ventilation is the coati. To determine whether coatis fit the pulmonary circulatory pattern of cattle and swine, we measured pulmonary arterial wall dimensions and pulmonary vascular responsiveness to acute airway hypoxia in 11 adult coatis. Hypoxia caused impressive pulmonary arterial hypertension [normoxia = 17 +/- 1 (SE) Torr, hypoxia = 40 +/- 2 Torr, cardiac output unchanged]. The medial thickness of muscular pulmonary arteries (50–300 microns) was 17.1 +/- 1.8% (SD) of external diameter, a thickness unprecedented in normotensive adult mammals. We conclude that coatis fit the pattern of other species lacking collateral ventilation, since they have thick-walled pulmonary arteries and a vigorous pressor response to hypoxia.
Regulation of expiratory muscles during postnatal development in anesthetized piglets
Authors: Litmanovitz I. , Martin R. J. , Haxhiu M. A. , Cattarossi L. , Haxhiu-Poskurica B. , Carlo W. A.
Published: December 2017

We compared maturation of the responses of the rib cage [triangularis sterni (TS)] and abdominal [transversus abdominis (TA)] expiratory muscles with each other and with the responses of the diaphragm (DIA) during hypercarbic and hypoxic stimulation. Studies were performed in anesthetized (urethan and chloralose) piglets of two age groups (< 6 days, n = 10; 14–21 days, n = 11) before and after bilateral cervical vagotomy. Hypercarbia (7% CO2–93% O2) was associated with comparable sustained increases in the minute electromyograms (EMGs) of both TS and TA, which were closely coupled to the DIA responses in both age groups. Hypoxia (12% O2–88% N2) caused a biphasic response of the minute EMG of both expiratory muscles and DIA; these biphasic responses were less prominent at 14-21 days than at < 6 days. Vagotomy caused an increase in the amplitude of both TS and TA (38 +/- 30 and 27 +/- 21%, respectively) as well as the DIA (45 +/- 16%) but did not affect their relative responses to chemostimulation. We conclude that during postnatal development 1) the rib cage and abdominal expiratory muscle responses to chemostimulation are coupled to each other and parallel those of the DIA and 2) the presence of vagal afferents attenuates the drive to both inspiratory and expiratory motoneurons under the current experimental conditions but does not influence the relative responses of expiratory muscles and DIA to hypercarbia or hypoxia. We speculate that comparable activation of inspiratory and expiratory pumping muscles serves to stabilize respiratory control in the face of altered chemosensory or vagal inputs during early postnatal life.
Static mechanics of the velopharynx of patients with obstructive sleep apnea
Authors: Isono S. , Morrison D. L. , Launois S. H. , Feroah T. R. , Whitelaw W. A. , Remmers J. E.
Published: December 2017

The static mechanics of the hypotonic pharynx were endoscopically evaluated in nine sleeping patients with obstructive sleep apnea, having a primary narrowing only at the velopharynx. The velopharynx closed completely at a mean pressure of 0.18 +/- 1.21 cmH2O, and the mean half-dilation pressure was 1.93 cmH2O above closing pressure. The dependence of area on pressure was distinctly curvilinear, being steep near closing pressure and asymptotically approaching maximum area (mean = 1.32 cm2). The data for each patient were satisfactorily fitted by an exponential function (mean R2 = 0.98), and a single exponential relationship usefully represented the dependence of relative area on pressure above closing pressure for the population (R2 = 0.85). During the test inspiration, flow limitation was consistently observed when mask pressure exceeded closing pressure by 0.5–3.0 cmH2O. In summary, the static mechanics of the hypotonic velopharynx of patients with obstructive sleep apnea can be described by an exponential pressure-area relationship, with a closing pressure near atmospheric pressure and a high compliance in the range of airway pressure 0–3 cmH2O above closing pressure.
Simulations of washout experiments in postmortem rat lungs
Authors: Verbanck S. , Weibel E. R. , Paiva M.
Published: December 2017

We developed a rat lung model to simulate single-breath and multiple-breath washout experiments performed by Verbanck et al. (J. Appl. Physiol. 71: 847–854, 1991) and Gonzalez Mangado et al. (J. Appl. Physiol. 71: 855–862, 1991). The multi-branch-point rat lung model is based on anatomic data of the rat airway tree as obtained by Rodriguez et al. (Am. J. Anat. 180: 143–155, 1987). We simulated single- and multiple-breath washout maneuvers and computed the slope of the alveolar plateaus and Fowler and Bohr dead spaces. In general, the comparison between experiments and simulations shows a good agreement, suggesting that the mechanism of diffusion-convection interaction in an asymmetric structure entirely accounts for the ventilation maldistribution in the rat lung. In particular, it is shown that the marked asymmetry of the rat lung structure is responsible for the fact that He slopes are larger than SF6 slopes in rat lungs, as opposed to what is observed in other species.
Optimal ventilation waveforms for estimating low-frequency respiratory impedance
Authors: Lutchen K. R. , Yang K. , Kaczka D. W. , Suki B.
Published: December 2017

We present a broad-band optimal ventilator waveform (OVW), the concept of which was to create a computer-driven ventilator waveform containing increased energy at specific frequencies (f). Values of f were chosen such that nonlinear harmonic distortion and intermodulation were minimized. The phases at each f were then optimized such that the resulting flow waveform delivered sufficient volume to maintain gas exchange while minimizing peak-to-peak airway opening pressure. Simulations with a linear anatomically consistent branching airway model and a nonlinear viscoelastic model showed that respiratory resistance (Rrs) and elastance (Ers) estimates at 0.1–2 Hz from the OVW are far superior to those from a standard step ventilator waveform (SVW) during healthy and obstructed conditions and that the OVW reduces the influences of harmonic interactions. Using a servo-controlled oscillator, we applied individual sine waves, an OVW containing energy at 0.15625–2.4 Hz, and an SVW to healthy humans and one symptomatic asthmatic subject before and after bronchodilation. The OVW was markedly superior to the SVW and always provided smooth estimates of Rrs and Ers. Before bronchodilation in the asthmatic subject Rrs was highly elevated and Ers was markedly increased with f; after bronchodilation the level of Rrs and the f dependence of Ers decreased. Although based on results from only one asthmatic subject, these data suggest a dominant influence of airway constriction and lung inhomogeneities during asthmatic bronchoconstriction that is alleviated by bronchodilators. These and other results indicate that the OVW approach has high potential for simultaneously probing f and amplitude dependence in the mechanical properties of clinical subjects during physiological breathing conditions and perhaps during dynamic bronchoconstriction.
Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle
Authors: Reid M. B. , Khawli F. A. , Moody M. R.
Published: December 2017

This study tested the hypothesis that reactive oxygen intermediates present in unfatigued skeletal muscle act to enhance contractile function. Fiber bundles from rat diaphragm were incubated with exogenous catalase (an antioxidant enzyme that dehydrates hydrogen peroxide to molecular oxygen and water) to decrease the tissue concentration of reactive oxygen intermediates. Catalase (10(3) U/ml) significantly decreased twitch characteristics (time to peak tension, half-relaxation time, peak force, and twitch-to-tetanus force ratio), thereby shifting the force-frequency relationship to the right. Catalase effects were dose dependent. Concentrations of 1 to 10(5) U/ml progressively depressed submaximal (30-Hz) tetanic stress, whereas concentrations > 10(5) U/ml were toxic, inhibiting maximal (200-Hz) tetanic stress (P < 0.0001). Exogenous hydrogen peroxide (10(-4) to 10(-2)M) increased peak twitch stress (P < 0.03) and lengthened both time to peak tension (P < 0.02) and half-relaxation time (P < 0.02). Selective removal of superoxide anion radicals with the use of superoxide dismutase produced dose-dependent contractile inhibition similar to that produced by catalase. We conclude that the reactive oxygen intermediates present in unfatigued skeletal muscle have a positive effect on excitation-contraction coupling and are obligatory for optimal contractile function.
Prediction of body composition in premenopausal females from dual-energy X-ray absorptiometry
Authors: Hansen N. J. , Lohman T. G. , Going S. B. , Hall M. C. , Pamenter R. W. , Bare L. A. , Boyden T. W. , Houtkooper L. B.
Published: December 2017

Four methods for predicting body composition were compared in premenopausal females (n = 100), 28#x2013;39 yr old, by using underwater weighing (UWW) as the criterion method. The four methods were dual energy X-ray absorptiometry (DEXA), skinfolds, bioelectrical impedance, and body mass index. The sample had a mean percent fat (%fat) of 29.7 +/- 6.8% (SD) by DEXA and 29.9 +/- 5.8% measured by UWW. DEXA yielded a standard error of estimate (SE) of 2.4% (r = 0.91) for the prediction of %fat from UWW. When %fat was estimated from other methods, larger SEs were obtained: 3.0% for skin-folds, 3.3% for body mass index, and 2.9% for bioelectrical impedance (height2/resistance) plus weight. Individual body density values derived from UWW were corrected for bone mineral variation. DEXA predicted the corrected body density with a lower SE (0.0040 vs. 0.0053 g/ml) than the original density values. We conclude that DEXA was a precise method and correlated highly with fat-free body weight and %fat from UWW in this homogeneous female sample.
Micropipette and vascular occlusion pressures in isolated lungs of newborn lambs
Authors: Fike C. D. , Gordon J. B. , Kaplowitz M. R.
Published: December 2017

We compared measurements made by vascular occlusion, double occlusion, and micropuncture techniques in isolated perfused lungs of 3- to 10-day-old lambs. After adding indomethacin to the perfusate of 16 lungs, we used the micropuncture technique to measure pressures in 20- to 80-microns-diam arterioles (Pa80), 20- to 50-microns-diam venules (Pv20), and 50- to 150-microns-diam venules (Pv150). The vascular occlusion and double occlusion techniques were used in these same lungs to measure inflow occlusion (Pao), outflow occlusion (Pvo), and double occlusion pressures (Pdo). In 14 other lungs without indomethacin added to the perfusate, we measured Pv20 and Pvo before and during alveolar hypoxia and/or before and after the addition of papaverine to the perfusate. In indomethacin-treated lungs, Pao was greater than Pa80, Pvo equaled Pv20 and Pv150, and Pdo was the same as Pa80, Pv20, and Pv150. In lungs without indomethacin treatment, Pvo was less than Pv20 both before and during hypoxia but Pvo equaled Pv20 after papaverine was added to the perfusate. Thus, in indomethacin-treated lungs of newborn lambs, Pao reflected pressure in arteries > 80 microns diam, Pdo reflected pressure between 80-microns-diam arteries and 150-microns-diam veins, and Pvo was similar to pressure in veins both as small as 20 microns diam and as large as 150 microns diam. However, without indomethacin there was a gradient between Pvo and Pv20 both before and during hypoxia but not after vasomotor tone was reduced with papaverine. Thus, the correlation between Pvo and micropuncture pressure in Pv20 and Pv150 was not constant and appeared related to vasomotor tone.