bluuebunny/crossref_metadata_2025 huggingface dataset:
Smoke inhalation injury in sheep is caused by the particle phase, not the gas phase
Authors: Lalonde C. , Demling R. , Brain J. , Blanchard J.
Published: December 2017

The inhalation of smoke can produce severe lung injury, particularly to airways. We assessed the role of the toxic compounds in the particle phase vs. those in the gas phase of smoke in the injury process by filtering out all particles > 0.3 micron diam before exposure. Adult sheep (n = 16) were insufflated with a well-characterized cellulose smoke. Mean particle size was 3 +/- 0.4 micron diam. A standardized dose of 12 breaths of whole or filtered smoke (n = 8/group) was given to sheep under anesthesia with a tidal volume of 20 ml/kg. Sheep were awakened and monitored for 24 h and then killed. Peak carboxyhemoglobin levels were 40–45% in both groups. Severe respiratory failure occurred only in the whole-smoke group, as evidenced by an increase in shunt fraction from a control of 0.04 +/- 0.02 to 0.28 +/- 0.05, a decrease in lung compliance of 50%, and histological evidence of severe airway mucosal edema, ulceration, and bronchorrhea. No significant physiological, histological, or biochemical changes were noted in the filtered-smoke group.
Effect of age on L-3,5,3'-triiodothyronine-induced ethane exhalation
Authors: Mooradian A. D. , Habib M. P. , Dickerson F. , Yetskievych T.
Published: December 2017

The effect of age on thyroid hormone-induced lipid peroxidation in rats was determined by measuring ethane exhalation (EE) rate. The mean basal EE rates (in pmol.min-1 x 100 g-1) at room air in 25-mo-old aged rats [3.07 +/- 0.26 (SE)] and in intermediate age (18-mo-old) rats (3.42 +/- 0.18) were significantly lower than that in young (3- to 5-mo-old) rats (4.44 +/- 0.27) (P < 0.01). After 8 days of L-3,5,3′-triiodothyronine (T3) administration, EE rates in aged rats (4.10 +/- 0.25) and in intermediate-age rats (4.16 +/- 0.35) were significantly lower than that in young rats (5.61 +/- 0.36) (P < 0.01). T3-treated young rats pair-fed with aged rats for 2 wk had EE rates (5.53 +/- 0.18) comparable to ad libitum-fed young rats, although the basal rate of EE was significantly reduced with partial food restriction (4.44 +/- 0.27 vs. 3.50 +/- 0.24) (P < 0.01). These observations indicate that reduced food intake with age cannot account for the age-related changes in T3-stimulated peroxidation rate of lipids.
Recovery from increased pressure or increased leakiness edema in perfused sheep lungs
Authors: Fukue M. , Serikov V. B. , Jerome E. H.
Published: December 2017

Two routes by which interstitial pulmonary edema liquid may leave the lung during recovery are reabsorption into the pulmonary circulation and clearance by lung lymphatics. We hypothesized that reabsorption of edema liquid of low protein concentration into the pulmonary circulation would be greater than reabsorption of edema liquid of high protein concentration because of the greater protein osmotic gradient in the former. On the basis of previous studies, lymph flow should contribute minimally to the recovery. In 22 in situ perfused sheep lungs with lymph fistulas, we produced approximately 100 g of osmotic or hydrostatic edema (low protein) or increased leakiness edema by calcium depletion (high protein). To induce reabsorption, we changed the perfusate from low- (1% albumin, osmotic pressure = 4 cmH2O) to high-protein (7% albumin, osmotic pressure = 22 cmH2O) solution in the osmotic group, decreased capillary pressure from 29 +/- 9 to 11 +/- 6 cmH2O in the hydrostatic group, or reversed leakiness by adding CaCl2 to the perfusate in the increased leakiness group. Reabsorption occurred only during recovery from osmotic (40 +/- 22% of filtered liquid) and hydrostatic (15 +/- 11%) edema. Total lung lymph flow during recovery from osmotic, hydrostatic, or increased leakiness edema was 4.9 +/- 3.4, 4.3 +/- 3.4, or 3.5 +/- 1.9 g, respectively. We conclude that during recovery from pulmonary edema interstitial liquid is reabsorbed into the circulation in inverse proportion to its protein concentration. We confirm that only a small fraction of the interstitial edema liquid is cleared by the lymphatics during recovery from any type of edema.
Lactate and acid-base exchange during brief intense contractions of skeletal muscle in situ
Authors: Brechue W. F. , Stainsby W. N.
Published: December 2017

Our goal was to design a stimulation-contraction paradigm using an isolated in situ dog gastrocnemius muscle preparation that would provide an experimental model for brief intense intermittent (IC) exercise in humans. Second, acid-base and ion exchanges across the muscle were investigated using four 30-s bouts of isotonic tetanic contractions (2 s-1, 100-ms train, 50 impulses/s) with 4 min of rest between bouts. During the bouts, peak power output (W) was 18.2 mW/g in the first bout; it declined by 4.4% by the fourth bout and by 12–16% in each bout. Compared with repetitive continuous contractions (CC) at maximal O2 uptake (VO2), W was greater and VO2 (approximately 3.5 mumol.g-1.min-1) and CO2 production (approximately 4.5 mumol.g-1.min-1) were less with IC. Venous-arterial (v-a) differences and lactate output peaked immediately after each bout and were not different from the values reported for CC at maximal VO2. Thus, with IC, VO2/W was lower and the CO2 production/VO2 and lactate output/VO2 ratios were greater than those seen with CC. These differences suggest that this stimulation-contraction paradigm may be an appropriate model for brief intense exercise. The v-a [H+] difference was a direct result of the v-a PCO2 difference. The venous strong ion difference was always greater than or equal to the arterial strong ion difference because the v-a [Cl-] difference was opposite and greater than the v-a lactate concentration difference, whereas the v-a [Na+] and [K+] differences were small.(ABSTRACT TRUNCATED AT 250 WORDS)
Time course of augmentation and depression of hypoxic ventilatory responses at altitude
Authors: Sato M. , Severinghaus J. W. , Bickler P.
Published: December 2017

Hypoxic ventilatory response (HVR) and hypoxic ventilatory depression (HVD) were measured in six subjects before, during, and after 12 days at 3,810-m altitude (barometric pressure approximately 488 Torr) with and without 15 min of preoxygenation. HVR was tested by 5-min isocapnic steps to 75% arterial O2 saturation measured by pulse oximetry (Spo2) at an isocapnic PCO2 (P*CO2) chosen to set hyperoxic resting ventilation to 140 ml.kg-1.min-1. Hypercapnic ventilatory response (HCVR, 1.min-1.Torr-1) was tested at ambient and high SPO2 6–8 min after a 6- to 10-Torr step increase of end-tidal PCO2 (PETCO2) above P*CO2. HCVR was independent of preoxygenation and was not significantly increased at altitude (when corrected to delta logPCO2). Preoxygenated HVR rose from -1.13 +/- 0.23 (SE) l.min-1.%SPO2(-1) at sea level to -2.17 +/- 0.13 by altitude day 12, without reaching a plateau, and returned to control after return to sea level for 4 days. Ambient HVR was measured at P*CO2 by step reduction of SPO2 from its ambient value (86–91%) to approximately 75%. Ambient HVR slope was not significantly less, but ventilation at equal levels of SPO2 and PCO2 was lower by 13.3 +/- 2.4 l/min on day 2 (SPO2 = 86.2 +/- 2.3) and by 5.9 +/- 3.5 l/min on day 12 (SPO2 = 91.0 +/- 1.5; P < 0.05). This lower ventilation was estimated (from HCVR) to be equivalent to an elevation of the central chemoreceptor PCO2 set point of 9.2 +/- 2.1 Torr on day 2 and 4.5 +/- 1.3 on day 12.(ABSTRACT TRUNCATED AT 250 WORDS)
Isoproterenol decreases protein permeability in edematous isolated rabbit lungs: estimation of PS and sigma
Authors: Kreienberg P. B. , Vincent P. A. , Bell D. R. , Saba T. M. , Minnear F. L.
Published: December 2017

The objective of the present study was to determine whether the ability of the beta-adrenergic agonist isoproterenol to attenuate pulmonary edema occurs via a permeability and/or hemodynamic mechanism. In isolated perfused rabbit lungs, the restrictive property of the vascular barrier to the movement of fluid and protein was assessed by measurements of the capillary filtration coefficient (Kf) and the transvascular clearance of 125I-labeled albumin, respectively. Regression analysis of albumin clearance vs. transvascular fluid flux was performed to estimate the permeability-surface area product (PS) and the reflection coefficient (sigma) by use of the linear or nonlinear flux equation. Arterial, capillary, and venous pressures and resistances, weight gain, and the wet-to-dry weight ratio were also assessed. Isoproterenol (8 ng.ml-1.min-1) attenuated the arachidonic acid (4 mg)-induced increases in fluid flux, wet-to-dry weight ratio, albumin clearance, and PS and the decrease in sigma. Isoproterenol had no effect on the increase in Kf, and there was no correlation between capillary pressure and fluid flux in any of the four groups. Regression analysis revealed that the non-linear flux equation provided estimates of PS and sigma that more accurately described the statistical differences in albumin clearance among the groups studied than the linear flux equation. These findings demonstrate that isoproterenol attenuated the increased transvascular flux of albumin in edematous lungs by modifying the protein permeability of the vascular barrier.
Pulmonary capillary transport function from flow-limited indicators
Authors: Audi S. H. , Krenz G. S. , Linehan J. H. , Rickaby D. A. , Dawson C. A.
Published: December 2017

The objective of this study was to examine the use of rapidly diffusing (flow-limited) indicators for estimating the pulmonary capillary blood volume (i.e., fraction of the lung blood volume wherein the diffusible indicators equilibrate with the tissue) and the capillary transit time distribution. Supporting theory and an application to experimental data are presented. The theory leads to the following equations, which relate the mean transit time (t), the variance (sigma 2), and the third central moment (m3) of the capillary transport function, hc(t), to the moments of the venous concentration-time curves for a vascular reference indicator, CR(t), and a flow-limited diffusible indicator, CD(t), after a bolus injection of the indicators upstream from an organ: sigma 2D - sigma 2R = ([1 + (te/tc)]2–1)sigma 2c and m3D-m3R = ([1 + (te/tc)]3–1)m3c, where te = tD - tR and tc is capillary t. The moments of hc(t) can be estimated if the injected bolus includes, along with the vascular reference indicator, at least two flow-limited diffusible indicators, each with a different te. A least-squares optimization procedure can then be used to specify the moments of hc(t). This approach was applied to isolated dog lung lobes with [14C]-diazepam as the diffusible indicator. The tissue-to-perfusate partition coefficient for [14C]diazepam could be adjusted to any desired value by altering the perfusate albumin concentration. Thus, by making a number of injections, each at a different perfusate albumin concentration, data were obtained in a manner equivalent to making one injection with a number of flow-limited diffusible indicators, each with a different te. On average, the estimated capillary volume and mean transit time were approximately 48% of the total lobar volume and mean transit time, and the relative dispersion of the hc(t) was approximately 75%.
Coordination of oral cavity and laryngeal movements during swallowing
Authors: Gay T. , Rendell J. K. , Spiro J. , Mosier K. , Lurie A. G.
Published: December 2017

In this study, dynamic imaging was used to track the movements of oral cavity and laryngeal structures during swallowing in 10 normal adults subjects. The movements of tiny lead pellet markers attached to the lips, tongue, mandible, and soft palate, as well as anatomic landmarks on the hyoid bone, were measured in relation to a reference pellet affixed to the upper central incisors. Sagittal views of the oral cavity were obtained using standard videofluorography. Each subject produced 10 swallows of 12 ml of tap water followed by 5 swallows with a bite block placed between the molars. The recorded video images were input to a microcomputer where the x- and y-coordinates of the pellets were measured. Results of the analyses revealed considerable temporal overlap in the timing of oral cavity and laryngeal movements, widespread individual variability in coordination patterns and movement trajectories, and selective effects of the bite block. These data suggest the existence of individual adaptive strategies in the programming and control of swallowing movements.
Airway geometry and wall mechanical properties estimated from subglottal input impedance in humans
Authors: Habib R. H. , Chalker R. B. , Suki B. , Jackson A. C.
Published: December 2017

We measured input impedance between 16 and 2,048 Hz in intubated subjects at functional residual capacity. The corresponding subglottal impedances (ZSG) were then computed using a model where the endotracheal tube was represented by a distributed-parameter two-port network. ZSG was well described by a model based on Horsfield's asymmetric airway geometry at total lung capacity (TLC) with nonrigid walls. The walls of the cartilaginous airways included separate cartilage and soft tissue compartments, whereas the noncartilaginous airway walls had only a soft tissue compartment. Both compartments consisted of a series resistance, inertance, and compliance, the values of which were computed from airway dimensions and wall material properties (viscosity, density, and Young's modulus). Airway wall thickness was determined by scaling an airway wall area-diameter relationship. Airway lengths and diameters were scaled from the Horsfield TLC values by a single factor and by an order-dependent sigmoidal curve, respectively. The estimated soft tissue viscosity and Young's modulus were 1.04 +/- 0.21 cmH2O.s and 593 +/- 319 cmH2O, respectively. Airway lengths and tracheal diameters were not statistically different from the Horsfield values. The estimated diameters of the more peripheral airways were significantly reduced compared with the Horsfield TLC values (e.g., approximately 40% at the terminal airway), which is consistent with the reduction in airway caliber when the lung deflates from TLC to functional residual capacity. These results indicate that high-frequency ZSG is sensitive to subglottal airway geometry and wall properties and that by use of appropriate structural models one can estimate airway geometry and airway wall parameters.
Reduced spontaneous baroreflex response slope during lower body negative pressure after 28 days of head-down bed rest
Authors: Hughson R. L. , Maillet A. , Gharib C. , Fortrat J. O. , Yamamoto Y. , Pavy-Letraon A. , Riviere D. , Guell A.
Published: December 2017

Effects of 28 days of continuous 6 degrees head-down tilt bed rest on spontaneous vagally mediated baroreflex response slope were evaluated from beat-by-beat relationships between R-R interval and systolic arterial blood pressure. Twelve healthy men (age 27–42 yr) were assigned to either countermeasure (CM) or no-countermeasure (no-CM) groups. CM consisted of strenuous short-term exercise once per day 6 days/wk from days 7 to 28 and lower body negative pressure (LBNP) for 15 min on days 16, 18, 20, and 22–28. Spontaneous baroreflex slope was evaluated by application of linear regression to sequences of at least three beats in which systolic blood pressure and R-R interval changed in the same direction. Measurements were made pre-, mid- (day 15), and post-bed rest at rest and during progressive LBNP tests (3 min at each of -20, -30, -40, and -50 mmHg). R-R interval decreased progressively and significantly (P < 0.0001) over duration of bed rest. Spontaneous baroreflex slope at rest in pre-bed rest was 18.5 +/- 2.1 ms/mm Hg for CM and 14.9 +/- 1.6 ms/mmHg for no-CM. There was a significant reduction in baroreflex slope as a function of bed rest, and it was further reduced during LBNP (P < 0.0001). Between CM and no-CM groups differences existed, but these were present pre-bed rest and appeared unaffected by countermeasures.(ABSTRACT TRUNCATED AT 250 WORDS)
Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC
Authors: Ullum H. , Haahr P. M. , Diamant M. , Palmo J. , Halkjaer-Kristensen J. , Pedersen B. K.
Published: December 2017

The present study investigated the effect of concentric exercise on cytokine plasma levels and cytokine pre-mRNA in blood mononuclear cells (BMNCs). Healthy young moderately trained men performed ergometer bicycle exercise for 1 h at 75% of maximal oxygen uptake. The levels of plasma interleukin (IL)-6 increased significantly during exercise, but plasma levels of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were below the detection limit in most subjects. Pre-mRNA for IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha could be detected in BMNCs, but the amounts did not change in relation to exercise. These results indicate that, although the absolute number of monocytes increases during exercise and the percentage of CD14+/HLA-DR+ and CD14+/HLA-DR- monocytes increases after exercise, the increased plasma levels of IL-6 during exercise is not likely to be a result of activated monocytes in peripheral blood.
Effects of acute running exercise on whole body insulin action in obese male SHHF/Mcc-facp rats
Authors: Gao J. , Sherman W. M. , McCune S. A. , Osei K.
Published: December 2017

This study utilized the obese male spontaneously hypertensive heart failure rat (SHHF/Mcc-facp), which has metabolic features very similar to human non-insulin-dependent diabetes mellitus. The purpose of this study was to assess the insulin sensitivity and responsiveness of whole body glucose disposal and insulin suppressability of hepatic glucose production with use of the euglycemic-hyperinsulinemic clamp procedure in 12- to 15-wk-old SHHF/Mcc-facp rats at rest (OS) and 2.5 h after a single session of acute exercise (OE). Lean male SHHF/Mcc-facp rats were sedentary (LS) control animals. At least three clamps producing different insulin-stimulated responses were performed on each animal in a randomized order. At this age the obese animals are normotensive and have not developed congestive heart failure. Compared with LS, OS were significantly hyperglycemic and hyperinsulinemic and insulin sensitivity and responsiveness of whole body glucose uptake and insulin suppressability of hepatic glucose production were significantly decreased. Compared with LS and OS, acute exercise significantly decreased resting plasma glucose but did not alter plasma insulin. Compared with OS, acute exercise significantly increased the insulin responsiveness of whole body glucose disposal but did not affect the sensitivity of whole body glucose disposal or insulin suppressability of hepatic glucose production. Compared with LS, however, acute exercise did not “normalize” the insulin responsiveness of whole body glucose disposal. Thus a single acute exercise session improves but does not normalize whole body insulin resistance in the SHHF/Mcc-facp rat.
Interleukin-2 therapy reverses some immunosuppressive effects of skeletal unloading
Authors: Armstrong J. W. , Balch S. , Chapes S. K.
Published: December 2017

Using antiorthostatic suspension, we characterized hematopoietic changes that may be responsible for the detrimental effect of skeletal unloading on macrophage development. Skeletally unloaded mice had suppressed macrophage development in unloaded and loaded bones, which indicated a systemic effect. Bone marrow cells from unloaded mice secreted less macrophage colony-stimulating factor and interleukin-6 than control mice. Additionally, T-lymphocyte proliferation was reduced after skeletal unloading. We show that polyethylene glycol-interleukin-2 therapy reversed the effects of skeletal unloading on macrophage development and cell proliferation.
Simulation of cardiovascular response to lower body negative pressure from 0 to -40 mmHg
Authors: Melchior F. M. , Srinivasan R. S. , Thullier P. H. , Clere J. M.
Published: December 2017

This paper presents a mathematical model for simulation of the human cardiovascular response to lower body negative pressure (LBNP) up to -40 mmHg both under normal conditions and when arterial baroreflex sensitivity or leg blood capacity (LBC) is altered. Development of the model assumes that the LBNP response could be explained solely on the bases of 1) blood volume redistribution, 2) left ventricular end-diastolic filling, 3) interaction between left ventricle and peripheral circulation, and 4) modulations of peripheral resistances and heart rate by arterial and cardiopulmonary baroreflexes. The model reproduced well experimental data obtained both under normal conditions and during complete autonomic blockade; thus it is validated for simulation of the cardiovascular response from 0 to -40 mmHg LBNP. We tested the ability of the model to simulate the changes in LBNP response due to a reduction in LBC. To assess these changes experimentally, six healthy men were subjected to LBNP of -15, -30, and -38 mmHg with and without wearing elastic compression stockings. Stockings significantly reduced LBC (from 3.9 +/- 0.3 to 1.8 +/- 0.4 ml/100 ml tissue at -38 mmHg LBNP; P < 0.01) and attenuated the change in heart rate (from 23 +/- 4 to 8 +/- 3% at -38 mmHg LBNP; P < 0.05). The model accurately reproduced this result. The model is useful for assessing the influence of LBC or other parameters such as arterial baroreflex sensitivity in diminishing the orthostatic tolerance of humans after spaceflight, bed rest, or endurance training.
Performance and metabolic effects of benzodiazepine during submaximal exercise
Authors: Collomp K. , Fortier M. , Cooper S. , Long A. , Ahmaidi S. , Prefaut C. , Wright F. , Picot M. , Cote M. G.
Published: December 2017

The present study examined whether benzodiazepine (BZ) intake alters performance and selected hormonal and metabolic variables during submaximal exercise. Seven triathletes completed two cycling trials at 85% maximum O2 uptake starting 3 h after an ingestion of either a placebo (PLA) of gelatin or BZ (1.5 mg lorazepam) and continuing until exhaustion, according to a double-blind randomized protocol. Blood samples were collected at rest; 5, 10, and 15 min; and exhaustion for dopamine (DA), norepinephrine (NE), epinephrine (Epi), adrenocorticotropic hormone (ACTH), cortisol (CORT), insulin (INS), free fatty acid, blood glucose, and lactate (La) determinations. Time of cycling was not significantly changed after BZ or PLA administration (22.9 +/- 2.5 vs. 23.5 +/- 3.8 min, respectively). A decrease in CORT and an increase in INS (P < 0.05) were observed with BZ before cycling. In comparison with rest, exercise resulted in a decrease in INS and an increase in all the other variables investigated (P < 0.001), but DA, NE, Epi, ACTH, CORT, La, and free fatty acid were significantly less elevated under BZ (P < 0.05). No change was found in glucose and INS levels between the two treatments at the end of the test. There was a strong correlation under both PLA and BZ conditions between DA, NE, Epi, and ACTH and also between Epi and La levels. From these data, BZ intake did appear to alter metabolism but did not influence performance during intense submaximal exercise.
Effect of sleep and sighing on upper airway resistance in mongrel dogs
Authors: Issa F. G. , Porostocky S. , Feroah T.
Published: December 2017

We investigated the effect of sleep and sighing on supratracheal resistance in unrestrained mongrel dogs breathing through the nose by comparing within-breath changes in upper airway pressure-flow relationship in control, sigh, and five postsigh breaths recorded during wakefulness and during non-rapid-eye-movement and rapid-eye-movement sleep. A sigh breath was characterized by a high tidal volume and was typically followed by an apnea of a variable duration. Sleep had little or no effect on supratracheal resistance, measured at peak flow rates, during quiet breathing (awake 7.3 +/- 0.4, non-rapid eye movement 8.3 +/- 0.4, and rapid eye movement 6.8 +/- 0.4 cmH2O.l–1.s). The resistance was identical in the early part of inspiration in control and sigh breaths but increased during the augmented phase of sigh breaths. Resistance at peak inspiratory flow was higher in sigh breaths than in control breaths in all sleep states. The flow-pressure profile of postsigh breaths was identical to that of control breaths in all sleep states. We conclude that upper airway resistance is essentially unaffected by sleep state in the mongrel dog and that sighing increases upper airway resistance regardless of sleep state.
Chest wall interrupter resistance in anesthetized paralyzed humans
Authors: D'Angelo E. , Prandi E. , Tavola M. , Calderini E. , Milic-Emili J.
Published: December 2017

Tracheal (Ptr) and esophageal (Pes) pressure and flow were measured in 12 supine anesthetized paralyzed normal subjects aged 16–22 yr. The subjects were ventilated with a fixed inflation volume (range 0.57–0.62 liter) and with different constant flows ranging between 0.24 and 1.12 l/s. A rapid airway shutter (closing time 10–15 ms) was used to briefly occlude (0.4–0.9) the airways at end inspiration for 33–44 consecutive breaths. At each flow level, Ptr and Pes records obtained during end-inspiratory occlusions were ensemble averaged to allow for the cardiac artifacts. The interrupter resistances of the chest wall and respiratory system were assessed as the rapid fall in Pes and Ptr with occlusion divided by the flow preceding the occlusion. Interrupter resistances of both the chest wall and lung were independent of flow and averaged 0.4 +/- 0.1 and 1.5 +/- 0.4 (SD) cmH2O.s.l–1, respectively. The contribution of the chest wall to the total interrupter resistance was approximately 27% at flows < or = 1 l/s.
Upper airway collapsibility in children with obstructive sleep apnea syndrome
Authors: Marcus C. L. , McColley S. A. , Carroll J. L. , Loughlin G. M. , Smith P. L. , Schwartz A. R.
Published: December 2017

In adults, the critical nasal pressure (Pcrit) at which the upper airway collapses is higher in patients with the obstructive sleep apnea syndrome (OSAS) than in those with primary snoring. Pediatric OSAS differs clinically from adult OSAS. We therefore compared Pcrit between prepubertal children with OSAS and primary snoring. Pcrit was determined by correlating the maximal inspiratory airflow with the level of positive or negative nasal pressure applied via a nasal mask. As in adults, we found that the maximal inspiratory airflow varied in proportion to the upstream (nasal) rather than the downstream (esophageal) pressure changes. Pcrit was 1 +/- 3 cmH2O in OSAS compared with -20 +/- 9 cmH2O in primary snorers (P < 0.002). In three OSAS patients reevaluated after tonsillectomy and adenoidectomy, Pcrit declined to -7.2 +/- 4.0 cmH2O. We conclude that the pediatric airway behaved as predicted by the Starling resistor model and that Pcrit, a measure of airway collapsibility, correlated with the degree of upper airway obstruction and was reduced postoperatively, consistent with increased upper airway stability.
High physiological levels of epinephrine do not enhance muscle glycogenolysis during tetanic stimulation
Authors: Chesley A. , Dyck D. J. , Spriet L. L.
Published: December 2017

This study examined whether high physiological concentrations of epinephrine (EPI) would enhance muscle glycogenolysis during intense muscular contractions. Muscles of the rat hindlimb were perfused for 12 min at rest and 45 s of tetanic stimulation (1.0-Hz train rate, 100-ms train duration at 80 Hz) without EPI (control) or with 15 or 35 nM EPI. In the EPI groups the muscles were perfused with EPI for the last 2 min of rest perfusion and throughout stimulation. Glycogenolysis in the white gastrocnemius, red gastrocnemius, plantaris, and soleus muscles during stimulation was unaffected by the presence of EPI in the perfusion medium. In addition, muscle lactate and hindlimb lactate efflux were similar in EPI and control groups. It is concluded that EPI is not important for enhancing glycogenolysis in rat muscles composed predominantly of fast-twitch fibers during intense short-term tetanic stimulation.
Index finger position and force of the human first dorsal interosseus and its ulnar nerve antagonist
Authors: Zijdewind I. , Kernell D.
Published: December 2017

In normal subjects, maximum voluntary contraction (MVC) and electrical ulnar nerve stimulation (UNS; 30-Hz bursts of 0.33 s) were systematically compared with regard to the forces generated in different directions (abduction/adduction and flexion) and at different degrees of index finger abduction. With a “resting” hand position in which there was no index finger abduction, UNS produced about one-half of the abduction force elicited by an MVC (mean ratio 51%). Qualitatively, such a discrepancy would be expected, because UNS activates two index finger muscles with opposing actions in the abduction/adduction plane of torques: the first dorsal interosseus (FDI) and the first palmar interosseus (FPI). The abduction forces produced by MVC and UNS were very sensitive to index finger abduction angle: at a maximum degree of abduction, the UNS-generated force even reversed its direction of action to adduction (with FPI dominating) and the abduction MVC declined to 37% of that in the resting hand position. Inasmuch as these declines in MVC- and UNS-generated abduction force could not be explained by a change in moment arm, the main alternative seemed to be abduction-associated alterations in FDI fiber length (analysis by previously published biomechanical data). The FDI and FPI were further compared by application of a UNS-generated fatigue test (5-min burst stimulation), with the index finger kept at a "neutral" angle, i.e., the abduction angle at which, in the unfatigued state, the forces of the FDI and FPI were in balance (zero net UNS-generated abduction/adduction force).(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic and ventilatory responses to anemic hypoxia in conscious rats
Authors: Matsuoka T. , Saiki C. , Mortola J. P.
Published: December 2017

We investigated the metabolic and ventilatory effects of anemia, which is characterized by a decrease in blood O2 content with no changes in arterial PO2 (PaO2). Anemia was obtained in conscious chronically instrumented adult male rats by substituting blood with equal volumes of Ringer lactate solution via the tail artery. Three hours later, we measured resting O2 consumption (VO2) by an open flow method and ventilation (VE) by the barometric method. Hemodilution to 80–90, 70–80, or 60–70% of the starting hematocrit and hemoglobin values had no major effects on VO2, VE, or mean arterial blood pressure (MAP). A 50–60% hemodilution reduced VO2 and MAP, with a modest increase in VE; the rats were hypocapnic, with normal PaO2. Infusion of vasopressin in a dosage sufficient to increase MAP to the basal value resulted in a reduction in VE, a further drop in VO2, and a return to normocapnia. Three days after hemodilution, hematocrit and hemoglobin were still low but ventilatory and metabolic parameters were normal. In conclusion, in this rat model of anemic hypoxia, 1) hypometabolism occurred without a drop in PaO2, implying that its manifestation does not require activation of the carotid body, and 2) the transient hypocapnia resulted from the VE stimulating effects of the hypotension.
Cerebellar modulation of ventilatory response to progressive hypercapnia
Authors: Xu F. , Owen J. , Frazier D. T.
Published: December 2017

The cerebellar contribution to the ventilatory response to progressive hypercapnia was examined in 18 anesthetized tracheotomized spontaneously breathing cats. The absolute values for minute ventilation (VE), tidal volume (VT), respiratory frequency (f), inspiratory duty cycle (TI/TT), and mean inspiratory flow (VT/TI) were measured. Progressive hypercapnia [35–65 Torr end-tidal PCO2 (PETCO2)] was induced using the rebreathing method. The respiratory variables at each level of PETCO2 and the slopes of ventilatory (VT and f) responses to hypercapnia were compared across the intact, decerebellate, and decerebellate-vagotomized preparations. In 12 cats, decerebellation preceded vagotomy, and in 6 cats the order of the surgical procedures was reversed. The results show that, compared with intact control, decerebellation had little effect on respiratory variables when PETCO2 was 30–35 Torr. However, during a hypercapneic challenge (40–65 Torr PETCO2), VE and the slope of the VE response were significantly reduced. Bilateral vagotomy increased VT and decreased f but failed to alter the ventilatory response in the PETCO2 range of 35–55 Torr. However, combination of decerebellation and vagotomy, regardless of the surgical order, severely blunted VE (35–65 Torr PETCO2) and the slopes of VE, VT and f responses. When decerebellation followed vagotomy, significant decreases in VT (absolute values and slopes) were noted with little further alteration in f response. We conclude that the cerebellum and its interaction with the vagus nerves play a facilitatory or disinhibitory role in the ventilatory responses to hypercapnia.
Protein accumulation in cerebrospinal fluid during -90 degrees head-down tilt in rabbit
Authors: Wen T. S. , Randall D. C. , Zolman J. F.
Published: December 2017

Plasma proteins are only somewhat larger than the intercellular spaces of the cerebral microvessels that constitute the blood-brain barrier or of the choroid plexus villi that elaborate cerebrospinal fluid (CSF). We hypothesized that the integrity of these barriers in anesthetized rabbits might be compromised during head-down tilt (HDT). Plasma protein and osmolality, hematocrit, and CSF protein concentration were compared in rabbits exposed to 1 h of HDT (n = 20) and prone rabbits (n = 10). In addition, the concentration of trypan blue dye, injected intravenously at the end of HDT or the prone position, was measured in brain homogenate. Finally, arterial blood pressure was measured via a catheterized carotid artery. HDT disrupted the barrier between blood and CSF, as indicated by a significantly (P < 0.01) greater brain trypan blue concentration in the HDT rabbits [172.2 +/- 14.4 (SD) micrograms/g dry wt] than in the prone rabbits (29.8 +/- 4.4 micrograms/g dry wt). Moreover CSF protein 5 min after HDT onset was significantly increased compared with control in HDT rabbits (54.6 +/- 1.9 vs. 81.4 +/- 5.2 mg/dl; n = 8) but not in prone rabbits (55.6 +/- 2.7 vs. 57.2 +/- 5.0 mg/dl; n = 6). Changes in the plasma protein-to-hematocrit ratio in the HDT animals, but not in the prone animals, were also compatible with a loss of fluid from the vascular compartment.(ABSTRACT TRUNCATED AT 250 WORDS)
5-HT modulates noncholinergic contraction in guinea pig airways in vitro by prejunctional 5-HT1-like receptor
Authors: Pype J. L. , Verleden G. M. , Demedts M. G.
Published: December 2017

5-Hydroxytryptamine (5-HT) has been demonstrated to cause both constriction and relaxation of guinea pig airways, partly through direct action on airway smooth muscle and partly through postganglionic facilitation of cholinergic neurotransmission. We performed an in vitro study to investigate whether 5-HT can modulate the noncholinergic contraction in guinea pig airways due to release of neuropeptides from airway sensory nerves. In the presence of atropine (1 microM), ketanserin (10 microM), and indomethacin (10 microM), 5-HT (0.1–100 microM) produced concentration-dependent inhibition of electrical field stimulation-induced noncholinergic contraction with maximal inhibition of approximately 72 +/- 4%. Tropisetron (ICS-205–930, 1 microM), a 5-HT3 and 5-HT4 receptor antagonist, was unable to prevent the inhibition produced by 5-HT. Methiothepin (1–100 nM), a 5-HT1 and 5-HT2 receptor antagonist, produced a concentration-dependent inhibition of the effect of 5-HT (1 microM) with a 50% inhibition concentration value of 66 nM. 5-HT (100 microM) had no effect on the cumulative concentration-response relationship to exogenous substance P (10 nM-10 microM). The concentration of agonist causing 35% inhibition of the noncholinergic contraction (EC35) was calculated, and a rank order of potency was established: 5-carboxamidotryptamine (EC35 = 0.24 microM) > 5-HT (EC35 = 0.77 microM) > 8-hydroxy-2-(dipropylamino)tetralin (EC35 = 8.1 microM) > sumatriptan (EC35 = 18 microM). We conclude that 5-HT concentration dependently modulates noncholinergic contraction in guinea pig airways in vitro by a prejunctional mechanism. This effect is probably mediated through a 5-HT1-like receptor; however, the exact subtype remains to be elucidated.
Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung
Authors: Sugiura M. , McCulloch P. R. , Wren S. , Dawson R. H. , Froese A. B.
Published: December 2017

Both ventilator pattern and neutrophil activation influence lung injury in adult respiratory distress syndrome (ARDS). We therefore questioned whether ventilator pattern independently affects neutrophil accumulation and function in early ARDS. Thirty-five New Zealand White rabbits were anesthetized, paralyzed, and prepared using sterile techniques. Fifteen surfactant-depleted animals were randomized and ventilated for 4 h using high-frequency oscillatory ventilation (HFO) at 15 Hz with an inspired O2 fraction = 1.0 and arterial PO2 (PaO2) > 400 Torr (a pattern known to reverse atelectasis) or conventional mechanical ventilation (CMV) with PaO2 = 80–100 Torr (a pattern with some atelectasis despite positive end-expiratory pressure). Eight normal animals on CMV with PaO2 > 400 Torr served as a reference group (NorCMV). NorCMV animals progressively increased circulating polymorphonuclear neutrophil (PMN) numbers and had minor pressure-volume curve alterations but no other significant changes. Lavaged CMV animals developed the characteristic gas exchange and marked pressure-volume curve abnormalities of ARDS. Circulating PMNs remained constant but developed decreased chemotactic activity, whereas lung neutrophil numbers increased significantly (P = 0.0002) and had substantially enhanced chemiluminescence (P = 0.0003 vs. NorCMV animals). Although lavaged HFO animals accumulated an intermediate number of lung neutrophils (lung myeloperoxidase > NorCMV animals; P = 0.003), the chemiluminescence and chemotaxis of these PMNs were the same as in cells from NorCMV animals. We concluded that both the degree of neutrophil activation and lung injury can be minimized by preventing cyclic alveolar/airway expansion and collapse in the surfactant-deficient lung by use of appropriate ventilator patterns.
Alteration of plasma endothelin-1 by exercise at intensities lower and higher than ventilatory threshold
Authors: Maeda S. , Miyauchi T. , Goto K. , Matsuda M.
Published: December 2017

The purpose of this study was to investigate whether the release of endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, is induced by exercise. Venous plasma concentrations of ET-1 were measured by sandwich-enzyme immunoassay before and after endurance exercise with a cycle ergometer at different intensities. Male intercollegiate athletes participated in the study and performed cycle ergometer exercise of 30 min duration at intensities of 90 or 130% of their individual ventilatory threshold (VT). The plasma concentration of ET-1 was slightly but significantly increased after exercise at 90% and markedly increased after exercise at 130% of individual VT. The increase in ET-1 was greatest 30 min after exercise at both intensities. It was first demonstrated that the plasma concentration of ET-1 was significantly increased after exercise: the greater the intensity, the greater the extent of the increase in plasma ET-1 concentration. However, the precise physiological roles of ET-1 during exercise remain to be elucidated.
Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia
Authors: Li H. , Chen S. J. , Chen Y. F. , Meng Q. C. , Durand J. , Oparil S. , Elton T. S.
Published: December 2017

To test the hypothesis that endothelin (ET)-1 synthesis and ET receptor levels are increased selectively in the lung of rats with chronic hypoxic pulmonary hypertension, the current study examined the effects of exposure to chronic hypoxia (10% O2, 1 atm, 4 wk) on pulmonary arterial pressure, ET-1 levels in plasma and lung, and ET-1 and ETA and ETB receptor mRNA levels in lung, heart, pulmonary artery, aorta, kidney, spleen, and liver. Hypoxic exposure was associated with increases in pulmonary arterial pressure, plasma ET-1 levels, ET-1 mRNA in lung and pulmonary artery, and ET-1 stores and ETA and ETB receptor mRNA levels in lung. In thoracic aorta and the four heart chambers, ETA and ETB receptor mRNA levels were increased, but ET-1 mRNA levels were unchanged from air control levels. No change in ET-1 or ET receptor mRNA levels was seen in organs perfused by the systemic vascular bed, except in liver, where ETA receptor mRNA levels were decreased. The findings of concomitant increases in gene transcript levels for ET-1 and the ETA and ETB receptors in lung, but not in the great vessels or any other organ examined, are consistent with the hypothesis that increased ET-1 synthesis in the lung contributes to pulmonary vascular remodeling and the maintenance of chronic hypoxic pulmonary hypertension.
Reduction and accumulation of methylene blue by the lung
Authors: Bongard R. D. , Krenz G. S. , Linehan J. H. , Roerig D. L. , Merker M. P. , Widell J. L. , Dawson C. A.
Published: December 2017

We studied the disposition of methylene blue added to the perfusate passing through isolated perfused rabbit lungs. Experiments were carried out in a recirculating or single-pass mode, the latter with either a steady infusion or bolus injection of the dye in its blue oxidized form (MB+) or in its colorless reduced leukomethylene blue form (MBH). The recirculation experiments revealed that the dye was taken up by the lungs and that a substantial fraction (approximately 16%) of the MB+ entering the pulmonary artery was reduced before it emerged from the pulmonary veins. Sequestration of the dye by the lungs was a relatively slow process, and the blue color of the lungs at a time when there was little dye left in the perfusate suggests that much of the sequestered dye was in the oxidized form. The results from the single-pass bolus and steady infusion experiments suggest that MBH diffuses rapidly between perfusate and tissue and that it is more soluble in the tissue than in the perfusates used in the study. In this context, the concept of “solubility” includes the impact of the rapidly equilibrating associations of the dye with the perfusate albumin and tissue components. The observed characteristics of the disposition of the methylene blue within the lungs and the rapid rate of its reduction on passage through the lungs suggest that it may be useful to evaluate the possibility that changes in reduction, uptake, and/or sequestration rates may reflect alterations in the metabolic function of the lungs.
Compared with crystalloid, colloid therapy slows progression of extrapulmonary tissue injury in septic sheep
Authors: Morisaki H. , Bloos F. , Keys J. , Martin C. , Neal A. , Sibbald W. J.
Published: December 2017

We tested the hypothesis that the type of fluid infused to chronically maintain intravascular volumes would modify both microvascular integrity and cellular structure in extrapulmonary organs in hyperdynamic sepsis. After cecal ligation and perforation, awake sheep were treated for 48 h with 10% pentastarch (n = 9), 10% pentafraction (Du Pont Critical Care; n = 8), or Ringer lactate (n = 8) titrated to maintain a constant left atrial pressure. After 48 h of fluid therapy, biopsy samples were taken from the left ventricle and gastrocnemius for electron microscopy. At this time, all groups demonstrated a similar hyperdynamic circulatory response, increased systemic O2 utilization and organ blood flows, measured by radioactive microsphere injection. However, greater capillary luminal areas with less endothelial swelling and less parenchymal injury were found in septic sheep treated with pentastarch vs. Ringer lactate infusion in both muscle types. Pentafraction showed few benefits in study end points over pentastarch. Thus, we conclude that chronic intravascular volume resuscitation of hyperdynamic sepsis with pentastarch ameliorated the progression of both microvascular and parenchymal injury. These findings indicate that microvascular surface area for tissue O2 exchange in sepsis may be better preserved with chronically infused colloid, resulting in less parenchymal injury.
Effect of detraining on GLUT-4 protein in human skeletal muscle
Authors: McCoy M. , Proietto J. , Hargreves M.
Published: December 2017

The present study was undertaken to examine the effect of 10 days of detraining levels of GLUT-4 protein expression and citrate synthase (CS) activity in the vastus lateralis of trained men. During the course of normal training, seven endurance-trained (T) men and eight age- and weight-matched active but untrained (UT) men underwent an oral glucose tolerance test (OGTT) after an overnight fast. Muscle samples were obtained from the vastus lateralis by needle biopsy for measurement of GLUT-4 protein and CS activity. The tests were repeated on six of the T subjects after 10 days of detraining (DT men). The area under the insulin response curve during OGTT was lower in T men than in DT and UT men (22.4 +/- 2.8, 32.1 +/- 5.9, and 39.9 +/- 4.7 x 10(-3) pmol.l-1.min-1, respectively; P < 0.05). There were no differences between groups in the glucose responses to OGTT. GLUT-4 protein levels and CS activity were higher in T men than in DT and UT men (GLUT-4: 4.37 +/- 0.40, 2.92 +/- 0.53, and 1.71 +/- 0.22 arbitrary standard units and CS: 47.12 +/- 4.75, 33.63 +/- 3.98, and 24.51 +/- 2.97 mumol.min-1.g-1, respectively; both P < 0.05). Muscle GLUT-4 protein content was correlated with CS activity in all three groups (r = 0.64, 0.68, and 0.96 for UT, T, and DT men, respectively). These results suggest that muscle GLUT-4 protein content and oxidative capacity undergo parallel adaptations after detraining in previously well-trained men.
Efficiency function: improvement of classical bioheat approach
Authors: Brinck H. , Werner J.
Published: December 2017

In view of the complex vascular architecture and the intricate physical heat transfer processes in the human body, convective heat transfer via the blood is generally described by simple substitutional processes (“non-vascular models”). The classical “bioheat” approach of Pennes (J. Appl. Physiol. 1: 93–122, 1948), defining the heat flow to or from the tissue as being proportional to the product of perfusion rate and the difference of arterial and tissue temperature, has been seriously questioned after having been used for > 40 yr in many applications. In our laboratory, we have at our disposal a complex three-dimensional vascular model for the special case of tissue in a human extremity. This was used to test the performance of simple nonvascular models. It turned out that the Pennes approach may deliver acceptable results if the body is in the thermoneutral zone or if heat stress acts uniformly on the whole body. However, when cold stress or local hyperthermia is present, unreliable results must be expected. As the vascular model is not generally practicable because of its extreme complexity, we offer the efficiency function concept as a simple way of correcting the classical bioheat approach by factor multiplication. Efficiency function is determined as a function of perfusion rate and tissue depth in a way that compensates for the deficiencies of the Pennes bioheat term. The results are reasonable compared with those of the vascular model and experimental results.