bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible sensory receptor of nonadrenergic inhibitory nervous system
Authors: Ichinose M. , Inoue H. , Miura M. , Yafuso N. , Nogami H. , Takishima T.
Published: December 2017

To determine the sensory receptor of the nonadrenergic inhibitory nervous system (NAIS), 22 cats were anesthetized and serotonin was continuously administered (50–250 micrograms.kg-1.min-1 iv) to increase pulmonary resistance (RL) to 377 +/- 57% (SE) of the control value. We then 1) mechanically irritated the trachea, 2) intravenously administered capsaicin (5 micrograms/kg), or 3) induced hypoxia (arterial PO2 30–40 Torr) to stimulate irritant and bronchial C-fiber receptors, pulmonary C-fiber receptors, or the carotid body (chemoreceptors), respectively. After treatment with atropine (3 mg/kg iv) and propranolol (2 mg/kg iv), the serotonin-induced change in RL was reduced by 58.6 +/- 14.3% by mechanical irritation and 63.3 +/- 12.1% by intravenous capsaicin. However, hypoxia produced no dilatation of the airways. In further experiments, we employed capsaicin inhalation to stimulate bronchial C-fiber receptors. Inhaled capsaicin (0.1%, for 5 breaths) also reduced RL by 79.2 +/- 9.2% of the elevated value, after atropine and propranolol. Treatment with a ganglionic blocking agent, hexamethonium (2 mg/kg iv), abolished bronchodilator responses, implying that a reflex pathway through vagal nerves is involved in this phenomenon. These results suggest that pulmonary and bronchial C-fiber receptors may be involved as sensory receptors in NAIS reflex bronchodilatation.
Gastrointestinal transit during mild exercise
Authors: Keeling W. F. , Martin B. J.
Published: December 2017

Although exercise is often recommended as therapy for constipation, almost nothing is known of the effects of exercise on rates of movement of material in the gastrointestinal tract. In this study we investigated the influence of mild exercise on transit of a liquid meal from the mouth to the large intestine. Orocecal transit time was determined by a consistent elevation of H2 concentration in a rebreathing apparatus after ingestion of 30 g lactulose; the lactulose was part of a 360-kcal, 350-ml liquid meal. Comparison of transit time was made, in 12 young healthy subjects, between seated rest and a treadmill walk at 5.6 km/h up a 2% grade. The walk elevated heart rate from 64 +/- 4 to 109 +/- 5 beats/min, O2 uptake (VO2) from 0.29 +/- 0.02 to 1.20 +/- 0.07 l/min STPD, and final rectal temperature from 37.0 +/- 0.1 to 38.3 +/- 0.1 degrees C (all P less than 0.01). Exercise speeded transit of the liquid meal, with mean rises in H2 concentration taking place 66 +/- 10 min after ingestion at rest, compared with 44 +/- 6 min after food intake during exercise (P less than 0.02). H2 concentrations in the rebreathing apparatus showed similar base lines in the two experiments, and quantitative increases in H2 concentration, although shifted in time by exercise, were otherwise identical. Subjects with the slowest resting transit rates showed the largest exercise effects (r = 0.79, P less than 0.05). These results indicate that mouth-to-cecum transit of at least the first portion of a liquid meal-based nonabsorbable carbohydrate marker is significantly accelerated during mild exercise.
Ozone exposure alters tracheobronchial mucociliary function in humans
Authors: Foster W. M. , Costa D. L. , Langenback E. G.
Published: December 2017

Mucociliary function is a primary defense mechanism of the tracheobronchial airways, and yet the response of this system to an inhalational hazard, such as ozone, is undefined in humans. Utilizing noninvasive techniques to measure deposition and retention of insoluble radiolabeled particles on airway mucous membranes, we studied the effect on mucus transport of 0.2 and 0.4 ppm ozone compared with filtered air (FA) in seven healthy males. During 2-h chamber exposures, subjects alternated between periods of rest and light exercise with hourly spirometric measurement of lung function. Mechanical and mucociliary function responses to ozone by lung airways appeared concentration dependent. Reduction in particle retention was significant (P less than 0.005) (i.e., transport of lung mucus was increased during exposure to 0.4 ppm ozone and was coincident with impaired lung function; e.g., forced vital capacity and midmaximal flow rate fell by 12 and 16%, respectively, and forced expiratory volume at 1 s by 5%, of preexposure values). Regional analysis indicated that mucus flow from distal airways into central bronchi was significantly increased (P less than 0.025) by 0.2 ppm ozone. This peripheral effect, however, was buffered by only a marginal influence of 0.2 ppm ozone on larger bronchi, such that the resultant mucus transport for all airways of the lung in aggregate differed only slightly from FA exposures. These data may reflect differences in regional diffusion of ozone along the respiratory tract, rather than tissue sensitivity. In conclusion, mucociliary function of humans is acutely stimulated by ozone and may result from fluid additions to the mucus layer from mucosal and submucosal secretory cells and/or alteration of epithelial permeability.
Regional lung density and blood volume in nonsmoking and smoking subjects measured by PET
Authors: Brudin L. H. , Rhodes C. G. , Valind S. O. , Wollmer P. , Hughes J. M.
Published: December 2017

Regional lung density (DL) and regional fractional pulmonary blood volume (VB) were measured quantitatively during tidal breathing in 30 healthy supine subjects (15 smokers and 15 nonsmokers) in a 1.7-cm-thick midthoracic cross section using positron emission tomography (PET) and 11CO (inhaled)-labeled erythrocytes. Regional alveolar volume (VA), extravascular lung density (DEV), and relative alveolar size (Valv = VA/DEV) were calculated. For the nonsmokers, mean values (+/- SD between subjects) for the right lung were as follows: DL, 0.28 +/- 0.03 g/cm3; DEV, 0.10 +/- 0.02 g/cm3; and Valv, 7.1 +/- 1.9 ml/g lung tissue. In the smoking subjects DEV (right plus left lung) was 16% higher. No significant difference in VB between smokers and nonsmokers was found. The differences in DEV and VB between right and left lung were not significant. Mean values (+/- SD) of the dorsal-to-ventral ratios calculated for the right lung in the nonsmokers were as follows: DL, 1.34 +/- 0.16; VA, 0.90 +/- 0.05; VB, 1.52 +/- 0.26; DEV, 1.10 +/- 0.17; and Valv, 0.85 +/- 0.19. Almost identical ratios were found in the smokers. The influence of overall thoracic expansion was investigated in one subject restudied during voluntary hyperinflation and during positive end-expiratory pressure.
Effects of acute hyperinflation on chest wall mechanics in dogs
Authors: Decramer M. , Jiang T. X. , Demedts M.
Published: December 2017

We studied chest wall mechanics at functional residual capacity (FRC) and near total lung capacity (TLC) in 14 supine anesthetized and vagotomized dogs. During breathing near TLC compared with FRC, tidal volume decreased (674 +/- 542 vs. 68 +/- 83 ml; P less than 0.025). Both inspiratory changes in gastric pressure (4.5 +/- 2.5 vs. -0.2 +/- 2.0 cmH2O; P less than 0.005) and changes in abdominal cross-sectional area (25 +/- 17 vs. -1.0 +/- 4.2%; P less than 0.001) markedly decreased; they were both often negative during inspiration near TLC. Parasternal intercostal shortening decreased (-3.0 +/- 3.7 vs. -2.0 +/- 2.7%), whereas diaphragmatic shortening decreased slightly more in both costal and crural parts (costal -8.4 +/- 2.9 vs. -4.3 +/- 4.1%, crural -22.8 +/- 13.2 vs. -10.0 +/- 7.5%; P less than 0.05). As a result, the ratio of parasternal to diaphragm shortening increased near TLC (0.176 +/- 0.135 vs. 0.396 +/- 0.340; P less than 0.05). Electromyographic (EMG) activity in the parasternals slightly decreased near TLC, whereas the EMG activity in the costal and crural parts of the diaphragm slightly increased. We conclude that 1) the mechanical outcome of diaphragmatic contraction near TLC is markedly reduced, and 2) the mechanical outcome of parasternal intercostal contraction near TLC is clearly less affected.
Force-velocity properties of fatigue-resistant units in cat fast-twitch muscle after fatigue
Authors: Hatcher D. D. , Luff A. R.
Published: December 2017

The isometric and force-velocity properties of an identified and uniform population of fast-twitch, fatigue-resistant (FR) fibers within the flexor digitorum longus (FDL) muscle were investigated before, immediately after, and during recovery from a fatiguing repetitive isometric stimulus regime (40 Hz for 330 ms every s for 180 s) in the anesthetized cat. It was necessary to determine the smallest fraction of muscle that had the same force-velocity properties as the whole muscle. This was approximately 15% for FDL; if the fraction was less, the maximum speed of shortening was depressed and the a/Po value increased. Motor units were enlarged by partial denervation of the muscle, causing the intact motoneurons to sprout and incorporate more muscle fibers; FR units showed the greatest increase. Immediately after the fatigue regime, maximum isometric tetanic tension declined to 67% but subsequently recovered to 90% of the control value by the end of the 60-min recovery period. Maximum speed of shortening dropped to 71% of the control but after 30 min had recovered and did not differ significantly from control values. It is concluded that the capacity for recovery from fatigue is greater for FR units than for a whole muscle, which also contains fast-fatiguable units, and that the mechanisms involved in the recovery of the maximum isometric tension and maximum speed of shortening are independently regulated.
Mediation of reduced ventilatory response to exercise after endurance training
Authors: Casaburi R. , Storer T. W. , Wasserman K.
Published: December 2017

To investigate the mechanism by which ventilatory (VE) demand is modulated by endurance training, 10 normal subjects performed cycle ergometer exercise of 15 min duration at each of four constant work rates. These work rates represented 90% of the anaerobic threshold (AT) work rate and 25, 50, and 75% of the difference between maximum O2 consumption and AT work rates for that subject (as determined from previous incremental exercise tests). Subjects then underwent 8 wk of strenuous cycle ergometer exercise for 45 min/day. They then repeated the four constant work rate tests at work rates identical to those used before training. During tests before and after training, VE and gas exchange were measured breath by breath and rectal temperature (Tre) was measured continuously. A venous blood sample was drawn at the end of each test and assayed for lactate (La), epinephrine (EPI), and norepinephrine (NE). We found that the VE for below AT work was reduced minimally by training (averaging 3 l/min). For the above AT tests, however, training reduced VE markedly, by an average of 7, 23, and 37 l/min for progressively higher work rates. End-exercise La, NE, EPI, and Tre were all lower for identical work rates after training. Importantly, the magnitude of the reduction in VE was well correlated with the reduction in end-exercise La (r = 0.69) with an average decrease of 5.8 l/min of VE per milliequivalent per liter decrease in La. Correlations of VE with NE, EPI, and Tre were much less strong (r = 0.49, 0.43, and 0.15, respectively).
Extrathoracic airway stability during resistive loading in preterm infants
Authors: Duara S. , Gerhardt T. , Bancalari E.
Published: December 2017

Extrathoracic airway (ETA) stability was tested in 10 preterm infants during sleep with a drop in intraluminal pressure produced by the application of an external inspiratory flow-resistive load (IRL, 125 cmH2O.1–1.s at 1 l/min). An increase in total pulmonary resistance was sought as the measure of airway narrowing. The role of the ETA in the increased pulmonary resistance with loading was examined by testing the same infants while endotracheally intubated and after extubation. Total pulmonary resistance decreased with loading during the intubated studies (102.5 +/- 41.2 to 82.4 +/- 33.3 cmH2O.1–1.s, P less than 0.05), whereas a significant increase in pulmonary resistance was seen with loading in the extubated studies (101 +/- 58.1 to 128 +/- 68.6 cmH2O.1–1.s, P less than 0.01). Intraluminal pressure in the ETA, measured by the lowest proximal airway pressure, fell significantly with loading in both conditions, with values changing from -0.7 +/- 0.3 to -4.7 +/- 2.7 cmH2O in the intubated infants and from -0.9 +/- 0.3 to -4.6 +/- 0.9 cmH2O) in the extubated infants (P less than 0.01). The results suggest ETA narrowing with loading in extubated infants despite the absence of overt obstructive apnea. Measurements of total pulmonary resistance with IRL can be used as a simple test of ETA stability.
Effect of high-frequency ventilation on lung mechanics at high transpulmonary pressure
Authors: Weinmann G. G. , Huang Y. C. , Mitzner W.
Published: December 2017

The different tidal volumes and frequencies of high-frequency ventilation (HFV) compared with conventional mechanical ventilation (CMV) may have different effects on lung mechanics. To test this hypothesis, we compared the effects of 3 h of HFV and CMV on total lung capacity (TLC), functional residual capacity (FRC), the shape of the pressure-volume (PV) curve (%V10), and dynamic compliance (Cdyn), as well as venous admixture and alveolar-arterial O2 gradient. We studied a total of 12 dogs at lung inflations equivalent to 15 cmH2O positive end-expiratory pressure (PEEP) (group I) and 8 dogs at lung inflations equivalent to 0 cmH2O PEEP (group II). For CMV, we used a standard-volume ventilator at a mean tidal volume of 13.8 ml/kg. For HFV, we used an oscillator-type ventilator at 15 Hz and an average tidal volume of 4.3 ml/kg. Our results showed that ventilation with 3 h of PEEP raised lung volume, and lung volumes on HFV were higher than those on CMV in both groups. Specifically, in group I, the volume during ventilation rose on both CMV (150 ml) and HFV (250 ml). These volume changes persisted beyond the ventilation period, such that TLC was unchanged on CMV but had risen 200 ml on HFV. FRC also rose 200 and 300 ml after HFV and CMV, respectively. In group II, the volume during ventilation fell 100 ml on CMV and rose slightly (40 ml) on HFV. TLC and FRC both tended to fall more on CMV.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanics in rats by end-inflation occlusion and single-breath methods
Authors: Saldiva P. H. , Cardoso W. V. , Caldeira M. P. , Zin W. A.
Published: December 2017

In six mechanically ventilated anesthetized (pentobarbital sodium, 30 mg/kg) paralyzed rats (187–253 g body wt) volume, airflow, and tracheal, esophageal, and transpulmonary pressures were measured. Respiratory system elastic and resistive properties were partitioned into their lung and chest wall components after end-inflation occlusion of the airways subsequent to constant-flow inspirations and during relaxed expiration ensuing release of occlusion. The values provided by both methods were similar. Mean respiratory system, lung, and chest wall elastances amounted to, respectively, 5.536, 3.440, and 2.097 cmH2O.ml-1. Mean values of intrinsic respiratory system, pulmonary, and chest wall resistances (at flows of 3.5 ml.s-1) were 0.235, 0.144, and 0.091 cmH2O.ml-1.s, respectively. Resistive pressure-flow relationships for the respiratory system, lung, and chest wall were also determined during the entire tidal expiration. A linear relationship was found for the former, whereas power functions best described the others: the pulmonary pressure-flow relationship exhibited an upward concavity and that for the chest wall presented an upward convexity.
Different effects of halothane on diaphragm and hindlimb muscle in rats
Authors: Dureuil B. , Viires N. , Nivoche Y. , Fiks M. , Pariente R. , Aubier M. , Desmonts J. M.
Published: December 2017

The effects of halothane administration on diaphragm and tibialis anterior (TA) muscle were investigated in 30 anesthetized mechanically ventilated rats. Diaphragmatic strength was assessed in 17 rats by measuring the abdominal pressure (Pab) generated during supramaximal stimulation of the intramuscular phrenic nerve endings at frequencies of 0.5, 30, and 100 Hz. Halothane was administered during 30 min at a constant minimum alveolar concentration (MAC): 0.5, 1, and 1.5 MAC in three groups of five rats. For each MAC, Pab was significantly reduced for all frequencies of stimulation except at 100 Hz during 0.5 MAC halothane exposure. The effects of halothane (0.5, 1, and 1.5 MAC) on diaphragmatic neuromuscular transmission were assessed in five other rats by measuring the integrated electrical activity of the diaphragm (Edi) during electrical stimulation of the phrenic nerve. No change in Edi was observed during halothane exposure. In five other rats TA contraction was studied by measuring the strength of isometric contraction of the muscle during electrical stimulation of its nerve supply at different frequencies (0.5, 30, and 100 Hz). Muscle function was unchanged during administration of halothane in a cumulative fashion from 0.5 to 1.5 MAC. These results demonstrate that halothane does not affect hindlimb muscle function, whereas it had a direct negative inotropic effect on rat diaphragmatic muscle.
Lung endothelial and epithelial permeability after platelet-activating factor
Authors: Bolin R. W. , Martin T. R. , Albert R. K.
Published: December 2017

We investigated whether platelet-activating factor (PAF) increased epithelial or endothelial permeability in isolated-perfused rabbit lungs. PAF was either injected into the pulmonary artery or instilled into the airway of lungs perfused with Tyrode's solution containing 1% bovine serum albumin. The effect of adding neutrophils or platelets to the perfusate was also tested. Perfusion was maintained 20–40 min after adding PAF and then a fluid filtration coefficient (Kf) was determined to assess vascular permeability. At the end of each experiment, one lung was lavaged, and the lavagate protein concentration (BALP) was determined. Wet weight-to-dry weight ratios (W/D) were determined on the other lung. PAF added to the vascular space increased peak pulmonary arterial pressure (Ppa) from 13.5 +/- 3.1 (mean +/- SE) to 24.2 +/- 3.3 cmH2O (P less than 0.05). The effect was amplified by platelets [Ppa to 70.8 +/- 8.0 cmH2O (P less than 0.05)] but not by neutrophils [Ppa to 22.0 +/- 1.4 cmH2O (P less than 0.05)]. Minimal changes in Ppa were observed after instilling PAF into the airway. The Kf, W/D, and BALP of untreated lungs were not increased by injecting PAF into the vasculature or into the air space. The effect of PAF on Kf, W/D, and BALP was unaltered by adding platelets or neutrophils to the perfusate. PAF increases intravascular pressure (at a constant rate of perfusion) but does not increase epithelial or endothelial permeability in isolated-perfused rabbit lungs.
Effects of prolonged exercise in highly trained traumatic paraplegic men
Authors: Gass G. C. , Camp E. M.
Published: December 2017

This study investigated the cardiovascular and metabolic responses to prolonged wheelchair exercise in a group of highly trained, traumatic paraplegic men. Six endurance-trained subjects with spinal cord lesions from T10 to T12/L3 underwent a maximal incremental exercise test in which they propelled their own track wheelchairs on a motor-driven treadmill to exhaustion to determine maximal O2 uptake (VO2max) and related variables. One week later each subject exercised in the same wheelchair on a motorized treadmill at 60–65% of VO2max for 80 min in a thermoneutral environment (dry bulb 22 degrees C, wet bulb 17 degrees C). Approximately 10 ml of venous blood were withdrawn both 20 min and immediately before exercise (0 min), after 40 and 80 min of exercise, and 20 min postexercise. Venous blood was analyzed for hematocrit (Hct), hemoglobin (Hb), and lactate, and the separated plasma was analyzed for glucose, K+, Na+, Cl-, free fatty acid (FFA), and osmolality. VO2, CO2 production (VCO2), minute ventilation (VE), respiratory exchange ratio (R), net efficiency, and wheelchair strike rate were determined at four intervals throughout the exercise period. Data were analyzed with an analysis of variance repeated-measures design and a Scheffe post hoc test. VO2max was 47.5 +/- 1.8 (SE) ml.min-1.kg-1 with maximal VE BTPS and maximal heart rate (HR) being 100.1 +/- 3.8 l/min and 190 +/- 1 beats/min, respectively. During prolonged exercise there were no significant changes in VO2, VCO2, VE, R, net efficiency, wheelchair strike rate, and lactate, glucose, and Na+ concentrations. Significant increases occurred in HR, FFA, K+, Cl-, osmolality, Hb, and Hct throughout exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Autonomic nervous control of postprandial hemodynamic changes at rest and upright exercise
Authors: Kelbaek H. , Munck O. , Christensen N. J. , Godtfredsen J.
Published: December 2017

Postprandial hemodynamic changes were studied in healthy subjects at rest and during exercise in the upright position with and without autonomic blockade of the heart. At rest cardiac output increased 61% mostly because of a stroke volume increase accomplished by left ventricular end-diastolic dilation. These changes seemed to be dependent on the autonomic nervous system, whereas the postprandial heart rate increase did not. During exercise cardiac output was 23% higher after food intake due to a rise in both stroke volume and heart rate. These changes were apparently under influence of the autonomic nervous system, whereas left ventricular dilation was not. The present findings indicate that most of the postprandial changes in the central circulation are under control of the autonomic nervous system.
Interindividual variation in hypoxic ventilatory response: potential role of carotid body
Authors: Vizek M. , Pickett C. K. , Weil J. V.
Published: December 2017

There is considerable interindividual variation in ventilatory response to hypoxia in humans but the mechanism remains unknown. To examine the potential contribution of variable peripheral chemorecptor function to variation in hypoxic ventilatory response (HVR), we compared the peripheral chemoreceptor and ventilatory response to hypoxia in 51 anesthetized cats. We found large interindividual differences in HVR spanning a sevenfold range. In 23 cats studied on two separate days, ventilatory measurements were correlated (r = 0.54, P less than 0.01), suggesting stable interindividual differences. Measurements during wakefulness and in anesthesia in nine cats showed that although anesthesia lowered the absolute HVR it had no influence on the range or the rank of the magnitude of the response of individuals in the group. We observed a positive correlation between ventilatory and carotid sinus nerve (CSN) responses to hypoxia measured during anesthesia in 51 cats (r = 0.63, P less than 0.001). To assess the translation of peripheral chemoreceptor activity into expiratory minute ventilation (VE) we used an index relating the increase of VE to the increase of CSN activity for a given hypoxic stimulus (delta VE/delta CSN). Comparison of this index for cats with lowest (n = 5, HVR A = 7.0 +/- 0.8) and cats with highest (n = 5, HVR A = 53.2 +/- 4.9) ventilatory responses showed similar efficiency of central translation (0.72 +/- 0.06 and 0.70 +/- 0.08, respectively). These results indicate that interindividual variation in HVR is associated with comparable variation in hypoxic sensitivity of carotid bodies. Thus differences in peripheral chemoreceptor sensitivity may contribute to interindividual variability of HVR.
Effect of hyperoxia on glutathione levels and glutamic acid uptake in endothelial cells
Authors: Deneke S. M. , Steiger V. , Fanburg B. L.
Published: December 2017

Intracellular glutathione was increased by 80% after exposure of bovine pulmonary arterial endothelial cells to 80% O2 (hyperoxia) for 24 h. No change in glutathione occurred in cells exposed to hypoxia (3% O2) for a corresponding period of time. The rate of uptake of [3H]glutamic acid also increased by 35–55% after 24 h of exposure of cells to hyperoxia, whereas exposure to hypoxia had no effect on the [3H]glutamic acid uptake. The increase in glutamic acid uptake reflected a specific effect on amino acid transport systems rather than a change in cell membrane permeability. The major portion of the increased uptake was inhibited by the elimination of sodium and the addition of the competitive inhibitor, cystine, to the incubation medium. Thus increases in glutamic acid uptake parallel increases in cellular glutathione, and glutamic acid may be a regulating factor in the increase in glutathione after exposure to hyperoxia.
Chemoreflex modulation of ventilatory dynamics during exercise in humans
Authors: Ward S. A. , Blesovsky L. , Russak S. , Ashjian A. , Whipp B. J.
Published: December 2017

The precision of arterial blood gas homeostasis following a change of work rate depends on the response kinetics of ventilation. The carotid bodies (CB's) have been proposed as modulators of these kinetics. The present investigation was undertaken to determine whether the effect is specific to CB activation or whether other factors that augment the exercise hyperpnea would produce a similar response. We therefore established the effects of increased CB and central (C) chemoreflex activation on the inspired ventilatory (VI) dynamics for moderate-intensity cycling. Work tests were separately performed with air, 12% O2 to increase CB activity, 100% O2 to “abolish” CB activity, and CO2 in O2 to increase C activity. The time constant of the VI response was substantially shortened by hypoxia (40 s) compared with air breathing (58 s) and increased by 100% O2 (92 s) and, even more so, by CO2 in O2 (101 s). We conclude that increased carotid (but not central) chemoreflex responsiveness speeds the kinetics of the exercise hyperpnea by a process that is not merely the consequence of increased ventilatory drive.
Mechanisms of airway hypercontractility in basenji-greyhound dogs
Authors: Murphy T. M. , Munoz N. M. , Hirshman C. A. , Blake J. S. , Leff A. R.
Published: December 2017

The comparative effects of contractile agonists and physiological stimulation of the tracheal and bronchial smooth muscle (BSM) response were studied isometrically in situ in five Basenji-greyhound (BG) and six mongrel dogs. Frequency-response curves generated by bilateral stimulation of the vagus nerves (0–20 Hz, 15–20 V, 2-ms duration) elicited greater maximal contraction in mongrel trachea (36.8 +/- 8.1 vs. 26.9 +/- 4.0 g/cm; P less than 0.02) and exhibited greater responsiveness in mongrel BSM (half-maximal response to electrical stimulation 3.0 +/- 1.1 vs. 7.0 +/- 0.5 Hz; P less than 0.05) compared with BG dogs. However, muscarinic sensitivity to intravenous methacholine (MCh) was substantially greater in BG dogs; MCh caused contraction greater than 1.5 g/cm at a mean dose of 3.0 X 10(-10) mol/kg for BG dogs compared with 5.1 X 10(-9) mol/kg for mongrel controls (P less than 0.03, Mann-Whitney rank-sum test). In contrast to the muscarinic response, the contractile response elicited by intravenous norepinephrine after beta-adrenergic blockade was similar in trachea and bronchus for both mongrel and BG dogs. Our data confirm previous in vitro demonstration of tracheal hyporesponsiveness in BG dogs and demonstrate that the contraction resulting from efferent parasympathetic stimulation is less in the BG than mongrel dogs. However, postsynaptic muscarinic responsiveness of BG BSM is substantially increased. We conclude that a component of airway responsiveness in BG dogs depends directly on contractile forces generated postsynaptically that are nongeometry dependent, postjunctional, and agonist specific.
Time course adaptations in rat skeletal muscle isomyosins during compensatory growth and regression
Authors: Tsika R. W. , Herrick R. E. , Baldwin K. M.
Published: December 2017

The purpose of this study was to ascertain the time course of change during both compensatory growth (hypertrophy) and subsequent growth regression on myosin isoform expression in rodent fast-twitch plantaris muscle in response to functional overload (induced by removal of synergists). Peak hypertrophy of the plantaris muscle (92%) occurred after 9 wk of overload. After 7 wk of overload regression (induced by a model of hindlimb unweighting), muscle weight returned to within 30% of control values. Myofibril protein content (mg/g muscle) remained relatively constant throughout the overload period but became significantly depressed relative to control values after 7 wk of regression. However, when expressed on a per muscle basis (mg/muscle) no differences existed at this time point (t = 7 wk regression). The distribution of native myosin isoforms in the myofibril protein pool of the overloaded plantaris muscle reflected a progressive increase (23% at t = 9 wk; P less than 0.001) in the relative proportion of slow myosin (Sm). This change was also accompanied by increases in intermediate myosin (Im) as well as the repression of the fast myosin one (Fm1) isoform (P less than 0.001). These shifts in Sm and Fm1 isoform expression were gradually reversed during the regression period, whereas Im remained elevated relative to control values. These adaptive changes in myosin isoform expression during both hypertrophy and regression were further supported by concomitant shifts in both myosin adenosinetriphosphatase (ATPase) activity (decreased during overload) and slow myosin light chain (SLC) expression. However, during regression the changes in myosin isoform expression and myosin ATPase were not as synchronous as they were during overload. Estimation of the mixed myosin heavy chain (MHC) half-life (t 1/2), using a linear model that assumes zero-order synthesis and first-order degradation kinetics, revealed t 1/2 values of approximately 19 and 10 days for the overload and regression periods, respectively. Collectively these data suggest that 1) skeletal muscle myosin isoforms and corresponding ATPase activity are in a dynamic state of change, although not completely synchronous, in response to altered muscle stress, and 2) the kinetics of change in the mixed MHC protein pool are slower during compensatory growth compared with regression of growth.
Inhibition of mitochondrial carbonic anhydrase and ureagenesis: a discrepancy examined
Authors: Dodgson S. J.
Published: December 2017

The amount of urea synthesized in intact guinea pig hepatocytes in 60 min ([urea]t=60), was determined at 37 degrees C in Krebs-Henseleit buffer plus (in mM) 10 NH4Cl, 5 lactate, and 10 ornithine in 5% CO2–95% O2. The concentrations of sulfonamide carbonic anhydrase (CA) inhibitors required to reduce the rate of urea synthesis by 50% (I50) were (in mM): 0.07 ethoxzolamide, 0.5 methazolamide, 0.7 acetazolamide, and 5.0 p-aminomethylbenzenesulfonamide. At 37 degrees C acetazolamide and ethoxzolamide reduced citrulline synthesis by intact mitochondria in medium containing (in mM) 50 3-(N-morpholino)propanesulfonic acid, 35 KCl, 5 KH2PO4, 2 adenosine triphosphate, 10 ornithine, 10 NH4Cl, 1 [ethylene-bis(oxyethylenenitrile)]tetraacetic acid, 1 MgCl2, 20 pyruvate, and 25 KHCO3 (pH 7.4) in 5% CO2–95% O2; the inhibition by ethoxzolamide was not decreased greater than 50%; 25% inhibition was achieved by 0.65 microM ethoxzolamide. Inhibition constant (Ki) values for CA activity of disrupted mitochondria at 37 degrees C were 0.03 microM ethoxzolamide and 0.16 microM acetazolamide, and for disrupted hepatocytes were 150 microM ethoxzolamide and 50 microM acetazolamide. p-Aminomethylaminosulfonamide-affinity column purification yields one band of 29,000 mol wt for CA V purified from disrupted mitochondria; homogenized whole-liver supernatant yields an additional band of 20,000 mol wt (at greater than 100 times the concentration of CA V), which has some glutathione S-transferase activity. It is concluded that this 20,000-mol wt protein modifies the potency of ethoxzolamide in the liver cytosol.
A model-free method for mass spectrometer response correction
Authors: Shykoff B. E. , Swanson H. T.
Published: December 2017

A new method for correction of mass spectrometer output signals is described. Response-time distortion is reduced independently of any model of mass spectrometer behavior. The delay of the system is found first from the cross-correlation function of a step change and its response. A two-sided time-domain digital correction filter (deconvolution filter) is generated next from the same step response data using a regression procedure. Other data are corrected using the filter and delay. The mean squared error between a step response and a step is reduced considerably more after the use of a deconvolution filter than after the application of a second-order model correction. O2 consumption and CO2 production values calculated from data corrupted by a simulated dynamic process return to near the uncorrupted values after correction. Although a clean step response or the ensemble average of several responses contaminated with noise is needed for the generation of the filter, random noise of magnitude less than or equal to 0.5% added to the response to be corrected does not impair the correction severely.
Estimating diffusion distances in muscle
Authors: Snyder G. K.
Published: December 2017

Models of fibers and capillaries in cross sections of muscle were used to quantify the relationships between diffusion distances and tissue capillarity. The fibers were constructed as square and hexagonal arrays, and the placement of capillaries around the perimeters of the fibers ordered them in similar arrays. Diffusion distances were measured as the percent cumulative frequency of fiber area within a given distance of a capillary when capillary-to-fiber ratio was increased from 0.5 to 4.0. Equations fitted to the data make it possible to estimate diffusion distances in muscle and to correlate changes in diffusion distances with fiber growth, capillary growth, and the geometrical arrangement of capillaries in the muscle bed.
Insulin action and secretion in endurance-trained and untrained humans
Authors: King D. S. , Dalsky G. P. , Staten M. A. , Clutter W. E. , Van Houten D. R. , Holloszy J. O.
Published: December 2017

To evaluate insulin sensitivity and responsiveness, a two-stage hyperinsulinemic euglycemic clamp procedure (insulin infusions of 40 and 400 mU.m-2.min-1) was performed on 11 endurance-trained and 11 untrained volunteers. A 3-h hyperglycemic clamp procedure (plasma glucose approximately 180 mg/dl) was used to study the insulin response to a fixed glycemic stimulus in 15 trained and 12 untrained subjects. During the 40-mU.m-2.min-1 insulin infusion, the glucose disposal rate was 10.2 +/- 0.5 mg.kg fat-free mass (FFM)-1.min-1 in the trained group compared with 8.0 +/- 0.6 mg.kg FFM-1.min-1 in the untrained group (P less than 0.01). In contrast, there was no significant difference in maximally stimulated glucose disposal: 17.7 +/- 0.6 in the trained vs. 16.7 +/- 0.7 mg.kg FFM-1.min-1 in the untrained group. During the hyperglycemic clamp procedure, the incremental area for plasma insulin was lower in the trained subjects for both early (0–10 min: 140 +/- 18 vs. 223 +/- 23 microU.ml–1.min; P less than 0.005) and late (10–180 min: 4,582 +/- 689 vs. 8,895 +/- 1,316 microU.ml–1.min; P less than 0.005) insulin secretory phases. These data demonstrate that 1) the improved insulin action in healthy trained subjects is due to increased sensitivity to insulin, with no change in responsiveness to insulin, and 2) trained subjects have a smaller plasma insulin response to an identical glucose stimulus than untrained individuals.
Venous occlusion measurement of pulmonary capillary pressure: effects of embolization
Authors: Roselli R. J. , Parker R. E.
Published: December 2017

The effects of pulmonary arterial embolization on calculated pulmonary capillary pressure as determined by the venous occlusion technique are examined using a simple pressure-flow model for the lung. It is predicted that pulmonary, arterial embolization can induce significant underestimation of pulmonary capillary pressure in flowing vessels. This underestimation is related to the percent of vessels embolized and the caliber of pulmonary arteries that are embolized (i.e., the size of the emboli). Experimental verification of these theoretical findings is necessary before the conclusions can be extended to the interpretation of venous occlusion experiments in the lung.
Dimethylthiourea attenuates endotoxin-induced acute respiratory failure in pigs
Authors: Olson N. C. , Anderson D. L. , Grizzle M. K.
Published: December 2017

We hypothesized that toxic O2 radicals might be important mediators of endotoxin-induced acute respiratory failure in pigs. As a relatively specific scavenger of .OH, we infused dimethylthiourea (DMTU, 1 g/kg) before endotoxemia. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3.5 h. During phase 1 (i.e., 0–2 h) and phase 2 (i.e., 2–4.5 h), endotoxin decreased cardiac index (CI) and increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), alveolar-arterial O2 gradient (AaDo2), and hematocrit (Hct). Endotoxemia also caused leukopenia and increased the postmortem bronchoalveolar lavage fluid (BALF) albumin concentration and wet weight-to-dry weight ratio of bloodless lung. Dimethylthiourea did not significantly modify the phase 1 response. However, during phase 2, DMTU attenuated the endotoxin-induced decrease in CI and increases in Ppa, PVR, Hct, AaDo2, lung water, and BALF albumin concentration. In separate groups of endotoxin- and DMTU + endotoxin-treated pigs, lung microvascular hydrostatic pressure was increased to approximately 16 Torr (by fluid overload) to assess alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced increase in alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced induced increase in alveolar-capillary membrane permeability. We conclude that .OH (and possibly H2O2) significantly contributes to endotoxin-induced lung injury in anesthetized pigs.
Central venous pressure in humans during short periods of weightlessness
Authors: Norsk P. , Foldager N. , Bonde-Petersen F. , Elmann-Larsen B. , Johansen T. S.
Published: December 2017

Central venous pressure (CVP) was measured in 14 males during 23.3 +/- 0.6 s (mean +/- SE) of weightlessness (0.00 +/- 0.05 G) achieved in a Gulfstream-3 jet aircraft performing parabolic flight maneuvers and during either 60 or 120 s of +2 Gz (2.0 +/- 0.1 Gz). CVP was obtained using central venous catheters and strain-gauge pressure transducers. Heart rate (HR) was measured simultaneously in seven of the subjects. Measurements were compared with values obtained inflight at 1 G with the subjects in the supine (+1 Gx) and upright sitting (+1 Gz) positions, respectively. CVP was 2.6 +/- 1.5 mmHg during upright sitting and 5.0 +/- 0.7 mmHg in the supine position. During weightlessness, CVP increased significantly to 6.8 +/- 0.8 mmHg (P less than 0.005 compared with both upright sitting and supine inflight). During +2 Gz, CVP was 2.8 +/- 1.4 mmHg and only significantly lower than CVP during weightlessness (P less than 0.05). HR increased from 65 +/- 7 beats/min at supine and 70 +/- 5 beats/min during upright sitting to 79 +/- 7 beats/min (P less than 0.01 compared with supine) during weightlessness and to 80 +/- 6 beats/min (P less than 0.01 compared with upright sitting and P less than 0.001 compared with supine) during +2 Gz. We conclude that the immediate onset of weightlessness induces a significant increase in CVP, not only compared with the upright sitting position but also compared with the supine position at 1 G.
Systemic adenosine deaminase administration does not reduce active hyperemia in running rats
Authors: Klabunde R. E. , Laughlin M. H. , Armstrong R. B.
Published: December 2017

The importance of adenosine in controlling the magnitude and distribution of blood flow among and within skeletal muscles in rats during slow locomotor exercise was tested by systemic infusion of adenosine deaminase (ADA). Blood flows were measured using labeled microspheres before exercise and at 0.5, 15, and 30 min of fast treadmill walking at 15 m/min. An initial infusion of ADA (1,000 U/kg) was given 30 min before the first blood flow measurement and a second injection (1,000 U/kg) was given 5 min into exercise. These infusions maintained ADA activity above 5 U/ml blood throughout the experimental period. This plasma concentration of ADA was shown to be sufficient to result in a 64% decrease in muscle adenosine levels during ischemic contraction. Blood flows were measured in all of the muscles of the hindlimb (28 samples) and in various nonmuscular tissues in ADA-treated and control rats. Preexercise blood flows were primarily directed to slow-twitch muscles and exercise blood flows were highest in muscles with fast-twitch oxidative fibers. ADA treatment did not reduce total muscle blood flow or exercise blood flows in any of the muscles at any time. These findings do not support the hypothesis that adenosine plays an essential role in controlling muscle blood flow in skeletal muscles during normal locomotor activity.
Muscarinic stimulation of submucosal glands in swine trachea
Authors: Yang C. M. , Farley J. M. , Dwyer T. M.
Published: December 2017

The properties of muscarinic acetylcholine receptors (mAChR) on tracheal explants and isolated submucosal gland cells were determined using [3H]quinuclidinyl benzilate ([3H]QNB) and N-[3H]methylscopolamine ([3H]NMS) as ligands. Analysis of competitive displacement of ([3H]NMS binding by pirenzepine demonstrated the presence of M1- (27 +/- 2%) and M2G- (73 +/- 2%) receptors on isolated tracheal submucosal gland cells (TSGC's) in control. Daily administration of diisopropylfluorophosphate (DFP) inhibited cholinesterase activity by greater than 95%. After 7 days of DFP treatment, [3H]QNB binding to intact TSGC's decreased from 14.2 +/- 0.6 to 6.3 +/- 0.8 fmol/10(6) cells; similarly, [3H]NMS binding fell from 8.1 +/- 1.9 to 2.0 +/- 0.8 fmol/10(6) cells. The loss of mAChR's was predominantly of the M2G subtype with the relative proportion dropping to 33%. In addition, 90% of the receptors assumed the high-affinity state for carbachol displacement of [3H]NMS. Mucus secretion was quantitated by measuring the release of 3H-labeled mucus macromolecules from explants of tracheal submucosal glands and isolated cells. Acetylcholine (ACh), 2 X 10(-5) M, stimulated mucus secretion by 2.5 and 2.3 times the basal rate, respectively. Elimination of acetylcholinesterase (AChe) by DFP increased the ACh sensitivity by 18- and 5-fold. Tracheal explants or TSGC's obtained 2 h after an in vivo DFP treatment showed a 6- and 3-fold ACh stimulation. This ACh sensitivity decreased during the continued daily dosing with DFP such that only a 1.3- and 1.1-fold ACh stimulation was apparent after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of hypobaria on lung fluid balance in awake sheep
Authors: Hirai K. , Kobayashi T. , Kubo K. , Shibamoto T.
Published: December 2017

Effects of hypobaria on lung fluid balance were studied in five awake sheep with chronic lung lymph fistulas using a decompression chamber. Each sheep was exposed to three conditions of 6,600-m-simulated high altitude in random order as follows: 1) 6,600-m-simulated hypoxic hypobaria (barometric pressure 326 Torr, 21% inspired O2 fraction), 2) 6,600-m-simulated normoxic hypobaria (barometric pressure 326 Torr, 65% inspired O2 fraction), and 3) 6,600-m-simulated normoxic hypobaria (barometric pressure 326 Torr, 65% inspired O2 fraction) after pretreatment with a 2-h pure O2 inhalation (i.e., denitrogenation) to allow elimination of dissolved gases, especially N2, from the blood and tissues. We observed that under both hypoxic hypobaria and normoxic hypobaria, lung lymph flow (Qlym) significantly increased from the base-line values of 6.4 +/- 0.3 to 13.0 +/- 1.0 ml/h and 6.0 +/- 0.2 to 9.4 +/- 0.3 ml/h, respectively (P less than 0.05) and that the lymph-to-plasma protein concentration ratio remained unchanged. Moreover, pretreatment with a 2-h denitrogenation inhibited the increase in Qlym. These results suggest that rapid exposure to hypobaria causes an increase in pulmonary vascular permeability and that intravascular air bubble formation may account for this permeability change.
Permeability characteristics of cultured endothelial cell monolayers
Authors: Albelda S. M. , Sampson P. M. , Haselton F. R. , McNiff J. M. , Mueller S. N. , Williams S. K. , Fishman A. P. , Levine E. M.
Published: December 2017

The purpose of this study was to characterize the permeability characteristics of an in vitro endothelial cell monolayer system and relate this information to available in vivo data. We cultured bovine fetal aortic endothelial cells on fibronectin-coated polycarbonate filters and confirmed that our system was similar to others in the literature with regard to morphological appearance, transendothelial electrical resistance, and the permeability coefficient for albumin. We then compared our system with in vivo endothelium by studying the movement of neutral and negatively charged radiolabeled dextran tracers across the monolayer and by using electron microscopy to follow the pathways taken by native ferritin. There were a number of differences. The permeability of our monolayer was 10-100 times greater than seen in intact endothelium, there was no evidence of "restricted" diffusion or charge selectivity, and ferritin was able to move freely into the subendothelial space. The reason for these differences appeared to be small (0.5-2.0 micron) gaps between 5 and 10% of the endothelial cells. Although the current use of cultured endothelial cells on porous supports may provide useful information about the interaction of macromolecules with the endothelium, there appear to be differences in the transendothelial permeability characteristics of these models and in vivo blood vessels.
Recovery of the ventilatory response to hypoxia in normal adults
Authors: Easton P. A. , Slykerman L. J. , Anthonisen N. R.
Published: December 2017

Recovery of the initial ventilatory response to hypoxia was examined after the ventilatory response had declined during sustained hypoxia. Normal young adults were exposed to two consecutive 25-min periods of sustained isocapnic hypoxia (80% O2 saturation in arterial blood), separated by varying interludes of room air breathing or an increased inspired O2 fraction (FIO2). The decline in the hypoxic ventilatory response during the 1st 25 min of hypoxia was not restored after a 7-min interlude of room air breathing; inspired ventilation (VI) at the end of the first hypoxic period was not different from VI at the beginning and end of the second hypoxic period. After a 15-min interlude of room air breathing, the hypoxic ventilatory response had begun to recover. With a 60-min interlude of room air breathing, recovery was complete; VI during the second hypoxic exposure matched VI during the first hypoxic period. Ventilatory recovery was accelerated by breathing supplemental O2. With a 15-min interlude of 0.3 FIO2 or 7 min of 1.0 FIO2, VI of the first and second hypoxic periods were equivalent. Both the decline and recovery of the hypoxic ventilatory response were related to alterations in tidal volume and mean inspiratory flow (VT/TI), with little alteration in respiratory timing. We conclude that the mechanism of the decline in the ventilatory response with sustained hypoxia may require up to 1 h for complete reversal and that the restoration is O2 sensitive.