bluuebunny/crossref_metadata_2025 huggingface dataset:
Alveolar pressure inhomogeneity and gas exchange during constant-flow ventilation in dogs
Authors: Sznajder J. I. , Nahum A. , Crawford G. , Pollak E. R. , Schumacker P. T. , Wood L. D.
Published: December 2017

Analysis of momentum transfer between inflow jets and resident gas during constant-flow ventilation (CFV) predicts inhomogeneity of alveolar pressures (PA) and volume, which might account for specific ventilation-variance in the lung. Using alveolar needles to measure pressures (PA) during CFV in eight anesthetized dogs with wide thoracotomy, we observed random dispersion of PA among lobes of up to 12.5 cmH2O. Within each lobe, the PA dispersion was up to 10 cmH2O at CFV of 90 l/min; when flow decreased, PA at all sites decreased, as did the intralobar dispersion. These pressure differences were not observed during conventional mechanical ventilation (CMV). During CFV with room air, dogs were hypoxemic [arterial PO2 (Pao2) 54 +/- 15 Torr] and the venous admixture (Qva/QT) was 50 +/- 15%. When inspiratory O2 fraction was increased to 0.4, Pao2 increased to 172 +/- 35 Torr and Qva/QT dropped to 13.5 +/- 8.4%, confirming considerable ventilation-perfusion (VA/Q) variance not observed during CMV. We conclude that momentum transfer between the inflow stream and resident gas caused inhomogeneities of alveolar pressures, volumes, and ventilation responsible for VA/Q variance and hypoxemia during CFV. Conceivably, the abnormal ventilation distribution is minimized by collateral ventilation and forces of interdependence between regions of high and low alveolar pressures. Momentum transfer also predicted the mucosal damage observed on histological evaluation of the bronchial walls near the site of inflow jet impact.
Rabbit hindlimb glucose uptake assessed with positron-emitting fluorodeoxyglucose
Authors: Mossberg K. A. , Rowe R. W. , Tewson T. J. , Taegtmeyer H.
Published: December 2017

The feasibility of estimating skeletal muscle glucose uptake in vivo was examined by using the glucose analogue 2-[18F]deoxy-2-fluoro-D-glucose (2-[18F]FDG) in the rabbit hindlimb. A pair of collimated coincidence gamma photon detectors was used to monitor the accumulation of tracer in the tissue after 2-[18F]FDG injection. Time-activity curves were generated on a second-by-second basis under control conditions, during increased contractile activity, or hyperinsulinemia. The arterial input of 2-[18F]FDG, plasma glucose, lactate, free fatty acids, and insulin were determined. A graphical (Patlak plot) procedure was used to determine the fractional rate of tracer phosphorylation and therefore trapping in the muscle. From the graphical analysis, the estimated rate of glucose phosphorylation (R) in the unperturbed state was calculated to be 0.037 mumol.min-1.ml-1 of tissue. During perturbation by electrical stimulation, an increase in the rate of tracer phosphorylation (K) was observed. No change in the rate of tracer phosphorylation was observed during hyperinsulinemia. The results support the use of 2-[18F]FDG and the graphical procedure for the noninvasive assessment of glucose uptake by skeletal muscle in vivo. The method described is sensitive to changes in the rate of tracer uptake with respect to time and physiological interventions.
Influence of age and exercise training on lipid metabolism in Fischer-344 rats
Authors: Barakat H. A. , Dohm G. L. , Shukla N. , Marks R. H. , Kern M. , Carpenter J. W. , Mazzeo R. S.
Published: December 2017

The influence of training on fatty acid and glyceride synthesis by liver and adipose tissue homogenates of young and old Fischer-344 rats was examined. Four groups of rats (10 animals/group) were studied: young untrained, young trained, old untrained, and old trained. Training of each group was for 10 wk at 75% maximal O2 uptake. Young rats were killed at 6 mo of age and old rats were killed at 27 mo of age. Fatty acid synthesis was assessed by measuring the activities of acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, "malic" enzyme, and glucose-6-phosphate dehydrogenase. Glyceride synthesis was evaluated by determining the rate of incorporation of [14C]glycerol 3-phosphate into lipids. In addition, lipoprotein lipase activity was measured in acetone-ether powders of adipose tissue from the four groups of rats. In liver, training had no effect on fatty acid or glyceride synthesis in either group. However, aging caused a significant decrease in the activities of four of the lipogenic enzymes but had no effect on glyceride synthesis. Training caused an increase in fatty acid synthase and glyceride synthesis in adipose tissue, and aging decreased lipoprotein lipase activity. It was concluded that training enhances the synthetic capacity of lipids by adipose tissue but that aging had a more profound effect in that the activities of the enzymes involved in these processes were lower in the old rats. Furthermore, the decreased activity of lipoprotein lipase in the older rats may explain the higher plasma triglyceride levels that were observed in these animals.
Permeation of inert gases through human skin: modeling the effect of skin blood flow
Authors: Whang J. M. , Quinn J. A. , Graves D. J. , Neufeld G. R.
Published: December 2017

We present an analytic method for determining the effects of skin perfusion--vasculature and flow rates--on the flux of inert gases through human skin. We systematically specify the underlying blood flow and examine the resulting fluxes of several gases, allowing for the appropriate tissue resistances. For physiological flows, the stratum corneum has an effect equivalent to a series resistance. Helium flux at low total flow depends primarily on subdermal perfusion, but at higher flow, middermal and subpapillary effects become important. The fluxes of less permeable gases, such as argon and xenon, depend on middermal and subpapillary flow at lower total flows. From any single measurement of gas flux, it is difficult to establish an unambiguous value for the underlying blood flow, but the simultaneous measurement of different gases narrows the range of plausible conditions.
Control of shunt pathway perfusion in diffuse granulomatous lung disease
Authors: Schulman L. L. , Wood J. A. , Enson Y.
Published: December 2017

To assess the roles of cyclooxygenase inhibition and alveolar hypoxia in controlling the distribution of pulmonary perfusion in granulomatous lung injury, we studied 15 dogs (anesthetized and ventilated) 4 wk after intravenous injection of complete Freund's adjuvant (0.5-0.75 ml/kg). Base-line hemodynamic and blood gas observations were obtained at fractional O2 concentration (FIO2) 0.21 and 0.10. Observations at each FIO2 were repeated 30 min after infusion of meclofenemate (2 mg/kg; n = 10) or saline (n = 5). Resistance to pulmonary blood flow was assessed using the difference between pulmonary arterial diastolic and left atrial pressures (PDG). Distribution of blood flow between normal and diseased regions of the lung was evaluated with measurement of inert gas shunt flow. Before infusion, there were no significant differences between the two groups at either FIO2. At FIO2 0.10 PDG rose from 3 +/- 1 to 7 +/- 3 mmHg in the saline group and from 3 +/- 1 to 8 +/- 3 mmHg in the meclofenemate group, although the shunt flow increased from 8.7 +/- 7.7 to 12.2 +/- 9.2% and from 10.7 +/- 11.0 to 17.6 +/- 18.3 in the two groups, respectively. Saline induced no significant changes at either FIO2. After meclofenemate, PDG at FIO2 0.21 rose to 7 +/- 4 mmHg (P less than 0.015) while shunt flow fell to 5.2 +/- 6.2% (P less than 0.0125), whereas at FIO2 0.10 PDG rose to 15 +/- 5 mmHg (P less than 0.001) while shunt flow rose only to 14.3 +/- 16.4% (P = NS). We propose that perivascular inflammation enhanced perfusion of abnormal lung by elaborating vasodilator prostanoids. By inhibiting prostanoid biosynthesis, meclofenemate selectively increased resistance in diseased lung at FIO2 0.21 and lowered shunt flow. The persistent rise in shunt during hypoxia after meclofenemate suggests that factors other than prostanoids may account for the apparent attenuation of hypoxic vasoconstriction in diseased lung.
Naloxone alters the early response to an inspiratory flow-resistive load
Authors: Scardella A. T. , Santiago T. V. , Edelman N. H.
Published: December 2017

In a previous study in unanesthetized goats, we demonstrated that cerebrospinal fluid levels of beta-endorphin were significantly elevated after 2.5 h of inspiratory flow-resistive loading. Naloxone (NLX) (0.1 mg/kg) administration partially and transiently reversed the tidal volume depression seen during loading. In the current study, we tested the hypothesis that endogenous opioid elaboration results in depression of respiratory output to the diaphragm. In six studies of five unanesthetized goats, tidal volume (VT), transdiaphragmatic pressure (Pdi), diaphragmatic electromyogram (EMGdi), and arterial blood gases were monitored. A continuous NLX (0.1 mg/kg) or saline (SAL) infusion was begun 5 min before an inspiratory flow-resistive load of 120 cmH2O.l-1.s was imposed. Our data show that the depression of VT induced by the load was prevented by NLX as early as 15 min and persisted for 2 h. At 2 h, Pdi was still 294 +/- 45% of the base-line value compared with 217 +/- 35% during SAL. There was no difference in EMGdi between the groups at any time. However, the augmentation of Pdi was associated with a greater increase in end-expiratory gastric pressure in the NLX group. We conclude that the reduction in VT and Pdi associated with endogenous opioid elaboration is not mediated by a decrease in neural output to the diaphragm, but it appears to be the result of a decrease in respiratory output to the abdominal muscles.
Effect of a synthetic progestin on ventilatory response to hypoxia in anesthetized rats
Authors: Kimura H. , Mikami M. , Kuriyama T. , Fukuda Y.
Published: December 2017

Effects on ventilatory responses to progressive isocapnic hypoxia of a synthetic potent progestin, chlormadinone acetate (CMA), were determined in the halothane-anesthetized male rat. Ventilation during the breathing of hyperoxic gas was largely unaffected by treatment with CMA when carotid chemoreceptor afferents were kept intact. The sensitivity to hypoxia evaluated by hyperbolic regression analysis of the response curve did not differ between the control and CMA groups. The reduction of ventilation after bilateral section of the carotid sinus nerve (CSN) in hyperoxia was less severe in CMA-treated than in untreated animals. Furthermore, the CMA-treated rats showed a larger increase in ventilation during the hypoxia test and a lower PO2 break point for ventilatory depression. Inhibition of hypoxic ventilatory depression by CMA persisted even after the denervation of CSN. We conclude that exogenous progestin likely protects regulatory mechanism(s) for respiration against hypoxic depression through a stimulating action independent of carotid chemoreceptor afferents and without a change in the sensitivity of the ventilatory response to hypoxia.
Step response of lung surface-to-volume ratio by light-scattering stereology
Authors: Butler J. P. , Miki H. , Suzuki S. , Takishima T.
Published: December 2017

By means of backscattered light from a pointlike source on the pleural surface, we investigated the dynamic behavior of the surface-to-volume ratio (S/V) in excised dog lobes subjected to small volume steps both in and out on both the inflation and deflation limb of standard pressure-volume maneuvers. The technique utilizes the established correlation of the pattern of backscattered light with morphometric mean linear intercept and is suitable for dynamic studies. We hypothesized that 1) there would be a difference in the timing of stress relaxation or recovery between alveolar septa and the fibromuscular tissue in the alveolar duct that would reveal itself as a temporally changing S/V after a step-volume change and 2) that geometric hysteresis (looping of S/V with volume), as seen with large volume excursion histories, would be similarly present in small tidal volume loops. Our experimental results contradicted both hypotheses. In particular, we found virtually no change in S/V after a step-volume change, even in the presence of substantial stress adaptation. In addition, when geometric hysteresis of small loops was present, it was always in the sense opposite to the geometric hysteresis of large loops. We conclude that 1) there is a functional “matchin” of the stress-adaptive timing between alveolar septa and ductal mouths and 2) during small volume looping, the stress hysteresis (looping of stress with volume) in the ductal tissue may be larger than that of the septa, including surface tension.
Relative importance of aerobic and anaerobic energy release during short-lasting exhausting bicycle exercise
Authors: Medbo J. I. , Tabata I.
Published: December 2017

Anaerobic energy release is of great importance for shortlasting exercise but has been difficult to quantify. In order to determine the amount of anaerobic energy release during shortlasting exercise we let 17 healthy young males exercise on the ergometer bike to exhaustion. The power during exercise was kept constant and selected to cause exhaustion in approximately 30 s, 1 min, or 2-3 min. The O2 uptake was measured continuously during the exercise, and the anaerobic energy release was quantified by the accumulated O2 deficit. The work done as well as the total energy release rose linearly with the exercise duration and was therefore a sum of a component proportional to time plus a constant addition. The accumulated O2 deficit increased from 1.86 +/- 0.07 (SE) mmol/kg for 30 s exercise to 2.25 +/- 0.06 mmol/kg for 1 min exercise and further to 2.42 +/- 0.08 mmol/kg for exercise lasting 2 min or more (P less than 0.01). The accumulated O2 uptake increased linearly with the duration, and as a consequence of this the relative importance of aerobic processes increased from 40% at 30 s duration to 50% at 1 min duration and further to 65% for exercise lasting 2 min. These results show that both aerobic and anaerobic processes contribute significantly during intense exercise lasting from 30 s to 3 min.
Simultaneous measurement of O2 radicals and pulmonary vascular reactivity in rat lung
Authors: Archer S. L. , Nelson D. P. , Weir E. K.
Published: December 2017

The role of endogenous radicals in the regulation of pulmonary vascular tone was evaluated by simultaneous measurement of pulmonary artery pressure and lung radical levels during exposure of isolated rat lungs to varying inspired O2 concentrations (0-95%) and angiotensin II. Lung radical levels, measured “on-line” using luminol and lucigenin-enhanced chemiluminescence, decreased in proportion to the degree of alveolar hypoxia. Radical levels fell during hypoxia before the onset of pulmonary vasoconstriction and promptly returned to basal levels with restoration of normoxic ventilation. Mild alveolar hypoxia (10% O2), which failed to decrease chemiluminescence, did not trigger pulmonary vasoconstriction. Although chemiluminescence tended to decrease more as the hypoxic response strengthened, there was not a simple correlation between the magnitude of the change in chemiluminescence induced by hypoxia and the strength of the hypoxic pressor response. Normoxic chemiluminescence was largely inhibited by superoxide dismutase but not catalase. Superoxide dismutase also increased normoxic pulmonary vascular tone and the strength of the pressor response to hypoxia and angiotensin II. Thus the predominant activated O2 species in the lung, during normoxia, was the superoxide anion or a closely related substance. Alteration of endogenous radical levels can result in changes in vascular tone. It remains uncertain whether the decrease in lung radical production during hypoxia caused pulmonary vasoconstriction or was merely associated with hypoxic ventilation.
Field use of D2 18O to measure energy expenditure of soldiers at different energy intakes
Authors: DeLany J. P. , Schoeller D. A. , Hoyt R. W. , Askew E. W. , Sharp M. A.
Published: December 2017

To test the application of doubly labeled water under adverse field conditions, energy expenditures of 16 special operations soldiers were measured during a 28-day field training exercise. Subjects were matched by fat-free mass and divided equally between an ad libitum ready-to-eat meal diet and a 2,000 kcal/day lightweight ration. Subjects recorded intakes daily, and body composition was measured before and after the exercise. At the beginning of the study, subjects moved to a new northerly location and, therefore, a new water supply. To compensate for this, a group of soldiers who did not receive heavy water was followed to measure isotopic base-line changes. Energy expenditure by doubly labeled water was in agreement with intake/balance (3,400 +/- 260 vs. 3,230 +/- 520 kcal/day). The overall coefficient of variation of energy expenditure by doubly labeled water was half that of intake/balance (7.6 vs. 16.1%). The coefficient of variation of repeat measures with doubly labeled water was 7.3%. Energy expenditure of the ready-to-eat meal group, 3,540 +/- 180 kcal/day, was not significantly different from the lightweight ration group, 3,330 +/- 301 kcal/day. Doubly labeled water was valid under field conditions.
Lengths and topology of alveolar septal borders
Authors: Oldmixon E. H. , Butler J. P. , Hoppin F. G.
Published: December 2017

To clarify the mechanics of alveolar parenchyma, we undertook a stereological and topological study in perfusion-fixed canine lungs of the borders of alveolar septa. We defined the principal borders as those along which one septum 1) joins two others (J), 2) joins one other at a distinct angle (B), or 3) joins no other structure (E). E and B borders are invariably reinforced with heavy connective tissue cables; J borders are not. Relative net lengths, determined from the number of traces per section area, were J, 45%; E, 19%; and B, 25%. These were remarkably constant over 10 canine lobes (5 animals, 4 volumes). Parenchyma, then, departs from the simple models that comprise only Js and Es. Bs are important; their net length exceeds that of Es. With lobe deflation, E shortened somewhat more than required to maintain geometric similarity, suggesting that the alveolar duct contracted disproportionately. A three-dimensional reconstruction was made from serial sections, and individual border segments were followed through the reconstruction. Typical lengths of individual J, B, and E borders were nearly equal. To characterize how the network of borders were interconnected, we counted the nodes at which they meet by class, e.g., EBE for the meeting of one B, two Es. The most common are JJJJ, 26%; EEEJ, 10%; EBJ, 24%; EBE, 8%; BBJJ, 12%. If parenchyma were constructed only from free-standing entrance rings and septal junctions, only JJJJ and EEEJ would be anticipated. The presence of EBJ, EBE, and BBJJ underscores parenchymal complexity. Only 7% of septa examined were bordered entirely by Js. Connective tissue cables were not confined to the alveolar duct's lumen but often extended to the primary septa at the periphery of the ductal unit. They rarely linked adjacent alveolar ducts; only 1 in 200 cable segments crossed from one duct to another. These observations support the concept that the parenchyma is an elastic network, characterized in part by a serial mechanical linkage from connective tissue cable to septal membrane to cable again.
Size-related differences in parietal extrapleural and pleural liquid pressure distribution
Authors: Negrini D. , Miserocchi G.
Published: December 2017

The hydraulic pressure in the extrapleural parietal interstitium (Pepl) and in the pleural space over the costal side (Pliq) was measured in anesthetized spontaneously breathing supine adult mammals of increasing size (rats, dogs, and sheep) using saline-filled catheters and cannulas, respectively. From the Pliq and Pepl vs. lung height regressions it appears that in all species Pliq was significantly more subatmospheric than Pepl simultaneously measured at the same lung height. The vertical pleural liquid pressure gradient increased with size, amounting to -1, -0.69, and -0.44 cmH2O/cm in rats, dogs, and sheep, respectively. The vertical extrapleural liquid pressure gradient also increased with size, being -0.6, -0.52, and -0.33 cmH2O/cm in rats, dogs, and sheep, respectively. With increasing body size, the transpleural hydraulic pressure gradient (Ptp = Pepl - Pliq) at the level of the right atrium increased from 1.45 to 5.6 cmH2O going from rats to sheep. In all species Ptp increased, with lung height being greatest in the less dependent part of the pleural space.
Chromatographic demonstration of reversible changes in endothelial permeability
Authors: Haselton F. R. , Mueller S. N. , Howell R. E. , Levine E. M. , Fishman A. P.
Published: December 2017

This report describes a new in vitro method for measuring the diffusional permeability of an endothelial monolayer and its use in investigating the modulation of permeability by various agents, e.g., isoproterenol, propranolol, dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP), and cytochalasin D. To determine permeability, tracers of different molecular weights were applied simultaneously on a chromatography column containing confluent endothelial cells cultured on porous microcarrier beads. The Sangren-Sheppard model was used to determine the permeability of the endothelial monolayer from the tracer elution profiles. For six radiolabeled tracers the mean (+/- SD) permeabilities (cm/s x 10(-5)) in order of increasing tracer molecular weight were [3H]water, 82.0 +/- 28.8; [14C]urea, 49.5 +/- 9.5; [14C]mannitol, 13.3 +/- 4.7; [14C]-sucrose, 14.1 +/- 2.5; [3H]polyethylene glycol (900 mol wt), 4.80 +/- 1.61; and [3H]polyethylene glycol (4,000 mol wt), 1.97 +/- 1.01. These permeabilities deviate less from in vivo values than those obtained in other in vitro systems and are 10 times higher than in vivo estimates. The values were reproducible for up to the 4 h tested. Modulation of endothelial monolayer permeability was studied in a separate series of experiments. The beta-adrenergic agonist isoproterenol (10(-6) M) decreased the permeability to mannitol by 36% and to polyethylene glycol (900 mol wt) by 49%; in both instances the decrease in permeability was reversed by propranolol. Propranolol alone had no effect. Dibutyryl cAMP (10(-3) M) decreased the permeability to mannitol by 40% and to polyethylene glycol by 47%; permeability returned to base line when dibutyryl cAMP was removed. Cytochalasin D (1 microgram/ml) increased permeability by 350% for mannitol and 380% for polyethylene glycol; the permeability change was reversed after removal of cytochalasin D. The results indicate that cell-column chromatography is a powerful method that can be used to characterize the permeability of endothelial monolayers and to investigate permeability changes produced by various agents.
Diaphragm, genioglossus, and triangularis sterni responses to poikilocapnic hypoxia
Authors: van Lunteren E. , Martin R. J. , Haxhiu M. A. , Carlo W. A.
Published: December 2017

Both isocapnic and poikilocapnic hypoxia may elicit a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a reduction in breathing and diaphragm (DIA) electrical activity. To ascertain whether during adulthood other respiratory muscles have biphasic hypoxic responses similar to the DIA, in nine anesthetized cats electromyograms (EMG) were recorded from the DIA, genioglossus (GG), and triangularis sterni (TS) (n = 7) muscles during poikilocapnic hypoxia. DIA and GG EMG started at 60 +/- 4 and 9 +/- 3 units, respectively, during O2 breathing, increased to a maximum of 100 units during the 10-min hypoxic stimulus, and subsequently declined to 81 +/- 6 and 58 +/- 12 units, respectively, by the end of 10 min of hypoxia. The time course of the increase and subsequent decline was similar for the DIA and GG and for GG activity during both inspiration and expiration. Furthermore the degree to which GG EMG declined after reaching its peak activity level correlated with the magnitude of the respective decline in DIA EMG (r = 0.79, P less than 0.02). The TS, in contrast, was maximally active either during O2 breathing or very early during hypoxia, and its activity declined progressively thereafter (to 13 +/- 6% of its peak value at the end of 10 min of hypoxia). The degree to which TS EMG declined did not correlate with the degree to which DIA or GG EMG declined.(ABSTRACT TRUNCATED AT 250 WORDS)
Influences of exogenous insulin on arterial blood pressure measurements of the rat
Authors: Edwards J. G. , Tipton C. M.
Published: December 2017

Studies were undertaken with adult male rats to test the hypothesis that euglycemic hyperinsulinemia would alter mean arterial blood pressure (MAP) and heart rate (HR) relationships by activation of the sympathetic nervous system. Conscious rats were infused either with insulin or control vehicle (0, 0.47, 1.5, 4.7, 15.0 mU.kg-1.min-1) for 75 min before injection of hexamethonium. Compared with the control period, insulin infusion significantly increased MAP by 7.1 +/- 0.1, 12.7 +/- 2.0, and 19.7 +/- 0.3 (SE) mmHg and HR by 44 +/- 8.4, 66 +/- 10.3, and 95 +/- 6.3 beats/min, respectively, during the three highest rates of infusion. The dose-dependent increases in MAP and HR were due to increases in the activity of hexamethonium-sensitive pathways. In chemically sympathectomized rats, insulin infusion did not produce a significant increase in either MAP or HR. The influence of exogenous norepinephrine on MAP and HR was also studied after insulin infusion. Compared with the insulin-vehicle infusion, insulin infusion significantly depressed (P less than 0.05) the norepinephrine dose-response increase in MAP. In addition, isolated smooth muscle strips were studied to determine the influence of insulin on their in vitro responses to increasing doses of norepinephrine. Although insulin did not alter contractility, it significantly (P less than 0.05) decreased the sensitivity of the vascular strips to norepinephrine. Collectively, the data from these euglycemic experiments indicated that infusions of insulin caused increases in HR and MAP because of activation of the sympathetic nervous system, even though the responsiveness of the vascular smooth muscle was depressed.
Effect of training on muscle metabolism during treadmill sprinting
Authors: Nevill M. E. , Boobis L. H. , Brooks S. , Williams C.
Published: December 2017

Sixteen subjects volunteered for the study and were divided into a control (4 males and 4 females) and experimental group (4 males and 4 females, who undertook 8 wk of sprint training). All subjects completed a maximal 30-s sprint on a nonmotorized treadmill and a 2-min run on a motorized treadmill at a speed designed to elicit 110% of maximum oxygen uptake (110% run) before and after the period of training. Muscle biopsies were taken from vastus lateralis at rest and immediately after exercise. The metabolic responses to the 110% run were unchanged over the 8-wk period. However, sprint training resulted in a 12% (P less than 0.05) and 6% (NS) improvement in peak and mean power output, respectively, during the 30-s sprint test. This improvement in sprint performance was accompanied by an increase in the postexercise muscle lactate (86.0 +/- 26.4 vs. 103.6 +/- 24.6 mmol/kg dry wt, P less than 0.05) and plasma norepinephrine concentrations (10.4 +/- 5.4 vs. 12.1 +/- 5.3 nmol/l, P less than 0.05) and by a decrease in the postexercise blood pH (7.17 +/- 0.11 vs. 7.09 +/- 0.11, P less than 0.05). There was, however, no change in skeletal muscle buffering capacity as measured by the homogenate technique (67.6 +/- 6.5 vs. 71.2 +/- 4.5 Slykes, NS).
On the imperfect elasticity of lung tissue
Authors: Fredberg J. J. , Stamenovic D.
Published: December 2017

This paper deals with a unifying hypothesis addressed at lung tissue resistance and its responses to neurohumoral and biophysical stimuli. The hypothesis holds that dissipative and elastic processes within lung tissue are coupled at the level of the stress-bearing element. Such a description leads naturally to consideration of a readily measured attribute of organ-level dissipative behavior called lung tissue hysteresivity, eta. On preliminary analysis this attribute is found to be nearly frequency independent and numerically conserved across species. To the degree that the numerical value of eta might be conserved during an intervention in which tissue dynamic elastance changes, such behavior would be consistent with the notion that elastic energy storage and dissipative energy loss reside within the very same stress-bearing element and, moreover, that those processes within the stress-bearing element bear an approximately fixed relationship. Tissue hysteresivity is closely related to the parameter K used by Bachofen and Hildebrandt (J. Appl. Physiol. 30: 493-497, 1971) to describe energy dissipation per cycle, and both lend themselves directly to interpretation based on processes ongoing at the levels of microstructure and molecule. Intraparenchymal connective tissues, surface film, and contractile elements appear to submit individually to this description and, in doing so, yield respective hysteresivities that are relatively well matched; this suggests that such hysteretic matching may be a necessary condition for synchronous expansion of the alveolar duct. The overriding simplicity with which this description organizes diverse observations implies that it may capture some unifying attribute of underlying mechanism.
Diaphragm atrophy and weakness in cortisone-treated rats
Authors: Moore B. J. , Miller M. J. , Feldman H. A. , Reid M. B.
Published: December 2017

Despite frequent therapeutic use, the potential of corticosteroids to produce respiratory muscle myopathy is unknown. We studied effects of chronic steroid treatment on diaphragm mass and function. Eleven Sprague-Dawley rats were treated with cortisone acetate (100 mg.kg-1.day-1 im) for 10 days. Controls (injected with vehicle) included 11 freely eating rats and 11 animals pair fed to match food intake of cortisone rats. Steroid treatment depressed body weight 30% compared with controls. Mass of diaphragm, gastrocnemius, and extensor digitorum longus showed significant atrophy (30%); heart and soleus were unaffected. Isometric contractile properties of costal diaphragm strips were studied in vitro using direct stimulation. The force-frequency relationship was markedly depressed by steroid treatment, both at low and high frequencies. However, force developed per unit cross-sectional area was similar among all three groups, as were twitch characteristics. When stimulated every minute, forces developed by control strips fell progressively, whereas the forces of cortisone-treated strips remained unchanged. When stimulated every 5 s, the fall in force was not different between groups. We conclude that cortisone weakened the diaphragm by decreasing muscle mass but made the diaphragm more resistant to one form of fatigue in vitro.
Blood gas changes during and after nonspecific airway challenge in asthmatic and normal subjects
Authors: Dal Negro R. , Allegra L.
Published: December 2017

Twenty-eight asymptomatic asthmatics and 28 healthy volunteers were challenged with ultrasonically nebulized distilled water (UNDW). Blood gas composition was monitored transcutaneously (PtCO2 and PtcCO2) over 42 min (20 min for electrode stability, 3 min base line, 5 min during UNDW, and 14 min after UNDW). Flow-volume curves were recorded before and 15 min after UNDW. Forced expiratory volume in 1 s and expiratory flows decreased in asthmatics but not in normal subjects after UNDW. Mean base-line PtCO2 and PtcCO2 were comparable in the two groups. UNDW in normal subjects produced no significant changes in mean PtcCO2 and PtCO2. In asthmatics, the UNDW-induced decrease in mean PtcCO2 was greater and longer lasting, accompanied by a prolonged decrease in mean PtCO2. PtcCO2 and PtCO2 trends showed highly significant differences compared with healthy volunteers (P less than 0.001). Arterial blood gas measurements validated these changes. UNDW in asymptomatic asthmatics gives rise to a greater and more prolonged hyperventilation than in normal subjects and to gas-exchange abnormalities presumably reflecting a ventilation-perfusion mismatching.
Effects of phorbol myristate acetate-stimulated human leukocytes on rat lung
Authors: Perry M. L. , Kayes S. G. , Barnard J. W. , Taylor A. E.
Published: December 2017

Human blood was separated into polymorphonuclear (PMN) and mononuclear (MN) leukocyte fractions, and 3 x 10(7) cells (PMN or MN) were added to isolated rat lungs perfused with 5% human albumin in buffer and stimulated with phorbol myristate acetate (PMA). Lungs perfused with either albumin alone, PMN, or MN but not stimulated with PMA showed no change in vascular resistance or endothelial permeability measured as the capillary filtration coefficient (Kf,c). Lungs that were stimulated with PMA with no cells showed no change in Kf,c (0.34 +/- 0.07 vs. 0.37 +/- 0.7), but vascular resistance increased in all segments of the circulation. Capillary pressure, the major force responsible for edema formation, nearly doubled in the absence of cells 40 min after PMA. Lungs perfused with either PMN or MN and stimulated with PMA were injured. Kf,c increased from 0.41 +/- 0.03 to 0.87 +/- 0.10 (PMN) and from 0.36 +/- 0.07 to 0.81 +/- 0.23 (MN) 90 min after PMA. In addition to the increased endothelial permeability, vascular resistances and pressures also increased in the cell-perfused PMA-stimulated lungs. These results demonstrate that cells other than granulocytes are capable of producing severe acute lung injury and cannot be ignored when the effects of PMA on neutrophil-depleted lungs are studied.
Contractile properties of rat soleus muscle after 15 days of hindlimb suspension
Authors: Stevens L. , Mounier Y. , Holy X. , Falempin M.
Published: December 2017

The properties of the contractile elements interacting to develop force in atrophied rat soleus muscle were studied by using single skinned fibers, which permitted direct access to the contractile apparatus. Muscle atrophy was induced by 15 days of hindlimb suspension. Suspension resulted in a decrease of maximal tension relative to an important decline in fiber diameter. Ca affinity of the contractile proteins was not changed insofar as the tension-pCa relationship was not shifted along the pCa axis. However, after hindlimb suspension 1) the value of the Hill coefficient from the tension-pCa curve was found to be higher, 2) a higher Ca threshold for activation was reported, and 3) a significant increase in contraction kinetics was described. All these results suggested that after suspension the mechanical properties of the slow-twitch soleus appeared to resemble more closely those of a fast-twitch muscle. Our results were in complete agreement with published histochemical data.
Clearance of charged and uncharged dextrans from normal and injured lungs
Authors: Barrowcliffe M. P. , Zanelli G. D. , Ellison D. , Jones J. G.
Published: December 2017

To examine how molecular charge affects the transfer of molecules across the alveolar-capillary barrier, we prepared the following dextrans of equivalent molecular size (mol wt 10,000) but varying molecular charge: neutral dextran, cationic DEAE dextran, and anionic dextran sulfate. These were labeled with 99mTc. The lungs of three groups of anesthetized rabbits were insufflated with dextran aerosols, with six rabbits receiving each type, and the half-time pulmonary clearance (t1/2) was measured. Control t1/2's (95% confidence limits) were 95 (74-120), 227 (192-268), and 291 (246-345) min for neutral, cationic, and anionic dextrans, respectively. One week later, when the same animals were restudied 4 h after 3 micrograms/kg iv endotoxin, t1/2's were 102 (75-139), 167 (149-187), and 126 (102-154) min, respectively. After 30 min during this repeat study, animals were ventilated with 20 breaths of cigarette smoke, which acutely increased the clearance rate to 34 (26-46), 25 (20-31), and 13 (7-24) min, respectively. Mean carboxyhemoglobin levels were not significantly different in the three groups: 13.6, 12.7, and 11.1%, respectively. These results demonstrated that neutral dextrans showed the same clearance rate before and after endotoxin, whereas the charged dextrans had a significantly faster clearance after endotoxin. After smoke exposure the anionic dextran left the lung more rapidly than the neutral dextran. Thus molecular charge affects solute transfer across the alveolar-capillary barrier in both normal and injured lungs, and an effect of endotoxin on the lung can be detected with charged dextrans but not with neutral dextran.
Effect of sampling on variability and plateau in oxygen uptake
Authors: Myers J. , Walsh D. , Sullivan M. , Froelicher V.
Published: December 2017

To evaluate the effect of the gas exchange sampling interval on variability and plateau in O2 uptake (VO2), 10 subjects underwent steady-state treadmill exercise at 50% maximal VO2 and 6 subjects underwent maximal testing using a ramp protocol. During steady-state exercise, gas exchange data were acquired by using 10 different sampling intervals. The variability in VO2 was greater as the sampling interval shortened (SD = 4.5 ml.kg-1.min-1 for breath-by-breath vs. 0.8 ml.kg-1.min-1 for 60-s samples). The breath-by-breath data suggested a Gaussian distribution, and most of the variability was attributable to tidal volume (51%). During ramp testing, the slope of the change in VO2 (for each sample) was regressed with time. Considerable variability in the slopes was observed throughout exercise, and in each subject the slopes varied about zero, demonstrating both positive and negative values throughout submaximal effort. These observations were made despite the use of large sampling intervals. Shortening the sample resulted in even greater variability. We conclude that 1) the sampling interval can have a major impact on gas exchange data during exercise and 2) considerable variability exists in the slope of the change in VO2 with a consistent change in external work regardless of the sample used, suggesting that a plateau (defined as the slope of a VO2 sample at peak exercise that does not differ significantly from a slope of zero) in VO2 is not a reliable physiological marker for maximal effort.
Effect of paraxanthine on FFA mobilization after intravenous caffeine administration in humans
Authors: Hetzler R. K. , Knowlton R. G. , Somani S. M. , Brown D. D. , Perkins R. M.
Published: December 2017

Because it has previously been shown that it takes much more caffeine to cause fat mobilization in vitro than in vivo, it has been suggested that there may be an active metabolite working with caffeine causing an increase in lipolysis in vivo. To determine the relationship between the appearance of paraxanthine (caffeine's major dimethylxanthine metabolite) and free fatty acid (FFA) mobilization after intravenous caffeine administration, 10 men were studied at rest after receiving a dose of 4 mg/kg lean body mass. Venous blood samples were obtained before dosing and at minutes 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180. Serum levels of FFA, glycerol, caffeine, and paraxanthine were determined in duplicate. Concentrations of FFA and glycerol were corrected for plasma volume changes. A high negative correlation was seen between decreases in caffeine and increases in FFA (r = -0.90) and a high positive correlation was seen between the appearance of paraxanthine and FFA (r = 0.93). It was concluded that paraxanthine may play a role in increased lipolysis after caffeine administration in humans.
Cervical sympathetic and phrenic nerve responses to progressive brain hypoxia
Authors: Wasicko M. J. , Melton J. E. , Neubauer J. A. , Krawciw N. , Edelman N. H.
Published: December 2017

To determine if depression of central respiratory output during progressive brain hypoxia (PBH) can be generalized to other brain stem outputs, we examined the effect of PBH on the tonic (tSCS) and inspiratory-synchronous (iSCS) components of preganglionic superior cervical sympathetic (SCS) nerve activity. Peak phrenic and SCS activity were measured in nine anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats. PBH was produced by inhalation of 0.5% CO in 40% O2 while blood pressure and end-tidal CO2 were maintained constant. A progressive reduction in arterial O2 content from 14.3 +/- 0.6 to 4.5 +/- 0.3 vol% caused a 79 +/- 7% depression of peak phrenic activity and an 84 +/- 10% reduction of iSCS activity, but tSCS activity increased 42 +/- 21%. During CO2 rebreathing, iSCS activity increased in parallel with peak phrenic activity while tSCS activity was unchanged. The slopes of the CO2 responses of both phrenic (6.3 +/- 1.2%max/mmHg) and iSCS (4.6 +/- 0.8%max/mmHg) activity were unaffected by PBH. In four of nine hypocapnic and three of nine hypoxic studies, inspiratory activity in the SCS nerve was observed even after completely silencing the phrenic neurogram.(ABSTRACT TRUNCATED AT 250 WORDS)
Heat loss responses in rats acclimated to heat loaded intermittently
Authors: Shido O. , Nagasaka T.
Published: December 2017

The present study examined the heat loss response of heat-acclimated rats to direct body heating with an intraperitoneal heater or to indirect warming by elevating the ambient temperature (Ta). The heat acclimation of the rats was attained through exposure to Ta of 33 or 36 degrees C for 5 h daily during 15 consecutive days. Control rats were kept at Ta of 24 degrees C for the same acclimation period. Heat acclimation lowered the body core temperature at Ta of 24 degrees C, and the core temperature level was lowered as acclimation temperature increased. When heat was applied by direct body heating, the threshold hypothalamic temperature (Thy) for the tail skin vasodilation was also lower in heat-acclimated rats than in the control rats. However, the amount of increase in Thy from the resting level to the threshold was the same in all three groups. When heat was applied by indirect warming, threshold Thy was slightly higher in heat-acclimated than in control rats. The amount of increase in Thy from the resting level to the threshold was significantly greater in heat-acclimated rats. In addition, Ta and the skin temperature at the onset of skin vasodilation were significantly higher in heat-acclimated rats. The results indicate that heat-acclimated rats were less sensitive to the increase in skin temperature in terms of threshold Thy. The gain constant of nonevaporative heat loss response was assessed by plotting total thermal conductance against Thy.(ABSTRACT TRUNCATED AT 250 WORDS)
Diffusivity dependence of multiple-breath washouts of lung periphery
Authors: Berdine G. G. , Dale D. , Johnson J. E. , Lehr J. L.
Published: December 2017

Subpleural concentrations of He and SF6 were measured during multiple-breath washouts from isolated dog lungs. Tidal volume, inspiratory flow, and frequency were in the normal range of canine ventilation. For each gas, there was a local minimum in concentration during inspiration (Cinsp) and a local maximum in concentration during exhalation (Cexp). SF6 exhibited a deeper inspiratory trough than He for each breath of every washout. For large tidal volumes (10-20 ml/kg), Cexp approximated a single exponential decay and He was cleared more rapidly than SF6. For small tidal volumes (2.5 ml/kg), Cexp was multiexponential and SF6 was cleared more rapidly than He. Cinsp/Cexp (a measure of the depth of the inspiratory trough) and the kinetics of Cexp decay were determined for washouts using a tidal volume of 10 and 20 ml/kg and different inspiratory flows. Under all conditions, an increase of inspiratory flow resulted in a deeper inspiratory trough for both He and SF6. For washouts using 10 ml/kg and 60 breaths/min, an increase of inspiratory flow increased the clearance of both gases. In washouts using lower ventilatory frequencies, gas clearance was independent of inspiratory flow. These findings are contrary to predictions of contemporary models of convection and diffusion in the lung. This study suggests that convective axial mixing and radial diffusion in the airways are important determinants of pulmonary gas transport.
Endotoxin protection of rats from pulmonary oxygen toxicity: possible cytokine involvement
Authors: Berg J. T. , Allison R. C. , Prasad V. R. , Taylor A. E.
Published: December 2017

Treatment with endotoxin protects rats against lung injury during hyperoxia (greater than 98% oxygen at 1 atmosphere absolute for 60 h). This study demonstrates that serum from endotoxin-treated donor rats also protects recipients from oxygen toxicity. Rats treated with serum from saline-treated donors were not protected, and protection was not explained by residual endotoxin in protective sera. Unlike endotoxin-protected rats (where lung antioxidant enzyme activity is elevated after hyperoxia), postexposure superoxide dismutase (SOD) and catalase (CAT) activities in the lungs of serum-protected rats were not affected. Levels of tumor necrosis factor (TNF) and interleukin 1 (IL-1) in protective sera were increased. This study demonstrates that increases in lung SOD and CAT activity are not required for endotoxin protection from hyperoxia and suggests that TNF and IL-1 may participate in the mechanism of endotoxin protection.
Energy expenditure during bicycling
Authors: McCole S. D. , Claney K. , Conte J. C. , Anderson R. , Hagberg J. M.
Published: December 2017

This study was designed to measure the O2 uptake (VO2) of cyclists while they rode outdoors at speeds from 32 to 40 km/h. Regression analyses of data from 92 trials using the same wheels, tires, and tire pressure with the cyclists riding in their preferred gear and in an aerodynamic position indicated the best equation (r = 0.84) to estimate VO2 in liters per minute VO2 = -4.50 + 0.17 rider speed + 0.052 wind speed + 0.022 rider weight where rider and wind speed are expressed in kilometers per hour and rider weight in kilograms. Following another rider closely, i.e., drafting, at 32 km/h reduced VO2 by 18 +/- 11%; the benefit of drafting a single rider at 37 and 40 km/h was greater (27 +/- 8%) than that at 32 km/h. Drafting one, two, or four riders in a line at 40 km/h resulted in the same reduction in VO2 (27 +/- 7%). Riding at 40 km/h at the back of a group of eight riders reduced VO2 by significantly more (39 +/- 6%) than drafting one, two, or four riders in a line; drafting a vehicle at 40 km/h resulted in the greatest decrease in VO2 (62 +/- 6%). VO2 was also 7 +/- 4% lower when the cyclists were riding an aerodynamic bicycle. An aerodynamic set of wheels with a reduced number of spokes and one set of disk wheels were the only wheels to reduce VO2 significantly while the cyclists were riding a conventional racing bicycle at 40 km/h.(ABSTRACT TRUNCATED AT 250 WORDS)
Tracheal dead space influences regional ventilation measurement in dogs
Authors: Delaunois L. , Boileau R. , Martin R. R.
Published: December 2017

The lung volume at which airway closure begins during expiration (closing volume, CV) can be measured 1) with a radioactive bolus inspired at residual volume (RV) and 2) with the single-breath N2 elimination test. In previous studies in dogs, we observed that N2 CV was systematically larger than 133Xe bolus CV (Xe CV) [N2 CV %vital capacity (VC) = 35 +/- 2.3 (SE) vs. Xe CV %VC = 24 +/- 2.2, P less than 0.01]. Because the regional RV in the dog is evenly distributed throughout the lung and all airways closed at RV, N2 CV is related to the regional distribution of the tracheal N2; differences between N2 and Xe CV could then be related to the size of the inhaled dead space. Simultaneous measurements of Xe and N2 CV were performed at various sites of Xe bolus injection while the regional distribution of the bolus was measured. Injections at the level of the carina increased Xe CV to a value (30 +/- 1.4%VC) near simultaneous N2 CV (32 +/- 1.5%VC) and increased the unevenness of regional distribution of the Xe bolus. The difference between N2 and Xe CV is then the result of the size of the inspired tracheal dead space. Moreover, comparisons between different values of Xe CV require injections of the boluses at the same distance from the carina.