bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsazepine abolishes pulmonary chemoreflexes induced by capsaicin in anesthetized rats
Authors: Lee L. Y. , Lundberg J. M.
Published: December 2017

Capsaicin stimulates vagal pulmonary C-fiber afferents and elicits pulmonary chemoreflex, characterized by apnea, bradycardia, and hypotension. Similar reflex responses can be also evoked by phenylbiguanide (PBG), another potent and commonly used stimulant of these afferents. This study was carried out to determine the effect of capsazepine, a competitive antagonist of capsaicin, on the reflex responses and C-fiber afferent activity evoked by capsaicin and PBG in anesthetized rats. Intravenous infusion of capsazepine did not cause any significant change in the baseline breathing pattern, but it completely abolished the pulmonary chemoreflex elicited by bolus injection of capsaicin (1–2 micrograms/kg iv) and its blocking effect was rapidly reversible. In contrast, the reflex responses to PBG (1–4 micrograms/kg iv) were not altered by capsazepine despite the fact that they could be effectively prevented by the desensitization of C-fiber afferents resulting from a prior capsaicin treatment. Indeed, although both capsaicin and PBG evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs, the stimulatory effect of the former, but not the latter, was abolished in the same fibers by capsazepine. In summary, capsazepine selectively blocks the stimulatory effect of capsaicin on the vagal C-fiber afferents in the lungs and the consequent pulmonary chemoreflex, presumably by blocking the putative “capsaicin receptors” located in the membrane of these afferent endings.
Maturational differences in step vs. ramp hypoxic and hypercapnic ventilatory responses
Authors: Gozal D. , Arens R. , Omlin K. J. , Marcus C. L. , Keens T. G.
Published: December 2017

The influence of the speed of stimulus presentation on hypoxic and hypercapnic ventilatory responses (step vs. ramp) is not known. Furthermore, it is unclear whether children and adults respond similarly. We tested ramp ventilatory responses to hypercapnia and hypoxia with use of rebreathing in 8 prepubertal children and 11 adults. We tested step ventilatory responses to hypercapnia with single vital capacity breaths of 15% CO2 in O2 and to hypoxia with five tidal breaths of 100% N2. For children, slopes of step hypercapnic ventilatory responses were always greater than those of ramp responses (0.85 +/- 0.07 vs. 0.71 +/- 0.07 l.min-1.Torr end-tidal PCO2-1; P < 0.0005). Conversely, for adults, step responses were always less than ramp responses (0.88 +/- 0.19 vs. 2.10 +/- 0.29 l.min-1.Torr end-tidal PCO2-1; P < 0.0007). Similarly, for children, the slopes of step hypoxic ventilatory responses were always greater than those of ramp responses (-0.71 +/- 0.09 vs. -0.45 +/- 0.04 l.min-1.Torr O2 saturation-1; P < 0.02), and for adults, step responses were always less than ramp responses (-0.68 +/- 0.14 vs. -1.85 +/- 0.46 l.min-1.Torr O2 saturation-1; P < 0.04). We conclude that ventilatory responses vary depending on step vs. ramp presentation of hypercapnia or hypoxia and that the ratio of these responses is reversed in children compared with adults. We speculate that the responsiveness of peripheral chemoreceptors is increased in children compared with adults and that it may play a role in the mechanisms leading to increased ventilatory responses observed during childhood.
Assessment of acute pleural effusion in dogs by computed tomography
Authors: Dechman G. , Mishima M. , Bates J. H.
Published: December 2017

We used computed tomography (CT) to examine the effects of infusing 60 ml/kg of saline into the pleural space of four anesthetized paralyzed dogs ventilated with a constant tidal volume at a positive end-expiratory pressure of 0.5 kPa. The dogs were positioned supine, and the thoracic cavity was scanned from apex to base before and immediately after effusate loading. Each CT image was analyzed semi-automatically on a 486 personal computer with custom-designed software. We found that, despite right-side infusion, the effusate was distributed bilaterally no doubt because of the incomplete canine mediastinum. In general, the volume change of the lung was one-third and that of the chest wall was two-thirds that of the total volume infused. Most of the lung volume was contained in the caudal one-third of the lung pre-effusion, and most of the lung volume loss due to effusion was from this same region. Chest wall volume increased and in a more uniform manner post-effusion. The decrease in lung volume resulted in an increase in the mean density of the lung and an increase in its vertical density gradient as the lung was lifted upward toward the sternum by the effusate. The lung lost vertical height while the chest wall increased both its vertical and lateral dimensions after effusate loading. These results suggest that expansion of the chest wall helps preserve lung volume in the presence of acute pleural effusion. We have also demonstrated that CT is a useful tool for assessing changes in volume, shape, and density of the respiratory system.
Changes in magnetic resonance images of muscle depend on exercise intensity and duration, not work
Authors: Jenner G. , Foley J. M. , Cooper T. G. , Potchen E. J. , Meyer R. A.
Published: December 2017

Echo-planar magnetic resonance imaging was used to study the effect of exercise rate and duration on magnetic resonance imaging signal intensity (SI) of anterior tibialis muscle in normal human subjects (mean age 35 yr, n = 6). Axial midcalf echo-planar images (repetition time/echo time = 6,000/45, acquisition time = 80 ms) were acquired every 6 s for 1 min before and during 15 min of dynamic ankle dorsiflexion exercise (peak force 36% of 1 repetition maximum) at 10, 20, and 30 contractions/min. At each rate, muscle SI rose along an approximately exponential time course (mean time constant 1.8 min) toward a plateau that was linearly dependent on force times contraction rate (r = 0.64, P < 0.01) but varied significantly among subjects. The results confirm previous reports that changes in muscle SI correlate with exercise intensity, but not with total work performed, over a submaximal range of exercise intensities.
Assessment of cardiorespiratory function using oscillating inert gas forcing signals
Authors: Williams E. M. , Aspel J. B. , Burrough S. M. , Ryder W. A. , Sainsbury M. C. , Sutton L. , Xiong L. , Black A. M. , Hahn C. E.
Published: December 2017

A theoretical model (Hahn et al. J. Appl. Physiol. 75: 1863–1876, 1993) predicts that the amplitudes of the argon and nitrous oxide inspired, end-expired, and mixed expired sinusoids at forcing periods in the range of 2–3 min (frequency 0.3–0.5 min-1) can be used directly to measure airway dead space, lung alveolar volume, and pulmonary blood flow. We tested the ability of this procedure to measure these parameters continuously by feeding monosinusoidal argon and nitrous oxide forcing signals (6 +/- 4% vol/vol) into the inspired airstream of nine anesthetized ventilated dogs. Close agreement was found between single-breath and sinusoid airway dead space measurements (mean difference 15 +/- 6%, 95% confidence limit), N2 washout and sinusoid alveolar volume (mean difference 4 +/- 6%, 95% confidence limit), and thermal dilution and sinusoid pulmonary blood flow (mean difference 12 +/- 11%, 95% confidence limit). The application of 1 kPa positive end-expiratory pressure increased airway dead space by 12% and alveolar volume from 0.8 to 1.1 liters but did not alter pulmonary blood flow, as measured by both the sinusoid and comparator techniques. Our findings show that the noninvasive sinusoid technique can be used to measure cardiorespiratory lung function and allows changes in function to be resolved in 2 min.
Ventilatory responses to CO2 and hypoxia after sustained hypoxia in awake cats
Authors: Long W. , Lobchuk D. , Anthonisen N. R.
Published: December 2017

In humans and cats the ventilatory response to 30 min of isocapnic hypoxia is biphasic with an initial increase followed by a decrease, termed “hypoxic depression.” In humans, 30 min of hypoxia reduces the initial response to a subsequent hypoxic exposure. These experiments were to determine whether the same occurred in cats. Cats were studied while awake. End-tidal Po2 and Pco2 were measured by sampling tracheal gas, and ventilation was measured plethysmographically. In seven cats we measured ventilatory responses to two 30-min periods of isocapnic hypoxia (end-tidal Po2 = 60–65 Torr) separated by 5 min of room air breathing. The first hypoxic response was biphasic, with ventilation increasing to 149% of control at 5 min and decreasing to 117% of control at 25 min. During the second exposure, ventilation was 119% of control at 5 min and 113% of control at 25 min; 30 min of hypoxia depressed the subsequent hypoxic response. Hypoxic depression outlasted the hypoxia, suggesting that it was mediated by relatively slow neurochemical events. In five cats ventilatory responses to 5% CO2 were measured before and 5 min after 30 min of isocapnic hypoxia and before and after 30 min of room air breathing. Hypoxia did not affect CO2 responses. Thus the neurochemical events that cause hypoxic depression appear not to involve the neurons generating the response to CO2 and may be specific to those involved in the hypoxic response.
Diffusing capacity dependent on lung volume and age in normal subjects
Authors: Stam H. , Hrachovina V. , Stijnen T. , Versprille A.
Published: December 2017

In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO) and DLCO per liter alveolar volume (DLCO/VA) at total lung capacity (TLC) and at lung volumes below TLC in sitting position. In 55 healthy nonsmoking volunteers (20–85 yr old), we determined reference values at TLC level in which age was the only parameter. In a subgroup (n = 16) these references did not change by correction for normal variability in hemoglobin concentration. In all volunteers DLCO decreased and DLCO/VA increased with decreasing VA. The increase in DLCO/VA was linear and less in older subjects. We derived equations to calculate reference values of DLCO/VA for lung volumes at and below TLC with two methods: 1) “random coefficients linear” model, which calculates the reference values directly, and 2) a conversion method, which calculates DLCO/VA for lower VA levels from reference values at TLC. An advantage of the conversion method is the suitability of DLCO/VA reference values at TLC of other populations. A disadvantage is the greater standard deviation of these reference values compared with those obtained by the random coefficients linear method. DLCO can be found by multiplying DLCO/VA with VA.
Mechano- and chemoreceptor modulation of respiratory muscles in response to upper airway negative pressure
Authors: Gauda E. B. , Carroll T. P. , Schwartz A. R. , Smith P. L. , Fitzgerald R. S.
Published: December 2017

To investigate the influence of phasic pulmonary stretch receptors (n = 6) and chemoreceptors (n = 7) on the reflex response of the genioglossus (GG) muscle and diaphragm (DIA) to upper airway (UAW) negative pressure, we measured the response of the GG and DIA electromyogram (EMG) to three challenges: 1) negative pressure applied to the UAW during normoxia and hypercapnia, 2) end-expiratory tracheal occlusion, and 3) application of UAW negative pressure simultaneous with tracheal occlusion in spontaneously breathing tracheotomized anesthetized cats. Peak GG EMG was greatest when UAW negative pressure and end-expiratory tracheal occlusion were combined. No GG EMG activity was seen when UAW negative pressure was applied alone unless the animal was vagotomized or hypercapnic. DIA EMG increased in response to UAW negative pressure combined with occlusion. However, the increase in peak GG EMG was significantly greater than for the DIA with the same challenge. DIA EMG amplitude increased in response to occlusion alone but did not change when UAW negative pressure was applied alone. In the cat, phasic feedback from phasic pulmonary stretch receptors is a potent inhibitor of reflex activation of the GG in response to negative pressure applied to the UAW, which can be overridden by an increase in chemoreceptor drive.
Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition
Authors: Meyer J. , Hinder F. , Stothert J. , Traber L. D. , Herndon D. N. , Flynn J. T. , Traber D. L.
Published: December 2017

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.
Albumin exchange and inflammatory cell recruitment in lungs of antigen-challenged guinea pigs: role of histamine
Authors: Bureau M. F. , Arreto C. D. , Lefort J. , Vargaftig B. B.
Published: December 2017

Microvascular albumin exchange and sequestration of inflammatory cells into the lungs of anesthetized guinea pigs immunized to ovalbumin were evaluated using radioactive tracers. Increased exchange of radiolabeled (*) albumin from airways to blood was noted in immunized and boosted animals under basal conditions. After the intratracheal injection of 300 micrograms of ovalbumin, an additional increase in exchange through epithelium occurred, since the rate of appearance of *albumin in blood was enhanced compared with control (140 +/- 30 vs. 54 +/- 20% in 1 h). The augmentation of lung content in extravascular *albumin compared with control (16.2 +/- 4.0 vs. 5.9 +/- 1.6%) indicates that transendothelial exchange was also facilitated. Concomitment with the sequestration of *platelets into the lungs of antigen-challenged sensitized animals (59.2 +/- 20% in 1 h), leukocytes (> 60% polymorphonuclear neutrophils) did not marginate. Histamine released during antigenic shock might promote leukocyte demargination from the vascular bed through its vasomotor effect and/or by inhibiting leukocyte activation and consequently may counteract the effects of other inflammatory mediators acting to sequester neutrophils. In confirmation, perfusion of histamine to the immunized animals induced demargination of lung leukocytes. Histamine antagonists prevented the increased exchange of *albumin through the epithelial and endothelial barriers and uncovered *leukocyte sequestration (100.7 +/- 28.9% in 1 h) in the lungs of antigen-challenged animals. Histamine antagonists may favor antigen-induced leukocyte sequestration in the lungs by preventing the effects of endogenous histamine on capillary recruitment and blood flow.
Contributions of thromboxane and leukotrienes to PAF-induced impairment of lung function in the rat
Authors: Uhlig S. , Wollin L. , Wendel A.
Published: December 2017

This study was carried out to further clarify the role of eicosanoids in platelet-activating factor (PAF)-induced pulmonary vasoconstriction, bronchoconstriction, and edema formation in the isolated perfused rat lung. Infusion of PAF into the isolated perfused rat lung caused vasoconstriction [mean effective concn (EC50) = 0.88 nmol], caused bronchoconstriction (EC50 = 0.71 nmol), and increased the capillary filtration coefficient (EC50 = 1.4 nmol). Two minutes after injection of 50 nmol PAF, a high thromboxane concentration (3,000 pg/ml) and a low peptidoleukotriene concentration (150 pg/ml) were found in the effluent perfusate. PAF-induced vaso- and bronchoconstriction were unaffected by the non-redox 5-lipoxygenase inhibitor ZM-230,487 but were markedly attenuated by inhibition of cyclooxygenase with acetylsalicylic acid or thromboxane-receptor antagonism with BM-13177. Dual inhibition of cyclooxygenase and 5-lipoxygenase had the most pronounced inhibitory effect on PAF-induced vaso- and bronchoconstriction. None of the inhibitors tested prevented the increase in vascular permeability. We conclude that thromboxane is the major vasoconstrictor and bronchoconstrictor induced by PAF, whereas leukotrienes contribute a significant but minor part in this system. PAF-induced microvascular permeability was not inhibited by blockade of arachidonate metabolism and therefore seems to be mediated by a mechanism independent of eicosanoids.
Effect of dopamine on hypoxic ventilatory response of sedated piglets with intact and denervated carotid bodies
Authors: Suguihara C. , Hehre D. , Bancalari E.
Published: December 2017

To determine whether the neonatal hypoxic ventilatory depression is in part produced by an increased endogenous dopamine release that can depress the activity of central and peripheral chemoreceptors, 31 sedated and spontaneously breathing newborn piglets [age 5 +/- 1 (SD) days; weight 1.7 +/- 0.4 kg] were randomly assigned to an intact carotid body or a chemodenervated group. Minute ventilation (VE), arterial blood pressure, and cardiac output (CO) were measured in room air before infusion of saline or the dopamine antagonist flupentixol (0.2 mg/kg i.v.) and 15 min after drug infusion and were repeated after 10 min of hypoxia (inspiratory O2 fraction = 0.10). VE increased significantly after 10 min of hypoxia in the piglets that received flupentixol independent of whether the carotid bodies were intact or denervated. However, the increase in VE was largest and sustained throughout the 10 min of hypoxia only in the intact carotid body flupentixol group. As expected, the initial increase in VE with hypoxia was abolished by carotid body denervation. Changes in arterial blood gases, CO, and mean arterial blood pressure with hypoxia were not different among groups. These results demonstrate that flupentixol reverses the late hypoxic decrease in VE, acting through peripheral and central dopamine receptors. This effect is not related to changes in cardiovascular function or acid-base status.
Effects of increased energy intake and/or physical activity on energy expenditure in young healthy men
Authors: Goran M. I. , Calles-Escandon J. , Poehlman E. T. , O'Connell M. , Danforth E.
Published: December 2017

This study was designed to examine effects of alterations in energy balance on adaptive changes in components of total energy expenditure (TEE). Nineteen young healthy males were studied during a 10-day sedentary energy balance baseline period and then randomly assigned to one of four 10-day treatment groups: 1) no change in energy intake (EI) or physical activity (PA; energy balance at low energy flux), 2) EI increased by 50% with no change in PA (positive energy balance), 3) TEE increased by 50% by increasing PA, matched by a 50% increase in EI (energy balance at high energy flux), and 4) TEE increased by 50% by increasing PA with no change in EI (negative energy balance). TEE was measured with doubly labeled water, resting metabolic rate (RMR) by indirect calorimetry, and thermic response to feeding (TEF) by indirect calorimetry; energy expenditure of physical activity (EEPA) was estimated by subtracting RMR, TEF, and prescribed PA from TEE. TEE was significantly increased by PA (by design) but not EI. There was a significant main effect of intake and a significant intake-by-activity interaction for changes in RMR. In post hoc analysis, RMR was significantly increased during positive energy balance and energy balance at high energy flux relative to change in RMR when energy balance was maintained at low energy flux. A significant increase in RMR was also noted during negative energy balance after adjustment for change in fat-free mass. There was no significant difference in change in RMR among the three treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary arterial smooth muscle contractility in hypoxia-induced pulmonary hypertension
Authors: Griffith S. L. , Rhoades R. A. , Packer C. S.
Published: December 2017

The highly compliant low-resistance pulmonary vasculature is markedly altered with chronic hypoxia. Remodeling in response to hypoxia and/or hypertension involves hypertrophy and hyperplasia of smooth muscle and excessive deposition of connective tissue that likely contributes to the maintenance or exasperates the already elevated pulmonary arterial (PA) pressure. The purpose of this study was to investigate the effect of chronic hypoxia on the contractile properties of PA smooth muscle. Isometric and isotonic experiments were performed on excised PA rings from pulmonary hypertensive (induced by 14 days of hypoxia) Sprague-Dawley rats. A doubling of the vessel wall thickness occurred during the development of hypoxia-induced pulmonary hypertension. Functionally, there was a decrease in isometric stress (force to cross-sectional area ratio). No difference was detected in the velocity of shortening or in total shortening ability. This study provides evidence that, in addition to the morphological changes, changes in PA smooth muscle contractility also appear to play a role in the development and/or maintenance of hypoxia-induced pulmonary hypertension.
Cardiovascular effects of NG-methyl-L-arginine in chronically instrumented conscious dogs
Authors: Lechevalier T. , Doursout M. F. , Chelly J. E. , Kilbourn R. G.
Published: December 2017

The cardiovascular effects of nitric oxide blockade were examined in five conscious chronically instrumented dogs. The hypothesis tested was that nitric oxide release plays a role in vascular tone and regional organ blood flow under physiological conditions. Aortic pressures; the first derivative of the left ventricular pressure; cardiac output (CO); heart rate; and carotid, coronary, renal, hepatic, and portal blood flows were recorded before and after bolus injection of 5, 10, and 20 mg/kg of NG-methyl-L-arginine (L-NMA). In response to L-NMA, mean arterial pressure increased by 7, 20, and 35%, respectively, in a dose-dependent manner, whereas CO decreased. CO reduction was sustained at the highest dose, whereas peripheral blood flows were not altered. These data suggest that blocking basal nitric oxide synthesis by administering L-NMA leads to a modest dose-dependent pressor response despite a marked and sustained reduction in CO recorded at the highest dose of L-NMA. Moreover, within our dose range, although the nitric oxide synthase inhibition provides a significant pressor response, it does not alter the resting carotid, coronary, renal, hepatic, and portal blood flows.
Myosin isoforms in mammalian skeletal muscle
Authors: Schiaffino S. , Reggiani C.
Published: December 2017

Skeletal muscles of different mammalian species contain four major myosin heavy-chain (MHC) isoforms: the “slow” or beta-MHC and the three “fast” IIa-, IIx-, and IIb-MHCs; and three major myosin light-chain (MLC) isoforms, the “slow” MLC1s and the two “fast” MLC1f and MLC3f. The differential distribution of the MHCs defines four major fiber types containing a single MHC isoform and a number of intermediate hybrid fiber populations containing both beta/slow- and IIa-MHC, IIa- and IIx-MHC, or IIx- and IIb-MHC. The IIa-, IIx-, and IIb-MHCs were first detected in neonatal muscles, and their expression in developing and adult muscle is regulated by neural, hormonal, and mechanical factors. The transcriptional mechanisms responsible for the fiber type-specific regulation of MHC and MLC gene expression are not known and are presently being explored by in vivo transfection experiments. The functional role of MHC isoforms has been in part clarified by correlated biochemical-physiological studies on single skinned fibers: these studies, in agreement with results from in vitro motility assays, indicate that both MHC and MLC isoforms determine the maximum velocity of shortening of skeletal muscle fibers.
Systemic and diaphragmatic oxygen delivery-consumption relationships during hemorrhage
Authors: Ward M. E. , Chang H. , Erice F. , Hussain S. N.
Published: December 2017

When tissue O2 delivery falls below a critical threshold, tissue O2 uptake (VO2) becomes limited. We compared critical O2 delivery and critical and maximum O2 extraction ratios of the resting and contracting left hemidiaphragm with those of nondiaphragmatic tissues in seven dogs. The left hemidiaphragm was perfused through the left inferior phrenic artery with blood from the left femoral artery. Phrenic venous blood was sampled through a catheter in the inferior phrenic vein. Systemic O2 delivery was reduced in stages by controlled hemorrhage. Left diaphragmatic VO2 during rest and during 3 min of continuous stimulation (3 Hz) of the left phrenic nerve and VO2 of the remaining nonleft hemidiaphragmatic tissues were measured at each stage. Critical diaphragmatic O2 delivery for the resting diaphragm averaged 0.8 +/- 0.16 ml.min-1.100 g-1 with a critical O2 extraction ratio of 65.5 +/- 6%. In the contracting diaphragm, they averaged 5.1 +/- 0.9 ml.min-1.100 g-1 and 81 +/- 5%, respectively. Whole body O2 delivery at which resting diaphragmatic VO2 became supply limited was similar to that for nondiaphragmatic tissues. By comparison, supply limitation of VO2 occurred at a higher systemic O2 delivery in the contracting diaphragm than in the rest of the body despite the increase in critical diaphragmatic extraction ratio. Thus, oxygenation of the isolated diaphragm does not appear to be preferentially preserved during generalized reductions in O2 delivery. These results suggest that, in diseases associated with increased work of breathing and decreased O2 delivery, the diaphragm may become metabolically impaired before limitation of VO2 is observed systemically.
Excitatory connections between upper cervical inspiratory neurons and phrenic motoneurons in cats
Authors: Nakazono Y. , Aoki M.
Published: December 2017

This study aimed to determine whether upper cervical inspiratory neurons (UCINs), which are localized in the intermediolateral part of the gray matter of the upper cervical segments, have propriospinal connections to phrenic motoneurons of the ipsilateral lower cervical segment in anesthetized cats. Unit action potentials of UCINs were extracellularly recorded simultaneously with ipsilateral phrenic nerve activity. To eliminate the descending influences from medullary respiratory neurons to phrenic motoneurons, bulbospinal conduction paths were temporarily blocked by focal cooling applied to the ventral caudal medulla at the pyramidal decussation level by means of a cooling thermode (1 mm tip diam). By using a spike-triggered method, during cooling phrenic nerve activities were evoked by UCIN spikes that were elicited by microinjection of L-glutamate for 20 of the 55 (36%) UCIN units examined. The onset latencies of these phrenic motoneuron responses ranged from 1.5 to 7.1 ms (mean 3.6 ms), depending on synaptic transmission delays. These results clearly demonstrate that UCINs have, at least in part, excitatory mono- and paucisynaptic connections with ipsilateral phrenic motoneurons.
Reversal of pulmonary capillary ischemia-reperfusion injury by rolipram, a cAMP phosphodiesterase inhibitor
Authors: Barnard J. W. , Seibert A. F. , Prasad V. R. , Smart D. A. , Strada S. J. , Taylor A. E. , Thompson W. J.
Published: December 2017

Isoproterenol (ISO) and forskolin, agents that increase adenosine 3′,5′-cyclic monophosphate (cAMP) via adenylyl cyclase activation, reverse lung injury associated with increased microvascular permeability. We studied the role of rolipram, a relatively isozyme-selective cAMP phosphodiesterase (PDE) inhibitor, in reversing increased capillary permeability due to ischemia-reperfusion (I/R), a form of oxidant injury in the lung, by using the isolated perfused rat lung model. Rolipram (2 microM) administered after 45 min of ischemia and 45 min of reperfusion reduced I/R-increased permeability as measured by the capillary filtration coefficient to control lung values. Computer image analysis of air space edema and perivascular cuffing, as well as wet-to-dry weight ratios, confirms the permeability reversal by rolipram administration. Rolipram inhibition of cAMP PDE in the lung was assessed by using [3H]adenine prelabeling adapted for the whole lung and perfusate [3H]cAMP accumulation. Rolipram failed to increase perfusate cAMP alone but dramatically increased perfusate cAMP above ISO alone. Dose-response relationships of ISO or rolipram show a close correlation of the half-maximal effective dose (ED50) for injury reversal and perfusate cAMP production. The combination of rolipram and ISO produced synergistic reversal of I/R injury. We conclude that reversal of I/R-induced increased microvascular permeability can be achieved with rolipram and that the mechanism of action of rolipram is probably through PDE isozyme-selective inhibition. The similarity of the ED50 values for cAMP efflux and reversal of permeability increases also supports a close coupling between cAMP accumulation and endothelial cell permeability.
Interactive effects of emphysema and malnutrition on diaphragm structure and function
Authors: Lewis M. I. , Monn S. A. , Zhan W. Z. , Sieck G. C.
Published: December 2017

Interactive effects of emphysema (EMP) and prolonged nutritional deprivation (ND) on contractile, morphometric, and metabolic properties of hamster diaphragm muscle (DIA) were examined. Six months after induction of EMP (intratracheal elastase), saline-treated controls (CTL) and EMP hamsters of similar body weights were subjected to ND over 6 wk. Isometric contractile and fatigue properties of costal DIA were determined in vitro. DIA fibers were histochemically classified as type I or II, and fiber succinate dehydrogenase activity and cross-sectional area were determined using quantitative microscopic procedures. From histochemical sections, the number of capillaries per fiber (C/F) and per fiber cross-sectional area (C/A) were determined. ND resulted in progressive loss of body weight (ND-CTL, 23.8%; ND-EMP, 28.4%; P = NS). ND did not affect reduction in optimal length (Lo) of DIA fibers in EMP compared with CTL and ND-CTL hamsters. Maximum specific force (i.e., force/unit area) was reduced by approximately 25% in EMP animals compared with CTL. ND did not improve or exacerbate the reduction in specific force with EMP. ND attenuated improved fatigue resistance of DIA in EMP animals. No differences in fiber type proportions were noted among experimental groups. Significant atrophy of type I and II DIA fibers was noted after ND. Atrophy was proportionately greater in type II fibers of ND-EMP when referenced to EMP animals. Thus adaptive hypertrophy of type II DIA fibers in EMP animals was abolished. Fiber succinate dehydrogenase activity was significantly increased in type I and II fibers in EMP DIA. ND did not affect this metabolic adaptation of DIA fibers to persistent loads imposed by EMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of resistance exercise on glucose tolerance in normal and glucose-intolerant subjects
Authors: Fluckey J. D. , Hickey M. S. , Brambrink J. K. , Hart K. K. , Alexander K. , Craig B. W.
Published: December 2017

This study was conducted to determine whether improvements in glucose tolerance could be observed after a single bout of resistance exercise in young (27.1 +/- 1.24 yr) control subjects, older (53.3 +/- 1.7 yr) patients with non-insulin-dependent diabetes mellitus (NIDDM), and older (50.7 +/- 1.9 yr) age-matched control subjects. Each subject was screened for fitness level and any contraindications to exercise before inclusion in the study. A 75-g oral glucose tolerance test was administered 2 wk after the subjects were screened, and the subjects were familiarized with the exercise equipment. The maximum weight that could be lifted with one repetition was determined on seven Nautilus machines that utilized the upper and lower body. After a 48-h rest period, a 3-set x 10-repetition protocol based on the subject's one repetition maximum was completed by each participant on each machine. Eighteen hours after the lifting protocol, a second oral glucose tolerance test was administered. There was no change in the pre- to post-exercise glucose levels in any of the treatment groups, but the total insulin responses (area under the curve) of the young control and NIDDM groups were significantly lower after exercise: from 6.93 +/- 0.8 x 10(3) to 5.38 +/- 0.65 x 10(3) pM in the young control group and from 9.83 +/- 1.95 x 10(3) to 7.77 +/- 1.50 x 10(3) pM in the NIDDM group. The postexercise C-peptide levels were unchanged in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Edema development and recovery in neurogenic pulmonary edema
Authors: Maron M. B. , Holcomb P. H. , Dawson C. A. , Rickaby D. A. , Clough A. V. , Linehan J. H.
Published: December 2017

We determined the time course of changes in extravascular lung water (EVLW) that occur after massive sympathetic activation produced by intracisternal veratrine administration in chloralose-anesthetized dogs. Three groups of dogs were studied. In the first group (n = 9), acute increases in EVLW (occurring within minutes) were determined both by measuring extravascular thermal volume and by gravimetric analysis. In the second (n = 6) and third (n = 7) groups, changes in EVLW were followed for 2–3 h after veratrine administration. Extravascular thermal volume was measured in the second group. In the third group, right atrial injections of a vascular indicator (125I-labeled serum albumin) and an extravascular indicator (3HOH) were made while blood was sampled from the pulmonary artery (PA) and left atrium, and EVLW was determined by deconvolution of the left atrial and PA concentration-time curves. Indicator-dilution and gravimetric EVLW increased acutely only in dogs in which PA pressure exceeded 60 Torr, with two- to four-fold increases in EVLW being observed in dogs that developed the highest PA pressures (maximum 94 Torr). Thus, severe edema can develop rapidly after massive sympathetic nervous system activation but requires extreme degrees of pulmonary hypertension. In several dogs after the acute increase in EVLW associated with the pulmonary hypertension, the indicator-dilution EVLW decreased with time. These decreases appear to effect clearance of edema fluid rather than alterations in perfusion.
Interactive effects of K+, acidosis, and catecholamines on isolated rabbit heart: implications for exercise
Authors: Leitch S. P. , Patterson D. J.
Published: December 2017

Intense exercise can double arterial K+ concentration, decrease pH by 0.4 units, and increase catecholamines 15-fold. Any one of these changes may be cardiotoxic in a subject at rest, yet these changes are well tolerated in exercise. We tested the interactive effects of extracellular K+ concentration ([K+]o), metabolic acidosis (pH 7.0), and raised catecholamines in the isolated working rabbit heart when they were changed with similar kinetics and concentrations to those seen in exercise. Raised [K+]o (8 and 12 mM) significantly decreased aortic flow (AF) by 23 and 76%, respectively (P < 0.01). Acidosis decreased AF by 19% (P < 0.05) and by 38% in combination with 8 mM [K+]o (P < 0.05), making their combined effect additive. Either epinephrine (80 nM), norepinephrine (80 nM) or extracellular Ca2+ concentration (5 mM) offset the negative effects of 8 and 12 mM [K+]o on AF. Norepinephrine also improved AF in 8 mM [K+]o with acidosis. Thus, there may be a beneficial interaction among changes in K+, catecholamines, and acidosis during exercise such that each could offset the others' potentially harmful effects.
Effects of detection and classification of resistive and elastic loads on endogenous event-related potentials
Authors: Bloch-Salisbury E. , Harver A.
Published: December 2017

Resistive and elastic loads added to inspiration are readily detected, and detection latencies vary as a function of load magnitude and load type. In the present study, we recorded endogenous event-related potentials (i.e., N2 and P3) to the detection and classification of large (15.0 cmH2O.1–1.s and 70.0 cmH2O/l) and small (1.45 cmH2O.1–1.s and 19.0 cmH2O/l) loads equated for subjective magnitude in 14 men (mean age 21.14 yr). In blocks of trials comprised of either large or small loads, subjects made a button-press response upon detecting a load and then classified the load as resistive or elastic. Loads were presented briefly (for approximately 200 ms) early in inspiration and at the same level of inspiratory pressure. For loads of comparable magnitude, subjects detected equivalent numbers of resistive and elastic loads but could not discriminate reliably between load types. On the other hand, the latency of N2 was shorter to larger than to smaller loads, to resistive than to elastic loads, and to correct than to incorrect load classifications. The latency of P3 was affected similarly by load magnitude and load type. These findings demonstrate that event-related potentials are elicited by brief presentations of resistive and elastic loads and that N2 and P3 latencies vary reliably as a function of load magnitude and load type. Most importantly, event-related potential latencies are sensitive to load type and to classification accuracy even when resistive and elastic loads are not distinguishable subjectively.
Effects of domperidone on neonatal and adult carotid chemoreceptors in the cat
Authors: Tomares S. M. , Bamford O. S. , Sterni L. M. , Fitzgerald R. S. , Carroll J. L.
Published: December 2017

It has been postulated that the weak carotid chemoreceptor responses of neonatal mammals may be due to inhibition produced by high levels of endogenous dopamine release or exaggerated sensitivity to dopaminergic inhibition. This was studied by measuring the effect of domperidone, a selective dopamine D2-receptor antagonist, on the carotid chemoreceptor response to O2 and CO2 in anesthetized neonatal and adult cats. The animals were exposed to four levels of isocapnic O2 (arterial PO2 of approximately 35–45, 55–65, 80–90, > 300 Torr) and four levels of isoxic CO2 (end-tidal PCO2 of approximately 21, 40, 58, and 78 Torr) before and after D2-receptor blockade. Whole nerve activity was recorded from the carotid sinus nerve (CSN). Both neonatal and adult cats increase CSN activity during hypoxia and hypercapnia (P < 0.001). Domperidone caused an increase in CSN activity at all O2 levels in adults (P < 0.01) but only during hypoxia in neonates (P < 0.001). Domperidone caused an increase in CSN activity during normo- and hypercapnia in adults but only during hypercapnia in neonates (P < 0.001). Domperidone approximately doubled an index of hypoxic sensitivity in the normoxia-hypoxia range (100 to 40 Torr) in the neonatal group but had little effect on sensitivity to hypoxia in adults. We conclude that the inhibitory role of endogenous dopamine in the carotid chemoreceptors changes with postnatal development.
Removal of albumin microinjected in rat lung perimicrovascular space
Authors: Ying X. , Qiao R. , Ishikawa S. , Bhattacharya J.
Published: December 2017

We used a microinjection approach to assess hydraulic properties of lung perimicrovascular adventitia (interstitial cuff surrounding microvessels). Isolated blood-perfused rat lungs held at constant airway pressure were microscopically viewed to identify subpleural venules (20 microns diam). Venular adventitia were microinjected with 20 nl of fluorescent albumin (4 g/dl), and then adventitial fluorescence was quantified at the injection site by either photometery or imaging. Nonlinear decay of adventitial fluorescence indicated liquid flux from the injection site into normal interstitium. In some experiments, we determined that the adventitial fluorescence flowed longitudinally along the venule length and filled single lymphatics. The fluorescence decay at the injection site was best described by equations of convective but not diffusive transport. The decay time constant (time to 37% initial), which relates inversely to hydraulic conductivity, increased 10-fold above baseline on lung expansion with airway pressure from 5 to 15 cmH2O (P < 0.05). However, presence or absence of blood flow, increase in filtration pressure, and tissue edema were all without effect on the time constant. Our estimate of the lower limit of baseline adventitial hydraulic conductivity was 5 x 10(-6) ml.cm-2.s-1.cmH2O-1. We conclude that hydraulic conductivity of perimicrovascular adventitia is not augmented by edema but that it is decreased by lung expansion.
Respiratory motor nerve activities during spontaneous bladder contractions
Authors: Gdovin M. J. , Knuth S. L. , Bartlett D.
Published: December 2017

We monitored spontaneous bladder contractions (SBCs) in decerebrate vagotomized paralyzed ventilated cats while recording respiratory motor nerve activities and intravesical pressure under isovolumetric conditions. Phrenic nerve discharge diminished during SBCs, as did the activities of the hypoglossal nerve, the nasolabial branch of the facial nerve, and inspiratory (posterior cricoarytenoid) and expiratory (thyroarytenoid) branches of the recurrent laryngeal nerve. Hypoglossal activity was most strikingly reduced during SBCs, disappearing completely in some animals. The triangularis sterni nerve exhibited an initial decrease, followed by an increase in activity during SBCs, whereas the cranial iliohypogastric nerve showed increased activity. The changes in nerve activities during SBCs could also be elicited by passive distension of the bladder and were abolished by bilateral section of the pelvic nerves. These findings extend the understanding of reflexes originating from the urinary bladder to include a coordinated respiratory response and suggest that these reflexes may compromise upper airway patency under some conditions.
An approach to the study of upper airway function in humans
Authors: Younes M. , Sanii R. , Patrick W. , Marantz S. , Webster K.
Published: December 2017

Current methods for testing upper airway (UA) collapsibility in humans tend to produce intervention-related changes in some of the variables that affect UA stability. Therefore, their results may not reflect UA stability under the experimental conditions of interest. In the proposed method, the subject lies in a body enclosure with head and neck out. Pressure is altered in brief (approximately 0.2-s) pulses to avoid behavioral responses. The collapsibility of UA under “static” conditions is tested by delivering identical pressure pulses simultaneously to the airway and body surface inside the shell. Because the pressure applied to the respiratory system is not altered, cessation of flow indicates closure, and the pressure at which this happens is Pclosure. Collapsibility under dynamic conditions is tested by applying brief negative pulses to the shell only, thereby forcing an increase in inspiratory flow. Ten normal awake subjects were tested. None of the subjects developed closure when negative pulses (0 to -16 cmH2O) were applied to both airway and shell during inspiration or expiration with either nose or mouth breathing. There were only small reductions in flow, indicating minor narrowing. By contrast, pressure pulses of similar magnitude applied to the shell alone were associated with closure in 5 of 10 subjects. We conclude that the UA of normal awake humans is fairly stable under the influence of statistically applied pressure but susceptible to collapse under conditions of increased flow. Pclosure determined under static conditions underestimates the vulnerability of the UA to collapse under dynamic conditions.
Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction
Authors: Cassin S. , DeMarco V. , Perks A. M. , Kuck H. , Ellis T. M.
Published: December 2017

The present studies were designed to test the hypothesis that arginine vasopressin (AVP) can interact with hydrocortisone and 3,5,3 ′-triiodothyronine (T3) to induce maturation of lung liquid reabsorptive processes in fetal sheep < 130 days gestation. Lung liquid production rates were measured in chronically catheterized thyroidectomized fetal sheep during eight different experimental treatments. Each experiment consisted of a 2-h control period followed by a 5-h treatment period. Net secretion or reabsorption of lung liquid was measured by using impermeant marker dilution techniques. AVP alone (50 mU/kg bolus plus 5.0 mU.kg-1.min-1 i.v. infusion) does not alter lung liquid secretion in fetal sheep 125 +/- 0.72 (SE) days gestation. In contrast, AVP (same dose as above) with T3 (30 micrograms) and hydrocortisone (6.94 mg/min) depressed lung liquid secretion and caused reabsorption of fluid. T3 alone, T3 and hydrocortisone, T3 and AVP, hydrocortisone alone, hydrocortisone and AVP, and saline did not result in net lung liquid reabsorption over a 5-h treatment period. These investigations demonstrate that AVP, T3, and hydrocortisone interact to cause lung liquid reabsorption in immature fetal lungs.
Effects of pulmonary blood flow on the fractal nature of flow heterogeneity in sheep lungs
Authors: Caruthers S. D. , Harris T. R.
Published: December 2017

The spatial heterogeneity of pulmonary blood flow can be described by the relative dispersion (RD) of weight-flow histograms (RD = SD/mean). Glenny and Robertson (J. Appl. Physiol. 69: 532–545, 1990) showed that RD of flow in the lung is fractal in nature, characterized by the fractal dimension (D) and RD for the smallest realizable volume element (RDref). We studied the effects of increasing total pulmonary blood flow on D and RDref. In eight in situ perfused sheep lung preparations, 15-microns radio-labeled microspheres were injected into the pulmonary artery at five different blood flows ranging, in random order, from 1.5 to 5.0 l/m. The lungs were in zone 2 at the lower flows and in zone 3 at the higher flows. The lungs were removed, dried, cut into 2 x 2 x 2-cm3 pieces, weighed, and then counted for microsphere radioactivity. Fractal plots of log(weight) vs. log(RD) were constructed by iteratively combining neighboring pieces and then calculating RD with the increasingly larger portion size. D, which is one minus the slope of the fit through this plot, was 1.14 +/- 0.09 and did not change as blood flow increased. However, RDref decreased significantly (P < 0.01) as total flow increased. We conclude that the fractal nature of pulmonary blood flow distribution is not altered by changes in overall flow.