bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal diaphragmatic blood perfusion
Authors: Hu F. , Comtois A. , Grassino A. E.
Published: December 2017

The intrabreath time course of phrenic artery blood perfusion (Qpha) was studied in five anesthetized dogs. The diaphragm was paced with submaximal levels of stimulation at various duty cycles (DC) to achieve tension-time index below and above the fatigue threshold (0.03–0.60). Left Qpha was measured via Doppler technique during control (inactive diaphragm) and during two submaximal levels of bilateral phrenic nerve stimulation sustained for 1 min. Measurements were done when Qpha reached steady state in each run. The frequency of pacing of each run was 10/min, and the DC ranged from 0.1 to 0.9 in 0.1 increments. Shortening of costal and crural segments was measured by sonomicrometry. It was found that Qpha during the diaphragmatic contraction phase (QphaC) was a sigmoidal function of DC and was not affected by the levels of transdiaphragmatic pressure (Pdi) explored (34–64% of maximal Pdi). Qpha during the diaphragmatic relaxation phase (QphaR) was a parabolic function of the DC, reaching an optimal value at DC of approximately 0.3 at any given Pdi. QphaR increased significantly with the preceding level of Pdi. QphaT (the sum of QphaC and QphaR) was a parabolic function of DC, reaching peak values at DC of 0.4–0.6 and then decreasing. This function was similar at two levels of Pdi. Post-pacing hyperemia was directly related to tension-time index greater than 0.20.
Effect of bronchial smooth muscle contraction on lung compliance
Authors: Mitzner W. , Blosser S. , Yager D. , Wagner E.
Published: December 2017

Lung compliance is generally considered to represent a blend of surface and tissue forces, and changes in compliance in vivo are commonly used to indicate changes in surface forces. There are, however, theoretical arguments that would allow contraction of airway smooth muscle to affect substantially the elasticity of the lung. In the present study we evaluated the role of conducting airway contraction on lung compliance in vivo by infusing methacholine (MCh) at a constant rate into the bronchial circulation. With a steady-state MCh infusion of 2.4 micrograms/min into the bronchial perfusate (perfusate concentration = 0.7 microM), there was an approximate doubling of lung resistance and a 50% fall in dynamic compliance. There were also significant decreases in chord compliance measured from the quasi-static pressure-volume curves and in total lung capacity and residual volume. When the same infusion rate was administered into the pulmonary artery, no changes in lung mechanics were observed. These results indicate that the conducting airways may have a major role in regulating lung elasticity. This linkage between airway contraction and lung compliance may account for the common observation that pharmacological challenges given to the lung usually result in similar changes in lung compliance and airway conductance. Our results also suggest the possibility that the lung tissue resistance, which dominates the measurement of lung resistance in many species, might in fact reflect the physical properties of conducting airways.
Pressure-dependent increase in lung vascular permeability to water but not protein
Authors: Ehrhart I. C. , Hofman W. F.
Published: December 2017

Simultaneous measures of vascular permeability to fluid (capillary filtration coefficient, Kf) and to plasma proteins (solvent drag reflection coefficient, sigma) were obtained over venous pressures (Pv) from 14 to 105 Torr in the isolated ventilated canine lung lobe (n = 70) pump perfused with autologous blood. The sigma was obtained from the relative increase in the concentration of plasma proteins vs. erythrocytes during fluid filtration. Kf's were obtained from two gravimetric methods as well as from change in hematocrit. All Kf's increased (P less than 0.05) as Pv was increased. However, sigma averaged 0.59 +/- 0.01 (range 0.54–0.67) and was unchanged (P greater than 0.05) by elevation of Pv over 20–105 Torr. In 44 lobes where all three Kf measures were obtained, gravimetric measures of Kf did not differ (P greater than 0.05) and were highly correlated with Kf obtained from hematocrit change, Vf Kf (P less than 0.001). However, both weight-based Kf's exceeded Vf Kf (P less than 0.05), suggesting that fluid filtration was overestimated by rate of lung weight gain or underestimated by hematocrit change. Increased permeability to water but not to protein over Pv from 20 to 105 Torr indicates that permeability to both can change independently and is counter to the theory that elevated vascular pressure “stretches” vascular pores.
Long-lasting ventilatory response of humans to a single breath of hypercapnia in hyperoxia
Authors: Modarreszadeh M. , Bruce E. N.
Published: December 2017

It has often been assumed that under normoxia, closed-loop ventilatory responses to transient CO2 stimulation (i.e., lasting for 1–3 breaths) are less likely to be mediated by the slow-responding central (medullary) chemoreflex. This assumption, however, has not been quantitatively examined in humans. We hypothesized that in the closed-loop respiratory chemical feedback system [in which the centrally mediated ventilatory response to transient changes in the arterial PCO2 levels (PaCO2) will in turn affect the pulmonary CO2 and hence PaCO2], the contribution of the central chemoreflex pathways to brief disturbances in blood gases may be more important than considered previously. Using the technique of pseudorandom binary CO2 stimulation, we quantified the ventilatory response of normal humans to brief disturbances in arterial CO2 during hyperoxia. Tidal volume (VI), inspiratory ventilation (VI), inspiratory time (TI), expiratory time (TE), and end-tidal CO2 fraction (FETCO2) were measured in subjects who inhaled a mixture that was pseudorandomly switched between 95% O2–5% CO2 and 100% O2 (63 breath sequences). From these data, we calculated the responses of VI, VI, TI, TE, and FETCO2 to a single-breath inhalation of 1% CO2 in O2. Our results showed that in response to a brief increase of 0.75 Torr in alveolar CO2, VI showed a transient increase (average peak response of 0.12 1/min) that persisted for greater than or equal to 80 s in every subject. The response of VI was similar to that of VI, whereas TI and TE showed no consistent changes. Using these results we calculated that central chemoreflex pathways may contribute significantly to typical transient CO2 stimulation tests in hyperoxic and normoxic humans.
Effect of chronic respiratory load on cytochrome oxidase activity in diaphragmatic fibers
Authors: Bazzy A. R. , Kim Y. J.
Published: December 2017

To determine whether the increase in oxidative capacity after respiratory muscle training with chronic inspiratory loads in sheep is specific to a particular fiber type, we measured cytochrome c oxidase (COX) activity in type I and type II fibers. COX activity in individual fibers was examined histochemically and measured as relative optical density by use of an image processing system. Fiber types were differentiated by the myosin adenosine-triphosphatase reaction. We found that COX activity was higher in both fiber types in the trained diaphragms than in the control diaphragms (P less than 0.01). The increase with training was greater in type II (39%) than in type I fibers (21%), resulting in relatively homogeneous COX activity in all diaphragmatic fibers. The proportion of type I fibers increased from 43.4 +/- 5.4% in the control diaphragm to 53.1 +/- 2.9% in the trained diaphragm, whereas the proportion of type II fibers decreased (P less than 0.001). We conclude that respiratory muscle training activates oxidative enzyme activity in both diaphragmatic fiber types; this activation is differentially more in type II fibers, which also decrease in proportion, and less in type I fibers, which increase in proportion.
Group B Streptococcus-induced acidosis in newborn swine: regional oxygen transport and lactate flux
Authors: Barefield E. S. , Oh W. , Stonestreet B. S.
Published: December 2017

To investigate the mechanism of metabolic acidosis resulting from group B streptococcal sepsis, oxygen metabolism and lactate flux of the cerebrum, hindlimb, liver, splanchnic organs, and systemic vascular bed as a whole were examined. Nine 3- to 5-day-old awake and spontaneously breathing piglets were studied before and after 3, 4, and 5 h of continuous live group B Streptococcus infusion. After 5 h, oxygen delivery was decreased to all organs and to the whole systemic vascular bed. Increased oxygen extraction compensated for reduced oxygen delivery in the liver and splanchnic organs; however, it only partially offset reduced oxygen delivery to the hindlimb and systemic vascular bed. Cerebral oxygen extraction did not increase. As a result, oxygen uptake was reduced in the cerebrum, hindlimb, and systemic vascular bed. At 5 h of bacterial infusion, arterial lactate concentration was increased with regional lactate efflux from the cerebrum and hindlimb and influx to the liver (P less than 0.05 vs. zero or no net flux). We conclude that group B Streptococcus-induced metabolic acidosis is associated with regional lactate efflux from vascular beds in which oxygen uptake is reduced. We speculate that the quantity of net lactate efflux from vascular beds with insufficient oxygen uptake exceeds the net influx into organs such as the liver, resulting in metabolic acidosis.
Lung and chest wall impedances in the dog: effects of frequency and tidal volume
Authors: Barnas G. M. , Stamenovic D. , Lutchen K. R. , Mackenzie C. F.
Published: December 2017

Dependences of the mechanical properties of the respiratory system on frequency (f) and tidal volume (VT) in the normal ranges of breathing are not clear. We measured, simultaneously and in vivo, resistance and elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) of five healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50–300 ml, 0.2–2 Hz) delivered at a constant mean lung volume. Each dog showed the same f and VT dependences. The Ers and Ecw increased with increasing f to 1 Hz and decreased with increasing VT up to 200 ml. Although EL increased slightly with increasing f, it was independent of VT. The Rcw decreased from 0.2 to 2 Hz at all VT and decreased with increasing VT. Although the RL decreased from 0.2 to 0.6 Hz and was independent of VT, at higher f RL tended to increase with increasing f and VT (i.e., as peak flow increased). Finally, the f and VT dependences of Rrs were similar to those of Rcw below 0.6 Hz but mirrored RL at higher f. These data capture the competing influences of airflow nonlinearities vs. tissue nonlinearities on f and VT dependence of the lung, chest wall, and total respiratory system. More specifically, we conclude that 1) VT dependences in Ers and Rrs below 0.6 Hz are due to nonlinearities in chest wall properties, 2) above 0.6 Hz, the flow dependence of airways resistance dominates RL and Rrs, and 3) lung tissue behavior is linear in the normal range of breathing.
Menstrual cycle phase affects temperature regulation during endurance exercise
Authors: Pivarnik J. M. , Marichal C. J. , Spillman T. , Morrow J. R.
Published: December 2017

We investigated whether menstrual cycle phase would affect temperature regulation during an endurance exercise bout performed at room temperature (Ta) of 22 degrees C and 60% relative humidity. Nine eumenorrheic women [age 27.2 +/- 3.7 yr, peak O2 uptake (VO2) 2.52 +/- 0.35 l/min] performed 60 min of cycle exercise at 65% of peak VO2. Subjects were tested in both midfollicular (F) and midluteal (L) phases, although one woman did not show a rise in serum progesterone (P4) that is typically evident 1 wk after ovulation. VO2, rectal (Tre) and skin (Tsk) temperatures, heart rates (HR), and ratings of perceived exertion (RPE) were measured throughout exercise. Sweat loss (SL) was estimated from pre- and postexercise body weight differences. VO2, SL, and Tsk were not affected by menstrual cycle phase. Preexercise Tre was 0.3 degrees C higher during L than during F conditions, and this difference increased to 0.6 degrees C by the end of exercise (P less than 0.01). Compared with F, HRs during L were approximately 10 beats/min greater (P less than 0.001) at all times, whereas RPE responses were significantly greater (P less than 0.01) by 50 min of cycling. No differences in any measured values were found in the subject whose P4 was low in both test conditions. Results indicate that thermoregulation (specifically, regulation of Tre), as well as cardiovascular strain and perception of exercise, was adversely affected during the L phase.
Acute effects of acrolein on breathing: role of vagal bronchopulmonary afferents
Authors: Lee B. P. , Morton R. F. , Lee L. Y.
Published: December 2017

Spontaneous inhalation of acrolein vapor (350 ppm, 1 ml/100 g body wt) elicited an immediate and transient inhibitory effect on breathing in anesthetized rats, characterized by a prolongation of expiratory duration and accompanied by a bradycardia; ventilation was reduced by 47 +/- 6%, which returned to baseline after three to seven breaths. When both vagi were cooled to 6.6 +/- 0.1 degrees C, the reflex apneic response to lung inflation was completely abolished but the bradypneic response to acrolein was not affected. After perineural capsaicin treatment of both cervical vagi to selectively block the capsaicin-sensitive C-fiber afferents, acrolein no longer evoked an inhibitory effect on breathing; conversely, an augmented inspiration was consistently elicited with the first breath of acrolein inhalation, which was subsequently abolished by cooling both vagi to 6.5 degrees C. The inhibitory effect of inhaling acrolein at a lower concentration (200 ppm) was not detectable, whereas that of a higher concentration (600 ppm) was more intense and prolonged. All these responses were completely eliminated by bilateral vagotomy. These results suggest that inhaled acrolein activated both vagal C-fiber endings and rapidly adapting irritant receptors in the airways, but the acrolein-induced inhibitory effect on breathing was elicited primarily by the C-fiber afferent stimulation.
Characterization of thromboxane receptor blocking effects of SQ 29548 in the feline pulmonary vascular bed
Authors: McMahon T. J. , Hood J. S. , Nossaman B. D. , Hyman A. L. , Kadowitz P. J.
Published: December 2017

The effects of SQ 29548, a thromboxane (Tx) A2 receptor blocking agent, on responses to the TxA2 mimic U46619 were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 29548 in doses of 0.25–1 mg/kg iv reduced vasoconstrictor responses to U-46619; however, responses to prostaglandins (PG) F2 alpha and D2 and to serotonin were also decreased. After administration of SQ 29548 in doses of 0.05–0.1 mg/kg iv, responses to U-46619 and U-44069 were reduced significantly, and the dose-response curves for these TxA2 mimics were shifted to the right in a parallel manner at a time when responses to PGF2 alpha and PGD2 were not altered. The low doses of the TxA2 receptor blocking agent significantly reduced responses to the PG and TxA2 precursor arachidonic acid but were without significant effect on vasoconstrictor responses to serotonin; histamine; norepinephrine; angiotensin II; the major PGD2 metabolite 9 alpha,11 beta-PGF2; BAY K 8644, an agent that enhances calcium entry; and endothelin-1. The present data show that at low doses SQ 29548 selectively blocks TxA2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed. These data suggest that responses to arachidonic acid are mediated in large part by the formation of TxA2 and provide evidence in support of the hypothesis that a discrete TxA2 receptor unrelated to PGF2 alpha or PGD2 receptors is present in undefined resistance vessel elements in the feline pulmonary vascular bed.
Potassium and ventilation in exercise
Authors: Paterson D. J.
Published: December 2017

The drive to breathe in exercise is thought to result from a combination of neural and humoral factors, but the exact nature of the controlling signals is controversial. This review examines evidence suggesting that potassium could be a signal that drives ventilation (VE) in exercise. Potassium is lost from working muscle, which results in a marked hyperkalemia in the arterial plasma. The rise in potassium is directly proportional to the increase in carbon dioxide production during exercise and is also well correlated with VE in normal subjects and in subjects who do not produce acid (McArdle's syndrome). In the anesthetized and decerebrate cat, physiological levels of hyperkalemia stimulate VE by direct excitation of the peripheral arterial chemoreceptors, because surgical and chemical denervation of the chemoreceptors abolishes the increase in VE caused by potassium. The effect of hyperkalemia on chemoreceptor activity is further enhanced by hypoxia, but an abrupt switch to hyperoxia removes this effect. From these studies, it is suggested that potassium fulfills many of the criteria of being the special substance or “work factor” that was postulated over a century ago to stimulate VE in exercise. Although there is no direct proof that potassium causes an increase in breathing during exercise, circumstantial evidence strongly supports the idea that it should be considered as a stimulus to exercise hyperpnea.
Mechanisms of control of alae nasi muscle activity
Authors: Mezzanotte W. S. , Tangel D. J. , White D. P.
Published: December 2017

Human upper airway dilator muscles are clearly influenced by chemical stimuli such as hypoxia and hypercapnia. Whether in humans there are upper airway receptors capable of modifying the activity of such muscles is unclear. We studied alae nasi electromyography (EMG) in normal men in an attempt to determine 1) whether increasing negative intraluminal pressure influences the activity of the alae nasi muscle, 2) whether nasal airway feedback mechanisms modify the activity of this muscle, and 3) if so, whether these receptor mechanisms are responding to mucosal temperature/pressure changes or to airway deformation. Alae nasi EMG was recorded in 10 normal men under the following conditions: 1) nasal breathing (all potential nasal receptors exposed), 2) oral breathing (nasal receptors not exposed), 3) nasal breathing with splints (airway deformation prevented), and 4) nasal breathing after nasal anesthesia (mucosal receptors anesthetized). In addition, in a separate group, the combined effects of anesthesia and nasal splints were assessed. Under each condition, EMG activity was monitored during basal breathing, progressive hypercapnia, and inspiratory resistive loading. Under all four conditions, both load and hypercapnia produced a significant increase in alae nasi EMG, with hypercapnia producing a similar increment in EMG regardless of nasal receptor exposure. On the other hand, loading produced greater increments in EMG during nasal than during oral breathing, with combined anesthesia plus splinting producing a load response similar to that observed during oral respiration. These observations suggest that nasal airway receptors have little effect on the alae nasi response to hypercapnia but appear to mediate the alae nasi response to loading or negative airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Application of respiratory heat exchange for the measurement of lung water
Authors: Serikov V. B. , Rumm M. S. , Kambara K. , Bootomo M. I. , Osmack A. R. , Staub N. C.
Published: December 2017

A noninvasive method for measuring pulmonary blood flow and lung mass (called airway thermal volume), based on the measurements of lung heat exchange with environment, is described. The lungs function as a steady-state heat exchange system, having an inner heat source (pulmonary blood flow) and an external heat sink (ventilation). Sudden changes in the steady-state condition, such as caused by hyperventilation of dry air, lead to a new steady state after a few minutes. The expired air temperature difference between the initial and final steady states is proportional to pulmonary blood flow, whereas the rate at which the new steady state is achieved is proportional to airway thermal volume. The method was tested in 20 isolated dogs lungs, 9 perfused goat lungs, and 27 anesthetized sheep. The expired air temperature fall during hyperventilation was inversely proportional to the perfusion rate of the isolated lungs, and half-time of the temperature fall was proportional to the lung tissue mass. Experiments in anesthetized sheep showed that the measured airway thermal volume is close to the total mass of the excised lungs, including its residual blood (r = 0.98). Pulmonary edema and fluid instillation into the bronchial tree increased in the measured lung mass.
Structural change of the thorax in chronic obstructive pulmonary disease
Authors: Walsh J. M. , Webber C. L. , Fahey P. J. , Sharp J. T.
Published: December 2017

This study examines structural changes of the thorax in hyperinflated subjects with chronic obstructive pulmonary disease (COPD). Age-matched normal subjects were used for comparison. Thoracic dimensions were determined using anteroposterior and lateral chest radiographs performed at total lung capacity, functional residual capacity, and residual volume. Rib cage dimensions (lateral diameter, rib angle, anteroposterior diameter) and diaphragm position were determined at each lung volume. There were no significant differences in rib cage dimension between the COPD and normal subjects for all lung volumes. In contrast, the diaphragm was significantly lower in the COPD subjects. The change of rib cage dimensions in the COPD subjects (for a similar volume change) was not different from that in normal subjects, whereas the change of diaphragm position in the COPD subjects (for a similar volume change) was reduced. In conclusion, the primary structural change of the thorax in COPD with chronic hyperinflation is confined to the diaphragm, with no appreciable structural change in the rib cage.
Changes in plasma and erythrocyte K+ during hypercapnia and different grades of exercise in trout
Authors: Nielsen O. B. , Lykkeboe G.
Published: December 2017

Trout were exposed to hypercapnia, two levels of aerobic exercise, or three successive periods of supramaximal exercise to evaluate the effects on erythrocyte and plasma K+. During aerobic exercise, plasma K+ increased slightly with the intensity of work, while no change was found in the erythrocyte K+ content. In contrast, both hypercapnia and supramaximal exercise induced a net erythrocyte K+ uptake. This uptake changed to a net loss of K+ as arterial pH and hemoglobin-bound oxygen saturation returned to control values during recovery. The maximal rates of net K+ uptake found during hypercapnia and supramaximal exercise corresponded to 195 and 350 mumol.kg fish-1.h-1, respectively, and the maximal rates of net K+ loss found during recovery corresponded in both cases to approximately 130 mumol.kg fish-1.h-1. Hypercapnia had only a minor effect on plasma K+, but return to normocapnic conditions induced a 0.8 mM rise in plasma K+. Of this increase, approximately 70% could be accounted for by the simultaneous net release of erythrocyte K+. Each period of supramaximal exercise induced an elevated plasma K+ level, resulting in accumulation of plasma K+ despite slight decreases in plasma K+ in between the exercise periods. At the same time the net erythrocyte K+ uptake caused an estimated reduction in plasma K+ of 1.5 mM. It is concluded that both hypercapnia and supramaximal exercise cause profound net changes in the erythrocyte K+ content with significant effects on plasma K+.
Pulmonary hemodynamics and tissue damage after one lung infusion of Pseudomonas aeruginosa in sheep
Authors: Loick H. M. , Dehring D. J. , Tokyay R. , Linares H. A. , Evans M. J. , Traber L. D. , Guha S. C. , Flynn J. , Traber D. L.
Published: December 2017

The relative roles of hematogenous mediators and direct bacterial toxicity due to phagocytosis by pulmonary intravascular macrophages were determined by selective bacterial infusion into the left pulmonary artery and comparison of right and left lungs at 24 h. Chronically instrumented sheep received 15-min pulmonary arterial infusions of live Pseudomonas aeruginosa (0.35–2.9 x 10(9), n = 6) or saline (n = 5). The saline group demonstrated stable cardiopulmonary function over time. Left lung blood flow, measured by Doppler flow probe, decreased 15 min into the bacterial infusion, with a concomitant sevenfold increase in left lung pulmonary vascular resistance index. The right lung pulmonary vascular resistance index doubled at 1 h, in association with increased plasma thromboxane B2 levels. An increase in cardiac index and decrease in systemic vascular resistance occurred at 12 h. The wet-to-dry weight ratio of the Pseudomonas-infused left lung was increased compared with that of the sham-infused lung. The tissue count of neutrophils in the lungs was doubled in both sides, but neutrophils on the left were more degranulated. The left lung tissue damage was caused by direct bacterial toxicity, including activation of phagocytic cells. Hematogenous mediators induced pulmonary and systemic hemodynamic changes and right lung neutrophil sequestration, but they did not damage the noninfused lung.
Contractile properties of the rat external abdominal oblique and diaphragm muscles during development
Authors: Watchko J. F. , Brozanski B. S. , O'Day T. L. , Guthrie R. D. , Sieck G. C.
Published: December 2017

We studied the in vitro contractile and fatigue properties of the rat external abdominal oblique (EAO) and costal diaphragm (DIA) muscles during postnatal development. Isometric twitch contraction (CT) and half-relaxation (RT1/2) times were longer in both the EAO and DIA muscles during the early postnatal period and decreased with age. In the first postnatal week, the CT and RT1/2 were longer in the EAO than the DIA muscle. At 14 days of age and thereafter, the CT and RT1/2 were shorter in the EAO than in the DIA muscle. Force-frequency relationships of the EAO and DIA muscles changed during postnatal development such that the relative force (percent maximum) generated at lower frequencies (less than 15 pulses/s) decreased with age. Moreover the relative force generated by the EAO muscle at lower frequencies was greater than that of the DIA muscle during the early postnatal period but less than that of the DIA muscle in adults. The specific force of both the EAO and DIA muscles increased progressively with age. There were no differences in specific force between the EAO and DIA muscles at any age. The fatigability of the EAO and DIA muscles was comparable during the early postnatal period and increased in both muscles with postnatal development. In adults the EAO muscle was more fatigable than the DIA muscle. We conclude that the contractile and fatigue properties of the EAO and DIA muscles undergo significantly different postnatal transitions, which may reflect their functional involvement in sustaining ventilation.
Adaptations of diaphragm and medial gastrocnemius muscles to inactivity
Authors: Zhan W. Z. , Sieck G. C.
Published: December 2017

The effects of 2 wk of inactivity on in vitro contractile properties of diaphragm and medial gastrocnemius (MG) muscles were examined in adult hamsters. In addition, inactivity effects on fiber-type proportions and cross-sectional areas were studied. Inactivity of the right hemidiaphragm or MG muscle was induced by either tetrodotoxin (TTX) blockade of nerve impulses or denervation (DNV). Inactivity effects on diaphragm or MG were compared with corresponding sham (saline-treated or untreated control) muscles. After both TTX- and DNV-induced inactivity, isometric twitch contraction and half-relaxation times were prolonged, maximum tetanic force decreased, and fatigue resistance improved. Proportions of type I and II fibers in both diaphragm and MG were unaffected by TTX- and DNV-induced inactivity. However, in both muscles, type I fibers hypertrophied, whereas type II fibers atrophied. In diaphragm, contractile and morphometric adaptations after DNV were generally more pronounced than those induced by TTX. In addition, compared with corresponding untreated or saline-treated control groups, inactivity effects (both TTX and DNV) on MG were generally greater than those induced in diaphragm, with the exception of hypertrophy of type I fibers. We conclude that inactivity exerts differential effects on type I and II fibers in both diaphragm and MG. Yet, these morphometric adaptations cannot completely account for the adaptations in muscle contractile and fatigue properties after inactivity.
Structural changes in elastic fibers after pancreatic elastase administration in hamsters
Authors: Mercer R. R. , Crapo J. D.
Published: December 2017

Ultrastructural changes in lung parenchymal elastic fibers were studied morphometrically 1, 4, and 12 wk after a single 12-unit dose of pancreatic elastase and in a saline-instilled control group. The mean linear intercept of the parenchymal air spaces was increased in the 1-, 4-, and 12-wk post-elastase instillation groups compared with age-matched controls. The volume of alveolar connective tissue fibers predominantly composed of elastin (elastic fibers) was decreased by 35% 1 wk after the instillation of elastase but returned to control levels by 4 wk. Although the total volume of elastic fibers was normal 12 wk after instillation of elastase, the volume of elastic fibers in alveolar entrance rings remained significantly reduced. In serial sections of elastic fibers, numerous gaps or separations in the normally continuous band of elastic fibers that encircle each alveolus were identified 1 wk after elastase instillation. There were 169 +/- 8 (SE), 62 +/- 32, and 12 +/- 6 gaps per millimeter of alveolar entrance ring circumference at 1, 4, and 12 wk, respectively, in the elastase-treated groups. The number of gaps at 12 wk was equivalent to two gaps or discontinuities in the elastic fibers of every alveolar entrance ring. No gaps or separations in elastic fibers were detected at 1, 4, or 12 wk in the control groups. These defects occur in concordance with the progression of air space enlargement and presumably contribute to the progression of air space enlargement that occurs after the elastin content of the tissue has returned to normal.
Training-induced alterations in young and senescent rat diaphragm muscle
Authors: Gosselin L. E. , Betlach M. , Vailas A. C. , Thomas D. P.
Published: December 2017

The current study sought to examine the effects of chronic endurance treadmill running on oxidative capacity and capillary density in specific diaphragm muscle fiber types in young (5 mo) and senescent (greater than or equal to 23 mo) female Fischer 344 rats. Both young and senescent animals trained at approximately 75% of maximal O2 consumption for 1 h/day 5 days/wk for 10 wk. Plantaris citrate synthase activity was significantly increased (P less than 0.01) in both young and old trained groups. Densitometric analysis of succinate dehydrogenase (SDH) activity in diaphragm type I, IIa, and IIb muscle fibers was done using a computerized image-processing system. There were no age-related differences in SDH activity between the young and old groups for any of the fiber types. In addition, SDH activity was found to be significantly increased (P less than 0.05) in all three fiber types in both the young and senescent trained animals compared with their sedentary counterparts. Fiber size and capillary density did not differ between young and senescent rats, nor did exercise affect this measure. Each fiber, irrespective of type, had an average of approximately four capillaries in contact with it. However, type IIb fibers had a significantly lower capillary density per unit area than type I or IIa muscle fibers. The results indicate that the senescent costal diaphragm maintains its ability to adapt to an increased metabolic demand brought about by locomotor exercise. Of further interest is the finding that training adaptations occurred in all three fiber types, suggesting that increased work of breathing from moderate exercise leads to recruitment of all three fiber types.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of blood flow on net lactate uptake during steady-level contractions in canine skeletal muscle
Authors: Gladden L. B. , Crawford R. E. , Webster M. J.
Published: December 2017

The purpose of this study was to determine the effect of blood flow on net lactate uptake (L) at constant elevated blood lactate concentration and metabolic rate in the in situ dog gastrocnemius-plantaris (GP) muscle. In all experiments, an infusion of lactate/lactic acid at a pH of 3.8 established a blood lactate concentration of 10–13 mM while maintaining normal blood gas/pH status as the GP was stimulated to contract with twitches at 1 Hz. In series 1 (n = 14), blood flow (ml.kg-1.min-1) was controlled by a pump at either 1) the spontaneous level for 1-Hz contractions (control flow = 332 +/- 23) or 2) a level estimated to be approximately 65% greater (high flow = 543 +/- 42). In series 2 (n = 7), perfusion pressure was varied during 1-Hz contractions. Four different perfusion pressures (80, 120, 155, and 180 Torr) were presented to each GP preparation, resulting in mean flow rates of 308 +/- 34, 419 +/- 30, 492 +/- 37, and 646 +/- 30 ml.kg-1.min-1. Increasing blood flow had no significant effect on net L in series 1. Similarly, there was no significant change in net L across the first three perfusion pressures/flow rates in series 2. However, net L (mmol.kg-1.min-1) was significantly increased in the highest perfusion pressure/flow rate period (from 0.335 +/- 0.029 at 80 Torr to 0.431 +/- 0.034 at 180 Torr). This study suggests that blood flow may have an independent effect on net L at the upper extreme of the normal blood flow range during contractions but very little effect over a fairly wide low-to-middle range of flow rates.
Mechanisms of metabisulfite-induced bronchoconstriction: evidence for bradykinin B2-receptor stimulation
Authors: Mansour E. , Ahmed A. , Cortes A. , Caplan J. , Burch R. M. , Abraham W. M.
Published: December 2017

Sodium metabisulfite (MBS) is a food preservative that can trigger bronchoconstriction in asthmatic subjects. Previous studies designed to identify the mechanisms involved in this response have yielded conflicting results. We noted certain similarities between the pharmacology of MBS-induced airway responses and those elicited by bradykinin (BK), another provocating agent in asthmatic subjects. Therefore we used allergic sheep to determine whether MBS-induced bronchoconstriction 1) had a pharmacology similar to that previously seen with BK in this model, including protection by a BK B2-receptor antagonist, NPC-567, and 2) was associated with increased concentrations of immunoreactive kinins in bronchoalveolar lavage. We measured specific lung resistance before and immediately after inhaled buffer and increasing concentrations of MBS (30 breaths of 25, 50, and 100 mg/ml) and calculated the concentration producing 100% increase in specific lung resistance over baseline (PC100). In seven sheep, geometric mean control PC100 was 33.1 mg/ml. Pretreatment with either the anticholinergic agent ipratropium bromide (180 micrograms; PC100 87.1 mg/ml) or the antiasthma drug nedocromil sodium (1 mg/kg aerosol; PC100 97.7 mg/ml) blocked the MBS-induced bronchoconstriction (P less than 0.05), whereas the histamine H1-receptor antagonist chlorpheniramine (2 mg/kg iv) was ineffective. Furthermore the MBS-induced bronchoconstriction was not affected by the neutral endopeptidase inhibitor thiorphan (40 breaths of a 1 mg/ml solution) or the angiotensin-converting enzyme inhibitor enalaprilat (2.5 mg aerosol). In six sheep the MBS-induced bronchoconstriction was completely blocked by NPC-567 (20 breaths, 5 mg/ml aerosol): after treatment with NPC-567 mean PC100 was 100 mg/ml compared with 57.5 mg/ml in the control trial (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Is flow in subpleural region typical of the rest of the lung? A study using laser-Doppler flowmetry
Authors: Hakim T. S.
Published: December 2017

The microcirculation in the subpleural region of the lung is thought to be physiologically typical of the entire vasculature. To investigate this issue, an in situ blood-perfused dog lung lobe (500 ml/min) was prepared and the blood flow in the subpleural region (Qs) was monitored with laser-Doppler flowmetry (LDF). The flow rates into and out of the lobe were monitored with in-line flow probes, and the arterial and venous pressures were recorded from side ports in the cannulas. The LDF signal measures flow in arbitrary units over a region less than 2 mm deep and 1 mm2. The LDF signal was independent of site of measurement and was linearly proportional to total flow rate (r2 greater than 0.9), suggesting that during baseline conditions Qs behaves similarly to, although not necessarily the same as, blood flow in the rest of the lung. However, if the vasculature is constricted by serotonin (arterial constriction) or by histamine (venous constriction), Qs decreases significantly relative to total flow. In fact, in some cases Qs approached zero during vasoconstriction, despite the fact that total flow was maintained constant and the pulmonary arterial pressure became elevated. Reduction in Qs most likely reflects a redistribution from the subpleural to the central regions of the lung. The results of this study suggest that LDF is a useful tool for monitoring flow in the subpleural region of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Finger-specific flexor recruitment in humans: depiction by exercise-enhanced MRI
Authors: Fleckenstein J. L. , Watumull D. , Bertocci L. A. , Parkey R. W. , Peshock R. M.
Published: December 2017

To evaluate the spatial distribution of human forearm musculature stressed by finger-specific exercise, magnetic resonance imaging was performed in conjunction with exercise protocols designed to separately stress the flexor digitorum superficialis and flexor digitorum profundus. These muscles were shown to consist of subvolumes selectively recruited by flexion of the individual fingers. Knowledge of the finger-specific regions of muscle recruitment during finger flexion could improve sampling accuracy in electromyography, biopsy, magnetic resonance spectroscopy, and invasive vascular sampling studies of hand exercise.
Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation
Authors: Dreyfuss D. , Soler P. , Saumon G.
Published: December 2017

Mechanical ventilation with high or even moderate peak inspiratory pressure produces pulmonary permeability edema. Besides the level of overinflation, duration may affect both severity and type of edema. We studied the effect of 2 min of 35-mmHg peak pressure mechanical ventilation (HV) on microvascular permeability and deep lung fluid balance in rats. It resulted in increased extravascular lung water (+50%), bloodless dry lung weight (+25%), and albumin uptake in lungs (+450%). The increase in dry lung weight and albumin uptake compared with that of lung water suggested major permeability alterations. Ultrastructural examination showed the presence of numerous endothelial blebs. Epithelial lining fluid (ELF) volume, its potassium and protein concentrations, and cellular composition were assessed by bronchoalveolar lavage. There was an increase in ELF volume (+180%), a decrease in ELF potassium concentration (-50%), and an increase in ELF protein content (+76%). A few blood cells were recovered, suggesting the presence of a few large epithelial breaks. Some animals were allowed to recover for periods less than or equal to 180 min after HV. Extravascular lung water, dry lung weight, and albumin distribution space returned to control levels within 45 min. ELF volume diminished but remained larger than in controls, and ELF protein concentration increased probably because of alveolar fluid resorption. No further hemorrhage was observed. These results indicate that periods of HV as short as 2 min transiently alter microvascular permeability in rats.
Influence of airway resistance on hypoxia-induced periodic breathing
Authors: Series F. , Series I. , Atton L. , Blouin A.
Published: December 2017

We studied the effects of changing upper airway pressure on the variability of the dynamic response of ventilation to a hypoxic disturbance in 11 spontaneously breathing dogs. Supralaryngeal pressure, instantaneous inspiratory flow, end-expiratory lung volume, and the inspiratory and expiratory O2 and CO2 concentrations were continuously recorded at baseline and after a 1.5-min hypoxic stimulus (abrupt normoxic recovery). Arterial blood gases were obtained at baseline, at the end of the hypoxic period, and after 1 min of recovery. Airway resistances were modified during the recovery by changing the composition of the inspired gas (all with an inspiratory O2 fraction of 20.9%) among four different trials: two trials were realized with air (density 1.12 g/l), and the other two were with He or SF6 (respective density 0.42 and 4.20) in random order. There was no difference between baseline minute ventilation, arterial blood gases, and supralaryngeal resistance values preceding the trials. The hypoxemic and hypocapnic levels and the hypoxia-induced hyperventilation reached during the hypoxic tests were identical for the different hypoxic stimuli. The supralaryngeal resistance measured at peak flow was dramatically influenced by the composition of the inspired gas: 8.8 +/- 1.8 and 6.9 +/- 1.7 (SE) cmH2O.l-1.s with air, 7.2 +/- 2.2 with He, 21.9 +/- 5.5 with SF6 (P less than 0.05). Ventilatory fluctuations were consistently seen during the posthypoxic period. They were characterized by a strength index value (M) (Waggener et al. J. Appl. Physiol. 56: 576–581, 1984).(ABSTRACT TRUNCATED AT 250 WORDS)
Spatial correlation of regional pulmonary perfusion
Authors: Glenny R. W.
Published: December 2017

Despite the heterogeneous distribution of pulmonary blood flow, perfusion appears to be spatially ordered, with neighboring regions of lung having similar magnitudes of flow. This premise was tested by determining the spatial correlation of regional flow [rho(d)] as a function of distance (d) between regions. Regional pulmonary perfusion was measured in both supine and prone positions in seven anesthetized mechanically ventilated dogs with radiolabeled microspheres. After excision and drying, the lungs were cubed into pieces 1.2 cm on a side, with a three-dimensional coordinate assigned to each piece. The microsphere-determined flow to each piece was measured by radioactive counts, and rho(d) was calculated for all paired pieces within the same lobe. rho(d) was greatest for adjacent pieces (d = 1.2 cm) and decreased with increasing d, becoming negative at large distances in all dogs and positions. The spatial correlation of flow between adjacent pieces, rho(1.2 cm), was greater in the supine than in the prone position (0.66 vs. 0.72, P less than 0.05). The observations for each dog and position were fit to the equation rho(d) = d(a)+b.d+c, and the coefficients were used to compare rho(d) in the supine and prone positions. rho(d) differed in the two positions (P less than 0.05), with rho(d) falling off more rapidly with distance in the supine position. When trends in flow due to gravity were mathematically removed, differences between supine and prone positions were no longer observed. The spatial correlation of regional pulmonary perfusion was anisotropic in both supine and prone positions. The observation that regional pulmonary perfusion is highly correlated over large spatial distances has important implications for models of flow distribution.
Physical models of the smaller pulmonary airways
Authors: Hammersley J. R. , Olson D. E.
Published: December 2017

Any internalized flow exhibits closely coupled interactions with its confining geometry. Efforts to gain an understanding of in vivo airway transport phenomena, therefore, dictate that careful attention to be paid to those anatomic airway features that constrain and modify regional air movement. We present a series of analyses of human small airway casts to refine and extend the current geometric description of small airway bifurcations. Airway shape factors believed to have a high propensity to alter the fluid dynamics of airflows within this region are specifically addressed. The results of these anatomic and fluidic analyses are used to develop two average symmetrical and asymmetrical bifurcation patterns. Finally, methods for the production of physical bifurcation models conforming to these requirements are presented to develop a rational representation of anatomic as well as flow similitude during airway research.
Effect of vagal stimulation and parenteral acetylcholine on canine trachealis muscle shortening
Authors: Okazawa M. , Wakai Y. , Osborne S. , Pare P. D. , Road J. D.
Published: December 2017

Canine trachealis smooth muscle shortening (TMS) in response to vagal nerve stimulation is approximately 30%, far less than the 70% predicted from in vitro studies. We hypothesized that in vivo airway smooth muscle activation during vagal stimulation may be submaximal, and in this study we wished to determine TMS during maximal activation. TMS was studied in 12 alpha-chloralose-anesthetized dogs during vagal stimulation, systemic acetylcholine injection, and local acetylcholine injection. Bilateral vagal stimulation produced TMS of 26 +/- 5% (SE) length at functional residual capacity (LFRC). Maximal TMS during systemic injection of acetylcholine was 28 +/- 12% LFRC but may have been limited by delivery of acetylcholine to the muscle because asystole occurred at higher concentrations. TMS was greatest during local injection of acetylcholine (48 +/- 7% LFRC). There was a greater increase in pulmonary resistance and decrease in dynamic compliance during systemic acetylcholine injection than during vagal stimulation. We conclude that bilateral vagal nerve stimulation does not maximally activate trachealis smooth muscle but that the maximal shortening achieved with local injection of acetylcholine is still less than isotonic shortening in vitro. These data suggest that maximal shortening in vivo is limited by the afterload provided by the tracheal cartilaginous rings.
Augmented hypoxic ventilatory response in men at altitude
Authors: Sato M. , Severinghaus J. W. , Powell F. L. , Xu F. D. , Spellman M. J.
Published: December 2017

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1–5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P′CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P′CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4–7). HVR was independent of test SaO2 (range 60–90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)