bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenal response to long-term hypoxia is still increased after carotid body denervation in rat
Authors: Dalmaz Y. , Pequignot J. M. , Cottet-Emard J. M. , Peyrin L.
Published: December 2017

This study investigated the effects of long-term normobaric hypoxia (10% O2 in N2 for 2, 7, 14, and 28 days) on the metabolism of catecholamines in rat adrenals and the role of the carotid body chemoreceptors in the adrenal response. The content and utilization of dopamine were significantly increased from the 7th day of hypoxia and remained enhanced thereafter. The content of norepinephrine and epinephrine decreased after 2 days of hypoxia and increased thereafter; after 28 days of hypoxia the norepinephrine amounts remained enhanced but the epinephrine levels were no longer significantly increased. In vivo tyrosine hydroxylation increased after 7 days of hypoxia. Bilateral transection of the carotid sinus nerve 1 wk before hypoxia failed to abolish the increase in the content and utilization of dopamine after 7, 14, or 21 days of hypoxic exposure. These results indicate that long-term normobaric hypoxia elicits a long-lasting increase in the metabolism of catecholamines in adrenals, especially as assessed by dopamine measurement, and that this response does not involve a carotid body chemoreflex pathway.
Effect of endurance training on atrial natriuretic peptide gene expression in normal and hypertrophied hearts
Authors: Mantymaa P. , Arokoski J. , Porsti I. , Perhonen M. , Arvola P. , Helminen H. J. , Takala T. E. , Leppaluoto J. , Ruskoaho H.
Published: December 2017

We studied the effects of physical endurance training on atrial natriuretic peptide (ANP) gene expression in beagle dogs, Wistar rats, and spontaneously hypertensive rats (SHR). The dogs underwent a gradually increased running training up to 40 km/day on a treadmill for 55 wk while the nontrained sibling control dogs were kept in their cages throughout the study. Endurance training caused a significant 13% (P < 0.05) increase in ventricular hypertrophy but did not change plasma immunoreactive (ir)-ANP levels at rest or ventricular ANP mRNA or irANP levels. When normotensive Wistar rats ran up to 2,200 m/day for 8 wk, no significant change was seen in ventricular hypertrophy or in plasma or ventricular irANP levels at rest compared with nontrained controls. However, endurance training caused a 2.2-fold increase in epicardial ANP mRNA levels (P < 0.05). In the SHR strain, running training up to 900 m/day for 31 wk increased ventricular hypertrophy of trained SHR by 7% (P < 0.01) and caused a concomitant 1.6- to 1.7-fold elevation in ventricular irANP and ANP mRNA levels (P < 0.01–0.001) compared with nontrained SHR. In contrast, changes in atrial ANP mRNA or irANP levels in response to training were small in all three protocols. This study shows that in the normal heart induction of ANP synthesis by endurance training is not associated with ventricular hypertrophy. Moreover, the common stimulus for ventricular ANP synthesis induced by both chronic pressure overload and physical training may be mechanical stretching of cardiac myocytes, because endurance training further stimulated ANP synthesis in hypertrophied ventricles in SHR.
Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs
Authors: Romand J. A. , Pinsky M. R. , Firestone L. , Zar H. A. , Lancaster J. R.
Published: December 2017

Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. We studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial beta-adrenergic blockade (propranolol, 0.15 mg/kg i.v.) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa (from 19.8 +/- 6.1 to 28.3 +/- 8.7 mmHg, P < 0.01) and calculated PVR (from 437 +/- 139 to 720 +/- 264 dyn.s.cm-5, P < 0.01), both of which decreased with 17 ppm NO. ALI decreased arterial PO2 and increased airway pressure, shunt, and dead space ventilation. Ppa (19.8 +/- 6.1 vs. 23.4 +/- 7.7 mmHg) and PVR (437 +/- 139 vs. 695 +/- 359 dyn.s.cm-5, P < 0.05) were greater during ALI than during hyperoxia. No inhalation had no measureable effect during ALI before or after beta-adrenergic blockade. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 micrograms) induced an immediate decrease in Ppa and PVR during ALI.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of pressure-driven captive bubble surfactometer
Authors: Putz G. , Goerke J. , Schurch S. , Clements J. A.
Published: December 2017

We modified the captive bubble surfactometer [S. Schurch et al. J. Appl. Physiol. 67: 2389–2396, 1989] to facilitate the measurement of surface adsorption rates and to simplify its construction. We used a range of standards and monolayers of dipalmitoylphosphatidylcholine to check the calibration of the device against measurements made in a Wilhelmy surface balance and in the captive bubble by using a cathetometer, and we found good agreement. As a further test we measured the surface properties of rabbit lavage lung surfactant (60,000 x average g for 60 min) at 1.0 mg phospholipid/ml. This material adsorbed within 1 s to near-equilibrium surface tension, reached surface tensions of < 5 mN/m on the second compression, and formed very stable films. We conclude that a captive bubble surfactometer can provide accurate information about important surface properties of lung surfactant films.
Contribution of arterial feed vessels to skeletal muscle functional hyperemia
Authors: Lash J. M.
Published: December 2017

The purpose of this study was to determine whether dilation of arterial vessels preceding the microcirculation contributes differentially to increases in skeletal muscle blood flow during contractions in anesthetized sedentary (SED) or trained (TR) rats. Experiments were performed in the spinotrapezius muscle of adult male Sprague-Dawley rats. Before and immediately after muscle contractions (2, 4, or 8 Hz), intravascular pressures, red blood cell velocities, and vessel diameters were measured in terminal feed arteries at a site before penetration into the tissue. Pressure was also measured in the accompanying vein. Contraction-induced changes in vascular resistance were calculated for upstream (Rup), spinotrapezius muscle microvascular (Rst), and downstream segments. At rest, Rup accounted for less (32 vs. 40%) and Rst for more (59 vs. 47%) of total resistance in TR than in SED rats. At 8 Hz, contractions produced significantly greater functional dilation (SED, 138 +/- 14 microns; TR, 178 +/- 12 microns) and hyperemia (SED, 11.9 +/- 3.2 x control; TR, 16.8 +/- 3.1 x control) in TR than in SED rats. Inflow pressures did not change, and outflow pressures increased significantly with contractions. Rup and Rst each decreased 60–80% after 2-Hz contractions and > 90% after 8-Hz contractions. Therefore, feed artery dilation contributes significantly to functional hyperemia in the rat spinotrapezius muscle. Furthermore, it appears that aerobic exercise training results in a redistribution of segmental vascular resistance between feed vessels and the microcirculation.
Effect of long-term undernutrition on male and female rat diaphragm contractility, fatigue, and fiber types
Authors: Prezant D. J. , Richner B. , Aldrich T. K. , Valentine D. E. , Gentry E. I. , Cahill J.
Published: December 2017

The effects of long-term undernutrition (10 wk) on diaphragm contractility, fatigue, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by using direct stimulation at 37 degrees C. Undernutrition allowed for continued growth in males and females but with substantial reductions in weight gain. Relative to control rats of the same sex, final weights were significantly lower in undernourished males (74 +/- 3%) than females (90 +/- 5%), but weight gain was not significantly different between undernourished males (58 +/- 5%) and females (60 +/- 3%). Only in males did undernutrition significantly reduce costal diaphragm weight (to 77 +/- 5% of control). Diaphragm forces, normalized for cross-sectional area, were not significantly different from male or female control values. Fatigue resistance indexes (fatigue/baseline force) were increased at all stimulation frequencies in undernourished males but not in undernourished females. Costal diaphragm atrophy, involving types I and II fibers, occurred in undernourished males but not in undernourished females. In conclusion, despite long-term undernutrition reducing weight gain to similar levels in males and females (relative to control), there was excellent preservation of diaphragm weight, function, and structure in females but, although diaphragm atrophy occurred, there was preserved contractility and increased fatigue resistance in males.
Systemic hypertension at 4,300 m is related to sympathoadrenal activity
Authors: Wolfel E. E. , Selland M. A. , Mazzeo R. S. , Reeves J. T.
Published: December 2017

Residence at high altitude has been associated with elevation in systemic arterial blood pressure, but the time course has been little studied and the mechanism is unknown. Because plasma epinephrine (E) and norepinephrine (NE) also increase at altitude, we hypothesized that heightened sympathoadrenal activity may cause increased arterial pressure. We measured ambulatory blood pressure by cuff monitor in relation to 24-h urinary excretion of E and NE at sea level and during 3 wk of residence at 4,300 m (Pikes Peak, CO) in 11 healthy men. In five subjects taking placebo, arterial pressure progressively increased at 4,300 m from 82 +/- 1 (SE) mmHg at sea level to 88 +/- 3 on day 2, 91 +/- 3 on day 8, and 97 +/- 6 on day 17. In six subjects, propranolol (240 mg/day) decreased pressure from 85 +/- 4 to 77 +/- 1 mmHg at sea level but did not prevent sustained increase in pressure at 4,300 m (84 +/- 1, 81 +/- 1, and 85 +/- 3 mmHg on days 2, 8, and 17, respectively). Compared with the placebo group, blood pressure did not increase further over the initial elevation observed on day 2 in the propranolol group. There was interindividual variability in the blood pressure responses in both groups, with some subjects demonstrating a more marked increase in blood pressure. Urinary excretion of NE increased concomitantly with pressure at altitude in both groups, with a greater rise in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of chemoreceptor stimulation and inhibition on total pulmonary resistance in humans during NREM sleep
Authors: Badr M. S. , Skatrud J. B. , Dempsey J. A.
Published: December 2017

We investigated the effect of chemoreceptor stimulation and inhibition on total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep in healthy subjects. Chemoreceptor stimulation was accomplished with brief isocapnic hypoxia (n = 8). Minute ventilation increased to 150% of room air control. RL at peak inspiratory flow decreased to 66% of room air control. Resistive pressure-inspiratory flow plots demonstrated lower resistive pressures for a given inspiratory flow. Chemoreceptor inhibition was accomplished by abruptly terminating brief hypocapnic hypoxia with 100% O2 (n = 7). Minute ventilation decreased to 63% of room air control. RL calculated at peak inspiratory or fixed flow did not change significantly, and pressure-flow plots at nadir ventilation showed no systematic change from room air control. We conclude that 1) hypoxic chemoreceptor stimulation is associated with decreased RL and enhancement of pressure-flow relationships, suggesting increased upper airway caliber; 2) upper airway patency is not compromised during periods of low ventilatory drive in normal subjects; and 3) upper airway dilating muscles and thoracic pump muscles are optionally coordinated with increased and decreased ventilatory drive.
Effect of increasing flow on distribution of pulmonary capillary transit times
Authors: Presson R. G. , Hanger C. C. , Godbey P. S. , Graham J. A. , Lloyd T. C. , Wagner W. W.
Published: December 2017

The complex morphology of the pulmonary capillary network causes capillary transit times to be dispersed about a mean. It is known that flow-induced decreases in mean capillary transit time are partially offset by capillary recruitment and distension, but the effect of these factors on the rest of the distribution of transit times is unknown. We have studied the relationship between blood flow, capillary recruitment, and the distribution of transit times in isolated canine lungs with videomicroscopy. Doubling baseline lobar blood flow recruited capillaries. All transit times in the distribution decreased, as did relative dispersion. Doubling flow again caused a further decrease in transit times, but neither capillary recruitment nor relative dispersion changed significantly. We conclude that capillary transit times become more homogeneous as lobar flow increases from low to intermediate levels. Further increases in flow across a fully recruited network are associated with decreases in transit times but not with more homogeneous capillary perfusion.
Stimulation of parabrachial nuclei dilates airways in cats
Authors: Motekaitis A. M. , Solomon I. C. , Kaufman M. P.
Published: December 2017

Stimulation of the parabrachial nuclei has been shown to increase mean arterial pressure as well as to terminate inspiration. Nevertheless, the effect on airway caliber evoked by stimulation of the parabrachial nuclei is not known. Therefore, in chloralose-anesthetized cats, we microinjected DL-homocysteic acid (25 nl; 100 mM) into 44 sites in or near the lateral and medial parabrachial nuclei while calculating breath-by-breath total lung resistance and dynamic compliance. We found that, in 43 of these sites, microinjection of this excitatory amino acid consistently decreased total lung resistance but had no effect on dynamic compliance. The decrease in lung resistance was caused by a withdrawal of cholinergic tone to the airways. We could find no evidence that the decrease in total lung resistance evoked by stimulation of the parabrachial nuclei was caused by activation of either beta-adrenergic or nonadrenergic noncholinergic pathways. The decrease in total lung resistance evoked by stimulation of the parabrachial nuclei was not secondary to the baroreceptor reflex even though microinjection frequently increased mean arterial pressure. In addition, microinjection did not have consistent effects on phrenic nerve activity, although in individual circumstances the effect on this activity was quite large. We conclude that stimulation of cell bodies and dendrites in the parabrachial nuclei dilates the airways of anesthetized cats and that the effect is not secondary to the baroreceptor reflex.
Inhomogeneity of pulmonary perfusion during sustained microgravity on SLS-1
Authors: Prisk G. K. , Guy H. J. , Elliott A. R. , West J. B.
Published: December 2017

We studied the effects of gravity on the inhomogeneity of pulmonary perfusion in humans by performing hyperventilation-breath-hold single-breath measurements before, during, and after 9 days of continuous exposure to microgravity during the Spacelab Life Sciences-1 (SLS-1) mission. In microgravity the indicators of inhomogeneity of perfusion, especially the size of cardiogenic oscillations in expired CO2 and the height of phase IV, were markedly reduced. Cardiogenic oscillations were reduced to approximately 60% of their preflight standing size, and the height of phase IV was between 0 and -8% (a terminal fall became a small terminal rise) of the preflight standing value. The terminal change in expired CO2 was nearly abolished in microgravity, indicating more uniformity of blood flow between lung units that close and those that remain open at the end of expiration. A possible explanation of this observation is the disappearance of gravity-dependent topographic inequality of blood flow. The residual cardiogenic oscillations in expired CO2 imply a persisting inhomogeneity of perfusion in the absence of gravity, probably in lung regions that are not within the same acinus.
Lung volumes and distribution of regional air content determined by cine X-ray CT of pneumonectomized rabbits
Authors: Olson L. E. , Hoffman E. A.
Published: December 2017

Lung volume, gradients in lung air content, and maximum in vivo lung dimensions were determined in rabbits in the prone, supine, and right and left lateral positions with a high-speed electron beam X-ray computed tomography scanner (Imatron C-100). Measurements were made at lung volumes corresponding to tracheal pressures of 0, 10, and 25 cmH2O. Three groups of rabbits were studied > or = 8 wk after surgery: sham-operated controls, left pneumonectomized, and left pneumonectomized with wax plombage. The magnitudes of the gradients in each direction (lung, length, width, and height) depended on lung volume and body position. The vertical gradient in air content was the largest in each group in each posture. In general, pneumonectomy did not influence the effects of the prone and supine positions on lung volume and volume distribution but did influence the effects of the right and left lateral positions on those variables. These results may be attributed to the variable effects of the mediastinal and abdominal contents on regional distending pressures.
Adaptation and overtraining in horses subjected to increasing training loads
Authors: Bruin G. , Kuipers H. , Keizer H. A. , Vander Vusse G. J.
Published: December 2017

To evaluate markers for overtraining, seven male race horses were subjected to 272 days of training consisting of daily exercise bouts of either endurance running (heart rate 140/min) or interval training (maximal heart rate), both increasing in duration and intensity. An incremental exercise test was held every 4 wk, and from day 187 it was held every 2 wk. Muscle glycogen, muscle lactate, energy-rich phosphates, adrenal response to adrenocorticotropic hormone, plasma and red blood cell volumes, and a number of blood chemical variables were measured. The horses showed symptoms of weight loss, irritability, and an inability to complete the training after the intensity of the endurance exercise was increased. Test performance was not decreased. The adrenal response to adrenocorticotropic hormone was not changed during overtraining. The decline in muscle ATP concentration during maximal exercise was less during the period of staleness, whereas plasma volume, red blood cell volume, and blood chemical variables were unchanged. It was concluded that as long as exhaustive training is alternated by light exercise, overtraining is unlikely to occur. Furthermore, no single parameter can be used to detect early overtraining.
Disturbance of alveolar lining layer: effects on alveolar microstructure
Authors: Bachofen H. , Schurch S. , Possmayer F.
Published: December 2017

To further study the influence of altered surface tensions on alveolar micromechanics, we analyzed the structure-function relationships in excised rabbit lungs filled with or rinsed by a fluorocarbon (approximately 15 mN/m) or by hexadecane (approximately 25 mN/m). The lungs were fixed and dehydrated by vascular perfusion, and the tissue samples were analyzed by light, transmission, and scanning electron microscopy. We made three observations. 1) Pressure-volume (P-V) loops hexadecane-filled lungs are shifted to the left and coincide with those of saline-filled lungs, indicating near-zero interfacial tension. In accordance, the alveolar microstructure and surface area of hexadecane-filled lungs resemble those of saline-filled lungs. 2) The P-V loops of fluorocarbon-filled lungs are not shifted to the left but coincide with those of fluorocarbon-rinsed lungs. Under both conditions, the alveolar microstructure is qualitatively identical and the alveolar surface areas are markedly reduced compared with normal air-filled lungs. These findings show that fluorocarbon-filled or fluorocarbon-rinsed lungs are subjected to similar interfacial tensions at the alveolar level. 3) Hexadecane-rinsed lungs show a pear-shaped P-V curve and a complex surface texture of peripheral air spaces. These results, together with in vitro observations, suggest a metamorphic interplay between lung surfactant and hexadecane in lining the surface and determining the surface tension. Evidently, the effects of foreign liquids introduced into the lung on the structure-function relationship cannot accurately be predicted from their in vitro surface tensions. This fact should be considered in the development of artificial surfactants.
Changes in respiratory muscle activity in ponies when end-expiratory lung volume is increased
Authors: Erickson B. K. , Forster H. V. , Lowry T. F. , Pan L. G. , Korducki M. J. , Forster A. L. , Forster M. A.
Published: December 2017

The objective of the present study was to determine whether lung and diaphragm afferents contribute to the changes in respiratory muscle activity when end-expiratory lung volume (EELV) is changed in ponies. We studied the responses of the diaphragm and the transversus abdominis (TA) muscles to passive increases in EELV in awake intact (I), diaphragm-deafferented (DD), pulmonary vagal- (hilar nerve) denervated (HND), and DD + HND ponies. Negative pressure of -10 or -20 cmH2O applied around the ponies′ torsos [positive transrespiratory (TR) pressure] increased (P < 0.05) EELV in all ponies; the increases were more (P < 0.05) in HND and less (P < 0.05) in DD than in I ponies. In I ponies, positive TR pressure increased (P < 0.05) the rate of rise of the integrated diaphragmatic electromyogram (EMG), reflecting increased drive to the muscle. This increase was less (P < 0.05) in DD and HND than in I ponies. In DD + HND ponies, there was no significant (P > 0.10) change in drive to the diaphragm during positive TR pressure. In I ponies, positive TR pressure increased (P < 0.05) the duration and mean activity of the TA EMG. In HND and DD + HND ponies, the TA EMG was not altered by positive TR pressure. I and DD ponies decreased (P < 0.05) breathing frequency but maintained tidal volume (VT) during positive TR pressure. HND and DD+HND ponies increased breathing frequency (P < 0.05) and decreased (P < 0.05) VT during positive TR pressure. We conclude that, during positive TR pressure when the diaphragm is presumably at a mechanical disadvantage, diaphragm and vagal afferents mediate increased drive to the diaphragm to prevent VT from decreasing. In addition, during positive TR pressure, vagal afferents mediate an increase in duration of TA activity, which minimizes the increase in EELV.
Blood flow to the trachea and bronchi: the pulmonary contribution
Authors: Baile E. M. , Minshall D. , Dodek P. M. , Pare P. D.
Published: December 2017

It is generally assumed that when pulmonary vascular pressures are normal the pulmonary contribution to central airway blood flow (Qp) is negligible compared with systemic blood flow (Qs). However, it has been suggested in recent reports that a substantial portion of central airway blood flow is Qp. We have attempted to confirm whether there is a pulmonary contribution to central airway blood flow and to describe how it is anatomically distributed. Measurements of Qp were made using the radioactive microsphere technique in anesthetized ventilated dogs (n = 7) and sheep (n = 6). Qs to the central airways was also measured in another group of sheep (n = 10). At the end of each study, animals were killed and the lungs and trachea were excised. Qp to the upper and lower trachea, mainstem bronchi, and lobar bronchi was calculated, and the relative distribution of Qp and Qs to mucosa, cartilage, and adventitia was determined. Results showed a progressive increase (P < 0.01) in Qp (in ml.min-1 x 100 g-1) from upper trachea to lobar bronchi in both dogs and sheep. Qp and Qs supplied mainly the airway adventitia and the mucosa, respectively. Expressed as a percentage, 89 +/- 4% (SE) of Qp was to the adventitia and 0.1 +/- 0.07% was to the mucosa (P < 0.01), whereas 60 +/- 3.2% of Qs was to the mucosa and 22 +/- 4.6% was to the adventitia. In conclusion, in dogs and sheep there is a pulmonary contribution to central airway blood flow that increases from upper trachea to lobar bronchi and that supplies mainly the peritracheal adventitia.
A volume-dependent apneic threshold during NREM sleep in the dog
Authors: Chow C. M. , Xi L. , Smith C. A. , Saupe K. W. , Dempsey J. A.
Published: December 2017

We determined the causes of central apnea that commonly follow the hyperpnea resulting from brief airway occlusion during non-rapid-eye-movement (NREM) sleep. Ventilation and end-tidal gases were measured before, during, and after 214 trials of 15–20 s of tracheal occlusion in three dogs during NREM sleep. Airway occlusion was accompanied by progressive increases in inspiratory effort and was followed by transient one- to four-breath hyperapneas, with subsequent central apnea [3–15 times eupneic control expiratory duration (TE)] in 62% of occlusion trials. Significant TE prolongation after hyperventilation did not occur until tidal volume (VT) was three times greater than control; i.e., there was a volume-dependent apneic threshold. Transient electroencephalogram arousal at the end of the occlusion often augmented VT, thereby contributing to the subsequent central apnea; however, arousal was not required for the apnea to occur. Significant transient hypocapnia (up to -12 Torr arterial PCO2) commonly occurred after release of airway occlusion but was not closely correlated with the length of central apnea. During vagal blockade, after release of airway occlusion, significant transient hyperventilation occurred but at VT < 40% greater than control, and TE prolongation was markedly reduced. In summary, after release of airway occlusion in NREM sleep, 1) VT greater than three times eupnea was necessary to cause central apnea, 2) transient arousal at the termination of airway occlusion caused longer apneas by augmenting VT, and 3) transient hypocapnia per se made a significant but minor contribution to the postocclusion central apnea.
Effects of alveolated duct structure on aerosol kinetics. I. Diffusional deposition in the absence of gravity
Authors: Tsuda A. , Butler J. P. , Fredberg J. J.
Published: December 2017

We examined the effects of alveolar duct structure on particle deposition in the pulmonary acinus. The low Reynolds number velocity field of carrier gas in a geometric model of the alveolated duct was solved numerically. Particle trajectories were computed from the Langevin equation. Conditional probabilities of the trajectories were calculated with an eigenfunction expansion technique in the absence of gravity. For submicron particles, Brownian motion dominated the process; the deposition rate dramatically decreased with boundary layer growth. For fine particles, fully developed boundary layer profiles determined the deposition over most of the acinar length. The assumption of a uniform radial profile results in a substantial overestimation of the local deposition rate. The deposition rate in an alveolated duct was always smaller than that in an equivalent straight tube of the same volume. Within the alveolus the deposition pattern was markedly nonuniform, with higher deposition near the alveolar entrance ring; this finding is consistent with experimental observations in animals (e.g., see Zeltner et al. J. Appl. Physiol. 70: 1137–1145, 1991). We conclude that the structure of the alveolar duct has an important influence on aerosol particle deposition in the lung acinus.
Angiotensin mediates stimulation of ventilation after vasopressin V1 receptor blockade
Authors: Walker J. K. , Jennings D. B.
Published: December 2017

We tested the hypothesis that respiration would be stimulated after vasopressin (AVP) V1 receptor blockade because of disinhibition and activation of the renin-angiotensin system. Intravenous infusion of angiotensin II (ANG II) stimulates respiration, presumably centrally, via circumventricular organs. In the present study, the AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine]-Arg8-AVP (PMP; 10 micrograms/kg i.v.) was administered to six awake resting dogs. Measurements were made 30 min prior, and 60 min subsequent, to injection of PMP (protocol 1). In three other protocols, the ANG II blocker saralasin (0.5 microgram.kg-1.min-1 i.v.) was infused starting 20 min before PMP (protocol 2) and 30 min after PMP (protocol 4) and saline was infused (0.2 ml/min) over 90 min as a control (protocol 3). After PMP in protocol 1, alveolar ventilation increased and arterial PCO2 decreased (approximately 3 Torr). ANG II receptor blockade prevented (protocol 2) and reversed (protocol 4) respiratory stimulation by PMP. Despite ventilatory stimulation, plasma renin activity and ANG II were not increased after PMP relative to control (protocol 3). We conclude that AVP acts at V1 receptors to inhibit formation of brain ANG II. Brain ANG II must modulate respiratory control via a circumventricular organ, because systemically administered saralasin, which does not cross the blood-brain barrier, blocked stimulation of respiration.
Developmental changes of sheep surfactant: in vivo function and in vitro subtype conversion
Authors: Ueda T. , Ikegami M. , Jobe A. H.
Published: December 2017

Developmental differences in the intrinsic characteristics of surfactant have not been evaluated. Therefore, heavy-subtype surfactant was recovered from alveolar washes of 132-, 139-, and 148-day preterm lambs, 2- to 3-day-old newborn ventilated lambs, and adult sheep. The density of heavy-subtype surfactant and surfactant protein-A-to-saturated phosphatidylcholine ratios increased significantly with developmental age. In contrast, percent conversion from heavy to light surfactant forms was more rapid for surfactant from preterm animals than for surfactant from mature or adult animals. The function of the heavy-subtype surfactant was tested by treating ventilated 27-day gestational age preterm rabbits. The surfactant from the most immature animals was less effective at improving compliance or maintaining lung volumes on deflation than was surfactant from newborn or adult animals. These results demonstrate intrinsic and functional differences in surfactant from developing compared with mature sheep that correlated with the surfactant protein-A-content. The pattern of changes indicates that the preterm animal is at a disadvantage, because the surfactant is intrinsically abnormal relative to that of the adult.
Description of acute ozone response as a function of exposure rate and total inhaled dose
Authors: McDonnell W. F. , Smith M. V.
Published: December 2017

The magnitude of respiratory responses to short-term ozone exposure is known to be a function of the exposure variables concentration (C), duration of exposure (T), and minute ventilation (VE) during exposure. The purpose of this study was to identify a mathematical model that described ozone-induced mean decrements in forced expiratory volume in 1 s (FEV1) as a function of exposure rate (C x VE) and total inhaled dose (C x VE x T). Three hundred seventy-four young male nonsmokers participated in 504 exposures to several concentrations of ozone for 2 or 6.6 h. Mean percent change in FEV1 was calculated for each hour of exposure and was fit to the exposure variables by use of nonlinear models. We identified a general sigmoid-shaped model that well described the observed mean response in terms of exposure rate and total inhaled dose over a wide range of C and T. By fixing the value of a single parameter, this model reduces to a simpler form, which was adequate for description of responses over narrower ranges of exposure conditions. We concluded that the observed mean responses to short-term ozone exposure were adequately described by the nonlinear models identified in this study and that models of this form may be useful for description of responses over a wide range of C and T.
Mechanism of reduction in alveolar-arterial PO2 difference by helium breathing in the exercising horse
Authors: Erickson B. K. , Seaman J. , Kubo K. , Hiraga A. , Kai M. , Yamaya Y. , Wagner P. D.
Published: December 2017

Previous work has shown that replacing N2 in air with He at the same inspired O2 fraction reduces the exercise-induced alveolar-arterial PO2 difference (AaPO2) in horses but has provided no mechanism explaining this effect. We sought to distinguish among possible causes by using the multiple inert gas elimination technique. Six horses were studied on a high-speed treadmill while they breathed either ambient air or normoxic He-O2. O2 uptake reached 138.0 ml.min-1.kg-1 and was not affected by He-O2. Temperature-corrected arterial PO2 was 76.7 Torr (air) and 86.9 Torr (He-O2) (P < 0.01). Corresponding AaPO2 was 22.3 and 15.9 Torr, respectively (P < 0.01). Mean AaPO2 predicted from ventilation-perfusion inequality did not change with He-O2 (12.7 Torr with air and 11.9 Torr with He-O2). Mean arterial PCO2 was 50.1 Torr with air and 44.1 Torr with He-O2 (P < 0.01); minute ventilation and tidal volume were correspondingly higher by 140 l/min and 1.0 liter, respectively, with He-O2. Pulmonary O2 diffusing capacity, cardiac output, and all ventilation-perfusion dispersion indexes did not change with He-O2. Intrapulmonary shunt was insignificant. Higher ventilation with He-O2 explained only approximately 4 Torr of the 10-Torr rise observed in arterial PO2. The remainder (and the corresponding fall in AaPO2) was due to more complete diffusion equilibration as a consequence of the higher minute ventilation and thus alveolar PO2, which reduced the average slope of the O2 dissociation curve, thereby increasing the ratio of diffusive to perfusive conductance.
Anesthesia and chest wall function in dogs
Authors: Warner D. O. , Joyner M. J. , Ritman E. L.
Published: December 2017

Three anesthetics (pentobarbital, halothane, and isoflurane) were studied in six mongrel dogs to systematically compare their effects on chest wall function during spontaneous breathing. Each dog received each anesthetic on separate occasions. Electrical activities of several respiratory muscles were measured with chronically implanted electrodes, and chest wall motion was assessed by high-speed three-dimensional computed tomography scanning. Phasic expiratory muscle activity was markedly depressed by volatile anesthetics halothane and isoflurane compared with pentobarbital. In contrast, inspiratory activity in parasternal intercostal muscles was relatively well preserved during anesthesia with these volatile agents. The contribution of expiratory muscles to tidal volume was diminished during halothane and isoflurane compared with pentobarbital anesthesia. As anesthesia was deepened, expiratory muscle activity was unchanged during pentobarbital anesthesia, enhanced in some dogs during isoflurane anesthesia, and remained absent during halothane anesthesia. Activity in parasternal intercostal muscle was depressed as inspired concentration of halothane or isoflurane was increased, whereas diaphragmatic activity was unchanged. Depression of expiratory muscle activity by halothane persisted when breathing was stimulated by positive end-expiratory pressure, with significant mechanical consequences for chest wall configuration. Many of these findings are in contrast with previous observations in humans and suggest that the dog is not a suitable model for the study of the effects of anesthetic drugs on the pattern of human respiratory muscle activity.
Electromyographic evaluation of joint angle specificity and cross-training after isometric training
Authors: Weir J. P. , Housh T. J. , Weir L. L.
Published: December 2017

The purpose of this study was to examine the effects of unilateral strength training on the strength and integrated electromyogram (IEMG) of the trained and untrained limbs at several joint angles. A training group [TRN; 4 females and 3 males, age 22 +/- 4 yr (SD)] exercised for 6 wk with isometric leg extensions at 80% of maximal isometric torque. A control group (3 females and 3 males, age 24 +/- 4 yr) did not exercise. The training was performed three times per week at 0.79 rad below the horizontal plane. The subjects were tested at joint angles of 0.00, 0.26, 0.79, 1.31, and 1.57 rad. Bipolar surface electrodes were used to record the IEMG of the vastus lateralis. The results indicated a cross-training effect and joint angle specificity for isometric torque in TRN only, with significant (P < 0.0005) increases in torque (collapsed across limb) at 0.26 (23.3%) and 0.79 (22.3%) rad. There was a dissociation, however, between changes in torque and IEMG with an increase (P < 0.05) in IEMG (collapsed across limb and angle) for TRN. The dissociation between the IEMG and strength changes was possibly due to differential responses to training in the four muscles of the quadriceps femoris.
Physiological tolerance to uncompensable heat stress: effects of exercise intensity, protective clothing, and climate
Authors: Montain S. J. , Sawka M. N. , Cadarette B. S. , Quigley M. D. , McKay J. M.
Published: December 2017

This study determined the influence of exercise intensity, protective clothing level, and climate on physiological tolerance to uncompensable heat stress. It also compared the relationship between core temperature and the incidence of exhaustion from heat strain for persons wearing protective clothing to previously published data of unclothed persons during uncompensable heat stress. Seven heat-acclimated men attempted 180-min treadmill walks at metabolic rates of approximately 425 and 600 W while wearing full (clo = 1.5) or partial (clo = 1.3) protective clothing in both a desert (43 degrees C dry bulb, 20% relative humidity, wind 2.2 m/s) and tropical (35 degrees C dry bulb, 50% relative humidity, wind 2.2 m/s) climate. During these trials, the evaporative cooling required to maintain thermal balance exceeded the maximal evaporative capacity of the environment and core temperature continued to rise until exhaustion from heat strain occurred. Our findings concerning exhaustion from heat strain are 1) full encapsulation in protective clothing reduces physiological tolerance as core temperature at exhaustion was lower (P < 0.05) in fully than in partially clothed persons, 2) partial encapsulation results in physiological tolerance similar to that reported for unclothed persons, 3) raising metabolic rate from 400 to 600 W does not alter physiological tolerance when subjects are fully clothed, and 4) physiological tolerance is similar when subjects are wearing protective clothing in desert and tropical climates having the same wet bulb globe thermometer. These findings can improve occupational safety guidelines for human heat exposure, as they provide further evidence that the incidence of exhaustion from heat strain can be predicted from core temperature.
Naloxone does not affect the cardiovascular and sympathetic adjustments to static exercise in humans
Authors: Ray C. A. , Pawelczyk J. A.
Published: December 2017

Previous studies suggested that endogenous opiates may attenuate the cardiovascular and sympathetic adjustments to static exercise. We tested whether this effect originates from exercising skeletal muscle. Eight men performed 2 min of static handgrip (30% maximum) followed by 2 min of posthandgrip muscle ischemia after three interventions: 1) control, 2) intra-arterial injection of naloxone HCl (60 micrograms) or vehicle (saline) in the exercising arm, and 3) systemic infusion of naloxone (4 mg) or vehicle. Naloxone and vehicle trials were performed double blind on separate days. Preexercise baseline muscle sympathetic nerve activity (burst frequency), heart rate, and blood pressure were similar across interventions on either day. During static handgrip, control, intra-arterial, and systemic administration of vehicle and naloxone elicited similar increases in total muscle sympathetic nerve activity (58 +/- 24 vs. 68 +/- 26, 146 +/- 49 vs. 132 +/- 42, 137 +/- 54 vs. 164 +/- 44%, respectively), heart rate (9 +/- 2 vs. 8 +/- 3, 16 +/- 3 vs. 16 +/- 2, 20 +/- 4 vs. 19 +/- 3 beats/min, respectively), and mean arterial pressure (22 +/- 4 vs. 21 +/- 4, 29 +/- 5 vs. 26 +/- 3, 28 +/- 4 vs. 27 +/- 4 mmHg, respectively). Additionally, there were no differences between vehicle and naloxone trials during posthandgrip muscle ischemia. Thus, contrary to previous reports, we conclude that the endogenous opiate peptide system does not modulate cardiovascular and sympathetic responses to brief periods of static exercise or muscle ischemia in humans.
Effect of lipid on inert gas kinetics
Authors: Himm J. F. , Homer L. D. , Novotny J. A.
Published: December 2017

A Monte Carlo simulation of inert gas transit through skeletal muscle has been extended to include regions of increased gas solubility to simulate regions of high lipid content. Position of the regions within the simulation module was varied, as was the muscle-lipid partition coefficient (lambda). The volume percentage of the lipid regions (alpha) was varied from 0 to 25% while lambda covered the range from 1 to 50. The effects of alpha and lambda on mean transit time and on relative dispersion (RD; ratio of SD to the mean) were examined for a single lipid volume and compared with expected values under the assumption that the tissue is composed of two well-stirred compartments. Mean transit times varied from approximately 0.80 to 1.20 times the values predicted by a simple parallel two-compartment model, whereas RD varied from 0.9 to 3.6. For fixed lambda, RD as a function of lipid fraction passes through a maximum that is shifted and was also smaller than expected from a simple two-compartment model. For fixed alpha, RD approaches an asymptotic value for large lambda, but the asymptote is smaller than that expected from the two-compartment model. When lipid is distributed in only two regions, RD decreases with increasing separation of the regions and with increasing surface area of the fat regions. A model of two well-stirred compartments that allows mixing between the compartments yields results similar to those from the simulation.
Effects of hyperoxia on rat diaphragm function
Authors: Anzueto A. , Brassard J. M. , Andrade F. H. , Lawrence R. A. , Maxwell L. C. , Levine S. M. , Jenkinson S. G.
Published: December 2017

The association of oxygen radical generation with impaired diaphragm performance has previously been reported after inspiratory resistive loading (IRL). We hypothesized that exposure of rats to normobaric hyperoxia (O2) could produce impaired diaphragm function because of free radical production. Sprague-Dawley rats were divided into four groups: 1) room air (control), 2) > 95% O2 for 24 h, 3) > 95% O2 for 48 h, and 4) > 95% O2 for 60 h. Each group was studied at rest after the O2 exposure and then after IRL. During IRL, the animals breathed through an inspiratory resistor until they were unable to sustain > 70% of the maximum airway pressure. Diaphragm samples were obtained for analysis of glutathione (GSH) and glutathione disulfide (GSSG) concentrations. In vitro isometric contractile properties were also determined, including maximal tetanic tension (Po) and maximal twitch tension (Pt), in GSSG content and in GSSG-to-GSH ratios. Hyperoxia for > 48 h resulted in significant decreases in Po and Pt and an increase in GSSG content and in GSSG-to-GSH ratios compared with other groups. Those same animals subjected to IRL showed a further decrease in Po and Pt. These data suggest that free radical generation may occur in the diaphragm during a hyperoxia exposure associated with activation of the GSH redox cycle and impairment of diaphragm function.
Evans blue dye in the assessment of permeability-surface are product in perfused rat lungs
Authors: Dallal M. M. , Chang S. W.
Published: December 2017

Evans blue dye (EBD) has been used extensively as a marker of extravascular protein leakage. We assessed the utility of EBD as an albumin marker in the measurement of permeability-surface area product (PS) in perfused rat lungs and compared the results with PS values obtained using 125I-labeled albumin. In isolated perfused rat lungs, PS was measured by exposure to a perfusate containing EBD (600 micrograms/ml) and 125I-albumin (I microCi) for exactly 3 min, followed by washout of the intravascular space with fresh perfusate for 6 min. In lungs from normal rats, we found that PS obtained by EBD (PS-EBD) was fivefold higher than PS obtained by 125I-albumin (PS-125I) [1.92 +/- 0.32 (SE) vs. 0.42 +/- 0.03 x 10(-2) cm3.min-1.g-1, P < 0.05]. Similarly, in rats pretreated with Salmonella enteritidis lipopolysaccharide (2 mg/kg iv), PS-EBD was much higher than PS-125I (2.01 +/- 0.30 vs. 0.59 +/- 0.08 x 10(-2) cm3.min-1.g-1, P < 0.01). This discrepancy between PS-EBD and PS-125I was not explained by differences in the amount of free marker in perfusate, because the albumin-binding rate for both markers was very high. In addition, prolonged perfusion (40 min) with EBD did not significantly affect pulmonary vasoreactivity or water content in rat lungs. A detailed comparison of the kinetics of lung tissue uptake of EBD followed by parallel uptake of both markers up to 60 min of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Developmental differences in vascular responses to hypoxia in lungs of rabbits
Authors: Fike C. D. , Kaplowitz M. R.
Published: December 2017

Our purpose was to determine whether postnatal age and prostaglandins influence the sites of hypoxic vasoconstriction in lungs of rabbits. To do this, we used the micropuncture technique to measure pressures in 20- to 80-microns-diam subpleural arterioles and venules during sequential inflation of lungs of newborn and adult rabbits with normoxic (21% O2–7–10% CO2–69–72% N2) and hypoxic (90–93% N2–7–10% CO2) gas mixtures. Indomethacin (40 micrograms/ml) was added to the perfusate of some lungs of each age group. During hypoxia in untreated lungs of newborn rabbits, both pulmonary arterial and 20- to 80-microns-diam arteriolar pressure increased by 5%, whereas 20- to 80-microns-diam venular pressure remained the same. In contrast, during hypoxia in untreated lungs of adult rabbits, pulmonary arterial pressure increased by 48%, whereas 20- to 80-microns-diam arteriolar pressure decreased slightly and 20- to 80-microns-diam venular pressure did not change. Regardless of the presence of indomethacin, location of vessels used for micropuncture, or level of left atrial pressure, pulmonary arterial pressure was the only measured vascular pressure that increased with hypoxia in adult lungs. Thus, in adult lungs, the site of hypoxia-induced vasoconstriction was limited to arteries > 80 microns diam, whereas in newborn lungs the site of hypoxia-induced vasoconstriction included vessels both larger and smaller than 20- to 80-microns-diam arteries. This age-related difference in the sites of hypoxia-induced vasoconstriction was not found in indomethacin-treated lungs.