bluuebunny/crossref_metadata_2025 huggingface dataset:
Variant chicken AE1 anion exchangers possess divergent NH(2)-terminal cytoplasmic domains
Authors: Cox K. H. , Cox J. V.
Published: December 2017

Immunoblotting analyses have demonstrated that antibodies specific for the chicken erythroid AE1 anion exchanger recognize multiple polypeptides ranging in size from approximately 95 to 112 kDa in chicken kidney. To determine the origin of this diversity, we have cloned and characterized the kidney AE1 anion exchangers. These studies have shown that the kidney AE1 polypeptides are encoded by at least three transcripts, AE1-3, AE1-4, and AE1-5, which differ from the erythroid AE1-1 and AE1-2 transcripts in the sequences present at their 5'-ends. The AE1-3 and AE1-5 transcripts encode predicted polypeptides of approximately 94 kDa, which are identical to the erythroid AE1-1 anion exchanger except for the absence of the 78 NH(2)-terminal amino acids of the AE1-1 polypeptide. In contrast, the AE1-4 transcript encodes a predicted polypeptide of approximately 101 kDa, whose 21 NH(2)-terminal amino acids are unique. Characterization of the AE1 cDNAs has suggested that the AE1-3 and AE1-4 transcripts are generated by alternative splicing of a single primary transcript, while DNA blotting analyses have shown that the putative transcription initiation sites of the variant AE1-4 and AE1-5 transcripts lie several kilobases downstream of the transcription initiation sites of the erythroid AE1-1 and AE1-2 transcripts. These results suggest that the pattern of accumulation of the variant kidney AE1 anion exchangers is regulated by a complex pattern of alternative transcriptional initiation and differential RNA splicing.
Human initial responses to immersion in cold water at three temperatures and after hyperventilation
Authors: Tipton M. J. , Stubbs D. A. , Elliott D. H.
Published: December 2017

The present investigation was designed to examine the influence of water temperature and prior hyperventilation on some of the potentially hazardous responses evoked by immersion in cold water. Eight naked subjects performed headout immersions of 2-min duration into stirred water at 5, 10, and 15 degrees C and at 10 degrees C after 1 min of voluntary hyperventilation. Analysis of the respiratory and cardiac data collected during consecutive 10-s periods showed that, at the 0.18-m/s rate of immersion employed, differences between the variables recorded on immersion in water at 5 and 10 degrees C were due to the duration of the responses evoked rather than their magnitude during the first 20 s. The exception to this was the tidal volume of subjects, which was higher on immersion in water at 15 degrees C than at 5 or 10 degrees C. The results suggested that the respiratory drive evoked during the first seconds of immersion was more closely reflected in the rate rather than the depth of breathing at this time. Hyperventilation before immersion in water at 10 degrees C did not attenuate the respiratory responses seen on immersion. It is concluded that, during the first critical seconds of immersion, the initial responses evoked by immersion in water at 10 degrees C can represent as great a threat as those in water at 5 degrees C; also, in water at 10 degrees C, the respiratory component of this threat is not influenced by the biochemical alterations associated with prior hyperventilation.
Use of collateral airways to assess airway reactivity
Authors: Corddry D. H. , Sauder R. A. , Weinmann G. G. , Hirshman C. A. , Mitzner W.
Published: December 2017

We investigated the correlation between collateral airway reactivity and other indexes of lung reactivity in response to aerosol and intravenous (iv) challenges. In four anesthetized mongrel dogs, we measured the peripheral airway resistance (Rp) to gas flow out of a wedged lung segment in different lobes on multiple occasions. We obtained dose-response curves of peripheral airways challenged with iv histamine or aerosols through the bronchoscope. During the same iv bolus challenge, whole lung airway pressure (Paw) responses to histamine were also measured. On separate occasions, changes in lung resistance (RL) were measured after the whole lung was challenged with a histamine aerosol. Reactivity was assessed from the dose-response curves for Rp and RL as the PD50 (dose required to produce a 50% increase); for changes in Paw we calculated the PD15 (dose required to produce a 15% increase over baseline). Results for Rp showed considerably more variability among different lobes in a given animal with the aerosol challenge through the bronchoscope than with the iv challenge. With aerosol challenge there were no significant differences in the mean PD50 for Rp among any of the animals. However, with the iv challenge two of the dogs showed significant differences from the others in reactivity assessed with Rp (P less than 0.01). Moreover, the differences found in the peripheral airways with iv challenge reflected differences found in whole lung reactivity assessed with either iv challenge (Paw vs. Rp, r2 = 0.96) or whole lung aerosol challenge (RL vs. Rp, r2 = 0.84). We conclude that the measurement of the collateral resistance response to iv challenge may provide a sensitive method for assessing airway reactivity.
Muscle glucose uptake of obese Zucker rats trained at two different intensities
Authors: Willems M. E. , Brozinick J. T. , Torgan C. E. , Cortez M. Y. , Ivy J. L.
Published: December 2017

Exercise training reduces the muscle insulin resistance of the obese Zucker rat. The purpose of the present study was to determine whether the magnitude of this training response is exercise intensity specific. Obese Zucker rats were randomly divided into sedentary (SED), low-intensity (LI), and high-intensity (HI) exercise groups. For the LI rats, exercise training consisted of running on a rodent treadmill at 18 m/min up an 8% grade for 90 min. Rats in the HI group ran at 24 m/min up an 8% grade for four 17-min bouts with 3 min between bouts. Both exercise groups performed the same amount of work and trained 5 days/wk for 7 wk. To evaluate muscle insulin resistance, rat hindlimbs were perfused for 30 min with perfusate containing 6 mM glucose (0.15 mu Ci of D-[14C(U)] glucose/ml) and either a maximal (10.0 mU/ml) or a submaximal (0.50 mU/ml) insulin concentration. Perfusions were performed 48–56 h after the last exercise bout and a 12-h fast. In the presence of 0.5 mU/ml insulin, the rate of muscle glucose uptake was found to be significantly faster for the HI (9.56 +/- 0.66 mumol.h-1.g-1) than for the LI (7.72 +/- 0.65 mumol.h-1.g-1) and SED (6.64 +/- 0.44 mumol.h-1.g-1) rats. The difference in glucose uptake between the LI and SED rats was not significant. In the presence of 10.0 mU/ml insulin, the rate of glucose uptake was significantly faster for the HI (16.43 +/- 1.02 mumol.h-1.g-1) than for the LI rats (13.76 +/- 0.84 mumol.h-1.g-1) and significantly faster for the LI than for the SED rats (11.02 +/- 0.35 mumol.h-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of glucose on hypoxic vasoconstriction in isolated ferret lungs
Authors: Wiener C. M. , Sylvester J. T.
Published: December 2017

To characterize the effects of glucose on the pulmonary vascular response to anoxia and hypoxia, isolated ferret lungs were ventilated with 28% O2 and 5% CO2 and perfused at constant flow (100 ml.kg-1.min-1). Perfusate glucose concentrations were allowed to fall spontaneously to less than 1 mM (low glucose) or were controlled at 5–6 mM (normal glucose) or 12–17 mM (high glucose). At 60, 120, and 180 min of perfusion, the inspired O2 tension (PIO2) was reduced to 0, 10, or 30 Torr for 30 min, and vasomotor responses were quantified by continuous measurement of pulmonary arterial pressure. At PIO2 of 0 Torr, the response consisted of an early phase of transient intense vasoconstriction and a late phase of sustained slight vasoconstriction. High glucose markedly potentiated the magnitude of late-phase vasoconstriction with each successive anoxic exposure. This effect was not reproduced in normal glucose lungs and was not caused by a change in perfusate osmolarity, an action on blood cells, or an altered ability of pulmonary vascular smooth muscle to contract. At PIO2 of 10 Torr, high glucose not only potentiated late-phase vasoconstriction but also slowed the onset of early-phase vasoconstriction. At PIO2 of 30 Torr, high glucose had no effect on vasomotor responses, which were characterized by a slowly developing sustained vasoconstriction. Our results suggest that the vascular response of isolated ferret lungs to severe hypoxia consisted of separate early and late phases of vasoconstriction. This biphasic response may have resulted from two distinct vasoconstrictor mechanisms or from modulation of a single vasoconstrictor mechanism by a secondary vasodilator influence.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory adaptations to dead space loading during maximal incremental exercise
Authors: McParland C. , Mink J. , Gallagher C. G.
Published: December 2017

We examined the effects of dead space (VD) loading on breathing pattern during maximal incremental exercise in eight normal subjects. Addition of external VD was associated with a significant increase in tidal volume (VT) and decrease in respiratory frequency (f) at moderate and high levels of ventilation (VI); at a VI of 120 l/min, VT and f with added VD were 3.31 +/- 0.33 liters and 36.7 +/- 6.7 breaths/min, respectively, compared with 2.90 +/- 0.29 liters and 41.8 +/- 7.3 breaths/min without added VD. Because breathing pattern does not change with CO2 inhalation during heavy exercise (Gallagher et al. J. Appl. Physiol. 63: 238–244, 1987), the breathing pattern response to added VD is probably a consequence of alteration in the PCO2 time profile, possibly sensed by the carotid body and/or airway-pulmonary chemoreceptors. The increase in VT during heavy exercise with VD loading indicates that the tachypneic breathing pattern of heavy exercise is not due to mechanical limitation of maximum ventilatory capacity at high levels of VT.
Alveolar transepithelial potential difference and ion transport in adult rat lung
Authors: Ballard S. T. , Gatzy J. T.
Published: December 2017

The complex morphology of the mammalian lung complicates characterization of solute transport across the intact alveolar epithelium. We impaled the subpleural alveolar epithelium with microelectrodes and measured the transepithelial potential difference (PD) of the liquid-filled vascular-perfused left lobe of the rat lung. When the air space was filled entirely with Krebs-Ringer-bicarbonate, the PD was 4.7 mV (lumen negative). The PD was not affected significantly by agents that modify either Na+ or Cl- transport, but replacement of luminal Cl- with gluconate resulted in a fourfold hyperpolarization, a response also noted for large airways. When the airways were blocked by an immiscible nonconducting fluorocarbon, basal PD was not different from unblocked lobes (4.0 mV) but was inhibited 73% by luminal amiloride. Cl(-)-free Krebs-Ringer-bicarbonate blocked in the alveoli with fluorocarbon did not induce hyperpolarization. This result suggests that 1) Cl- permselectivity of the alveolar epithelium is less than that of large airway epithelium and 2) airway PD dominates the voltage across the liquid-filled lung, even when measurements are made from alveoli. When airways are blocked by fluorocarbon, the PD across the alveolar epithelium is largely dependent on Na+ flow through a path with amiloride-sensitive channels.
Initial blood pressure fall on stand up and exercise explained by changes in total peripheral resistance
Authors: Sprangers R. L. , Wesseling K. H. , Imholz A. L. , Imholz B. P. , Wieling W.
Published: December 2017

To elucidate the underlying mechanisms of the initial fall in blood pressure on standing upright from the supine position, we measured the beat-to-beat changes in intra-arterial pressure in eight healthy male subjects in response to standing. Changes in stroke volume, cardiac output, and total peripheral resistance were computed from the pressure waveform using a pulse contour method. To determine possible mechanisms for the changes observed on standing, similar measures were made on passive tilting and a brief (3-s) bout of cycle exercise. Standing elicited a transient 25% (23-mmHg) fall in mean blood pressure as a result of a 36% fall in total peripheral resistance. Head-up tilt elicited a gradual change in haemodynamic parameters, which reached plateau levels in 20-30 s. Cycling elicited a transient 17% (18-mmHg) fall in blood pressure and a 41% fall in total peripheral resistance. In addition, we measured right atrial and esophageal pressures in two subjects on standing and cycling and found a 10- to 15-mmHg rise in right atrial pressure without a corresponding change in esophageal pressure. This points to the cardiopulmonary reflex as the primary effector of peripheral vasodilation, but we cannot exclude the possibility that 1) local metabolic vasodilation and 2) central command-mediated cholinergic vasodilation contributed to the fall in vascular resistance.
Measurement of airway wall blood flow in sheep by laser-Doppler flowmetry: interpretation and problems
Authors: Godden D. J. , Wagner E. M. , Pare P. D. , Mitzner W. , Baile E. M.
Published: December 2017

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation frequency-dependent nonadrenergic noncholinergic airway responses of the guinea pig
Authors: Venugopalan C. S. , Holmes E. P. , Fucci V. , Guthrie A. J.
Published: December 2017

We examined the inhibitory and excitatory components of the nonadrenergic noncholinergic (NANC) innervation of the guinea pig airways by in vivo and in vitro methods. Electrical stimulation of the vagus in chloralose-urethan-anesthetized guinea pigs after cholinergic and adrenergic blockade produced peripheral airway constriction (insufflation pressure) and tracheal relaxation (pouch pressure). Vagal stimulation was applied for 90 s at 5-V pulses of 2-ms duration at frequencies of 5, 15, 25, and 35 Hz in each group (n = 6). The pouch relaxation peaked at 15 Hz. The insufflation pressure was highest at 5 Hz. Field stimulations of the same frequencies were applied on tracheal spirals and lung parenchymal strips. The maximal relaxation of the trachea occurred at 15-35 Hz. The lung parenchymal strip tensions increased almost linearly as the frequency increased from 5 to 35 Hz. The results of the study indicated a frequency-dependent response for both excitatory and inhibitory components of the NANC, which operate at different frequencies for optimal responses.
Refractoriness for ultrasonically nebulized distilled water and histamine after histamine challenge
Authors: Groot C. , Lammers J. W. , Festen J. , van Herwaarden C.
Published: December 2017

Refractoriness for bronchial provocation frequently occurs after different challenge tests used to assess bronchial hyperresponsiveness in asthmatic patients. We investigated whether histamine inhalation could cause refractoriness for bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) and whether histamine causes tachyphylaxis for a subsequent histamine challenge in nine stable asthmatic patients. Preinhalation of histamine induced a significant diminished bronchoconstrictor response to UNDW cumulative dose of inhaled UNDW causing a 20% fall in forced expired volume in 1 s. The mean increased from 3.5 +/- 0.8 to 11.8 +/- 2.6 (SE) ml after histamine challenge (P less than 0.01). However, repeated inhalation of histamine did not change the bronchoconstrictor response to histamine within 1 h after rechallenge (P greater than 0.5). The magnitude of refractoriness for UNDW inhalation after preinhalation of histamine was correlated to the bronchoconstrictor response to histamine (r = 0.73, P less than 0.05). We conclude that inhaled histamine can induce refractoriness for UNDW, which seems to be related to the degree of bronchial hyperresponsiveness.
Retention and clearance of 0.9-micron particles inhaled by hamsters during rest or exercise
Authors: Zeltner T. B. , Sweeney T. D. , Skornik W. A. , Feldman H. A. , Brain J. D.
Published: December 2017

We assessed the retention and clearance of inhaled particles in six anatomic compartments of the respiratory tract. Hamsters were exposed for 45 min to 0.9-micron fluorescent latex particles either at rest (n = 9) or while running on a laddermill (n = 9). Oxygen consumption, which was used to estimate minute ventilation, was continuously monitored. Three animals from each group, rest and exercise, were killed at 10 min, 24 h, or 7 days after the exposure. Morphometric techniques were used to determine the number of particles retained in nose and oropharynx (NOSE), trachea and extrapulmonary airways, intrapulmonary conducting airways, respiratory bronchioles, alveolar ducts (AD), and alveoli (ALV). At 10 min, total particle retention increased linearly as a function of O2 consumption (slope = 1.4 +/- 0.3 x 10(6) particles.ml-1.g-1.h-1, P less than 0.015). Exercised hamsters retained 4.4 times more total particles in their NOSE than rested hamsters, but parenchymal retention (AD + ALV) was unaffected. After 7 days, 95% of the particles were cleared from the NOSE, 80% from the trachea and extrapulmonary airways, 44% from intrapulmonary conducting airways and respiratory bronchioles, and 16% from AD and ALV. There was evidence of particle redistribution from AD to ALV during the 1st day. We conclude that exercise enhances the deposition of 0.9-micron particles in the upper respiratory tract but not in the parenchyma. Subsequently, the deposited particles are cleared at varying rates depending on the lung compartment.
Differential activation within costal diaphragm during rapid-eye-movement sleep in cats
Authors: Hendricks J. C. , Kline L. R.
Published: December 2017

Simultaneous recordings of the diaphragmatic electromyogram (EMG) were made from two separate regions of the costal diaphragm in six normal cats. The diaphragmatic activities were always synchronous and the amplitudes and rates of rise were similar during slow-wave sleep. In contrast, during natural rapid-eye-movement (REM) sleep, different activity was often present in the two leads. These differences were in the time of onset and offset, as well as in the amplitude and spike patterns, and occurred in approximately 5-20% of the diaphragmatic bursts averaged over the entire REM sleep period. With respect to eye movement density, the rate of differential activation was higher during periods of high density (26%) than in the absence of eye movements (1%) in the four animals for which these data were available. Differential activation of portions of the costal diaphragm is apparently a normal event of REM sleep. This could result from descending state-specific phasic neuronal activity that bypasses the medullary respiratory generator. Differential activation of portions of the diaphragm could contribute to disordered ventilation during REM sleep.
Development of the pulmonary vasculature in newborn lambs: structure-function relationships
Authors: Michel R. P. , Gordon J. B. , Chu K.
Published: December 2017

Our objectives were 1) to describe the quantitative light microscopy and ultrastructure of newborn lamb lungs and 2) to correlate hemodynamic changes during normoxia and hypoxia with the morphology. By light microscopy, we measured the percent muscle thickness (%MT) and peripheral muscularization of pulmonary arteries and veins from 25 lambs aged less than 24 h, 2-4 days, 2 wk, and 1 mo. At the same ages, lungs were isolated and perfused in situ and, after cyclooxygenase blockade with indomethacin, total, arterial (delta Pa), middle (delta Pm), and venous pressure gradients at inspired O2 fractions of 0.28 (mild hyperoxia) and 0.04 (hypoxia) were determined with inflow-outflow occlusion. During mild hyperoxia, delta Pa and delta Pm fell significantly between 2-4 days and 2 wk, whereas during hypoxia, only delta Pm fell. The %MT of all arteries (less than 50 to greater than 1,000 microns diam) decreased, and peripheral muscularization of less than 100-microns-diam arteries fell between less than 4 days and greater than 2 wk. Our data suggest that 1) the %MT of arteries determines normoxic pulmonary vascular resistance, because only arterial and middle segment resistance fell, 2) peripheral muscularization is a major determinant of hypoxic pulmonary vasoconstriction, because we observed a fall with age in peripheral muscularization of less than 100-micron-diam arteries and in delta Pm with hypoxia, and 3) the arterial limit of the middle segment defined by inflow-outflow occlusion lies in 100- to 1,000-microns-diam arteries.
Fetal breathing and development of control of breathing
Authors: Jansen A. H. , Chernick V.
Published: December 2017

Technical advances during the last several decades have greatly facilitated research into fetal physiology and behavior, specifically fetal breathing (FB). Breathing movements have been demonstrated in the fetuses of every mammalian species investigated and appear to be part of normal fetal development. In this review we focus on the methods of measuring FB and on some of the problems associated with these measurements and their interpretation. We also review fetal behavior, the role of the peripheral and central chemoreceptors in spontaneous FB, the fetal respiratory response to hypercapnia and hypoxia, and the transition to continuous breathing at birth. It is clear that in many ways the control of breathing movements in utero differs from that after birth. In particular, inhibitory influences are much more prominent before than after birth. Possibly this is due to the unique fetal situation, in which conservation of energy may be more important than any advantage breathing activity imparts to the fetus.
Hypohydration does not impair skeletal muscle glycogen resynthesis after exercise
Authors: Neufer P. D. , Sawka M. N. , Young A. J. , Quigley M. D. , Latzka W. A. , Levine L.
Published: December 2017

The purpose of this investigation was to examine the effects of moderate hypohydration (HY) on skeletal muscle glycogen resynthesis after exhaustive exercise. On two occasions, eight males completed 2 h of intermittent cycle ergometer exercise (4 bouts of 17 min at 60% and 3 min at 80% of maximal O2 consumption/10 min rest) to reduce muscle glycogen concentrations (control values 711 +/- 41 mumol/g dry wt). During one trial, cycle exercise was followed by several hours of light upper body exercise in the heat without fluid replacement to induce HY (-5% body wt); in the second trial, sufficient water was ingested during the upper body exercise and heat exposure to maintain euhydration (EU). In both trials, 400 g of carbohydrate were ingested at the completion of exercise and followed by 15 h of rest while the desired hydration level was maintained. Muscle biopsy samples were obtained from the vastus lateralis immediately after intermittent cycle exercise (T1) and after 15 h of rest (T2). During the HY trial, the muscle water content was lower (P less than 0.05) at T1 and T2 (288 +/- 9 and 265 +/- 5 ml/100 g dry wt, respectively; NS) than during EU (313 +/- 8 and 301 +/- 4 ml/100 g dry wt, respectively; NS). Muscle glycogen concentration was not significantly different during EU and HY at T1 (200 +/- 35 vs. 251 +/- 50 mumol/g dry wt) or T2 (452 +/- 34 vs. 491 +/- 35 mumol/g dry wt). These data indicate that, despite reduced water content during the first 15 h after heavy exercise, skeletal muscle glycogen resynthesis is not impaired.
Interaction between exercise and food restriction: effects on longevity of male rats
Authors: Holloszy J. O. , Schechtman K. B.
Published: December 2017

Male rats that exercise in running wheels have a longer average survival than freely eating sedentary controls but, in contrast to food-restricted sedentary controls of the same weight, show no extension of maximal life span (J. Appl. Physiol. 59: 826-831, 1985). To test the possibility that exercise may counteract a life-extending effect of decreased availability of energy for certain biological processes such as cell proliferation, we examined the combined effects of exercise and food restriction on longevity of male rats. As before, wheel running improved average length of life, 978 +/- 172 vs. 875 +/- 175 (SD) days, for the sedentary controls (P less than 0.01) without increasing maximal life span. Paired-weight controls, food restricted (approximately 30% below ad libitum) to weight the same as the runners, showed increases in both average (1,056 +/- 144 days) and maximal life span. Food-restricted runners, with intake restricted to the same extent (approximately 30%), had an increased mortality rate over the first approximately 50% of their survival curve up to approximately 900 days of age; their average life span (995 +/- 226) was similar to that of the control group of runners and shorter than that of their paired-weight food-restricted sedentary controls (1,088 +/- 159 days, P less than 0.05). However, after approximately 900 days of age the food-restricted runners' survival became similar to that of the food-restricted sedentary groups, with a comparable increase in maximal life span. Thus the exercise did not counteract the increase in maximal life span induced by food restriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of diaphragmatic lymphatic stomata
Authors: Negrini D. , Mukenge S. , Del Fabbro M. , Gonano C. , Miserocchi G.
Published: December 2017

In seven anesthetized rabbits we measured the size, shape, and density of lymphatic stomata on the peritoneal and pleural sides of the diaphragm. The diaphragm was fixed in situ and processed for scanning electron microscopy. Results are from 2,902 peritoneal and 3,086 pleural fields (each 1,620 microns 2) randomly chosen from the various specimens. Stomata were seen in 9% of the fields examined, and in 30% of the cases they appeared grouped in clusters with 2-14 stomata/field. Stoma density was 250 +/- 242 and 72 +/- 57 (SD) stomata/mm2 on peritoneal and pleural sides, respectively, and it was similar over the muscular and tendinous portion of the two surfaces. The maximum diameter ranged from less than 1 to approximately 30 microns, with an average value of 1.2 +/- 3.1 micron. The ratio of the maximum to the minimum diameter and the surface area averaged 2 +/- 1.4 and 0.7 +/- 2.4 micron 2, respectively. The maximum and minimum diameter and surface area values followed a lognormal frequency distribution, suggesting that stomata geometry is affected by diaphragmatic tension.
Volume flow across the alveolar epithelium of adult rat lung
Authors: Ballard S. T. , Gatzy J. T.
Published: December 2017

We separated the solute and water flow across the alveolar epithelium from flow across airway epithelia of the adult rat. Small volumes (0.5-1.0 ml) of Krebs-Ringer bicarbonate (KRB) were trapped in the distal air space of the isolated vascular-perfused left lung lobes while the airways were blocked by immiscible O2-carrying fluorocarbon. Lobe weight was lost or gained in response to colloid gradients and was raised by metabolic inhibitors but did not change with only fluorocarbon in the air space or in response to modifiers of epithelial ion transport. When serum was added to the KRB-colloid perfusion, weight loss occurred in the absence of a colloid gradient (3.4 ml/min) and was Na+ dependent (inhibited by luminal Na(+)-free KRB). The change in the concentration of blue dextran in liquid sampled by micropuncture from subpleural alveoli was smaller than expected from lobe weight under basal conditions or with a colloid gradient, even though the volume marker accurately detected edema formation (weight gain) induced by metabolic inhibitors. We conclude that 1) weight changes represent volume absorption from the air spaces, 2) serum stimulates a Na+ absorptive process, and 3) by exclusion, small airways and/or other subpopulations of alveoli are the site of this absorption.
Muscle glycogenolysis during differing intensities of weight-resistance exercise
Authors: Robergs R. A. , Pearson D. R. , Costill D. L. , Fink W. J. , Pascoe D. D. , Benedict M. A. , Lambert C. P. , Zachweija J. J.
Published: December 2017

Skeletal muscle glycogen metabolism was investigated in eight male subjects during and after six sets of 70% one repetition maximum (1 RM, I-70) and 35% 1 RM (I-35) intensity weight-resistance leg extension exercise. Total force application to the machine lever arm was determined via a strain gauge and computer interfaced system and was equated between trials. Compared with the I-70 trial, the I-35 trial was characterized by almost double the repetitions (13 +/- 1 vs. 6 +/- 0) and half the peak concentric torque for each repetition (12.4 +/- 0.5 vs. 24.2 +/- 1.0 Nm). After the sixth set, muscle glycogen degradation was similar between I-70 and I-35 trials (47.0 +/- 6.6 and 46.6 +/- 6.0 mmol/kg wet wt, respectively), as was muscle lactate accumulation (13.8 +/- 0.7 and 16.7 +/- 4.2 mmol/kg wet wt, respectively). After 2 h of passive recovery without caloric intake, muscle glycogen increased by 22.2 +/- 6.8 and 14.2 +/- 2.5 mmol/kg wet wt in the I-70 and I-35 trials, respectively. Optical absorbance measurement of periodic acid-Schiff-stained muscle sections after the 2 h of recovery revealed larger absorbance increases in fast-twitch than in slow-twitch fibers (0.119 +/- 0.024 and 0.055 +/- 0.024, P = 0.02). Data indicated that when external work was constant, the absolute amount of muscle glycogenolysis was the same regardless of the intensity of resistance exercise. Nevertheless the rate of glycogenolysis during the I-70 trial was approximately double that of the I-35 trial.
PEEP inhibits hypoxic pulmonary vasoconstriction in dogs
Authors: Lejeune P. , Vachiery J. L. , De Smet J. M. , Leeman M. , Brimioulle S. , Delcroix M. , Melot C. , Naeije R.
Published: December 2017

The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(ABSTRACT TRUNCATED AT 250 WORDS)
Early muscular and metabolic adaptations to prolonged exercise training in humans
Authors: Green H. J. , Jones S. , Ball-Burnett M. E. , Smith D. , Livesey J. , Farrance B. W.
Published: December 2017

A short-term training program involving 2 h of daily exercise at 59% of peak O2 uptake (VO2max) repeated for 10-12 consecutive days was employed to determine the significance of adaptations in energy metabolic potential on alterations in energy metabolism and substrate utilization in working muscle. The initial VO2max determined before training on the eight male subjects was 53.0 +/- 2.0 (SE) ml.kg-1.min-1. Analysis of samples obtained by needle biopsy from the vastus lateralis muscle before exercise (0 min) and at 15, 60, and 99 min of exercise indicated that on the average training resulted (P less than 0.05) in a 6.5% higher concentration of creatine phosphate, a 9.9% lower concentration of creatine, and a 39% lower concentration of lactate. Training had no effect on ATP concentration. These adaptations were also accompanied by a reduction in the utilization in glycogen such that by the end of exercise glycogen concentration was 47.1% higher in the trained muscle. Analysis of the maximal activities of representative enzymes of different metabolic pathways and segments indicated no change in potential in the citric acid cycle (succinate dehydrogenase, citrate synthase), beta-oxidation (3-hydroxyacyl CoA dehydrogenase), glucose phosphorylation (hexokinase), or potential for glycogenolysis (phosphorylase) and glycolysis (pyruvate kinase, phosphofructokinase, alpha-glycerophosphate dehydrogenase, lactate dehydrogenase). With the exception of increases in the capillary-to-fiber area ratio in type IIa fibers, no change was found in any fiber type (types I, IIa, and IIb) for area, number of capillaries, capillary-to-fiber area ratio, or oxidative potential with training.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct injury to the bronchial vasculature in anesthetized sheep
Authors: Dodek P. M. , Pare P. D. , Minshall D. K. , Wiggs B. R. , Doerschuk C. M. , Baile E. M.
Published: December 2017

Injury to the bronchial vasculature may contribute to liquid and solute leakage into the lung during noncardiac pulmonary edema. The purpose of this study was to measure changes in hemodynamics, pulmonary mechanics, extravascular lung water, and lung morphometry after selectively injuring the bronchial vasculature in anesthetized sheep. In two groups of seven sheep, we injected oleic acid (0.1 ml/kg) or normal saline directly into the bronchoesophageal artery. We measured systemic and pulmonary arterial pressures, cardiac output, oxygen saturation, pulmonary resistance and compliance, and lung volumes before and 1 and 4 h after injection. The lungs were removed for measurement of extravascular water, histology, and morphometry. Four hours after injection of oleic acid, cardiac output decreased but pulmonary arterial pressure did not change. In addition, pulmonary resistance increased and dynamic compliance and vital capacity decreased. Extravascular lung water was slightly but significantly greater in the oleic acid group. Histological examination showed interstitial edema and leukocytes in airway walls and sloughing of bronchial epithelium but little or no alveolar edema. Morphometric analysis showed significant thickening of airway walls. We conclude that direct injury to the bronchial vasculature increases lung resistance, decreases dynamic compliance, and increases extravascular lung water by the accumulation of an inflammatory infiltrate in airway walls.
Adipose tissue volume measured by magnetic resonance imaging and computerized tomography in rats
Authors: Ross R. , Leger L. , Guardo R. , De Guise J. , Pike B. G.
Published: December 2017

The primary purpose of this study was to investigate the viability of magnetic resonance imaging (MRI) as a means of measuring the body composition of rodents. To do so we compared adipose tissue (AT) volumes measured by MRI with those obtained by X-ray computerized tomography (CT) in a group of rats (n = 17) varying in weight (465-815 g) and percent body fat (5.4-31.1%), with the latter determined by chemical analysis. For both MRI and CT, AT volumes (cm3) per transverse slice (3-mm thickness, 21-mm centers) were determined using a computer-based image analysis system that permitted detailed comparisons of both visceral and subcutaneous AT depots. Total AT volumes were calculated using a linear interpolation of AT areas obtained on consecutive slices. Correlation coefficients between MRI and CT for visceral [r = 0.98, standard error of estimate (SEE) = 6.8 cm3], subcutaneous (r = 0.98, SEE = 6.5 cm3), and total AT volumes (r = 0.99, SEE = 9.0 cm3) were highly significant (P less than 0.001). Both MRI- and CT-predicted AT mass (assuming fat density = 0.90 g/ml) correlated strongly with chemically extracted lipid (grams) values (r = 0.98, SEE 9.6 g and r = 0.99, SEE = 6.9 g, respectively). Post hoc Scheffe contrasts demonstrated that the mean AT and lipid mass values derived by the three methods were not significantly different (P = 0.01). No systematic differences were observed because the regression lines derived for either MRI or CT vs. chemical analysis were not significantly different from the identity line.(ABSTRACT TRUNCATED AT 250 WORDS)
Pressure-diameter relationships of the upper airway in awake supine subjects
Authors: Wheatley J. R. , Kelly W. T. , Tully A. , Engel L. A.
Published: December 2017

In awake supine normal subjects, dimensional changes of the oropharyngeal airway were measured during exposure to negative intraluminal pressures. The pressure was generated 1) "actively" by subjects inspiring against an externally occluded airway or 2) "passively" by external suction at the mouth during voluntary glottic closure with no inspiratory effort. Airway dimensions were imaged with X-ray fluoroscopy and anteroposterior diameters measured at levels corresponding to cervical vertebra 3 and 4 (C3 and C4). Cephalad axial displacement of the hyoid bone (CDHY) was also measured. During the "active" maneuver, airway diameters and position were maintained at resting levels despite airway pressure up to -15 cmH2O. In contrast, during the passive maneuver at -15 cmH2O, C3 was only 15 +/- 9% and C4 only 47 +/- 8% of control; CDHY was 5.6 +/- 1.8 mm. In three subjects airway wall apposition occurred and persisted until an active inspiratory effort. We conclude that, in the absence of inspiratory effort, negative oropharyngeal airway pressures result in marked narrowing and cephalad displacement of the upper airway, even during wakefulness. Therefore, our data suggest that the complex interaction of upper airway and thoracic muscle activity is critical in determining the effective compliance and patency of the upper airway, which is readily collapsible even in normal subjects.
Adaptive modeling of the human rib cage in median sternotomy
Authors: Kenyon C. M. , Pedley T. J. , Higenbottam T. W.
Published: December 2017

This paper describes a limited computer-analyzed kinematic model of the rib cage that can be adapted to individual subjects. Also described is its validation and use in assessing the changes in chest wall shape after coronary artery bypass graft (CABG) surgery in 12 patients. The positions of a small number of anatomic locations on the thoracic spine, ribs, manubrium, and sternum are measured from lateral and posterior-anterior chest radiographs. The computer program puts these two views together removing the magnification and reconstructs any missing points to give a three-dimensional picture of the rib cage to which mathematical models of the bones are scaled. The patients had chest radiographs taken at total lung capacity (TLC) and residual volume (RV) to investigate the source of the restrictive ventilatory defect that follows CABG. The predictions from the model were tested by comparing full-sized computer plots with the actual chest radiographs. The estimates of the bony structures were accurate to +/- 3 degrees for orientations and +/- 6 mm for positions. We found reduced rib motion both "pump-handle" (theta) and "bucket handle" (psi) going from theta, psi left, psi right = 9 degrees, 10 degrees, 14 degrees to 4 degrees, 10 degrees, 9 degrees, respectively, after surgery with P less than 0.025, 0.42, 0.07. The angles were measured from the horizontal and increased caudally. There was also reduction in the range of angles subtended by the arc of the thoracic vertebrae between TLC and RV, which went from 12 degrees to -1 degrees (P less than 0.015). These data explain the fall in lung volumes that follow CABG and provide insight into the contribution made by the ribs and spine in full inspiration and full expiration.
Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits
Authors: Peters M. J. , Panaretto K. , Breslin A. B. , Berend N.
Published: December 2017

On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation.
Activation of neurons in the rostral ventrolateral medulla increases bronchomotor tone in dogs
Authors: Haselton J. R. , Padrid P. A. , Kaufman M. P.
Published: December 2017

Previous work from this laboratory has demonstrated that the chemical activation of cell bodies in the caudal ventrolateral medulla of chloralose-anesthetized dogs decreased bronchomotor tone by withdrawing cholinergic input to airway smooth muscle. In the present study we determined the bronchomotor responses to microinjection of DL-homocysteic acid (100 mM; 25–50 nl) into the rostral ventrolateral (RVL) medulla of chloralose-anesthetized dogs. Total lung resistance was used as a functional index of bronchomotor tone. Microinjection of DL-homocysteic acid into the 20 sites located in the lateral aspect of the RVL medulla increased both total lung resistance [from 6.5 +/- 0.4 to 9.1 +/- 0.8 (SE) cmH2O.l-1.s; P less than 0.05] and mean arterial pressure (from 125 +/- 5 to 148 +/- 8 mmHg; P less than 0.05). Microinjection of this amino acid into nine sites located in the medial aspect of the RVL medulla increased mean arterial pressure (from 130 +/- 6 to 153 +/- 6 mmHg; P less than 0.05) but had no effect on total lung resistance. We confirmed in three sites that the increase in total lung resistance evoked by microinjection of DL-homocysteic acid was accompanied by an increase in tracheal smooth muscle tension. The increase in total lung resistance evoked by DL-homocysteic acid was not affected by beta-adrenergic blockade but was abolished by muscarinic blockade.
Effect of lung inflation on regional lung expansion in supine and prone rabbits
Authors: Yang Q. H. , Lai-Fook S. J.
Published: December 2017

At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation.
Estimation of the pulmonary microvascular reflection coefficient to protein in dogs
Authors: Drake R. E. , Gabel J. C.
Published: December 2017

We used a new technique to estimate the pulmonary microvascular membrane reflection coefficient to plasma protein (sigma d) in anesthetized dogs. In five animals we continuously weighed the lower left lung lobe and used a left atrial balloon to increase the pulmonary microvascular pressure (Pc). We determined the relationship between the rate of edema formation (S) and Pc and estimated the fluid filtration coefficient (Kf) as delta S/delta Pc. From the S vs. Pc relationship and Kf, we estimated the Pc at which S/Kf = 10 mmHg for each dog. This pressure (P10) was 38.0 +/- 5.8 (SD) mmHg, and the plasma protein osmotic pressure (pi c) was 14.9 +/- 3.7 mmHg. In five additional dogs in which we decreased pi c to 2.9 +/- 1.7 mmHg, P10 = 27.2 +/- 2.6 mmHg. The P10 vs. pi c regression line fit to the data from all 10 dogs was P10 = 0.92 pi c +/- 24.4 mmHg (r = 0.88). We estimated sigma d from the slope of the regression line as sigma d = square root of delta P10/delta pi c. With this technique, we estimated that, with 95% probability, sigma d lies between 0.72 and unity. This is higher than most previous sigma d estimates.