bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in sodium and D-glucose transport between hamster and rat lungs
Authors: Goodman B. E. , Anderson J. L. , Clemens J. W. , Kircher K. J. , Stormo M. L. , Waltz J. S. , Waltz W. F. , White J. W.
Published: December 2017

The purpose of this study was to characterize phloridzin- and amiloride-sensitive transport across blood-gas barrier of hamster and rat lungs. Air spaces of isolated perfused lungs were instilled with a solution containing 22Na or L-[3H]glucose, D-[14C]glucose, and fluorescein isothiocyanate-labeled dextran. Apparent permeability-surface area products (PS) were calculated. Phloridzin (Na(+)-dependent D-glucose transport inhibitor) had no effect on D-glucose or sodium transport out of air spaces in hamster lungs. In contrast, in rat lungs, phloridzin decreased PS for D-glucose by 89% and that for Na by 28%. Trapping of 14CO2 in vascular samples was measured to estimate metabolism. Unlabeled air space D-glucose increased appearance of perfused D-[14C]glucose in air spaces of rat lungs. We conclude that Na(+)-dependent D-glucose transport is important for D-glucose uptake in rat lungs but not in hamster lungs. In hamster lungs, amiloride (Na+ transport inhibitor) also decreased PS for sodium, but drugs known to stimulate sodium transport in rat lungs had no effect. Thus, species differences in active transport processes exist in the distal air spaces of mammalian lungs.
Aging and stress-induced changes in complement activation and neutrophil mobilization
Authors: Cannon J. G. , Fiatarone M. A. , Fielding R. A. , Evans W. J.
Published: December 2017

We measured the extent of complement activation and neutrophil mobilization after eccentric exercise to determine whether these responses were age dependent and whether they were associated with changes in plasma creatine kinase (CK), a marker for muscle membrane integrity. Repeated forced lengthening of a muscle as it develops tension causes immediate ultrastructural damage to sarcomeres, followed by delayed-onset muscle soreness and release of myocellular enzymes. This can be accomplished in quadriceps muscles by running downhill or by resisting bicycle pedals driven backward by a motor. Twelve older (61–72 yr) and 9 younger (20–32 yr) subjects performed one of these activities for 45 min at an intensity of 78 +/- 2% of maximum heart rate. For all subjects, a median increase of 21% in plasma des-Arg-C3a levels occurred immediately after the protocol, circulating neutrophils increased 66 +/- 10% by 4-6 h, and plasma CK increased 135 +/- 25% by 24 h. The peak increases in neutrophils correlated with the peak increases in des-Arg-C3a (rho = 0.662, P = 0.006), and the peak increases in CK correlated with the rise in neutrophils (rho = 0.523, P = 0.027). The increases in neutrophils and plasma CK were significantly smaller in the older subjects (P < 0.05). The results indicate that increased concentrations of circulating CK after muscle injury are associated with a sequential cascade of inflammatory mediators. Furthermore, neutrophil mobilization, but not complement activation, was diminished in older subjects in response to this stress.
Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension
Authors: St Pierre B. A. , Tidball J. G.
Published: December 2017

The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1+ and Ia+ macrophages. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm2 compared with 0.2/mm2 in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1+ and Ia+ macrophages numbered 369 and 332/mm2, respectively, compared with 12 and 72/mm2, respectively, in control soleus. After 7 days of reloading, the number of ED1+ cells was similar to that of control. Ia+ macrophages decreased to 240/mm2 at 4 days but after 7 days rose above control values to 429/mm2. ED2+ macrophages in 4- and 7-day reloaded soleus increased 70–80% in the interstitial spaces compared with control but were not observed to infiltrate necrotic muscle fibers at any time points. Immunohistochemistry and immunoblots using a monoclonal anti-dMHC antibody demonstrate a greater proportion of myofibers expressing dMHC isoforms after 4 and 7 days of reloading. These findings indicate that macrophage subpopulations are associated with distinct stages during the recovery process from hindlimb suspension: ED1+ macrophages are associated with muscle necrosis, whereas ED2+ cells are associated with muscle regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
Sites of vasodilation by inhaled nitric oxide vs. sodium nitroprusside in endothelin-constricted isolated rat lungs
Authors: Roos C. M. , Rich G. F. , Uncles D. R. , Daugherty M. O. , Frank D. U.
Published: December 2017

We localized the sites of vasodilation of inhaled nitric oxide (NO), a selective pulmonary vasodilator, and sodium nitroprusside (SNP) in isolated rat lungs. The sites were determined by analyzing the arterial, venous, and double-occlusion data with a two-resistor (small arteries and veins) three-capacitor (large arteries, large veins, and capillaries) model of the pulmonary vascular bed. Inhaled NO (170 and 670 ppm) and SNP (22.5 and 45.0 micrograms) decreased the small-artery resistance by 7.4 +/- 1.6, 17.2 +/- 2.2, 14.2 +/- 2.8, and 21.4 +/- 3.4% and the small-vein resistance by 13.5 +/- 3.2, 20.3 +/- 3.4 (SNP of 22.5 micrograms not significant), and 9.3 +/- 3.3%, respectively, in blood-perfused lungs (n = 12). Similar results were observed in Krebs-perfused lungs (n = 12). Capillary compliance was unaffected by inhaled NO and SNP. SNP increased the large-artery capacitance by 40.0 +/- 8.6 and 69.3 +/- 9.7%, whereas inhaled NO had no effect. SNP increased the large-vein capacitance by 31.0 +/- 8.7 and 48.0 +/- 10.7%, whereas inhaled NO had no effect in blood-perfused lungs. However, in Krebs-perfused lungs inhaled NO and SNP (45.0 micrograms only) increased the large-vein capacitance by 43.3 +/- 11.9, 41.4 +/- 14.2, and 44.2 +/- 11.0%. In conclusion, in blood-perfused isolated rat lungs inhaled NO and SNP dilate small-resistance arteries and veins, whereas SNP but not inhaled NO dilates larger capacitance arteries and veins. Furthermore, blood appears to prevent the downstream vasodilation by inhaled NO on larger capacitance pulmonary veins.
Maximum rate of force development is increased by antagonist conditioning contraction
Authors: Grabiner M. D.
Published: December 2017

Nine subjects performed maximum contractions with the knee extensor muscles on an isokinetic device set at 4.36 rad/s. The knee extensions were preceded by isometric conditioning contractions of the antagonist knee flexor muscles. The conditioning contraction forces were 0, 25, 50, 75, and 100% of the maximum isometric force. The purpose of the study was to determine 1) the effects of graded conditioning contractions with the knee flexor muscles on the maximum performance of the quadriceps femoris and 2) whether the effects of the conditioning contractions are similarly distributed to components of the quadriceps femoris. The increased initial quadriceps femoris activation levels associated with the conditioning contractions were similarly distributed to quadriceps femoris components. In contrast with previously published research on exercise performed at substantially lower knee extension velocities, the maximum knee extension force and the work performed were not affected by the conditioning contractions. However, the maximum rate of force development increased significantly (P < 0.05). The intensity of the knee flexor conditioning contractions likely influences agonist motor unit activation variables, but this influence may be related to the speed of the agonist contraction.
Pathological O2 supply dependence of diaphragmatic and systemic O2 uptake during endotoxemia
Authors: Kim W. S. , Ward M. E. , Hussain S. N.
Published: December 2017

Our aim was to assess whether endotoxemia impairs the ability of the diaphragm to extract O2 and whether this defect leads to a greater dependence of O2 uptake on O2 delivery. In two groups of anesthetized mechanically ventilated dogs, the left hemidiaphragm was vascularly isolated. Diaphragmatic blood flow and cardiac output (CO) were measured simultaneously in all animals. Saline (S group) or Escherichia coli endotoxin (100 mg; E group) was infused intravenously over 60 min. In both groups, CO was reduced in stages by controlled hemorrhage, and systemic and diaphragmatic O2 deliveries and consumptions were measured at each stage to construct the O2 delivery-O2 consumption relationships. In the S group, the average systemic O2 delivery below which O2 uptake became supply dependent was 7.2 ml.kg-1.min-1. At this O2 delivery, systemic O2 extraction ratio (ER) averaged 67.9%, whereas the maximum O2 ER was 91.3%. Critical diaphragmatic O2 delivery and critical and maximum diaphragmatic O2 ER, by comparison, averaged 9.0 ml.kg-1.min-1, 65%, and 81.9%, respectively. Endotoxin infusion raised critical systemic O2 delivery to 16.7 ml.kg-1.min-1 (P < 0.05) and reduced critical and maximum systemic O2 ER to 55.5 and 77% (P < 0.05), respectively. Similarly, critical diaphragmatic O2 delivery in the E group increased to 14.8 ml.kg-1.min-1 (P < 0.05), whereas critical and maximum O2 ER declined to 51.8 and 72.8%, respectively (P < 0.05). Thus, endotoxemia impairs diaphragmatic O2 extraction. This, in turn, leads to a greater dependence of diaphragmatic O2 uptake on O2 delivery.
Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide
Authors: Gambone L. M. , Elbon C. L. , Fryer A. D.
Published: December 2017

We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen-free guinea pigs treated with cyclophosphamide (30 mg.kg-1.day-1 i.p. for 7 days) before exposure to ozone were compared with untreated ozone-exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1–100 micrograms/kg i.v.) and potentiated by the selective M2 antagonist gallamine (0.1–10 mg/kg i.v.), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone-induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.
A buoyancy-driven squeeze-film model of intrapleural fluid dynamics: basic concepts
Authors: Grotberg J. B. , Glucksberg M. R.
Published: December 2017

We propose a new model of pleural liquid mechanics in the apneic animal based on the observation that the lung, in its position within the serous fluid of the chest, is a buoyant object with few physical connections to the chest. The buoyancy force due to the lung's low density causes the lung to rise within the chest, which in turn causes fluid to be squeezed out from the regions above the lung. The result is the transient component of the downward flow of intrapleural liquid and the less-than-hydrostatic vertical intrapleural pressure gradient observed by other investigators. For the purposes of mathematical simplicity, we have modeled the lung and chest wall of a horizontal animal as a pair of concentric cylinders separated by a narrow gap representing the pleural space. In this first version of the model, we treat the pleurae of the lung and chest wall as impermeable rigid boundaries, but despite these limitations, our mathematical analysis agrees with observations from a number of groups and explains the flow direction from top to bottom as well as the reported changes in vertical pressure gradient in response to a change in body orientation.
Skeletal muscle GLUT-4 and glucose uptake during exercise in humans
Authors: McConell G. , McCoy M. , Proietto J. , Hargreaves M.
Published: December 2017

The present study examined the relationship between total skeletal muscle GLUT-4 protein level and glucose uptake during exercise. Eight active non-endurance-trained men cycled at 72 +/- 1% peak pulmonary oxygen consumption for 40 min, with rates of glucose appearance and disappearance (Rd) determined by utilizing a primed continuous infusion of [3–3H]glucose commencing 2 h before exercise. Muscle glycogen content and utilization, citrate synthase activity, and total GLUT-4 protein were measured on muscle biopsy samples obtained from the vastus lateralis. A direct relationship existed between preexercise muscle glycogen content and glycogen utilization during exercise (r = 0.76, P < 0.05). Citrate synthase activity and glucose Rd at the end of exercise averaged 21.9 +/- 3.0 mumol.min-1.g-1 and 27.3 +/- 2.5 mumol.kg-1.min-1, respectively. There was a direct correlation between citrate synthase activity and GLUT-4 protein (r = 0.78, P < 0.05); however, at the end of exercise, glucose Rd was inversely related to both GLUT-4 (r = -0.89, P < 0.01) and citrate synthase activity (r = -0.72, P < 0.05). Plasma insulin, which decreased during exercise, was not related to glucose Rd. In conclusion, glucose uptake during 40 min of exercise at 72% peak pulmonary oxygen consumption was inversely related to the total muscle GLUT-4 protein level. This suggests that factors other than the total GLUT-4 protein level are important in the regulation of glucose uptake during exercise.
Effect of liquid inflation on the viscoelastic behavior of the lungs in developing piglets
Authors: La Rocca J. , Perez Fontan J. J.
Published: December 2017

Viscoelastic dissipation through stress relaxation decreases during the first weeks after birth in the piglet's lungs (J. Appl. Physiol. 73: 1297–1309, 1992). To characterize the mechanism of this decrease, we compared the stress relaxation undergone by the lungs of six newborn and six 9-wk-old piglets when the airway opening was occluded in the course of air and saline inflations. The amplitude of stress relaxation, determined from the mono-exponential decay ultimately adopted by the transpulmonary pressure during the occlusions, related linearly to the increases in lung elastic recoil preceding the occlusions. The slope of this relationship was greater in the newborn than in the 9-wk-old piglets during air inflations and similar at the two ages during saline inflations. Both the ratio of stress relaxation to elastic recoil and the time constant of the relaxations were similar during air and saline inflations and were independent of inflation rate and lung volume at the start of the inflations. These findings indicate that the postnatal decrease in stress relaxation is caused primarily by developmental changes in the geometry of the gas-liquid interface. They are also consistent with the notion that the viscoelastic stresses generated by the gas liquid interface and lung tissue are well matched for a given elastic recoil.
Altered thermoregulatory responses after 15 days of head-down tilt
Authors: Crandall C. G. , Johnson J. M. , Convertino V. A. , Raven P. B. , Engelke K. A.
Published: December 2017

To determine whether extended exposure to a simulation of microgravity alters thermoregulatory reflex control of skin blood flow, six adult males (mean age 40 +/- 2 yr) were exposed to 15 days of 6 degrees head-down tilt (HDT). On an ambulatory control day before HDT exposure and on HDT day 15, the core temperature of each subject was increased by 0.5–1.0 degree C by whole body heating with a water-perfused suit. Mean skin temperature, oral temperature (Tor), mean arterial pressure, and forearm blood flow were measured throughout the protocol. Forearm vascular conductance (FVC) was calculated from the ratio of forearm blood flow to mean arterial pressure. After HDT exposure, the Tor threshold at which reflex thermally induced increases in FVC began was elevated (36.87 +/- 0.06 to 37.00 +/- 0.09 degrees C; P = 0.043), whereas the slope of the Tor-FVC relationship after this threshold was reduced (13.7 +/- 2.3 to 9.5 +/- 1.1 FVC units/degrees C; P = 0.038). Moreover, normothermic FVC and FVC at the highest common Tor between pre- and post-HDT trials were reduced after HDT (normothermic: 4.2 +/- 0.5 to 3.0 +/- 0.4 ml.100 ml-1.min-1.100 mmHg-1, P = 0.04; hyperthermic: 12.4 +/- 1.0 to 7.8 +/- 0.7 ml.100 ml-1.min-1.100 mmHg-1, P < 0.001). These data suggest that HDT exposure reduces thermoregulatory responses to heat stress. The mechanisms resulting in such an impaired thermoregulatory response are unknown but are likely related to the relative dehydration that accompanies this exposure.
A simple handheld push-button device for in situ calibration of pneumotachographs
Authors: Holland W. P. , Boender W. , Bos J. A. , Huygen P. E.
Published: December 2017

A simple and compact flow calibrator has been devised for generating precise predetermined constant flow rates for checking the calibration of laboratory and clinical flow transducers used in respiratory measurements. The standard version delivers preset flows of 0.5 and 1 l/s, whereas a tuned-up version can produce preset flows of 2.5 and 5 l/s, with an accuracy of +/- 2%. The pressure generated is sufficient to cope with most commonly used respiratory flowmeters. The flow calibrator is built from inexpensive components that are readily obtainable: a fan, a turbine flowmeter, and a feedback circuit in a compact housing. The device is easy to connect to other equipment and to operate. Three flow calibrators have been built and are in regular use in a lung function laboratory and on intensive care wards.
Streptococcus pneumoniae-induced pulmonary hypertension and systemic hypotension in anesthetized sheep
Authors: Charan N. B. , Mudumbi R. V. , Hawk P. , Vestal R. E. , Carvalho P.
Published: December 2017

Because some patients with Streptococcus pneumoniae bacteremia may present with shock, we reasoned that this organism may produce substances that cause shock. To test this hypothesis, type III pneumococcus supernatant, suspended in 10 ml of sterile water, was infused over 1 min in 8 adult anesthetized sheep. Normal saline was used as a control and had no effect on any of the hemodynamic parameters. Infusion of supernatant resulted in a precipitous fall in cardiac output from a control value of 4.25 +/- 0.54 to 2.80 +/- 0.43 (SE) l/min, a fall in mean systemic arterial pressure from 70 +/- 4 to 49 +/- 8 mmHg, and an increase in the mean pulmonary arterial pressure from 13 +/- 2 to 23 +/- 4 mmHg within 1 min after the infusion was completed. The peak hemodynamic effects were observed at approximately 3 min and returned to normal within 10 min after the infusion was completed. The thromboxane B2 level increased from a control value of 10 +/- 5 to 156 +/- 43 pg/ml at 3 min after the infusion was completed and decreased to 63 +/- 34 pg/ml at 20 min. A second identical dose of pneumococcal supernatant, repeated within 2 h of the first dose, had no effect on hemodynamic variables. Pretreatment with indomethacin, 5 mg/kg body wt, completely blocked the hemodynamic effects of pneumococcal supernatant (n = 3 sheep). Thus, we conclude that S. pneumoniae supernatant contains substances that cause septic shock syndrome through the synthesis of arachidonic acid metabolites and that a sublethal dose of the supernatant causes rapid tachyphylaxis.
Oxygen sensors in vascular smooth muscle
Authors: Katayama Y. , Coburn R. F. , Fillers W. S. , Baron C. B.
Published: December 2017

Inhibition or activation of cellular function due to acute decreases in PO2 can be considered in terms of two different processes: 1) a sensor that monitors PO2 decreases and 2) transduction systems directed from the O2 sensor to reactions that control cellular function. We used the norepinephrine-contracted aortic smooth muscle model to study the nature of the O2 sensor and transduction system during decreased PO2-evoked relaxations. The phosphorylation potential, a measurement of kinetic energy required for ATP hydrolysis, was decreased to 30% of control at the onset of relaxation and progressively fell as muscle relaxed. The free inorganic phosphate intracellular concentration ([Pi]) was experimentally increased approximately 0.6 mM during transients that followed a rapid decrease in PO2. Relaxations to 80% of maximal force were more rapid under conditions of an augmented [Pi] than in control rings, and they occurred at a higher phosphocreatine concentration and phosphocreatine-to-free creatine ratio but at the same phosphorylation potential. Results support the operation of a cytochrome aa3 O2 sensor in the mechanism of decreased PO2-evoked relaxations and implicate an increase in [Pi] and a decrease in kinetic energy in the transduction mechanism directed at rate-limiting reactions that control force.
Acute pulmonary response to intravenous histamine using forced oscillations through alveolar capsules in dogs
Authors: Mishima M. , Balassy Z. , Bates J. H.
Published: December 2017

We measured the time course of alveolar input impedance using two alveolar capsule oscillators after intravenous bolus administration of 20 mg of histamine in open-chest dogs. Impedances (24–200 Hz) were obtained every 2 s after an injection for 100 s. Each impedance was fit with a model consisting of a pathway (with resistance and inertance) leading from the alveolar capsule into a subpleural region (with elastance EA) that, in turn, was connected to the lung compartment (consisting of the remainder of the lung and positive end expiratory pressure system) via another pathway (with resistance RA). In all cases (6 dogs, 2 capsules each), the resistance and inertance leading from the alveolar capsules were negligible. The correlation of the relative increases in RA obtained from the two capsule oscillators in each dog was not significant. The correlation for EA also was not significant. The times at which RA achieved values of 20% greater than baseline were not significantly correlated between the two capsules, as was the case for EA. However, the baseline values of EA and RA from a given capsule were significantly correlated, as were their fractional increases with histamine. These results show that both the magnitude and timing of changes in local lung resistance and elastance are spatially extremely heterogeneous.
Histochemical and mechanical properties of diaphragm muscle in morbidly obese Zucker rats
Authors: Farkas G. A. , Gosselin L. E. , Zhan W. Z. , Schlenker E. H. , Sieck G. C.
Published: December 2017

The purpose of the present study was to evaluate the effects of chronic mass loading produced by obesity on the structural and functional characteristics of the diaphragm in lean and obese Zucker rats. The trapezius muscle served as an internal control. The studies were carried out on 17 lean (303 +/- 24 g) and 16 obese (698 +/- 79 g) Zucker rats. We observed that the diaphragms from obese animals were restructured such that the overall contribution of type I and IIa fibers was significantly increased. As a consequence of this remodeling, overall diaphragm thickness was selectively greater in obese animals. In small isolated diaphragm bundles studied in vitro, we also detected a reduction in specific force in obese animals that was not detected in the trapezius muscle. In vitro fatigue resistance, assessed by repeated stimulation, was similar in muscles of lean and obese animals. Diaphragm fiber oxidative capacity (succinate dehydrogenase activity) was also comparable in lean and obese animals. We conclude that in obesity the diaphragm undergoes modest remodeling that may be beneficial in enhancing force generation.
Changes in potassium contractures due to simulated weightlessness in rat soleus muscle
Authors: Khammari A. , Noireaud J.
Published: December 2017

Some contractile properties of soleus muscle (SOL) fibers isolated from tail-suspended (21 days) rats were compared with those determined in the slow-twitch SOL and the fast-twitch extensor digitorum longus muscle (EDL) of control rats. In SOL from suspended rats, the resting membrane potential and the intracellular Na+ activity were typical of fast-twitch muscles. The relationship between the amplitude of K+ contractures and the membrane potential was steeper for control SOL than for control EDL and suspended SOL. The inactivation curve was also shifted to more positive potentials after suspension. In the presence of perchlorate anions, the tension activation curves of control EDL and suspended SOL were similarly shifted to more negative potentials. Thus, in the present study, modifications induced by suspension in SOL, mainly related to changes in the voltage-sensing process involved in the excitation-contraction coupling mechanism, were that the SOL assumed some of the characteristics of fast-twitch muscles.
Comparative age-related acute and chronic pulmonary oxygen tolerance in rats
Authors: Laudert S. , Thibeault D. W. , Rezaiekhaligh M. M. , Mabry S. M. , Huntrakoon M.
Published: December 2017

Young rats are thought to be more tolerant to hyperoxia. We propose that this may not be proven and depends on how tolerance is defined. We assessed oxygen tolerance in Sprague-Dawley rats from birth to maturity by comparing survival, lung water, antioxidant enzyme activity, lung morphometrics, heart weight, and arterial blood gases in newborn and 27-, 44-, 48-, and 96-day-old rats exposed to 100% O2 or room air for 22 days. Some 96-day-old rats (rest group) received only 50% O2 between 48 and 72 h. Mortality after 5 days of O2 was 0% in newborn and 27-day-old rats and 27% in 44-day-old rats but was > 80% in 48- and 96-day-old rats. Between 5 and 22 days, the death rate was 100% in newborns, 25% in 27-day-old rats, and 0% in 44- to 96-day-old rats. Death occurred when lung water was > 84% except in newborns, which tolerated high lung water for the first 7 days. In chronically exposed 44- and 96-day-old rats, lung water returned to normal. Enzyme activity increased with O2 at all ages but did not relate to survival. In 96-day-old rats, the initial increase was suppressed on day 3. All chronically O2-exposed rats had minimal nonvascular parenchymal changes but developed right ventricular hypertrophy and increased alveolar ductal artery muscularization and lost alveolar capillaries. The most mature rats were least affected. In O2, there was pulmonary insufficiency the first 3 days, followed by recovery, and later hypercarbia and decreased arterial PO2. We conclude that young rats, 0–44 days old, are more O2 tolerant for 5 days. More mature animals, surviving 5 days, are more tolerant to chronic exposure.
Recovery of medial gastrocnemius muscle grafts in rats: implications for the plantar flexor group
Authors: Miller S. W. , Hassett C. A. , White T. P. , Faulkner J. A.
Published: December 2017

Medial gastrocnemius (MGN) muscles were grafted in 18 rats and evaluated at 60, 90, and 120 days after the operation. Our purpose was to investigate the degree of recovery of the vascularized MGN grafts and the entire plantar flexor muscle group. Compared with control values, muscle mass and maximum force of MGN grafts were decreased by 33 and 38% at 60 days, 22 and 32% at 90 days, and 13 and 15% at 120 days. At 60 and 90 days, the deficits in maximum force for the entire plantar flexor muscle group, including the graft, were 29 and 17%, respectively. No difference was observed at 120 days. At 60 days, the deficit in the total mass of the plantar flexor group was 14% compared with control values, but by 90 days no deficit was observed. The restoration of normal plantar flexor group structure and function indicates that the degree of recovery attained by MGN grafts, although not complete, was sufficient to ensure that the performance of the total muscle group was not compromised.
Role of reactive O2 in phagocyte-induced hypermetabolism and pulmonary injury
Authors: Vlessis A. A. , Bartos D. , Muller P. , Trunkey D. D.
Published: December 2017

Activated phagocytes possess an enormous capacity for O2 consumption via NADPH oxidase. NADPH oxidase partially reduces O2, forming superoxide (O2-). Host enzymes rapidly complete O2- reduction to H2O, leaving little trace of its prior existence. Our objectives were to estimate the magnitude of whole body phagocyte respiration and determine the contribution of NADPH-derived O2- to the ensuing phagocyte-induced pulmonary injury. These objectives were accomplished using specific inhibitors of NADPH oxidase, diphenyl iodonium (DPI) and di-2-thienyl iodonium (DTI). Guinea pigs received intravenous injections of DPI (3.5 mg/kg), DTI (7.5 mg/kg), or vehicle followed by phorbol myristate acetate (PMA). Phagocyte activation by PMA immediately increased whole body respiration from 13.6 to 16.1 ml O2.kg-1.min-1 (P < 0.05). DPI and DTI completely blocked the increase in respiration induced by PMA injection (P < 0.05). Baseline respiration was unchanged by the NADPH oxidase inhibitor alone. Likewise, there was no effect on the respiration of isolated heart and kidney mitochondria from animals receiving the inhibitor with or without PMA. DPI attenuated the pulmonary injury induced by PMA. DPI attenuated the pulmonary injury induced by PMA. The ratio of lung water weight to dry weight was lower (6.4 +/- 0.3 vs. 8.3 +/- 0.6) and arterial PO2 was higher (86 +/- 9 vs. 56 +/- 6 Torr) in animals receiving DPI plus PMA than in those receiving PMA alone. In conclusion, phagocyte activation in vivo increased total body respiration by approximately 18%. The burst in respiration is attributed to the phagocyte respiratory burst in which NADPH oxidase partially O2 to O2-.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of methysergide administration on edema formation at the site of scald
Authors: Ferrara J. J. , Franklin E. W. , Choe E. U. , Lippton H. L. , Hyman A. L. , Flint L. M.
Published: December 2017

Femoral blood flow (Qa), hind paw lymph flow (Qlym), and lymph-to-plasma protein concentration ratio (Clym/Cp) were monitored before and 4 h after 1) 5-s 100 degrees C paw scald, 2) methysergide (1 mg/kg iv) 20 min before scald, 3) methysergide 30 min after scald, and 4) methysergide only. Before experimentation, hind paw venous pressure was elevated and maintained until steady-state Qa, Qlym, and minimal Clym/Cp levels were reached. The reflection coefficient (sigma d) was determined as 1 - minimal Clym/Cp; the filtration coefficient (Kf) was calculated. Methysergide alone caused no changes. Increases in Qa, Qlym, Clym/Cp, and Kf were identified in all scald groups. Compared with scald only animals, pre- and postscald methysergide blunted the increases in Qa, Qlym, Kf, and paw weight gain without an effect on sigma d. These data demonstrate that methysergide reduces edema formation at the site of scald, perhaps by modulating the burn-induced vasodilator response and/or by limiting the burn-induced increase in microvascular surface area.
Investigation of hormonal effects during 10-h head-down tilt on heart rate and blood pressure variability
Authors: Hughson R. L. , Maillet A. , Gauquelin G. , Arbeille P. , Yamamoto Y. , Gharib C.
Published: December 2017

Head-down tilt (HDT) bed rest was used in this study to achieve physiological manipulation of the plasma concentrations of atrial natriuretic peptide (ANP) and the hormones of the renin-angiotensin system. The purpose of this was to achieve a parallel with previous animal experiments in which blockade of the renin-angiotensin system caused significant increases in low-frequency spectral power of heart rate variability, presumably as a consequence of increased blood pressure variability, although this was not measured in these animal experiments. Eight healthy young men completed 10 h of seated control and 6 degrees HDT. To gain a more complete understanding of the interactions between hormonal and neural factors involved in cardiovascular regulation, we measured heart rate, systolic and diastolic pressure variabilities, plasma hormone concentrations, and blood flow to selected vascular beds by pulsed Doppler. Resting R-R interval was not significantly different between seated and HDT tests. Stroke volume and cardiac output were elevated in the first 1–2 h of HDT (P < 0.05), whereas each of systolic (P < 0.01) and diastolic (P < 0.0001) pressures was lower during HDT. Plasma ANP increased as much as 70% during HDT (P < 0.0001). Total variability in each of R-R interval and diastolic blood pressure was reduced during HDT (P < 0.001). Thus, at a time when plasma renin activity was decreased as much as 40% (P < 0.0001), there was in fact a decrease in the variability of R-R interval and diastolic blood pressure in contrast to the hypothesized increase such as found in previous animal experimentation. The data were compatible with tighter autonomic regulation of heart rate about the ideal mean value during HDT.
Corticosteroid treatment and nutritional deprivation cause a different pattern of atrophy in rat diaphragm
Authors: Dekhuijzen P. N. , Gayan-Ramirez G. , Bisschop A. , De Bock V. , Dom R. , Decramer M.
Published: December 2017

Triamcinolone (TR) causes type IIb fiber atrophy in the rat diaphragm, which is associated with changes in contractile properties. We investigated whether this is a direct effect of TR or the result of an accompanying loss of body and diaphragm weights. For 6 wk, adult rats received saline intramuscularly, TR (0.5 mg/kg im), or nutritional depletion (ND) that resulted in a similar (approximately 40%) reduction in body weight as TR. In these animals, the half-relaxation time of the diaphragm bundles increased, the force-frequency relationship shifted leftward, and the resistance to fatigue was increased. No histological changes were found in the ND diaphragm, in contrast to severe myogenic alterations in the TR diaphragm. Type IIb fiber cross-sectional area (CSA) in the TR diaphragm was reduced by 51%, whereas type I and IIa CSAs were unaffected. In the ND animals, the CSAs of type I, IIa, and IIb fibers were reduced by 31, 33, and 52%, respectively. Similar changes occurred in the deep part of the m. gastrocnemius. In conclusion, myogenic changes and selective type IIb fiber atrophy were caused by TR, whereas ND induced generalized fiber type atrophy without histological changes.
A method for measuring Cl efflux from dispersed cells of airway epithelium
Authors: Ohrui T. , Shen B. Q. , Mrsny R. J. , Widdicombe J. H.
Published: December 2017

This paper describes a method for measuring the increase in halide permeability of isolated airway epithelial cells induced by adenosine 3′,5′-cyclic monophosphate (cAMP). Suspensions of isolated cells, known to contain the cystic fibrosis transmembrane conductance regulator (CFTR), were placed in the upper part of a Swinnex filter holder containing a filter with pores of 0.65 micron diameter. Medium was perfused over the cells at room temperature and collected at minute intervals following its passage through the filter. Experiments were performed on Calu-3 and T84 cells (human lung and colonic epithelial cell lines), primary cultures of dog and human tracheal epithelium, and Swiss 3T3 fibroblasts stably transfected with CFTR. In all cell types, addition of agents that elevate cAMP led to increases in the rates of loss of 36Cl and 125I. However, in human tracheal epithelial cells, warming the medium from room temperature to 37 degrees C was a more effective way of stimulating tracer efflux. Increases in efflux in response to either temperature or cAMP-elevating agents were inhibited by diphenylamine-2-carboxylate, a blocker of CFTR. Reproducible increases in tracer efflux were seen with as few as 10(6) cells. Cells that had been trypsinized off their culture dishes responded better than cells that had been scraped off, although treatment of scraped cells with trypsin enhanced their responsiveness to cAMP-elevating agents. Cystic fibrosis is characterized by the lack of a cAMP-activated Cl conductance in the apical membrane of airway epithlia.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship between MRI relaxation time and muscle fiber composition
Authors: Houmard J. A. , Smith R. , Jendrasiak G. L.
Published: December 2017

The relationship between nuclear magnetic resonance relaxation time obtained with magnetic resonance imaging (MRI) and muscle fiber composition of the lateral gastrocnemius was examined in 13 men. There was a positive correlation (r = 0.80, P < or = 0.001) between longitudinal relaxation time and the relative percentage of slow-twitch muscle fibers (type I). There was no relationship between transverse relaxation time and type I percentage (r = 0.17, P = 0.57). These results suggest that MRI longitudinal relaxation time can be used for the noninvasive estimation of muscle fiber composition in humans.
Skeletal muscle characteristics among distance runners: a 20-yr follow-up study
Authors: Trappe S. W. , Costill D. L. , Fink W. J. , Pearson D. R.
Published: December 2017

The purpose of this investigation was to examine the histochemical and enzymatic characteristics of skeletal muscle after 20 yr of distance running training. Twenty-eight men were first studied between 1966 and 1974 when they were all highly trained distance runners. On the basis of their training regimens in the interim between testing, subjects were described as highly trained (HI; n = 11), fitness trained (FIT; n = 10), or untrained (UT; n = 7). Gastrocnemius muscle biopsy samples revealed a mean increase (P < 0.05) in the proportion of type I fibers of the FIT and UT groups, whereas the HI group, which was initially characterized by a high percentage (> 70%) of type I fibers, was unchanged. Although the mean fiber type change of the HI group was similar between evaluations, 6 of the 11 subjects did elicit an increase in the percentage of type I fibers. A subgroup of elite distance runners who had continued to train for competition experienced an approximately 25% reduction (P > 0.05) in muscle succinate dehydrogenase activity and decreases (P > 0.05) in types I and II muscle fiber areas. On the average, in 1993 the HI group had higher (P < 0.05) succinate dehydrogenase and citrate synthase activities than the FIT and UT groups, whereas phosphorylase activity did not differ among the three groups. These data suggest that the middle-aged men in this study had a significantly greater proportion of type I muscle fibers than when they were 20 yr younger.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic, catecholamine, and exercise performance responses to various doses of caffeine
Authors: Graham T. E. , Spriet L. L.
Published: December 2017

This study examined the exercise responses of well-trained endurance athletes to various doses of caffeine to evaluate the impact of the drug on exercise metabolism and endurance capacity. Subjects (n = 8) withdrew from all dietary sources of caffeine for 48 h before each of four tests. One hour before exercise they ingested capsules of placebo or caffeine (3, 6, or 9 mg/kg), rested quietly, and then ran at 85% of maximal O2 consumption to voluntary exhaustion. Blood samples for methylxanthine, catecholamine, glucose, lactate, free fatty acid, and glycerol analyses were taken every 15 min. Plasma caffeine concentration increased with each dose (P < 0.05). Its major metabolite, paraxanthine, did not increase between the 6 and 9 mg/kg doses, suggesting that hepatic caffeine metabolism was saturated. Endurance was enhanced with both 3 and 6 mg/kg of caffeine (increases of 22 +/- 9 and 22 +/- 7%, respectively; both P < 0.05) over the placebo time of 49.4 +/- 4.2 min, whereas there was no significant effect with 9 mg/kg of caffeine. In contrast, plasma epinephrine was not increased with 3 mg/kg of caffeine but was greater with the higher doses (P < 0.05). Similarly only the highest dose of caffeine resulted in increases in glycerol and free fatty acids (P < 0.05). Thus the highest dose had the greatest effect on epinephrine and blood-borne metabolites yet had the least effect on performance. The lowest dose had little or no effect on epinephrine and metabolites but did have an ergogenic effect. These results are not compatible with the traditional theory that caffeine mediates its ergogenic effect via enhanced catecholamines.
Flow pulsatility does not increase mean microvascular pressure or filtration in zone 3 rabbit lungs
Authors: Saito O. , Lamm W. J. , Hildebrandt J. , Albert R. K.
Published: December 2017

We previously reported that mean pulmonary arterial pressure (Ppa) during pulsatile flow exceeded that for steady flow when flow was greater than the normal resting value and speculated that this was due to irregularities of the flow profiles in precapillary vessels, mainly the larger arteries. From this we hypothesized that neither mean microvascular pressure nor the rate of fluid filtration would be affected by flow pulsatility. We therefore compared the effects of steady vs. pulsatile flow on the double-occlusion pressure (Pdo) and on edema formation (rate of weight gain) in zone 3 rabbit lungs. Excised left lungs (n = 19) were perfused with Tyrode solution and ventilated with an end-expiratory pressure of 2.5 cmH2O. A diaphragm pump generated pulsatile flow with a stroke volume of 1.0 ml (approximately 0.8 the normal resting value for rabbit left lung). Nonpulsatile flow was generated by raising an arterial reservoir. Flow rate was set at 100 or 400 ml/min (approximately 0.4 or 1.6 x the normal resting cardiac output, respectively). Vascular pressures (referenced to the bottom of the lung) were measured after ventilation, at end expiration, was interrupted. Pdo values were obtained in random order at 15 time points that were evenly distributed within the pulse cycle, averaged across pulses to obtain the mean capillary pressure profile, and then averaged over time. At the lower flow of 100 ml/min, mean Ppa and Pdo were slightly lower (3–4%) during pulsatile compared with nonpulsatile conditions. At the higher flow of 400 ml/min, mean Ppa was higher under pulsatile conditions (13%), whereas downstream the mean Pdo values were equal.(ABSTRACT TRUNCATED AT 250 WORDS)
Daily spontaneous running alters behavioral and neurochemical indexes of nigrostriatal function
Authors: Dluzen D. E. , Liu B. , Chen C. Y. , DiCarlo S. E.
Published: December 2017

Behavioral and neurochemical indexes of nigrostriatal dopaminergic function were compared between sedentary control rats (n = 12) and daily spontaneous running (DSR) male rats (n = 10). Nine weeks of DSR did not significantly alter body, heart, pituitary, or testes weights. DSR and control animals did differ in performance on a sensorimotor beam walking task, with DSR rats showing significantly shorter times required to cross the beam (60 +/- 17 vs. 119 +/- 14s; P < 0.02) as well as fewer slips off the beam (3.0 +/- 0.8 vs 6.2 +/- 1.1; P < 0.05). DSR animals also engaged in significantly greater durations of social investigation than control rats (43 +/- 5 vs 25 +/- 3 s; P < 0.01) when tested in a social investigation memory-recognition test. Basal dopamine release rates from superfused corpus striatal tissue fragments of DSR rats were about one-half those obtained from control animals (18 +/- 5 vs. 34 +/- 6 pg.mg-1.min-1; P < 0.05), whereas responses of these striatal tissue fragments to a depolarizing concentration of potassium were virtually identical (45 +/- 10 vs. 47 +/- 8 pg.mg-1.min-1). These data indicate that a relatively limited intensity of DSR insufficient to alter cardiovascular function can exert substantial effects on behavioral and neurochemical indicators of nigrostriatal dopaminergic activity.
Autonomic regulation of tissue resistance in the guinea pig lung
Authors: Ingenito E. P. , Mark L. , Lilly C. , Davison B.
Published: December 2017

Although the autonomic nervous system is known to influence airway tone and resistance in both the normal and inflamed lung, its effects on tissue resistance (Rti) have not been defined. To characterize autonomic neural control of Rti in the lung, we measured airway resistance (Raw) and Rti, lung elastance, and lung hysteresivity after adrenergic, cholinergic, and nonadrenergic noncholinergic (NANC) blockade in anesthetized mechanically ventilated guinea pigs by using the alveolar capsule technique. Five animals received 1 mg/kg i.v. phentolamine (alpha-blocker), eight received 1 mg/kg i.v. propranolol (beta-blocker), six received 0.1 mg/kg i.v. atropine (parasympatholytic), six had surgical bilateral vagotomy, and five were treated 14 days before study with 50 mg/kg sc capsaicin (peptidergic neurotransmitter depleter). Measurements were recorded at 5- to 10-min intervals for 120 min after pharmacological induction of autonomic blockade. Capsaicin treatment resulted in decreases in lung resistance (RL), Raw, and dynamic elastance (Edyn) compared with controls but Rti was not significantly affected. beta-Blockade resulted in significant increases in RL, Raw, and Edyn but did not affect Rti. alpha-Blockade and vagolytic maneuvers had no effect on RL, Raw, Rti, or Edyn. Furthermore, there was no effect of cholinergic, adrenergic, or NANC blockade on the relationship between Rti or elastance and breathing frequency or mean lung volume during tidal breathing. Our results suggest that, in the normal guinea pig lung, baseline Raw is modulated by both the beta-adrenergic and NANC nervous systems but Rti tone is largely independent of nervous system regulation.
Muscarinic agonists and antagonists cause vasodilation in isolated rat lung
Authors: Wilson P. S. , Khimenko P. L. , Barnard J. W. , Moore T. M. , Taylor A. E.
Published: December 2017

The present study investigated the ability of atropine and different muscarinic receptor subtypes to affect acetylcholine (ACh)-induced bronchoconstriction and vasodilation in the isolated rat lung model. ACh (10(-7) M) given after U-46619 decreased total (RT), precapillary, and postcapillary vascular resistances and increased peak airway pressure. Atropine (20 microM) decreased RT and precapillary and postcapillary vascular resistances and blocked ACh-induced increases in peak airway pressure. The M1-selective agonist McN-A-343 (1.3 x 10(-5) M) decreased RT from 40.27 +/- 2.98 to 29.20 +/- 2.81 cmH2O.l–1.min-100 g lung wt (P = 0.01), and ACh caused no further dilation. The M1-selective antagonist pirenzepine (1.6 x 10(-6) M) blocked ACh-induced vasodilation. The M2-selective antagonist gallamine (7.5 x 10(-7) M) decreased RT from 45.50 +/- 3.19 to 34.86 +/- 1.25 cmH2O.l–1.min.100 g lung wt (P < 0.05), and after gallamine, ACh further decreased RT to 28.59 +/- 1.75 cmH2O.l–1.min.100 g lung wt (P < 0.01). Neither the selective muscarinic agonists nor antagonists affected peak airway pressures. We conclude that ACh-induced vasodilation in isolated rat lungs preconstricted with U-46619 is mediated by M1 receptors. Atropine-induced vasodilation in this model is mediated through the inhibition of the M2 receptor. We postulate that this represents either a blockade of postganglionic receptors, permitting release of vasodilator substances from local nerve terminals, or a direct vasodilatory effect on the vascular smooth muscle.