bluuebunny/crossref_metadata_2025 huggingface dataset:
Classic conditioning of the ventilatory responses in rats
Authors: Nsegbe Elise , Vardon Guy , Perruchet Pierre , Gallego Jorge
Published: December 2017

Nsegbe, Elise, Guy Vardon, Pierre Perruchet, and Jorge Gallego. Classic conditioning of the ventilatory responses in rats. J. Appl. Physiol. 83(4): 1174–1183, 1997.—Recent authors have stressed the role of conditioning in the control of breathing, but experimental evidence of this role is still sparse and contradictory. To establish that classic conditioning of the ventilatory responses can occur in rats, we performed a controlled experiment in which a 1-min tone [conditioned stimulus (CS)] was paired with a hypercapnic stimulus [8.5% CO2, unconditioned stimulus (US)]. The experimental group ( n = 9) received five paired CS-US presentations, followed by one CS alone to test conditioning. This sequence was repeated six times. The control group ( n = 7) received the same number of CS and US, but each US was delivered 3 min after the CS. We observed that after the CS alone, breath duration was significantly longer in the experimental than in the control group and mean ventilation was significantly lower, thus showing inhibitory conditioning. This conditioning may have resulted from the association between the CS and the inhibitory and aversive effects of CO2. The present results confirmed the high sensitivity of the respiratory controller to conditioning processes.
Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance
Authors: Lutchen Kenneth R. , Gillis Heather
Published: December 2017

Lutchen, Kenneth R., and Heather Gillis. Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance. J. Appl. Physiol.83(4): 1192–1201, 1997.—We present a dog lung model to predict the relation between inhomogeneous changes in airway morphometry and lung resistance (Rl) and elastance (El) for frequencies surrounding typical breathing rates. The Rl and El were sensitive in distinct ways to two forms of peripheral constriction. First, when there is a large and homogeneous constriction, the Rl increases uniformly over the frequency range. The El is rather unaffected below 1 Hz but then increases with frequencies up to 5 Hz. This increase is caused by central airway wall shunting. Second, the Rl and El are extremely sensitive to mild inhomogeneous constriction in which a few highly constricted or nearly closed airways occur randomly throughout the periphery. This results in extreme increases in the levels and frequency dependence of Rland El but predominantly at typical breathing rates (<1 Hz). Conversely, the Rl and El are insensitive to highly inhomogeneous airway constriction that does not produce any nearly closed airways. Similarly, alterations in the Rl and El due to central airway wall shunting are not likely until the preponderance of the periphery constricts substantially. The Rland El spectra are far more sensitive to these two forms of peripheral constriction than to constriction conditions known to occur in the central airways. On the basis of these simulations, we derived a set of qualitative criteria to infer airway constriction conditions from Rl and El spectra.
Lysophosphatidic acid enhances contractility of isolated airway smooth muscle
Authors: Toews M. L. , Ustinova E. E. , Schultz H. D.
Published: December 2017

Toews, M. L., E. E. Ustinova, and H. D. Schultz.Lysophosphatidic acid enhances contractility of isolated airway smooth muscle. J. Appl. Physiol.83(4): 1216–1222, 1997.—The effects of the simple phospholipid mediator lysophosphatidic acid (LPA) on the contractile responsiveness of isolated tracheal rings from rabbits and cats were assessed. In both species, LPA increased the contractile response to the muscarinic agonist methacholine, but LPA did not induce contraction on its own. Conversely, LPA decreased the relaxation response to the β-adrenergic-agonist isoproterenol in both species. Concentrations of LPA as low as 10−8M were effective, and the effects of LPA were rapidly reversed on washing. Phosphatidic acid was much less effective, requiring higher concentrations and producing only a minimal effect. Contractions induced by serotonin and by substance P also were enhanced by LPA, but KCl-induced contractions were unaffected. LPA inhibited the isoproterenol-induced relaxation of KCl-precontracted rings, similar to its effects on methacholine-precontracted rings, and relaxation induced by the direct adenylyl cyclase activator forskolin was inhibited in a manner similar to that induced by isoproterenol. Epithelium removal did not alter the contraction-enhancing effect of LPA. The ability of LPA to both enhance contraction and inhibit relaxation of airway smooth muscle suggests that LPA could contribute to airway hypercontractility in asthma, airway inflammation, or other types of lung injury.
V˙o 2 kinetics in the horse during moderate and heavy exercise
Authors: Langsetmo I. , Weigle G. E. , Fedde M. R. , Erickson H. H. , Barstow T. J. , Poole D. C.
Published: December 2017

Langsetmo, I., G. E. Weigle, M. R. Fedde, H. H. Erickson, T. J. Barstow, and D. C. Poole.V˙o 2 kinetics in the horse during moderate and heavy exercise. J. Appl. Physiol. 83(4): 1235–1241, 1997.—The horse is a superb athlete, achieving a maximal O2 uptake (∼160 ml ⋅ min−1 ⋅ kg−1) approaching twice that of the fittest humans. Although equine O2 uptake (V˙o 2) kinetics are reportedly fast, they have not been precisely characterized, nor has their exercise intensity dependence been elucidated. To address these issues, adult male horses underwent incremental treadmill testing to determine their lactate threshold (Tlac) and peakV˙o 2(V˙o 2 peak), and kinetic features of theirV˙o 2 response to “square-wave” work forcings were resolved using exercise transitions from 3 m/s to a below-Tlac speed of 7 m/s or an above-Tlac speed of 12.3 ± 0.7 m/s (i.e., between Tlac andV˙o 2 peak) sustained for 6 min. V˙o 2 and CO2 output were measured using an open-flow system: pulmonary artery temperature was monitored, and mixed venous blood was sampled for plasma lactate.V˙o 2 kinetics at work levels below Tlac were well fit by a two-phase exponential model, with a phase 2 time constant (τ1 = 10.0 ± 0.9 s) that followed a time delay (TD1 = 18.9 ± 1.9 s). TD1 was similar to that found in humans performing leg cycling exercise, but the time constant was substantially faster. For speeds above Tlac, TD1 was unchanged (20.3 ± 1.2 s); however, the phase 2 time constant was significantly slower (τ1 = 20.7 ± 3.4 s, P < 0.05) than for exercise below Tlac. Furthermore, in four of five horses, a secondary, delayed increase inV˙o 2 became evident 135.7 ± 28.5 s after the exercise transition. This “slow component” accounted for ∼12% (5.8 ± 2.7 l/min) of the net increase in exercise V˙o 2. We conclude that, at exercise intensities below and above Tlac, qualitative features ofV˙o 2 kinetics in the horse are similar to those in humans. However, at speeds below Tlac the fast component of the response is more rapid than that reported for humans, likely reflecting different energetics of O2utilization within equine muscle fibers.
Human respiratory muscle actions and control during exercise
Authors: Aliverti A. , Cala S. J. , Duranti R. , Ferrigno G. , Kenyon C. M. , Pedotti A. , Scano G. , Sliwinski P. , Macklem Peter T. , Yan S.
Published: December 2017

Aliverti, A., S. J. Cala, R. Duranti, G. Ferrigno, C. M. Kenyon, A. Pedotti, G. Scano, P. Sliwinski, Peter T. Macklem, and S. Yan. Human respiratory muscle actions and control during exercise. J. Appl. Physiol. 83(4): 1256–1269, 1997.—We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (W˙max) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of W˙max as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. ΔVrc,a/ΔVab was constant and independent ofW˙max. Thus we used ΔVab/time as an index of diaphragm velocity of shortening. From QB to 70%W˙max, diaphragmatic pressure (Pdi) increased ∼2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was ∼0 during QB but was equal to and 180° out of phase with rib cage muscle pressure at all percent W˙max. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% W˙max there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180° out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion .
Role of neutrophils in lung vascular injury and edema after premature birth in lambs
Authors: Carlton David P. , Albertine Kurt H. , Cho Soo Chul , Lont Menno , Bland Richard D.
Published: December 2017

Carlton, David P., Kurt H. Albertine, Soo Chul Cho, Menno Lont, and Richard D. Bland. Role of neutrophils in lung vascular injury and edema after premature birth in lambs. J. Appl. Physiol. 83(4): 1307–1317, 1997.—To investigate the role of neutrophils in the pathogenesis of respiratory distress after premature birth, we assessed the relationship between circulating neutrophil concentration and neutrophil accumulation in the lung, lung lymph and pleural liquid flow, and extravascular lung water in 10 chronically catheterized preterm lambs (127 ± 1 days gestation) that were mechanically ventilated for 8 h after birth. Circulating neutrophil concentration transiently decreased within 2 h after birth and then returned to prenatal values by 6–8 h. The decrease in circulating neutrophil concentration was related directly to the accumulation of neutrophils in the air spaces, drainage of liquid and protein from the lung 6–8 h after delivery, and postmortem extravascular lung water. In additional studies, we intravenously administered mechlorethamine to 5 fetal lambs to reduce circulating neutrophils before delivery (neutrophil concentration before birth: 9 ± 11 cells/μl). Compared with control lambs, neutrophil-depleted lambs had significantly less drainage of liquid (7.8 ± 5.9 vs. 2.6 ± 1.9 ml/h, respectively) and protein (116 ± 74 vs. 42 ± 27 mg/h, respectively) from the lung 6–8 h after birth and significantly less extravascular lung water at postmortem (6.5 ± 0.8 vs. 4.8 0.6 g/g dry lung, respectively). Thus neutrophils contribute to the pathogenesis of respiratory distress after premature birth by increasing lung vascular protein permeability and promoting lung edema.
Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans
Authors: Rådegran G.
Published: December 2017

Rådegran, G. Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. J. Appl. Physiol.83(4): 1383–1388, 1997.—Ultrasound Doppler has been used to measure arterial inflow to a human limb during intermittent static contractions. The technique, however, has neither been thoroughly validated nor used during dynamic exercise. In this study, the inherent problems of the technique have been addressed, and the accuracy was improved by storing the velocity tracings continuously and calculating the flow in relation to the muscle contraction-relaxation phases. The femoral arterial diameter measurements were reproducible with a mean coefficient of variation within the subjects of 1.2 ± 0.2%. The diameter was the same whether the probe was fixed or repositioned at rest (10.8 ± 0.2 mm) or measured during dynamic exercise. The blood velocity was sampled over the width of the diameter and the parabolic velocity profile, since sampling in the center resulted in an overestimation by 22.6 ± 9.1% ( P< 0.02). The femoral arterial Doppler blood flow increased linearly ( r = 0.997, P < 0.001) with increasing load [Doppler blood flow = 0.080 ⋅ load (W) + 1.446 l/min] and was correlated positively with simultaneous thermodilution venous outflow measurements ( r = 0.996, P < 0.001). The two techniques were linearly related (Doppler = thermodilution ⋅ 0.985 + 0.071 l/min; r = 0.996, P < 0.001), with a coefficient of variation of ∼6% for both methods.
Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs
Authors: Matsumoto Koichiro , Aizawa Hisamichi , Takata Shohei , Inoue Hiromasa , Takahashi Naotsugu , Hara Nobuyuki
Published: December 2017

Matsumoto, Koichiro, Hisamichi Aizawa, Shohei Takata, Hiromasa Inoue, Naotsugu Takahashi, and Nobuyuki Hara.Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs. J. Appl. Physiol. 83(5): 1432–1437, 1997.—Nitric oxide (NO), which can be derived from the nervous system or the epithelium of the airway, may modulate airway responsiveness. We investigated how NO derived from the airway nervous system would affect the airway responsiveness to histamine and acetylcholine in mechanically ventilated guinea pigs. An NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (1 mmol/kg ip) significantly enhanced airway responsiveness to histamine but not to acetylcholine. Its enantiomerd-NAME (1 mmol/kg ip), in contrast, had no effect. Thel-NAME-induced airway hyperresponsiveness was still observed in animals pretreated with propranolol (1 mg/kg iv) and atropine (1 mg/kg iv). Pretreatment with the ganglionic blocker hexamethonium (2 mg/kg iv) completely abolished enhancing effect of l-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter thel-NAME-induced airway hyperresponsiveness, whereas sympathetic stellatectomy completely abolished it. Results suggest that NO that was presumably derived from the sympathetic nervous system regulates airway responsiveness to histamine in guinea pigs.
Differential relaxant responses of pulmonary arteries and veins in lung explants of guinea pigs
Authors: Shi Weibin , Eidelman David H. , Michel René P.
Published: December 2017

Shi, Weibin, David H. Eidelman, and René P. Michel.Differential relaxant responses of pulmonary arteries and veins in lung explants of guinea pigs. J. Appl. Physiol. 83(5): 1476–1481, 1997.—The endothelium regulates vascular tone through release of relaxing or contracting factors, with nitric oxide (NO) being a major endothelium-derived relaxing factor. In the present study, we used a lung explant technique to determine the differential abilities and mechanisms of pulmonary arteries and veins of normal guinea pigs to relax after precontraction. Excised lungs of 15 guinea pigs were filled through the airways with 1% agarose, cut into 1-mm-thick slices, and cultured overnight. Luminal areas of vascular cross sections were measured with an image-analysis system. Vessels were precontracted with U-46619, and responses to histamine, acetylcholine (ACh), sodium nitroprusside, and papaverine were examined. We also determined the effects of N ω-nitro-l-arginine and of indomethacin on ACh-induced responses. We found that histamine relaxed arteries more than veins and that ACh relaxed only arteries. N ω-nitro-l-arginine pretreatment abolished ACh-induced relaxation of arteries and caused ACh-induced contraction of veins, whereas indomethacin markedly augmented ACh-induced relaxation of arteries (maximal relaxation: 48.5 ± 4.7 vs. 19.2 ± 5.1% without it) and induced a dose-dependent relaxation of veins (maximal relaxation: 17.0 ± 4.1%). Sodium nitroprusside induced a significantly greater relaxation of arteries than veins, whereas papaverine relaxed them equally. We conclude that in guinea pigs endothelial NO-mediated relaxation is greater in pulmonary arteries than in veins and that ACh-induced NO-mediated relaxation is reduced by the simultaneous production of cyclooxygenase-derived vasoconstrictors.
Stretch-induced enhancement of mechanical work production in frog single fibers and human muscle
Authors: Takarada Yudai , Iwamoto Hiroyuki , Sugi Haruo , Hirano Yuichi , Ishii Naokata
Published: December 2017

Takarada, Yudai, Hiroyuki Iwamoto, Haruo Sugi, Yuichi Hirano, and Naokata Ishii. Stretch-induced enhancement of mechanical work production in frog single fibers and human muscle. J. Appl. Physiol. 83(5): 1741–1748, 1997.—The relations between the velocity of prestretch and the mechanical energy liberated during the subsequent isovelocity release were studied in contractions of frog single fibers and human muscles. During isometric contractions of frog single fibers, a ramp stretch of varied velocity (amplitude, 0.02 fiber length; velocity, 0.08–1.0 fiber length/s) followed by a release (amplitude, 0.02 fiber length; velocity, 1.0 fiber length/s) was given, and the amount of work liberated during the release was measured. For human muscles, elbow flexions were performed with a prestretch of varied velocity (range, 40°; velocity, 30–180°/s) followed by an isokinetic shortening (velocity, 90°/s). In both frog single fibers and human muscles, the work production increased with both the velocity of stretch and the peak of force attained before the release up to a certain level; thereafter it declined with the further increases of these variables. In human muscles, the enhancement of work production was not associated with a significant increase in integrated electromyogram. This suggests that changes in intrinsic mechanical properties of muscle fibers play an important role in the stretch-induced enhancement of work production.
Redox behavior of cytochrome oxidase in the rat brain measured by near-infrared spectroscopy
Authors: Hoshi Yoko , Hazeki Osamu , Kakihana Yasuyuki , Tamura Mamoru
Published: December 2017

Hoshi, Yoko, Osamu Hazeki, Yasuyuki Kakihana, and Mamoru Tamura. Redox behavior of cytochrome oxidase in the rat brain measured by near-infrared spectroscopy. J. Appl. Physiol. 83(6): 1842–1848, 1997.—Using near-infrared spectroscopy, we developed a new approach for measuring the redox state of cytochrome oxidase in the brain under normal blood-circulation conditions. Our algorithm does not require the absorption coefficient of cytochrome oxidase, which differs from study to study. We employed this method for evaluation of effects of changes in oxygen delivery on cerebral oxygenation in rats. When fractional inspired oxygen was decreased in a stepwise manner from 100 to <10%, at which point the concentration of oxygenated hemoglobin ([HbO2]) decreased by ∼60%, cytochrome oxidase started to be reduced. Increases in arterial [Formula: see text] under hyperoxic conditions caused an increase in [HbO2], whereas further oxidation of cytochrome oxidase was not observed. The dissociation of the responses of hemogloblin and cytochrome oxidase was also clearly observed after the injection of epinephrine under severely hypoxic conditions; that is, cytochrome oxidase was reoxidized with increasing blood pressure, whereas hemoglobin oxygenation was not changed. These data indicated that oxygen-dependent redox changes in cytochrome oxidase occur only when oxygen delivery is extremely impaired. This is consistent with the in vitro data of our previous study.
Lower extremity muscle activation during horizontal and uphill running
Authors: Sloniger Mark A. , Cureton Kirk J. , Prior Barry M. , Evans Ellen M.
Published: December 2017

Sloniger, Mark A., Kirk J. Cureton, Barry M. Prior, and Ellen M. Evans. Lower extremity muscle activation during horizontal and uphill running. J. Appl. Physiol. 83(6): 2073–2079, 1997.—To provide more comprehensive information on the extent and pattern of muscle activation during running, we determined lower extremity muscle activation by using exercise-induced contrast shifts in magnetic resonance (MR) images during horizontal and uphill high-intensity (115% of peak oxygen uptake) running to exhaustion (2.0–3.9 min) in 12 young women. The mean percentage of muscle volume activated in the right lower extremity was significantly ( P <0.05) greater during uphill (73 ± 7%) than during horizontal (67 ± 8%) running. The percentage of 13 individual muscles or groups activated varied from 41 to 90% during horizontal running and from 44 to 83% during uphill running. During horizontal running, the muscles or groups most activated were the adductors (90 ± 5%), semitendinosus (86 ± 13%), gracilis (76 ± 20%), biceps femoris (76 ± 12%), and semimembranosus (75 ± 12%). During uphill running, the muscles most activated were the adductors (83 ± 8%), biceps femoris (79 ± 7%), gluteal group (79 ± 11%), gastrocnemius (76 ± 15%), and vastus group (75 ± 13%). Compared with horizontal running, uphill running required considerably greater activation of the vastus group (23%) and soleus (14%) and less activation of the rectus femoris (29%), gracilis (18%), and semitendinosus (17%). We conclude that during high-intensity horizontal and uphill running to exhaustion, lasting 2–3 min, muscles of the lower extremity are not maximally activated, suggesting there is a limit to the extent to which additional muscle mass recruitment can be utilized to meet the demand for force and energy. Greater total muscle activation during exhaustive uphill than during horizontal running is achieved through an altered pattern of muscle activation that involves increased use of some muscles and less use of others.
Resistance training and human cervical muscle recruitment plasticity
Authors: Conley Michael S. , Stone Michael H. , Nimmons Michael , Dudley Gary A.
Published: December 2017

Conley, Michael S., Michael H. Stone, Michael Nimmons, and Gary A. Dudley. Resistance training and human cervical muscle recruitment plasticity. J. Appl. Physiol. 83(6): 2105–2111, 1997.—This study examined cervical neuromuscular adaptations to resistance training. The ResX group performed conventional resistance training plus head-extension exercise. Another group performed only conventional resistance training, and the control group performed no resistance exercise. Muscle use during head extension was determined by quantifying shifts in T2 in serial-transaxial magnetic resonance images of the neck. ResX was the only group that showed a training effect. Training decreased ( P < 0.05) the cross-sectional area (CSA) of cervical muscle used to perform submaximal head extension by 31%. This reflected a decrease ( P < 0.05) in relative use of the splenius capitis, semispinalis capitis, and semispinalis cervicis and multifidus muscles by about one-third; their percentage of CSA showing contrast shift was reduced from 60 to 40% on average. This same exercise evoked no contrast shift in the levator scapulae, longissimus capitis and cervicis, and scalenus medius and anterior muscles posttraining, yet 20% or more of their CSA was engaged pretraining. The relative CSA of cervical musculature that was used to perform maximal head extension was increased ( P < 0.05) 16% by training. The findings suggest functional redundancy of neck musculature that can be modified by training; submaximal tasks can be performed despite cessation of recruitment of individual muscles, yet recruitment can be increased for maximal efforts. These results also suggest that neuromuscular adaptations to training require a specific cervical exercise
Alterations in the surface properties of lung surfactant in the torpid marsupialSminthopsis crassicaudata
Authors: Lopatko Olga V. , Orgeig Sandra , Daniels Christopher B. , Palmer David
Published: December 2017

Lopatko, Olga V., Sandra Orgeig, Christopher B. Daniels, and David Palmer. Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata. J. Appl. Physiol. 84(1): 146–156, 1998.—Torpor changes the composition of pulmonary surfactant (PS) in the dunnart Sminthopsis crassicaudata [C. Langman, S. Orgeig, and C. B. Daniels. Am. J. Physiol. 271 ( Regulatory Integrative Comp. Physiol. 40): R437–R445, 1996]. Here we investigated the surface activity of PS in vitro. Five micrograms of phospholipid per centimeter squared surface area of whole lavage (from mice or from warm-active, 4-, or 8-h torpid dunnarts) were applied dropwise onto the subphase of a Wilhelmy-Langmuir balance at 20°C and stabilized for 20 min. After 4 h of torpor, the adsorption rate increased, and equilibrium surface tension (STeq), minimal surface tension (STmin), and the %area compression required to achieve STmindecreased, compared with the warm-active group. After 8 h of torpor, STmindecreased [from 5.2 ± 0.3 to 4.1 ± 0.3 (SE) mN/m]; %area compression required to achieve STmindecreased (from 43.4 ± 1.0 to 27.4 ± 0.8); the rate of adsorption decreased; and STeqincreased (from 26.3 ± 0.5 to 38.6 ± 1.3 mN/m). ST-area isotherms of warm-active dunnarts and mice at 20°C had a shoulder on compression and a plateau on expansion. These disappeared on the isotherms of torpid dunnarts. Samples of whole lavage (from warm-active and 8-h torpor groups) containing 100 μg phospholipid/ml were studied by using a captive-bubble surfactometer at 37°C. After 8 h of torpor, STminincreased (from 6.4 ± 0.3 to 9.1 ± 0.3 mN/m) and %area compression decreased in the 2nd (from 88.6 ± 1.7 to 82.1 ± 2.0) and 3rd (from 89.1 ± 0.8 to 84.9 ± 1.8) compression-expansion cycles, compared with warm-active dunnarts. ST-area isotherms of warm-active dunnarts at 37°C did not have a shoulder on compression. This shoulder appeared on the isotherms of torpid dunnarts. In conclusion, there is a strong correlation between in vitro changes in surface activity and in vivo changes in lipid composition of PS during torpor, although static lung compliance remained unchanged (see Langman et al. cited above). Surfactant from torpid animals is more active at 20°C and less active at 37°C than that of warm-active animals, which may represent a respiratory adaptation to low body temperatures of torpid dunnarts.
Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled β-agonists
Authors: Carvalho Paula , Johnson Shane R. , Charan Nirmal B.
Published: December 2017

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled β-agonists. J. Appl. Physiol. 84(1): 215–221, 1998.—We studied the dose-dependent effects of inhaled isoetharine HCl, a β-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Q˙br) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Q˙br. With a total dose of 17.5 mg, Q˙br increased from baseline values of 22 ± 3.4 (SE) to 60 ± 16 ml/min ( P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects β-agonist-induced increases in Q˙br, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME). Intravenous l-NAME (30 mg/kg) rapidly decreased Q˙br by ∼80% of baseline, whereas l-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (∼22%) decrease. Pretreatment with l-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Q˙br in a dose-dependent manner and that β-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.
High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange
Authors: Sukumar Minakshi , Bommaraju Mahesh , Fisher John E. , Morin Frederick C. , Papo Michele C. , Fuhrman Bradley P. , Hernan Lynn J. , Leach Corinne Lowe
Published: December 2017

Sukumar, Minakshi, Mahesh Bommaraju, John E. Fisher, Frederick C. Morin III, Michele C. Papo, Bradley P. Fuhrman, Lynn J. Hernan, and Corinne Lowe Leach. High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange. J. Appl. Physiol. 84(1): 327–334, 1998.—Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 ± 21.3 vs. 17 ± 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% ( P < 0.001), pulmonary blood flow increased fivefold ( P < 0.001), and aortic pressure was maintained ( P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.
Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus)
Authors: Swallow John G. , Garland Theodore , Carter Patrick A. , Zhan Wen-Zhi , Sieck Gary C.
Published: December 2017

Swallow, John G., Theodore Garland, Jr., Patrick A. Carter, Wen-Zhi Zhan, and Gary C. Sieck. Effects of voluntary activity and genetic selection on aerobic capacity in house mice ( Mus domesticus). J. Appl. Physiol. 84(1): 69–76, 1998.—An animal model was developed to study effects on components of exercise physiology of both “nature” (10 generations of genetic selection for high voluntary activity on running wheels) and “nurture” (7–8 wk of access or no access to running wheels, beginning at weaning). At the end of the experiment, mice from both wheel-access groups were significantly lighter in body mass than mice from sedentary groups. Within the wheel-access group, a statistically significant, negative relationship existed between activity and final body mass. In measurements of maximum oxygen consumption during forced treadmill exercise (V˙o2 max), mice with wheel access were significantly more cooperative than sedentary mice; however, trial quality was not a significant predictor of individual variation in V˙o2 max. Nested two-way analysis of covariance demonstrated that both genetic selection history and access to wheels had significant positive effects on V˙o2 max. A 12% difference inV˙o2 maxexisted between wheel-access selected mice, which had the highest mass-correctedV˙o2 max, and sedentary control mice, which had the lowest. The respiratory exchange ratio at V˙o2 maxwas also significantly lower in the wheel-access group. Our results suggest the existence of a possible genetic correlation between voluntary activity levels (behavior) and aerobic capacity (physiology).
Stretch-shorten cycle compared with isometric preload: contributions to enhanced muscular performance
Authors: Walshe Andrew D. , Wilson Greg J. , Ettema Gertjan J. C.
Published: December 2017

Walshe, Andrew D., Greg J. Wilson, and Gertjan J. C. Ettema.Stretch-shorten cycle compared with isometric preload: contributions to enhanced muscular performance. J. Appl. Physiol. 84(1): 97–106, 1998.—To isolate any difference muscular contraction history may have on concentric work output, 40 trained male subjects performed three separate isokinetic concentric squats that involved differing contraction histories: 1) a concentric-only (CO) squat, 2) a concentric squat preceded by an isometric preload (IS), and 3) a stretch-shorten cycle (SSC) squat. Over the first 300 ms of the concentric movement, work output for both the SSC and IS conditions was significantly greater (154.8 ± 39.8 and 147.9 ± 34.7 J, respectively; P < 0.001) compared with the CO squat (129.7 ± 34.4 J). In addition, work output after the SSC test over the first 300 ms was also significantly larger than that for the corresponding period after the IS protocol ( P < 0.05). There was no difference in normalized, integrated electromyogram among any of the conditions. It was concluded that concentric performance enhancement derived from a preceding stretch of the muscle-tendon complex was largely due to the attainment of a higher active muscle state before the start of the concentric movement. However, it was also hypothesized that contractile element potentiation was a significant contributor to stretch-induced muscular performance under these conditions.
Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex
Authors: Ray Chester A. , Hume Keith M.
Published: December 2017

Ray, Chester A., and Keith M. Hume. Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl. Physiol. 84(2): 450–453, 1998.—We have shown previously that head-down neck flexion (HDNF) in humans elicits increases in muscle sympathetic nerve activity (MSNA). The purpose of this study was to determine the effect of neck muscle afferents on MSNA. We studied this question by measuring MSNA before and after head rotation that would activate neck muscle afferents but not the vestibular system (i.e., no stimulation of the otolith organs or semicircular canals). After a 3-min baseline period with the head in the normal erect position, subjects rotated their head to the side (∼90°) and maintained this position for 3 min. Head rotation was performed by the subjects in both the prone ( n = 5) and sitting ( n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed as burst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baseline and head rotation, respectively. There were no significant changes in calf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml ⋅ 100 ml−1 ⋅ min−1; n = 8) and calf vascular resistance (39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min; P = 0.058) and mean arterial pressure (90 ± 3 to 93 ± 3; P < 0.05) increased slightly during head rotation. Additional neck flexion studies were performed with subjects lying on their side ( n = 5). MSNA, heart rate, and mean arterial pressure were unchanged during this maneuver, which also does not engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% ( P < 0.001) during HDNF. These findings indicate that neck afferents activated by horizontal neck rotation or flexion in the absence of significant force development do not elicit changes in MSNA. These findings support the concept that HDNF increases MSNA by the activation of the vestibular system.
Pulmonary disposition of lipophilic amine compounds in the isolated perfused rabbit lung
Authors: Audi S. H. , Dawson C. A. , Linehan J. H. , Krenz G. S. , Ahlf S. B. , Roerig D. L.
Published: December 2017

Audi, S. H., C. A. Dawson, J. H. Linehan, G. S. Krenz, S. B. Ahlf, and D. L. Roerig. Pulmonary disposition of lipophilic amine compounds in the isolated perfused rabbit lung. J. Appl. Physiol. 84(2): 516–530, 1998.—We measured the pulmonary venous concentration vs. time curves for [3H]alfentanil, [14C]lidocaine, and [3H]codeine after the bolus injection of each of these lipophilic amine compounds (LAC) and a vascular-reference indicator (fluorescein isothiocyanate-dextran) into the pulmonary artery of isolated perfused rabbit lungs. A range of flows and perfusate albumin concentrations was studied. To evaluate the information content of the data, we developed a kinetic model describing the pulmonary disposition of these LAC that was based on indicator dilution theory, and we sought a robust approach for interpreting the estimated model parameters. We found that the distribution of the kinetic model rate constants of the lipophilic amine-tissue interactions can be described by α̃,H̃, and [Formula: see text], where α̃ is a measure of the capacity of the rapidly equilibrating interactions between the lipophilic amine and the tissue; H̃ is a measure of the equilibrium capacity of the slowly equilibrating interactions between the lipophilic amine and the tissue; and[Formula: see text] is the mean sojourn time. The values of α̃, H̃, and[Formula: see text]were 0.8 ± 0.1 (SE), 0.6 ± 0.1, and 1.6 ± 0.5 s; 1.9 ± 0.1, 5.3 ± 0.4, and 5.6 ± 0.5 s; and 1.1 ± 0.1, 9.8 ± 0.4, and 4.7 ± 0.2 s for alfentanil, lidocaine, and codeine, respectively. These values for α̃, H̃, and[Formula: see text]reveal the relative dominance of the slowly equilibrating interactions for lidocaine and codeine in comparison with alfentanil. This approach to data analysis may have utility for the potential use of LAC to reveal and to quantify changes in lung tissue composition associated with lung disease.
Influence of age and gender on cardiac output-V˙o2relationships during submaximal cycle ergometry
Authors: Proctor David N. , Beck Kenneth C. , Shen Peter H. , Eickhoff Tamara J. , Halliwill John R. , Joyner Michael J.
Published: December 2017

Proctor, David N., Kenneth C. Beck, Peter H. Shen, Tamara J. Eickhoff, John R. Halliwill, and Michael J. Joyner. Influence of age and gender on cardiac output-V˙o2relationships during submaximal cycle ergometry. J. Appl. Physiol. 84(2): 599–605, 1998.—It is presently unclear how gender, aging, and physical activity status interact to determine the magnitude of the rise in cardiac output (Q˙c) during dynamic exercise. To clarify this issue, the present study examined theQ˙c-O2uptake (V˙o2) relationship during graded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups ( n = 6–8/group): younger men (20–30 yr), older men (56–72 yr), younger women (24–31 yr), and older women (51–72 yr). Q˙c (acetylene rebreathing), stroke volume (Q˙c/heart rate), and whole bodyV˙o2were measured at rest and during submaximal exercise intensities (40, 70, and ∼90% of peakV˙o2). Baseline resting levels of Q˙c were 0.6–1.2 l/min less in the older groups. However, the slopes of theQ˙c-V˙o2relationship across submaximal levels of cycling were similar among all four groups (5.4–5.9 l/l). The absolute Q˙c associated with a given V˙o2(1.0–2.0 l/min) was also similar among groups. Resting and exercise stroke volumes (ml/beat) were lower in women than in men but did not differ among age groups. However, older men and women showed a reduced ability, relative to their younger counterparts, to maintain stroke volume at exercise intensities above 70% of peakV˙o2. This latter effect was most prominent in the oldest women. These findings suggest that neither age nor gender has a significant impact on theQ˙c-V˙o2relationships during submaximal cycle ergometry among chronically endurance-trained individuals.
Parallel airways inhomogeneity and lung tissue mechanics in transition to constricted state in rabbits
Authors: Romero P. V. , Rodriguez B. , Lopez-Aguilar J. , Manresa F.
Published: December 2017

To investigate whether changes of tissue resistance (Rti) during methacholine (MCh)-induced constriction correspond to an intrinsic mechanism or are an artifact of increased airways inhomogeneity, rabbits were studied after exposure to air ( n = 7) or 1.5 parts/million O3( n = 6). Animals were anesthetized and mechanically ventilated. Tracheal flow and pressure (Ptr) and four alveolar capsule pressures (Pcap) were measured during 3 min after administration of an intrajugular bolus of 0.8 mg/ml MCh. By adjustment of the equation of motion [P( t) = E ⋅ V( t) + R ⋅ dV( t)/d t+ P0] [where P( t), V( t), and dV( t)/d tare pressure, volume, and flow as a function of time, respectively, E is elastance, R is resistance, and P0 is end-expiratory pressure] to Ptr, lung resistance (Rl) and dynamic elastance (El) were determined breath by breath. Rti and airways resistance (Raw) were determined from Pcap in phase with rate of change of pulmonary expansion. Hysteresivity (η) was calculated. Parallel inhomogeneity was estimated from the coefficients of variation (CV) of every Pcap at end inspiration and end expiration. Increase in CV significantly lagged Rti, Rl, and η. A linear relationship between El and Raw was observed. Our results suggest that changes in tissue mechanics during the transition to the constricted state are not artifactual.
NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle
Authors: Baile Elisabeth M. , McKay Karen , Wang Lu , Bai Tony R. , Paré Peter D.
Published: December 2017

Endogenous nitric oxide (NO) influences acetylcholine-induced bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response in several species. This study was designed to determine the importance of NO as a neurally derived modulator of ovine airway and bronchial vascular smooth muscle. We measured the response of pulmonary resistance (Rl) and bronchial blood flow (Q˙br) to vagal stimulation in 14 anesthetized, ventilated, open-chest sheep during the following conditions: 1) control; 2) infusion of the α-agonist phenylephrine to reduce baseline Q˙br by the same amount as would be produced by infusion of N ω-nitro-l-arginine (l-NNA), a NO synthase inhibitor; 3) infusion ofl-NNA (10−2 M); and 4) after administration of atropine (1.5 mg/kg). The results showed that vagal stimulation produced an increase in Rl andQ˙br in periods 1, 2, and 3( P < 0.01) that was not affected byl-NNA. After atropine was administered, there was no increase inQ˙br or Rl. In vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect ofl-NNA on neural relaxation but showed a complete blockade with propranolol ( P < 0.01). In conclusion, the vagally induced airway smooth muscle contraction and bronchial vascular dilation are not influenced by NO, and the sheep’s trachealis muscle, unlike that in several other species, does not have inhibitory nonadrenergic, noncholinergic innervation.
Brain and abdominal temperatures at fatigue in rats exercising in the heat
Authors: Fuller Andrea , Carter Roderick N. , Mitchell Duncan
Published: December 2017

We measured brain and abdominal temperatures in eight male Sprague-Dawley rats (350–450 g) exercising voluntarily to a point of fatigue in two hot environments. Rats exercised, at the same time of the day, in three different trials, in random order: rest 23°C, exercise 33°C; rest 23°C, exercise 38°C; and rest 38°C, exercise 38°C. Running time to fatigue was 29.4 ± 5.9 (SD), 22.1 ± 3.7, and 14.3 ± 2.9 min for the three trials, respectively. Abdominal temperatures, measured with intraperitoneal radiotelemeters, at fatigue in the three trials (39.9 ± 0.3, 39.9 ± 0.3, and 39.8 ± 0.3°C, respectively) were not significantly different from each other. Corresponding brain temperatures, measured with thermocouples in the hypothalamic region (40.2 ± 0.4, 40.2 ± 0.4, and 40.1 ± 0.4°C), also did not differ. Our results are consistent with the concept that there is a critical level of body temperature beyond which animals will not continue to exercise voluntarily in the heat. Also, in our study, brain temperature was higher than abdominal temperature throughout exercise; that is, selective brain cooling did not occur when body temperature was below the level limiting exercise.
Effect of reduced bronchial circulation on lung fluid flux after smoke inhalation in sheep
Authors: Sakurai Hiroyuki , Johnigan Richard , Kikuchi Yuji , Harada Mikihiko , Traber Lillian D. , Traber Daniel L.
Published: December 2017

We determined the effect of reduced bronchial blood flow on lung fluid flux through changes in lung lymph flow, lung wet weight-to-dry weight (wet/dry) ratios, and pulmonary microvascular reflection coefficient (ς). In the first of two surgical procedures, Merino ewes ( n = 21) were surgically prepared for chronic study. Five to seven days later, in a second operation, the bronchial artery of the injection group ( n = 7) was ligated, and 4 ml of 70% ethanol were injected into the bronchial artery to cause sclerosis of the airway circulation. In the ligation group ( n = 7), only the bronchial artery was ligated. In the sham group ( n = 7), the bronchial artery was surgically exposed but left intact without ligation or ethanol injection. One day after these operations the animals received a tracheotomy and 48 breaths of cotton smoke. The value of ς was determined at two points: 24 h before the second surgical procedure and 24 h after smoke inhalation. Lung lymph flow, blood-gas parameters, and hemodynamic data were measured every 4 h after injury. At the end of investigation, samples of lung were taken for determination of blood-free wet/dry ratio. In the sham group, inhalation injury induced a gradual increase in pulmonary vascular resistance and lung lymph flow, which was associated with deterioration of oxygenation. Reduction of the bronchial blood flow attenuated these pathophysiological changes, and the degree of this attenuation was greater in the injection group than in the ligation group. The value of ς was significantly higher after smoke inhalation in the injection group compared with the sham group (0.77 ± 0.04 vs. 0.61 ± 0.03, means ± SE) at 24 h. The mean wet/dry ratio value of the injection group animals was 30% less than that of the sham group. Our data show that the bronchial circulation contributes to edema formation in the lung occurring after acute lung injury with smoke inhalation.
Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon
Authors: Solorzano Carmen C. , Kaibara Atsushi , Hess Phillip J. , Edwards Paul D. , Ksontini Riadh , Abouhamze Amer , McDaniel Sherry , Frazier Janet , Trujillo Deborah , Kieft Gary , Seely James , Kohno Tadahiko , Cosenza Mary Ellen , Clare-Salzler Michael , MacKay Sally L. D. , Martin Steven W. , Moldawer Lyle L. , Edwards Carl K.
Published: December 2017

Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher ( P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-α response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-α and to abrogate TNF-mediated pathology.