bluuebunny/crossref_metadata_2025 huggingface dataset:
Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons
Authors: Forster H. V. , Pan L. G. , Lowry T. F. , Feroah T. , Gershan W. M. , Whaley A. A. , Forster M. M. , Sprtel B.
Published: December 2017

Forster, H. V., L. G. Pan, T. F. Lowry, T. Feroah, W. M. Gershan, A. A. Whaley, M. M. Forster, and B. Sprtel. Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons. J. Appl. Physiol.84(1): 129–140, 1998.—Cooling the caudal M ventrolateral medullary (VLM) surface for 30 s results in a sustained apnea in anesthetized goats but only a 30% decrease in breathing in awake goats. The purpose of the present study was to determine, in the awake state, the effect of prolonged (minutes, hours) caudal M neuronal dysfunction on eupneic breathing and CO2 sensitivity. Dysfunction was created by ejecting excitatory amino acid receptor antagonists or a neurotoxin on the VLM surface through guide tubes chronically implanted bilaterally on a 10- to 12-mm2portion of the caudal M VLM surface of 12 goats. Unilateral and bilateral ejections (1 μl) of selective antagonists for N-methyl-d-aspartic acid or non- N-methyl-d-aspartic acid receptors had no significant effect on eupneic breathing or CO2 sensitivity. Unilateral ejection of a nonselective excitatory amino acid receptor antagonist generally had no effect on eupneic breathing or CO2 sensitivity. However, bilateral ejection of this antagonist resulted in a significant 2-Torr hypoventilation during eupnea and a significant reduction in CO2 sensitivity to 60 ± 9% of control. Unilateral ejection of the neurotoxin kainic acid initially stimulated breathing; however, breathing then returned to near control with no incidence of apnea. After the kainic acid ejection, CO2 sensitivity was reduced significantly to 60 ± 7% of control. We conclude that in the awake state a prolonged dysfunction of caudal M VLM neurons results in compensation by other mechanisms (e.g., carotid chemoreceptors, wakefulness) to maintain near-normal eupneic breathing, but compensation is more limited for maintaining CO2 sensitivity.
Neuromuscular drive and force production are not altered during bilateral contractions
Authors: Jakobi J. M. , Cafarelli E.
Published: December 2017

Jakobi, J. M., and E. Cafarelli. Neuromuscular drive and force production are not altered during bilateral contractions. J. Appl. Physiol. 84(1): 200–206, 1998.—Several investigators have studied the deficit in maximal voluntary force that is said to occur when bilateral muscle groups contract simultaneously. A true bilateral deficit (BLD) would suggest a significant limitation of neuromuscular control; however, some of the data from studies in the literature are equivocal. Our purpose was to determine whether there is a BLD in the knee extensors of untrained young male subjects during isometric contractions and whether this deficit is associated with a decreased activation of the quadriceps, increased activation of the antagonist muscle, or an alteration in motor unit firing rates. Twenty subjects performed unilateral (UL) and bilateral (BL) isometric knee extensions at 25, 50, 75, and 100% maximal voluntary contraction. Total UL and BL force (Δ3%) and maximal rate of force generation (Δ2.5%) were not significantly different. Total UL and BL maximal vastus lateralis electromyographic activity (EMG; 2.7 ± 0.28 vs. 2.6 ± 0.24 mV) and coactivation (0.17 ± 0.02 vs. 0.20 ± 0.02 mV) were also not different. Similarly, the ratio of force to EMG during submaximal UL and BL contractions was not different. Analysis of force production by each leg in UL and BL conditions showed no differences in force, rate of force generation, EMG, motor unit firing rates, and coactivation. Finally, assessment of quadriceps activity with the twitch interpolation technique indicated no differences in the degree of voluntary muscle activation (UL: 93.6 ± 2.51 Hz, BL: 90.1 ± 2.43 Hz). These results provide no evidence of a significant limitation in neuromuscular control between BL and UL isometric contractions of the knee extensor muscles in young male subjects.
A role for gastrointestinal endotoxins in enhancement of heat tolerance by physical fitness
Authors: Sakurada Sotaro , Hales J. Robert S.
Published: December 2017

Sakurada, Sotaro, and J. Robert S. Hales. A role for gastrointestinal endotoxins in enhancement of heat tolerance by physical fitness. J. Appl. Physiol.84(1): 207–214, 1998.—To further elucidate mechanisms underlying the higher heat tolerance of physically fit compared with sedentary people, we have investigated the possibility that endotoxins (of gastrointestinal origin) act, as in the normal development of fever, to raise body temperature and therefore reduce heat tolerance. In an initial series of experiments, five physically fit and four sedentary sheep were exposed twice at rest to an environment of 42/35°C (dry/wet bulb temperature). When animals were given normal saline iv, rectal temperature (Tre) rose at a significantly higher rate in sedentary than in fit animals; this confirms that heat tolerance is improved by physical fitness. Treatment with iv indomethacin did not affect the rate of rise of Trein fit animals. In sedentary animals, however, Trewas lowered to approximate that of fit animals. Because indomethacin blocks prostaglandin pathways involved in endotoxin-induced fever, the indomethacin-induced improvement of heat tolerance of sedentary but not fit animals supports the contention that endotoxins play a role in determining that difference in heat tolerance. In a second series of experiments, quantitative cardiovascular measurements were made by using radioactive microspheres. Under normothermic conditions, blood flows in the brain, ileum, and diaphragm were higher in fit than in sedentary animals. During hyperthermia up to Treof 42°C (in a 42/39°C environment), fit compared with sedentary animals exhibited 1) a greater increase in cardiac output, 2) an increase in blood flow through arteriovenous anastomoses to higher and better maintained levels, 3) less reduction in blood flow to the ileum, and 4) greater increase in blood flows to the myocardium, turbinates, nasal mucosa, and respiratory muscles. Endotoxins are likely to come from the gut lumen, because reduction of gut blood flow forms part of the normal response to heat stress. We suggest that improvement of heat tolerance by physical fitness is caused by a greater cardiovascular capacity that permits not only greater perfusion of heat-loss tissues but the maintenance of a better gastrointestinal tract blood supply, thereby better maintaining the normal barrier to movement of endotoxins from gut lumen to plasma. Sedentary people, with their lower cardiovascular capacity, redistribute more blood flow away from the gut during environmentally induced hyperthermia, thus allowing endotoxin-induced fever to aggravate hyperthermia.
Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: molecular-weight dependence
Authors: Martinez-Salas José , Mendelssohn Richard , Abraham William M. , Hsiao Bernard , Ahmed Tahir
Published: December 2017

Martinez-Salas, José, Richard Mendelssohn, William M. Abraham, Bernard Hsiao, and Tahir Ahmed. Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: molecular-weight dependence. J. Appl. Physiol. 84(1): 222–228, 1998.—Inhaled heparin prevents antigen-induced bronchoconstriction and inhibits anti-immunoglobulin E-mediated mast cell degranulation. We hypothesized that the antiallergic action of heparin may be molecular weight dependent. Therefore, we studied the effects of three different low-molecular-weight fractions of heparin [medium-, low-, and ultralow-molecular-weight heparin (MMWH, LMWH, ULMWH, respectively)] on the antigen-induced acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 22 sheep before and after airway challenge with Ascaris suum antigen, without and after pretreatment with inhaled fractionated heparins at doses of 0.31–5.0 mg/kg. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units that increased specific lung resistance by 400%. All fractionated heparins caused a dose-dependent inhibition of ABR and AHR. ULMWH was the most effective fraction, with the inhibitory dose causing 50% protection (ID50) against ABR of 0.5 mg/kg, whereas ID50values of LMWH and MMWH were 1.25 and 1.8 mg/kg, respectively. ULMWH was also the most effective fraction in attenuating AHR; the ID50values for ULMWH, LMWH, and MMWH were 0.5, 2.5, and 4.7 mg/kg, respectively. These data suggest that 1) fractionated low-molecular-weight heparins attenuate antigen-induced ABR and AHR; 2) there is an inverse relationship between the antiallergic activity of heparin fractions and molecular weight; and 3) ULMWH is the most effective fraction preventing allergic bronchoconstriction and airway hyperresponsiveness.
Potentiation of in vitro concentric work in mouse fast muscle
Authors: Grange R. W. , Vandenboom R. , Xeni J. , Houston M. E.
Published: December 2017

Grange, R. W., R. Vandenboom, J. Xeni, and M. E. Houston.Potentiation of in vitro concentric work in mouse fast muscle. J. Appl. Physiol. 84(1): 236–243, 1998.—Phosphorylation of myosin regulatory light chain (R-LC) is associated with potentiated work and power during twitch afterloaded contractions in mouse extensor digitorum longus muscle [R. W. Grange, C. R. Cory, R. Vandenboom, and M. E. Houston. Am. J. Physiol. 269 ( Cell Physiol. 38): C713–C724, 1995]. We now describe the association between R-LC phosphorylation and potentiated concentric work when the extensor digitorum longus muscle is rhythmically shortened and lengthened to simulate contractions in vivo. Work output (at 25°C) was characterized at sine frequencies of 3, 5, 7, 10, and 15 Hz at excursions of 0.6, 1.2, and 1.6 mm (∼5, 9, and 13% optimal muscle length) at a low level of R-LC phosphorylation. Muscles stimulated during the sine function with a single twitch at specific times before or after the longest muscle length yielded maximal concentric work near the longest muscle length at a sine frequency of 7 Hz (e.g., excursion ∼9% optimal muscle length = 1.6 J/kg). Power increased linearly between sine frequencies of 3 and 15 Hz at all excursions (maximum ∼29 W). After a 5-Hz 20-s conditioning stimulus and coincident with a 3.7-fold increase in R-LC phosphate content (e.g., from 0.19 to 0.70 mol phosphate/mol R-LC), work at the three excursions and a sine frequency of 7 Hz was potentiated a mean of 25, 44, and 50% ( P < 0.05), respectively. The potentiated work during rhythmic contractions is consistent with enhanced interaction between actin and myosin in the force-generating states. On the basis of observations in skinned skeletal muscle fibers (H. L. Sweeney and J. T. Stull. Proc. Natl. Acad. Sci. USA 87: 414–418, 1990), this enhancement could result from increased phosphate incorporation by the myosin R-LC. Under the assumption that the predominant effect of the conditioning stimulus was to increase R-LC phosphate content, our data suggest that a similar mechanism may be evident in intact muscle.
Anatomic distribution of pulmonary vascular compliance
Authors: Presson Robert G. , Audi Said H. , Hanger Christopher C. , Zenk Gerald M. , Sidner Richard A. , Linehan John H. , Wagner Wiltz W. , Dawson Christopher A.
Published: December 2017

Presson, Robert G., Jr., Said H. Audi, Christopher C. Hanger, Gerald M. Zenk, Richard A. Sidner, John H. Linehan, Wiltz W. Wagner, Jr., and Christopher A. Dawson. Anatomic distribution of pulmonary vascular compliance. J. Appl. Physiol. 84(1): 303–310, 1998.—Previously, the pressure changes after arterial and venous occlusion have been used to characterize the longitudinal distribution of pulmonary vascular resistance with respect to vascular compliance using compartmental models. However, the compartments have not been defined anatomically. Using video microscopy of the subpleural microcirculation, we have measured the flow changes in ∼40-μm arterioles and venules after venous, arterial, and double occlusion maneuvers. The quasi-steady flows through these vessels after venous occlusion permitted an estimation of the compliance in three anatomic segments: arteries >40 μm, veins >40 μm, and vessels <40 μm in diameter. We found that ∼65% of the total pulmonary vascular compliance was in vessels <40 μm, presumably mostly capillaries. The transient portions of the pressure and flow data after venous, arterial, and double occlusion were consistent with most of the arterial compliance being upstream from most of the arterial resistance and most of the venous compliance being downstream from most of the venous resistance.
Exercise training restores decreased cellular immune functions in obese Zucker rats
Authors: Moriguchi S. , Kato M. , Sakai K. , Yamamoto S. , Shimizu E.
Published: December 2017

Moriguchi, S., M. Kato, K. Sakai, S. Yamamoto, and E. Shimizu. Exercise training restores decreased cellular immune functions in obese Zucker rats. J. Appl. Physiol. 84(1): 311–317, 1998.—This study investigated whether exercise training had a beneficial effect on the decreased mitogen response and improved a decreased expression of glucose transporter 1 (GLUT-1) in splenocytes from obese Zucker rats. Experimental groups were lean and sedentary and exercise-trained obese Zucker rats. Exercise training, running on a motor-driven treadmill for 5 days/wk for 40 wk, did not induce a significant decrease in body weight in obese Zucker rats. The plasma insulin concentration, showing a significant increase compared with lean Zucker rats, was unaffected by exercise training. However, the plasma triglyceride concentration in obese Zucker rats was significantly depressed by exercise training, whereas it was still higher than that in lean Zucker rats. In addition, natural killer cell activity and concanavalin A-induced mitogenesis of splenic lymphocytes of obese Zucker rats were significantly restored. In these splenic lymphocytes, glucose uptake was significantly lower compared with that in lean Zucker rats, which was also improved by exercise training. Although the expression of GLUT-1, the major glucose transporter in immune cells, was depressed in splenic lymphocytes of obese Zucker rats, exercise training induced a significant improvement. These results suggest that exercise training has a beneficial effect on the decreased cellular immune functions in obese Zucker rats, which is associated, in part, with the improvement in GLUT-1 expression.
Validity of heart rate, pedometry, and accelerometry for predicting the energy cost of children’s activities
Authors: Eston Roger G. , Rowlands Ann V. , Ingledew David K.
Published: December 2017

Eston, Roger G., Ann V. Rowlands, and David K. Ingledew.Validity of heart rate, pedometry, and accelerometry for predicting the energy cost of children’s activities. J. Appl. Physiol. 84(1): 362–371, 1998.—Heart rate telemetry is frequently used to estimate daily activity in children and to validate other methods. This study compared the accuracy of heart rate monitoring, pedometry, triaxial accelerometry, and uniaxial accelerometry for estimating oxygen consumption during typical children’s activities. Thirty Welsh children (mean age 9.2 ± 0.8 yr) walked (4 and 6 km/h) and ran (8 and 10 km/h) on a treadmill, played catch, played hopscotch, and sat and crayoned. Heart rate, body accelerations in three axes, pedometry counts, and oxygen uptake were measured continuously during each 4-min activity. Oxygen uptake was expressed as a ratio of body mass raised to the power of 0.75 [scaled oxygen uptake (sV˙o 2)]. All measures correlated significantly ( P < 0.001) with sV˙o 2. A multiple-regression equation that included triaxial accelerometry counts and heart rate predicted sV˙o 2 better than any measure alone ( R 2 = 0.85, standard error of the estimate = 9.7 ml ⋅ kg−0.75 ⋅ min−1). The best of the single measures was triaxial accelerometry ( R 2 = 0.83, standard error of the estimate = 10.3 ml ⋅ kg−0.75 ⋅ min−1). It is concluded that a triaxial accelerometer provides the best assessment of activity. Pedometry offers potential for large population studies.
Low energy availability, not stress of exercise, alters LH pulsatility in exercising women
Authors: Loucks A. B. , Verdun M. , Heath E. M. ,   (With the Technical Assistance of T. Law, Sr. and J. R. Thuma)
Published: December 2017

Loucks, A. B., M. Verdun, and E. M. Heath. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J. Appl. Physiol.84(1): 37–46, 1998.—We tested two hypotheses about the disruption of luteinizing hormone (LH) pulsatility in exercising women by assaying LH in blood samples drawn at 10-min intervals over 24 h from nine young, habitually sedentary, regularly menstruating women on days 8, 9, or 10 of two menstrual cycles after 4 days of intense exercise [E = 30 kcal ⋅ kg lean body mass (LBM)−1 ⋅ day−1at 70% of aerobic capacity]. To test the hypothesis that LH pulsatility is disrupted by low energy availability, we controlled the subjects’ dietary energy intakes (I) to set their energy availabilities (A = I − E) at 45 and 10 kcal ⋅ kg LBM−1 ⋅ day−1during the two trials. To test the hypothesis that LH pulsatility is disrupted by the stress of exercise, we compared the resulting LH pulsatilities to those previously reported in women with similar controlled energy availability who had not exercised. In the exercising women, low energy availability reduced LH pulse frequency by 10% ( P < 0.01) during the waking hours and increased LH pulse amplitude by 36% ( P = 0.05) during waking and sleeping hours, but this reduction in LH pulse frequency was blunted by 60% ( P = 0.03) compared with that in the previously studied nonexercising women whose low energy availability was caused by dietary restriction. The stress of exercise neither reduced LH pulse frequency nor increased LH pulse amplitude (all P > 0.4). During exercise, the proportion of energy derived from carbohydrate oxidation was reduced from 73% while A = 45 kcal ⋅ kg LBM−1 ⋅ day−1to 49% while A = 10 kcal ⋅ kg LBM−1 ⋅day−1( P < 0.0001). These results contradict the hypothesis that LH pulsatility is disrupted by exercise stress and suggest that LH pulsatility in women depends on energy availability.
Effects of CO2- HCO 3 − on catecholamine efflux from cat carotid body
Authors: Iturriaga Rodrigo , Alcayaga Julio
Published: December 2017

Iturriaga, Rodrigo, and Julio Alcayaga. Effects of CO2-[Formula: see text]on catecholamine efflux from cat carotid body. J. Appl. Physiol. 84(1): 60–68, 1998.—Using a chronoamperometric technique with carbon-fiber microelectrodes and neural recordings, we simultaneously measured the effects of the following procedures on catecholamine efflux (ΔCA) and frequency of chemosensory discharges ( fx) from superfused cat carotid body: 1) the addition of CO2-[Formula: see text]to Tyrode solution previously buffered with N-2-hydroxyethylpiperazine- N′ -2-ethanesulfonic acid, maintaining pH at 7.40; 2) hypercapnia (10% CO2, pH 7.10); 3) hypoxia ([Formula: see text] h ≈ 40 Torr) with and without CO2-[Formula: see text]; and 4) the impact of several boluses of dopamine (DA; 10–100 μg) on hypoxic and hypercapnic challenges. With CO2-[Formula: see text], hypoxia increased fxwhich preceded ΔCA increases, whereas hypercapnia raised fxbut did not consistently increase ΔCA. Repeated stimuli induced similar fxincreases, but attenuated ΔCA. After DA, hypoxia produced larger ΔCA, which preceded chemosensory responses. Without CO2-[Formula: see text], hypoxia produced a similar pattern of ΔCA and fxresponses. Switching to Tyrode solution with CO2-[Formula: see text]at pH 7.40 raised fxbut did not increase ΔCA. With CO2-[Formula: see text]and after DA, hypoxic-induced ΔCAs were larger than in its absence. Results suggest that DA release is not essential for chemosensory excitation.
Role of pulmonary C fibers in adenosine-induced respiratory inhibition in anesthetized rats
Authors: Kwong Kevin , Hong Ju-Lun , Morton Robert F. , Lee Lu-Yuan
Published: December 2017

Kwong, Kevin, Ju-Lun Hong, Robert F. Morton, and Lu-Yuan Lee. Role of pulmonary C fibers in adenosine-induced respiratory inhibition in anesthetized rats. J. Appl. Physiol. 84(2): 417–424, 1998.—The clinical use of adenosine is commonly associated with pulmonary side effects, namely dyspnea, that suggest the possible involvement of bronchopulmonary sensory afferents. Our objective in this study was to characterize the effects of adenosine on breathing and to determine whether the vagal pulmonary afferents play a role in mediating these effects. We measured respiratory and cardiovascular changes in anesthetized, spontaneously breathing rats after bolus injections of adenosine at therapeutic doses. Right atrial injection of adenosine (0.04–0.6 mg/kg) elicits, in a dose-dependent manner, a pulmonary chemoreflex-like response consisting of a delayed apnea, bradycardia, and hypotension. In contrast, the classic capsaicin-elicited pulmonary chemoreflex occurs immediately after injection. Perineural capsaicin treatment of the cervical vagi blocked the adenosine-induced respiratory inhibition. Left ventricular administration of adenosine failed to elicit an apneic response. Pretreatment with the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine attenuated the adenosine-induced apnea. These results indicate that adenosine elicits a respiratory inhibition via stimulation of pulmonary C fibers and that activation of the A1-receptor is probably involved. It is unclear, however, what accounts for the exceedingly long latency in this response.
Plasma extravasation through neuronal stimulation in human nasal mucosa in the setting of allergic rhinitis
Authors: Sanico Alvin M. , Atsuta Satsuki , Proud David , Togias Alkis
Published: December 2017

Sanico, Alvin M., Satsuki Atsuta, David Proud, and Alkis Togias. Plasma extravasation through neuronal stimulation in human nasal mucosa in the setting of allergic rhinitis. J. Appl. Physiol. 84(2): 537–543, 1998.—We have previously shown that capsaicin nasal challenge in subjects with allergic rhinitis produces a dose-dependent increase in the albumin content of nasal lavage fluids. In the present set of studies, we determined whether this observation represents plasma extravasation that is neuronally mediated. To evaluate whether glandular secretions contribute to the albumin increase in nasal lavage fluids, volunteers with allergic rhinitis were pretreated with atropine or placebo before capsaicin challenge. Atropine significantly reduced the volume of returned lavage fluids and their lysozyme content but increased their albumin and fibrinogen content. To assess the contribution of sensory nerve stimulation, subjects with allergic rhinitis were pretreated in a second study with lidocaine or placebo before capsaicin challenge. Lidocaine significantly attenuated the capsaicin-induced increases in the volume of nasal lavage fluids, as well as their lysozyme and albumin content. To rule out the possibility of a direct effect of lidocaine on blood vessels rather than on nerves, healthy subjects were pretreated in a third study with lidocaine or placebo before bradykinin nasal challenge. Lidocaine did not affect the bradykinin-induced increase in the albumin content of nasal fluids. We conclude that, in allergic rhinitis, high-dose capsaicin induces plasma extravasation in the human nose and that this effect is neuronally mediated. This provides more definitive evidence that neurogenic inflammation can occur in vivo in the human upper airway.
Sympathetic discharge and vascular resistance after bed rest
Authors: Shoemaker J. Kevin , Hogeman Cynthia S. , Leuenberger Urs A. , Herr Michael D. , Gray Kristen , Silber David H. , Sinoway Lawrence I.
Published: December 2017

Shoemaker, J. Kevin, Cynthia S. Hogeman, Urs A. Leuenberger, Michael D. Herr, Kristen Gray, David H. Silber, and Lawrence I. Sinoway. Sympathetic discharge and vascular resistance after bed rest. J. Appl. Physiol. 84(2): 612–617, 1998.—The effect of −6° head-down-tilt bed rest (HDBR) for 14 days on supine sympathetic discharge and cardiovascular hemodynamics at rest was assessed. Mean arterial pressure, heart rate ( n = 25), muscle sympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow ( n = 14) were measured, and forearm vascular resistance (FVR) was calculated. Stroke distance, our index of stroke volume, was derived from measurements of aortic mean blood velocity (Doppler) and R-R interval ( n = 7). With these data, an index of total peripheral resistance was determined. Heart rate at rest was greater in the post (71 ± 2 beats/min)- compared with the pre-HDBR test (66 ± 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic stroke distance during post-HDBR (15.5 ± 1.1 cm/beat) was reduced from pre-HDBR levels (20.0 ± 1.5 cm/beat) ( P < 0.03). Also, MSNA burst frequency was reduced in the post (16.7 ± 2.8 beats/min)- compared with the pre (25.2 ± 2.6 beats/min)-HDBR condition ( P < 0.01). Bed rest did not alter forearm blood flow, FVR, or total peripheral resistance. Thus reductions in MSNA with HDBR were not associated with a decrease in FVR.
Parameter estimation and confidence intervals for Xe-CT ventilation studies: a Monte Carlo approach
Authors: Simon Brett A. , Marcucci Catherine , Fung Mansheung , Lele Subhash R.
Published: December 2017

Simon, Brett A., Catherine Marcucci, Mansheung Fung, and Subhash R. Lele. Parameter estimation and confidence intervals for Xe-CT ventilation studies: a Monte Carlo approach. J. Appl. Physiol. 84(2): 709–716, 1998.—Xenon-enhanced computed tomography (Xe-CT) is a technique for the noninvasive measurement of regional pulmonary ventilation from the washin and/or washout time constants of radiodense stable xenon gas, determined from serial computed tomography scans. Although the measurement itself is straightforward, there is a need for methods for the estimation of variability and confidence intervals so that the statistical significance of the information obtained may be evaluated, particularly since obtaining repeated measurements is often not practical. We present a Monte Carlo (MC) approach to determine the 95% confidence interval (CI) for any given measurement. This MC method was characterized in terms of its unbiasedness and coverage of the CI. In addition, 10 identical Xe-CT ventilation runs were performed in an anesthetized dog, and the time constant was determined for several regions of varying size in each run. The 95% CI, estimated from these repeated measurements as the mean ± 2 × SE, compared favorably with the CI obtained by the MC approach. Finally, a simulation was performed to compare the performance of three imaging protocols in estimating model parameters.
Role of metabolic gases in bubble formation during hypobaric exposures
Authors: Foster Philip P. , Conkin Johnny , Powell Michael R. , Waligora James M. , Chhikara Raj S.
Published: December 2017

Our hypothesis is that metabolic gases play a role in the initial explosive growth phase of bubble formation during hypobaric exposures. Models that account for optimal internal tensions of dissolved gases to predict the probability of occurrence of venous gas emboli were statistically fitted to 426 hypobaric exposures from National Aeronautics and Space Administration tests. The presence of venous gas emboli in the pulmonary artery was detected with an ultrasound Doppler detector. The model fit and parameter estimation were done by using the statistical method of maximum likelihood. The analysis results were as follows. 1) For the model without an input of noninert dissolved gas tissue tension, the log likelihood (in absolute value) was 255.01. 2) When an additional parameter was added to the model to account for the dissolved noninert gas tissue tension, the log likelihood was 251.70. The significance of the additional parameter was established based on the likelihood ratio test ( P < 0.012). 3) The parameter estimate for the dissolved noninert gas tissue tension participating in bubble formation was 19.1 kPa (143 mmHg). 4) The additional gas tissue tension, supposedly due to noninert gases, did not show an exponential decay as a function of time during denitrogenation, but it remained constant. 5) The positive sign for this parameter term in the model is characteristic of an outward radial pressure of gases in the bubble. This analysis suggests that dissolved gases other than N2in tissues may facilitate the initial explosive bubble-growth phase.
Effects of anaphylaxis mediators on partitioned pulmonary vascular resistance during ragweed shock in dogs
Authors: Mink S. N. , Becker A. , Unruh H. , Kepron W.
Published: December 2017

We examined the effect of anaphylactic shock on the longitudinal distribution of pulmonary vascular resistance (PVR) in ragweed-sensitized dogs in which PVR was partitioned into an upstream arterial component (Rus) and a downstream venous and capillary component (Rds). We also assessed whether Rus and Rds would be reduced by pretreatment with histamine H1- and H2-receptor blocking agents and with cyclooxygenase and lipoxygenase pathway inhibitors. Anesthetized animals were examined on separate occasions 3 wk apart in which one of the treatments was randomly given. The pulmonary arterial occlusion technique was used to determine segmental pressure drops. During ragweed challenge, PVR increased ≈4 times compared with the preshock value (3.04 vs. 12.07 mmHg ⋅ l−1⋅ min; P< 0.05). Although both Rus and Rds increased postshock, the greatest relative increase occurred in Rds. None of the treatments reduced partitioned resistances compared with no treatment. Our results show that, under conditions of anaphylactic shock, increases in Rus and Rds could not be ascribed to release of histamine or products of the cyclooxygenase and lipoxygenase pathways.
Activity of medullary respiratory neurons during ventilator-induced apnea in sleep and wakefulness
Authors: Orem John , Vidruk Edward H.
Published: December 2017

Mechanical ventilation of cats in sleep and wakefulness causes apnea, often within two to three cycles of the ventilator. We recorded 137 medullary respiratory neurons in four adult cats during eupnea and during apnea caused by mechanical ventilation. We hypothesized that the residual activity of respiratory neurons during apnea might reveal its cause(s). The results showed that residual activity depended on 1) the amount of nonrespiratory inputs to the cell (cells with more nonrespiratory inputs had greater amounts of residual activity); 2) the cell type (expiratory cells had more residual activity than inspiratory cells); and 3) the state of consciousness (more residual activity in wakefulness and rapid-eye-movement sleep than in non-rapid-eye-movement sleep). None of the cells showed an activation during ventilation that could explain the apnea. Residual activity of approximately one-half of the cells was modulated in phase with the ventilator. The strength of this modulation was quantified by using an effect-size statistic and was found to be weak. The patterns of modulation did not support the idea that mechanoreceptors excite some respiratory cells that, in turn, inhibit others. Indeed, most cells, inspiratory and expiratory, discharged during the deflation-inflation transition of ventilation. Residual activity failed to reveal the cause of apnea but showed that during apnea respiratory neurons act as if they were disinhibited and disfacilitated.
Training intensity-dependent and tissue-specific increases in lactate uptake and MCT-1 in heart and muscle
Authors: Baker Steven K. , McCullagh Karl J. A. , Bonen Arend
Published: December 2017

We investigated the effects of 3 wk of moderate- (21 m/min, 8% grade) and highintensity treadmill training (31 m/min, 15% grade) on 1) monocarboxylate transporter 1 (MCT-1) content in rat hindlimb muscles and the heart and 2) lactate uptake in isolated soleus (Sol) muscles and perfused hearts. In the moderately trained group MCT-1 was not increased in any of the muscles [Sol, extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG)] ( P > 0.05). Similarly, lactate uptake in Sol strips was also not increased ( P > 0.05). In contrast, in the heart, MCT-1 (+36%, P < 0.05) and lactate uptake (+72%, P < 0.05) were increased with moderate training. In the highly trained group, MCT-1 (+70%, P < 0.05) and lactate uptake (+79%, P < 0.05) were increased in Sol. MCT-1 was also increased in RG (+94%, P < 0.05) but not in WG and EDL ( P > 0.05). In the highly trained group, heart MCT-1 (+44%, P < 0.05) and lactate uptake (+173%, P < 0.05) were increased. In conclusion, it has been shown that 1) in both heart and skeletal muscle lactate uptake is increased only when MCT-1 is increased; 2) training-induced increases in MCT-1 occurred at a lower training intensity in the heart than in skeletal muscle; 3) in the heart, lactate uptake was increased much more after high-intensity training than after moderate-intensity training, despite similar increases in heart MCT-1 with these two training intensities; and 4) the increases in MCT-1 occurred independently of any changes in the heart’s oxidative capacity (as measured by citrate synthase activity).
Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs
Authors: Parker James C. , Ivey Claire L. , Tucker J. Allan
Published: December 2017

To determine the initial signaling event in the vascular permeability increase after high airway pressure injury, we compared groups of lungs ventilated at different peak inflation pressures (PIPs) with (gadolinium group) and without (control group) infusion of 20 μM gadolinium chloride, an inhibitor of endothelial stretch-activated cation channels. Microvascular permeability was assessed by using the capillary filtration coefficient ( K fc), a measure of capillary hydraulic conductivity. K fc was measured after ventilation for 30-min periods with 7, 20, and 30 cmH2O PIP with 3 cmH2O positive end-expiratory pressure and with 35 cmH2O PIP with 8 cmH2O positive end-expiratory pressure. In control lungs, K fc increased significantly to 1.8 and 3.7 times baseline after 30 and 35 cmH2O PIP, respectively. In the gadolinium group, K fc was unchanged from baseline (0.060 ± 0.010 ml ⋅ min−1 ⋅ cmH2O−1 ⋅ 100 g−1) after any PIP ventilation period. Pulmonary vascular resistance increased significantly from baseline in both groups before the last K fc measurement but was not different between groups. These results suggest that microvascular permeability is actively modulated by a cellular response to mechanical injury and that stretch-activated cation channels may initiate this response through increases in intracellular calcium concentration.
Differential respiratory muscle recruitment induced by clonidine in awake goats
Authors: Hedrick Michael S. , Dwinell Melinda R. , Janssen Patrick L. , Pizarro Josue , Bisgard Gerald E.
Published: December 2017

The purpose of this study was to test the hypothesis that dysrhythmic breathing induced by the α2-agonist clonidine is accompanied by differential recruitment of respiratory muscles. In adult goats ( n = 14) electromyographic (EMG) measurements were made from inspiratory muscles (diaphragm and parasternal intercostal) and expiratory muscles [triangularis sterni (TS) and transversus abdominis (Abd)]. EMG of the thyroarytenoid (TA) muscle was used as an index of upper airway (glottal) patency. Peak EMG activities of all spinal inspiratory and expiratory muscles were augmented by central and peripheral chemoreceptor stimuli. Phasic TA was apparent in the postinspiratory phase of the breathing cycle under normoxic conditions. During dysrhythmic breathing episodes induced by clonidine, TS and Abd activities were attenuated or abolished, whereas diaphragm and parasternal intercostal activities were unchanged. There was no tonic activation of TS or Abd EMG during apneas; however, TA activity became tonic throughout the apnea. We conclude that 1) α2-adrenoceptor stimulation results in differential recruitment of respiratory muscles during respiratory dysrhythmias and 2) apneas are accompanied by active glottic closure in the awake goat.
Early cerebral metabolic and electrophysiological recovery during controlled hypoxemic resuscitation in piglets
Authors: Feet Björn A. , Brun Nikolai C. , Hellström-Westas Lena , Svenningsen Niels W. , Greisen Gorm , Saugstad Ola D.
Published: December 2017

We tested the hypothesis that controlled hypoxemic resuscitation improves early cerebral metabolic and electrophysiological recovery in hypoxic newborn piglets. Severely hypoxic anesthetized piglets were randomly divided into three resuscitation groups: hypoxemic, 21% O2, and 100% O2groups (8 in each group). The hypoxemic group was mechanically ventilated with 12–18% O2adjusted to achieve a cerebral venous O2saturation of 17–23% (baseline; 45 ± 1%). Base excess (BE) reached −22 ± 1 mM at the end of hypoxia. During a 2-h resuscitation period, no significant differences in time to recovery of electroencephalography (EEG), quality of EEG at recovery, or extracellular hypoxanthine concentrations in the cerebral cortex and striatum were found among the groups. BE and plasma hypoxanthine, however, normalized significantly more slowly during controlled hypoxemic resuscitation than during resuscitation with 21 or 100% O2. We conclude that early brain recovery during controlled hypoxemic resuscitation was as efficient as, but not superior to, recovery during resuscitation with 21 or 100% O2. The systemic metabolic recovery from hypoxia, however, was delayed during controlled hypoxemic resuscitation.
Optical measurement of isolated canine lung filtration coefficients after alloxan infusion
Authors: Klaesner Joseph W. , Pou N. Adrienne , Parker Richard E. , Finney Charlene , Roselli Robert J.
Published: December 2017

In this study, lung filtration coefficient ( K fc) was measured in eight isolated canine lung preparations by using three methods: standard gravimetric (Std), blood-corrected gravimetric (BC), and optical. The lungs were held in zone III conditions and were subjected to an average venous pressure increase of 8.79 ± 0.93 (mean ± SD) cmH2O. The permeability of the lungs was increased with an infusion of alloxan (75 mg/kg). The resulting K fc values (in milliliters ⋅ min−1 ⋅ cmH2O−1 ⋅ 100 g dry lung weight−1) measured by using Std and BC gravimetric techniques before vs. after alloxan infusion were statistically different: Std, 0.527 ± 0.290 vs. 1.966 ± 0.283; BC, 0.313 ± 0.290 vs. 1.384 ± 0.290. However, the optical technique did not show any statistical difference between pre- and postinjury with alloxan, 0.280 ± 0.305 vs. 0.483 ± 0.297, respectively. The alloxan injury, quantified by using multiple-indicator techniques, showed an increase in permeability and a corresponding decrease in reflection coefficient for albumin (ςf). Because the optical method measures the product of K fc and ςf, this study shows that albumin should not be used as an intravascular optical filtration marker when permeability is elevated. However, the optical technique, along with another means of measuring K fc (such as BC), can be used to calculate the ςfof a tracer (in this study, ςfof 0.894 at baseline and 0.348 after injury). Another important finding of this study was that the ratio of baseline-to-injury K fc values was not statistically different for Std and BC techniques, indicating that the percent contribution of slow blood-volume increases does not change because of injury.
Grain sorghum dust increases macromolecular efflux from the in situ nasal mucosa
Authors: Gao Xiao-Pei
Published: December 2017

The purpose of this study was to determine whether an aqueous extract of grain sorghum dust increases macromolecular efflux from the nasal mucosa in vivo and, if so, whether this response is mediated, in part, by substance P. Suffusion of grain sorghum dust extract on the in situ nasal mucosa of anesthetized hamsters elicits a significant increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass, 70 kDa; P < 0.05). This response is significantly attenuated by CP-96345 and RP-67580, two selective, but structurally distinct, nonpeptide neurokinin 1 (substance P)-receptor antagonists, but not by CP-96344, the 2 R,3 Renantiomer of CP-96345 ( P < 0.05). CP-96345 has no significant effects on adenosine-induced increase in clearance of FITC-dextran from the in situ nasal mucosa. CP-96345 and RP-67580, but not CP-96344, significantly attenuate substance P-induced increases in clearance of FITC-dextran from the in situ nasal mucosa ( P < 0.05). Collectively, these data suggest that grain sorghum dust elicits neurogenic plasma exudation from the in situ nasal mucosa.
HRT preserves increases in bone mineral density and reductions in body fat after a supervised exercise program
Authors: Kohrt Wendy M. , Ehsani Ali A. , Birge Stanley J.
Published: December 2017

The aims of this study were to confirm our previous finding that hormone-replacement therapy (HRT) augments exercise-induced increases in bone mineral density (BMD) in older women and to determine whether HRT preserves the adaptations when exercise is reduced or discontinued. The study included an 11-mo treatment phase and a 6-mo follow-up phase. Participants, aged 66 ± 3 yr, were assigned to control (Con; n = 10), exercise (Ex; n = 18), HRT ( n = 10), and Ex+HRT ( n = 16) groups. HRT was continued during the follow-up. After the treatment phase, changes in total body BMD were −0.5 ± 1.7, 1.5 ± 1.4, 1.2 ± 0.8, and 2.7 ± 1.2% in Con, Ex, HRT, and Ex+HRT, respectively. Ex+HRT was more effective than HRT in increasing BMD of the total body and tended ( P = 0.08) to be more effective at the lumbar spine. Ex+HRT was more effective than Ex in increasing BMD of the total body, lumbar spine, and trochanter. Exercise-induced gains in BMD were preserved during the follow-up only in those individuals on HRT. HRT also attenuated fat accumulation, particularly in the abdominal region, after the exercise program. These findings suggest that HRT is an important adjunct to exercise for the prevention not only of osteoporosis but also of diseases related to abdominal obesity.
Acetylcholine and substance P stimulate bronchial epithelial cells to release eosinophil chemotactic activity
Authors: Koyama Sekiya , Sato Etsuro , Nomura Hiroshi , Kubo Keishi , Nagai Sonoko , Izumi Takateru
Published: December 2017

We investigated a role of neuroregulation in the release of eosinophil chemotactic activity (ECA) from bovine bronchial epithelial cells (BBEC). BBEC were stimulated with acetylcholine (ACh) and substance P (SP), and the supernatant fluids were tested for ECA by a blind-well chemotactic chamber technique. BBEC released ECA in response to ACh and SP in a dose- and time-dependent manner. Checkerboard analysis showed that ECA in regard to ACh and SP was chemotactic rather than chemokinetic. Partial characterization revealed that ECA involved both lipids and peptides. The release of ECA in response to ACh and SP was inhibited by nonspecific and 5-specific lipoxygenase inhibitors and by cycloheximide ( P < 0.01). Molecular-sieve column chromatography revealed that these mediators induced three molecular mass peaks (near 25 kDa, 9 kDa, and 400 Da, respectively). The lowest peak, which represented the predominant activity, was blocked by leukotriene B4-receptor antagonist ( P < 0.01) but not by platelet-activating factor-receptor antagonist. The release of leukotriene B4in the supernatant fluids was increased in response to ACh and SP stimulation ( P < 0.01). Platelet-activating factor was not detected. These results raise the possibility of a role of neuroregulation for the elaboration of ECA in the airway.
Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats
Authors: Klinger James R. , Warburton Rod R. , Pietras Linda , Hill Nicholas S.
Published: December 2017

Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 μg/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 μg/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 μg/h) increased plasma BNP (69 ± 8 vs. 35 ± 4 pg/ml, P < 0.05), lowered RV/BW (0.87 ± 0.05 vs. 1.02 ± 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 ± 3 vs. 64 ± 2, P = not significant). Infusion of ANP at 1.4 μg/h increased plasma ANP in hypoxic rats (759 ± 153 vs. 393 ± 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.
Repeated measurements of airway and parenchymal mechanics in rats by using low-frequency oscillations
Authors: Peták Ferenc , Hall Graham L. , Sly Peter D.
Published: December 2017

For studies investigating the mechanisms underlying the development of allergic conditions such as asthma, noninvasive methodologies for separating airway and parenchymal mechanics in animal models are required. To develop such a method, seven Brown Norway rats were studied on three occasions over a 14-day period. After the baseline measurements, on the third day inhaled methacholine was administered. Once lung function returned to the baseline level, a thoracotomy was performed to compare the lung mechanics in the intact- and open-chest conditions. On each occasion, the rats were anesthetized, paralyzed, and intubated. Small-amplitude oscillations between 0.5 and 21 Hz were applied through a wave tube to obtain respiratory impedance (Zrs). Esophageal pressure was measured to separate Zrs into pulmonary (Zl) and chest wall (Zw) components. A model containing a frequency-independent resistance and inertance and a tissue component, including tissue damping and elastance, was fitted to Zrs, Zl, and Zw spectra. Measurements of Zrs, Zl, or Zw and the model parameters calculated from them did not differ among tests. The number of animals required to show group changes in lung mechanics was significantly lower when animals were measured noninvasively than when the group changes were calculated from open-chest measurements. In conclusion, the method reported in this study can be used to separate airway and lung tissue mechanics noninvasively over a series of tests and can detect pulmonary constrictor responses for the airways and the parenchyma separately.