bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of tachykinins in airway responses to ozone in rats
Authors: Takebayashi Toru , Abraham Joseph , Murthy G. G. Krishna , Lilly Craig , Rodger Ian , Shore Stephanie A.
Published: December 2017

Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O3) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (V˙e) during O3 exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O3or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin-1- and -2-receptor antagonists, respectively, or with vehicle (Veh). O3 caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA-treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O3 exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O3 reducedV˙e in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 ± 3.7 vs. 27.8 ± 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats ( P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O3-induced lung inflammation. The results also indicate that the more pronounced effect of O3 on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O3 resulting from greaterV˙e.
Transient respiratory augmentation elicited by acute head-down tilt in the anesthetized cat
Authors: Xu Fadi , Zhang Zhong , Frazier Donald T.
Published: December 2017

Acute head-down tilt (AHDT, −30°) in humans induces a transient ventilatory augmentation for 1–2 min accompanied by a high venous return. However, the mechanisms underlying this respiratory response remain obscure because of limitations of experiments carried out in human subjects. The present study was undertaken to determine whether AHDT-induced respiratory augmentation exists in the anesthetized, paralyzed, and ventilated cat and, if so, whether this response depends on 1) the cerebellum, 2) the carotid sinus (CS) and/or vagal afferents, and 3) elevation of central venous return. The integrated phrenic neurogram, arterial blood pressure, central venous pressure (CVP), and end-tidal[Formula: see text] were recorded before, during, and after AHDT. The results showed that AHDT produced a transient (∼2 min) enhancement of minute phrenic activity (∼30%) primarily via an increase in peak integrated phrenic neurogram amplitude associated with a remarkable elevation of CVP (∼3 min). Cerebellectomy, CS denervation, bilateral vagotomy, or clamping CVP did not affect the presence of the AHDT-induced minute phrenic activity response. These findings demonstrate that the anesthetized cat is a suitable model for investigating the mechanisms involved in AHDT-induced respiratory augmentation. Preliminary studies suggest that this response does not require the cerebellum, CS/vagal afferents, or an associated rise in central venous return.
Thermoregulatory responses to cold transients: effects of menstrual cycle in resting women
Authors: Gonzalez Richard R. , Blanchard Laurie A.
Published: December 2017

Effects of the menstrual cycle on heat loss and heat production ( M) and core and skin temperature responses to cold were studied in six unacclimatized female nonsmokers (18–29 yr of age). Each woman, resting supine, was exposed to a cold transient (ambient temperature = mean radiant temperature = 20 to −5°C at −0.32°C/min, relative humidity = 50 ± 2%, wind speed = 1 m/s) in the follicular (F) phase ( days 2–6) and midluteal (L) phase ( days 19–23) of her menstrual cycle. Clothed in each of two ensembles with different thermal resistances, women performed multiple experiments in the F and L phases. Thermal resistance was 0.2 and 0.4 m2 ⋅ K ⋅ W−1for ensembles A and B, respectively. Esophageal temperature (Tes), mean weighted skin temperature (T sk), finger temperature (Tfing), and area-weighted heat flux were recorded continuously. Rate of heat debt (− S) and integrated mean body temperature (T b,i) were calculated by partitional calorimetry throughout the cold ramp. Extensive peripheral vasoconstriction in the F phase during early periods of the ramp elevated Tesabove thermoneutral levels. Shivering thermogenesis (Δ M = M − M basal, W /m2) was highly correlated with declines inT sk and Tfing( P <0.0001). There was a reduced slope in M as a function ofT b,i in the L phase with ensembles A( P < 0.02) and B ( P< 0.01). Heat flux was higher and − S was less in the L phases with ensemble A( P < 0.05). An analytic model revealed thatT sk and Tes contribute as additive inputs and Tfing has a multiplicative effect on the total control of Δ Mduring cold transients ( R 2 = 0.9). Endogenous hormonal levels at each menstrual cycle phase, core temperature andT skinputs, vascular responses, and variations in body heat balance must be considered in quantifying thermoregulatory responses in women during cold stress.
Influence of hydrostatic pressure gradients on regulation of plasma volume after exercise
Authors: Mack Gary W. , Yang Roger , Hargens Alan R. , Nagashima Kei , Haskell Andrew
Published: December 2017

The impact of posture on the immediate recovery of intravascular fluid and protein after intense exercise was determined in 14 volunteers. Forces which govern fluid and protein movement in muscle interstitial fluid pressure (PISF), interstitial colloid osmotic pressure (COPi), and plasma colloid osmotic pressure (COPp) were measured before and after exercise in the supine or upright position. During exercise, plasma volume (PV) decreased by 5.7 ± 0.7 and 7.0 ± 0.5 ml/kg body weight in the supine and upright posture, respectively. During recovery, PV returned to its baseline value within 30 min regardless of posture. PV fell below this level by 60 and 120 min in the supine and upright posture, respectively ( P < 0.05). Maintenance of PV in the upright position was associated with a decrease in systolic blood pressure, an increase in COPp (from 25 ± 1 to 27 ± 1 mmHg; P < 0.05), and an increase in PISF (from 5 ± 1 to 6 ± 2 mmHg), whereas COPi was unchanged. Increased PISFindicates that the hydrostatic pressure gradient favors fluid movement into the vascular space. However, retention of the recaptured fluid in the plasma is promoted only in the upright posture because of increased COPp.
Improved method of canine decerebration
Authors: Tonkovic-Capin Mislav , Krolo Mirko , Stuth Eckehard A. E. , Hopp Francis A. , Zuperku Edward J.
Published: December 2017

We describe an improved decerebration method for dogs that is suitable for studies of brain stem neurons in the absence of anesthesia. Previously reported techniques of canine decerebration often lead to respiratory and hemodynamic instability and lack of typical decerebrate rigidity. We have developed a precise, visually controlled, midcollicular brain stem transection technique that overcomes these problems. Our method results in only moderate blood loss while preserving carotid and basilar artery circulations. Consistent levels of brain stem transection routinely lead to stable postdecerebration hemodynamic parameters, allowing prolonged brain stem neuronal recordings. The same model should also be useful for a variety of studies involving other physiological systems in dogs in the absence of anesthesia and for studies of anesthetic effects.
Microdialysis ethanol removal reflects probe recovery rather than local blood flow in skeletal muscle
Authors: Rådegran G. , Pilegaard H. , Nielsen J. J. , Bangsbo J.
Published: December 2017

The present study compared the microdialysis ethanol outflow-inflow technique for estimating blood flow (BF) in skeletal muscle of humans with measurements by Doppler ultrasound of femoral artery inflow to the limb (BFFA). The microdialysis probes were inserted in the vastus lateralis muscle and perfused with a Ringer acetate solution containing ethanol, [2-3H]adenosine (Ado), andd-[14C(U)]glucose. BFFA at rest increased from 0.16 ± 0.02 to 1.80 ± 0.26 and 4.86 ± 0.53 l/min with femoral artery infusion of Ado (AdoFA,i) at 125 and 1,000 μg ⋅ min−1 ⋅ l−1thigh volume (low dose and high dose, respectively; P < 0.05) and to 3.79 ± 0.37 and 6.13 ± 0.65 l/min during one-legged, dynamic, thigh muscle exercise without and with high AdoFA,i, respectively ( P < 0.05). The ethanol outflow-to-inflow ratio (38.3 ± 2.3%) and the probe recoveries (PR) for [2-3H]Ado (35.4 ± 1.6%) and ford-[14C(U)]glucose (15.9 ± 1.1%) did not change with AdoFA,i at rest ( P = not significant). During exercise without and with AdoFA,i, the ethanol outflow-to-inflow ratio decreased ( P < 0.05) to a similar level of 17.5 ± 3.4 and 20.6 ± 3.2%, respectively ( P = not significant), respectively, while the PR increased ( P < 0.05) to a similar level ( P = not significant) of 55.8 ± 2.8 and 61.2 ± 2.5% for [2-3H]Ado and to 42.8 ± 3.9 and 45.2 ± 5.1% ford-[14C(U)]glucose. Whereas the ethanol outflow-to-inflow ratio and PR correlated inversely and positively, respectively, to the changes in BF during muscular contractions, neither of the ratio nor PR correlated to the AdoFA,i-induced BF increase. Thus the ethanol outflow-to-inflow ratio does not represent skeletal muscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.
Ocular and regional cerebral blood flow in aging Fischer-344 rats
Authors: Salter Jennifer M. , Cassone Vincent M. , Wilkerson M. Keith , Delp Michael D.
Published: December 2017

Vascular remodeling and changes in vascular responsiveness occur in the rat cerebrum with old age. This includes reductions in cerebral arteriolar numerical density, cross-sectional area, distensibility, the relative proportion of distensible elements in the cerebral arteriolar wall, and reduced endothelium-dependent relaxation. The purpose of this study was to test the hypothesis that old age results in an increase in vascular resistance and, correspondingly, a decrease in blood flow to ocular, regional cerebral, and spinal tissue in the rat. Blood flow was measured in the eye, olfactory bulb, left and right cerebrum, pituitary gland, midbrain, pons, cerebellum, medulla, and spinal cord of juvenile (2-mo-old, n = 6), adult (6-mo-old, n = 7), and aged (24-mo-old, n = 7) male Fischer-344 rats. Arterial pressure and blood flow were used to calculate vascular resistance. Vascular resistance in the eye of aged rats (6.03 ± 1.08 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g) was higher than that in juvenile (3.83 ± 0.38 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g) and adult rats (3.12 ± 0.24 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g). Similarly, resistance in the pons of older rats (2.24 ± 0.55 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g) was greater than in juvenile (0.66 ± 0.06 mmHg ⋅ml−1 ⋅ min ⋅ 100 g) and adult rats (0.80 ± 0.11 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g). In contrast, vascular resistance in the pituitary gland was lower in the aged rats (juvenile, 3.09 ± 0.22; adult, 2.79 ± 0.42; aged, 1.73 ± 0.32 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g, respectively). Vascular resistance was not different in other cerebral tissues or in the spinal cord in the aged rats. These data suggest that regional cerebral and spinal blood flow and vascular resistance remain largely unchanged in conscious aged rats at rest but that elevations in ocular vascular resistance and, correspondingly, decreases in ocular perfusion with advanced age could have serious adverse effects on visual function.
Relationship between T-wave amplitude and oxygen pulse in guinea pigs in hyperbaric helium and hydrogen
Authors: Kayar Susan R. , Parker Erich C. , Aukhert Eugenia O.
Published: December 2017

Diving is known to induce a change in the amplitude of the T wave (ATw) of electrocardiograms, but it is unknown whether this is linked to a change in cardiovascular performance. We analyzed ATw in guinea pigs at 10–60 atm and 25–36°C, breathing 2% O2 in either helium (heliox; n = 10) or hydrogen (hydrox; n = 9) for 1 h at each pressure. Core temperature and electrocardiograms were detected by using implanted radiotelemeters. O2 consumption rate was measured by using gas chromatography. In a previous study (S. R. Kayar and E. C. Parker. J. Appl. Physiol. 82: 988–997, 1997), we analyzed the O2 pulse, i.e., the O2 consumption rate per heart beat, in the same animals. By multivariate regression analysis, we identified variables that were significant to O2 pulse: body surface area, chamber temperature, core temperature, and pressure. In this study, inclusion of ATw made a significantly better model with fewer variables. After normalizing for chamber temperature and pressure, the O2 pulse increased with increasing ATw in heliox ( P = 0.001) but with decreasing ATw in hydrox ( P < 0.001). Thus ATw is associated with the differences in O2 pulse for animals breathing heliox vs. hydrox.
Zero-stress states of human pulmonary arteries and veins
Authors: Huang W. , Yen R. T.
Published: December 2017

The zero-stress states of the pulmonary arteries and veins from order 3 to order 9 were determined in six normal human lungs within 15 h postmortem. The zero-stress state of each vessel was obtained by cutting the vessel transversely into a series of short rings, then cutting each ring radially, which caused the ring to spring open into a sector. Each sector was characterized by its opening angle. The mean opening angle varied between 92 and 163° in the arterial tree and between 89 and 128° in the venous tree. There was a tendency for opening angles to increase as the sizes of the arteries and veins increased. We computed the residual strains based on the experimental measurements and estimated the residual stresses according to Hooke’s law. We found that the inner wall of a vessel at the state in which the internal pressure, external pressure, and longitudinal stress are all zero was under compression and the outer wall was in tension, and that the magnitude of compressive stress was greater than the magnitude of tensile stress.
Metabolic and exercise endurance effects of coffee and caffeine ingestion
Authors: Graham T. E. , Hibbert E. , Sathasivam P.
Published: December 2017

Caffeine (Caf) ingestion increases plasma epinephrine (Epi) and exercise endurance; these results are frequently transferred to coffee (Cof) consumption. We examined the impact of ingestion of the same dose of Caf in Cof or in water. Nine healthy, fit, young adults performed five trials after ingesting (double blind) either a capsule (Caf or placebo) with water or Cof (decaffeinated Cof, decaffeinated with Caf added, or regular Cof). In all three Caf trials, the Caf dose was 4.45 mg/kg body wt and the volume of liquid was 7.15 ml/kg. After 1 h of rest, the subject ran at 85% of maximal O2consumption until voluntary exhaustion (∼32 min in the placebo and decaffeinated Cof tests). In the three Caf trials, the plasma Caf and paraxanthine concentrations were very similar. After 1 h of rest, the plasma Epi was increased ( P < 0.05) by Caf ingestion, but the increase was greater ( P < 0.05) with Caf capsules than with Cof. During the exercise there were no differences in Epi among the three Caf trials, and the Epi values were all greater ( P < 0.05) than in the other tests. Endurance was only increased ( P < 0.05) in the Caf capsule trial; there were no differences among the other four tests. One cannot extrapolate the effects of Caf to Cof; there must be a component(s) of Cof that moderates the actions of Caf.
Caffeine ingestion and metabolic responses of tetraplegic humans during electrical cycling
Authors: Mohr T. , Van Soeren M. , Graham T. E. , Kjær M.
Published: December 2017

Normally, caffeine ingestion results in a wide spectrum of neural and hormonal responses, making it difficult to evaluate which are critical regulatory factors. We examined the responses to caffeine (6 mg/kg) ingestion in a group of spinal cord-injured subjects [7 tetraplegic (C5–7) and 2 paraplegic (T4) subjects] at rest and during functional electrical stimulation of their paralyzed limbs to the point of fatigue. Plasma insulin did not change, caffeine had no effect on plasma epinephrine, and there was a slight increase ( P < 0.05) in norepinephrine after 15 min of exercise. Nevertheless, serum free fatty acids were increased ( P < 0.05) after caffeine ingestion after 60 min of rest and throughout the first 15 min of exercise, but the respiratory exchange ratio was not affected. The exercise time was increased ( P < 0.05) by 6% or 1.26 ± 0.57 min. These data suggest that caffeine had direct effects on both the adipose tissue and the active muscle. It is proposed that the ergogenic action of caffeine is occurring, at least in part, by a direct action of the drug on muscle.
Comparison between the uptake of nitrous oxide and nitric oxide in the human nose
Authors: Kelley Patrick M. , DuBois Arthur B.
Published: December 2017

The absorption of nitrous oxide (N2O) during unidirectional flow was compared with the rate of uptake of nitric oxide (NO). At flow rates of 10, 20, and 60 ml/min from one nostril to the other, with the soft palate closed, the N2O reached a steady-state rate of absorption in 5–15 min. The mean superficial capillary blood flow ( n = 5) calculated from solubility and the steady-state rate of N2O absorption ranged from 13.3 to 15.9 ml/min. The relation between absorption of N2O in the nose and capillary blood flow fits a ventilation-perfusion model used by others to describe uptake of inert, soluble gases in the rat nose. By contrast, the rate of uptake of NO gas, which is chemically reactive, is 25–31 times as great as predicted by just its blood-to-air partition coefficient. Exogenous NO (16.9 parts/million) did not induce nasal vasodilation as measured with laser Doppler and N2O absorption methods. The difference between the measured rate of uptake of NO and the rate of uptake attributable to its partition coefficient in blood at the rate of blood flow calculated from N2O uptake is probably due to chemical reaction of NO in mucous secretions, nasal tissues, and capillary blood.
Important role of carotid afferents in control of breathing
Authors: Pan L. G. , Forster H. V. , Martino P. , Strecker P. J. , Beales J. , Serra A. , Lowry T. F. , Forster M. M. , Forster A. L.
Published: December 2017

The purpose of the present study was to determine the effect on breathing in the awake state of carotid body denervation (CBD) over 1–2 wk after denervation. Studies were completed on adult goats repeatedly before and 1) for 15 days after bilateral CBD ( n = 8), 2) for 7 days after unilateral CBD ( n = 5), and 3) for 15 days after sham CBD ( n = 3). Absence of ventilatory stimulation when NaCN was injected directly into a common carotid artery confirmed CBD. There was a significant ( P < 0.01) hypoventilation during the breathing of room air after unilateral and bilateral CBD. The maximum [Formula: see text] increase (8 Torr for unilateral and 11 Torr for bilateral) occurred ∼4 days after CBD. This maximum was transient because by 7 (unilateral) to 15 (bilateral) days after CBD, [Formula: see text]was only 3–4 Torr above control. CO2 sensitivity was attenuated from control by 60% on day 4 after bilateral CBD and by 35% on day 4after unilateral CBD. This attenuation was transient, because CO2 sensitivity returned to control temporally similar to the return of[Formula: see text] during the breathing of room air. During mild and moderate treadmill exercise 1–8 days after bilateral CBD, [Formula: see text] was unchanged from its elevated level at rest, but, 10–15 days after CBD,[Formula: see text] decreased slightly from rest during exercise. These data indicate that 1) carotid afferents are an important determinant of rest and exercise breathing and ventilatory CO2 sensitivity, and 2) apparent plasticity within the ventilatory control system eventually provides compensation for chronic loss of these afferents.
Effect of sodium in a rehydration beverage when consumed as a fluid or meal
Authors: Ray Melinda L. , Bryan Mark W. , Ruden Timothy M. , Baier Shawn M. , Sharp Rick L. , King Douglas S.
Published: December 2017

To investigate the impact of fluid composition on rehydration effectiveness, 30 subjects (15 men and 15 women) were studied during 2 h of rehydration after a 2.5% body weight loss. In a randomized crossover design, subjects rehydrated with water (H2O), chicken broth (CB: 109.5 mmol/l Na, 25.3 mmol/l K), a carbohydrate-electrolyte drink (CE: 16.0 mmol/l Na, 3.3 mmol/l K), and chicken noodle soup (Soup: 333.8 mmol/l Na, 13.7 mmol/l K). Subjects ingested 175 ml at the start of rehydration and 20 min later; H2O was given every 20 min thereafter for a total volume equal to body weight loss during dehydration. At the end of the rehydration period, plasma volume was not significantly different from predehydration values in the CB (−1.6 ± 1.1%) and Soup (−1.4 ± 0.9%) trials. In contrast, plasma volume remained significantly ( P < 0.01) below predehydration values in the H2O (−5.6 ± 1.1%) and CE (−4.2 ± 1.0%) trials after the rehydration period. Urine volume was greater in the CE (310 ± 30 ml) than in the CB (188 ± 20 ml) trial. Urine osmolality was higher in the CB and Soup trials than in the CE trial. Urinary sodium concentration was higher in the Soup and CB trials than in the CE and H2O trials. These results provide evidence that the inclusion of sodium in rehydration beverages, as well as consumption of a sodium-containing liquid meal, increases fluid retention and improves plasma volume restoration.
Effect of time-varying load on degree of bronchoconstriction in the dog
Authors: Shinozuka Norihiro , Lavoie Jean-Pierre , Martin James G. , Bates Jason H. T.
Published: December 2017

It is well established that the degree of airway smooth muscle shortening produced by a given dose of bronchial agonist is greatly affected by lung volume. The airways are tethered by parenchymal attachments, the tension of which increases progressively with lung volume, thereby presenting a commensurately increasing hindrance to smooth muscle contraction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska, and R. A. Murphy. Science 211: 495–497, 1981) presented evidence that smooth muscle contraction initially involves rapidly cycling cross bridges, which then change to noncycling (latch) bridges. They also suggested that most of the muscle shortening occurs during the early rapid cross-bridge phase. This implies that smooth muscle subject to a given load early in contraction should shorten less than when it is subject to the same load later on. An in vitro study (W. Li and N. L. Stephens. Can. J. Physiol. Pharmacol. 72: 1458–1463, 1994) obtained support for this notion. To test this hypothesis in vivo, we measured the changes in lung impedance at 1 and 6 Hz produced in dogs by a bolus intravenous injection of methacholine when lung volume was increased for 10 s at different times after injection. We found that the changes in mechanics were greatly inhibited, whereas lung volume was elevated. However, when lung volume was returned to its initial level, the lung mechanics continued to change at a rate unaffected by the preceding volume change. We conclude that temporary mechanical inhibition of airway smooth muscle shortening in the normal dog in vivo merely delays an otherwise normal course of contraction.
Size constraints of telemeters in rats
Authors: Moran M. M. , Roy R. R. , Wade C. E. , Corbin B. J. , Grindeland R. E.
Published: December 2017

This study was designed to determine the maximum-size subcutaneous telemeter that would enable long-term and multichannel data collection in a 170-g rat for 90 days. In phase 1, rats with implants weighing 5 (2.5 cm3), 15 (7.5 cm3), 25 (12.5 cm3), 35 (17.5 cm3), or 45 (22.5 cm3) g were compared with sham-operated (SOC) and nonoperated (NOC) control animals. Severe skin lesions, seromas, and lower growth rates were observed in rats having implants ≥35 g. Thus, in phase 2, rats implanted with 23.5 g (17.5 cm3; 11-g active telemeter and 12.5-g implant) were compared with rats implanted with 11 g (6 cm3; telemeter only) and with the SOC and NOC groups. No differences were found among implanted groups in mean arterial pressure (MAP), heart rate (HR), subcutaneous temperature, or spontaneous activity under standard housing conditions. All groups were more active and had a higher MAP during the dark than the light phase of the daily cycle. During 2 h of cold exposure (3°C), both telemetered groups exhibited similar changes in HR, MAP, temperature, and activity levels. Adrenal glands were larger in the 23.5-g group (51 ± 1.6 mg) than in the SOC (46 ± 1.0 mg) and the NOC groups (41 ± 2.0 mg). No other significant differences were found in organ, muscle, or bone weights. These data verify the feasibility of using 23.5-g (17.5 cm3) subcutaneous telemeters for chronic recordings in young adult rats.
Determining bone and total body mineral content from body density and bioelectrical response spectroscopy
Authors: Siconolfi Steven F. , Gretebeck Randal J. , Wong William W. , Moore Sheril S. , Gilbert John H.
Published: December 2017

We hypothesized that one could assess total body mineral (TBM) and bone mineral content (BMC) from measurements of body density and bioelectrical response spectroscopy (BRS)-determined total body water by using a three-compartment (3C) model. We compared TBM and BMC computed from measurements of water (2H2O dilution or BRS) and body density (underwater weighing) with [4-compartment (4C)] and without (3C) mineral (dual X-ray absorptiometry) in 15 women and 16 men. BRS used multifrequency or single-frequency estimates of water. Mean differences between the 3C and 4C models ranged from −6.1 to 2.2%. Correlations between models were 0.82–0.91. Standard errors of the estimate of 8.5–9.3% were within the range of those previously reported, i.e., 4.9–13%. Use of BRS did not significantly decrease the strength of the correlations between the models. A significant mean difference (only in women) was found only with 3C single-frequency BRS estimates of TBM and BMC. We concluded that investigators can assess TBM and BMC 3C multifrequency BRS estimates in men and women.
Effect of cardiogenic and noncardiogenic pulmonary edema on histamine responsiveness in sheep
Authors: Snapper James R. , Lefferts Peter L. , Lu Weixuan , Hwang Young Sil , Plitman Jonathan D.
Published: December 2017

We compared the effects of cardiogenic pulmonary edema, brief pulmonary vascular congestion without frank edema, and noncardiogenic pulmonary edema on responsiveness to inhaled histamine in chronically instrumented awake sheep. Histamine responsiveness was measured before and after 1) cardiogenic pulmonary edema induced by raising left atrial pressure to 35 cmH2O (↑Pla) for 3.5 h by partial obstruction of flow across the mitral valve, 2) brief cardiogenic congestion via ↑Pla for 0.5 h, 3) noncardiogenic pulmonary edema induced by 25 mg/kg intravenous perilla ketone (PK), and 4) 3.5 h of monitoring without ↑Pla or PK (controls). Treatment for 3.5 h with ↑Pla ( n = 9) and PK ( n = 11) each significantly lessened the histamine dose required to cause a fall to 65% of baseline dynamic lung compliance (ED65Cdyn), i.e., increased responsiveness. Sheep treated for 0.5 h with ↑Pla ( n = 7) and controls ( n = 5) showed no significant change in ED65Cdyn. Intravenous atropine (0.1 mg/kg) before the second histamine challenge altered neither the reduction of ED65Cdyn in ↑Pla ( n = 8) and PK ( n = 9) sheep nor the ED65Cdyn level of controls ( n = 9). These data imply that the local effects of edema, rather than bronchial vascular hemodynamics, cholinergic reflexes, and permeability changes, are germane to lung hyperresponsiveness during pulmonary edema in sheep.
Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans
Authors: Ahlborg Gunvor , Lundberg Jan M.
Published: December 2017

Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 77: 121–126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res. Commun. 180: 1298–1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin. Physiol. ( Colch.) 13: 653–662, 1993), the same increase in mean arterial blood pressure (4%), decreases in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 ± 3 vs. 23 ± 2%, P < 0.02), with a total reduction corresponding to 43 ± 3% ( P < 0.01 vs. 23 ± 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.
Increased capillarity in leg muscle of finches living at altitude
Authors: Hepple Russell T. , Agey Peter J. , Hazelwood Larnelle , Szewczak Joseph M. , MacMillen Richard E. , Mathieu-Costello Odile
Published: December 2017

An increased ratio of muscle capillary to fiber number (capillary/fiber number) at altitude has been found in only a few investigations. The highly aerobic pectoralis muscle of finches living at 4,000-m altitude ( Leucosticte arctoa; A) was recently shown to have a larger capillary/fiber number and greater contribution of tortuosity and branching to total capillary length than sea-level finches ( Carpodacus mexicanus; SL) of the same subfamily (O. Mathieu-Costello, P. J. Agey, L. Wu, J. M. Szewczak, and R. E. MacMillen. Respir. Physiol. 111: 189–199, 1998). To evaluate the role of muscle aerobic capacity on this trait, we examined the less-aerobic leg muscle (deep portion of anterior thigh) in the same birds. We found that, similar to pectoralis, the leg muscle in A finches had a greater capillary/fiber number (1.42 ± 0.06) than that in SL finches (0.77 ± 0.05; P < 0.01), but capillary tortuosity and branching were not different. As also found in pectoralis, the resulting larger capillary/fiber surface in A finches was proportional to a greater mitochondrial volume per micrometer of fiber length compared with that in SL finches. These observations, in conjunction with a trend to a greater (rather than smaller) fiber cross-sectional area in A than in SL finches (A: 484 ± 42, SL: 390 ± 26 μm2, both values at 2.5-μm sarcomere length; P = 0.093), support the notion that chronic hypoxia is also a condition in which capillary-to-fiber structure is organized to match the size of the muscle capillary-to-fiber interface to fiber mitochondrial volume rather than to minimize intercapillary O2diffusion distances.
Tumor necrosis factor-α in ischemia and reperfusion injury in rat lungs
Authors: Khimenko Pavel L. , Bagby G. J. , Fuseler J. , Taylor Aubrey E.
Published: December 2017

The effects of both recombinant rat tumor necrosis factor-α (TNF-α) and an anti-TNF-α antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V˙/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascular permeability, as measured by the filtration coefficient ( K fc), increased three- and fivefold above baseline after 30 and 90 min of reperfusion, respectively ( P < 0.001). Over the same time intervals, the K fc for theV˙/R group increased five- and tenfold above baseline values, respectively ( P < 0.001). TNF-α measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-α (50,000 U), placed into perfusate after baseline measurements, produced no measurable change in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the presence of TNF-α. An anti-TNF-α antibody (10 mg/rat) injected intraperitoneally into rats 2 h before the lung was isolated prevented the microvascular damage in lungs exposed to both I/R and V˙/R ( P < 0.001). These results indicate that TNF-α is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R andV˙/R models of lung ischemia.
Changes in lower limb volume in humans during parabolic flight
Authors: Bailliart Olivier , Capderou André , Cholley Bernard P. , Kays Christian , Rivière Daniel , Téchoueyres Pierre , Lachaud Jean-Luc , Vaïda Pierre
Published: December 2017

Variations in gravity [head-to-foot acceleration (Gz)] induce hemodynamic alterations as a consequence of changes in hydrostatic pressure gradients. To estimate the contribution of the lower limbs to blood pooling or shifting during the different gravity phases of a parabolic flight, we measured instantaneous thigh and calf girths by using strain-gauge plethysmography in five healthy volunteers. From these circumferential measurements, segmental leg volumes were calculated at 1, 1.7, and 0 Gz. During hypergravity, leg segment volumes increased by 0.9% for the thigh ( P < 0.001) and 0.5% for the calf ( P < 0.001) relative to 1-Gz conditions. After sudden exposure to microgravity following hypergravity, leg segment volumes were reduced by 3.5% for the thigh ( P< 0.001) and 2.5% for the calf ( P< 0.001) relative to 1.7-Gzconditions. Changes were more pronounced at the upper part of the leg. Extrapolation to the whole lower limb yielded an estimated 60-ml increase in leg volume at the end of the hypergravity phase and a subsequent 225-ml decrease during microgravity. Although quantitatively less than previous estimations, these blood shifts may participate in the hemodynamic alterations observed during hypergravity and weightlessness.
Effect of ventilation distribution on aerosol bolus dispersion and recovery
Authors: Brown James S. , Gerrity Timothy R. , Bennett William D.
Published: December 2017

It has been speculated that convective ventilatory inhomogeneities are an important factor influencing aerosol bolus behavior in the compromised lung. Multiple-breath133Xe washout (MBWXe) is a commonly accepted test of ventilation distribution. By comparing aerosol bolus parameters to MBWXein 9 healthy subjects and 14 cystic fibrosis patients with mild-to-moderate airway obstruction, we have attempted to discern the effect of altered ventilation distribution on aerosol bolus dispersion and recovery. Aerosol boluses (150-ml width) were delivered to the volumetric penetrations of 250 and 500 ml. Similar tidal volumes (∼1.25 liters) and flow rates (0.4 l/s) were used for aerosol bolus and MBWXemaneuvers. Associations between bolus parameters and ventilation distribution were only observed in the cystic fibrosis patients. We conclude that aerosol bolus dispersion and recovery are both influenced by convective ventilatory inhomogeneities induced by airway obstruction in these patients.
Strain dependence of the airway response to dry-gas hyperpnea challenge in the rat
Authors: Yang X. X. , Powell W. S. , Xu L. J. , Martin J. G.
Published: December 2017

The aim of the study was to investigate strain dependence and mechanisms of airway responses to dry-gas hyperpnea challenge in the rat. We studied responses in a strain that is hyperresponsive to methacholine, Fischer 344 (F-344); in two normoresponsive strains, Lewis and ACI; and in an atopic but normoresponsive strain, Brown Norway (BN). We examined the effects of a neurokinin (NK) 1-receptor (CP-99994), an NK2-receptor (SR-48968), and a leukotriene D4(LTD4)-receptor antagonist (pranlukast) on responses to hyperpnea challenge in BN rats. The animals were ventilated with a tidal volume of 8 ml/kg and a frequency of 150 breaths/min with either a dry or humidified mixture of 5% CO2-95% O2 for 5 min for hyperpnea challenge, whereas responses to challenge were measured during spontaneous breathing. Pulmonary resistance increased after dry-gas challenge in BN and ACI but not in F-344 and Lewis rats. CP-99994, SR-48968, and pranlukast significantly attenuated the increase in pulmonary resistance after dry-gas challenge. There were no significant differences in responsiveness to airway challenge with LTD4 among the BN, F-344 and ACI rats. We conclude that responses to dry-gas hyperpnea challenge are strain dependent in rats and are mediated by NKs and LTD4.
Walking in simulated reduced gravity: mechanical energy fluctuations and exchange
Authors: Griffin Timothy M. , Tolani Neil A. , Kram Rodger
Published: December 2017

Walking humans conserve mechanical and, presumably, metabolic energy with an inverted pendulum-like exchange of gravitational potential energy and horizontal kinetic energy. Walking in simulated reduced gravity involves a relatively high metabolic cost, suggesting that the inverted-pendulum mechanism is disrupted because of a mismatch of potential and kinetic energy. We tested this hypothesis by measuring the fluctuations and exchange of mechanical energy of the center of mass at different combinations of velocity and simulated reduced gravity. Subjects walked with smaller fluctuations in horizontal velocity in lower gravity, such that the ratio of horizontal kinetic to gravitational potential energy fluctuations remained constant over a fourfold change in gravity. The amount of exchange, or percent recovery, at 1.00 m/s was not significantly different at 1.00, 0.75, and 0.50 G (average 64.4%), although it decreased to 48% at 0.25 G. As a result, the amount of work performed on the center of mass does not explain the relatively high metabolic cost of walking in simulated reduced gravity.
Pulmonary gas exchange during exercise in pigs
Authors: Hopkins S. R. , Stary C. M. , Falor E. , Wagner H. , Wagner P. D. , McKirnan M. D.
Published: December 2017

Increased ventilation-perfusion (V˙a/Q˙) inequality is observed in ∼50% of humans during heavy exercise and contributes to the widening of the alveolar-arterial O2 difference (A-[Formula: see text]). Despite extensive investigation, the cause remains unknown. As a first step to more direct examination of this problem, we developed an animal model. Eight Yucatan miniswine were studied at rest and during treadmill exercise at ∼30, 50, and 85% of maximal O2 consumption (V˙o 2 max). Multiple inert-gas, blood-gas, and metabolic data were obtained. The A-[Formula: see text]increased from 0 ± 3 (SE) Torr at rest to 14 ± 2 Torr during the heaviest exercise level, but arterial[Formula: see text]([Formula: see text]) remained at resting levels during exercise. There was normalV˙a/Q˙inequality [log SD of the perfusion distribution (log[Formula: see text]) = 0.42 ± 0.04] at rest, and moderate increases (log[Formula: see text] = 0.68 ± 0.04, P < 0.0001) were observed with exercise. This result was reproducible on a separate day. TheV˙a/Q˙inequality changes are similar to those reported in highly trained humans. However, in swine, unlike in humans, there was no inert gas evidence for pulmonary end-capillary diffusion limitation during heavy exercise; there was no systematic difference in the measured[Formula: see text] and the[Formula: see text] as predicted from the inert gases. These data suggest that the pig animal model is well suited for studying the mechanism of exercise-inducedV˙a/Q˙inequality.
Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses
Authors: Campo Carlos , Molinari Jussara F. , Ungo Jaime , Ahmed Tahir
Published: December 2017

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by “nonanticoagulant fractions” (NAF-heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin ( n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin ( n = 8) showed intermediate efficacy (ABR ID50= 0.8 mg/kg, AHR ID50= 1.4 mg/kg), whereas ULMW NAF-heparin ( n = 7) was the most effective agent (ABR ID50= 0.4 mg/kg, AHR ID50= 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered “after” antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the <2,500 ULMW chains. The antiallergic activity of NAF-heparins is mediated by an unknown biological action and may have therapeutic potential.
Effects of chronic run training on Na+-dependent Ca2+efflux from rat left ventricular myocytes
Authors: Palmer Bradley M. , Lynch Joshua M. , Snyder Steven M. , Moore Russell L.
Published: December 2017

The effects of endurance run training on Na+-dependent Ca2+regulation in rat left ventricular myocytes were examined. Myocytes were isolated from sedentary and trained rats and loaded with fura 2. Contractile dynamics and fluorescence ratio transients were recorded during electrical pacing at 0.5 Hz, 2 mM extracellular Ca2+concentration, and 29°C. Resting and peak cytosolic Ca2+concentration ([Ca2+]c) did not change with exercise training. However, resting and peak [Ca2+]cincreased significantly in both groups during 5 min of continuous pacing, although diastolic [Ca2+]cin the trained group was less susceptible to this elevation of intracellular Ca2+. Run training also significantly reduced the rate of [Ca2+]cdecay during relaxation. Myocytes were then exposed to 10 mM caffeine in the absence of external Na+or Ca2+to trigger sarcoplasmic reticular Ca2+release and to suppress cellular Ca2+efflux. This maneuver elicited an elevated steady-state [Ca2+]c. External Na+was then added, and the rate of [Ca2+]cclearance was determined. Run training significantly reduced the rate of Na+-dependent clearance of [Ca2+]cduring the caffeine-induced contractures. These data demonstrate that the removal of cytosolic Ca2+was depressed with exercise training under these experimental conditions and may be specifically reflective of a training-induced decrease in the rate of cytosolic Ca2+removal via Na+/Ca2+exchange and/or in the amount of Ca2+moved across the sarcolemma during a contraction.
Regional clearance of solute from peripheral airway epithelia: recovery after sublobar exposure to ozone
Authors: Foster William Michael , Freed Arthur N.
Published: December 2017

The influence of local exposure to ozone (O3) on respiratory epithelial permeability of sublobar lung segments was studied by using aerosolized99mTc-diethylenetriamine pentaacetic acid (DTPA; mol wt, 492). Two bronchoscopes were inserted through an endotracheal tube in anesthetized, mechanically ventilated, mixed breed dogs and were wedged into sublobar bronchi located in the right and left lower lobes, respectively. Segments were ventilated via the bronchoscope with 5% CO2 in air delivered at 200 ml/min, and an aerosol of99mTc-DTPA was generated and delivered through the scope and into the sublobar segment over a 30-s period. Clearance of 99mTc-DTPA was measured simultaneously from right and left lower lung segments at baseline and 1, 7, and 14 days after a 6-h sublobar exposure to filtered air or 400 parts per billion O3. O3 treatment significantly decreased the clearance halftime ( t 50) of99mTc-DTPA by 50% from the baseline mean of 32.3 to 16.0 min at 1 day postexposure. After 7 days of recovery, t 50was still reduced by 28.8%; however, by 14 days postexposure, clearance of 99mTc-DTPA had recovered, and the t 50 had a mean value of 30.0 min. 99mTc-DTPA clearance was not altered by exposure to filtered air, and t 50 values were comparable to baseline at 1, 7, and 14 days postexposure. These results reveal that a single local exposure to O3 increases transepithelial clearance, but only for epithelia directly exposed to O3, and that 7–14 days of recovery are required before permeability to small-molecular-weight solutes returns to normal.
Infrared CO2 analyzer error: an effect of background gas (N2 and O2)
Authors: Arieli R. , Ertracht O. , Daskalovic Y.
Published: December 2017

Three infrared CO2 analyzers were tested for the effect of background gases: the Ametek CD-3A (Ametek, Thermox Instruments Division, Pittsburgh, PA), the Dräger Multiwarn P CO2 (Dräger, Lübeck, Germany), and the Servomex 1440 (Servomex, Crowborough, East Sussex, UK). Various CO2 concentrations were prepared with Wösthoff precision pumps (H. Wösthoff, Bochum, Germany). Calibration with a different background gas (O2 or N2) caused a similar but systematic error in the CO2readings of all three analyzers. When the CO2 analyzers were calibrated with N2 as the background gas, the CO2 reading in an O2-enriched atmosphere was 8% lower than the true value. Conversely, calibration with O2 as the background gas resulted in a 10% overestimation of CO2levels when N2 was the background gas. This error may be important in a few fields of respiratory physiology.
Measurement of tidal volume by using transthoracic impedance variations in rats
Authors: Davidson K. G. , Bersten A. D. , Nicholas T. E. , Ravenscroft P. R. , Doyle I. R.
Published: December 2017

The application of impedance pneumography for monitoring respiration in small animals has been limited by problems with calibration. With improved instrumentation, we describe the calibration of tidal volume in anesthetized rats. The detection of changes in voltage, reflecting the electrical impedance variations associated with respiration, was optimized by using disposable adhesive silver-silver chloride electrodes, advanced circuitry, and analog-to-digital recording instrumentation. We found a linear relationship between change in impedance and tidal volume in individual rats ( R2≥ 98%), which was strongly influenced by rat weight. Consequently, a calibration equation incorporating change in impedance and rat weight was derived to predict tidal volume. Comparison of the predicted and true tidal volumes revealed a mean R2≥ 98%, slopes of ∼1, intercepts of ∼0, and bias of ∼0.07 ml. The predicted volumes were not significantly affected by either frequency of respiration or pulmonary edema. We conclude that impedance pneumography provides a valuable tool for the noninvasive measurement of tidal volume in anesthetized rats.