bluuebunny/crossref_metadata_2025 huggingface dataset:
Products of cyclooxygenase mediate the responses of the guinea pig trachea to hydrogen peroxide
Authors: Gao Y. , Vanhoutte P. M.
Published: December 2017

The role of products of cyclooxygenase was investigated in the responses of isolated airways to H2O2. Strips of guinea pig trachea, in some of which the epithelium had been removed mechanically, were suspended in organ chambers, and isometric tension was recorded. Under basal conditions, H2O2 induced indomethacin-sensitive contractions, which were larger in preparations without than in those with epithelium; the difference was abolished by inhibitors of thromboxane synthase or thromboxane A2 receptors. During contractions to acetylcholine, low concentrations of H2O2 induced relaxation in preparations with but had no significant effect in those without epithelium. At higher concentrations of H2O2, the epithelium-dependent relaxation was attenuated but an epithelium-independent relaxation appeared. The epithelium-dependent but not the epithelium-independent responses to H2O2 were blocked by indomethacin. Under basal conditions, prostaglandin E2 (PGE2; < or = 10(-7) M), U-46619, prostaglandin PGF2 alpha (PGF2 alpha), prostaglandin PGD2 (PGD2), and prostacyclin (PGI2) caused contractions. During contractions to acetylcholine, PGE2 induced larger relaxations in preparations with than in those without epithelium. Radioimmunoassay revealed that lower concentrations of H2O2 predominantly increased the release of PGE2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha); in preparations without epithelium, the release of thromboxane B2 was augmented also. At higher concentrations of H2O2, the release of PGE2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha, and thromboxane B2 increased in preparations with and without epithelium. These findings demonstrate that the responses of the guinea pig trachea to H2O2 are mediated mainly by products of cyclooxygenase and that the effects of H2O2 are modulated by the epithelium.
Pattern of breathing and upper airway mechanics during wakefulness and sleep in healthy elderly humans
Authors: Hudgel D. W. , Devadatta P. , Hamilton H.
Published: December 2017

Elderly subjects are known to be prone to periodic breathing in sleep. Because periodic breathing may be associated with changes in upper airway caliber, we hypothesized that oscillations in upper airway caliber contribute to the increased prevalence of sleep-related periodic breathing in the elderly. We tested this hypothesis by measuring upper airway resistance, ventilatory variables, and the pattern of variation of these variables in groups of body size-matched young and elderly healthy individuals during wakefulness and stage 2 non-rapid-eye-movement sleep. No major differences existed between the two groups during either wakefulness or sleep in mean upper airway resistance or ventilation values. However, ventilation was more variable during sleep in the elderly; this variability was oscillatory in the majority of elderly subjects at an average rate of 0.04 breaths/cycle or one cycle approximately every 24 s. Oscillations in upper airway resistance during sleep were associated with reciprocal oscillations in tidal volume and/or minute ventilation at the same frequency. Those subjects who had significant oscillations in upper airway resistance had more apneas and hypopneas than those subjects without such oscillations. Oscillations in resistance and ventilation occurred in the supine but not in the lateral body position. We conclude that the wide oscillations in upper airway resistance present during sleep in supine healthy elderly subjects produce a fluctuating mechanical limitation of ventilation, which may contribute to periodic breathing.
Effects of mean airway pressure and tidal volume on lung and chest wall mechanics in the dog
Authors: Barnas G. M. , Sprung J.
Published: December 2017

Dependencies of the dynamic mechanical properties of the respiratory system on mean airway pressure (Paw) and the effects of tidal volume (VT) are not completely clear. We measured resistance and dynamic elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) in six healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50–300 ml; 0.4 Hz) delivered at mean Paw from -9 to +23 cmH2O. Changes in end-expiratory lung volume, estimated with inductance plethysmographic belts, showed a typical sigmoidal relationship to mean Paw. Each dog showed the same dependencies of mechanical properties on mean Paw and VT. All elastances and resistances were minimal between 5 and 10 cmH2O mean Paw. All elastances, Rrs, and RL increased greatly with decreasing Paw below 5 cmH2O. Ers and EL increased above 10 cmH2O. Ecw, Ers, Rcw, and Rrs decreased slightly with increasing VT, but RL and EL were independent of VT. We conclude that 1) respiratory system impedance is minimal at the normal mean lung volume of supine anesthetized paralyzed dogs; 2) the dependency of RL on lung volume above functional residual capacity is dependent on VT and respiratory frequency; and 3) chest wall, but not lung, mechanical behavior is nonlinear (i.e., VT dependent) at any given lung volume.
Effect of low O2 on glucose uptake in rabbit carotid body
Authors: Obeso A. , Gonzalez C. , Rigual R. , Dinger B. , Fidone S.
Published: December 2017

Glucose consumption in the rabbit carotid body was studied in vitro by measuring phosphorylation rates of tracer concentrations of 2-[3H]deoxy-glucose. The rate of glucose consumption measured in 100% O2-equilibrated modified Tyrode medium was 61 nmol.g tissue-1 x min-1 and was linear for up to 30 min. Incubation of carotid bodies for 5 or 10 min in moderately hypoxic solution (20% O2–80% N2) resulted in a 44% increase in the rate of glucose consumption. The glucose consumption of the nodose ganglion was not affected during similar incubation with low-O2 medium. High-resolution autoradiography of freeze-dried tissues revealed that the type I parenchymal cells are the principal site of glucose consumption in both 100% O2- and 20% O2-incubated carotid bodies. This metabolic response of the carotid body to hypoxia was not secondary to neurotransmitter release, because similar elevations in glucose utilization were observed with low-O2 medium containing zero Ca2+, a condition in which the release of neurotransmitters from type I cells is inhibited. Lowering the pH of the incubation medium from 7.4 to 7 or 6.8 markedly reduced the rate of glucose utilization by both the carotid body and the nodose ganglion. Ouabain (2 x 10(-4) and 1 x 10(-3) M) reduced by 20% the glucose consumption of carotid bodies incubated in 100% O2-equilibrated solution and abolished the metabolic response produced by low-O2 medium. The results suggest that the utilization of metabolic energy is an integral component of the chemoreceptor response to hypoxia.
Glucose dynamics and gluconeogenesis during and after prolonged swimming in rats
Authors: Ryan C. , Ferguson K. , Radziuk J.
Published: December 2017

Glucose fluxes and, in particular, gluconeogenic rate were examined during and after prolonged submaximal exercise represented by a 4-h swim and 3-h recovery in 12-h-fasted previously catheterized rats. The metabolic clearance rate and production rate of glucose were measured using an infusion of [6–3H]glucose, and gluconeogenesis was assessed from the incorporation of 14C from [14C]bicarbonate into glucose. Immediately after exercise and after the 3-h recovery, liver glycogen was also determined. During exercise, euglycemia was maintained while glucose production and utilization doubled from 1.58 +/- 0.17 to 3.58 +/- 0.21 mg/min. During recovery, glucose concentrations increased to 131.0 +/- 5.8 vs. 110.8 +/- 5.1 mg/dl for controls (P < 0.05), because the decline in glucose production rate lagged behind the decline in metabolic clearance rate. The index of gluconeogenesis coupled with a metabolic correction factor indicates that gluconeogenesis was the primary source of glucose during swimming and recovery and that the principal substrates were at the level of pyruvate. CO2 production rates calculated using plasma CO2 and label concentrations doubled during exercise. Little repletion of liver glycogen was seen after exercise, indicating that the increased production of glucose after exercise is directed primarily toward the repletion of muscle glycogen. Swimming is therefore a useful model of low-intensity exercise easily implemented in untrained animals. [14C]bicarbonate can be used in the estimation of gluconeogenic rates during exercise.
Activity-induced regulation of myosin isoform distribution: comparison of two contractile activity programs
Authors: Diffee G. M. , Caiozzo V. J. , McCue S. A. , Herrick R. E. , Baldwin K. M.
Published: December 2017

This study examined the role of specific types of contractile activity in regulating myosin heavy chain (MHC) isoform expression in rodent soleus. A combination of hindlimb suspension (SN) and two programmed contractile training activity paradigms, either isometric contractile activity (ST-IM) or high-load slowly shortening isovelocity activity, were utilized. Both training paradigms increased muscle mass compared with SN alone. However, only ST-IM resulted in a partial prevention of the suspension-induced decrease in type I MHC. With the use of a fluorescently labeled antibody to type IIa MHC, the distribution of MHCs among fibers was examined immunohistochemically. In SN, the percentage of cells staining positive for type IIa MHC was increased but the staining intensity of the positively staining cells was unchanged compared with control cells. In the ST-IM soleus, the percentage of positively staining fibers was unchanged but the intensity of the positively staining cells was decreased compared with SN values. These results suggest that: 1) isometric contractile activity is more effective than isovelocity activity in preventing suspension-induced shifts in soleus MHC distribution and 2) changes associated with both suspension and training occur in only a small number of fibers, with the majority of fibers apparently unresponsive to these interventions.
Control of malonyl-CoA by glucose and insulin in perfused skeletal muscle
Authors: Duan C. , Winder W. W.
Published: December 2017

This study was designed to determine the effects of glucose and insulin on malonyl-CoA, the potent inhibitor of carnitine palmitoyltransferase I, in the gastrocnemius/plantaris muscle group. Isolated rat hindlimbs were perfused with Krebs-Henseleit bicarbonate buffer containing fresh erythrocytes (hematocrit = 41) and albumin in a flow-through mode for 60 min. Two experiments were performed. In the first, hindlimbs were perfused with medium containing no glucose and no insulin (n = 9) or with medium containing 10 mM glucose and 100 microU/ml of insulin (n = 9). Gastrocnemius/plantaris malonyl-CoA was 0.6 +/- 0.1 nmol/g in the absence of glucose and insulin vs. 1.4 +/- 0.1 nmol/g when both glucose and insulin were added. In the second experiment, hindlimbs were perfused with medium containing 10 mM glucose alone, 200 microU insulin alone, or with a combination of 10 mM glucose and 200 microU/ml of insulin (n = 8 for each). Malonyl-CoA was decreased in gastrocnemius/plantaris perfused with glucose alone (0.7 +/- 0.2 nmol/g) and with insulin alone (0.7 +/- 0.1 nmol/g) compared with hindlimbs perfused with the combination of glucose and insulin (1.4 +/- 0.2 nmol/g). We conclude that both glucose and insulin are required for preventing a decline in muscle malonyl-CoA.
Cardiopulmonary reflexes do not modulate exercise pressor reflexes during isometric exercise in humans
Authors: Arrowood J. A. , Mohanty P. K. , McNamara C. , Thames M. D.
Published: December 2017

Previous studies that measured reflex vasoconstrictor responses during isometric exercise have suggested that these responses were modulated by arterial and cardiopulmonary baroreflexes. The purpose of these experiments was to determine forearm vasoconstrictor responses to isometric handgrip alone and during two levels of cardiopulmonary baroreceptor unloading with lower body negative pressure (-5 and -10 mmHg LBNP). Handgrip combined with -5 mmHg LBNP produced vasoconstrictor responses that were significantly greater than the algebraic sum of the separate responses to handgrip and LBNP alone, thus confirming earlier studies. However, with -10 mmHg LBNP, the vasoconstrictor responses to LBNP plus handgrip were not different from the algebraic sum of the separate response to LBNP and handgrip alone. These results indicate that when the influence of cardiac baroreceptors was reduced to a greater degree (-10 mmHg LBNP) than in previous studies, no interaction was observed, whereas with less reduction (-5 mmHg LBNP) an apparent interaction was noted. These data, together with recent studies in which sympathetic nerve activity to the lower leg was measured during similar protocols, suggest nonlinearities in the relationship between sympathetic nerve activity and vasoconstrictor responses.
Individual airway constrictor response heterogeneity to histamine assessed by high-resolution computed tomography
Authors: Brown R. H. , Herold C. J. , Hirshman C. A. , Zerhouni E. A. , Mitzner W.
Published: December 2017

We directly measured the range of individual airway responses to aerosol and intravenous administration of histamine by using high-resolution computed tomography and then compared the heterogeneity in constriction responses between these two routes. Seven dogs were used for a total of eleven studies. Six of the seven dogs received intravenous histamine (100–300 micrograms/min) and five of the seven dogs received aerosolized histamine (0.01–3.0 mg/ml for 5 breaths). Data were analyzed using linear regression models calculating residual mean square values for each route of histamine as a measure of variability in the change in airway size. The residual mean square values for the absolute airway size after the aerosol and intravenous histamine challenges were 17.73 and 15.42, respectively, which were not significantly different [F(331,166) = 1.15, P = 0.32]. Also, there were no significant differences when we compared the log or the percent change in airway area for the two routes of administration. We conclude that the route of histamine administration does not significantly affect the heterogeneity of airway response, suggesting that the heterogeneity observed after the histamine challenge is predominantly controlled by local mechanisms in the airways.
Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans
Authors: MacLean D. A. , Graham T. E.
Published: December 2017

This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/- 80 microM (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microM for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration.
Carbohydrate feedings and exercise performance: effect of initial muscle glycogen concentration
Authors: Widrick J. J. , Costill D. L. , Fink W. J. , Hickey M. S. , McConell G. K. , Tanaka H.
Published: December 2017

To determine whether the ergogenic benefits of carbohydrate (CHO) feedings are affected by preexercise muscle glycogen levels, eight cyclists performed four self-paced time trials on an isokinetic ergometer over a simulated distance of 70 km. Trials were performed under the following preexercise muscle glycogen and beverage conditions: 1) high glycogen (180.2 +/- 9.7 mmol/kg wet wt) with a CHO beverage (HG-CHO), 2) high glycogen (170.2 +/- 10.4 mmol/kg wet wt) with a non-CHO beverage (HG-NCHO), 3) low glycogen (99.8 +/- 6.0 mmol/kg wet wt) with a CHO beverage (LG-CHO), and 4) low glycogen (109.7 +/- 5.3 mmol/kg wet wt) with a non-CHO beverage (LG-NCHO). The CHO drink (ingested at the onset of exercise and every 10 km thereafter) provided 116 +/- 6 g CHO/trial and prevented the decline in serum glucose observed during both NCHO trials. Performance times ranged from 117.93 +/- 1.44 (HG-CHO) to 122.91 +/- 2.46 min (LG-NCHO). No intertrial differences (P > 0.05) were observed for O2 consumption (75% of maximal O2 consumption), power output (237 W), or self-selected pace (8.44 min/5 km) during the initial 71–79% of exercise. Over the final 14% of the time trial, power output and pace (231 W and 8.62 min/5 km) were similar for the HG-CHO, HG-NCHO, and LG-CHO conditions, but both variables were significantly lower during the LG-NCHO trial (198 W and 9.67 min/5 km, P < 0.05 vs. all other trials).(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of gastric and diaphragmatic height during slow breathing maneuvers
Authors: Marchesseault L. , Mungiole M. , Loring S. H.
Published: December 2017

Changes in height of the gastric air bubble can be inferred, in theory, from the difference between gastric pressures measured with water- and air-filled balloon-catheter systems. We describe an apparatus that satisfactorily measures changes in height of gastric balloons in vitro. During slow breathing maneuvers in standing subjects, the apparatus measured changes in height of the balloons in the stomach that were consistent with expected changes in height of the diaphragmatic dome. In four subjects, balloon movements were nearly always less than movements of the costal margin of the diaphragmatic dome observed by ultrasonography; the average ratio of height changes was 0.73. We conclude that changes in height of the diaphragmatic dome can be measured with this method during slow breathing maneuvers in upright subjects.
Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity
Authors: Prisk G. K. , Guy H. J. , Elliott A. R. , Deutschman R. A. , West J. B.
Published: December 2017

We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to 9 days of microgravity (weightlessness, 0 G). The same subjects were studied standing and supine numerous times preflight and in the week immediately after return from space. DL in microgravity was elevated (28%) compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc (28%) and Dm (27%). The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value (which was unchanged). We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to 8 days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased (18%) inflight and decreased (9%) post-flight compared with preflight standing. Compared with preflight standing, SV was increased 46% inflight and decreased 14% in the 1st wk postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.
Metabolic, hemodynamic, and ventilatory responses to respiratory load in sedated neonatal piglets
Authors: Duara S. , Suguihara C. , Gerhardt T. , Bancalari E.
Published: December 2017

Some neonatal species fail to develop the expected degree of hypercapnia during hypoventilation with mechanical loads. We studied 13 spontaneously breathing, sedated piglets (1–9 days old), grouped by age as young (< or = 3 day old) or old (> 3 day old). Baseline measurements of minute ventilation, arterial blood pressure (BP), cardiac output, and O2 consumption were repeated after continuous (inspiratory and expiratory) flow-resistive loading of 330 cmH2O.l-1 x s for 10 min. Older animals [n = 6, age 6.6 +/- 1.9 (SD) days, wt 1.99 +/- 0.5 kg] increased metabolic rate (9.8 +/- 1.4 to 10.5 +/- 1.3 ml.min-1 x kg-1, P < 0.01), whereas younger animals (n = 7, 2.6 +/- 0.6 days, 1.37 +2- 0.3 kg) invariably decreased metabolic rate with loading (9.7 +/- 1.6 to 7.9 +/- 2.6 ml.min-1 x kg-1); changes were different between groups (P < 0.02). Although ventilation decreased with loading in both groups (P < 0.01), younger animals showed a relatively greater fall from baseline values (38 vs. 27%). Despite differences in the degree of hypoventilation, arterial CO2 tension increased similarly in both groups (21%). BP increased (P < 0.01) with loading in older but not younger animals. We conclude that the decreased metabolic rate and limited hemodynamic response in younger piglets reflect an accomodative response to hypoventilation in contrast to that of older animals, which display an adult pattern of increased metabolic rate and BP with loaded breathing.
Morphometry of the dog pulmonary venous tree
Authors: Gan R. Z. , Tian Y. , Yen R. T. , Kassab G. S.
Published: December 2017

The biophysical approach to the study of blood flow in the pulmonary vasculature requires a detailed description of vascular geometry and branching pattern. The description of the pulmonary venous morphometry in the dog is the focus of this paper. Silicone elastomer casts of a dog lung were made and were used to measure the diameters, lengths, and branching pattern of the pulmonary venous vasculature. The anatomic data are presented statistically with a diameter-defined Strahler ordering scheme, a rule for assigning the order numbers of the vessels on the basis of a diameter criterion. The asymmetric branching pattern of the pulmonary venous vasculature is described with a connectivity matrix. Results show that for the dog's right pulmonary venous tree 1) a total of 11 orders of vessels lay between the left atrium and the capillary bed; 2) the average ratios of the diameter, length, and number of branches of successive orders of veins were 1.701, 1.556, and 3.762, respectively; and 3) a fractal description of the tree geometry resulted in diameter and length fractal dimensions of 2.49 and 2.99, respectively. The morphometric data were used to compute the cross-sectional area, vascular volume, and Poiseuillean resistance in the venous vessels.
Central cardiovascular pressures during graded water immersion in humans
Authors: Gabrielsen A. , Johansen L. B. , Norsk P.
Published: December 2017

Thermoneutral (34.9 degrees C) water immersion (WI) was conducted with 12 upright seated normal males at four consecutive water levels (5–10 min each): knee (reference), xiphoid process, fourth intercostal space, and sternoclavicular notch. Thereafter, water was let out of the tank and the experiment was repeated from the neck to the knees at the same levels. Arterial pulse pressure (PP), central venous pressure (CVP), and transmural CVP (TCVP = CVP - esophageal pressure; n = 4) gradually increased with increasing water levels (P < 0.05). Heart rate (HR) decreased at WI to the xiphoid process (P < 0.05) and thereafter remained at this level, whereas mean arterial pressure remained unchanged. There was a closer linear correlation between HR and PP (r = -0.35, P < 0.01) than between HR and CVP (r = -0.13, P > 0.05). Furthermore, there was a significant positive linear correlation between CVP and TCVP (r = 0.83, P < 0.01). We conclude that WI in humans induces an increase in cardiac filling pressures with an increase in PP and a consequent decrease in HR. Furthermore, changes in CVP accurately reflect changes in cardiac distension (TCVP) during WI.
Exercise increases inflammatory macrophage antitumor cytotoxicity
Authors: Woods J. A. , Davis J. M. , Mayer E. P. , Ghaffar A. , Pate R. R.
Published: December 2017

This study determined the effects of exercise on the ability of inflammatory macrophages to inhibit tumor cell growth in vitro (macrophage cytotoxicity). Thioglycollate injection (1 ml ip) was used as an inflammatory challenge and to partially activate macrophages for cytotoxicity. Inbred male C3H/HeN mice (n = 180) exercised moderately (MOD, 18 m/min, 30 min/day, 5% grade) or to exhaustion (EXH, 18–35 m/min, 2–4 h, 5% grade) on a motor-driven treadmill for 3 consecutive days after injection. Control (CON) mice were kept in stimulated treadmill lanes directly over the runners. Mice were killed immediately or 3 or 8 h postexercise. Macrophages from both MOD and EXH exercise groups manifested significantly (P < 0.05) enhanced (approximately 50%) cytotoxicity compared with those from CON group at all time points postexercise. This potentially beneficial exercise effect was not related to macrophage production of interleukin-1 beta, reactive nitrogen or oxygen intermediates, or number of macrophages in the assay but may have been manifested, in part, by tumor necrosis factor-alpha. Plasma corticosterone was significantly elevated immediately postexercise in MOD and EXH compared with CON mice; however, no evidence existed for an immuno-suppressive effect of corticosterone on macrophage cytotoxicity, perhaps because of insensitivity of inflammatory macrophages to glucocorticoid suppression seen in vitro. These data only partially support the "inverted U hypothesis," which states that moderate exercise may enhance, whereas very heavy exercise or a lack of exercise may attenuate, the immune response. Further study is needed to determine the physiological significance of these findings and the effects of exercise on macrophage subsets sensitive to glucocorticoid suppression (i.e., fully activated macrophages).
Isoproterenol antagonizes endothelial permeability induced by thrombin and thrombin receptor peptide
Authors: Minnear F. L. , DeMichele M. A. , Leonhardt S. , Andersen T. T. , Teitler M.
Published: December 2017

We determined whether 1) amino-terminal peptides of the thrombin receptor increase endothelial permeability to a comparable extent as alpha-thrombin does, 2) isoproterenol attenuates the thrombin-induced increase in endothelial permeability by an antagonistic action to that of thrombin or by lowering baseline permeability, and 3) isoproterenol decreases permeability via stimulation of the beta 2-adrenergic receptor. Permeability across monolayers of bovine pulmonary artery endothelial cells (CCL 209) was assessed by the clearance of 125I-labeled albumin. Thrombin receptor peptides increased permeability at 1 microM but required a dose of between 10 and 100 microM to equal the permeability response of 1 microM alpha-thrombin. Dose-response experiments demonstrated that isoproterenol antagonized the action of alpha-thrombin and a thrombin receptor peptide on endothelial permeability and that it lowered baseline permeability. This permeability-decreasing action of isoproterenol occurred via stimulation of the beta 2-adrenergic receptor. Terbutaline, a partial beta 2-agonist, prevented the thrombin-induced permeability, but dobutamine, a partial beta 1-agonist, did not. The active stereoisomer of terbutaline and the racemic form mimicked the action of isoproterenol, but the inactive stereoisomer had no effect. ICI-118,551, a specific beta 2-receptor antagonist, prevented the permeability-decreasing action of isoproterenol, whereas ICI-89,406, a specific beta 1-receptor antagonist, did not. Competitive binding studies of 125I-pindolol with ICI-118,551 or ICI-89,406 demonstrated the presence of beta-adrenergic receptors, predominantly beta 2-receptors, on cell membrane homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
Urea kinetics in humans at two levels of exercise intensity
Authors: Carraro F. , Kimbrough T. D. , Wolfe R. R.
Published: December 2017

A primed constant infusion of [15N2]urea was used to quantify the response of urea production to exercise at 40 and 70% maximal oxygen consumption on a treadmill. Total urea production, urea production from recycled N, urea production from nonrecycled N, and urea N recycled back into body protein were calculated. Most components of urea kinetics were unaffected by exercise at either intensity. The rate of urea reincorporated into protein was significantly increased during exercise and recovery at both levels of exercise. We conclude that exercise does not stimulate urea production but that there may be an accelerated reincorporation of urea N back into body protein.
Role of protein intake on protein synthesis and fiber distribution in the unweighted soleus muscle
Authors: Taillandier D. , Bigard X. , Desplanches D. , Attaix D. , Guezennec C. Y. , Arnal M.
Published: December 2017

Protein turnover in skeletal muscle is very sensitive to protein intake. To examine whether protein intake is able to affect protein synthesis in the atrophied soleus muscle, the effects of a high-protein (30%, HP) and a medium-protein (15%, MP) diet were studied in rats after 21 days of hindlimb unweighting. Three weeks of unweighting induced a sharp decrease in food intake (30%). The fractional rate of protein synthesis (ks) was determined in vivo in the slow-twitch soleus muscle by use of a flooding-dose method. With respect to pair-fed animals, a significant reduction in ks occurred (33%) in MP non-weight-bearing rats, whereas it was of lesser magnitude and not significant in HP rats. In the atrophied soleus muscle of non-weight-bearing MP rats, a large decrease (42%) in type I fiber distribution was accompanied by an increase in intermediate and type IIa fibers. By contrast, a higher percentage of type I fiber was maintained with the HP diet. However, the HP diet had no beneficial effect in preventing the decrease in either type I fiber cross-sectional area (65%) or the average decrease in absolute myofibrillar and mitochondrial volumes (69 and 52%, respectively). These results demonstrate that an HP intake did not prevent soleus muscle atrophy but may sustain protein synthesis and partly preserve fiber type distribution without affecting the ultrastructural composition of fibers. Because the circulating level of free 3,5,3'-triiodothyronine was reduced by 14% with the HP diet, this effect on fiber type distribution, and possibly protein synthesis, may involve thyroid hormones.
Interaction of aerobic exercise training and clenbuterol: effects on insulin-resistant muscle
Authors: Torgan C. E. , Etgen G. J. , Brozinick J. T. , Wilcox R. E. , Ivy J. L.
Published: December 2017

The effects of aerobic exercise training, chronic administration of the selective beta 2-adrenergic agonist clenbuterol, and the combination of these two treatments on muscle insulin resistance were compared in female obese (fa/fa) Zucker rats. Rats were randomly assigned to trained, clenbuterol, clenbuterol-trained, or control groups. Training consisted of treadmill running for 2 h/day at 18 m/min up an 8% grade. Clenbuterol was administered by intubation (0.4–0.8 mg.kg body wt-1 x day-1) approximately 30 min before the rats ran each day. After 8 wk of treatment, muscle insulin resistance was assessed via hindlimb perfusion in the presence of 8 mM glucose and a submaximal (500 microU/ml) insulin concentration. Training increased citrate synthase activity (mumol.g wet wt-1 x min-1) by 32–74% and insulin-stimulated glucose uptake by 45%. Clenbuterol ingestion induced a 17–29% increase in muscle mass but decreased citrate synthase activity by 34–42% and had no effect on muscle glucose uptake. Administration of clenbuterol to rats that exercise trained prevented the training-induced improvement in insulin-stimulated glucose uptake and attenuated the increases in citrate synthase activity. In addition, both clenbuterol-treated groups displayed a 42% decrease in beta-adrenergic receptor density. The results indicate that clenbuterol administration, possibly through beta-adrenergic receptor downregulation, attenuated a cellular reaction essential for the exercise training-induced increase in citrate synthase activity and improvement in skeletal muscle insulin resistance of the obese Zucker rat.
Carnitine delays rat skeletal muscle fatigue in vitro
Authors: Brass E. P. , Scarrow A. M. , Ruff L. J. , Masterson K. A. , Van Lunteren E.
Published: December 2017

Carnitine has been used to enhance human exercise performance. To test the hypothesis that carnitine can directly modify skeletal muscle function, fatigue of isolated rat skeletal muscle strips was studied in vitro. Carnitine (10 mM) did not modify the initial force of soleus contraction. The time over which force declined by 50% during repetitive electrical stimulation of the soleus muscle (fiber type I) was prolonged 25% in the presence of 10 mM carnitine. In contrast, carnitine had no effect on the fatigue of extensor digitorum longus muscle strips (fiber type II). The beneficial effect of carnitine on soleus muscle strips was not observed if the routine 30-min preincubation in the presence of carnitine was decreased to 5 min; it was associated with a five- to sixfold increase in muscle total carnitine content and a 50#x2013;150% increase in muscle long-chain acylcarnitine content. Carnitine did not consistently modify lactate accumulation or glycogen depletion during the fatigue protocol. Incubation with propionyl-L-carnitine resulted in a decreased initial force of contraction and a delay in reaching maximal contractile force. Thus, carnitine can directly improve the fatigue characteristics of muscles enriched in type I fibers.
Interaction among cardiac, respiratory, and locomotor rhythms during cardiolocomotor synchronization
Authors: Niizeki K. , Kawahara K. , Miyamoto Y.
Published: December 2017

The nature of entrainment between cardiac and locomotor rhythms was investigated while normal human subjects walked or ran on a treadmill. To detect the incidence of entrainment occurrence, the phase relationships among cardiac, respiratory, and locomotor rhythms were analyzed. The phase relationship between heartbeats and gait signals showed that entrainment of cardiac rhythm to locomotor rhythm occurred in all subjects at one or more treadmill speeds. To elucidate interactions among cardiac, respiratory, and locomotor rhythms during the cardiolocomotor synchronization, spectral and coherence analyses were done for these three rhythms. Spectral and coherence analyses on fluctuations in the heart period and respiratory rhythms revealed that the strength of coupling between cardiac and respiratory rhythms decreased in the presence of cardiolocomotor synchronization. In addition, the coupling of cardiac and locomotor rhythms appeared to induce dissociation of coupling between respiratory and locomotor rhythms. These results were similar to those observed when stepping was voluntarily synchronized with cardiac rhythm. Possible mechanisms to explain coordination and interaction among the neural oscillators innervating these three rhythms are discussed.
Effect of ventilation frequency and tidal volume on pleural space thickness in rabbits
Authors: Wang P. M. , Lai-Fook S. J.
Published: December 2017

The thickness of the pleural space was measured by fluorescence video-microscopy during mechanical ventilation in anesthetized paralyzed rabbits. A transparent parietal pleural window was made in the fourth or sixth intercostal space near midchest by dissection of intercostal muscle and endothoracic fascia. Fluorescence-labeled (fluorescein isothiocyanate) dextran solution (1 ml) was injected into the pleural space via a rib capsule and allowed to mix with the pleural liquid. With the rabbit in the left lateral decubitus position and the pleural window superior, the light emitted from the pleural liquid through the pleural window was measured through the videomicroscope. Both ventilation frequency and tidal volume were varied. Pleural space thickness was determined by in vitro calibration of the pleural liquid at the end of the experiment. At a frequency of 40 breaths/min and a tidal volume of 20 ml, pleural space thickness averaged 35 +/- 15 (SD) microns (n = 7). When frequency was reduced to 8 breaths/min, this value was reduced by 40% to 22 +/- 11 microns. A reduction in tidal volume from 20 to 6 ml at a frequency of 40 breaths/min produced a similar reduction in pleural space thickness. During apnea, pleural space thickness averaged 11 +/- 3 microns. Cardiogenic motion had no measurable effect on pleural space thickness. The increased pleural space thickness with ventilation might serve to reduce the power dissipated due to sliding of the lung relative to the chest wall. Results support the concept of lubrication as the primary function of the pleural space.
Responsiveness of the guinea pig trachea to stretch: role of the epithelium and cyclooxygenase products
Authors: Gao Y. , Vanhoutte P. M.
Published: December 2017

The role of the epithelium and cyclooxygenase products was investigated in the responses of isolated airways to sudden stretch. Strips of guinea pig trachea, in some of which the epithelium had been removed mechanically, were suspended in organ chambers; isometric tension was recorded. After rapid stretching to their optimal tension, the preparations (with and without epithelium) relaxed initially and then contracted to a level close to the imposed tension. Afterward, tissues with epithelium maintained this level of tension, but those without epithelium relaxed. After treatment with papaverine or isoproterenol (at concentrations causing maximal relaxation), stretch was followed only by a decrease in tension; a similar response to stretch was also obtained in tissues treated with indomethacin or acetylsalicylic acid (inhibitors of cyclooxygenase). Dazmegrel (an inhibitor of thromboxane synthase) and SQ-29548 (an antagonist of prostaglandin H2 or thromboxane A2 receptors) did not affect the response of tissues with epithelium but abolished the stretch-induced contraction in those without epithelium. Tranylcypromine, which inhibits prostacyclin synthase, and tetrodotoxin, which blocks local reflexes, did not significantly affect the responses of the tissues to stretch. These observations suggest that thromboxane may mediate the epithelium-independent contraction and that another product of cyclooxygenase contributes to the maintenance of tension on stretching observed in tissues with epithelium.
Gender differences in leucine kinetics and nitrogen balance in endurance athletes
Authors: Phillips S. M. , Atkinson S. A. , Tarnopolsky M. A. , MacDougall J. D.
Published: December 2017

The current Canadian Recommended Nutrient Intake (RNI) for protein (0.86 g.kg-1.day-1) makes no allowance for an effect of habitual physical activity. In addition, Tarnopolsky et al. (J. Appl. Physiol. 68: 302–308, 1990) showed that males may catabolize more protein than females consequent to endurance exercise. We examined nitrogen (N) balance and leucine kinetics during submaximal endurance exercise to determine the adequacy of the current Canadian RNI for protein for male and female endurance athletes. Athletes were matched for equal training volume, competitive status, and conditioning and were fed diets isoenergetic with their habitual intake, containing protein at the Canadian RNI. Subjects were adapted to the diet for 10 days before completing a 3-day measurement of N balance. N balance showed that the RNI was inadequate for females (-15.9 +/- 6.0 mg.kg-1.day-1) and males (-26.3 +/- 11.0 mg.kg-1.day-1). Leucine kinetics during exercise were determined for each subject on day 3 of the N balance experiment by use of a primed continuous infusion of L-[1–13C]leucine and the reciprocal pool model. Exercise resulted in a significant (P < 0.01) increase in leucine oxidation for both groups. Males oxidized a greater amount of leucine during the infusion than females (P < 0.01). Leucine flux also increased significantly (P < 0.01) during exercise in both groups. We conclude that the current Canadian RNI for protein is inadequate for those who chronically engage in endurance exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of effects of exercise and hyperventilation on leukocyte kinetics in humans
Authors: Fairbarn M. S. , Blackie S. P. , Pardy R. L. , Hogg J. C.
Published: December 2017

The circulating leukocyte (WBC) count increases with exercise, because WBCs enter the circulation from the marginated pool. The lung is a major source of the demarginating cells, but it is unclear whether this occurs because of increased ventilatory movements, increased cardiac output, or both. The present study examined the mechanical effect of ventilation (VE) in six healthy men with three different protocols on three separate occasions. First, the subjects cycled for 5-min intervals at 50, 100, 150, and 200 W, and we measured heart rate (HR), minute ventilation (VE), tidal volume (VT), respiratory rate, and end-tidal CO2. Second, each subject reproduced his exercise VE by matching VT, respiratory rate, and end-tidal CO2 on a circuit designed for isocapnic hyperpnea (matched VE). The subjects then performed a hyperventilation (hyper-VE) protocol with a minimum VT of 1.5 liters and a respiratory rate of 20 breaths/min. Blood samples were drawn at rest and throughout each protocol for measurement of WBCs, hematocrit, and band cells. During cycling, VE increased (9 +/- 1 to 66 +/- 7 l/min), HR increased (71 +/- 7 to 172 +/- 10 beats/min), and WBCs increased (5.5 +/- 0.9 to 7.8 +/- 1.3 x 10(9)/l). During matched VE, VE increased (11 +/- 2 to 69 +/- 11 l/min), but neither HR nor WBCs increased (67 +/- 13 to 78 +/- 12 beats/min and 5.3 +/- 1.6 to 5.7 +/- 1.5 x 10(9)/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary interstitial edema in the pig after heavy exercise
Authors: Schaffartzik W. , Arcos J. , Tsukimoto K. , Mathieu-Costello O. , Wagner P. D.
Published: December 2017

During exercise (especially in hypoxia), the alveolar-arterial O2 tension difference increases. This impairment of pulmonary gas exchange is caused partly by diffusion disequilibrium, but it has also been shown that an exercise-induced increase in ventilation-perfusion (VA/Q) inequality develops. Possible explanations of increased VA/Q mismatch include nonuniform pulmonary vasoconstriction, reduced gas mixing in the large airways, airway obstruction, and the development of interstitial pulmonary edema. To directly determine whether the latter develops in high-intensity short-term exercise, we exercised pigs on a motor-driven treadmill at the highest speed that they could sustain for 6–7 min. Heart rate reached 274 +/- 5 min-1 in the exercised group, confirming that the pigs reached a near-maximal level of exercise. While running, the pigs were killed by an intravenous overdose of pentobarbital. Postmortem, the lungs were immediately removed, drained of blood, weighed, and then airway fixed with 10% formaldehyde. Four tissue blocks of the right lung of each pig were taken from the ventral and dorsal areas of the upper and lower lobes, respectively. They were stained with hematoxylin and eosin and prepared for histological examination by light microscopy. There was no difference in the lung-to-body weight ratio between exercised pigs (7.72 +/- 0.87 g/kg) and a nonexercised control group (7.70 +/- 0.68 g/kg). However, we found a significantly higher percentage of pulmonary arteries with perivascular edema in exercised (33.8 +/- 3.4%) than in nonexercised pigs (20.0 +/- 4.0%; P < 0.02). Thus, perivascular edema (and thus possibly also parenchymal interstitial edema) can occur during short-term heavy exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung inflation distends small arteries (< 1 mm) in excised dog lungs
Authors: Albert R. K. , Lamm W. J. , Rickaby D. A. , al-Tinawi A. , Dawson C. A.
Published: December 2017

We utilized microfocal fluoroscopic angiography to study the influence of lung inflation on small (0.2- to 1.3-mm-diam) pulmonary arteries in isolated left lower lobes from dog lungs during both flow and no-flow conditions. Alveolar pressure, which in this preparation was equal to transpulmonary pressure, was set at 2, 8, or 14 mmHg while vascular pressure was varied from 0 to 24 mmHg. The diameters of these small arterial vessels increased with lung inflation. No differences were observed between the results obtained during flow and no-flow conditions. Thus, arteries in this diameter range can be considered as extra-alveolar, and the effect of lung inflation on these small extra-alveolar arteries was qualitatively similar to that previously described for larger extra-alveolar vessels. Quantitatively, the degree of vessel distension was about the same per unit increase in transpulmonary pressure at constant vascular pressure as for a change in vascular pressure at constant transpulmonary pressure. Accordingly, inflation produced a decrease in perivascular pressure surrounding these small arteries that was approximately equal to the increase in transpulmonary pressure.
Hypercapnic ventilatory responses in mice differentially susceptible to acute ozone exposure
Authors: Tankersley C. G. , Fitzgerald R. S. , Mitzner W. A. , Kleeberger S. R.
Published: December 2017

Susceptibility to ozone (O3)-induced pulmonary inflammation is greater in C57BL/6J (B6) than in C3H/HeJ (C3) strain of mice. We tested the hypothesis that altered ventilatory control occurs in B6 mice to a greater extent than in C3 mice after acute O3 exposure. Age-, sex-, and weight-matched C3 and B6 mice were exposed for 3 h to either 2 ppm O3 or filtered air. One and 24 h after O3 or air exposure, whole body plethysmography was used to measure breathing frequency (f), tidal volume (VT), and minute ventilation (VE). To assess changes in ventilatory control, mice were challenged by the elevation of fractional concentration of inspired CO2 levels to 5 and 8% in air for 10 min. After air exposure, there were significantly (P < 0.01) greater changes in VE in B6 than in C3 mice. Hypercapnia-induced changes in VE were significantly (P < 0.01) attenuated in B6 mice 1 h after O3 exposure. VT was significantly (P < 0.01) reduced 1 h after O3 in B6 and C3 mice; however, C3 mice increased f to sustain the hypercapnic VE response similar to air exposure. In contrast, the diminished VT in B6 mice 1 h after O3 occurred coincident with significantly (P < 0.01) reduced f, mean inspiratory flow, and slope of VE-to-%CO2 relationship compared with air exposure. Altered hypercapnic VE in B6 mice was partially reversed 24 h after O3 relative to air-exposed levels. These data suggest that control of ventilation during phenotypic response to CO2 is governed, in part, by genetic factors in inbred strains of mice.(ABSTRACT TRUNCATED AT 250 WORDS)