bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of ventilation and pleural effusion on measurements of airway thermal volume and blood flow in dog lungs
Authors: Kano A. , Kambara K. , Arakawa M. , Ando F. , Ohno M. , Tsuchiya M. , Nishigaki K. , Fujiwara H.
Published: December 2017

We studied the effects of ventilation and pleural effusion on measurements of airway thermal volume (ATV) and pulmonary blood flow (PBF) by using the airway gas thermometry method of V. B. Serikov, M. S. Rumm, K. Kambara, M. I. Bootomo, A. R. Osmack, and N. C. Staub (J. Appl. Physiol. 72: 944–953, 1992) in 39 anesthetized dogs with or without lung edema or pleural effusion. To examine the differential effects of increased-pressure and increased-permeability lung edema on accuracy and sensitivity of ATV and PBF, two models of lung edema were induced by intravenous infusion of a Dextran 70 solution and alloxan monohydrate, respectively. Dogs were hyperventilated for 3 min by using a wide range of minute ventilation (VE) to produce two steady-state conditions of airway temperature. Higher levels of VE increased an estimated amount of ATV. The ATV produced by hyperventilation at VE values of 559, 158, and 72 ml.min-1.kg-1 was consistent with the gravimetric total lung mass, the blood-free wet lung weight, and the extravascular lung water volume, respectively. The coefficient of lung thermal conductivity, a practical index of the rate of heat conduction through tissue from lung vessels, was related to the ratio of the decrease in expired air temperature to VE, and estimated PBF was consistent with the thermodilution cardiac output. Pleural effusion had little effect on measurements of ATV and PBF. However, ATV and PBF showed increased variation in dogs with dextran-induced lung edema.
Hormonal secretion during nighttime sleep indicating stress of daytime exercise
Authors: Kern W. , Perras B. , Wodick R. , Fehm H. L. , Born J.
Published: December 2017

We tested the hypothesis that long-duration exercise (LDE) of moderate intensity, but not LDE of low intensity, during the daytime changes the typical temporal patterns of hormone release during subsequent nocturnal sleep. Ten trained healthy men participated in a balanced crossover study including three conditions: 1) no exercise, 2) LDE of low intensity (biking 40 km; 1800–2030), and 3) LDE of moderate intensity (biking 120–150 km; 1600–2030). During the subsequent night (2300–0700), somnopolygraphic sleep recordings were obtained, and concentrations of cortisol, growth hormone (GH), and testosterone were measured every 15 min. During the no exercise nights, the typical secretory patterns were present with peak concentrations of GH but nadir concentrations of cortisol during the first half of sleep but increased cortisol levels and minimum GH levels during the second part of sleep. Testosterone concentrations increased during the second half of sleep. LDE of moderate intensity reduced rapid-eye-movement sleep [13.9 vs. 16.9% (no exercise); P < 0.01]. Levels of testosterone decreased with increasing intensity of daytime exercise (P < 0.05). Moderate-, but not low-intensity, LDE decreased GH levels in the first half (P < 0.05) and increased GH levels in the second half (P < 0.005) of sleep. Also, LDE of moderate intensity but not LDE of low intensity increased cortisol levels during the first half (P < 0.005) and decreased cortisol secretion during the second half (P < 0.05) of sleep. Results suggest that nocturnal profiles of GH and cortisol concentrations may serve to indicate the disturbance of normal anabolic functions of sleep due to daytime exercise.
Effect of 7-10 days of cycle ergometer exercise on skeletal muscle GLUT-4 protein content
Authors: Gulve E. A. , Spina R. J.
Published: December 2017

Previous studies in animals and humans have shown that endurance exercise-training protocols of several weeks to many months in duration induce adaptive increases in skeletal muscle GLUT-4 protein concentration. It is generally assumed that the increase in GLUT-4 concentration is a long-term adaptation to training. The present study examined whether 7–10 days of cycle ergometer exercise could induce increases in skeletal muscle GLUT-4 levels. Eight healthy subjects (4 men, 4 women) aged 31 +/- 2 (SE) yr exercised 2 h daily at 65–70% of peak O2 uptake (VO2peak) for either 7 (n = 3) or 10 (n = 5) consecutive days. Muscle biopsies (vastus lateralis) were obtained before initiation of the exercise program and 36–48 h after the final bout of exercise. Glucose transporter protein was quantitated by Western blotting using antiserum specific for GLUT-4. VO2peak was increased by 10% (from 3.0 +/- 0.2 to 3.3 +/- 0.2 l/min; P < 0.01) in response to the training. Body weight did not change (74.3 +/- 4.6 before vs. 75.0 +/- 4.2 kg after) as a result of training. Muscle GLUT-4 immunoreactivity was increased 98% (from 584 +/- 50 to 1,154 +/- 40 counts per minute 125I/25 micrograms protein; P < 0.001) in response to training. Increase in VO2peak and GLUT-4 protein were similar for 7 and 10 days of training. These results suggest that, given an adequate training stimulus, adaptations in skeletal muscle GLUT-4 protein occur very rapidly. Furthermore, the increase in GLUT-4 after 7–10 days of exercise is as large as that reported in studies employing long-term training protocols.
Growth hormone does not prevent corticosteroid-induced changes in rat diaphragm structure and function
Authors: Petrof B. J. , Gottfried S. B. , Eby J. , Lamanca J. , Levine S.
Published: December 2017

The present study tested the hypothesis that growth hormone (GH), an anabolic agent, could prevent the abnormalities of diaphragm structure and function associated with short-term administration of the corticosteroid triamcinolone (TR). During a 10-day period, male rats (n = 33) were assigned to control (CTL), TR (1 mg.kg-1.day-1 im), and TR-GH (2 mg.kg-1.day-1 im) groups. Diaphragm weight was significantly reduced in the TR and TR-GH animals compared with the CTL animals, but there was no difference in the diaphragm-to-body weight ratio. Fiber type (I, IIa, and IIx/b) proportions did not differ among the three groups. However, in TR rats there was a significant reduction in the contribution of type IIx/b fibers to total diaphragm cross-sectional area due to marked atrophy (approximately 42% decrease in mean fiber cross-sectional area). There was no significant reversal of TR-induced type IIx/b fiber atrophy by concomitant GH administration. TR and TR-GH groups both exhibited a left-ward shift of the force-frequency relationship and enhanced in vitro fatigue resistance, whereas maximal specific force was unaltered. We conclude that GH does not prevent corticosteroid-induced effects on the diaphragm under these conditions, possibly as a result of reduced nutritional intake associated with TR administration.
Myoneural interactions affect diaphragm muscle adaptations to inactivity
Authors: Miyata H. , Zhan W. Z. , Prakash Y. S. , Sieck G. C.
Published: December 2017

We hypothesized that inactivity effects on diaphragm muscle contractile and morphometric properties are attenuated if phrenic motoneurons are also inactive. Three models of rat diaphragm inactivity were compared: 1) spinal isolation; 2) tetrodotoxin (TTX) nerve blockade; and 3) denervation (Dnv). Motoneuron and muscle fiber inactivities were matched only in spinal isolated animals. After 2 wk, maximum tetanic force decreased in all three groups compared with control group but to a greater extent in TTX and Dnv animals. Fatigue resistance improved, and maximum unloaded shortening velocity slowed only in TTX and Dnv groups. Type IIa fiber proportions decreased in all three groups, and type IIx fiber proportions increased in TTX and Dnv animals. Type I fiber cross-sectional area increased in all three groups but to a greater extent in TTX and Dnv animals. Type IIa fibers hypertrophied, whereas type IIx and IIb fibers atrophied only in TTX and Dnv groups. These results support the hypothesis that muscle adaptations to prolonged inactivity are attenuated when muscle fiber and motoneuron inactivities are matched.
Prolonged stimulation of respiration by brain stem metabotropic glutamate receptors
Authors: Li A. , Nattie E. E.
Published: December 2017

Stimulation of metabotropic glutamate receptors (mGluRs) in the retrotrapezoid nucleus (RTN) of chloralose-urethan-anesthetized rats by the mGluR agonist (1S,3R)-aminocyclopentanedicarboxylic acid [(1S,3R)-ACPD; 10 nl, 1 mM] increases integrated phrenic nerve amplitude (PNA) for > 60 min. Here we ask if the mGluR antagonist (+-)-alpha-methyl-4-carboxyphenylglycine [(+-)-MCPG] can block this effect. Using multibarreled micropipettes, we first identified RTN sites that affect respiration by noting short-lived stimulation of PNA produced by brief-duration injection of glutamate (10 nl, 100 mM), a presumed ionotropic receptor response. We then injected the active or inactive isomer of (+-)-MCPG (10 nl, 10 mM) followed by (1S,3R)-ACPD or by a long-duration (60-s) injection of glutamate (10 nl, 100 mM) at the same site. Each injection location was verified anatomically. The active antagonist (+-)-MCPG itself had no significant effect on PNA, but it blocked 1) subsequent (1S,3R)-ACPD-induced PNA stimulation for 99 +/- 11 (SE) min and 2) the PNA response to 60-s glutamate injection for 66 +/- 6 min. The inactive form (-)-MCPG had no effect on (1S,3R)-ACPD-induced PNA stimulation. We conclude that 1) RTN mGluRs may be involved in respiratory control, 2) RTN mGluRs are not active in eupnea, and 3) stimulation of RTN mGluRs may require prolonged glutamate release.
Pulmonary chemoreflex sensitivity is enhanced by prostaglandin E2 in anesthetized rats
Authors: Lee L. Y. , Morton R. F.
Published: December 2017

Stimulation of vagal pulmonary C-fiber afferents by chemical irritants is believed to be responsible for eliciting the pulmonary chemoreflex (apnea, bradycardia, and hypotension). This study was carried out in anesthetized Sprague-Dawley rats to determine whether the pulmonary chemoreflex was altered by prostaglandin E2 (PGE2), which is one of the major inflammatory mediators in the lungs and is known to enhance the sensitivity of C-fiber afferents in several other organ systems. Capsaicin injected at a dose just above the stimulation threshold (0.25 or 0.5 microgram/kg i.v.) elicited a very mild respiratory and cardiovascular depression. In sharp contrast, during a constant infusion of PGE2 (1.5 micrograms.kg-1.min-1 i.v.), the same dose of capsaicin triggered a long apnea, with the expiratory duration reaching 843% of the baseline expiratory duration, accompanied by intense bradycardia and hypotension. Similarly, the pulmonary chemoreflex response elicited by a bolus injection of phenyl biguanide (1 or 2 micrograms/kg i.v.) was also greatly augmented by PGE2. These enhanced responses were completely abolished, by a perineural capsaicin treatment of both cervical vagi to selectively block the conduction of C fibers, suggesting the involvement of these afferents. Electrophysiological recording of pulmonary C-fiber afferent activity further supported our conclusion that the sensitivity of these sensory endings to capsaicin challenge was potentiated by PGE2.
Expression of ICAM-1 in airway epithelium after acute ozone exposure in the mouse
Authors: Takahashi N. , Yu X. Y. , Schofield B. H. , Kleeberger S. R. , Scott A. L. , Hasegawa S. , Spannhake E. W.
Published: December 2017

We investigated the time course and regional distribution of the expression of intercellular adhesion molecule-1 (ICAM-1) on airway epithelial cells and the polymorphonuclear leukocyte (PMN) inflammatory response in the lung after acute exposure to ozone (O3). C57BL/6J mice were exposed to air or 2 ppm O3 for 3 h and killed immediately or 3, 6, 9, or 21 h after exposure. Expression of ICAM-1 was examined by immunohistochemical staining of frozen sections. PMN influx was evaluated by lavage and by histochemical staining of myeloperoxidase (MPO) and measurement of tissue MPO activity. ICAM-1 expression exhibited regional selectivity and temporal patterns that were unique to each region. Upregulation of ICAM-1 expression on the epithelial cells in the trachea, and to a lesser extent in the lobar and segmental bronchi, was observed 3–9 h after exposure and remained present at 21 h. Enhanced ICAM-1 expression in bronchioles and terminal bronchiole/alveolar duct regions was evident earlier (immediately to 3 h after exposure) but returned to baseline levels by 21 and 9 h, respectively. Maximal ICAM-1 expression and PMN influx in the lung parenchyma were concurrently observed at 3 h, followed by transepithelial migration of PMNs to the airway lumen. These results demonstrate regional variations in airway inflammatory activity and are supportive of the notion that upregulation of ICAM-1 on the airway epithelium may play a role in local regulation of PMN influx to the airways after acute O3 exposure.
Influence of simulated microgravity on cardiac output and blood flow distribution during exercise
Authors: Woodman C. R. , Sebastian L. A. , Tipton C. M.
Published: December 2017

Rats exposed to simulated conditions of microgravity by head-down suspension (HDS) exhibit reductions in aerobic capacity. This may be due to an impaired ability to augment cardiac output and to redistribute blood flow during exercise. The purpose of this investigation was to measure cardiac output and blood flow distribution in rats that were exposed to 14 days of HDS or cage control conditions. Measurements were obtained at rest and during light-intensity (15 m/min) and heavy-intensity (25 m/min; 10% grade) treadmill exercise. Cardiac output was similar in HDS and cage control rats at rest and light exercise but was significantly lower in HDS rats (-33%) during heavy exercise. Soleus muscle blood flow (ml/min) was lower at rest and during exercise in HDS rats; however, when expressed relative to muscle mass (ml.min-1.100 g-1), soleus blood flow was lower only during light exercise. Plantaris muscle blood flow was lower in HDS rats during heavy exercise. Blood flow to the ankle flexor, knee extensor, and knee flexor muscles was not altered by HDS. Blood flow to the spleen and kidney was significantly higher in HDS rats. It was concluded that the reduction in aerobic capacity associated with HDS is due in part to an impaired ability to augment cardiac output during exercise.
Effects of physical properties of the breathing gas on decompression-sickness bubbles
Authors: Burkard M. E. , Van Liew H. D.
Published: December 2017

To explore the relative dangers of different inert gases, we developed mathematical relationships concerned with bubble growth, using equations that separate gas properties from other variables. Predictions for saturation exposures were as follows. 1) Peak volume of a bubble is proportional to solubility in tissue when bubble density is high and to the 3/2 power of the ratio of the permeation coefficient to the partition coefficient when density is low. 2) Bubble duration is inversely proportional to the partition coefficient for the inert gas. 3). Sizes and durations of bubbles for one inert gas relative to another depend on whether the tissue is aqueous or lipid but are independent of the magnitude of the decompression and tissue half time. 4). He should give smaller bubbles than N2, except in aqueous tissue with low bubble density; our prediction correlates qualitatively with relative dangers observed with animals but seems to overestimate the safety afforded by He. Numerical simulations illustrate how nonsaturation dives are less predictable because more variables are involved.
Increased clearance of lactate after short-term training in men
Authors: Phillips S. M. , Green H. J. , Tarnopolsky M. A. , Grant S. M.
Published: December 2017

A short-term training model previously shown to result in a tighter metabolic control in working muscle in the absence of an increase in mitochondrial potential was used to examine changes in lactate turnover. Lactate flux was studied before and after 10 days of cycle training [2 h/day at 59% maximal oxygen consumption (VO2max)] in untrained men [VO2max = 45.5 +/- 2.4 (SE) ml.kg-1.min-1). A primed constant infusion of L-[1–13C]lactate was used to examine lactate kinetics during a prolonged exercise protocol (90 min at 59% VO2max). Rate of appearance of lactate increased with exercise (P < 0.01), both pretraining (rest = 30.3 +/- 4.9 ml.kg-1.min-1, exercise = 115 +/- 14 ml.kg-1.min-1) and posttraining (rest = 28.4 +/- 4.7 ml.kg-1.min-1, exercise = 112 +/- 13 ml.kg-1.min-1). Despite a lower blood lactate concentration (P < 0.05) during exercise after training, there was no difference in the rate of appearance of lactate. Training increased (P < 0.05) the metabolic clearance rate of lactate during exercise from 36.8 +/- 4.8 to 51.4 +/- 6.8 ml.kg-1.min-1. These findings indicate that at least part of the lower exercising blood lactate observed after training is due to an increase in metabolic clearance rate. In addition, the lower intramuscular lactate levels suggest a decreased recruitment of glycolysis particularly early in exercise.
Role of ventilatory response to exercise in determining exercise capacity in COPD
Authors: Bauerle O. , Younes M.
Published: December 2017

The progression of chronic obstructive pulmonary disease (COPD) is generally associated with decreased exercise capacity. Differences in forced expired volume in 1 s (FEV1) among patients account for only a fraction of the variability in maximal oxygen consumption (VO2max). We hypothesized that variability in ventilatory response to exercise and in inspiratory mechanics and body mass index contributes importantly to variability in VO2max in this disease. We analyzed the files of 53 patients with established diagnosis of COPD who underwent a recent symptom-limited exercise test. We used inspiratory capacity and maximum inspiratory flow as measures of variability in inspiratory mechanics. The minute ventilation (VE) at the subject's VO2max was divided by the predicted in a normal subject at the same VO2 to obtain a ratio (VE,max/VE,pred). The ventilatory response during exercise provided the best correlation with peak VO2 (r = 0.62). FEV1 and inspiratory capacity also correlated with peak oxygen consumption but not as well as the ventilatory response (r = 0.49 and r = 0.46, respectively). Maximum inspiratory flow and body mass index showed only weak positive correlations (r = 0.23, not significant). The stepwise analysis generated the following equation: VO2max (%predicted) = (77.26 x VE,pred/VE,max) + [0.45 x FEV1 (%predicted)] - 23.66; r = 0.76, P < 0.001. We conclude that variability in the ventilatory response during exercise is one of the main determinants of variability in exercise capacity in COPD patients.
Role of tryptase in immediate cutaneous responses in allergic sheep
Authors: Molinari J. F. , Moore W. R. , Clark J. , Tanaka R. , Butterfield J. H. , Abraham W. M.
Published: December 2017

In this study, we used a specific tryptase inhibitor, APC-366 [N-(1-hydroxy-2-napthoyl)-L-arginyl-L- prolinamide hydrochloride] to investigate the effect of intradermally administered tryptase and tryptase released by antigen challenge on the immediate cutaneous reaction (ICR) in allergic sheep. The surface areas of cutaneous wheals produced by intradermal injections (0.05 ml) of 1 and 10 ng tryptase alone, tryptase combined with 3 U heparin (tryptase-heparin), or Ascaris suum antigen (10(-5) dilution) with or without pretreatment with APC-366 (1 mg/ml) were measured at 20 and 60 min after challenge. Intradermal injections of 1 and 10 ng tryptase alone (n = 7) produced an ICR of < or = 20% of that obtained after injection of histamine (5% wt/vol). Intradermal injection of tryptase-heparin (n = 7), however, resulted in 50 (1 ng) and 82% (10 ng) of the ICR to histamine (both, P < 0.05 vs. tryptase alone). APC-366 inhibited (P < 0.05) the ICR to 1 and 10 ng tryptase-heparin by > or = 70% at all times (n = 8) but had no effect on the histamine-induced ICR (n = 3). A combination of the histamine H1 antagonist chlorpheniramine (2 mg/kg iv) and the H2 antagonist metiamide (3 mg/kg iv) given 40 min before challenge (n = 8) inhibited the response to 1 and 10 ng tryptase-heparin by 42 and 62% at 20 min and by 96 and 86% at 60 min, respectively (all, P < 0.05). APC-366 also blocked the ICR to A. suum antigen by 68% (P < 0.05) in nine sheep. These results indicate that intradermal injection of tryptase-heparin can induce an ICR. This ICR can be inhibited by APC-366 or a combination of the histamine H1 and H2 antagonists, suggesting that the tryptase response is mediated by histamine. APC-366 also blocks the mast cell-mediated ICR to intradermally injected A. suum antigen. Collectively, these results suggest that tryptase may modulate mast cell histamine release.
Altered beta-adrenergic and cholinergic pulmonary vascular responses after total cardiopulmonary bypass
Authors: Friedman M. , Wang S. Y. , Stahl G. L. , Johnson R. G. , Sellke F. W.
Published: December 2017

Cardiopulmonary bypass (CPB) is often followed by pulmonary hypertension, but the effects of extracorporeal circulation on vascular reactivity remain largely unknown. In this study, the influence of total CPB (t-CPB) on beta-adrenergic and cholinergic receptor-mediated pulmonary microvascular responses was examined. Sheep were placed on t-CPB without ventilation. After 90 min, sheep were separated from t-CPB and the lungs were perfused normally for 60 min. Pulmonary artery infusion of acetylcholine (muscarinic cholinergic agonist, ACh) increased pulmonary vascular resistance significantly more and isoproterenol (beta-adrenergic agonist, Iso) decreased pulmonary vascular resistance less after than before t-CPB. The response to sodium nitroprusside (SNP, guanylate cyclase activator) was similar before and after t-CPB. Relaxations (in vitro) of isolated pressurized (20 mmHg) microvessels to Iso and ACh were markedly reduced after t-CPB. Treatment with NPC-15669 (N-[9H-(2,7,-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine) did not affect these changes in vessel reactivity, although leukocyte sequestration in the lungs was reduced with the drug. The in vitro response to forskolin (adenylate cyclase activator) and SNP was similar before and after t-CPB. Complement-activated serum caused microvessels to contract in response to ACh, but it had no effect on Iso, forskolin, or SNP responses, suggesting that activation of the alternate complement pathway causes a selective reduction in endothelium-dependent relaxation. We conclude that t-CPB impairs cholinergic and beta-adrenergic pulmonary vascular responses due to effects at the level of the transmembrane receptor or coupling to the second messenger systems.
Estimation of arterial PCO2 in the elderly
Authors: St Croix C. M. , Cunningham D. A. , Kowalchuk J. M. , McConnell A. K. , Kirby A. S. , Scheuermann B. W. , Petrella R. J. , Paterson D. H.
Published: December 2017

Arterial PCO2 (PaCO2), determined directly in the radial artery, was compared with indirect estimates of PCO2 in six elderly men (mean age 73.8 yr). Estimates of PaCO2 included arterialized venous PCO2 (PavCO2); end-tidal PCO2; mean alveolar PCO2, calculated by using a reconstruction of the alveolar oscillation in PCO2 and accounting for the presence of dead space (time-weighted mean for PCO2 throughout the respiratory cycle); and values calculated by using the empirical formula developed by Jones et al. (N. L. Jones, D. G. Robertson, and J. W. Kane. J. Appl. Physiol. 47: 954–960, 1979), which incorporates end-tidal PCO2 and tidal volume (PaCO2 derived from end-tidal PCO2 and VT). Measurements were made at rest and during cycle ergometry at 25 and 50 W while the subjects breathed various gas mixtures (euoxic-eucapnic, hypoxic-eucapnic, hyperoxic-eucapnic, and hyperoxic-hypercapnic). The mean differences between the estimates and the actual PaCO2 at rest and in 25- and 50-W exercise were as follows: PavCO2, 0.3 +/- 0.7 (SD), -0.1 +/- 0.7, and 1.8 +/- 1.2 Torr; end-tidal PCO2, 2.9 +/- 1.7, 4.0 +/- 3.1, and 3.7 +/- 3.2 Torr; time-weighted mean of alveolar PCO2, 2.6 +/- 1.9, 3.3 +/- 3.1, and 3.6 +/- 3.8 Torr; and PaCO2 derived from end-tidal PCO2 and VT, 2.4 +/- 1.3, 1.3 +/- 3.0, and 0.6 +/- 2.9 Torr. It is concluded that mean PavCO2 agreed most closely with mean PaCO2 both at rest and in exercise. All methods of deriving PaCO2 using measurements from the respired gases overestimated arterial values at rest. Of the noninvasive techniques, mean estimates calculated using the regression equation developed by Jones et al. corresponded most closely with PaCO2 in exercise.
Lung water measurement by nuclear magnetic resonance: correlation with morphometry
Authors: Cutillo A. G. , Goodrich K. C. , Ganesan K. , Watanabe S. , Ailion D. C. , Albertine K. H. , Morris A. H. , Durney C. H.
Published: December 2017

Estimates of lung water content obtained from nuclear magnetic resonance (NMR) and morphometric and gravimetric measurements were compared in normal and experimentally injured rats. Average lung water density (rho H2O) was measured by an NMR technique in excised unperfused rat lungs (20 normal lungs and 12 lungs with oleic acid-induced edema) at 0 (full passive deflation) and 30 cmH2O lung inflation pressure and in vivo (4 normal rats and 8 rats with lung injury induced by oleic acid or rapid saline infusion). The rho H2O values were compared with morphometric measurements of lung tissue volume density (Vv) obtained from the same lungs fixed at corresponding liquid-instillation pressures. A close correlation was observed between rho H2O and Vv in normal and injured excised lungs [correlation coefficient (r) = 0.910, P < 0.01]. In vivo rho H2O was also closely correlated with Vv (r = 0.897, P < 0.01). The correlation coefficients between rho H2O and gravimetric lung water content (LWGr) were lower in the excised lung group (r = 0.663 and 0.692, respectively, for rho H2O at 0 and 30 cmH2O lung inflation pressure, P < 0.01) than in the in vivo study (r = 0.857, P < 0.01). Our results indicate that NMR techniques, which are noninvasive and nondestructive, provide reliable estimates of lung water density and that the influence of lung inflation on rho H2O is important (compared with the effect of lung water accumulation in lung injury) only in the presence of deliberately induced very large variations in the lung inflation level.
Architectural modifications and cellular response during disuse-related bone loss in calcaneus of the sheep
Authors: Thomas T. , Vico L. , Skerry T. M. , Caulin F. , Lanyon L. E. , Alexandre C. , Lafage M. H.
Published: December 2017

The results of simple biomechanical unloading in models of acute-disuse osteoporosis are influenced by systemic and regional effects of the method used to generate the bone loss. A model in which strain-gauge measurements confirmed that the os calcis was unloaded in healthy ewes during ambulation was assessed by histomorphometry. Twelve nonovariectomized adult female Welsh mountain sheep were submitted to hock joint immobilization by an external fixation procedure from the tibia to the metatarsus for a period of 12 wk. Histomorphometric analysis showed that this model was able to produce pure local bone loss, as transiliac bone biopsies failed to reveal any difference between the initial and final results. Immobilized and nonimmobilized calcanei were both removed postmortem. After the 12 wk of the study, osteoclastic activity was increased in accordance with the usual disuse process. An unexpected increase of osteoblastic activity was also observed, possibly related to recovery after the initial dramatic bone loss, but an artifact of the surgical procedure such as a regional acceleration phenomenon cannot be definitively excluded. However, the increased osteoblastic activity was not sufficient to prevent accentuation of the negative bone balance, resulting in a 29% decrease of trabecular bone volume in immobilized calcanei compared with nonimmobilized calcanei. This reduction was due to thinning of trabeculae (72.4 +/- 12.1 vs. 98.9 +/- 15.9 microns; P < 0.05) without any change in trabecular number (2.74 +/- 0.72 vs. 2.79 +/- 0.40/mm2; not significant). In conclusion, this model only locally increased both osteoclastic and osteoblastic activities leading to bone loss and architectural modifications. The decreased bone formation usually observed in other models of disuse osteoporosis may therefore not constitute a local phenomenon generated by unloading.
Blocked ETA receptors prevent ischemia and reperfusion injury in rat lungs
Authors: Khimenko P. L. , Moore T. M. , Taylor A. E.
Published: December 2017

The effects of endothelin (ET)-A (ETA)- and ETB-receptor agonist and antagonists were studied in isolated buffer-perfused rat lungs subjected to 45 min of ischemia followed by 105 min of reperfusion (I/R). For the I/R group after 30 and 90 min of reperfusion, the Kfc had increased three- and fivefold above control values, respectively (P < 0.01), and the number of circulating neutrophils in the perfusate decreased by 65 +/- 7.65%. Both an ETA-receptor antagonist (BQ-610) and an ETAB-receptor antagonist (PD-156707-0015) given before the ischemic period protected the lung endothelial barrier from injury associated with I/R. Also, these compounds attenuated the I/R-induced neutrophil accumulation in the lung (31.94 +/- 4.16 and 34.38 +/- 1.05%, respectively; P < 0.01 compared with I/R). Neither an ETB-receptor agonist (IRL-1620) nor an ETB-receptor antagonist (IRL-1038) affected the I/R-induced endothelial injury. In addition, they did not alter the number of circulating polymorphonuclear cells during I/R. ET-1 administration alone caused a dose-dependent increase in pulmonary arterial pressure, but no measurable increase in microvascular permeability occurred. We conclude that ET-1 is involved in I/R-induced lung endothelial injury and speculate that it acts in concert with some other coactivator(s), most likely platelet-activating factor, through ETA receptors. This mechanism requires polymorphonuclear leukocyte activation with subsequent release of oxygen radicals and/or expression of adhesive molecules on the neutrophil surface.
Effects of exercise training on responses of peripheral and visceral arteries in swine
Authors: McAllister R. M. , Kimani J. K. , Webster J. L. , Parker J. L. , Laughlin M. H.
Published: December 2017

Blood flow to skeletal muscle during exercise is greater in the trained state. We hypothesized that intrinsic vasomotor reactivity of arteries to active muscle during training bouts would be altered to favor a relative vasodilation after training. To test this hypothesis, miniature swine were pen confined (Sed; n = 30) or treadmill trained for 5 days/wk over 16-20 wk (Trn; n = 32). Efficacy of training was indicated by myocardial hypertrophy (4.84 +/- 0.11 and 5.81 +/- 0.12 g/kg body wt for Sed and Trn, respectively, P < 0.0005), training bradycardia at several submaximal running speeds of a maximal exercise test, increased running time to exhaustion (26 +/- 1 and 35 +/- 1 min for Sed and Trn, respectively, P < 0.0005), and increased oxidative capacities of several locomotory skeletal muscles. Segments of femoral, brachial, mesenteric, renal, and hepatic arteries were isolated from Sed and Trn swine. Isometric contractile and relaxation properties of vascular rings cut from these segments were determined in vitro. Contractile responses to KCl and norepinephrine (NE) were determined, as were relaxation responses to sodium nitroprusside and adenosine, agents acting directly on vascular smooth muscle, and the endothelium-dependent agents bradykinin and the calcium ionophore A-23187. Responses to vasocontractile and vasorelaxation agents were not different between Sed and Trn swine for vessels serving active muscles (i.e., femoral, brachial). On the other hand, renal arterial rings from Trn swine exhibited lesser contractile responses than those from Sed swine across a range of NE concentrations (P < 0.05) and approximately 25% less maximal contractile response to NE (32.7 +/- 2.6 and 24.2 +/- 2.1 g for Sed and Trn, respectively, P < 0.01). Responses of other vessels serving viscera (i.e., mesenteric, hepatic) were unchanged with training. These data indicate that vasomotor reactivity of porcine conduit-type arteries generally does not change with exercise training. An exception is the lesser contractile response to NE in renal artery, which could permit better preservation of renal blood flow during acute exercise in trained animals.
Effect of past gymnastics participation on adult bone mass
Authors: Kirchner E. M. , Lewis R. D. , O'Connor P. J.
Published: December 2017

The purposes of this study were to determine bone mineral density (BMD) of former female college gymnasts (FG; n = 18) and controls (FC; n = 15) by using dual-energy X-ray absorptiometry (Hologic QDR 1000W) and to examine the relationships between current and former activity levels, diet, menstrual history and BMD. Current physical activity, dietary intake, and menstrual irregularity were assessed with the use of standardized questionnaires. A study-designed questionnaire was used to assess past physical activity. The BMDs of the FG were significantly higher (P < 0.001) than the BMDs of FC for the lumbar spine, femoral neck, Ward's triangle, and whole body, even when the influences of current and past physical activity levels were statistically controlled via analysis of covariance. FG and FC did not differ in nutrient intakes, and there were no BMD differences between FG who always had regular menstrual cycles vs. those who had an interruption (= or = 3 mo) of their menstrual cycle in the past. The higher BMD in FG compared with FC suggests that past participation in college gymnastics may provide a residual effect on adult BMD.
Nitric oxide and cGMP do not affect fluid flux in isolated rat lungs
Authors: Eichinger M. R. , Walker B. R.
Published: December 2017

We sought to examine the influence of nitric oxide (NO) and the second messengers guanosine 3′,5′-cyclic monophosphate (cGMP) and intracellular Ca2+ on fluid flux in lungs isolated from male Sprague-Dawley rats and perfused with saline (containing 4% albumin) or with whole blood. Lungs were allowed to equilibrate for a period of 30 min without treatment (control group) or with one of the following agents: the exogenous NO donor spermine NONOate, the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA), 8-BrcGMP, the Ca2- ionophore ionomycin, or the endothelial injurious agent protamine. After equilibration, perfusate reservoir height was increased to five incremental settings to increase pulmonary venous pressure and enhance fluid flux. Perfusate reservoir weight was monitored continuously as an index of fluid flux. The lung wet-to-dry weight ratio was determined on completion of the experiments. Increasing reservoir height was associated with an increase in pulmonary arterial, pulmonary capillary, and pulmonary venous pressures and an increase in fluid flux. However, treatment with exogenous NO or inhibition of endogenous NO was without effect on fluid flux in saline lungs at two different flow rates or in whole blood-perfused lungs. Similarly, treatment with cGMP and ionomycin did not alter fluid flux. Protamine pretreatment resulted in a significant increase in fluid flux at the highest reservoir setting, although exogenous NO and L-NNA pretreatments were without further effect on the protamine-treated lungs. Thus a role for NO and the second messengers cGMP and Ca2+ in modulating fluid flux could not be demonstrated in the isolated rat lung.
Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone is modulated by potassium channels
Authors: Barman S. A.
Published: December 2017

The role of K+ channels on the pressor effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood-perfused dog lungs when vascular tone was elevated with U-46619: 1) 10(-6) M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca(2+)-dependent K+ channels; and 3) 10(-4) M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10(-8) M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4-aminopyridine at elevated vascular tone significantly potentiated the pressor effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca(2+)-dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca(2+)-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.
Effects of changes in dietary fatty acids on isolated skeletal muscle functions in rats
Authors: Ayre K. J. , Hulbert A. J.
Published: December 2017

The effects of manipulating dietary levels of essential polyunsaturated fatty acids on the function of isolated skeletal muscles in male Wistar rats were examined. Three isoenergetic diets were used: an essential fatty acid-deficient diet (EFAD), a diet high in essential (n-6) fatty acids [High (n-6)], and a diet enriched with essential (n-3) fatty acids [High (n-3)]. After 9 wk, groups of rats on each test diet were fed a stock diet of laboratory chow for a further 6 wk. Muscle function was examined by using a battery of five tests for soleus (slow twitch) and extensor digitorum longus (EDL; fast twitch). Tests included single muscle twitches, sustained tetanic contractions, posttetanic potentiation, sustained high-frequency stimulation, and intermittent low-frequency stimulation. Results for muscles from the High (n-6) and High (n-3) groups were very similar. However, the EFAD diet resulted in significantly lower muscular tensions and reduced response times compared with the High (n-6) and High (n-3) diets. Peak twitch tension in soleus muscles was 16-21% less in the EFAD group than in the High (n-6) and High (n-3) groups, respectively [analysis of variance (ANOVA), P < 0.01). During high-frequency stimulation, EDL muscles from the EFAD rats fatigued 32% more quickly (ANOVA, P < 0.01)]. Also, twitch contraction and half-relaxation times were significantly 5-7% reduced in the EFAD group (ANOVA, P < 0.01). During intermittent low-frequency stimulation, soleus muscles from the EFAD group generated 25-28% less tension than did the other groups (ANOVA, P < 0.01), but in EDL muscles from the EFAD group, endurance was 20% greater than in the High (n-6) group (ANOVA, P < 0.05). After 6 wk on the stock diet, there were no longer any differences between the dietary groups. Manipulation of dietary fatty acids results in significant, but reversible, effects in muscles of rats fed an EFAD diet.
Enhanced beta-adrenergic-mediated cardiovascular responses in endurance athletes
Authors: Hopkins M. G. , Spina R. J. , Ehsani A. A.
Published: December 2017

To determine whether the adaptive increase in left ventricular systolic function in the trained state is mediated by enhanced responses to beta-adrenergic stimulation, we studied eight male endurance athletes [age 27 +/- 1.8 yr; maximal O2 uptake (VO2max) 60 +/- 0.9 (SE) ml x kg-1 x min-1] and eight sedentary men (age 27 +/- 1.4 yr; VO2max 43.1 +/- 1.7 ml x kg-1 x min-1). Left ventricular function was evaluated with two-dimensional echocardiography and pulsed Doppler transmitral flow velocity profile in the basal state, after parasympathetic blockade by atropine, and during infusion of dobutamine. Cardiac output and stroke volume, determined with the acetylene rebreathing technique, during maximal exercise were significantly higher in the endurance athletes than in the sedentary men (28.9 +/- 1.7 vs. 23 +/- 1.23 1/min, P = 0.019, and 162 +/- 12 vs. 125 +/- 7 ml/min, P = 0.029). Endurance athletes showed physiological volume overload-left ventricular hypertrophy and greater enhancements of left ventricular systolic function and filling dynamics in response to dobutamine than did the sedentary men as reflected in 1) a steeper slope of the fractional shortening-end-systolic wall stress relationship (-0.986 +/- 0.16 vs. -0.508 +/- 0.054, P = 0.014, athletes vs. controls) and 2) a higher early-to-late transmitral diastolic Doppler velocity ratio (2.14 +/- 0.14 vs. 1.74 +/- 0.12, P = 0.016) at a comparable heart rate. Although endurance athletes had a significantly greater inotropic response to dobutamine, they demonstrated a markedly attenuated chronotropic response to beta1-adrenergic stimulation compared with sedentary subjects. Our findings suggest that, even with a blunted chronotropic response, endurance-trained young men show an augmented inotropic response to a beta1-adrenergic agonist that, along with physiological volume overload hypertrophy and increased diastolic filling, can contribute to a larger stroke volume during maximal exercise in the trained state.
Contribution of PO2, P50, and Hb to changes in arteriovenous O2 content during exercise in heart failure
Authors: Perego G. B. , Marenzi G. C. , Guazzi M. , Sganzerla P. , Assanelli E. , Palermo P. , Conconi B. , Lauri G. , Agostoni P. G.
Published: December 2017

Arteriovenous O2 content (a-vCO2) differences increase during exercise in normal subjects through several mechanisms including PO2, O2 pressure at which hemoglobin (Hb) is half saturated with O2 (P50), and Hb concentration changes. The present study was undertaken to evaluate how much these biochemical changes are relevant to a-vCO2 difference through exercise in patients with heart failure. Twenty-seven patients with congestive heart failure [10 patients in functional class A (peak exercise O2 uptake =20 ml x kg-1 x min-1), 9 in class B (20-15 ml x kg-1 x min-1), and 8 in class C (15-10 ml x kg-1 x min-1)] underwent a cardiopulmonary exercise test with once-per-minute simultaneous blood sampling from the pulmonary and systemic arteries for determination of Hb, PO2, PCO2, pH, O2 content (CO2), Hb saturation and lactic acid (pulmonary artery only), and calculation of P50. Analysis of data was done at six exercise stages: the first at rest, the last at peak exercise, and the second to the fifth at one-, two-, three-, and four-fifths of O2 consumption increase. a-vCO2 difference at peak exercise was 14.3 +/- 2.1, 16.9 +/- 2.4, and 14.7 +/- 2.1 (SD) ml/dl in class A, B, and C patients, respectively. The contribution of Hb, P50, and PO2 changes to the increments of a-vCO2 difference during exercise was 21, 17, and 63%, respectively; the only interclass difference observed was for P50, which plays a greater role in a-vCO2 difference in class A. Hb changes act mainly at the arterial site, whereas P50 and PO2 act at the venous site. Hb increase was constant through the test, venous P50 increase was greater above anaerobic threshold, and venous PO2 reduction was most remarkable at the onset of exercise; in class C patients, no venous PO2 change was recorded in the second half of exercise. Thus a-vCO2 difference increase during exercise is notable in patients with heart failure but unrelated to the severity of the syndrome. Hb, P50, and, to the greatest degree, PO2 changes participate in the increment of a-vCO2 difference. In class C patients, the lack of PO2 reduction in the second half of exercise suggests the achievement of a “whole body critical venous PO2.”
Increased myosin light chain kinase content in sensitized canine saphenous vein
Authors: Liu G. , Liu X. , Rao K. , Jiang H. , Stephens N. L.
Published: December 2017

Our previous studies revealed that smooth muscle from sensitized canine saphenous vein (SCSV) demonstrated greater active shortening capacity, maximum shortening velocity, and prolonged relaxation vis-a-vis the control muscle. These changes could be responsible for the in vivo hyperreactivity of venous smooth muscle observed in anaphylactic shock. Because smooth muscle cross-bridge cycling is regulated by myosin light chain kinase (MLCK)-dependent phosphorylation of the 20-kDa myosin light chain (MLC20), we studied MLC20 and MLCK phosphorylation in homogenates of SCSV and veins from littermate control dogs. We found that phosphorylation of MLC20 in SCSV homogenate was higher (42.26 +/- 5.10%) compared with control homogenates (26.69 +/- 3.30%; P < 0.05); MLCK content was significantly higher in SCSV homogenates [0.169 +/- 0.019 (SE) mu g/mg protein] than in control homogenates (0.075 +/- 0.004 mu g/mg protein; P < 0.05). Total MLCK activity increased from 6.16 +/- 0.60 x 10(-5) nmol Pi x mg fresh weight of tissue-1 x min-1 in control homogenates to 12.50 +/- 2.50 x 10(-5) nmol Pi x mg fresh weight of tissue-1 x min-1 in sensitized homogenates (P < 0.05). Specific MLCK activity was, however, similar in sensitized and control homogenates. The results of our study suggest that elevation of MLCK content in the homogenate could account for the increased contractility of the SCSV in anaphylactic shock.
Brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats
Authors: Kao T. Y. , Lin M. T.
Published: December 2017

To explore the importance of brain serotonin (5-hydroxytryptamine) in the heatstroke-induced cerebral ischemia and neuronal injury, we evaluated the effects of heatstroke on brain serotonin release, survival time, cerebral hemodynamic changes, and neuronal cell damage in rats with or without brain serotonin depletion produced by 5,7-dihydroxytryptamine. In vivo voltammetry was used to measure changes in extracellular concentrations of serotonin in the anterior hypothalamus, striatum, and frontal cortex. After the onset of heatstroke, rats without brain serotonin depletion displayed hyperthermia, decreased mean arterial pressure, increased intracranial pressure, decreased cerebral perfusion pressure, decreased cerebral blood flow, increased cerebral serotonin release, and increased cerebral neuronal damage compared with those of normothermic control rats. However, when the cerebral serotonin system was destroyed by 5,7-dihydroxytryptamine, the heatstroke-induced arterial hypotension, intracranial hypertension, ischemic damage to the brain, and elevated cerebral serotonin release were reduced. In addition, the survival time of the heatstroke rats was prolonged after the depletion of brain serotonin. The data indicate that brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats.