bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation varies among the knee extensor muscles during a submaximal fatiguing contraction in the seated and supine postures
Authors: Rochette L , Hunter S. K. , Place N , Lepers R
Published: March 2015

Ten young men sustained an isometric contraction of the knee extensor muscles at 20% of the maximum voluntary contraction (MVC) torque on three separate occasions in a seated posture. Subjects performed an isometric knee extension contraction on a fourth occasion in a supine posture. The time to task failure for the seated posture was similar across sessions (291 ± 84 s; P > 0.05), and the MVC torque was similarly reduced across sessions after the fatiguing contraction (42 ± 12%). The rate of increase in electromyograph (EMG) activity (%MVC) and torque fluctuations during the fatiguing contractions were similar across sessions. However, the rate of increase in EMG differed among the knee extensor muscles: the rectus femoris began at a greater amplitude (31.5 ± 11.0%) compared with the vastus lateralis and vastus medialis muscles (18.8 ± 5.3%), but it ended at a similar value (45.4 ± 3.1%). The time to task failure and increase in EMG activity were similar for the seated and supine tasks; however, the reduction in MVC torque was greater for the seated posture. These findings indicate that the time to task failure for the knee extensor muscles that have a common tendon insertion did not alter over repeat sessions as had been observed for the elbow flexor muscles (Hunter SK and Enoka RM. J Appl Physiol 94: 108-118, 2003).
Muscle pump does not enhance blood flow in exercising skeletal muscle
Authors: Hamann Jason J. , Valic Zoran , Buckwalter John B. , Clifford Philip S.
Published: March 2015

The muscle pump theory holds that contraction aids muscle perfusion by emptying the venous circulation, which lowers venous pressure during relaxation and increases the pressure gradient across the muscle. We reasoned that the influence of a reduction in venous pressure could be determined after maximal pharmacological vasodilation, in which the changes in vascular tone would be minimized. Mongrel dogs ( n = 7), instrumented for measurement of hindlimb blood flow, ran on a treadmill during continuous intra-arterial infusion of saline or adenosine (15–35 mg/min). Adenosine infusion was initiated at rest to achieve the highest blood flow possible. Peak hindlimb blood flow during exercise increased from baseline by 438 ± 34 ml/min under saline conditions but decreased by 27 ± 18 ml/min during adenosine infusion. The absence of an increase in blood flow in the vasodilated limb indicates that any change in venous pressure elicited by the muscle pump was not adequate to elevate hindlimb blood flow. The implication of this finding is that the hyperemic response to exercise is primarily attributable to vasodilation in the skeletal muscle vasculature.
C-reactive protein correlates with macrophage accumulation in coronary arteries of hypercholesterolemic pigs
Authors: Turk James R. , Carroll Jeffery A. , Laughlin M. Harold , Thomas Tom R. , Casati Jennifer , Bowles Douglas K. , Sturek Michael
Published: March 2015

A growing body of evidence supports the hypothesis that C-reactive protein (CRP) is a marker of inflammation in coronary artery disease. The purpose of the present study was to test the hypothesis that CRP correlates with macrophage accumulation during the initial stages of coronary vascular disease. Adult male pigs were fed a normal chow (NF) or a high-fat high-cholesterol (HF) diet for 20 wk. After 20 wk, blood was collected for analyses of interleukin-6 (IL-6), CRP, and lipids. After blood collection, the pigs were euthanized and the right coronary arteries (RCA) were harvested and fixed in neutral buffered formalin. Paraffin-embedded sections of RCA were stained immunohistochemically for CRP, scavenger receptor A (SRA), and monocyte chemoattractant protein-1 (MCP-1). All cholesterol fractions were elevated in the HF vs. the NF group ( P < 0.05). There was little or no positive staining for CRP, SRA, or MCP-1 in the RCA of NF pigs, but there was extensive staining in lipidladen macrophage foam cells in the HF pigs. Double staining revealed colocalization of CRP with SRA and CRP with MCP-1 in foam cells. Serum IL-6 was below the assay detection limit in all pigs. Serum CRP correlated directly with plasma total cholesterol ( R = 0.727, P = 0.041) and accumulation of SRA-positive macrophages ( R = 0.938, P < 0.001) in RCA of HF pigs. We conclude that serum CRP correlates with macrophage accumulation and coronary artery disease in hypercholesterolemic pigs.
Lung albumin accumulation is spatially heterogeneous but not correlated with regional pulmonary perfusion
Authors: Gerbino Anthony J. , Glenny Robb W.
Published: March 2015

10.1152/japplphysiol.00353.2001.—The contribution of pulmonary perfusion heterogeneity to the development of regional differences in lung injury and edema is unknown. To test whether regional differences in pulmonary perfusion are associated with regional differences in microvascular function during lung injury, pigs were mechanically ventilated in the prone position and infused with endotoxin ( Escherichia coli 055:B5, 0.15 μg · kg−1 · h−1; n = 8) or saline ( n = 4) for 4 h. Extravascular albumin accumulation and perfusion were measured in multiple ∼0.7-ml lung regions by injecting pigs with radiolabeled albumin and radioactive microspheres, respectively. Extravascular albumin accumulation was spatially heterogeneous but not correlated with regional perfusion. Extravascular albumin accumulation was greater in dorsal than ventral regions, and regions with similar albumin accumulation were spatially clustered. This spatial organization was less evident in endotoxemic than control pigs. We conclude that there are regional differences in lung albumin accumulation that are spatially organized but not mediated by regional differences in pulmonary perfusion. We speculate that regional differences in microvascular pressure or endothelial function may account for the observed distribution of extravascular albumin accumulation.
Influence of sleep state on frequency of swallowing, apnea, and arousal in human infants
Authors: Don Garrick W. , Waters Karen A.
Published: March 2015

Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and measurement of swallowing allowed time-matched analysis of 3,092 swallows, 482 apneas, and 771 arousals in 17 infants aged 1–34 wk. The mean rates of swallowing, apnea, and arousal were significantly different, being 23.3 ± 8.5, 9.4 ± 8.8, and 15.5 ± 10.6 h−1, respectively ( P < 0.001 ANOVA). Swallows occurred before 25.2 ± 7.9% and during 74.8 ± 6.3% of apneas and before 39.8 ± 6.0% and during 60.2 ± 6.0% of arousals. The frequencies of apneas and arousals were both strongly influenced by sleep state (active sleep > indeterminate > quiet sleep, P < 0.001), whether or not the events coincided with swallowing, but swallowing rate showed minimal independent interaction with sleep state. Interactions between swallowing and sleep state were predominantly influenced by the coincidence of swallowing with apnea or arousal.
Effects of hypoxia on rat airway smooth muscle cell proliferation
Authors: Cogo A. , Napolitano G. , Michoud M. C. , Barbon D. Ramos , Ward M. , Martin J. G.
Published: March 2015

Although it is well known that hypoxemia induces pulmonary vasoconstriction and vascular remodeling, due to the proliferation of both vascular smooth muscle cells and fibroblasts, the effects of hypoxemia on airway smooth muscle cells are not well characterized. The present study was designed to assess the in vitro effects of hypoxia (1 or 3% O2) on rat airway smooth muscle cell growth and response to mitogens (PDGF and 5-HT). Cell growth was assessed by cell counting and cell cycle analysis. Compared with normoxia (21% O2), there was a 42.2% increase in the rate of proliferation of cells exposed to 3% O2(72 h, P = 0.006), as well as an enhanced response to PDGF (13.9% increase; P = 0.023) and to 5-HT (17.2% increase; P = 0.039). Exposure to 1% O2(72 h) decreased cell proliferation by 21.0% ( P = 0.017) and reduced the increase in cell proliferation induced by PGDF and 5-HT by 16.2 and 15.7%, respectively ( P = 0.019 and P = 0.011). A significant inhibition in hypoxia-induced cell proliferation was observed after the administration of bisindolylmaleimide GF-109203X (a specific PKC inhibitor) or downregulation of PKC with PMA. Pretreatment with GF-109203X decreased proliferation by 21.5% ( P = 0.004) and PMA by 31.5% ( P = 0.005). These results show that hypoxia induces airway smooth muscle cell proliferation, which is at least partially dependent on PKC activation. They suggest that hypoxia could contribute to airway remodeling in patients suffering from chronic, severe respiratory diseases.
Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats
Authors: Zaninovich Angel A. , Rebagliati Inés , Raíces Marcela , Ricci Conrado , Hagmüller Karl
Published: March 2015

The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4°C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24°C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of β- and α1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3′-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.
Effect of inspiratory muscle strength training on inspiratory motor drive and RREP early peak components
Authors: Huang Chien Hui , Martin A. Daniel , Davenport Paul W.
Published: March 2015

This study investigated the effect of inspiratory muscle strength training (IMST) on inspiratory motor drive [mouth occlusion pressure at 0.1 s (P0.1)] and respiratory-related evoked potentials (RREP). It was hypothesized that, if IMST increased inspiratory muscle strength, inspiratory motor drive would decrease. If motor drive were related to the RREP, it was further hypothesized that an IMST-related decrease in drive would change RREP latency and/or amplitude. Twenty-three subjects received IMST at 75% of their maximal inspiratory pressure (Pimax) with the use of a pressure threshold valve. IMST consisted of four sets of six breaths daily for 4 wk. P0.1and the RREP were recorded before and after IMST. Posttraining, Pimaxincreased significantly by 36.0 ± 2.7%. P0.1decreased significantly by 21.9 ± 5.2%. The increase in Pimaxwas significantly correlated to the decrease in P0.1. RREP peaks P1a, Nf, P1, and N1were identified pre- and post-IMST, and there was no difference in either amplitude or latency for those peaks. These results demonstrate that high-intensity IMST significantly increased Pimax, decreased P0.1, but did not change the RREP.
Time course of hemorheological alterations after heavy anaerobic exercise in untrained human subjects
Authors: Yalcin Ozlem , Erman Alpaslan , Muratli Sedat , Bor-Kucukatay Melek , Baskurt Oguz K.
Published: March 2015

The time course of hemorheological alterations was investigated after heavy anaerobic exercise in untrained male human subjects. The Wingate protocol was performed by each subject, and blood lactate, red blood cell (RBC) deformability and aggregation, white blood cell (WBC) activation, and several hematological parameters were investigated during 24 h after the exercise and compared with preexercise values. Compared with the preexercise value, blood lactate level was found to be ∼10-fold higher immediately after the exercise. There was a transient, significant increment of RBC and WBC counts immediately after exercise that was followed by a decrement of RBC count. There was a second increase of WBC count, accompanied with increased percentages of granulocytes and granulocyte activation, starting 45 min after exercise. RBC deformability was found to be impaired immediately after exercise and remained reduced for at least 12 h; RBC aggregation was also found to be decreased after exercise, with the onset of this decrease delayed by 30 min. The results of this study indicate that a single bout of heavy anaerobic exercise may induce significant hemorheological deterioration lasting for up to 12 h and thus suggest the need to consider such effects in individuals with impaired cardiovascular function.
Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures
Authors: Chang Hung , Lai-Fook Stephen J. , Domino Karen B. , Schimmel Carmel , Hildebrandt Jack , Robertson H. Thomas , Glenny Robb W. , Hlastala Michael P.
Published: March 2015

We aimed to assess the influence of lateral decubitus postures and positive end-expiratory pressure (PEEP) on the regional distribution of ventilation and perfusion. We measured regional ventilation (V˙a) and regional blood flow (Q˙) in six anesthetized, mechanically ventilated dogs in the left (LLD) and right lateral decubitus (RLD) postures with and without 10 cmH2O PEEP. Q˙ was measured by use of intravenously injected 15-μm fluorescent microspheres, and V˙a was measured by aerosolized 1-μm fluorescent microspheres. Fluorescence was analyzed in lung pieces ∼1.7 cm3 in volume. Multiple linear regression analysis was used to evaluate three-dimensional spatial gradients ofQ˙, V˙a, the ratio V˙a/Q˙, and regional Po 2 (PrO2 ) in both lungs. In the LLD posture, a gravity-dependent vertical gradient in Q˙ was observed in both lungs in conjunction with a reduced blood flow and PrO2 to the dependent left lung. Change from the LLD to the RLD or 10 cmH2O PEEP increased localV˙a/Q˙ and PrO2 in the left lung and minimized any role of hypoxia. The greatest reduction in individual lung volume occurred to the left lung in the LLD posture. We conclude that lung distortion caused by the weight of the heart and abdomen is greater in the LLD posture and influences both Q˙ andV˙a, and ultimately gas exchange. In this respect, the smaller left lung was the most susceptible to impaired gas exchange in the LLD posture.
Laryngeal activity during upright vs. supine swallowing
Authors: Barkmeier Julie M. , Bielamowicz Steve , Takeda Naoya , Ludlow Christy L.
Published: March 2015

Previous investigations of human pharyngeal muscle activation patterns during swallowing found a relatively invariant muscle activation onset sequence in the upright position. However, different gravitational forces influence a liquid bolus when supine and could modify the central timing control of laryngeal airway protection during swallowing. The purpose of this study was to determine whether laryngeal muscle onset timing during swallowing differed between the supine and upright positions. Nine subjects performed six swallowing trials with a 2-ml water bolus in each position. Simultaneous electromyographic recordings were obtained from the submental complex (SMC) and the right and left thyroarytenoid (TA) muscles. Regardless of body position, the timing, amplitude, and duration of the TA muscles did not vary relative to the SMC. Therefore, the sequence of TA muscle activation relative to the SMC during swallowing appeared unaffected by gravitational influences.
Peak exercise stroke volume: associations with cardiac structure and diastolic function
Authors: Peterson Linda R. , Rinder Morton R. , Schechtman Kenneth B. , Spina Robert J. , Glover Kathryn L. , Villareal Dennis T. , Ehsani Ali A.
Published: March 2015

One of the most debilitating effects of primary aging is the decline in aerobic exercise capacity. One of its causes is an age-related decline in peak exercise stroke volume. This study's main purpose was to determine the cardiovascular adaptations to aging that most influence peak exercise stroke volume in the elderly. We hypothesized that increased left ventricular (LV) filling and mild concentric LV remodeling would be associated with an increase in peak exercise stroke volume corrected for lean body mass (LBM) and that an increased augmentation index (AI), which is a marker of arterial stiffness, would be associated with a decrease. A second aim was to determine the adaptations to aging that most influence LV concentric remodeling in the elderly. We hypothesized that AI would be a predictor of LV mass/LBM and the LV posterior wall thickness-to-LV radius ratio ( h/ r). We performed a cross-sectional study of cardiac and vascular adaptations to aging in 52 sedentary, elderly subjects. LV filling [as measured by the early-to-late transmitral flow velocity ratio (E/A)] was inversely correlated with and was an independent predictor of peak exercise stroke volume/LBM and was also a predictor of LV remodeling. AI was a predictor of LV remodeling (LV mass/LBM) but not of peak exercise stroke volume/LBM. We conclude that 1) maintenance of LV filling (E/A <1) is associated with a higher peak exercise stroke volume/LBM in very elderly subjects and thus may be a useful adaptation that enhances stroke volume during peak exercise, 2) LV remodeling and AI are less influential on peak exercise stroke volume/LBM, and 3) AI was the most important predictor of LV remodeling.
Bicarbonate attenuates arterial desaturation during maximal exercise in humans
Authors: Nielsen Henning B. , Bredmose Per P. , Strømstad Morten , Volianitis Stefanos , Quistorff Bjørn , Secher Niels H.
Published: March 2015

The contribution of pH to exercise-induced arterial O2 desaturation was evaluated by intravenous infusion of sodium bicarbonate (Bic, 1 M; 200–350 ml) or an equal volume of saline (Sal; 1 M) at a constant infusion rate during a “2,000-m” maximal ergometer row in five male oarsmen. Blood-gas variables were corrected to the increase in blood temperature from 36.5 ± 0.3 to 38.9 ± 0.1°C ( P < 0.05; means ± SE), which was established in a pilot study. During Sal exercise, pH decreased from 7.42 ± 0.01 at rest to 7.07 ± 0.02 but only to 7.34 ± 0.02 ( P < 0.05) during the Bic trial. Arterial Po 2 was reduced from 103.1 ± 0.7 to 88.2 ± 1.3 Torr during exercise with Sal, and this reduction was not significantly affected by Bic. Arterial O2 saturation was 97.5 ± 0.2% at rest and decreased to 89.0 ± 0.7% during Sal exercise but only to 94.1 ± 1% with Bic ( P < 0.05). Arterial Pco 2 was not significantly changed from resting values in the last minute of Sal exercise, but in the Bic trial it increased from 40.5 ± 0.5 to 45.9 ± 2.0 Torr ( P < 0.05). Pulmonary ventilation was lowered during exercise with Bic (155 ± 14 vs. 142 ± 13 l/min; P < 0.05), but the exercise-induced increase in the difference between the end-tidal O2 pressure and arterial Po 2 was similar in the two trials. Also, pulmonary O2 uptake and changes in muscle oxygenation as determined by near-infrared spectrophotometry during exercise were similar. The enlarged blood-buffering capacity after infusion of Bic attenuated acidosis and in turn arterial desaturation during maximal exercise.
Selected Contribution: Carotid body as a model for aging studies: is there a link between oxygen and aging?
Authors: Di Giulio C. , Cacchio M. , Bianchi G. , Rapino C. , Di Ilio C.
Published: March 2015

The carotid body (CB) is the site in the body that triggers awareness of changes in blood oxygen pressure. Aging is characterized by a decrease in oxygen supply to tissues, in reduction of tissue Po2, and in the activity of several enzymes and metabolic factors. The ventilatory response to hypoxia is attenuated with aging related to the age-dependent structure modifications including the basal reduction of oxygen requirements. The aged CB shows an increase in extracellular matrix, a reduction in number and volume of type I cells, and a reduction in volume of mitochondria that was consistent with and similar to that during chronic hypoxia; this phenomenon seems to operate also during aging as shown by the reduced volume of mitochondria in the aged CB. During chronic hypoxia, CB hypertrophy is less evident in aged CB than in young CB. Therefore, hypoxia and aging seem to share some type of link at different cell sites. CB represents an experimental model adequate for studying aging processes because of its high blood flow and metabolism, and thus it serves as a means to understanding the oxygen modulation of the aging process.
Loss of desmin leads to impaired voluntary wheel running and treadmill exercise performance
Authors: Haubold Kurt W. , Allen David L. , Capetanaki Yassemi , Leinwand Leslie A.
Published: March 2015

We examined voluntary wheel running and forced treadmill running exercise performance of wild-type mice and mice null for the desmin gene. When given access to a cage wheel, desmin null mice spent less time running and ran less far than wild-type mice. Wild-type mice showed a significant training effect with prolonged voluntary wheel running, as evidenced by an increase in mean running speed across the 3-wk exercise period, whereas desmin null mice did not. Desmin null mice also performed less well in acute treadmill stress and endurance tests compared with wild-type mice. We also evaluated serum creatine kinase (CK) activity in wild-type and desmin null mice in response to running. Voluntary running did not result in elevated CK activity in either wild-type or desmin null mice, whereas downhill treadmill running caused significant increases in serum CK activity in both wild-type and desmin null mice. However, the increase in serum CK was significantly less in desmin null mice than in wild-type mice. These results suggest that the lack of desmin adversely affects the ability of mice to engage in both chronic and acute bouts of endurance running exercise but that this decrement in performance is not associated with an increase in serum CK activity.
Local and systemic autonomic nervous effects on cell migration to the spleen
Authors: Rogausch Heiner , Zwingmann Detlev , Trudewind Mirjam , del Rey Adriana , Voigt Karl-Heinz , Besedovsky Hugo
Published: March 2015

This work is based on the hypothesis that sympathetic nerves regulate the uptake of circulating cells by the spleen by affecting splenic blood flow and that the quantity of cells sequestered depends on whether changes in noradrenergic transmission occur at local or systemic levels. Fluorescently labeled lymphoid cells were injected into rats, and organ blood flow was measured by the microsphere method. Increased retention of cells in the spleen paralleled by increased blood flow was detected after local denervation of this organ or administration of bacterial endotoxin. A comparable enhanced splenic blood flow was observed after general sympathectomy. However, the redistribution of blood perfusion during general vasodilatation resulted in deviation of leukocyte flow from the spleen, thus resulting in reduced uptake of cells by this organ. These results indicate that, although the uptake of cells by the spleen depends on arterial blood supply, enhanced perfusion does not always result in increased cell sequestration because general vasodilatation reduces cell uptake by this organ and even overrides stimulatory effects of endotoxin.
Methacholine responsiveness of proximal and distal airways of monkeys and rats using videomicrometry
Authors: Kott Kayleen S. , Pinkerton Kent E. , Bric John M. , Plopper Charles G. , Avadhanam Krishna P. , Joad Jesse P.
Published: March 2015

Rat and monkey are species that are used in models of human airway hyperresponsiveness. However, the wall structures of rat and monkey airways are different from each other, with that of the monkey more closely resembling that of humans. We hypothesized that differences in wall structure would explain differences in airway responsiveness. Using videomicrometry, we measured airway luminal area in lung slices to compare proximal and distal airway responsiveness to methacholine in the rat and monkey. The airway type was then histologically identified. Proximal airways of the young rat and monkey were equally responsive to methacholine. In contrast, respiratory bronchioles of monkeys were less responsive than were their proximal bronchi, whereas the distal bronchioles of rats were more responsive than their proximal bronchioles. Both proximal and distal airways of younger monkeys were more responsive than those of older monkeys. Airway heterogeneity in young monkeys was greatest with regard to degree of airway closure of respiratory bronchioles. We conclude that responsiveness to methacholine varies with airway wall structure and location.
Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia
Authors: Zhu Xiaoping , Heunks Leo M. A. , Machiels Herwin A. , Ennen Leo , Dekhuijzen P. N. Richard
Published: March 2015

Nitric oxide (NO) is essential for optimal myofilament function of the rat diaphragm in vitro during active shortening. Little is known about the role of NO in muscle contraction under hypoxic conditions. Hypoxia might increase the NO synthase (NOS) activity within the rat diaphragm. We hypothesized that NO plays a protective role in isotonic contractile and fatigue properties during hypoxia in vitro. The effects of the NOS inhibitor N G-monomethyl-l-arginine (l-NMMA), the NO scavenger hemoglobin, and the NO donor spermine NONOate on shortening velocity, power generation, and isotonic fatigability during hypoxia were evaluated (Po 2 ∼ 7 kPa). l-NMMA and hemoglobin slowed the shortening velocity, depressed power generation, and increased isotonic fatigability during hypoxia. The effects ofl-NMMA were prevented by coadministration with the NOS substrate l-arginine. Spermine NONOate did not alter isotonic contractile and fatigue properties during hypoxia. These results indicate that endogenous NO is needed for optimal muscle contraction of the rat diaphragm in vitro during hypoxia.
Glycine at hypoglossal motor nucleus: genioglossus activity, CO2 responses, and the additive effects of GABA
Authors: Morrison Janna L. , Sood Sandeep , Liu Xia , Liu Hattie , Park Eileen , Nolan Philip , Horner Richard L.
Published: March 2015

There is evidence for glycine and GABAA-receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo, and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. This study tests the hypotheses that glycine at the hypoglossal motor nucleus (HMN) will suppress genioglossus (GG) muscle activity, even in the presence of hypercapnic respiratory stimulation, and the effects of glycine will be blocked by strychnine. We also determined whether coapplication of glycine and muscimol (GABAA- receptor agonist) to the HMN is additive in suppressing GG activity. Twenty-four urethane-anesthetized, tracheotomized, and vagotomized rats were studied. Diaphragm and GG activities, the electroencephalogram, and blood pressure were recorded. Microdialysis probes were implanted into the HMN for delivery of artificial cerebrospinal fluid (control), glycine (0.0001–10 mM), or muscimol (0.1 μM). Increasing glycine at the HMN produced graded suppression of GG activity ( P < 0.001), although the GG still responded to stimulation with 7% inspired CO2( P = 0.002). Strychnine (0.1 mM) reversed the glycine-mediated suppression of GG activity, whereas combined glycine and muscimol were additive in GG muscle suppression. It remains to be determined whether the recruitment of such glycine and GABA mechanisms explains the periods of major GG suppression in behaviors such as rapid eye movement sleep.
Insulin sensitivity and big ET-1 conversion to ET-1 after ETA- or ETB-receptor blockade in humans
Authors: Ahlborg Gunvor , Lindström Jonas
Published: March 2015

Cardiovascular diseases are characterized by insulin resistance and elevated endothelin (ET)-1 levels. Furthermore, ET-1 induces insulin resistance. To elucidate this mechanism, six healthy subjects were studied during a hyperinsulinemic euglycemic clamp during infusion of (the ET-1 precursor) big ET-1 alone or after ETA- or ETB-receptor blockade. Insulin levels rose after big ET-1 with or without the ETB antagonist BQ-788 ( P < 0.05) but were unchanged after the ETA antagonist BQ-123 + big ET-1. Infused glucose divided by insulin fell after big ET-1 with or without BQ-788 ( P < 0.05). Insulin and infused glucose divided by insulin values were normalized by ETA blockade. Mean arterial blood pressure rose during big ET-1 with or without BQ-788 ( P < 0.001) but was unchanged after BQ-123. Skeletal muscle, splanchnic, and renal blood flow responses to big ET-1 were abolished by BQ-123. ET-1 levels rose after big ET-1 ( P< 0.01) in a similar way after BQ-123 or BQ-788, despite higher elimination capacity after ETA blockade. In conclusion, ET-1-induced reduction in insulin sensitivity and clearance as well as splanchnic and renal vasoconstriction are ETA mediated. ETA-receptor stimulation seems to inhibit the conversion of big ET-1 to ET-1.
Fever induction by localized subcutaneous inflammation in guinea pigs: the role of cytokines and prostaglandins
Authors: Ross Günter , Hübschle Thomas , Pehl Ulrich , Braun Hans-Albert , Voigt Karlheinz , Gerstberger Rüdiger , Roth Joachim
Published: March 2015

In guinea pigs, dose-dependent febrile responses can be induced by injection of a high (100 μg/kg) or low (10 μg/kg) dose of bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. In this fever model, LPS does not enter the systemic circulation from the site of localized tissue inflammation in considerable amounts but causes a local induction of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6), which can be measured in lavage fluid collected from the chamber area. Only in response to the high LPS dose, small traces of TNF are measurable in blood plasma. A moderate increase of circulating IL-6 occurs in response to administration of both LPS doses. To investigate the putative roles of TNF and prostaglandins in this fever model, a neutralizing TNF binding protein (TNF-bp) or a nonselective inhibitor of cyclooxygenases (diclofenac) was injected along with the high or low dose of LPS into the subcutaneous chamber. In control groups, both doses of LPS were administered into the chamber along with the respective vehicles for the applied drugs. The fever response to the high LPS dose remained unimpaired by treatment with TNF-bp despite an effective neutralization of bioactive TNF in the inflamed tissue area. In response to the low LPS dose, there was an accelerated defervescence under the influence of TNF-bp. Blockade of prostaglandin formation with diclofenac completely abolished fever in response to both LPS doses. In conclusion, prostaglandins seem to be essential components for the manifestation of fever in this model.
Effects of exercise and β2-agonists on lung function in chronic obstructive pulmonary disease
Authors: Corsico Angelo , Fulgoni Paola , Beccaria Massimiliano , Zoia Maria Cristina , Barisione Giovanni , Pellegrino Riccardo , Brusasco Vito , Cerveri Isa
Published: March 2015

The effects of inhaled bronchodilators at rest and during exercise were studied in 15 subjects with chronic obstructive pulmonary disease. In a crossover study against placebo, albuterol caused a significant increase in expiratory flow and reduced lung hyperinflation and dyspnea at rest, but this was not associated with differences in symptoms with exercise or any relevant parameter of physical performance. Dynamic hyperinflation occurred during exercise similarly after placebo or albuterol and was associated with a reduction of forced expiratory flows. This, in turn, was correlated with the bronchoconstrictor effect of deep inhalation determined at rest. In a parallel group study, expiratory flow was increased by 3-wk treatment with salmeterol ( n = 9) but not with placebo ( n = 6). However, in neither group was the response to exercise different from baseline. These results suggest that in chronic obstructive pulmonary disease effective pharmacological bronchodilation at rest may not be predictive of benefits of exercise tolerance. This may be related to the occurrence of airway narrowing during exercise, particularly when a deep inhalation at rest is followed by a decrease in expiratory flow.
Dexfenfluramine protects against pulmonary hypertension in rats
Authors: Mitani Yoshihide , Mutlu Asuman , Russell James C. , Brindley David N. , DeAlmeida John , Rabinovitch Marlene
Published: March 2015

Dexfenfluramine (Dex), an appetite suppressant and serotonin reuptake inhibitor, is associated with pulmonary vascular disease (PVD) in some patients. The variability might be related to undetermined genetic abnormalities interacting with factors such as gender, weight loss, and vascular injury. We, therefore, assessed the effect of Dex (5 mg · kg−1· day−1) in female obese rats, designated JCR:LA-cp or cp/ cp; in lean rats, designated (+/?); and in normal Sprague-Dawley (S-D) rats under control conditions or after endothelial injury induced by monocrotaline (60 mg/kg). Pulmonary arterial pressure, right ventricular hypertrophy, percent medial wall thickness of muscular arteries, and muscularization of peripheral arteries were assessed as indexes of PVD. Although Dex reduced weight gain in cp/ cp and S-D rats ( P < 0.05 for both), it did not cause PVD. Moreover, PVD in S-D rats after monocrotaline injection was paradoxically ameliorated by Dex ( P < 0.05) despite induction of pulmonary artery elastase ( P < 0.05), which we showed is critical in inducing experimental PVD. Thus it is possible that Dex is concomitantly offsetting the sequelae of elastase activity.
C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women
Authors: Roth Stephen M. , Metter E. Jeffrey , Lee Mechele R. , Hurley Ben F. , Ferrell Robert E.
Published: March 2015

We performed gene screening of the ciliary neurotrophic factor receptor (CNTFR) gene and genotyped three newly identified polymorphisms: C-1703T in the 5′ promoter region, T1069A in intron 5, and C174T in exon 9. We studied the association of these CNTFR variants with muscle strength, mass, and body composition in 465 men and women (20-90 yr) from the Baltimore Longitudinal Study of Aging. Only the C174T variant was significantly associated with muscle-related phenotypes. In the entire cohort, when corrected for age, sex, race, physical activity, and height, homozygotes for the common C allele at C174T (CC) exhibited lower total body mass and body mass index than carriers of the rare T allele, which appeared to be due to significant differences in total nonosseous fat-free mass (FFM) (48.0 ± 0.4 vs. 50.0 ± 0.7 kg; P = 0.011) and lower limb FFM (16.5 ± 0.1 vs. 17.2 ± 0.2 kg; P = 0.002). The CC group also exhibited significantly lower quadriceps concentric and eccentric isokinetic strength values at both 30 and 180°/s than the T allele carriers (all P < 0.04), but these differences were no longer significant after adjustment for lower limb FFM. There were no significant sex-by-genotype interactions. The results indicate that the C174T polymorphism in exon 9 of CNTFR is significantly associated with FFM in men and women, with concomitant differences in muscular strength.
Dynamic cerebral autoregulation is preserved during acute head-down tilt
Authors: Cooke William H. , Pellegrini Guy L. , Kovalenko Olga A.
Published: March 2015

Complete ganglion blockade alters dynamic cerebral autoregulation, suggesting links between systemic autonomic traffic and regulation of cerebral blood flow velocity. We tested the hypothesis that acute head-down tilt, a physiological maneuver that decreases systemic sympathetic activity, would similarly disrupt normal dynamic cerebral autoregulation. We studied 10 healthy young subjects (5 men and 5 women; age 21 ± 0.88 yr, height 169 ± 3.1 cm, and weight 76 ± 6.1 kg). ECG, beat-by-beat arterial pressure, respiratory rate, end-tidal CO2 concentration, and middle cerebral blood flow velocity were recorded continuously while subjects breathed to a metronome. We recorded data during 5-min periods and averaged responses from three Valsalva maneuvers with subjects in both the supine and -10° head-down tilt positions (randomized). Controlled-breathing data were analyzed in the frequency domain with power spectral analysis. The magnitude of input-output relations were determined with cross-spectral techniques. Head-down tilt significantly reduced Valsalva phase IV systolic pressure overshoot from 36 ± 4.0 (supine position) to 25 ± 4.0 mmHg (head down) ( P = 0.03). Systolic arterial pressure spectral power at the low frequency decreased from 5.7 ± 1.6 (supine) to 4.4 ± 1.6 mmHg2 (head down) ( P = 0.02), and mean arterial pressure spectral power at the low frequency decreased from 3.3 ± 0.79 (supine) to 2.0 ± 0.38 mmHg2 (head down) ( P = 0.05). Head-down tilt did not affect cerebral blood flow velocity or the transfer function magnitude and phase angle between arterial pressure and cerebral blood flow velocity. Our results show that in healthy humans, mild physiological manipulation of autonomic activity with acute head-down tilt has no effect on the ability of the cerebral vasculature to regulate flow velocity.
Respiratory effects in humans of a 5-day elevation of end-tidal PCO2 by 8 Torr
Authors: Crosby Alexi , Talbot Nick P. , Balanos George M. , Donoghue Simon , Fatemian Marzieh , Robbins Peter A.
Published: March 2015

The aims of this study were to determine 1) whether ventilatory adaptation occurred over a 5-day exposure to a constant elevation in end-tidal Pco2 and 2) whether such an exposure altered the sensitivity of the chemoreflexes to acute hypoxia and hypercapnia. Ten healthy human subjects were studied over a period of 13 days. Their ventilation, chemoreflex sensitivities, and acid-base status were measured daily before, during, and after 5 days of elevated end-tidal Pco2 at 8 Torr above normal. There was no major adaptation of ventilation during the 5 days of hypercapnic exposure. There was an increase in ventilatory chemosensitivity to acute hypoxia (from 1.35 ± 0.08 to 1.70 ± 0.07 l/min/%; P < 0.01) but no change in ventilatory chemosensitivity to acute hypercapnia. There was a degree of compensatory metabolic alkalosis. The results do not support the hypothesis that the ventilatory adaptation to chronic hypercapnia would be much greater with constant elevation of alveolar Pco2 than with constant elevation of inspired Pco2, as has been used in previous studies and in which the feedback loop between ventilation and alveolar Pco2 is left intact.
Endurance training-induced changes in alkali light chain patterns in type IIB fibers of the rat
Authors: Wada Masanobu , Inashima Shuichiro , Yamada Takashi , Matsunaga Satoshi
Published: March 2015

The effects of endurance training on the expression of myosin were electrophoretically analyzed in the deep portion of vastus lateralis muscle from the rat. A 10-wk running program led to increases ( P < 0.01) in myosin heavy chain (MHC) 2a and 2d with a decrease ( P < 0.01) in MHC2b. Training also evoked a rearrangement of the isomyosin pattern with decreases in fast isomyosin (FM) 1 ( P < 0.01) and FM2 ( P < 0.05) and a rise in intermediate isomyosin ( P < 0.01). These changes were accompanied by a 61% decrease ( P < 0.01) in myosin light chain (MLC) 3F (11.8 ± 2.7 vs. 4.6 ± 4.2%). Two-dimensional electrophoresis made it possible to separate the triplet of isomyosins (FMb) consisting of MHC2b. Training elicited a 26% decrease ( P < 0.05) in the FM1b fraction within FMb, i.e., FM1b/(FM1b + FM2b + FM3b) (24.2 ± 5.5 vs. 18.0 ± 4.3%). These changes resulted in a 10% decrease ( P < 0.05) in the MLC3Ffraction, i.e., MLC3F/(MLC1F+ MLC3F), in FMb (44.9 ± 4.5 vs. 40.3 ± 3.2%). These results suggest that endurance training may exert the depressive effect on the contractile velocity of type IIB fibers and that a training-induced decrease in the contractile velocity of whole muscle may be caused by alterations in fast alkali MLC complements within a given fiber type as well as by transitions in MHC-based fiber populations.
Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats
Authors: Brooks-Asplund Esther M. , Shoukas Artin A. , Kim Soon-Yul , Burke Sean A. , Berkowitz Dan E.
Published: March 2015

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17β-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50but impaired function by decreasing maximal VD. The shift in EC50corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.
Sexually dimorphic effects of morphine and MK-801: sex steroid-dependent and -independent mechanisms
Authors: D'Souza Deborah N. , Harlan Richard E. , Garcia Meredith M.
Published: March 2015

Rats show gender differences in responses to morphine and the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801); the role of sex steroids in mediating these differences is unclear. We tested the overall hypothesis that circulating gonadal steroids determine the gender differences in morphine- and MK-801-induced behavior and c-Fos expression. Morphine caused a greater expression of c-Fos in the striatum of intact males than of that females, which was independent of sex steroids. MK-801 completely inhibited morphine-induced c-Fos in intact females but only caused partial inhibition in intact males; castrated males showed complete inhibition, which was reversed by testosterone, but gonadal steroids had no effect on this response in females. In thalamus, there was a large sex difference in the response to MK-801 that was independent of gonadal steroids. Behavioral responses to morphine were greater in males, but responses to MK-801 were greater in females; both were sex steroid independent. These findings show significant sex differences in response to morphine and MK-801 that are mediated by sex steroid-dependent and -independent mechanisms, which may be important in treatment outcomes of drug addiction.
Similar ventilation distribution in normal subjects prone and supine during tidal breathing
Authors: Rodríguez-Nieto M. J. , Peces-Barba G. , González Mangado N. , Paiva M. , Verbanck S.
Published: March 2015

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O2, 5% He, and 5% SF6as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N2concentrations was evaluated in terms of its curvilinearity. The MBW N2normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907–1916, 1997). Also, the difference between SF6and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures ( P > 0.1; n= 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N2normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF6-He normalized phase III slope difference in the first MBW expiration ( P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.
Alteration of contractile force and mass in the senescent diaphragm with β2-agonist treatment
Authors: Smith Wesley N. , Dirks Amie , Sugiura Takao , Muller Susan , Scarpace Phillip , Powers Scott K.
Published: March 2015

Aging is associated with a decrease in diaphragmatic maximal tetanic force production (Po) in senescent rats. Treatment with the β2-agonist clenbuterol (CB) has been shown to increase skeletal muscle mass and Po in weak locomotor skeletal muscles from dystrophic rodents. It is unknown whether CB can increase diaphragmatic mass and Po in senescent rats. Therefore, we tested the hypothesis that CB treatment will increase specific Po (i.e., force per cross-sectional area) and mass in the diaphragm of old rats. Young (5 mo) and old (23 mo) male Fischer 344 rats were randomly assigned to one of the following groups ( n = 10/group): 1) young CB treated; 2) young control; 3) old CB treated; and 4) old control. Animals were injected daily with either CB (2 mg/kg) or saline for 28 days. CB increased ( P < 0.05) the mass of the costal diaphragm in both young and old animals. CB treatment increased diaphragmatic-specific Po in old animals (∼15%; P < 0.05) but did not alter ( P > 0.05) diaphragmatic-specific Po in young animals. Biochemical analysis indicated that the improved maximal specific Po in the diaphragm of CB-treated old animals was not due to increased myofibrillar protein concentration. Analysis of the myosin heavy chain (MHC) content of the costal diaphragm revealed a CB-induced increase ( P < 0.05) in type IIb MHC and a decrease in type I, IIa, and IIx MHC in both young and old animals. These data support the hypothesis that CB treatment can restore the age-associated decline in both diaphragmatic-specific Po and muscle mass.