bluuebunny/crossref_metadata_2025 huggingface dataset:
Endurance training increases fatty acid turnover, but not fat oxidation, in young men
Authors: Friedlander Anne L. , Casazza Gretchen A. , Horning Michael A. , Usaj Anton , Brooks George A.
Published: December 2017

We examined the effects of exercise intensity and a 10-wk cycle ergometer training program [5 days/wk, 1 h, 75% peak oxygen consumption (V˙o 2 peak)] on plasma free fatty acid (FFA) flux, total fat oxidation, and whole body lipolysis in healthy male subjects ( n= 10; age = 25.6 ± 1.0 yr). Two pretraining trials (45 and 65% ofV˙o 2 peak) and two posttraining trials (same absolute workload, 65% of oldV˙o 2 peak; and same relative workload, 65% of newV˙o 2 peak) were performed by using an infusion of [1-13C]palmitate and [1,1,2,3,3-2H]glycerol. An additional nine subjects (age 25.4 ± 0.8 yr) were treated similarly but were infused with [1,1,2,3,3-2H]glycerol and not [1-13C]palmitate. Subjects were studied postabsorptive for 90 min of rest and 1 h of cycling exercise. After training, subjects increasedV˙o 2 peak by 9.4 ± 1.4%. Pretraining, plasma FFA kinetics were inversely related to exercise intensity with rates of appearance (Ra) and disappearance (Rd) being significantly higher at 45 than at 65%V˙o 2 peak(Ra: 8.14 ± 1.28 vs. 6.64 ± 0.46, Rd: 8.03 ± 1.28 vs. 6.42 ± 0.41 mol ⋅ kg−1 ⋅ min−1) ( P ≤ 0.05). After training, when measured at the same absolute and relative intensities, FFA Ra increased to 8.84 ± 1.1, 8.44 ± 1.1 and Rd to 8.82 ± 1.1, 8.35 ± 1.1 mol ⋅ kg−1 ⋅ min−1, respectively ( P ≤ 0.05). Total fat oxidation determined from respiratory exchange ratio was elevated during exercise compared with rest, but did not differ among the four conditions. Glycerol Ra was elevated during exercise compared with rest but did not demonstrate significant intensity or training effects during exercise. Thus, in young men, plasma FFA flux is increased during exercise after endurance training, but total fat oxidation and whole-body lipolysis are unaffected when measured at the same absolute or relative exercise intensities.
Specific strength and voluntary muscle activation in young and elderly women and men
Authors: Kent-Braun Jane A. , Ng Alexander V.
Published: December 2017

The extents to which decreased muscle size or activation are responsible for the decrease in strength commonly observed with aging remain unclear. Our purpose was to compare muscle isometric strength [maximum voluntary contraction (MVC)], cross-sectional area (CSA), specific strength (MVC/CSA), and voluntary activation in the ankle dorsiflexor muscles of 24 young (32 ± 1 yr) and 24 elderly (72 ± 1 yr) healthy men and women of similar physical activity level. Three measures of voluntary muscle activation were used: the central activation ratio [MVC/(MVC + superimposed force)], the maximal rate of voluntary isometric force development, and foot tap speed. Men had higher MVC and CSA than did women. Young men had higher MVC compared with elderly men [262 ± 19 (SE) vs. 197 ± 22 N, respectively], whereas MVC was similar in young and elderly women (136 ± 15 vs. 149 ± 16 N, respectively). CSA was greater in young compared with elderly subjects. There was no age-related impairment of specific strength, central activation ratio, or the rate of voluntary force development. Foot tap speed was reduced in elderly (34 ± 1 taps/10 s) compared with young subjects (47 ± 1 taps/10 s). These results suggest that isometric specific strength and the ability to fully and rapidly activate the dorsiflexor muscles during a single isometric contraction were unimpaired by aging. However, there was an age-related deficit in the ability to perform rapid repetitive dynamic contractions.
Thermoregulation during cold exposure: effects of prior exercise
Authors: Castellani John W. , Young Andrew J. , Kain James E. , Rouse Amy , Sawka Michael N.
Published: December 2017

This study examined whether acute exercise would impair the body’s capability to maintain thermal balance during a subsequent cold exposure. Ten men rested for 2 h during a standardized cold-air test (4.6°C) after two treatments: 1) 60 min of cycle exercise (Ex) at 55% peak O2uptake and 2) passive heating (Heat). Ex was performed during a 35°C water immersion (WI), and Heat was conducted during a 38.2°C WI. The duration of Heat was individually adjusted (mean = 53 min) so that rectal temperature was similar at the end of WI in both Ex (38.2°C) and Heat (38.1°C). During the cold-air test after Ex, relative to Heat 1) rectal temperature was lower ( P < 0.05) from minutes 40–120, 2) mean weighted heat flow was higher ( P < 0.05), 3) insulation was lower ( P < 0.05), and 4) metabolic heat production was not different. These results suggest that prior physical exercise may predispose a person to greater heat loss and to experience a larger decline in core temperature when subsequently exposed to cold air. The combination of exercise intensity and duration studied in these experiments did not fatigue the shivering response to cold exposure.
A technique to measure the ability of the human nose to warm and humidify air
Authors: Rouadi Philip , Baroody Fuad M. , Abbott David , Naureckas Edward , Solway Julian , Naclerio Robert M.
Published: December 2017

To assess the ability of the nose to warm and humidify inhaled air, we developed a nasopharyngeal probe and measured the temperature and humidity of air exiting the nasal cavity. We delivered cold, dry air (19–1°C, <10% relative humidity) or hot, humid air (37°C, >90% relative humidity) to the nose via a nasal mask at flow rates of 5, 10, and 20 l/min. We used a water gradient across the nose (water content in nasopharynx minus water content of delivered air) to assess nasal function. We studied the characteristics of nasal air conditioning in 22 asymptomatic, seasonally allergic subjects (out of their allergy season) and 11 nonallergic normal subjects. Inhalation of hot, humid air at increasingly higher flow rates had little effect on both the relative humidity and the temperature of air in the nasopharynx. In both groups, increasing the flow of cold, dry air lowered both the temperature and the water content of the inspired air measured in the nasopharynx, although the relative humidity remained at 100%. Water gradient values obtained during cold dry air challenges on separate days showed reproducibility in both allergic and nonallergic subjects. After exposure to cold, dry air, the water gradient was significantly lower in allergic than in nonallergic subjects (1,430 ± 45 vs. 1,718 ± 141 mg; P = 0.02), suggesting an impairment in their ability to warm and humidify inhaled air.
Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis
Authors: Roum James H. , Borok Zea , McElvaney Noel G. , Grimes George J. , Bokser Allan D. , Buhl Roland , Crystal Ronald G.
Published: December 2017

Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified, since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to seven patients with CF. ELF total, reduced, and oxidized GSH increased ( P < 0.05, all compared with before GSH therapy), suggesting adequate RES delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated superoxide anion ([Formula: see text]) release by ELF inflammatory cells decreased after GSH therapy ( P < 0.002). This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed [Formula: see text] release ( P < 0.001). No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF and support the rationale for further clinical evaluation.
Monitoring respiratory function and sleep in the obese Vietnamese pot-bellied pig
Authors: Tuck Stephanie A. , Dort Joseph C. , Olson Merle E. , Remmers John E.
Published: December 2017

Development of drug treatments for obstructive sleep-disordered breathing has been impeded by the lack of animal models. The obese pig may be a suitable animal model, as it has been reported to experience sleep-disordered breathing resembling human obstructive sleep apnea. The purpose of this paper is to describe in detail techniques for chronic instrumentation of the obese Vietnamese pot-bellied pig and to study respiratory function during sleep. Under general anesthesia, four obese pigs were instrumented for long-term recording of intrapleural and tracheal pressures, genioglossal EMG, and bioelectric signals related to sleep. A custom-fitted face mask was used to record respiratory variables including airflow, snoring, and expired CO2. Most chronic instrumentation provided robust signals for up to 6 wk after installation. All pigs displayed sleep-disordered breathing characterized by increased resistance to airflow, snoring, inspiratory flow limitation, and possible sleep disruption. Apneas and hypopneas were not a feature of breathing during sleep in these animals. Nonetheless, this animal preparation may be useful for exploring possible drug treatments for obstructive sleep-disordered breathing.
Increased expression of transferrin receptor on membrane of erythroblasts in strenuously exercised rats
Authors: Qian Zhong Ming , Xiao De Sheng , Tang Pak Lai , Yao Fiona Yan Dong , Liao Qing Kui
Published: December 2017

This study investigated the effects of strenuous exercise on transferrin (Tf)-receptor (TfR) expression and Tf-bound iron (Tf-Fe) uptake in erythroblasts of rat bone marrow. Female Sprague-Dawley rats were randomly assigned to either an exercise or sedentary group. Animals in the exercise group swam 2 h/day for 3 mo in a glass swimming basin. Both groups received the same amount of handling. At the end of 3 mo, the bone marrow erythroblasts were freshly isolated for Tf-binding assay and determination of Tf-Fe uptake in vitro. Tissue nonheme iron and hematological iron indexes were measured. The number of Tf-binding sites found in erythroblasts was ∼674,500 ± 132,766 and 1,270,011 ± 235,321 molecules/cell in control and exercised rats, respectively ( P < 0.05). Total Fe and Tf uptake by the cells was also significantly increased in the exercised rats after 30 min of incubation. Rates of cellular Fe accumulation were 5.68 and 2.58 fmol ⋅ 106cells−1⋅ min−1in the exercised and control rats, respectively ( P < 0.05). Tf recycling time and TfR affinity were not different in exercised and control rats. Increased cellular Fe was mainly located in the stromal fraction, suggesting that most of accumulated Fe was transported to the mitochondria for heme synthesis. The findings demonstrated that the increased cellular Fe uptake in exercised rats was a consequence of the increased TfR expression rather than the changes in TfR affinity and Tf recycling time. The increase in TfR expression and cellular Fe accumulation, as well as the decreased serum Fe concentration and nonheme Fe in the liver and the spleen induced by exercise, probably represented the early signs of Fe deficiency.
Differential effects of clonidine on upper airway abductor and adductor muscle activity in awake goats
Authors: O’Halloran K. D. , Herman J. K. , Bisgard G. E.
Published: December 2017

The purpose of this study was to determine the extent to which α2-adrenoceptor (α2-AR) pathways affect the central motor output to upper airway muscles that regulate airflow. Electromyogram (EMG) measurements were made from posterior cricoarytenoid (PCA), cricothyroid (CT), thyroarytenoid (TA), and middle (MPC) and inferior (IPC) pharyngeal constrictor muscles in awake standing goats. Systemic administration of the α2-AR agonist clonidine induced a highly dysrhythmic pattern of ventilation in all animals that was characterized by alternating episodes of tachypnea and slow irregular breathing patterns, including prolonged and variable expiratory time intervals. Periods of apnea were commonly observed. Dysrhythmic ventilatory patterns induced by clonidine were associated with differential recruitment of upper airway muscles. α2-AR stimulation preferentially decreased the activity of the PCA, CT, and IPC muscles while increasing TA and MPC EMG activities. Clonidine-induced apneas were associated with continuous tonic activation of laryngeal (TA) and pharyngeal (MPC) adductors, leading to airway closure and arterial oxygen desaturation. Tonic activation of the TA and MPC muscles was interrupted only during the first inspiratory efforts after central apnea. Laryngeal abductor, diaphragm, and transversus abdominis EMG activities were completely silenced during apneic events. Ventilatory and EMG effects were reversed by selective α2-AR blockade with SKF-86466. The results demonstrate that α2-AR pathways are important modulators of central respiratory motor outputs to the upper airway muscles.
Influence of respiratory muscle work onV˙o2and leg blood flow during submaximal exercise
Authors: Wetter Thomas J. , Harms Craig A. , Nelson William B. , Pegelow David F. , Dempsey Jerome A.
Published: December 2017

The work of breathing (Wb) normally incurred during maximal exercise not only requires substantial cardiac output and O2consumption (V˙o2) but also causes vasoconstriction in locomotor muscles and compromises leg blood flow (Q˙leg). We wondered whether the Wbnormally incurred during submaximal exercise would also reduceQ˙leg. Therefore, we investigated the effects of changing the WbonQ˙legvia thermodilution in 10 healthy trained male cyclists [maximalV˙o2(V˙o2 max) = 59 ± 9 ml ⋅ kg−1⋅ min−1] during repeated bouts of cycle exercise at work rates corresponding to 50 and 75% ofV˙o2 max. Inspiratory muscle work was 1) reduced 40 ± 6% via a proportional-assist ventilator, 2) not manipulated (control), or 3) increased 61 ± 8% by addition of inspiratory resistive loads. Increasing the Wbduring submaximal exercise caused V˙o2to increase; decreasing the Wbwas associated with lowerV˙o2(ΔV˙o2= 0.12 and 0.21 l/min at 50 and 75% ofV˙o2 max, respectively, for ∼100% change in Wb). There were no significant changes in leg vascular resistance (LVR), norepinephrine spillover, arterial pressure, orQ˙legwhen Wbwas reduced or increased. Why are LVR, norepinephrine spillover, andQ˙leginfluenced by the Wbat maximal but not submaximal exercise? We postulate that at submaximal work rates and ventilation rates the normal Wbrequired makes insufficient demands forV˙o2and cardiac output to require any cardiovascular adjustment and is too small to activate sympathetic vasoconstrictor efferent output. Furthermore, even a 50–70% increase in Wbduring submaximal exercise, as might be encountered in conditions where ventilation rates and/or inspiratory flow resistive forces are higher than normal, also does not elicit changes in LVR orQ˙leg.
Mechanical stretching of alveolar epithelial cells increases Na+-K+-ATPase activity
Authors: Waters Christopher M. , Ridge Karen M. , Sunio G. , Venetsanou K. , Sznajder Jacob Iasha
Published: December 2017

Alveolar epithelial cells effect edema clearance by transporting Na+and liquid out of the air spaces. Active Na+transport by the basolaterally located Na+-K+-ATPase is an important contributor to lung edema clearance. Because alveoli undergo cyclic stretch in vivo, we investigated the role of cyclic stretch in the regulation of Na+-K+-ATPase activity in alveolar epithelial cells. Using the Flexercell Strain Unit, we exposed a cell line of murine lung epithelial cells (MLE-12) to cyclic stretch (30 cycles/min). After 15 min of stretch (10% mean strain), there was no change in Na+-K+-ATPase activity, as assessed by86Rb+uptake. By 30 min and after 60 min, Na+-K+-ATPase activity was significantly increased. When cells were treated with amiloride to block amiloride-sensitive Na+entry into cells or when cells were treated with gadolinium to block stretch-activated, nonselective cation channels, there was no stimulation of Na+-K+-ATPase activity by cyclic stretch. Conversely, cells exposed to Nystatin, which increases Na+entry into cells, demonstrated increased Na+-K+-ATPase activity. The changes in Na+-K+-ATPase activity were paralleled by increased Na+-K+-ATPase protein in the basolateral membrane of MLE-12 cells. Thus, in MLE-12 cells, short-term cyclic stretch stimulates Na+-K+-ATPase activity, most likely by increasing intracellular Na+and by recruitment of Na+-K+-ATPase subunits from intracellular pools to the basolateral membrane.
Regeneration of new fibers in muscles of old rats reduces contraction-induced injury
Authors: Devor Steven T. , Faulkner John A.
Published: December 2017

Skeletal muscles are injured by their own contractions. Compared with muscles in young animals, those in old animals are injured more easily and more severely and regenerate less well afterward. Injection of a myotoxin (bupivacaine) causes complete degeneration of fibers in extensor digitorum longus (EDL) muscles of rats, followed by full regeneration within 60 days. We tested the specific hypothesis that, 3 days after a protocol of pliometric (lengthening) contractions, the newly regenerated muscle fibers in bupivacaine-treated EDL muscles in both young and old rats would show a lesser deficit in maximum force and fewer damaged fibers than muscles in nontreated EDL muscles. The treated and nontreated EDL muscles of young and old male Wistar rats were administered a protocol of 225 pliometric contractions and were evaluated 3 days afterward, when morphological damage to muscle fibers is most severe. In treated compared with nontreated EDL muscles of both young and old rats, the force deficit and the number of damaged fibers were each reduced by ∼75%. We conclude that newly regenerated fibers in muscles of young and old animals are resistant to injury and that maintenance of newly regenerated fibers by conditioning may prevent inadvertent damage, particularly in muscles of elderly people.
Postexercise responses of muscle sympathetic nerve activity and blood flow to hyperinsulinemia in humans
Authors: Forjaz Cláudia L. M. , Ramires Paulo R. , Tinucci Taís , Ortega Kátia C. , Salomão Heloísa E. H. , Ignês Edna C. , Wajchenberg Bernardo L. , Negrão Carlos E. , Mion Décio
Published: December 2017

Although insulin and exercise cause dramatic changes in physiological parameters, the impact of exercise on neural and hemodynamic responses to insulin administration has not been described. In a study of the effects of a single bout of exercise on blood pressure (BP), muscle sympathetic nerve activity (MSNA), and forearm blood flow (FBF) responses to insulin infusion during the postexercise period, 11 healthy men underwent, in a random order, two hyperinsulinemic euglycemic clamps performed after 45 min of 1) bicycle exercise (50% peak O2 uptake, Exercise session) and 2) seated rest (Control session). Data were analyzed during baseline and steady-state periods. Although insulin levels and insulin sensitivity were similar, baseline plasma glucose levels were significantly lower in the Exercise than in the Control session. Mean BP was significantly lower (3%) and FBF was higher (27%) in the Exercise session. Exercise increased insulin-induced MSNA enhancement (84%) without changing FBF and BP responses to hyperinsulinemia. In conclusion, a single bout of exercise that does not alter insulin sensitivity exacerbates insulin-induced increase in MSNA without changing FBF and BP responses to hyperinsulinemia.
Postinspiratory activity of the parasternal and external intercostal muscles in awake canines
Authors: Easton Paul A. , Hawes Harvey G. , Rothwell Bruce , de Troyer Andre
Published: December 2017

Previous studies have shown in awake dogs that activity in the crural diaphragm, but not in the costal diaphragm, usually persists after the end of inspiratory airflow. It has been suggested that this difference in postinspiratory activity results from greater muscle spindle content in the crural diaphragm. To evaluate the relationship between muscle spindles and postinspiratory activity, we have studied the pattern of activation of the parasternal and external intercostal muscles in the second to fourth interspaces in eight chronically implanted animals. Recordings were made on 2 or 3 successive days with the animals breathing quietly in the lateral decubitus position. The two muscles discharged in phase with inspiration, but parasternal intercostal activity usually terminated with the cessation of inspiratory flow, whereas external intercostal activity persisted for 24.7 ± 12.3% of inspiratory time ( P < 0.05). Forelimb elevation in six animals did not affect postinspiratory activity in the parasternal but prolonged postinspiratory activity in the external intercostal to 45.4 ± 16.3% of inspiratory time ( P < 0.05); in two animals, activity was still present at the onset of the next inspiratory burst. These observations support the concept that muscle spindles are an important determinant of postinspiratory activity. The absence of such activity in the parasternal intercostals and costal diaphragm also suggests that the mechanical impact of postinspiratory activity on the respiratory system is smaller than conventionally thought.
Splanchnic hemodynamics and gut mucosal-arterial P CO 2 gradient during systemic hypocapnia
Authors: Guzman Jorge A. , Kruse James A.
Published: December 2017

The effects of hypocapnia [arterial[Formula: see text]([Formula: see text]) 15 Torr] on splanchnic hemodynamics and gut mucosal-arterial[Formula: see text] were studied in seven anesthetized ventilated dogs. Ileal mucosal and serosal blood flow were estimated by using laser Doppler flowmetry, mucosal[Formula: see text] was measured continuously by using capnometric recirculating gas tonometry, and serosal surface[Formula: see text] was assessed by using a polarographic electrode. Hypocapnia was induced by removal of dead space and was maintained for 45 min, followed by 45 min of eucapnia. Mean [Formula: see text] at baseline was 38.1 ± 1.1 (SE) Torr and decreased to 13.8 ± 1.3 Torr after removal of dead space. Cardiac output and portal blood flow decreased significantly with hypocapnia. Similarly, mucosal and serosal blood flow decreased by 15 ± 4 and by 34 ± 7%, respectively. Also, an increase in the mucosal-arterial[Formula: see text] gradient of 10.7 Torr and a reduction in serosal [Formula: see text] of 30 Torr were observed with hypocapnia ( P < 0.01 for both). Hypocapnia caused ileal mucosal and serosal hypoperfusion, with redistribution of flow favoring the mucosa, accompanied by increased [Formula: see text]gradient and diminished serosal [Formula: see text].
Drug-induced arterial pressure elevation is associated with arousal from NREM sleep in normal volunteers
Authors: Kesler Branko , Anand Amit , Launois Sandrine H. , Weiss J. Woodrow
Published: December 2017

Abrupt changes in arterial pressure produce arousal in sleeping animals. To determine whether arterial pressure elevations can cause arousal from sleep in humans, we studied five healthy individuals without sleep complaints or cardiac abnormalities. Monitoring included electroencephalogram, electrooculogram, and electromyogram to determine stage sleep; finger cuff to measure arterial pressure; and electrocardiogram to measure heart rate. We administered intravenous bolus doses of either phenylephrine or saline after performing a dose-response curve to establish the amount of phenylephrine that produced a 20-mmHg increase in mean arterial pressure. Ten boluses of phenylephrine and ten boluses of saline were then administered in random order during stable non-rapid-eye-movement sleep. An observer blinded to the order of drug administration identified arousals using a standard definition. Arousals were five times more likely to occur after phenylephrine than after saline (58 vs. 12%; P = 0.0071). Phenylephrine administration produced heart rate slowing, indicative of baroreflex stimulation. We conclude that pharmacologically induced arterial pressure elevation is associated with arousal from sleep in normal volunteers.
Influence of upper airway shunt on total respiratory impedance in infants
Authors: Desager K. N. , Cauberghs M. , Naudts J. , van de Woestijne K. P.
Published: December 2017

When input impedance is determined by means of the forced oscillation technique, part of the oscillatory flow measured at the mouth is lost in the motion of the upper airway wall acting as a shunt. This is avoided by applying the oscillations around the subject’s head (head generator) rather than at the mouth (conventional technique). In seven wheezing infants, we compared both techniques to estimate the importance of the upper airway wall shunt impedance (Zuaw) for the interpretation of the conventional technique results. Computation of Zuaw required, in addition, estimation of nasal impedance values, which were drawn from previous measurements (K. N. Desager, M. Willemen, H. P. Van Bever, W. De Backer, and P. A. Vermeire. Pediatr. Pulmonol. 11: 1–7, 1991). Upper airway resistance and reactance at 12 Hz ranged from 40 to 120 and from 0 to −150 hPa ⋅ l−1 ⋅ s, respectively. Varying nasal impedance within the range observed in infants did not result in major changes in the estimates of Zuaw or lung impedance (Zl), the impedance of the respiratory system in parallel with Zuaw. The conventional technique underestimated Zl, depending on the value of Zuaw. The head generator technique slightly overestimated Zl, probably because the pressure gradient across the upper airway was not completely suppressed. Because of the need to enclose the head in a box (which is not required with the conventional technique), the head generator technique is difficult to perform in infants.
Dobutamine as selective β1-adrenoceptor agonist in in vivo studies on human thermogenesis and lipid utilization
Authors: Schiffelers S. L. H. , van Harmelen V. J. A. , de Grauw H. A. J. , Saris W. H. M. , van Baak M. A.
Published: December 2017

The use of dobutamine as selective β1-adrenoceptor agonist in in vivo studies on human thermogenesis and lipid utilization was investigated in 20 men. At 2.5, 5, and 10 μg ⋅ kg−1 ⋅ min−1, dobutamine induced significant increases in energy expenditure, lipid oxidation, and lipolysis. The β1-adrenoceptor antagonist atenolol (bolus: 42.5 μg/kg, infusion: 1.02 μg ⋅ kg−1 ⋅ min−1) blocked all dobutamine-induced effects on thermogenesis and lipid utilization. All parameters remained at levels comparable to those during saline infusion. The dose of atenolol used did not inhibit β2-adrenoceptor-specific changes in energy expenditure, lipid oxidation, and lipolysis during salbutamol infusion (85 ng ⋅ kg−1 ⋅ min−1). This indicates that atenolol was specific for β1-adrenoceptors and did not camouflage concomitant β2-adrenoceptor stimulation during dobutamine infusion. Therefore, we conclude that dobutamine can be used as a selective β1-adrenoceptor agonist at dosages ≤10 μg ⋅ kg−1 ⋅ min−1in in vivo studies on human thermogenesis and lipid utilization.
Sepsis increases contraction-related generation of reactive oxygen species in the diaphragm
Authors: Nethery D. , DiMarco A. , Stofan D. , Supinski G.
Published: December 2017

Recent work indicates that free radicals mediate sepsis-induced diaphragmatic dysfunction. These previous experiments have not, however, established the source of the responsible free radical species. In theory, this phenomenon could be explained if one postulates that sepsis elicits an upregulation of contraction-related free radical formation in muscle. The purpose of the present study was to test this hypothesis by examination of the effect of sepsis on contraction-related free radical generation [i.e., formation of reactive oxygen species (ROS)] by the diaphragm. Rats were killed 18 h after injection with either saline or endotoxin. In vitro hemidiaphragms were then prepared, and ROS generation during electrically induced contractions (20-Hz trains delivered for 10 min) was assessed by measurement of the conversion of hydroethidine to ethidium. ROS generation was negligible in noncontracting diaphragms from both saline- and endotoxin-treated groups (2.0 ± 0.6 and 2.8 ± 1.0 ng ethidium/mg tissue, respectively), but it was marked in contracting diaphragms from saline-treated animals (19.0 ± 2.8 ng/mg tissue) and even more pronounced (30.0 ± 2.8 ng/mg tissue) in diaphragms from septic animals ( P < 0.01). This enhanced free radical generation occurred despite the fact that the force-time integral (i.e., the area under the curve of force vs. time) for control diaphragms was higher than that for the septic group. In additional studies, in which we altered the stimulation paradigm in control muscles to achieve a force-time integral similar to that achieved in septic muscles, an even greater difference between control and septic muscle ROS formation was observed. These data indicate that ROS formation during contraction is markedly enhanced in diaphragms from endotoxin-treated septic animals. We speculate that ROS generated in this fashion plays a central role in producing sepsis-related skeletal muscle dysfunction.
Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats
Authors: Peták Ferenc , Wale Janet L. , Sly Peter D.
Published: December 2017

We investigated the effects of a selective β2-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (Zl) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to Zl spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.
Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats
Authors: Cardin Sylvain , Emshwiller Maya , Jackson Patricia A. , Snead Wanda L. , Hastings Jon , Edgerton Dale S. , Cherrington Alan D.
Published: December 2017

It has been demonstrated in the conscious dog that portal glucose infusion creates a signal that increases net hepatic glucose uptake and hepatic glycogen deposition. Experiments leading to an understanding of the mechanism by which this change occurs will be facilitated if this finding can be reproduced in the rat. Rats weighing 275–300 g were implanted with four indwelling catheters (one in the portal vein, one in the left carotid artery, and two in the right jugular vein) that were externalized between the scapulae. The rats were studied in a conscious, unrestrained condition 7 days after surgery, following a 24-h fast. Each experiment consisted of a 30- to 60-min equilibration, a 30-min baseline, and a 120-min test period. In the test period, a pancreatic clamp was performed by using somatostatin, insulin, and glucagon. Glucose was given simultaneously either through the jugular vein to clamp the arterial blood level at 220 mg/dl (Pe low group) or at 250 mg/dl (Pe high group), or via the hepatic portal vein (Po group; 6 mg ⋅ kg−1 ⋅ min−1) and the jugular vein to clamp the arterial blood glucose level to 220 mg/dl. In the test period, the arterial plasma glucagon and insulin levels were not significantly different in the three groups (36 ± 2, 33 ± 2, and 30 ± 2 pg/ml and 1.34 ± 0.08, 1.37 ± 0.18, and 1.66 ± 0.11 ng/ml in Po, Pe low, and Pe high groups, respectively). The arterial blood glucose levels during the test period were 224 ± 4 mg/dl for Po, 220 ± 3 for Pe low, and 255 ± 2 for Pe high group. The liver glycogen content (μmol glucose/g liver) in the two Pe groups was not statistically different (51 ± 7 and 65 ± 8, respectively), whereas the glycogen level in the Po group was significantly greater (93 ± 9, P< 0.05). Because portal glucose delivery also augments hepatic glycogen deposition in the rat, as it does in the dogs, mechanistic studies relating to its function can now be undertaken in this species.
Muscle interstitial glucose and lactate levels during dynamic exercise in humans determined by microdialysis
Authors: MacLean Dave A. , Bangsbo Jens , Saltin Bengt
Published: December 2017

The purpose of the present study was to use the microdialysis technique to determine skeletal muscle interstitial glucose and lactate concentrations during dynamic incremental exercise in humans. Microdialysis probes were inserted into the vastus lateralis muscle, and subjects performed knee extensor exercise at workloads of 10, 20, 30, 40, and 50 W. The in vivo probe recoveries determined at rest by the internal reference method for glucose and lactate were 28.7 ± 2.5 and 32.0 ± 2.7%, respectively. As exercise intensity increased, probe recovery also increased, and at the highest workload probe recovery for glucose (61.0 ± 3.9%) and lactate (66.3 ± 3.6%) had more than doubled. At rest the interstitial glucose concentration (3.5 ± 0.2 mM) was lower than both the arterial (5.6 ± 0.2 mM) and venous (5.3 ± 0.3 mM) plasma water glucose levels. The interstitial glucose levels remained lower ( P < 0.05) than the arterial and venous plasma water glucose concentrations during exercise at all intensities and at 10, 20, 30, and 50 W, respectively. At rest the interstitial lactate concentration (2.5 ± 0.2 mM) was higher ( P < 0.05) than both the arterial (0.9 ± 0.2 mM) and venous (1.1 ± 0.2 mM) plasma water lactate levels. This relationship was maintained ( P < 0.05) during exercise at workloads of 10, 20, and 30 W. These data suggest that interstitial glucose delivery at rest is flow limited and that during exercise changes in the interstitial concentrations of glucose and lactate mirror the changes observed in the venous plasma water compartments. Furthermore, skeletal muscle contraction results in an increase in the diffusion coefficient of glucose and lactate within the interstitial space as reflected by an elevation in probe recovery during exercise.
Differential microvascular response to disuse in rat hindlimb skeletal muscles
Authors: Tyml Karel , Mathieu-Costello Odile , Cheng Linong , Noble Earl G.
Published: December 2017

The aim of the study was to address discrepant findings in the literature regarding coupling between decreased functional demand during disuse and reduced capillarity. We previously reported [K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17–32, 1995] that severe disuse of rat extensor digitorum longus (EDL) muscle caused by a 2-wk application of tetrodotoxin (TTX) on the sciatic nerve is not accompanied by capillary loss. Using the same animal model, the present study examined whether this absence of coupling could be explained in terms of 1) too short a duration of disuse and 2) muscle-specific response to disuse. Fischer 344 rats were exposed to either no treatment (control) or to 2- or 8-wk TTX applications. Fiber size, capillary density per fiber cross-sectional area, and capillary-to-fiber (C/F) ratio were determined by morphometry in the EDL muscle (control, 2- and 8-wk groups) and in the superficial portion of medial gastrocnemius (Gas) muscle (control, 2 wk). In both muscles, microvascular blood flow was evaluated by intravital microscopy [red blood cell velocity in capillaries ( V RBC)] and by laser Doppler flowmetry (LDF). Regardless of duration of TTX application or muscle type, TTX-induced disuse resulted in a significant reduction of fiber area (44–71%). However, capillary density increased in EDL muscle (both at 2 and 8 wk) but not in Gas muscle. C/F ratio decreased in EDL muscle at 8 wk (18%) and in Gas muscle (39%). This indicates that the effect on capillarity depended on duration of disuse and on muscle type. V RBC and LDF signal were significantly larger in EDL than in Gas muscle. Analysis of change in capillarity vs. V RBC suggested that the outcome of disuse may be modulated by blood flow. We conclude that the duration of skeletal muscle disuse per se does not dictate capillary loss, and we hypothesize that discrepant findings of coupling between functional demand and capillarity could be due to the presence/absence of flow-related angiogenesis superimposed on the capillary removal process during disuse.
Measurement of cardiac output during exercise by open-circuit acetylene uptake
Authors: Barker Rebecca C. , Hopkins Susan R. , Kellogg Nancy , Olfert I. Mark , Brutsaert Tom D. , Gavin Timothy P. , Entin Pauline L. , Rice Anthony J. , Wagner Peter D.
Published: December 2017

Noninvasive measurement of cardiac output (Q˙t) is problematic during heavy exercise. We report a new approach that avoids unpleasant rebreathing and resultant changes in alveolar[Formula: see text] or[Formula: see text] by measuring short-term acetylene (C2H2) uptake by an open-circuit technique, with application of mass balance for the calculation ofQ˙t. The method assumes that alveolar and arterial C2H2pressures are the same, and we account for C2H2recirculation by extrapolating end-tidal C2H2back to breath 1 of the maneuver. We correct for incomplete gas mixing by using He in the inspired mixture. The maneuver involves switching the subject to air containing trace amounts of C2H2and He; ventilation and pressures of He, C2H2, and CO2are measured continuously (the latter by mass spectrometer) for 20–25 breaths. Data from three subjects for whom multiple Fick O2measurements ofQ˙t were available showed that measurement ofQ˙t by the Fick method and by the C2H2technique was statistically similar from rest to 90% of maximal O2consumption (V˙o2 max). Data from 12 active women and 12 elite male athletes at rest and 90% ofV˙o2 maxfell on a single linear relationship, with O2consumption (V˙o2) predictingQ˙t values of 9.13, 15.9, 22.6, and 29.4 l/min atV˙o2of 1, 2, 3, and 4 l/min. Mixed venous [Formula: see text] predicted from C2H2-determinedQ˙t, measuredV˙o2, and arterial O2concentration was ∼20–25 Torr at 90% ofV˙o2 maxduring air breathing and 10–15 Torr during 13% O2breathing. This modification of previous gas uptake methods, to avoid rebreathing, produces reasonable data from rest to heavy exercise in normal subjects.
An alternative view of the role(s) of surfactant and the alveolar model
Authors: Hills Brian A.
Published: December 2017

Currently, the study of surfactant proteins is much in vogue, but, in the early days, the physics underlying surfactant function was treated somewhat superficially, leaving assumptions that have become culturally embedded, such as the “bubble” model of the alveolus. This review selectively reexamines these assumptions, comparing each combination of alveolar model and role of surfactant for compatibility with the major features of pulmonary mechanics and alveolar stability, morphology, and fluid balance.
Cerebral metabolic response to submaximal exercise
Authors: Ide Kojiro , Horn Allan , Secher Niels H.
Published: December 2017

We studied cerebral oxygenation and metabolism during submaximal cycling in 12 subjects. At two work rates, middle cerebral artery blood velocity increased from 62 ± 3 to 63 ± 3 and 70 ± 5 cm/s as did cerebral oxygenation determined by near-infrared spectroscopy. Oxyhemoglobin increased by 10 ± 3 and 25 ± 3 μmol/l ( P < 0.01), and there was no significant change in brain norepinephrine spillover. The arterial-to-internal-jugular-venous (a-v) difference for O2 decreased at low-intensity exercise (from 3.1 ± 0.1 to 2.9 ± 0.1 mmol/l; P < 0.05) and recovered at moderate exercise (to 3.3 ± 0.1 mmol/l). The profile for glucose was similar: its a-v difference tended to decrease at low-intensity exercise (from 0.55 ± 0.05 to 0.50 ± 0.02 mmol/l) and increased during moderate exercise (to 0.64 ± 0.04 mmol/l; P < 0.05). Thus the molar ratio (a-v difference, O2 to glucose) did not change significantly. However, when the a-v difference for lactate (0.02 ± 0.03 to 0.18 ± 0.04 mmol/l) was taken into account, the O2-to-carbohydrate ratio decreased (from 6.1 ± 0.4 to 4.7 ± 0.3; P < 0.05). The enhanced cerebral oxygenation suggests that, during exercise, cerebral blood flow increases in excess of the O2demand. Yet it seems that during exercise not all carbohydrate taken up by the brain is oxidized, as brain lactate metabolism appears to lower the balance of O2-to-carbohydrate uptake.
Airway hyperresponsiveness induced by chronic exposure to cigarette smoke in guinea pigs: role of tachykinins
Authors: Wu Zhong-Xin , Lee Lu-Yuan
Published: December 2017

This study was carried out to determine whether tachykinins released from lung C-fiber afferents play a part in the bronchial hyperreactivity induced in guinea pigs by chronic exposure to cigarette smoke (CS). Two matching groups of young guinea pigs were exposed to either mainstream CS (CS group) or air (control group) for 20 min twice daily for 14–17 days. There was no difference in the baseline total pulmonary resistance (Rl) between the two groups, but the baseline dynamic lung compliance was reduced (∼19%) in CS animals. The responses of Rl to intravenous injections of ACh, neurokinin (NK) A, and capsaicin were all markedly increased in CS animals; for example, ACh at the same dose of 5.06 μg/kg increased Rl by 207% in the control group and by 697% ( n = 8; P < 0.001) in the CS group. The increased responsiveness was accompanied by significant increases in the numbers of neutrophils, eosinophils, and macrophages in the bronchoalveolar lavage fluid in CS animals. Pretreatment with SR-48968 and CP-99994, antagonists of NK1and NK2 receptors, respectively, did not alter the response of Rlto ACh in control animals, but it abolished the elevated bronchoconstrictive response in the CS animals. Furthermore, the immunoreactivities of substance P and calcitonin gene-related peptide in the bronchoalveolar lavage fluid collected after capsaicin challenge were significantly increased in CS animals. These results show that chronic exposure to CS induced airway mucosal inflammation accompanied by bronchial hyperreactivity in guinea pigs and that the tachykininergic mechanism plays an important role in this augmented responsiveness.
Interactions between the right ventricle and pulmonary vasculature in the fetus
Authors: Grant Daniel A. , Hollander Ellen , Skuza Elizabeth M. , Fauchère Jean-Claude
Published: December 2017

A midsystolic plateau differentiates the pattern of fetal pulmonary trunk blood flow from aortic flow. To determine whether this plateau arises from interactions between the left (LV) and right ventricle (RV) via the ductus arteriosus or from interactions between the RV and the lung vasculature, we measured blood flows and pressures in the pulmonary trunk and aorta of eight anesthetized (ketamine and α-chloralose) fetal lambs. Wave-intensity analysis revealed waves of energy traveling forward, away from the LV and the RV early in systole. During midsystole, a wave of energy traveling back toward the RV decreased blood flow velocity from the RV and produced the plateau in blood flow. Calculations revealed that this backward-traveling wave originated as a forward-traveling wave generated by the RV that was reflected from the lung vasculature back toward the heart and not as a forward-traveling wave generated by the LV that crossed the ductus arteriosus. Elimination of this backward-traveling wave and its associated effect on RV flow may be an important component of the increase in RV output that accompanies birth.
Active muscle and whole body lactate kinetics after endurance training in men
Authors: Bergman Bryan C. , Wolfel Eugene E. , Butterfield Gail E. , Lopaschuk Gary D. , Casazza Gretchen A. , Horning Michael A. , Brooks George A.
Published: December 2017

We evaluated the hypotheses that endurance training decreases arterial lactate concentration ([lactate]a) during continuous exercise by decreasing net lactate release (L˙) and appearance rates (Ra) and increasing metabolic clearance rate (MCR). Measurements were made at two intensities before [45 and 65% peak O2consumption (V˙o 2 peak)] and after training [65% pretrainingV˙o 2 peak, same absolute workload (ABT), and 65% posttrainingV˙o 2 peak, same relative intensity (RLT)]. Nine men (27.4 ± 2.0 yr) trained for 9 wk on a cycle ergometer, 5 times/wk at 75%V˙o 2 peak. Compared with the 65%V˙o 2 peakpretraining condition (4.75 ± 0.4 mM), [lactate]a decreased at ABT (41%) and RLT (21%) ( P < 0.05). L˙ decreased at ABT but not at RLT. Leg lactate uptake and oxidation were unchanged at ABT but increased at RLT. MCR was unchanged at ABT but increased at RLT. We conclude that 1) active skeletal muscle is not solely responsible for elevated [lactate]a; and 2) training increases leg lactate clearance, decreases whole body and leg lactate production at a given moderate-intensity power output, and increases both whole body and leg lactate clearance at a high relative power output.
Time course of changes in markers of myogenesis in overloaded rat skeletal muscles
Authors: Adams Gregory R. , Haddad Fadia , Baldwin Kenneth M.
Published: December 2017

During the process of compensatory muscle hypertrophy, satellite cells are thought to proliferate, differentiate, and then fuse with existing myofibers. We hypothesized that early in this process changes occur in the expression of cellular markers indicative of the onset of myogenic processes. The plantaris muscles of rats were overloaded via the unilateral ablation of synergists. Groups of rats were killed at time points from 6 h to 12 days. Changes in muscle gene expression (mRNA) of cyclin D1, p21, myogenin, MyoD, and insulin-like growth factor I (IGF-I, mRNA and peptide) were measured. Cyclin D1 (a cell cycle marker) was increased after 24 h of overloading and corresponded with changes in muscle DNA content. In contrast, p21 and myogenin, markers of cellular differentiation, were increased after just 12 h. Muscle IGF-I peptide levels were also increased at early time points. The results of this study indicate that myogenic processes are activated in response to increased loading at very early time points (e.g., 12 h) and that IGF-I may be modulating this response. Furthermore, these findings suggest that some cells may have been differentiating very early in the adaptation process before events leading to cellular proliferation have been initiated.
Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1
Authors: Brooks George A. , Brown Marcia A. , Butz C. E. , Sicurello James P. , Dubouchaud Hervé
Published: December 2017

To evaluate the potential role of monocarboxylate transporter-1 (MCT1) in tissue lactate oxidation, isolated rat subsarcolemmal and interfibrillar cardiac and skeletal muscle mitochondria were probed with an antibody to MCT1. Western blots indicated presence of MCT1 in sarcolemmal membranes and in subsarcolemmal and interfibrillar mitochondria. Minimal cross-contamination of mitochondria by cell membrane fragments was verified by probing for the sarcolemmal protein GLUT-1. In agreement, immunolabeling and electron microscopy showed mitochondrial MCT1 in situ. Along with lactic dehydrogenase, the presence of MCT1 in striated muscle mitochondria permits mitochondrial lactate oxidation and facilitates function of the “intracellular lactate shuttle.”