bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the shear modulus of mature and immature rabbit lungs
Authors: Tepper Robert S. , Wiggs Barry , Gunst Susan J. , Paré Peter D.
Published: December 2017

Maximal airway narrowing during bronchoconstriction is greater in immature than in mature rabbits. At a given transpulmonary pressure (Pl), the lung parenchyma surrounding the airway resists local deformation and provides a load that opposes airway smooth muscle shortening. We hypothesized that the force required to produce lung parenchymal deformation, quantified by the shear modulus, is lower in immature rabbit lungs. The shear modulus and the bulk modulus were measured in isolated mature ( n = 8; 6 mo) and immature ( n = 9; 3 wk) rabbit lungs at Pl of 2, 4, 6, 8, and 10 cmH2O. The bulk modulus increased with increasing Pl for mature and immature lungs; however, there was no significant difference between the groups. The shear modulus was lower for the immature than the mature lungs ( P < 0.025), progressively increasing with increasing Pl( P < 0.001) for both groups, and there was no difference between the slopes for shear modulus vs. Pl for the mature and the immature lungs. The mean value of the shear modulus for mature and immature rabbit lungs at Pl = 6 cmH2O was 4.5 vs. 3.8 cmH2O. We conclude that the shear modulus is less in immature than mature rabbit lungs. This small maturational difference in the shear modulus probably does not account for the greater airway narrowing in the immature lung, unless its effect is coupled with a relatively thicker and more compliant airway wall in the immature animal.
Glucose uptake during centrally induced stress is insulin independent and enhanced by adrenergic blockade
Authors: Lekas Michael C. , Fisher Simon J. , El-Bahrani Ban , van Delangeryt Mayliza , Vranic Mladen , Shi Z. Qing
Published: December 2017

Glucose utilization increases markedly in the normal dog during stress induced by the intracerebroventricular (ICV) injection of carbachol. To determine the extent to which insulin, glucagon, and selective (α/β)-adrenergic activation mediate the increment in glucose metabolic clearance rate (MCR) and glucose production (Ra), we used five groups of normal mongrel dogs: 1) pancreatic clamp (PC; n = 7) with peripheral somatostatin (0.8 μg ⋅ kg−1⋅ min−1) and intraportal replacement of insulin (1,482 ± 84 pmol ⋅ kg−1⋅ min−1) and glucagon (0.65 ng ⋅ kg−1⋅ min−1) infusions; 2) PC plus combined α (phentolamine)- and β (propranolol)-blockade (7 and 5 μg ⋅ kg−1⋅ min−1, respectively; α+β; n = 5); 3) PC plus α-blockade (α; n = 6); 4) PC plus β-blockade (β; n = 5); and 5) a carbachol control group without PC (Con; n = 10). During ICV carbachol stress (0–120 min), catecholamines, ACTH, and cortisol increased in all groups. Baseline insulin and glucagon levels were maintained in all groups except Con, where glucagon rose 33%, and α, where insulin increased slightly but significantly. Stress increased ( P < 0.05) plasma glucose in Con, PC, and α but decreased it in β and α+β. The MCR increment was greater ( P < 0.05) in β and α+β than in Con, PC, and α. Raincreased ( P < 0.05) in all groups but was attenuated in α+β. Stress-induced lipolysis was abolished in β ( P < 0.05). The marked rise in lactate in Con, PC, and α was abolished in α+β and β. We conclude that the stress-induced increase in MCR is largely independent of changes in insulin, markedly augmented by β-blockade, and related, at least in part, to inhibition of lipolysis and glycogenolysis, and that Rais augmented by glucagon and α- and β-catecholamine effects.
Chemotactic peptide uptake in acute pancreatitis: correlation with tissue accumulation of leukocytes
Authors: Hartwig Werner , Carter Edward A. , Jimenez Ramon E. , Werner Jens , Fischman Alan J. , Castillo Carlos Fernandez-Del , Warshaw Andrew L.
Published: December 2017

Chemotactic peptides bind specifically to receptors on leukocyte membranes. This property makes them prospective vehicles to evaluate inflammation and infection. We used two well-established models of acute pancreatitis to quantitate the binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine-lysine (fMLFK) to leukocytes and its correlation to degree of organ inflammation. Uptake of the99mTc-labeled nicotinyl hydrazine-derivatized chemotactic peptide analog fMLFK-HYNIC was measured in blood, pancreas, lung, and muscle specimens in rats with edematous or necrotizing pancreatitis and was compared with neutrophil sequestration assessed by myeloperoxidase activity and histology. Chemotactic peptide uptake in the pancreas was increased in mild and severe pancreatitis compared with controls, with higher levels in severe than in mild disease, and correlated with tissue myeloperoxidase activity ( r = 0.7395, P < 0.001). Increased pulmonary uptake only in severe pancreatitis reflected pancreatitis-induced neutrophil sequestration in the lungs. Muscle uptake was unchanged compared with controls. Edema formation did not affect chemotactic peptide uptake. The data suggest that uptake of chemotactic peptides can contribute to quantitative assessment of neutrophils in localized inflammatory processes and is independent of associated edema formation or microcirculatory compromise.
Motor unit firing rates and contractile properties in tibialis anterior of young and old men
Authors: Connelly Denise M. , Rice Charles L. , Roos Martin R. , Vandervoort Anthony A.
Published: December 2017

The effects of aging on motoneuron firing rates and muscle contractile properties were studied in tibialis anterior muscle by comparing results from six young (20.8 ± 0.8 yr) and six old men (82.0 ± 1.7 yr). For each subject, data were collected from repeated tests over a 2-wk period. Contractile tests included maximal voluntary contraction (MVC) with twitch interpolation and stimulated twitch contractions. The old men had 26% lower MVC torque ( P < 0.01) than did the young men, but percent activation was not different (99.1 and 99.3%, respectively). Twitch contraction durations were 23% longer ( P < 0.01) in the old compared with the young men. During a series of repeated brief steady-state contractions at 10, 25, 50, 75, and 100% MVC, motor unit firing rates were recorded. Results from ∼950 motor unit trains in each subject group indicated that at all relative torque levels mean firing rates were 30–35% lower ( P < 0.01) in the old subjects. Comparisons between young and old subjects’ mean firing rates at each of 10%, 50%, and MVC torques and their corresponding mean twitch contraction duration yielded a range of moderate-to-high correlations ( r = −0.67 to −0.84). That lower firing rates were matched to longer twitch contraction durations in the muscle of old men, and relatively higher firing rates were matched with shorter contraction times from the young men, indirectly supports the neuromuscular age-related remodeling principle.
Elite athletes and the gene for angiotensin-converting enzyme
Authors: Taylor Roger R. , Mamotte Cyril D. S. , Fallon Kieran , van Bockxmeer Frank M.
Published: December 2017

The deletion (D) allele of the gene for angiotensin-converting enzyme (ACE) is associated with higher plasma and tissue levels of the enzyme and has also been related to a variety of cardiovascular complications, particularly myocardial infarction. On the basis of indirect evidence, we hypothesized that inheritance of the D allele would contribute to elite athletic ability. Over a period of 4 yr, 120 Caucasian athletes who were national (Australian) representatives in sports demanding a high level of aerobic fitness were recruited. Their ACE genotypes were compared with those of a community control group recruited randomly from the electoral roll. There was no difference in ACE genotype frequencies between the two groups. The DD genotype frequency was 30% in athletes and 29% in the control group, and the II genotype frequency was 22.5 and 22%, respectively. The results do not exclude the possibility that ACE genotype could be related to some attribute relating to a specific type of elite athletic ability or that there may be a difference between genders. Larger studies are desirable.
Single- and multifrequency models for bioelectrical impedance analysis of body water compartments
Authors: Gudivaka R. , Schoeller D. A. , Kushner R. F. , Bolt M. J. G.
Published: December 2017

The 1994 National Institutes of Health Technology Conference on bioelectrical impedance analysis (BIA) did not support the use of BIA under conditions that alter the normal relationship between the extracellular (ECW) and intracellular water (ICW) compartments. To extend applications of BIA to these populations, we investigated the accuracy and precision of seven previously published BIA models for the measurement of change in body water compartmentalization among individuals infused with lactated Ringer solution or administered a diuretic agent. Results were compared with dilution by using deuterium oxide and bromide combined with short-term changes of body weight. BIA, with use of proximal, tetrapolar electrodes, was measured from 5 to 500 kHz, including 50 kHz. Single-frequency, 50-kHz models did not accurately predict change in total body water, but the 50-kHz parallel model did accurately measure changes in ICW. The only model that accurately predicted change in ECW, ICW, and total body water was the 0/∞-kHz parallel (Cole-Cole) multifrequency model. Use of the Hanai correction for mixing was less accurate. We conclude that the multifrequency Cole-Cole model is superior under conditions in which body water compartmentalization is altered from the normal state.
Activation of the insular cortex is affected by the intensity of exercise
Authors: Williamson J. W. , McColl R. , Mathews D. , Ginsburg M. , Mitchell J. H.
Published: December 2017

The purpose of this investigation was to determine whether there were differences in the magnitude of insular cortex activation across varying intensities of static and dynamic exercise. Eighteen healthy volunteers were studied: eight during two intensities of leg cycling and ten at different time periods during sustained static handgrip at 25% maximal voluntary contraction or postexercise cuff occlusion. Heart rate, blood pressure (BP), perceived exertion, and regional cerebral blood flow (rCBF) distribution data were collected. There were significantly greater increases in insular rCBF during lower (6.3 ± 1.7%; P < 0.05) and higher (13.3 ± 3.8%; P < 0.05) intensity cycling and across time during static handgrip (change from rest for right insula at 2–3 min, 3.8 ± 1.1%, P < 0.05; and at 4–5 min, 8.6 ± 2.8%, P < 0.05). Insular rCBF was decreased during postexercise cuff occlusion (−5.5 ± 1.2%; P < 0.05) with BP sustained at exercise levels. Right insular rCBF data, but not left, were significantly related, with individual BP changes ( r2= 0.80; P < 0.001) and with ratings of perceived exertion ( r2= 0.79; P < 0.01) during exercise. These results suggest that the magnitude of insular activation varies with the intensity of exercise, which may be further related to the level of perceived effort or central command.
Human bronchial artery blood flow after lung Tx with direct bronchial artery revascularization
Authors: Nørgaard Martin A. , Hove Jens D. , Efsen Fritz , Saunamäki Kari , Hesse Birger , Pettersson Gösta
Published: December 2017

The inaccuracy of measuring human bronchial artery blood flow has previously been considerable. En bloc double-lung transplantation with bronchial artery revascularization (BAR) using a single conduit offers the unique opportunity of direct measurement of the total bronchial artery blood flow. In eight en bloc double-lung-transplanted patients with complete BAR, the basal blood flow was measured by using a 0.014-in. Doppler guide wire and arteriography. The average peak velocity in the conduit was 12–73 cm/s [±2.1 (SD) cm/s], and the conduit diameter was 1.7–3.1 mm [±0.10 (SD) mm], giving individual basal flow values between 19 and 67 ml/min [±5 (SD) ml/min], or 0.2–1.9% of estimated cardiac output. In three patients basal measurements were followed by injection of nitroglycerin and verapamil into the conduit. This increased the bronchial artery flow to 121–262% of basal values (31–89 ml/min). The measured values appear more physiologically plausible than previous bronchial artery blood flow measurements in humans.
CO2 microdialysis in retrotrapezoid nucleus of the rat increases breathing in wakefulness but not in sleep
Authors: Li Aihua , Randall Margaret , Nattie Eugene E.
Published: December 2017

Central chemoreceptors are widespread within the brain stem. We suggest that their function at some sites may vary with the state of arousal. In this study, we tested the hypothesis that the function of chemoreceptors in the retrotrapezoid nucleus (RTN) varies with sleep and wakefulness. In unanesthetized rats, we produced focal acidification of the RTN by means of a microdialysis probe (tip containing the semipermeable membrane = 1-mm length, 240-μm diameter, and 45-nl volume). With the use of a dialysate equilibrated with 25% CO2, the tissue pH change (measured in anesthetized animals) was 1) limited to within 550 μm of the probe and, 2) at the probe tip, was equivalent to that observed with end-tidal[Formula: see text] of 63 Torr. This focal acidification of the RTN increased ventilation significantly by 24% above baseline, on average, in 13 trials in seven rats only during wakefulness. The effect was entirely due to an increase in tidal volume. During sleep defined by behavioral criteria, ventilation was unaffected, on average, in 10 trials in seven rats. During sleep, the chemoreceptors in the RTN appear to be inactive, or, if active, the respiratory control system either is not responding or is responding with very low gain. Because ventilation is increased during sleep with all central chemoreceptor sites stimulated via systemic CO2 application, other central chemoreceptor locations must have enhanced effectiveness.
Effects of hyper- and hypoventilation on gastric and sublingual P CO 2
Authors: Pernat Andrej , Weil Max Harry , Tang Wanchun , Yamaguchi Hitoshi , Pernat Andreja Marn , Sun Shijie , Bisera Joe
Published: December 2017

We investigated the effects of hyper- and hypoventilation on gastric ([Formula: see text]) and sublingual (P[Formula: see text]) tissue[Formula: see text] before, during, and after reversal of hemorrhagic shock. [Formula: see text] was measured with ion-sensitive field-effect transistor sensor and P[Formula: see text] with a CO2 microelectrode. Under physiological conditions and during hemorrhagic shock, decreases in arterial ([Formula: see text]) and end-tidal ([Formula: see text])[Formula: see text] induced by hyperventilation produced corresponding decreases in[Formula: see text] and P[Formula: see text]. Hypoventilation produced corresponding increases in[Formula: see text],[Formula: see text],[Formula: see text], and P[Formula: see text]. Accordingly, acute decreases and increases in[Formula: see text] and[Formula: see text] produced statistically similar decreases and increases in[Formula: see text] and P[Formula: see text]. No significant changes in the tissue[Formula: see text]-[Formula: see text]gradients were observed during hemorrhagic shock in the absence or in the presence of hyper- or hypoventilation. Acute changes in[Formula: see text] and P[Formula: see text] should, therefore, be interpreted in relationship with concurrent changes in[Formula: see text] and/or[Formula: see text].
Negative interstitial pressure in the peritendinous region during exercise
Authors: Langberg Henning , Skovgaard Dorthe , Bülow Jens , Kjær Michael
Published: December 2017

In the present study, tissue pressure in the peritendinous area ventral to the human Achilles tendon was determined. The pressure was measured during rest and intermittent isometric calf muscle exercise at three torques (56, 112, and 168 Nm) 20, 40 and 50 mm proximal to the insertion of the tendon in 11 healthy, young individuals. In all experiments a linear significant decrease in pressure was obtained with increasing torque [e.g., at 40 mm: −0.4 ± 0.3 mmHg (rest) to −135 ± 12 mmHg (168 Nm)]. No significant differences were obtained among the three areas measured. On the basis of these observations, microdialysis was performed in the peritendinous region with a colloid osmotic active substance (Dextran 70, 0.1 g/ml) added to the perfusate with the aim of counteracting the negative tissue pressure. Dialysate volume was found to be fully restored (100 ± 4%) during exercise. It is concluded that a marked negative tissue pressure is generated in the peritendinous space around the Achilles tendon during exercise in humans. Negative tissue pressure could lead to fluid shift and could be involved in the increase in blood flow previously noted in the peritendinous tissue during exercise (H. Langberg, J. Bülow, and M. Kjær. Acta Physiol. Scand. 163: 149–153, 1998; H. Langberg, J. Bülow, and M. Kjær. Clin. Physiol. 19: 89–93, 1999).
Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide
Authors: Holden William E. , Wilkins John P. , Harris Michelle , Milczuk Henry A. , Giraud George D.
Published: December 2017

Nitric oxide (NO) is released into nasal air, but its function is unknown. We hypothesized that nasal vascular tone and/or flow influences temperature conditioning of nasal air and that NO participates in this process. We measured nasal air temperature (via a thermocouple) and exhaled nasal NO release (by chemiluminescence) in five humans and examined the effects of an aerosolized vasoconstrictor (oxymetazoline), a vasodilator (papaverine), NG-nitro-l-arginine methyl ester, an inhibitor of NO synthase, or saline (control). Compared with saline (which caused no changes in nasal air temperature or exhaled NO release), oxymetazoline (0.05%) reduced nasal air temperature and NO release (130.8 ± 15.1 to 81.3 ± 12.8 nl ⋅ min−1⋅ m−2; P < 0.01). Papaverine (0.01 M) increased nasal air temperature and NO release (131.8 ± 13.1 to 157.2 ± 17.4 nl ⋅ min−1⋅ m−2; P < 0.03). NG-nitro-l-arginine methyl ester reduced nasal air temperature and NO release (123.7 ± 14.2 to 44.2 ± 23.7 nl ⋅ min−1⋅ m−2; P < 0.01). The results suggest that vascular tone and/or flow modulates temperature conditioning and that NO may participate in that function.
Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans
Authors: Pietropaoli Anthony P. , Perillo Irene B. , Torres Alfonso , Perkins Peter T. , Frasier Lauren M. , Utell Mark J. , Frampton Mark W. , Hyde Richard W.
Published: December 2017

Human airways produce nitric oxide (NO), and exhaled NO increases as expiratory flow rates fall. We show that mixing during exhalation between the NO produced by the lower, alveolar airways (V˙l NO) and the upper conducting airways (V˙u NO) explains this phenomenon and permits measurement ofV˙l NO,V˙u NO, and the NO diffusing capacity of the conducting airways (Du NO). After breath holding for 10–15 s the partial pressure of alveolar NO (Pa) becomes constant, and during a subsequent exhalation at a constant expiratory flow rate the alveoli will deliver a stable amount of NO to the conducting airways. The conducting airways secrete NO into the lumen (V˙u NO), which mixes with Pa during exhalation, resulting in the observed expiratory concentration of NO (Pe). At fast exhalations, Pa makes a large contribution to Pe, and, at slow exhalations, NO from the conducting airways predominates. Simple equations describing this mixing, combined with measurements of Pe at several different expiratory flow rates, permit calculation of Pa,V˙u NO, and Du NO.V˙l NOis the product of Pa and the alveolar airway diffusion capacity for NO. In seven normal subjects, Pa = 1.6 ± 0.7 × 10−6 (SD) Torr,V˙l NO= 0.19 ± 0.07 μl/min,V˙u NO= 0.08 ± 0.05 μl/min, and Du NO = 0.4 ± 0.4 ml ⋅ min−1 ⋅ Torr−1. These quantitative measurements ofV˙l NOandV˙u NOare suitable for exploring alterations in NO production at these sites by diseases and physiological stresses.
Regulation of pulmonary circulation by alveolar oxygen tension via airway nitric oxide
Authors: Ide Hiroshi , Nakano Hitoshi , Ogasa Toshiyuki , Osanai Shinobu , Kikuchi Kenjirou , Iwamoto Jun
Published: December 2017

The effects of airway (AH) and vascular hypoxia (VH) on the production of nitric oxide (NO;V˙no) were tested in isolated buffer-perfused (BFL) and blood-perfused rabbit lungs (BLL). To produce AH and/or VH, the lung was ventilated with 1% O2gas, and/or the perfusate was deoxygenated by a membrane oxygenator located on the inlet limb to the pulmonary artery. We measured exhaled NO (V˙no), accumulation of perfusate NOx, and pulmonary arterial pressure (Ppa) during AH (inspired O2fraction = 0.01) and/or VH (venous [Formula: see text] = 26 Torr). In BFL, a pure AH without VH caused decreases inV˙no and NOx accumulation with a rise in Ppa. However, neitherV˙no, NOx accumulation, nor Ppa changed during VH. Similarly, in BLL, only AH reduced V˙no, although NOx accumulation was not measurable because of Hb. When alveolar [Formula: see text] was gradually reduced from 152 to 0 Torr for 20 min, AH reducedV˙nocurvilinearly from 73.9 ± 8 to 25.6 ± 8 nl/min in BFL and from 26.0 ± 2 to 5.2 ± 1 nl/min in BLL. This plot was analogous to that of a substrate-velocity curve for an enzyme obeying Michaelis-Menten kinetics. The apparent Michaelis-Menten constant for O2was calculated to be 23.2 μM for BLL and 24.1 μM for BFL. These results indicate that theV˙no in the airway epithelia is dependent on the level of inspired O2fraction, leading to the tentative conclusion that epithelial NO synthase is O2sensitive over the physiological range of alveolar [Formula: see text]and controls pulmonary circulation.
Eccentric exercise markedly increases c-Jun NH2-terminal kinase activity in human skeletal muscle
Authors: Boppart Marni D. , Aronson Doron , Gibson Lindsay , Roubenoff Ronenn , Abad Leslie W. , Bean Jonathan , Goodyear Laurie J. , Fielding Roger A.
Published: December 2017

Eccentric contractions require the lengthening of skeletal muscle during force production and result in acute and prolonged muscle injury. Because a variety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH2-terminal kinase (JNK) intracellular signaling cascade in skeletal muscle, we investigated the effects of eccentric exercise on the activation of this stress-activated protein kinase in human skeletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal concentric or eccentric knee extensions on a KinCom isokinetic dynamometer (10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from the vastus lateralis muscle 24 h before exercise (basal), immediately postexercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a much higher activation (15.4 ± 4.5 vs. 3.5 ± 1.4-fold increase above basal, eccentric vs. concentric). By 6 h after exercise, JNK activity decreased back to baseline values. In contrast to the greater activation of JNK with eccentric exercise, the mitogen-activated protein kinase kinase 4, the immediate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylation of a variety of transcription factors, including c-Jun, the results from this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human skeletal muscle.
Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training
Authors: Pellegrino Riccardo , Villosio Carlo , Milanese Ugo , Garelli Giuseppe , Rodarte Joseph R. , Brusasco Vito
Published: December 2017

In this study we explored the effects of physical training on the response of the respiratory system to exercise. Eight subjects with irreversible mild-to-moderate airflow obstruction [forced expiratory volume in 1 s of 85 ± 14 (SD) % of predicted and ratio of forced expiratory volume in 1 s to forced vital capacity of 68 ± 5%] and six normal subjects with similar anthropometric characteristics underwent a 2-mo physical training period on a cycle ergometer three times a week for 31 min at an intensity of ∼80% of maximum heart rate. At this work intensity, tidal expiratory flow exceeded maximal flow at control functional residual capacity [FRC; expiratory flow limitation (EFL)] in the obstructed but not in the normal subjects. An incremental maximum exercise test was performed on a cycle ergometer before and after training. Training improved exercise capacity in all subjects, as documented by a significant increase in maximum work rate in both groups ( P < 0.001). In the obstructed subjects at the same level of ventilation at high workloads, FRC was greater after than before training, and this was associated with an increase in breathing frequency and a tendency to decrease tidal volume. In contrast, in the normal subjects at the same level of ventilation at high workloads, FRC was lower after than before training, so that tidal volume increased and breathing frequency decreased. These findings suggest that adaptation to breathing under EFL conditions does not occur during exercise in humans, in that obstructed subjects tend to increase FRC during exercise after experiencing EFL during a 2-mo strenuous physical training period.
Skeletal muscle metabolism during high-intensity sprint exercise is unaffected by dichloroacetate or acetate infusion
Authors: Howlett Richard A. , Heigenhauser George J. F. , Spriet Lawrence L.
Published: December 2017

This study investigated whether increased provision of oxidative substrate would reduce the reliance on nonoxidative ATP production and/or increase power output during maximal sprint exercise. The provision of oxidative substrate was increased at the onset of exercise by the infusion of acetate (AC; increased resting acetylcarnitine) or dichloroacetate [DCA; increased acetylcarnitine and greater activation of pyruvate dehydrogeanse (PDH- a)]. Subjects performed 10 s of maximal cycling on an isokinetic ergometer on three occasions after either DCA, AC, or saline (Con) infusion. Resting PDH- a with DCA was increased significantly over AC and Con trials (3.58 ± 0.4 vs. 0.52 ± 0.1 and 0.74 ± 0.1 mmol ⋅ kg wet muscle−1 ⋅ min−1). DCA and AC significantly increased resting acetyl-CoA (35.2 ± 4.4 and 22.7 ± 2.9 vs. 10.2 ± 1.3 μmol/kg dry muscle) and acetylcarnitine (12.9 ± 1.4 and 11.0 ± 1.0 vs. 3.3 ± 0.6 mmol/kg dry muscle) over Con. Resting contents of phosphocreatine, lactate, ATP, and glycolytic intermediates were not different among trials. Average power output and total work done were not different among the three 10-s sprint trials. Postexercise, PDH- a in AC and Con trials had increased significantly but was still significantly lower than in DCA trial. Acetyl-CoA did not increase in any trial, whereas acetylcarnitine increased significantly only in DCA. Exercise caused identical decreases in ATP and phosphocreatine and identical increases in lactate, pyruvate, and glycolytic intermediates in all trials. These data suggest that there is an inability to utilize extra oxidative substrate (from either stored acetylcarnitine or increased PDH- a) during exercise at this intensity, possibly because of O2 and/or metabolic limitations.
Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion
Authors: Griffin Kawanza L. , Laughlin M. Harold , Parker Janet L.
Published: December 2017

The present study evaluated combined effects of chronic coronary occlusion and exercise training on endothelial function. Gradual occlusion was produced by placement of an ameroid constrictor around the proximal left circumflex (LCX) coronary artery of female swine. Two months after placement of the ameroid, animals were restricted to their pens or exercise trained for 16 wk. Epicardial arteries (>500 μm ID) were isolated from the collateral-dependent LCX coronary artery distal to the occlusion and the nonoccluded left anterior descending (LAD) coronary artery. Bradykinin- and ADP-mediated relaxation of LCX and LAD coronary arteries was enhanced after exercise training. Inhibition of nitric oxide synthase with N G-nitro-l-arginine methyl ester decreased bradykinin- and ADP-mediated relaxation in LCX and LAD myocardial regions. Importantly, combined inhibition of effects of endothelium-derived hyperpolarizing factor with increased extracellular K+ (20–30 mM) and nitric oxide synthase completely abolished coronary LAD and LCX relaxation to bradykinin. Our data indicate that exercise training improves endothelium-mediated relaxation of arteries isolated after chronic coronary artery occlusion, likely as a result of enhanced production of nitric oxide and endothelium-derived hyperpolarizing factor.
Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle
Authors: Holmes B. F. , Kurth-Kraczek E. J. , Winder W. W.
Published: December 2017

This study was designed to determine whether chronic chemical activation of AMP-activated protein kinase (AMPK) would increase glucose transporter GLUT-4 and hexokinase in muscles similarly to periodic elevation of AMPK that accompanies endurance exercise training. The adenosine analog, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), has previously been shown to be taken up by cells and phosphorylated to form a compound (5-aminoimidazole-4-carboxamide ribonucleotide) that mimics the effect of AMP on AMPK. A single injection of AICAR resulted in a marked increase in AMPK in epitrochlearis and gastrocnemius/plantaris muscles 60 min later. When rats were injected with AICAR (1 mg/g body wt) for 5 days in succession and were killed 1 day after the last injection, GLUT-4 was increased by 100% in epitrochlearis muscle and by 60% in gastrocnemius muscle in response to AICAR. Hexokinase was also increased ∼2.5-fold in the gastrocnemius/plantaris. Gastrocnemius glycogen content was twofold higher in AICAR-treated rats than in controls. Chronic chemical activation of AMPK, therefore, results in increases in GLUT-4 protein, hexokinase activity, and glycogen, similarly to those induced by endurance training.
Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia
Authors: Kraiczi Holger , Magga Jarkko , Sun Xiang Ying , Ruskoaho Heikki , Zhao Xiaohe , Hedner Jan
Published: December 2017

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.
Electron spin resonance spectroscopy, exercise, and oxidative stress: an ascorbic acid intervention study
Authors: Ashton Tony , Young Ian S. , Peters John R. , Jones Eleri , Jackson Simon K. , Davies Bruce , Rowlands Christopher C.
Published: December 2017

Oxygen free radicals are highly reactive species that are produced in increased quantities during strenuous exercise and can damage critical biological targets such as membrane phospholipids. The present study examined the effect of acute ascorbic acid supplementation on exercise-induced free radical production in healthy subjects. Results demonstrate increases in the intensity of the α-phenyl- tert-butylnitrone adduct (0.05 ± 0.02 preexercise vs. 0.19 ± 0.03 postexercise, P = 0.002, arbitrary units) together with increased lipid hydroperoxides (1.14 ± 0.06 μmol/l preexercise vs. 1.62 ± 0.19 μmol/l postexercise, P = 0.005) and malondialdehyde (0.70 ± 0.04 μmol/l preexercise vs. 0.80 ± 0.04 μmol/l postexercise, P = 0.0152) in the control phase. After supplementation with ascorbic acid, there was no significant increase in the electron spin resonance signal intensity (0.02 ± 0.01 preexercise vs. 0.04 ± 0.02 postexercise, arbitrary units), lipid hydroperoxides (1.12 ± 0.21 μmol/l preexercise vs. 1.12 ± 0.08 μmol/l postexercise), or malondialdehyde (0.63 ± 0.07 μmol/l preexercise vs. 0.68 ± 0.05 μmol/l postexercise). The results indicate that acute ascorbic acid supplementation prevented exercise-induced oxidative stress in these subjects.
Chronic recordings of hypoglossal nerve activity in a dog model of upper airway obstruction
Authors: Sahin Mesut , Durand Dominique M. , Haxhiu Musa A.
Published: December 2017

The activity of the hypoglossal nerve was recorded during pharyngeal loading in sleeping dogs with chronically implanted cuff electrodes. Three self-coiling spiral-cuff electrodes were implanted in two beagles for durations of 17, 7, and 6 mo. During quiet wakefulness and sleep, phasic hypoglossal activity was either very small or not observable above the baseline noise. Applying a perpendicular force on the submental region by using a mechanical device to narrow the pharyngeal airway passage increased the phasic hypoglossal activity, the phasic esophageal pressure, and the inspiratory time in the next breath during non-rapid-eye-movement sleep. The phasic hypoglossal activity sustained at the elevated level while the force was present and increased with increasing amounts of loading. The hypoglossal nerve was very active in rapid-eye-movement sleep, especially when the submental force was present. The data demonstrate the feasibility of chronic recordings of the hypoglossal nerve with cuff electrodes and show that hypoglossal activity has a fast and sustained response to the internal loading of the pharynx induced by applying a submental force during non-rapid-eye-movement sleep.
Women at altitude: energy requirement at 4,300 m
Authors: Mawson Jacinda T. , Braun Barry , Rock Paul B. , Moore Lorna G. , Mazzeo Robert , Butterfield Gail E.
Published: December 2017

To test the hypotheses that prolonged exposure to moderately high altitude increases the energy requirement of adequately fed women and that the sole cause of the increase is an elevation in basal metabolic rate (BMR), we studied 16 healthy women [21.7 ± 0.5 (SD) yr; 167.4 ± 1.1 cm; 62.2 ± 1.0 kg]. Studies were conducted over 12 days at sea level (SL) and at 4,300 m [high altitude (HA)]. To test that menstrual cycle phase has an effect on energetics at HA, we monitored menstrual cycle in all women, and most women ( n = 11) were studied in the same phase at SL and HA. Daily energy intake at HA was increased to respond to increases in BMR and to maintain body weight and body composition. Mean BMR for the group rose 6.9% above SL by day 3 at HA and fell to SL values by day 6. Total energy requirement remained elevated 6% at HA [∼670 kJ/day (160 kcal/day) above that at SL], but the small and transient increase in BMR could not explain all of this increase, giving rise to an apparent “energy requirement excess.” The transient nature of the rise in BMR may have been due to the fitness level of the subjects. The response to altitude was not affected by menstrual cycle phase. The energy requirement excess is at present unexplained.
Global field power helps separate respiratory-related evoked potentials from EMG contamination
Authors: Daubenspeck J. Andrew , Lim Lisa M. , Akay Metin
Published: December 2017

Respiratory-related evoked potentials (RREPs) were stimulated by brief (200-ms) oral pressure pulses (−10 cmH2O) applied at the onset of inspiration in 12 subjects. Scalp potentials were measured at 30 sites on a rectangular grid that encompassed the right side of the scalp overlying the somatosensory cortex (SSC). Concurrent and significant masseter EMG (mEMG) activity was evoked by the pressure pulse, and we found correlational evidence for contamination of the RREP by the mEMG. The global field power (GFP) was used to provide a robust, reference-independent measure of SSC activation that provided partial insulation from mEMG contamination. The mean GFP from all subjects, reflective of afferent information from respiratory mechanoreceptors, showed a latency to onset of significant afferent SSC activity of ∼25 ms. Scalp GFP activity during control experiments (absence of applied pressure) was significant and may reflect ongoing afferent activity from inspiration.
Effects of ventilation on the surfactant system in sepsis-induced lung injury
Authors: Malloy Jaret L. , Veldhuizen Ruud A. W. , Lewis James F.
Published: December 2017

The present study examined the effects of mechanical ventilation, with or without positive end-expiratory pressure (PEEP), on the alveolar surfactant system in an animal model of sepsis-induced lung injury. Septic animals ventilated without PEEP had a significant deterioration in oxygenation compared with preventilated values (arterial[Formula: see text]/inspired O2fraction 316 ± 16 vs. 151 ± 14 Torr; P < 0.05). This was associated with a significantly lower percentage of the functional large aggregates (59 ± 3 vs. 72 ± 4%) along with a significantly reduced function (minimum surface tension 17.7 ± 1.8 vs. 11.8 ± 3.8 mN/m) compared with nonventilated septic animals ( P < 0.05). Sham animals similarly ventilated without PEEP maintained oxygenation, percent large aggregates and surfactant function. With the addition of PEEP, the deterioration in oxygenation was not observed in the septic animals and was associated with no alterations in the surfactant system. We conclude that animals with sepsis-induced lung injury are more susceptible to the harmful effects of mechanical ventilation, specifically lung collapse and reopening, and that alterations in alveolar surfactant may contribute to the development of lung dysfunction.
Enhanced inotropic response to dobutamine in strength-trained subjects with left ventricular hypertrophy
Authors: Suman Oscar E. , Hasten Deborah , Turner Michael J. , Rinder Morton R. , Spina Robert J. , Ehsani Ali A.
Published: December 2017

To determine whether strength-trained individuals with physiological concentric left ventricular (LV) hypertrophy exhibit enhanced inotropic responses to catecholamines, we studied 11 bodybuilders, aged 33.0 ± 2 (SE) yr old, and 10 sedentary healthy subjects, aged 31.3 ± 2.4 yr old, at baseline and during infusion of incremental doses of dobutamine after atropine. The bodybuilders had larger LV mass, posterior wall and septal wall thicknesses, and wall thickness-to-radius ratio, assessed with two-dimensional echocardiography, than did the sedentary subjects. There was a significant correlation between LV mass and lean body mass irrespective of training status. Baseline LV fractional shortening was similar in the two groups. There was a greater inotropic response to dobutamine in the strength-trained individuals, as evidenced by a steeper slope of the fractional shortening-end-systolic wall stress relationship with a higher y-axis intercept and by a shallower end-systolic wall stress-end systolic diameter relationship without changes in end-diastolic diameter. The heart rate response to dobutamine was attenuated in the strength-trained athletes. There was a significant correlation ( r = 0.604, P < 0.05) between the inotropic sensitivity to dobutamine and LV mass normalized for lean body mass in the bodybuilders. The data suggest that concentric LV physiological hypertrophy in the resistance-trained individuals is associated with enhanced inotropic but not chronotropic responses to catecholamines.
Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study*
Authors: Bouchard Claude , Rankinen Tuomo , Chagnon Yvon C. , Rice Treva , Pérusse Louis , Gagnon Jacques , Borecki Ingrid , An Ping , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Province Michael , Rao D. C.
Published: December 2017

This study aimed to identify human genomic regions that are linked to maximal oxygen uptake (V˙o 2 max) in sedentary individuals or to the responsiveness ofV˙o 2 max to a standardized endurance training program. The results of a genomic scan based on 289 polymorphic markers covering all 22 pairs of autosomes performed on the Caucasian families of the HERITAGE Family Study are presented. The mean spacing of the markers was 11 cM, and a total of 99 families and 415 pairs of siblings were available for the study.V˙o 2 max in the sedentary state was adjusted for the effects of age, sex, body mass, fat mass, and fat-free mass, whereas theV˙o 2 maxresponse was adjusted for age and baseline level of the phenotype. Two analytic strategies were used: a single-point linkage procedure using all available pairs of siblings (SIBPAL) and a multipoint variance components approach using all the family data (SEGPATH). Results indicate that linkages at P values of 0.01 and better are observed with markers on 4q, 8q, 11p, and 14q forV˙o 2 max before training and with markers on 1p, 2p, 4q, 6p, and 11p for the change inV˙o 2 max in response to a 20-wk standardized endurance training program. These chromosomal regions harbor many genes that may qualify as candidate genes for these quantitative traits. They should be investigated in this and other cohorts.
Diuretic effect of hypoxia, hypocapnia, and hyperpnea in humans: relation to hormones and O2chemosensitivity
Authors: Hildebrandt Wulf , Ottenbacher Andy , Schuster Markus , Swenson Erik R. , Bärtsch Peter
Published: December 2017

We studied the contributions of hypoxemia, hypocapnia, and hyperpnea to the acute hypoxic diuretic response (HDR) in humans and evaluated the role of peripheral O2chemosensitivity and renal hormones in HDR. Thirteen healthy male subjects (age 19–38 yr) were examined after sodium equilibration (intake: 120 mmol/day) during 90 min of normoxia (NO), poikilocapnic hypoxia (PH), and isocapnic hypoxia (IH) ( days 1–3, random order, double blind), as well as normoxic voluntary hyperpnea (HP; day 4), matching ventilation during IH. O2saturation during PH and IH was kept equal to a mean level measured between 30 and 90 min of breathing 12% O2in a pretest. Urine flow during PH and IH (1.81 ± 0.92 and 1.94 ± 1.03 ml/min, respectively) but not during HP (1.64 ± 0.96 ml/min) significantly exceeded that during NO (control, 1.38 ± 0.71 ml/min). Urine flow increases vs. each test day's baseline were significant with PH, IH, and HP. Differences in glomerular filtration rate, fractional sodium clearance, urodilatin, systemic blood pressure, or leg venous compliance were excluded as factors of HDR. However, slight increases in plasma and urinary endothelin-1 and epinephrine with PH and IH could play a role. In conclusion, the early HDR in humans is mainly due to hypoxia and hypocapnia. It occurs without natriuresis and is unrelated to O2chemosensitivity (hypoxic ventilatory response).
Reciprocal activation of hypopharyngeal muscles and their effect on upper airway area
Authors: Feroah T. R. , Forster H. V. , Pan L. G. , Rice T.
Published: December 2017

We examined in awake goats, 1) with intact upper airways (UAW), the effect of altering chemical drive on pharyngeal constrictors [thyropharyngeus (TP) and hypopharyngeus (HP)] and a dilator [stylopharyngeus (SP)], and 2) with an isolated UAW, the effect of activation of these muscles on supraglottic UAW (UAWSG) area. During eupnea in nine goats with intact UAW, the TP and HP were active during expiration, whereas the SP exhibited tonic expiratory and phasic inspiratory activity. After mechanically induced apneas (MIA), TP activity increased (263%, P < 0.02), HP activity exhibited a small, varied response, and SP activity greatly decreased (10%, P < 0.02). During resumption of respiratory effort, all goats exhibited absent/reduced airflow, and when diaphragm activity was 95% of control, TP activity remained elevated (135%) and SP activity was reduced (56%, P < 0.02). During hypercapnia, 1) TP activity decreased ( P < 0.02), 2) HP response varied, and 3) SP activity increased ( P < 0.02). After MIA in six goats with isolated UAW, TP activity increased 198% ( P < 0.02) and UAWSGarea (endoscopically determined) decreased (to 15% of control, P < 0.02). During recovery from MIA, a correlation was found between UAWSGarea and the ratio of SP to TP activity. We conclude that the reciprocal activation of mechanically opposing dilator and constrictor muscles in the hypopharynx is correlated to changes in the UAWSGarea, and an imbalance in activity of these opposing muscles can lead to UAWSGnarrowing.
Effect of recombinant SP-C surfactant in a porcine lavage model of acute lung injury
Authors: Spragg R. G. , Smith R. M. , Harris K. , Lewis J. , Häfner D. , Germann P.
Published: December 2017

Synthetic surfactants allow examination of the effects of specific components of natural surfactant. To determine whether surfactant containing apoprotein C, dipalmitoyl-phosphatidylcholine, phosphatidylglycerol, and palmitic acid restores gas-exchanging function in acute lung injury (ALI), we administered such surfactant (in doses of 50 or 100 mg/kg and in volumes from 1 to 6 ml/kg) or phospholipid (PL) alone, by intratracheal instillation, to pigs with ALI induced by massive saline lavage. Animals ventilated with 100% O2and receiving 1, 2, 4, or 6 ml/kg of 50 mg/kg recombinant surfactant apoprotein C (rSP-C) surfactant or 2 ml/kg of 50 mg/kg PL (control) had mean arterial[Formula: see text] values, 4 h after treatment, of 230, 332, 130, 142, or 86 Torr, respectively. Animals receiving 1, 2, or 4 ml/kg of 100 mg/kg rSP-C surfactant or 2 ml/kg of 100 mg/kg PL (control) had mean arterial[Formula: see text] values of 197, 214, 148, or 88 Torr, respectively. Surfactant PL distribution was homogeneous. Hyaline membrane formation was reduced in treated animals. Thus, in this model of ALI, rSP-C with PL has the capacity to improve gas exchange and possibly modify lung injury.