bluuebunny/crossref_metadata_2025 huggingface dataset:
Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance
Authors: McKenna Michael J. , Morton Judith , Selig Steve E. , Snow Rodney J.
Published: December 2017

This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 × (5 g Cr-H2O + 5 g dextrose)/day)] or a placebo (6 × 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased ( P < 0.05) at 0 [by 22.9 ± 4.2, 8.9 ± 1.9, and 14.0 ± 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS.
Cardiovascular hemodynamics with increasing exercise intensities in postmenopausal women
Authors: McCole Steve D. , Brown Michael D. , Moore Geoffrey E. , Zmuda Joseph M. , Cwynar Jeffrey D. , Hagberg James M.
Published: December 2017

We sought to determine the cardiovascular responses to increasing exercise intensities in postmenopausal women with different physical activity levels and hormone replacement therapy (HRT) status. Forty-four women (11 sedentary, 19 physically active, 14 master athletes; 24 not on HRT, 20 on HRT) completed treadmill exercise at 40, 60, 80, and 100% of maximal oxygen consumption. Oxygen consumption, heart rate, blood pressure, and cardiac output, determined via acetylene rebreathing, were measured at each exercise intensity. HRT did not affect cardiovascular hemodynamics. Stroke volume (SV) decreased significantly between 40 and 100% of maximal oxygen consumption in all groups, and the decrease did not differ among groups. The greater oxygen consumption of the athletes at each intensity was due to their significantly greater cardiac output, which was the result of a significantly greater SV, compared with both of the less active groups. The athletes had significantly lower total peripheral resistance at each exercise intensity than did the two less active groups. There were no consistent significant hemodynamic differences between the physically active and sedentary women. These results indicate that SV decreases in postmenopausal women as exercise intensity increases to maximum, regardless of their habitual physical activity levels or HRT status.
V-shaped cushion at the origin of bovine pulmonary supernumerary arteries: structure and putative function
Authors: Shaw Angus M. , Bunton David C. , Fisher Alan , McGrath John C. , Montgomery Ian , Daly Craig , MacDonald Allan
Published: December 2017

This study investigates the anatomic structure at the origin of pulmonary supernumerary arteries and their parent conventional artery. Histological examination showed that at the origin of each supernumerary artery the wall of the parent conventional artery is organized into a distinct V-shaped structure, which begins on the hilum side of each supernumerary artery as a funnel-shaped channel running into the supernumerary artery. The base of the channel is particularly thin walled. The lateral walls of the channel are composed of musculoelastic cushions that become more pronounced toward the supernumerary artery and fuse on its distal side, forming a baffle that projects over the supernumerary artery lumen. These V-shaped structures/cushions were observed with video stereo dissecting microscopy in both an open and closed state in isolated arteries in vitro. Pulmonary vasoconstriction of isolated arteries with the thromboxane A2 mimetic U-46619 increased the number of V-shaped structures in the closed state. These studies indicate the presence of a novel anatomic structure at the origin of pulmonary supernumerary arteries, which may be able to regulate blood flow into the supernumerary artery.
Errors in estimating lung liquid volume in fetal lambs when using radiolabeled serum albumin and blue dextran
Authors: Pfister Riccardo E. , Ramsden C. Andrew , Neil Heather L. , Kyriakides Mary A. , Berger Philip J.
Published: December 2017

Fetal lung liquid volume is usually determined by using radio-iodinated serum albumin (RISA) or blue dextran (BD) as volume tracers. We tested the reliability of both tracers at 124 (G124) and 142 days of gestation (G142; term = G147) when the labels were employed simultaneously. We measured the proportion of label bound reversibly to the lung, or apparently lost from the lung compartment, by washing out the lung with saline and 5% albumin. At G124, volume estimates with the two labels were similar. At G142, the volume estimate with BD (36.3 ± 8.7 ml/kg of body wt) was higher ( P < 0.05) than with RISA (22.3 ± 3.5 ml/kg). This difference resulted from reversible binding of BD, because 5% albumin washout released 38.5 ± 4.0% of the BD added at the start of the experiment but a lesser amount of RISA (9.8 ± 0.7%; P < 0.05). At G142, when RISA was used alone, its reversible binding was 1.3 ± 0.2%. Background absorbance increased during experiments, giving rise to an apparent increase in BD concentration. We conclude that RISA is an effective tracer for lung liquid volume determination in the fetal lamb, whereas our findings of substantial epithelial binding of BD and large changes in background absorbance demonstrate that, under the conditions of our experiments, BD is a poor tracer close to term.
Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass
Authors: Rådegran G. , Blomstrand E. , Saltin B.
Published: December 2017

The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O2 uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233–249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the133Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O2 uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 ± 0.17 (range 1.31–3.27) liters, corresponding to 2.48 ± 0.18 (range 1.37–3.43) kg. Anthropometry overestimated the muscle volume by ∼21–46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 ± 7 (range 55–100) W rendered peak values for leg blood flow (thermodilution) of 5.99 ± 0.66 (range 4.15–9.52) l/min and leg O2 uptake of 856 ± 109 (range 590–1,521) ml/min. Muscle perfusion and O2 uptake reached peak values of 246 ± 24 (range 149–373) and 35.2 ± 3.7 (range 22.6–59.6) ml ⋅ min−1 ⋅ 100 g muscle−1, respectively. These peak values are ∼19–33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O2 uptake in human skeletal muscle may be up to ∼30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow measurements.
Magnetic stimulation of the human motor cortex evokes skin sympathetic nerve activity
Authors: Silber David H. , Sinoway Lawrence I. , Leuenberger Urs A. , Amassian Vahe E.
Published: December 2017

Single-pulse magnetic coil stimulation (Cadwell MES 10) over the cranium induces without pain an electric pulse in the underlying cerebral cortex. Stimulation over the motor cortex can elicit a muscle twitch. In 10 subjects, we tested whether motor cortical stimulation could also elicit skin sympathetic nerve activity (SSNA; n = 8) and muscle sympathetic nerve activity (MSNA; n = 5) in the peroneal nerve. Focal motor cortical stimulation predictably elicited bursts of SSNA but not MSNA; with successive stimuli, the SSNA responses did not readily extinguish (94% of discharges to the motor cortex evoked SSNA responses) and had predictable latencies [739 ± 33 (SE) to 895 ± 13 ms]. The SSNA responses were similar after stimulation of dominant and nondominant sides. Focal stimulation posterior to the motor cortex elicited extinguishable SSNA responses. In three of six subjects, anterior cortical stimulation evoked SSNA responses similar to those seen with motor cortex stimulation but without detectable movement; in the other subjects, anterior stimulation evoked less SSNA discharge than that seen with motor cortex stimulation. Contrasting with motor cortical stimulation, evoked SSNA responses were more readily extinguished with 1) peripheral stimulation that directly elicited forearm muscle activation accompanied by electromyograms similar to those with motor cortical stimulation; 2) auditory stimulation by the click of the energized coil when off the head; and 3) in preliminary experiments, finger afferent stimulation sufficient to cause tingling. Our findings are consistent with the hypothesis that motor cortex stimulation can cause activation of both α-motoneurons and SSNA.
Ca2+measurements in skinned cardiac fibers: effects of Mg2+on Ca2+activation of force and fiber ATPase
Authors: Allen Keri , Xu Yuan Yuan , Kerrick W. Glenn L.
Published: December 2017

In contrast to previous studies, a new fluorescent method was used to accurately determine the Ca2+concentration in test solutions used to activate skinned rat cardiac cells. This method used the calcium green-2 fluorescent indicator, which is shown to change its fluorescence over the Ca2+range responsible for Ca2+activation of force and ATPase. The dissociation constant ( Kd) of calcium green-2 for Ca2+was determined for three different Mg2+concentrations in solutions similar to those used in the experiment. Increasing Mg2+concentration from 1.0 to 8.0 mM had no significant effect on the Ca2+sensitivity of either force or actomyosin ATPase activity, in contrast to previous reported studies on force. The ATPase activity was activated at lower Ca2+concentration than the force. The ratio (ATPase/force) is proportional to the dissociation rate of force-generating myosin cross bridges and decreased during Ca2+activation. These findings are consistent with the hypothesis that cardiac muscle contraction is activated by a single Ca2+-specific binding site on troponin C.
Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro
Authors: Breen Ellen C.
Published: December 2017

Tissue remodeling is an adaptive response to mechanical tension in the lung. However, the role of pulmonary fibroblasts in this response has not been well characterized. This study investigates the influence of extracellular matrix on the response of fibroblasts to mechanical strain. Cells were cultured on flexible-bottom surfaces coated with fibronectin, laminin, or elastin and exposed to strain. Under these conditions, fibroblasts align perpendicular to the force vector. This stimulus results in an increase in α1(I) procollagen mRNA in cells cultured on laminin or elastin but not fibronectin. Increased α1(I) procollagen mRNA was detected 6 h after exposure to strain and reached control levels by 72 h. [3H]proline incorporation into newly synthesized procollagen reflects changes in mRNA levels. Strained fibroblasts cultured on laminin or elastin incorporated 190 and 114%, respectively, more [3H]proline into procollagen than did unstrained cells. No difference was detected in strained fibroblasts cultured on fibronectin. These results suggest that fibroblasts respond to mechanical strain in vitro , and this response is signaled by cell-extracellular matrix interactions.
Effects of exercise on muscle transverse relaxation determined by MR imaging and in vivo relaxometry
Authors: Saab George , Thompson R. Terry , Marsh Greg D.
Published: December 2017

The purpose of this study was to determine the effects of intense exercise on the proton transverse (T2) relaxation of human skeletal muscle. The flexor digitorium profundus muscles of 12 male subjects were studied by using magnetic resonance imaging (MRI; 6 echoes, 18-ms echo time) and in vivo magnetic resonance relaxometry (1,000 echoes, 1.2-ms echo time), before and after an intense handgrip exercise. MRI of resting muscle produced a single T2 value of 32 ms that increased by 19% ( P < 0.05) with exercise. In vivo relaxometry showed at least three T2 components (>5 ms) for all subjects with mean values of 21, 40, and 137 ms and respective magnitudes of 34, 49, and 14% of the total magnetic resonance signal. These component magnitudes changed with exercise by −44% ( P < 0.05), +52% ( P < 0.05), and +23% ( P < 0.05), respectively. These results demonstrate that intense exercise has a profound effect on the multicomponent T2 relaxation of muscle. Changes in the magnitudes of all the T2 components synergistically increase MRI T2, but changes in the two shortest T2components predominate.
Ventilatory decline after hypoxia and hypercapnia is not different between healthy young men and women
Authors: Jordan A. S. , Catcheside P. G. , Orr R. S. , O'Donoghue F. J. , Saunders N. A. , McEvoy R. D.
Published: December 2017

The gradual decay in ventilation after removal of a respiratory stimulus has been proposed to protect against cyclic breathing disorders such as obstructive sleep apnea (OSA). The male predominance of OSA, and the increased incidence of OSA in women after menopause, indicates that the respiratory-stimulating effect of progesterone may provide protection against OSA by altering the rate of poststimulus ventilatory decline (PSVD). It was therefore hypothesized that PSVD is longer in premenopausal women than in men and is longer in the luteal menstrual phase compared with the follicular phase. PSVD was measured in 12 men and in 11 women at both their luteal and follicular phases, after cessation of isocapnic hypoxia and normoxic hypercapnia. PSVD was compared between genders and between women in the luteal and follicular phases by repeated-measures ANOVA. There were no significant differences in PSVD between any of the groups after either respiratory stimulus. This suggests that the higher occurrence of OSA in men does not reflect an underlying gender difference in PSVD and implies the increased prevalence of OSA in women after menopause is not representative of an effect of progesterone on PSVD.
Skeletal muscle adaptation to exercise: a century of progress
Authors: Hamilton Marc T. , Booth Frank W.
Published: December 2017

Skeletal muscle physiology and biochemistry is an established field with Nobel Prize-winning scientists, dating back to the 1920s. Not until the mid to late 1960s did there appear a major focus on physiological and biochemical training adaptations in skeletal muscle. The study of adaptations to exercise training reveals a wide range of integrative approaches, from the systemic to the molecular level. Advances in our understanding of training adaptations have come in waves caused by the introduction of new experimental approaches. Research has revealed that exercise can be effective at preventing and/or treating some of the most common chronic diseases of the latter half of the 20th century. Endurance-trained muscle is more effective at clearing plasma triglyceride, glucose, and free fatty acids. However, at the present time, most of the mechanisms underlying the adaptation of human skeletal muscle to exercise still remain to be discovered. Little is known about the regulatory factors (e.g., trans-acting proteins or signaling pathways) directly modulating the expression of exercise-responsive genes. Because so many potential physiological and biochemical signals change during exercise, it will be an important challenge in the next century to move beyond “correlational studies” and to identify responsible mechanisms. Skeletal muscle metabolic adaptations may prove to be a critical component to preventing diseases such as coronary heart disease, type 2 diabetes, and obesity. Therefore, training studies have had an impact on setting the stage for a potential “preventive medicine reformation” in a society needing a return to a naturally active lifestyle of our ancestors.
Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion
Authors: Takarada Yudai , Nakamura Yutaka , Aruga Seiji , Onda Tetuya , Miyazaki Seiji , Ishii Naokata
Published: December 2017

Hormonal and inflammatory responses to low-intensity resistance exercise with vascular occlusion were studied. Subjects ( n = 6) performed bilateral leg extension exercise in the seated position, with the proximal end of their thigh compressed at 214 ± 7.7 (SE) mmHg throughout the session of exercise by means of a pressure tourniquet. Mean intensity and quantity of the exercise were 20% of 1 repetition maximum and 14 repetitions × 5 sets, respectively. In each set, the subjects repeated the movement until exhaustion. Plasma concentrations of growth hormone (GH), norepinephrine (NE), lacate (La), lipid peroxide (LP), interleukin-6 (IL-6), and activity of creatine phosphokinase (CPK) were measured before and after the exercise was finished and the tourniquet was released. Concentrations of GH, NE, and La consistently showed marked, transient increases after the exercise with occlusion, whereas they did not change a great deal after the exercise without occlusion (control) done at the same intensity and quantity. Notably, concentration of GH reached a level ∼290 times as high as that of the resting level 15 min after the exercise. IL-6 concentration showed a much more gradual increase and was maintained at a slightly higher level than in the control even 24 h after exercise. Concentrations of LP and CPK showed no significant change. The results suggest that extremely light resistance exercise combined with occlusion greatly stimulates the secretion of GH through regional accumulation of metabolites without considerable tissue damage.
Myosin heavy chains in fibers of TTX-paralyzed rat soleus and medial gastrocnemius muscles
Authors: Cormery Bruno , Pons Françoise , Marini Jean-François , Gardiner Phillip F.
Published: December 2017

The expression of five myosin heavy chain (MHC) isoforms was analyzed in the rat soleus (Sol) and the deep and superficial medial gastrocnemius (dGM, sGM) muscle after 2 and 4 wk of TTX paralysis by using immunohistochemical techniques. In Sol, after 4 wk of paralysis, fibers containing type I MHC were either pure type I (14%) or also contained developmental (D; 76%), IIa (26%), or IIx (18%) MHC. Values for corresponding fibers in dGM were 8.5, 65, 38, and 22%. Also, by 4 wk an increase was seen in the proportions of fibers expressing IIa MHC in Sol (from 16 to 38%) and dGM (from 24 to 74%). In a region of sGM in control muscles containing pure IIb fibers, a major proportion (86%) remained pure after 4 wk of paralysis, with the remainder coexpressing IIb and IIx. The results indicate that TTX-induced muscle paralysis results in an increase in fibers containing multiple MHC isoforms and that the D isoform appears in a major proportion of these hybrid fibers.
Hypoxic depression of circadian rhythms in adult rats
Authors: Mortola Jacopo P. , Seifert Erin L.
Published: December 2017

Because the circadian rhythms of oxygen consumption (V˙o 2) and body temperature (Tb) could be contributed to by differences in thermogenesis and because hypoxia depresses thermogenesis in its various forms, we tested the hypothesis that hypoxia blunts the normal daily oscillations in V˙o 2and Tb. Adult rats were instrumented for measurements of Tb and activity by telemetry;V˙o 2 was measured by an open-flow method. Animals were exposed to normoxia (21% O2), hypoxia (10.5% O2), and normoxia again, each 1 wk in duration, in either a 12:12-h light-dark cycle (“synchronized”) or constant light (“free running”). In this latter case, the period of the cycle was ∼25 h. In synchronized conditions, hypoxia almost eliminated the Tb circadian oscillation, because of the blunting of the Tb rise during the dark phase. On return to normoxia, Tb rapidly increased toward the maximum normoxic values, and the normal cycle was then reestablished. In hypoxia, the amplitude of the activity andV˙o 2 oscillations averaged, respectively, 37 and 56% of normoxia. In free-running conditions, on return to normoxia the rhythm was reestablished at the expected phase of the cycle. Hence, the action of hypoxia was not on the clock itself but probably at the hypothalamic centers of thermoregulation. Hyperoxia (40% O2) or hypercapnia (3% CO2) had no significant effects on circadian oscillations, indicating that the effects of hypoxia did not reflect an undifferentiated response to changes in environmental gases. Modifications of the metabolism and Tb rhythms during hypoxia could be at the origin of sleep disturbances in cardiorespiratory patients and at high altitude.
Bronchial vasodilation evoked by increased lower airway osmolarity in dogs
Authors: Zimmerman Michael P. , Pisarri Thomas E.
Published: December 2017

Hyperosmotic saline solutions stimulate lower airway sensory nerves. To determine whether airway hyperosmolarity evokes neurally mediated changes in bronchial artery blood flow (Q˙br), we measured the effect of injection of small volumes (1 ml) of hyperosmotic saline into a right lobar bronchus on Q˙br of anesthetized, artificially ventilated dogs. In 14 dogs, hyperosmotic saline (1,200 and 2,400 mmol/l) increased Q˙br by 58 ± 12 (SE) and 118 ± 12%, respectively, from a baseline of 8 ± 2 ml/min.Q˙br increased within 6–8 s of the injections, peaked at 20 s, and returned to control over 2–3 min. Isosmotic saline had minimal effects. In contrast, hyperosmotic saline decreased flow in an intercostal artery that did not supply the airways. The bronchial vasodilation was decreased by 72 ± 11% after combined blockade of α-adrenoceptors and muscarinic cholinergic receptors and by 66 ± 6% when the cervical vagus nerves were cooled to 0°C. Blockade of H1 and H2 histamine receptors did not reduce the nonvagal response. We conclude that hyperosmolarity of the lower airways evokes bronchial vasodilation by both a centrally mediated reflex that includes cholinergic and adrenergic efferent pathways and by unidentified local mechanisms.
Vascular hyporesponsiveness in simulated microgravity: role of nitric oxide-dependent mechanisms
Authors: Sangha D. Sara , Vaziri N. D. , Ding Y. , Purdy R. E.
Published: December 2017

Simulated microgravity depresses the ability of arteries to constrict to norepinephrine (NE). In the present study the role of nitric oxide-dependent mechanisms on the vascular hyporesponsiveness to NE was investigated in peripheral arteries of the rat after 20 days of hindlimb unweighting (HU). Blood vessels from control rats and rats subjected to HU (HU rats) were cut into 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. Mechanical removal of the endothelium from carotid artery rings, but not from aorta or femoral artery rings, of HU rats restored the contractile response to NE toward control. A 10-fold increase in sensitivity to ACh was observed in phenylephrine-precontracted carotid artery rings from HU rats. In the presence of the nitric oxide synthase (NOS) substratel-arginine, the inducible NOS inhibitor aminoguanidine (AG) restored the contractile responses to NE to control levels in the femoral, but not carotid, artery rings from HU rats. In vivo blood pressure measurements revealed that the peak blood pressure increase to NE was significantly greater in the control than in the HU rats, but that to AG was less than one-half in control compared with HU rats. These results indicate that the endothelial vasodilator mechanisms may be upregulated in the carotid artery, whereas the inducible NOS expression/activity may be increased in the femoral artery from HU rats. These HU-mediated changes could produce a sustained elevation of vascular nitric oxide levels that, in turn, could contribute to the vascular hyporesponsiveness to NE.
Skeletal muscle contractile and noncontractile components in young and older women and men
Authors: Kent-Braun Jane A. , Ng Alexander V. , Young Karl
Published: December 2017

To examine the influences of age, gender, and habitual physical activity level on human skeletal muscle composition, we developed a relatively simple magnetic resonance imaging method for the quantitation of leg anterior compartment contractile and noncontractile content. We studied 23 young (11 women and 12 men, 26–44 yr old) and 21 older (10 women and 11 men, 65–83 yr old) healthy adults. Analysis was by two-factor (age, gender) ANOVA. Physical activity, quantitated by three-dimensional accelerometer worn about the waist for 1 wk, was not different between groups. Men had larger contractile and noncontractile cross-sectional areas (cm2) than women, with no gender effect on percent noncontractile area. Young subjects had larger contractile areas and smaller absolute (cm2) and relative (percent total) noncontractile areas than older subjects. There was a significant linear relationship between physical activity and percent noncontractile area in older ( r = −0.68, P = 0.002) but not young subjects. These data demonstrate a more than twofold increase in the noncontractile content of locomotor muscles in older adults and provide novel support for physical activity as a modulator of this age-related change in muscle composition.
Intracellular mechanisms responsible for exercise-induced suppression of macrophage antigen presentation
Authors: Ceddia M. A. , Voss E. W. , Woods J. A.
Published: December 2017

In a previous study, we demonstrated that exhaustive exercise suppressed peritoneal macrophage antigen presentation (AP). In this study, we explored the intracellular mechanism(s) responsible for this suppression. Pathogen-free male BALB/c mice (8 ± 2 wk) were randomly assigned to either home cage control (HCC) or exhaustive exercise stress (Exh, 18–30 m/min for 3 h/day) treatment groups. The mice underwent treatments for a period of 4 days during induced peritoneal thioglycollate inflammation. Elicited macrophages were harvested, purified, and incubated with chicken ovalbumin (C-Ova, 2.5 and 10 mg/ml) for 18 h. After macrophages were washed, they were cocultured with C-Ova-specific T cells for 48 h at which time the supernates were harvested and analyzed via ELISA for interleukin (IL)-2 as an indication of macrophage AP. There was no significant ( P > 0.05) difference in macrophage AP between cells fixed with paraformaldehyde vs. those that remained unfixed, suggesting that Exh did not affect production of soluble factors influencing macrophage AP (i.e., IL-1, IL-4, PGE2). The ability of macrophages to generate C-Ova immunogenic peptides was analyzed using FITC-labeled C-Ova, which shows fluorescence only when degraded intracellularly. There was a significant (∼20%, P< 0.05) suppression in fluorescence in the Exh compared with HCC, indicating a possible defect in the ability of macrophages from Exh to degrade C-Ova into immunogenic peptides. Macrophages were also incubated with C-Ova immunogenic peptide in a manner identical to that for native C-Ova. We found a similar suppression (∼22–38%, P < 0.05) in macrophage AP using a C-Ova peptide when compared with native C-Ova in the Exh group, indicating reduced major histocompatibility complex (MHC) II loading and/or C-Ova-MHC II complex cell surface expression. In conclusion, these data indicate an intracellular defect in the macrophage antigen processing pathway induced by Exh.
Heat acclimation improves regulation of plasma volume and plasma Na+content during exercise in horses
Authors: Lindinger Michael I. , McCutcheon L. J. , Ecker G. L. , Geor R. J.
Published: December 2017

This study determined the plasma volume (PV) and ion responses to heat acclimation and exercise in six trained Thoroughbred horses during 21 days of exposure to heat and humidity (33°C, 83% relative humidity) for 4 h/day. During the 2nd h on days 0, 3, 7, 14, and 21, horses performed a standardized treadmill test, running at 50% of peak O2uptake until pulmonary artery temperature reached 41.5°C. Heat acclimation resulted in an increase in PV from 21.3 ± 1.1 liters on day 0 to 24.3 ± 1.0 liters on day 14, returning to 22.6 ± 0.9 liters on day 21. The corresponding total plasma protein contents were 1,273 ± 53, 1,455 ± 81, and 1,377 ± 57 g, respectively, and increases in total plasma Na+plus Cl−content were 5,145 ± 126, 5,749 ± 146, and 5,394 ± 114 mmol, respectively. Thus changes in PV were accompanied by direct changes in plasma protein and osmolyte contents. With exercise on day 0, PV decreased by 7.1 ± 0.7% at 5 min of exercise and remained decreased (−6.7 ± 1.3%) at 5 min of recovery. By day 21, PV decreased significantly less than on day 0 (by 5.2 ± 0.9% at 5 min of exercise), was decreased by only 2.0 ± 1.6% at 5 min of recovery, and was fully restored at 15 min of recovery. Plasma Na+concentration increased 3 meq/l during the first 5 min of exercise and was normalized by 5 min of recovery on day 0 and by end exercise on day 21. It is concluded that improved ability to regulate PV during exercise in response to heat acclimatization is associated with an increased PV and an improved conservation of Na+.
Chronic contractile activity upregulates the proteasome system in rabbit skeletal muscle
Authors: Ordway George A. , Neufer P. Darrell , Chin Eva R. , DeMartino George N.
Published: December 2017

Remodeling of skeletal muscle in response to altered patterns of contractile activity is achieved, in part, by the regulated degradation of cellular proteins. The ubiquitin-proteasome system is a dominant pathway for protein degradation in eukaryotic cells. To test the role of this pathway in contraction-induced remodeling of skeletal muscle, we used a well-established model of continuous motor nerve stimulation to activate tibialis anterior (TA) muscles of New Zealand White rabbits for periods up to 28 days. Western blot analysis revealed marked and coordinated increases in protein levels of the 20S proteasome and two of its regulatory proteins, PA700 and PA28. mRNA of a representative proteasome subunit also increased coordinately in contracting muscles. Chronic contractile activity of TA also increased total proteasome activity in extracts, as measured by the hydrolysis of a proteasome-specific peptide substrate, and the total capacity of the ubiquitin-proteasome pathway, as measured by the ATP-dependent hydrolysis of an exogenous protein substrate. These results support the potential role of the ubiquitin-proteasome pathway of protein degradation in the contraction-induced remodeling of skeletal muscle.
Endothelium-dependent relaxation differs in porcine pulmonary arteries from the left and right caudal lobes
Authors: Johnson Lynelle R. , Dodam John R. , Laughlin M. Harold
Published: December 2017

We hypothesized that pulmonary arteries (PA) from identical branch orders within left and right caudal lung lobes would exhibit similar vasomotor responses. Arterial rings from caudal lung lobes of female swine were examined in vitro. Vascular smooth muscle contraction to KCl and norepinephrine did not differ. Vascular relaxation to endothelium-dependent (bradykinin, acetylcholine, A-23187) and -independent (sodium nitroprusside, zero-calcium Krebs solution) vasodilators was assessed. Right PA exhibited less maximal relaxation to acetylcholine (50%) than did left PA (69%; P< 0.001). Maximal relaxation to sodium nitroprusside did not differ, although right PA had a lower drug concentration resulting in half-maximal relaxation (6.26 × 10−8M) than did left PA (9.57 × 10−8 M; P< 0.05). Nitric oxide synthase inhibition with an arginine analog ( N ω-nitro-l-arginine methyl ester) depressed acetylcholine-induced relaxation but the left vs. right difference persisted. Indomethacin enhanced relaxation to acetylcholine and abolished the difference between left and right. We conclude that endothelium-dependent vasorelaxation is less in porcine right than in left PA because of greater release of one or more constricting prostanoids in arteries from the right caudal lobe.
Ligation of the bronchial artery in sheep attenuates early pulmonary changes following exposure to smoke
Authors: Efimova Olga , Volokhov A. B. , Iliaifar Sakineh , Hales C. A.
Published: December 2017

Smoke inhalation can produce acute pulmonary edema. Previous studies have shown that the bronchial arteries are important in acute pulmonary edema occurring after inhalation of a synthetic smoke containing acrolein, a common smoke toxin. We hypothesized that inhalation of smoke from burning cotton, known to contain acrolein, would produce in sheep acute pulmonary edema that was mediated by the bronchial circulation. We reasoned that occluding the bronchial arteries would eliminate smoke-induced pulmonary edema, whereas occlusion of the pulmonary artery would not. Smoke inhalation increased lung lymph flow from baseline from 2.4 ± 0.7 to 5.6 ± 1.2 ml/0.5 h at 30 min ( P < 0.05) to 9.1 ± 1 ml/0.5 h at 4 h ( P < 0.05). Bronchial artery ligation diminished and delayed the rise in lymph flow with baseline at 2.8 ± 0.7 ml/0.5 h rising to 3.1 ± 0.8 ml/0.5 h at 30 min to 6.5 ± 1.5 ml/0.5 h at 240 min ( P < 0.05). Wet-to-dry ratio was 4.1 ± 0.2 in control, 5.1 ± 0.3 in smoke inhalation ( P< 0.05), and 4.4 ± 0.4 in bronchial artery ligation plus smoke-inhalation group. Smoke inhalation after occlusion of the right pulmonary artery resulted in a wet-to-dry ratio after 4 h in the right lung of 5.5 ± 0.8 ( P < 0.05 vs. control) and in the left nonoccluded lung of 5.01 ± 0.7 ( P < 0.05). Thus the bronchial arteries may be major contributors to acute pulmonary and airway edema following smoke inhalation because the edema occurs in the lung with the pulmonary artery occluded but not in the lungs with bronchial arteries ligated.
Effects of loaded breathing and hypoxia on diaphragm metabolism as measured by 31P-NMR spectroscopy
Authors: Radell Peter J. , Eleff Scott M. , Nichols David G.
Published: December 2017

Diaphragm fatigue may contribute to respiratory failure.31P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by Pi accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism. Seven piglets were anesthetized by using halothane inhalation. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at end expiration with the airway occluded. A nuclear magnetic resonance surface coil placed under the right hemidiaphragm measured Pi and PCr during four conditions: control, inspiratory resistive breathing (IRB), IRB with hypoxia, and recovery (IRB without hypoxia). IRB alone resulted in hypercarbia (32 ± 7 to 61 ± 21 Torr) and respiratory acidosis but no change in diaphragm force output or aerobic metabolism. Combined IRB and hypoxia resulted in decreased force output (Pdi decreased by 40%; from 30 ± 17 to 19 ± 11 mmHg) and evidence of metabolic stress (ratio of Pi to PCr increased by 290%; from 0.19 ± 0.09 to 0.74 ± 0.27). We conclude that diaphragm fatigue associated with inadequate aerobic oxidative metabolism occurs in the setting of loaded breathing and hypoxia. Conversely, aerobic metabolism and force output of the diaphragm remain unchanged from control during loaded normoxic or hyperoxic breathing despite the onset of respiratory failure.
Effect of sleep restriction on orthostatic cardiovascular control in humans
Authors: Muenter N. K. , Watenpaugh D. E. , Wasmund W. L. , Wasmund S. L. , Maxwell S. A. , Smith M. L.
Published: December 2017

We hypothesized that sleep restriction (4 consecutive nights, 4 h sleep/night) attenuates orthostatic tolerance. The effect of sleep restriction on cardiovascular responses to simulated orthostasis, arterial baroreflex gain, and heart rate variability was evaluated in 10 healthy volunteers. Arterial baroreflex gain was determined from heart rate responses to nitroprusside-phenylephrine injections, and orthostatic tolerance was tested via lower body negative pressure (LBNP). A Finapres device measured finger arterial pressure. No difference in baroreflex function, heart rate variability, or LBNP tolerance was observed with sleep restriction ( P > 0.3). Systolic pressure was greater at −60 mmHg LBNP after sleep restriction than before sleep restriction (110 ± 6 and 124 ± 3 mmHg before and after sleep restriction, respectively, P = 0.038), whereas heart rate decreased (108 ± 8 and 99 ± 8 beats/min before and after sleep restriction, respectively, P = 0.028). These data demonstrate that sleep restriction produces subtle changes in cardiovascular responses to simulated orthostasis, but these changes do not compromise orthostatic tolerance.
Myofibrillar or mitochondrial creatine kinase deficiency alone does not impair mouse diaphragm isotonic function
Authors: Watchko Jon F. , Daood Monica J. , Wieringa Bé , Koretsky Alan P.
Published: December 2017

Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. The diaphragm (Dia) expresses both M-CK and ScCKmit in abundance. We compared the power and work output of 1) control CK-sufficient (Ctl), 2) M-CK-deficient [M-CK(−/−)], 3) ScCKmit-deficient [ScCKmit(−/−)], and 4) combined M-CK/ScCKmit-deficient null mutant [CK(−/−)] Dia during repetitive isotonic activations to determine the effect of CK phenotype on Dia function. Maximum power was obtained at ∼0.4 tetanic force in all groups. M-CK(−/−) and ScCKmit(−/−) Dia were able to sustain power and work output at Ctl levels during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load), and the duration of sustained Dia shortening was 67 ± 4 s in M-CK(−/−), 60 ± 4 s in ScCKmit(−/−), and 62 ± 5 s in Ctl Dia. In contrast, CK(−/−) Dia power and work declined acutely and failed to sustain shortening altogether by 40 ± 6 s. We conclude that Dia power and work output are not absolutely dependent on the presence of either M-CK or ScCKmit, whereas the complete absence of CK acutely impairs Dia shortening capacity during repetitive activation.
Functional, cellular, and biochemical adaptations to elastase-induced emphysema in hamster medial scalene
Authors: Fournier Mario , Lewis Michael I.
Published: December 2017

The scalene has been reported to be an accessory inspiratory muscle in the hamster. We hypothesize that with the chronic loads and/or dynamic hyperinflation associated with emphysema (Emp), the scalene will be actively recruited, resulting in functional, cellular, and biochemical adaptations. Emp was induced in adult hamsters. Inspiratory electromyogram (EMG) activity was recorded from the medial scalene and costal diaphragm. Isometric contractile and fatigue properties were evaluated in vitro. Muscle fibers were classified histochemically and immunohistochemically. Individual fiber cross-sectional areas (CSA) and succinate dehydrogenase (SDH) activities were determined quantitatively. Myosin heavy chain (MHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. All Emp animals exhibited spontaneous scalene inspiratory EMG activity during quiet breathing, whereas the scalene muscles of controls (Ctl) were silent. There were no differences in contractile and fatigue properties of the scalene between Ctl and Emp. In Emp, the relative amount of MHC2Awas 15% higher whereas that of MHC2X was 14% lower compared with Ctl. Similarly, the proportion of type IIa fibers increased significantly in Emp animals with a concomitant decrease in IIx fibers. CSA of type IIx fibers were significantly smaller in Emp compared with Ctl. SDH activities of all fiber types were significantly increased by 53 to 63% in Emp. We conclude that with Emp the actively recruited scalene exhibits primary-like inspiratory activity in the hamster. Adaptations of the scalene with Emp likely relate both to increased loads and to factors intrinsic to muscle architecture and chest mechanics.
Force production of the genioglossus as a function of muscle length in normal humans
Authors: Sha B. F. Bu , England S. J. , Parisi R. A. , Strobel R. J.
Published: December 2017

Resting muscle length affects both maximum force production and force maintenance. The strength and force maintenance characteristics of the genioglossus as a function of resting muscle length have not been described. We hypothesized that genioglossus optimum length ( L o) could be defined in vivo and that the ability of the genioglossus to sustain a given workload would decrease as resting length deviated from L o. To test this, 11 normal men repeated maximal isometric genioglossus protrusions at different muscle lengths to determine L o. L o was also obtained by using submaximal efforts while simultaneously recording electromyographic activity of the genioglossus, with L o defined as the length at which the force-to-genioglossus electromyographic activity ratio was maximum. Both methods provided similar results. Force maintenance was measured at four muscle lengths on separate days. Target efforts representing 60% of each subject's maximum at L o and lasting 5 s were performed at 12-s intervals. Time limit of endurance of the genioglossus was defined as the time from trial onset at which 90% of the target could not be maintained for three consecutive efforts. Time limit of endurance was greatest at L o and fell to 47.5% at L o + 1 cm, 53.8% at L o − 1 cm, and 47.4% at L o − 1.5 cm. We conclude that L o of the genioglossus can be determined in vivo and that force maintenance of the genioglossus is decreased when operating length deviates from L o.
l-Arginine increases nitric oxide production in isolated lungs of chronically hypoxic newborn pigs
Authors: Fike Candice D. , Kaplowitz Mark R. , Rehorst-Paea Linda A. , Nelin Leif D.
Published: December 2017

Previously, our laboratory found that pulmonary hypertension developed and lung nitric oxide (NO) production was reduced when piglets were exposed to chronic hypoxia (Fike CD, Kaplowitz MR, Thomas CJ, and Nelin LD. Am J Physiol Lung Cell Mol Physiol 274: L517–L526, 1998). The purposes of this study were to determine whetherl-arginine addition augments NO production and to evaluate whether l-arginine uptake is impaired in isolated lungs of chronically hypoxic newborn piglets. Studies were performed by using 1- to 3-day-old piglets raised in room air (control) or 10% O2 (chronic hypoxia) for 10–12 days. Lung NO production was assessed in isolated lungs from both groups by measuring the perfusate accumulation of nitrites and nitrates (collectively termed [Formula: see text]) before and after addition of l-arginine (10−2 M) to the perfusate. The rate of perfusate[Formula: see text] accumulation increased by 220% (from 0.8 ± 0.4 to 2.5 ± 0.5 nmol/min, P < 0.05) after l-arginine addition to chronic hypoxic lungs but remained unchanged (3.2 ± 0.8 before vs. 3.3 ± 0.4 nmol/min afterl-arginine) in control lungs. In the second series of studies, l-arginine uptake was evaluated by measuring the perfusate concentration ofl-[3H]arginine at fixed time intervals. The perfusate concentration ofl-[3H]arginine at each time point was less ( P < 0.05) in control than in chronic hypoxic lungs. Thus l-arginine uptake was impaired and may underlie in part the reduction in lung NO production that occurs when piglets are exposed to 10–12 days of chronic hypoxia. Moreover, these findings in isolated lungs lead to the possibility that l-arginine supplementation might increase in vivo lung NO production in piglets with chronic hypoxia-induced pulmonary hypertension.
Correlation between ventilation and perfusion determinesV˙a/Q˙ heterogeneity in endotoxemia
Authors: Gerbino Anthony J. , McKinney Steven , Glenny Robb W.
Published: December 2017

Endotoxin increases ventilation-to-perfusion ratio (V˙a/Q˙) heterogeneity in the lung, but the precise changes in alveolar ventilation (V˙a) and perfusion that lead toV˙a/Q˙heterogeneity are unknown. The purpose of this study was to determine how endotoxin affects the distributions of ventilation and perfusion and the impact of these changes onV˙a/Q˙heterogeneity. Seven anesthetized, mechanically ventilated juvenile pigs were given E. coli endotoxin intravenously, and regional ventilation and perfusion were measured simultaneously by using aerosolized and injected fluorescent microspheres. Endotoxemia significantly decreased the correlation between regional ventilation and perfusion, increased perfusion heterogeneity, and redistributed perfusion between lung regions. In contrast, ventilation heterogeneity did not change, and redistribution of ventilation was modest. The decrease in correlation between regional ventilation and perfusion was responsible for significantly moreV˙a/Q˙ heterogeneity than were changes in ventilation or perfusion heterogeneity. We conclude that V˙a/Q˙heterogeneity increases during endotoxemia primarily as a result of the decrease in correlation between regional ventilation and perfusion, which is in turn determined primarily by changes in perfusion.
Effects of exercise on insulin distribution and action in testosterone-treated oophorectomized female rats
Authors: Niklasson Maria , Daneryd Peter , Lönnroth Peter , Holmäng Agneta
Published: December 2017

Administration of testosterone (T) to oophorectomized (Ovx) female rats is followed by severe insulin resistance, localized to postreceptor cellular events in the muscle. In this study, intervention by exercise was introduced to examine whether circulatory adaptations are involved in insulin resistance. Two groups of Ovx rats were studied: one group was given T (Ovx+T); another group had free access to running wheels (Ovx+T+Ex). In addition, one control group (sham operated) was studied. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp technique (submaximal) for 150 min. Muscle interstitial glucose and insulin concentrations were measured by microdialysis. The measurements showed that, in Ovx+T rats, the onset of insulin action was significantly ( P < 0.05) slower during the first 95 min of the clamp compared with that in Ovx+T+Ex and controls. Muscle interstitial concentrations of insulin but not glucose were lower in both Ovx+T and Ovx+T+Ex rats than in controls throughout the clamp. It was concluded that physical exercise prevented the slow onset of insulin action in Ovx+T rats without changing the distribution time of muscle interstitial insulin. The results indicate that hyperandrogenicity is characterized by delayed muscle insulin action. Physical exercise reverses these defects without any beneficial effect on muscle interstitial insulin concentrations.