bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of acute and chronic exercise on vasoconstrictor responsiveness of rat abdominal aorta
Authors: Spier Scott A. , Laughlin M. Harold , Delp Michael D.
Published: December 2017

Reductions in blood pressure that are associated with exercise training have been hypothesized to be the result of a sustained postexertional vascular alteration following single bouts of exercise. The purpose of this study was to determine whether a decrease in vascular sensitivity to vasoconstrictor agonists occurs after a single bout of exercise and whether this vascular alteration is sustained through various periods of exercise training. Vascular responses of abdominal aortic rings to norepinephrine (NE; 10−9–10−4M) were determined in vitro. Aortas were isolated from sedentary rats immediately after rats performed a single bout of treadmill exercise (30 m/min for 1 h); 24 h after the last exercise bout in rats exercised for 1 day; and 1, 2, 4, and 10 wk of training at 30 m/min, 60 min, 5 days/wk. Sensitivity to NE was only diminished after 10 wk of training. This diminished vascular sensitivity to NE was abolished with the removal of the endothelial cell layer. Furthermore, there were no reductions in developed tension or vascular sensitivity to the vasoconstrictor agonists KCl (10–100 mM), phenylephrine (10−8–10−4M), and arginine vasopressin (10−9–10−5M) in vessels either with or without the endothelial layer after a single bout of exercise. These data indicate that a single bout of exercise does not diminish aortic responsiveness to vasoconstrictor agonists and thus is not responsible for the diminished contractile responsiveness that occurs between 4 and 10 wk of moderate-intensity exercise training in rats. This vascular adaptation to exercise training appears to be mediated through an endothelium-dependent mechanism.
Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle
Authors: Combs C. A. , Aletras A. H. , Balaban R. S.
Published: December 2017

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867–874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo ( n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and31P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 μM or decrease the free energy of ATP hydrolysis to −55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 μmol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions ( P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.
Remodeling of lung interstitium but not resistance vessels in canine pacing-induced heart failure
Authors: Townsley Mary I. , Snell Kenneth S. , Ivey Claire L. , Culberson Donald E. , Liu Da Chang , Reed Rolf K. , Mathieu-Costello Odile
Published: December 2017

We previously showed that pacing-induced heart failure in dogs results in an enhancement of pulmonary vascular reactivity. In the present study we hypothesized that enhanced matrix deposition and structural remodeling of lung resistance microvessels would underlie these functional changes. Using biochemical measures, we found no difference in the normalized lung content of hyaluronan, uronic acid, and collagen between control dogs and dogs paced for 1 mo, although lung dry weight and noncollagen protein content increased significantly in the paced group ( P < 0.05). From separate Formalin-fixed lung lobes, 5-μm frozen sections were prepared and stained with Masson's trichrome, and vascular structure was evaluated using standard morphometric techniques. When perivascular fluid cuffs were excluded from the measure of wall thickness, collagen and media volume fractions in any size range did not differ between paced and control groups. Similarly, in the paced group, medial thickness in <400-μm arterial or venular microvessels did not vary significantly from that in the controls. In contrast, the relationship of interstitial fluid pressure to lung water was significantly shifted to the right in the paced group, such that normal tissue pressures were observed, despite the increased water content. We conclude that although 1 mo of pacing-induced heart failure results in altered interstitial function, the attendant pulmonary hypertension and/or hormonal responses are insufficient to induce medial hypertrophy or other remodeling of the extra-alveolar microvasculature.
Force-calcium relationship depends on myosin heavy chain and troponin isoforms in rat diaphragm muscle fibers
Authors: Geiger Paige C. , Cody Mark J. , Sieck Gary C.
Published: December 2017

The present study examined Ca2+sensitivity of diaphragm muscle (Diam) fibers expressing different myosin heavy chain (MHC) isoforms. We hypothesized that Diamfibers expressing the MHCslowisoform have greater Ca2+sensitivity than fibers expressing fast MHC isoforms and that this fiber-type difference in Ca2+sensitivity reflects the isoform composition of the troponin (Tn) complex (TnC, TnT, and TnI). Studies were performed in single Triton-X-permeabilized Diamfibers. The Ca2+concentration at which 50% maximal force was generated (pCa50) was determined for each fiber. SDS-PAGE and Western analyses were used to determine the MHC and Tn isoform composition of single fibers. The pCa50for Diamfibers expressing MHCslowwas significantly greater than that of fibers expressing fast MHC isoforms, and this greater Ca2+sensitivity was associated with expression of slow isoforms of the Tn complex. However, some Diamfibers expressing MHCslowcontained the fast TnC isoform. These results suggest that the combination of TnT, TnI, and TnC isoforms may determine Ca2+sensitivity in Diamfibers.
Role of the spleen in the exaggerated polycythemic response to hypoxia in chronic mountain sickness in rats
Authors: Kam H. Y. , Ou L. C. , Thron C. D. , Smith R. P. , Leiter J. C.
Published: December 2017

In a rat model of chronic mountain sickness, the excessive polycythemic response to hypoxic exposure is associated with profound splenic erythropoiesis. We studied the uptake and distribution of radioactive iron and red blood cell (RBC) morphology in intact and splenectomized rats over a 30-day hypoxic exposure. Retention of59Fe in the plasma was correlated with59Fe uptake by both spleen and marrow and the appearance of59Fe-labeled RBCs in the blood.59Fe uptake in both the spleen and the marrow paralleled the production of nucleated RBCs. Splenic59Fe uptake was ∼10% of the total marrow uptake under normoxic conditions but increased to 60% of the total marrow uptake during hypoxic exposure. Peak splenic59Fe uptake and splenomegaly occurred at the most intense phase of erythropoiesis and coincided with the rapid appearance of59Fe-labeled RBCs in the blood. The bone marrow remains the most important erythropoietic organ under both resting and stimulated states, but inordinate splenic erythropoiesis in this rat strain accounts in large measure for the excessive polycythemia during the development of chronic mountain sickness in chronic hypoxia.
Purine loss after repeated sprint bouts in humans
Authors: Stathis C. G. , Zhao S. , Carey M. F. , Snow R. J.
Published: December 2017

The influence of the number of sprint bouts on purine loss was examined in nine men (age 24.8 ± 1.6 yr, weight 76 ± 3.9 kg, peak O2 consumption 3.87 ± 0.16 l/min) who performed either one (B1), four (B4), or eight (B8) 10-s sprints on a cycle ergometer, 1 wk apart, in a randomized order. Forearm venous plasma inosine, hypoxanthine (Hx), and uric acid concentrations were measured at rest and during 120 min of recovery. Urinary inosine, Hx, and uric acid excretion were also measured before and 24 h after exercise. During the first 120 min of recovery, plasma inosine and Hx concentrations, and urinary Hx excretion rate, were progressively higher ( P < 0.05) with an increasing number of sprint bouts. Plasma uric acid concentration was higher ( P < 0.05) in B8 compared with B1 and B4 after 45, 60, and 120 min of recovery. Total urinary excretion of purines (inosine + Hx + uric acid) was higher ( P < 0.05) at 2 h of recovery after B8 (537 ± 59 μmol) compared with the other trials (B1: 270 ± 76; B4: 327 ± 59 μmol). These results indicate that the loss of purine from the body was enhanced by increasing the number of intermittent 10-s sprint bouts.
Effects of hindlimb unloading on rat cerebral, splenic, and mesenteric resistance artery morphology
Authors: Wilkerson M. Keith , Muller-Delp Judy , Colleran Patrick N. , Delp Michael D.
Published: December 2017

Hindlimb unloading (HU) of rats induces a cephalic shift in body fluids. We hypothesized that the putative increase in cranial fluid pressure and decrease in peripheral fluid pressure would alter the morphology of resistance arteries from 2-wk HU male Sprague-Dawley rats. To test this hypothesis, the cerebral basilar, mesenteric, and splenic arteries were removed from control (C) and HU animals. The vessels were cannulated, and luminal pressure was set to 60 cmH2O. The resistance arteries were then relaxed with 10−4 M nitroprusside, fixed, and cut into transverse cross sections (5 μm thick). Media cross-sectional area (CSA), intraluminal CSA, media layer thickness, vessel outer perimeter, and media nuclei number were determined. In the basilar artery, both media CSA (HU 17,893 ± 2,539 μm2; C 12,904 ± 1,433 μm2) and thickness (HU 33.9 ± 4.1 μm; C 22.3 ± 3.2 μm) were increased with hindlimb unloading ( P < 0.05), intraluminal CSA decreased (HU 7,816 ± 3,045 μm2; C 13,469 ± 5,500 μm2) ( P < 0.05), and vessel outer perimeter and media nuclei number were unaltered. There were no differences in mesenteric or splenic resistance artery morphology between HU and C rats. These findings suggest that hindlimb unloading-induced increases in cephalic arterial pressure and, correspondingly, increases in circumferential wall stress result in the hypertrophy of basilar artery smooth muscle cells.
Enhanced endothelial vasoreactivity in endurance-trained older men
Authors: Rywik Tomasz M. , Blackman Marc R. , Yataco Alberto R. , Vaitkevicius Peter V. , Zink Richard C. , Cottrell Ernest H. , Wright Jeanette G. , Katzel Leslie I. , Fleg Jerome L.
Published: December 2017

Using external vascular ultrasound, we measured brachial artery diameter (Diam) at rest, after release of 4 min of limb ischemia, i.e., endothelium-dependent dilation (EDD), and after sublingual nitroglycerin, i.e., non-endothelium-dependent dilation (NonEDD), in 35 healthy men aged 61–83 yr: 12 endurance athletes (A) and 23 controls (C). As anticipated, treadmill exercise maximal oxygen consumption (V˙o 2 max) was significantly higher in A than in C (40.2 ± 6.6 vs. 27.9 ± 3.8 ml ⋅ kg−1 ⋅ min−1; respectively, P < 0.0001). With regard to arterial physiology, A had greater EDD (8.9 ± 4.2 vs. 5.7 ± 3.5%; P = 0.02) and a tendency for higher NonEDD (13.9 ± 6.7 vs. 9.7 ± 4.2%; P = 0.07) compared with C. By multiple linear regression analysis in the combined sample of older men, only baseline Diam (β = −2.0, where β is the regression coefficient; P = 0.005) andV˙o 2 max (β = 0.23; P = 0.003) were independent predictors of EDD; similarly, only Diam (β = −4.0; P = 0.003) andV˙o 2 max (β = 0.27; P = 0.01) predicted NonEDD. Thus endurance-trained older men demonstrate both augmented EDD and NonEDD, consistent with a generalized enhanced vasodilator responsiveness, compared with their sedentary age peers.
Role of nitric oxide in hypoxia inhibition of fever
Authors: Almeida Maria C. , Carnio Evelin C. , Branco Luiz G. S.
Published: December 2017

Hypoxia causes a regulated decrease in body temperature (Tb), and nitric oxide (NO) is now known to participate in hypoxia-induced hypothermia. Hypoxia also inhibits lipopolysaccharide (LPS)-induced fever. We tested the hypothesis that NO may participate in the hypoxia inhibition of fever. The rectal temperature of awake, unrestrained rats was measured before and after injection of LPS, with or without concomitant exposure to hypoxia, in an experimental group treated with N ω-nitro-l-arginine (l-NNA) for 4 consecutive days before the experiment and in a saline-treated group (control).l-NNA is a nonspecific NO synthase inhibitor that blocks NO production. LPS caused a dose-dependent typical biphasic rise in Tb that was completely prevented by hypoxia (7% inspired oxygen).l-NNA caused a significant drop in Tb during days 2–4 of treatment. When LPS was injected intol-NNA-treated rats, inhibition of fever was observed. Moreover, the effect of hypoxia during fever was significantly reduced. The data indicate that the NO pathway plays a role in hypoxia inhibition of fever.
Exercise suppresses macrophage antigen presentation
Authors: Ceddia M. A. , Woods J. A.
Published: December 2017

This study determined the effects of exercise on the ability of macrophages (Mφ) to present antigen to T cells. Pathogen-free male Balb/c mice (8 ± 2 wk of age) were randomly assigned to either home cage control, moderate exercise (Mod; 18 m/min, 5% grade, 0.5 h/day), exhaustive exercise (Exh, 18–30 m/min, 3 h/day), or treadmill control groups. The mice underwent treatments for 4 days during peritoneal thioglycolate inflammation. Peritoneal Mφ were harvested, purified, and incubated with chicken ovalbumin (C-OVA; 0–10 mg/ml) for 18 h. Mφ were then cocultured with C-OVA-specific T cells for 48 h, and the supernatants were analyzed via ELISA for interleukin-2 as an indication of Mφ antigen presentation (AP). Exh exhibited suppressed (∼25–34%) Mφ AP across a wide range of C-OVA doses when measured immediately, 3, and 24 h postexercise. In contrast, Mod had reduced Mφ AP only at 3 h postexercise. Mφ AP was also lower in the treadmill control (4–27%) compared with the home cage control group, but was significantly higher than Exh. The reduction in Mφ AP was not due to exercise-induced differences in Mφ number, percentage, or expression of intercellular adhesion molecule-1, B7–2, or major histocompatability complex II, molecules important in AP. In conclusion, our data lend evidence that may help explain the increased incidence of infection observed after prolonged exhaustive exercise or overtraining.
Noninvasive cardiac output measurement in orthostasis: pulse contour analysis compared with acetylene rebreathing
Authors: Stok W. J. , Stringer R. C. O. , Karemaker J. M.
Published: December 2017

We tested the reliability of noninvasive cardiac output (CO) measurement in different body positions by pulse contour analysis (COpc) by using a transmission line model (K. H. Wesseling, B. De Wit, J. A. P. Weber, and N. T. Smith. Adv. Cardiol. Phys.5, Suppl. II: 16–52, 1983). Acetylene rebreathing (COrebr) was used as a reference method. Twelve subjects (age 21–34 yr) were studied: 1) six in whom COrebr and COpc were measured in the standing and 6° head-down tilt (HDT) postures and 2) six in whom CO was measured in the 30° HDT, supine, 30° head up-tilt (HUT), and 70° HUT postures on a tilt table. The COrebr-to-COpcratio in (near) the supine position during rebreathing was used as the calibration factor for COpcmeasurements. Calibrated COpc(COcal sup) consistently overestimated CO in the upright posture. The drop in CO with upright posture was underestimated by ∼50%. COcal sup and COrebr values did not differ in the 30° HDT position. Changes in the COrebr-to-COpcratio are highly variable among subjects in response to a change in posture. Therefore, COpc must be recalibrated for each subject in each posture.
MR measurements of muscle damage and adaptation after eccentric exercise
Authors: Foley Jeanne M. , Jayaraman Roop C. , Prior Barry M. , Pivarnik James M. , Meyer Ronald A.
Published: December 2017

The purposes of this study were, first, to clarify the long-term pattern of T2 relaxation times and muscle volume changes in human skeletal muscle after intense eccentric exercise and, second, to determine whether the T2 response exhibits an adaptation to repeated bouts. Six young adult men performed two bouts of eccentric biceps curls (5 sets of 10 at 110% of the 1-repetition concentric maximum) separated by 8 wk. Blood samples, soreness ratings, and T2-weighted axial fast spin-echo magnetic resonance images of the upper arm were obtained immediately before and after each bout; at 1, 2, 4, 7, 14, 21, and 56 days after bout 1; and at 2, 4, 7 and 14 days after bout 2. Resting muscle T2 [27.6 ± 0.2 (SE) ms] increased immediately postexercise by 8 ± 1 ms after both bouts. T2 peaked 7 days after bout 1 at 47 ± 4 ms and remained elevated by 2.5 ms at 56 days. T2 peaked lower (37 ± 4 ms) and earlier (2–4 days) after bout 2, suggesting an adaptation of the T2 response. Peak serum creatine kinase values, pain ratings, and flexor muscle swelling were also significantly lower after the second bout ( P < 0.05). Total volume of the imaged arm region increased transiently after bout 1 but returned to preexercise values within 2 wk. The exercised flexor compartment swelled by over 40%, but after 2 wk it reverted to a volume 10% smaller than that before exercise and maintained this volume loss through 8 wk, consistent with partial or total destruction of a small subpopulation of muscle fibers.
Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration
Authors: Kyriakides Constantinos , Austen William , Wang Yong , Favuzza Joanne , Kobzik Lester , Moore Francis D. , Hechtman Herbert B.
Published: December 2017

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus acid aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a.
Influence of tension time on muscle fiber sarcolemmal injury in rat diaphragm
Authors: Zhu Ercheng , Comtois Alain S. , Fang Liwei , Comtois Norman R. , Grassino Alejandro E.
Published: December 2017

We hypothesized that the amount of sarcolemmal injury is directly related to the total tension time (TTtot), calculated as mean tension × total stimulation time. Diaphragm strips from Sprague-Dawley rats were superfused at optimal muscle length with Krebs containing procion orange to identify sarcolemmal injury. TTtot was induced by stimulation with 100 Hz for 3 min at duty cycles of 0.02, 0.15, 0.3, and 0.6, or with continuous contractions at 0.2, 0.4, 0.6, and 1.0 of maximal tension. A significant positive correlation between TTtot and the percentage of fibers with injured sarcolemma ( r 2 = 0.63, P < 0.05) is seen. Stimulation (at 100 Hz, duty cycle = 1) resulted in fast fatigue with low injury, likely caused by altered membrane conductivity. Stimulations inducing the largest injury are those showing progressive force loss and high TTtot, where injury may be due to activation of membrane degradative enzymes. The maximal tension measured at 20 min poststimulation was inversely related to the number of fibers injured, suggesting loss of force is caused by cellular injury.
Altered reactivity of pulmonary vessels in postobstructive pulmonary vasculopathy
Authors: Shi Weibin , Hu Fu , Kassouf Wassim , Michel René P.
Published: December 2017

Chronic ligation of one pulmonary artery results in pulmonary vascular remodeling and bronchial angiogenesis, collectively known as postobstructive pulmonary vasculopathy (POPV). To investigate pulmonary vascular reactivity in POPV, we ligated the left main pulmonary artery of guinea pigs and, after 1–10 mo, prepared explants by inflating lungs with agarose and sectioning them into ∼1-mm-thick slices; we measured areas of pulmonary vessels and determined contractile responses to histamine and serotonin (5-HT) and relaxant responses to ACh and sodium nitroprusside. We found maximal contractions of arteries to 5-HT (24.4 ± 2.6%) and of veins to histamine (53.9 ± 4.7%) were significantly increased in POPV of 3-mo duration compared with those of controls (16.8 ± 1.5 and 40.8 ± 5.0%, respectively). Relaxation of arteries with ACh was enhanced at 10 mo but not at 1 mo after ligation. Relaxation with sodium nitroprusside was increased in veins at 1 mo after ligation but was not altered in arteries. Morphometry revealed reduced diameters of arteries and veins without increased medial thickness. Our data suggest that the enhanced contractile responses of pulmonary vessels to histamine and 5-HT in POPV were not a result of endothelial dysfunction or of structural alterations but might be caused by as-yet-undiscovered mechanisms.
Human cardiovascular and humoral responses to moderate muscle activation during dynamic exercise
Authors: Nishiyasu Takeshi , Nagashima Kei , Nadel Ethan R. , Mack Gary W.
Published: December 2017

We examined the hypothesis that activation of the muscle metaboreflex during dynamic exercise would augment influences tending to cause a rise in arginine vasopressin, plasma renin activity, and catecholamines during dynamic exercise in humans. Ten healthy adults performed 30 min of supine cycle ergometer exercise at ∼50% of peak oxygen consumption with or without moderate muscle metaboreflex activation by application of 35 mmHg lower body positive pressure (LBPP). Application of LBPP during the first 15 or last 15 min of exercise increased mean arterial blood pressure, plasma lactate concentration, and minute ventilation, indicating an activation of the muscle metaboreflex. These changes were rapidly reversed when LBPP was removed. During exercise at this intensity, LBPP augmented the release of arginine vasopressin and catecholamines but not of plasma renin activity. These results suggest that, although in humans hormonal responses are induced by moderate activation of the muscle metaboreflex during dynamic exercise, the thresholds for these responses may not be uniform among the various glands and hormones.
Intense exercise stimulates albumin synthesis in the upright posture
Authors: Nagashima Kei , Cline Gary W. , Mack Gary W. , Shulman Gerald I. , Nadel Ethan R.
Published: December 2017

We tested the hypothesis that an elevation in albumin synthetic rate contributes to increased plasma albumin content during exercise-induced hypervolemia. Albumin synthetic rate was measured in seven healthy subjects at 1–5 and 21–22 h after 72 min of intense (85% peak oxygen consumption rate) intermittent exercise and after 5 h recovery in either upright (Up) or supine (Sup) postures. Deuterated phenylalanine (d5-Phe) was administrated by a primed-constant infusion method, and fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin were calculated from the enrichment of d5-Phe in plasma albumin, determined by gas chromatography-mass spectrometry. FSR of albumin in Up increased significantly ( P < 0.05) from 4.9 ± 0.9%/day at control to 7.3 ± 0.9%/day at 22 h of recovery. ASR of albumin increased from 87.9 ± 17.0 to 141.1 ± 16.6 mg albumin ⋅ kg body wt− 1 ⋅ day− 1. In contrast, FSR and ASR of albumin were unchanged in Sup (3.9 ± 0.4 to 4.0 ± 1.4%/day and 74.2 ± 8.9 to 85.3 ± 23.9 mg albumin ⋅ kg body wt− 1 ⋅ day− 1at control and 22 h of recovery, respectively). Increased albumin synthesis after upright intense exercise contributes to the expansion of greater albumin content and its maintenance. We conclude that stimuli related to posture are critical in modulating the drive for albumin synthesis after intense exercise.
An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise
Authors: Rasmussen Blake B. , Tipton Kevin D. , Miller Sharon L. , Wolf Steven E. , Wolfe Robert R.
Published: December 2017

This study was designed to determine the response of muscle protein to the bolus ingestion of a drink containing essential amino acids and carbohydrate after resistance exercise. Six subjects (3 men, 3 women) randomly consumed a treatment drink (6 g essential amino acids, 35 g sucrose) or a flavored placebo drink 1 h or 3 h after a bout of resistance exercise on two separate occasions. We used a three-compartment model for determination of leg muscle protein kinetics. The model involves the infusion of ring-2H5-phenylalanine, femoral arterial and venous blood sampling, and muscle biopsies. Phenylalanine net balance and muscle protein synthesis were significantly increased above the predrink and corresponding placebo value ( P < 0.05) when the drink was taken 1 or 3 h after exercise but not when the placebo was ingested at 1 or 3 h. The response to the amino acid-carbohydrate drink produced similar anabolic responses at 1 and 3 h. Muscle protein breakdown did not change in response to the drink. We conclude that essential amino acids with carbohydrates stimulate muscle protein anabolism by increasing muscle protein synthesis when ingested 1 or 3 h after resistance exercise.
Microvascular and myocardial contractile responses to ischemia: influence of exercise training
Authors: Symons J. David , Rendig Stephen V. , Stebbins Charles L. , Longhurst John C.
Published: December 2017

We hypothesized that exercise training preserves endothelium-dependent relaxation, lessens receptor-mediated constriction of coronary resistance arteries, and reduces myocardial contractile dysfunction in response to ischemia. After 10 wk of treadmill running or cage confinement, regional and global indexes of left ventricular contractile function were not different between trained and sedentary animals in response to three 15-min periods of ischemia (long-term; n = 17), one 5-min bout of ischemia (short-term; n = 18), or no ischemia (sham-operated; n = 24). Subsequently, coronary resistance vessels (∼106 ± 4 μm ID) were isolated and studied using wire myographs. Maximal ACh-evoked relaxation was ∼25, 40, and 60% of KCl-induced preconstriction after the long-term, short-term, and sham-operated protocols, respectively, and was similar between groups. Maximal sodium nitroprusside-evoked relaxation also was similar between groups among all protocols, and vasoconstrictor responses to endothelin-1 and U-46619 were not different in trained and sedentary rats after short-term ischemia or sham operation. We did observe that, after long-term ischemia, maximal tension development in response to endothelin-1 and U-46619 was blunted ( P < 0.05) in trained animals by ∼70 and ∼160%, respectively. These results support our hypothesis that exercise training lessens receptor-mediated vasoconstriction of coronary resistance vessels after ischemia and reperfusion. However, training did not preserve endothelial function of coronary resistance vessels, or myocardial contractile function, after ischemia and reperfusion.
Structural basis of muscle O2 diffusing capacity: evidence from muscle function in situ
Authors: Hepple Russell T. , Hogan Michael C. , Stary Creed , Bebout Donald E. , Mathieu-Costello Odile , Wagner Peter D.
Published: December 2017

Although evidence for muscle O2 diffusion limitation of maximal O2 uptake has been found in the intact organism and isolated muscle, its relationship to diffusion distance has not been examined. Thus we studied six sets of three purpose-bred littermate dogs (aged 10–12 mo), with 1 dog per litter allocated to each of three groups: control (C), exercise trained for 8 wk (T), or left leg immobilized for 3 wk (I). The left gastrocnemius muscle from each animal was surgically isolated, pump-perfused, and electrically stimulated to peak O2 uptake at three randomly applied levels of arterial oxygenation [normoxia, arterial[Formula: see text]([Formula: see text]) 77 ± 2 (SE) Torr; moderate hypoxia, [Formula: see text]: 33 ± 1 Torr; and severe hypoxia, [Formula: see text]: 22 ± 1 Torr]. O2 delivery (ml ⋅ min−1 ⋅ 100 g− 1) was kept constant among groups for each level of oxygenation, with O2 delivery decreasing with decreasing [Formula: see text]. O2extraction (%) was lower in I than T or C for each condition, but calculated muscle O2 diffusing capacity (Dm[Formula: see text]) per 100 grams of muscle was not different among groups. After the experiment, the muscle was perfusion fixed in situ, and a sample from the midbelly was processed for microscopy. Immobilized muscle showed a 45% reduction of muscle fiber cross-sectional area ( P < 0.05), and a resulting 59% increase in capillary density ( P < 0.05) but minimal reduction in capillary-to-fiber ratio (not significant). In contrast, capillarity was not significantly different in T vs. C muscle. The results show that a dramatically increased capillary density (and reduced diffusion distance) after short-term immobilization does not improve Dm[Formula: see text] in heavily working skeletal muscle.
Downregulation in muscle Na+-K+-ATPase following a 21-day expedition to 6,194 m
Authors: Green Howard , Roy Brian , Grant Susan , Burnett Margaret , Tupling Russ , Otto Christian , Pipe Andrew , McKenzie Donald
Published: December 2017

To investigate the hypothesis that acclimatization to altitude would result in a downregulation in muscle Na+-K+-ATPase pump concentration, tissue samples were obtained from the vastus lateralis muscle of six volunteers (5 males and 1 female), ranging in age from 24 to 35 yr, both before and within 3 days after a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m). Na+-K+-ATPase, measured by the [3H]ouabain-binding technique, decreased by 13.8% [348 ± 12 vs. 300 ± 7.6 (SE) pmol/g wet wt; P< 0.05]. No changes were found in the maximal activities (mol ⋅ kg protein− 1 ⋅ h− 1) of the mitochondrial enzymes, succinic dehydrogenase (3.63 ± 0.20 vs. 3.25 ± 0.23), citrate synthase (4.76 ± 0.44 vs. 4.94 ± 0.44), and malate dehydrogenase (12.6 ± 1.8 vs. 12.7 ± 1.2). Similarly, the expedition had no effect on any of the histochemical properties examined, namely fiber-type distribution (types I, IIA, IIB, IC, IIC, IIAB), area, capillarization, and succinic dehydrogenase activity. Peak aerobic power (52.3 ± 2.1 vs. 50.6 ± 1.9 ml ⋅ kg− 1 ⋅ min− 1) and body mass (76.9 ± 3.7 vs. 75.5 ± 2.9 kg) were also unaffected. We concluded that acclimatization to altitude results in a downregulation in muscle Na+-K+-ATPase pump concentration, which occurs without changes in oxidative potential and other fiber-type histochemical properties.
Effects of positive end-expiratory pressure ventilation on cerebral venous pressure with head elevation in dogs
Authors: Toung Thomas J. K. , Aizawa H. , Traystman Richard J.
Published: December 2017

Mechanical ventilation with positive end-expiratory pressure (PEEP) may prevent venous air embolism in the sitting position because cerebral venous pressure (Pcev) could be increased by the PEEP-induced increase in right atrial pressure (Pra). Whereas it is clear that there is a linear transmission of the PEEP-induced increase in Pra to Pcev while the dog is in the prone position, the mechanism of the transmission with the dog in the head-elevated position is unclear. We tested the hypothesis that a Starling resistor-type mechanism exists in the jugular veins when the head is elevated. In one group of dogs, increasing PEEP linearly increased Pcev with the dog in the prone position (head at heart level, slope = 0.851) but did not increase Pcev when the head was elevated. In another group of dogs, an external chest binder was used to produce a larger PEEP-induced increase in Pra. Further increasing Pra increased Pcev only after Pra exceeded a pressure of 19 mmHg (break pressure). This sharp inflection in the upstream (Pcev)-downstream (Pra) relationship suggests that this may be caused by a Starling resistor-type mechanism. We conclude that jugular venous collapse serves as a significant resistance in the transmission of Pra to Pcev in the head-elevated position.
Glycogen loading alters muscle glycogen resynthesis after exercise
Authors: Price Thomas B. , Laurent Didier , Petersen Kitt F. , Rothman Douglas L. , Shulman Gerald I.
Published: December 2017

This study compared muscle glycogen recovery after depletion of ∼50 mmol/l (ΔGly) from normal (Nor) resting levels (63.2 ± 2.8 mmol/l) with recovery after depletion of ∼50 mmol/l from a glycogen-loaded (GL) state (99.3 ± 4.0 mmol/l) in 12 healthy, untrained subjects (5 men, 7 women). To glycogen load, a 7-day carbohydrate-loading protocol increased muscle glycogen 1.6 ± 0.2-fold ( P ≤ 0.01). GL subjects then performed plantar flexion (single-leg toe raises) at 50 ± 3% of maximum voluntary contraction (MVC) to yield ΔGly = 48.0 ± 1.3 mmol/l. The Nor trial, performed on a separate occasion, yielded ΔGly = 47.5 ± 4.5 mmol/l. Interleaved natural abundance13C-31P-NMR spectra were acquired and quantified before exercise and during 5 h of recovery immediately after exercise. During the initial 15 min after exercise, glycogen recovery in the GL trial was rapid (32.9 ± 8.9 mmol ⋅ l−1⋅ h−1) compared with the Nor trial (15.9 ± 6.9 mmol ⋅ l−1⋅ h−1). During the next 45 min, GL glycogen synthesis was not as rapid as in the Nor trial (0.9 ± 2.5 mmol ⋅ l−1⋅ h−1for GL; 14.7 ± 3.0 mmol ⋅ l−1⋅ h−1for Nor; P ≤ 0.005) despite similar glucose 6-phosphate levels. During extended recovery (60–300 min), reduced GL recovery rates continued (1.3 ± 0.5 mmol ⋅ l−1⋅ h−1for GL; 3.9 ± 0.3 mmol ⋅ l−1⋅ h−1for Nor; P ≤ 0.001). We conclude that glycogen recovery from heavy exercise is controlled primarily by the remaining postexercise glycogen concentration, with only a transient synthesis period when glycogen levels are not severely reduced.
Muscle metabolism during heavy-intensity exercise after acute acetazolamide administration
Authors: Scheuermann Barry W. , Kowalchuk John M. , Paterson Donald H. , Taylor Albert W. , Green Howard J.
Published: December 2017

Carbonic anhydrase (CA) inhibition is associated with a lower plasma lactate concentration ([La−]pl), but the mechanism for this association is not known. The effect of CA inhibition on muscle high-energy phosphates [ATP and phosphocreatine (PCr)], lactate ([La−]m), and glycogen was examined in seven men [28 ± 3 (SE) yr] during cycling exercise under control (Con) and acute CA inhibition with acetazolamide (Acz; 10 mg/kg body wt iv). Subjects performed 6-min step transitions in work rate from 0 W to a work rate corresponding to ∼50% of the difference between the O2 uptake at the ventilatory threshold and peak O2 uptake. Muscle biopsies were taken from the vastus lateralis at rest, at 30 min postinfusion, at end exercise (EE), and at 5 and 30 min postexercise. Arterialized venous blood was sampled from a dorsal hand vein and analyzed for [La−]pl. ATP was unchanged from rest values; no difference between Con and Acz was observed. The fall in PCr from rest [72 ± 3 and 73 ± 3.6 (SE) mmol/kg dry wt for Con and Acz, respectively] to EE (51 ± 4 and 46 ± 5 mmol/kg dry wt for Con and Acz, respectively) was similar in Con and Acz. At EE, glycogen (mmol glucosyl units/kg dry wt) decreased to similar values in Con and Acz (307 ± 16 and 300 ± 19, respectively). At EE, no difference was observed in [La−]mbetween conditions (46 ± 6 and 43 ± 5 mmol/kg dry wt for Con and Acz, respectively). EE [La−]plwas higher during Con than during Acz (11.4 ± 1.0 vs. 8.2 ± 0.6 mmol/l). The similar [La−]mbut lower [La−]plsuggests that the uptake of La− by other tissues is enhanced after CA inhibition.
Segregated signal averaging of sympathetic baroreflex responses in humans
Authors: Halliwill John R.
Published: December 2017

The goal of this study was to merge the methods currently used to assess beat-by-beat changes in muscle sympathetic nerve activity with a signal-averaging approach and overcome the inherent subjectivity and time-consuming nature of manual analysis of baroreflex-mediated sympathetic responses in humans. This is a retrospective study using data obtained during two prior studies [J. R. Halliwill, J. A. Taylor, and D. L. Eckberg. J. Physiol. (Lond.) 495: 279–288, 1996; C. T. Minson, J. R. Halliwill, T. Young, and M. J. Joyner. FASEB J. 13: A1044, 1999]. Beat-by-beat arterial pressure (Finapres device) and muscle sympathetic nerve activity (microneurography) were recorded in seven healthy, nonsmoking, normotensive subjects (2 men, 5 women) between the ages of 23 and 32 yr during arterial pressure changes induced by bolus injections of nitroprusside and phenylephrine. The muscle sympathetic nerve activity-diastolic pressure relationship was analyzed by both the traditional manual detection method and a novel segregated signal-averaging method. The results show the two analysis approaches are highly correlated across subjects ( r = 0.914, P < 0.05) and are in close agreement [slope for manual detection −6.17 ± 0.91 (SE) vs. slope for segregated signal averaging −5.98 ± 0.83 total integrated activity ⋅ beat−1 ⋅ mmHg−1; P = 0.60]. However, a considerable time savings is seen with the new method (min vs. h). Segregated signal averaging as developed here provides a valid alternative to “by-hand” analysis of beat-by-beat changes in muscle sympathetic nerve activity that occur during dynamic baroreflex-mediated changes in sympathetic outflow. This approach provides an objective, rapid method to analyze nerve recordings.
Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle
Authors: Kirwan John P. , del Aguila Luis F. , Hernandez Jazmir M. , Williamson David L. , O'Gorman Donal J. , Lewis Rebecca , Krishnan Raj K.
Published: December 2017

Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU ⋅ m−2⋅ min−1)-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 ± 1 yr, 71.8 ± 2.0 kg, maximal O2uptake (V˙o2 max) of 56.1 ± 2.5 ml ⋅ kg−1⋅ min−1] and eight healthy sedentary men and women (24 ± 1 yr, 64.7 ± 4.4 kg,V˙o2 maxof 44.4 ± 2.7 ml ⋅ kg−1⋅ min−1). A [6,6-2H]glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 ± 22 and 311 ± 22 pM for trained and sedentary, respectively). Insulin-mediated glucose disposal rates (GDR) were greater ( P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 ± 0.95 vs. 6.36 ± 0.57 mg ⋅ kg fat-free mass−1⋅ min−1). Insulin-stimulated PI3-kinase activation was also greater ( P< 0.004) in the trained compared with the sedentary group (3.8 ± 0.5- vs. 1.8 ± 0.2-fold increase from basal). Endurance capacity (V˙o2 max) was positively correlated with PI3-kinase activation ( r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation ( r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.
High-volume, heavy-resistance strength training and muscle damage in young and older women
Authors: Roth Stephen M. , Martel Gregory F. , Ivey Frederick M. , Lemmer Jeffrey T. , Metter E. Jeffrey , Hurley Ben F. , Rogers Marc A.
Published: December 2017

To determine possible age differences in muscle damage response to strength training, ultrastructural muscle damage was assessed in seven 20- to 30-yr-old and six 65- to 75-yr-old previously sedentary women after heavy-resistance strength training (HRST). Subjects performed unilateral knee-extension exercise 3 days/wk for 9 wk. Bilateral muscle biopsies from the vastus lateralis were assessed for muscle damage via electron microscopy. HRST resulted in a 38 and 25% increase in strength in the young and older women, respectively ( P < 0.05), but there were no between-group differences. In the young women, 2–4% of muscle fibers exhibited damage before and after training in both the trained and untrained legs ( P = not significant). In contrast, muscle damage increased significantly after HRST, from 5 to 17% of fibers damaged ( P < 0.01), in the older women in the trained leg compared with only 2 and 5% of fibers damaged in the untrained leg before and after training, respectively. The present results indicate that older women exhibit higher levels of muscle damage after chronic HRST than do young women.
Sprint performance is related to muscle fascicle length in male 100-m sprinters
Authors: Kumagai Kenya , Abe Takashi , Brechue William F. , Ryushi Tomoo , Takano Susumu , Mizuno Masuhiko
Published: December 2017

The purpose of this study was to investigate the relationship between muscle fascicle length and sprint running performance in 37 male 100-m sprinters. The sample was divided into two performance groups by the personal-best 100-m time: 10.00–10.90 s (S10; n = 22) and 11.00–11.70 s (S11; n = 15). Muscle thickness and fascicle pennation angle of the vastus lateralis and gastrocnemius medialis and lateralis muscles were measured by B-mode ultrasonography, and fascicle length was estimated. Standing height, body weight, and leg length were similar between groups. Muscle thickness was similar between groups for vastus lateralis and gastrocnemius medialis, but S10 had a significantly greater gastrocnemius lateralis muscle thickness. S10 also had a greater muscle thickness in the upper portion of the thigh, which, given similar limb lengths, demonstrates an altered “muscle shape.” Pennation angle was always less in S10 than in S11. In all muscles, S10 had significantly greater fascicle length than did S11, which significantly correlated with 100-m best performance ( rvalues from −0.40 to −0.57). It is concluded that longer fascicle length is associated with greater sprinting performance.
Differential facilitation of high- and low-output nerve terminals from a single motoneuron
Authors: Crider Misty E. , Cooper Robin L.
Published: December 2017

In the crayfish opener neuromuscular preparation, regional differences in synaptic transmission are observed among the terminals of a single motoneuron. With a single stimulus, the high-output terminals of the proximal region of the muscle produce a larger excitatory postsynaptic potential than do the low-output terminals of the central region of the muscle. We tested the hypothesis that the low-output terminals exhibit more facilitation than do high-output terminals for twin-pulse, train, and continuous-stimulation paradigms. Previous studies have not employed several stimulation paradigms to induce facilitation among high- and low-output terminals of a single motoneuron. We found that the high-output terminals on the proximal fibers facilitate more than the low-output terminals on the central muscle fibers, in contrast with previous studies on similar muscles. The difference in measured facilitation is dependent on the stimulation paradigm. These results are important because ultrastructural differences between these high- and low-output terminals are known and can be used for correlatation with physiological measurements. Short-term facilitation is a form of short-term memory at the synaptic level, and the processes understood at the crayfish neuromuscular junction may well be applicable to all chemical synapses.
Sustained microgravity reduces the human ventilatory response to hypoxia but not to hypercapnia
Authors: Prisk G. Kim , Elliott Ann R. , West John B.
Published: December 2017

We measured the isocapnic hypoxic ventilatory response and the hypercapnic ventilatory response by using rebreathing techniques in five normal subjects (ages 37–47 yr) before, during, and after 16 days of exposure to microgravity (μG). Control measurements were performed with the subjects in the standing and supine postures. In both μG and in the supine position, the hypoxic ventilatory response, as measured from the slope of ventilation against arterial O2 saturation, was greatly reduced, being only 46 ± 10% (μG) and 52 ± 11% (supine) of that measured standing ( P < 0.01). During the hypercapnic ventilatory response test, the ventilation at a[Formula: see text] of 60 Torr was not significantly different in μG (101 ± 5%) and the supine position (89 ± 3%) from that measured standing. Inspiratory occlusion pressures agreed with these results. The findings can be explained by inhibition of the hypoxic but not hypercapnic drive, possibly as a result of an increase in blood pressure in carotid baroreceptors in μG and the supine position.
Embryonic quail eye development in microgravity
Authors: Barrett Joyce E. , Wells Diane C. , Paulsen Avelina Q. , Conrad Gary W.
Published: December 2017

The US-Russian joint quail embryo project was designed to study the effects of microgravity on development of Japanese quail embryos incubated aboard Mir. For this part of the project, eyes from embryonic days 14 and 16 (E14 and E16) flight embryos were compared with eyes from several groups of ground-based control embryos. Measurements were recorded for eye weights; eye, corneal, and scleral ring diameters; and numbers of bones in scleral ossicle rings. Transparency of E16 corneas was documented, and immunohistochemical staining was performed to observe corneal innervation. In addition, corneal ultrastructure was observed at the electron microscopic level. Except for corneal diameter of E16 flight embryos, compared with that of one of the sets of controls, results reported here indicate that eye development occurred normally in microgravity. Fixation by cracking the shell and placing the egg in paraformaldehyde solution did not adequately preserve corneal nerves or cellular ultrastructure.