bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural inhibition during maximal eccentric and concentric quadriceps contraction: effects of resistance training
Authors: Aagaard P. , Simonsen E. B. , Andersen J. L. , Magnusson S. P. , Halkjær-Kristensen J. , Dyhre-Poulsen P.
Published: December 2017

Despite full voluntary effort, neuromuscular activation of the quadriceps femoris muscle appears inhibited during slow concentric and eccentric contractions. Our aim was to compare neuromuscular activation during maximal voluntary concentric and eccentric quadriceps contractions, hypothesizing that inhibition of neuromuscular activation diminishes with resistance training. In 15 men, pretraining electromyographic activity of the quadriceps muscles [vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF)] was 17–36% lower during slow and fast (30 and 240°/s) eccentric and slow concentric contractions compared with fast concentric contractions. After 14 wk of heavy resistance training, neuromuscular inhibition was reduced for VL and VM and was completely removed for RF. Concurrently, electromyographic activity increased 21–52, 22–29, and 16–32% for VL, VM, and RF, respectively. In addition, median power frequency decreased for VL and RF. Eccentric quadriceps strength increased 15–17%, whereas slow and fast concentric strength increased 15 and 8%, respectively. Pre- and posttraining median power frequency did not differ between eccentric and concentric contractions. In conclusion, quadriceps motoneuron activation was lower during maximal voluntary eccentric and slow concentric contractions compared with during fast concentric contraction in untrained subjects, and, after heavy resistance training, this inhibition in neuromuscular activation was reduced.
Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity
Authors: Horowitz Jeffrey F. , Klein Samuel
Published: December 2017

We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 ± 1 vs. 38 ± 1 kg/m2), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([13C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 ± 0.4 vs. 4.0 ± 0.3 μmol · kg fat free mass (FFM)−1 · min−1]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 ± 1.7 vs. 14.5 ± 1.8 μmol · kg FFM−1 · min−1; P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 ± 1.2 vs. 17.5 ± 1.6 μmol · kg FFM−1 · min−1; P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.
Effects of prenatal spaceflight on vestibular responses in neonatal rats
Authors: Ronca April E. , Alberts Jeffrey R.
Published: December 2017

Ten pregnant Norway rats (Rattus norvegicus) were flown for 11 days on board the NASA space shuttle from gestational day 9 (launch) until gestational day 20 (landing) of the rats' 22-day pregnancy. After the birth of the pups, vestibular responses were analyzed from postnatal day (P) 0 until P5. In the first test, P0 neonates were supported on a platform in a side-lying position. Skyward head movements (i.e., movements performed against the gravity vector) were more frequent than head movements toward Earth in both flight and control neonates. In the second test, the contact-righting reflex, composed of stereotyped movements that rotate the body from supine to prone on a solid surface, was analyzed in P0 neonates. The frequency and latency of contact-righting responses did not differ in flight and control neonates. In the third test, vestibular head righting, with tactile and proprioceptive cues removed, was tested in neonates on P1, P3, and P5 by using a water-immersion test. Righting responses were observed less frequently in P1 and P3 flight neonates compared with controls. However, this deficit was transient, as evidenced by complete response recovery on P5. Collectively, these findings provide evidence for a selective disruption of vestibular-mediated responses after prenatal exposure to spaceflight.
Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lepob ) mice
Authors: Winters Bradford , Mo Zhiping , Brooks-Asplund Esther , Kim Soonyul , Shoukas Artin , Li Dechun , Nyhan Daniel , Berkowitz Dan E.
Published: December 2017

Obesity is a major health care problem and is associated with significant cardiovascular morbidity. Leptin, a neuroendocrine hormone released by adipose tissue, is important in modulating obesity by signaling satiety and increasing metabolism. Moreover, leptin receptors are expressed on vascular endothelial cells (ECs) and mediate angiogenesis. We hypothesized that leptin may also play an important role in vasoregulation. We investigated vasoregulatory mechanisms in the leptin-deficient obese ( ob/ob) mouse model and determined the influence of leptin replacement on endothelial-dependent vasorelaxant responses. The direct effect of leptin on EC nitric oxide (NO) production was also tested by using 4,5-diaminofluorescein-2 diacetate staining and measurement of nitrate and nitrite concentrations. Vasoconstrictor responses to phenylephrine, norepinephrine, and U-46619 were markedly enhanced in aortic rings from ob/ob mice and were modulated by NO synthase inhibition. Vasorelaxant responses to ACh were markedly attenuated in mesenteric microvessels from ob/ob mice. Leptin replacement resulted in significant weight loss and reversal of the impaired endothelial-dependent vasorelaxant responses observed in ob/ob mice. Preincubation of ECs with leptin enhanced the release of NO production. Thus leptin-deficient ob/ob mice demonstrate marked abnormalities in vasoregulation, including impaired endothelial-dependent vasodilation, which is reversed by leptin replacement. These findings may be partially explained by the direct effect of leptin on endothelial NO production. These vascular abnormalities are similar to those observed in obese, diabetic, leptin-resistant humans. The ob/ob mouse may, therefore, be an excellent new model for the study of the cardiovascular effects of obesity.
Insulin stimulation of glucose uptake fails to decrease palmitate oxidation in muscle if AMPK is activated
Authors: Winder W. W. , Holmes B. F.
Published: December 2017

Fatty acid oxidation in muscle has been reported to be diminished when insulin and glucose levels are elevated. This study was designed to determine whether activation of AMP-activated protein kinase (AMPK) will prevent inhibitory effects of insulin and glucose on the rate of fatty acid oxidation. Rat hindlimbs were perfused with medium containing 0, 0.3, or 60 nM insulin with or without 2 mM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR). Glucose uptake was stimulated four- to fivefold by inclusion of insulin in the medium. Insulin attenuated the increase in AMPK caused by AICAR both in perfused hindlimbs and in isolated epitrochlearis muscles. The activation constant for citrate activation of acetyl-CoA carboxylase (ACC) was significantly increased in response to AICAR, and the increase was slightly attenuated if insulin was present in the perfusion medium. Insulin stimulated an increase in malonyl-CoA content of the muscles in the absence of AICAR. Malonyl-CoA was decreased to approximately the same value in AICAR-perfused muscle, regardless of insulin concentration. Muscle glucose 6-phosphate and citrate were significantly increased in response to AICAR and insulin. The rate of palmitate oxidation tended to decrease in response to insulin and in the absence of AICAR. AICAR increased palmitate oxidation to approximately the same level regardless of the insulin concentration or the rate of glucose uptake into the muscle. The rate of palmitate oxidation showed a curvilinear relationship as a function of muscle malonyl-CoA content, with half-maximal inhibition at ∼0.6 nmol/g. We conclude that AMPK activation can prevent high rates of glucose uptake and glycolytic flux from inhibiting palmitate oxidation in predominantly fast-twitch muscle under these conditions.
Effects of long-term exercise on the biomechanical properties of the Achilles tendon of guinea fowl
Authors: Buchanan Cindy I. , Marsh Richard L.
Published: December 2017

The purpose of this study was to determine the effect of long-term exercise on tendon compliance and to ascertain whether tendons adapt differently to downhill running vs. running on a level surface. We carried out this investigation on the gastrocnemius tendon of helmeted guinea fowl ( Numida meleagris) that were trained for 8–12 wk before commencing experimental procedures. We used an in situ technique to measure tendon stiffness. The animals were deeply anesthetized with isofluorane during all in situ procedures. Our results indicate that long-term exercise increased tendon stiffness. This finding held true after normalization for the cross-sectional area of the free tendon, likely reflecting a change in the material properties of the exercised tendons. Whether training consisted of level or downhill running did not appear to influence response of the tendon to exercise. We hypothesize that the increased stiffness observed in tendons after a long-term running program may be a response to repeated stress and may function as a mechanism to resist tendon damage due to mechanical fatigue.
Alveolar metabolism of natural vs. synthetic surfactants in preterm newborn rabbits
Authors: Allen Victoria , Oulton Margaret , Stinson Dora , MacDonald Josee , Allen Alexander
Published: December 2017

We compared the recoveries of four surfactant preparations: two natural [term fetal rabbit surfactant (FRS) and adult rabbit surfactant (ARS)] and two commercially available preparations [apoprotein-based Survanta (S) and synthetic Exosurf (E)] from 27-day gestation rabbit pups treated at birth and ventilated up to 120 min. At 5, 60, and 120 min, we measured the recovery of the heavy-aggregate, metabolically active form (H) and the light-aggregate, nonsurface active metabolic breakdown form (L) of alveolar surfactant and determined the phospholipid content and composition of the intracellularly stored lamellar body (LB) pool. Pups treated with FRS had <15% loss of H by 2 h. ARS-treated pups had a >50% loss of H by 1 h, and E- and S-treated pups had ∼50% loss by 5 min, with a slower rate of continuing loss of up to 80% by 2 h. The major losses of H phospholipid were not explained by the L-form recovery. LB phospholipid significantly increased only in the E-treated pups and only at 2 h. FRS provides a biologically active form (H) of surfactant that appeared to remain in the airway for a significantly longer time than the other surfactant preparations. The unique properties of FRS merit further study.
Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries
Authors: Laughlin M. Harold , Schrage William G. , McAllister Richard M. , Garverick H. A. , Jones A. W.
Published: December 2017

The purpose of the present study was to test the hypothesis that gender influences exercise training-induced adaptations of vascular reactivity of porcine arteries that provide blood flow to skeletal muscle and femoral and brachial arteries. Male and female Yucatan miniature swine were exercise trained on a motor-driven treadmill or cage confined for 16–20 wk. Contractile responses of arterial rings were evaluated in vitro by determining concentration-response curves for endothelin-1 (ET-1; 10−10 to 10−7 M) and norepinephrine (NE; 10−10 to 10−4 M). Relaxation responses of arteries precontracted with 30 μM PGF2αwere examined for endothelium-dependent agents [bradykinin (BK; 10−11 to 10−6 M), ACh (10−10 to 10−4 M), and a Ca2+ ionophore, A-23187 (10−6 M)] and a endothelium-independent agent [sodium nitroprusside (10−10 to 10−4 M)]. Arteries from female pigs developed greater contractile force in response to ET-1 than arteries from male pigs, whereas contractile responses to NE and KCl were similar in arteries from both genders. Femoral arteries from females exhibited greater endothelium-mediated vasorelaxation (BK and ACh) than did those from males. In contrast, brachial arteries of males were more responsive to BK and ACh than brachial arteries of females. Exercise training increased ET-1-induced contractions in arteries from males (without endothelium) but not in arteries from females. Training had no effect on endothelium-dependent relaxation in arteries from males but increased relaxation responses in brachial arteries from females. We conclude that both gender and anatomic origin of the artery influence exercise training-induced adaptations of vascular reactivity of porcine skeletal muscle conduit arteries.
Training, muscle volume, and energy expenditure in nonobese American girls
Authors: Eliakim Alon , Scheett Tim , Allmendinger Nicki , Brasel Jo Anne , Cooper Dan M.
Published: December 2017

Little is known about the relationship among training, energy expenditure, muscle volume, and fitness in prepubertal girls. Because physical activity is high in prepubertal children, we hypothesized that there would be no effect of training. Forty pre- and early pubertal (mean age 9.1 ± 0.1 yr) nonobese girls enrolled in a 5 day/wk summer school program for 5 wk and were randomized to control ( n = 20) or training groups ( n = 20; 1.5 h/day, endurance-type exercise). Total energy expenditure (TEE) was measured using doubly labeled water, thigh muscle volume using magnetic resonance imaging, and peak O2uptake (V˙o2 peak) using cycle ergometry. TEE was significantly greater (17%, P < 0.02) in the training girls. Training increased thigh muscle volume (+4.3 ± 0.9%, P < 0.005) andV˙o2 peak(+9.5 ± 6%, P < 0.05), effects surprisingly similar to those observed in adolescent girls using the same protocol (Eliakim A, Barstow TJ, Brasel JA, Ajie H, Lee W-NP, Renslo R, Berman N, and Cooper DM, J Pediatr 129: 537–543, 1996). We further compared these two sample populations: thigh muscle volume per weight was much lower in adolescent compared with prepubertal girls (17.0 ± 0.3 vs. 27.8 ± 0.6 ml/kg body mass; P < 0.001), and allometric analysis revealed remarkably low scaling factors relating muscle volume (0.34 ± 0.05, P < 0.0001), TEE (0.24 ± 0.06, P < 0.0004), andV˙o2 peak(0.28 ± 0.07, P < 0.0001) to body mass in all subjects. Muscle and cardiorespiratory functions were quite responsive to brief training in prepubertal girls. Moreover, a retrospective, cross-sectional analysis suggests that increases in muscle mass andV˙o2 peakmay be depressed in nonobese American girls as they mature.
Selected Contribution: Mechanisms underlying increased force generation by rat diaphragm muscle fibers during development
Authors: Geiger Paige C. , Cody Mark J. , Macken Rebecca L. , Bayrd Megan E. , Fang Yun-Hua , Sieck Gary C.
Published: December 2017

It has been found that maximum specific force (Fmax; force per cross-sectional area) of rat diaphragm muscle doubles from birth to 84 days (adult). We hypothesize that this developmental change in Fmax reflects an increase in myosin heavy chain (MHC) content per half-sarcomere (an estimate of the number of cross bridges in parallel) and/or a greater force per cross bridge in fibers expressing fast MHC isoforms compared with slow and neonatal MHC isoforms (MHCslow and MHCneo, respectively). Single Triton 100-X-permeabilized fibers were activated at a pCa of 4.0. MHC isoform expression was determined by SDS-PAGE. MHC content per half-sarcomere was determined by densitometric analysis and comparison to a standard curve of known MHC concentrations. MHC content per half-sarcomere progressively increased during early postnatal development. When normalized for MHC content per half-sarcomere, fibers expressing MHCslow and coexpressing MHCneoproduced less force than fibers expressing fast MHC isoforms. We conclude that lower force per cross bridge in fibers expressing MHCslow and MHCneo contributes to the lower Fmax seen in early postnatal development.
Peripheral circulatory factors limit rate of increase in muscle O2 uptake at onset of heavy exercise
Authors: MacDonald Maureen J. , Naylor Heather L. , Tschakovsky Michael E. , Hughson Richard L.
Published: December 2017

We used an exercise paradigm with repeated bouts of heavy forearm exercise to test the hypothesis that alterations in local acid-base environment that remain after the first exercise result in greater blood flow and O2 delivery at the onset of the second bout of exercise. Two bouts of handgrip exercise at 75% peak workload were performed for 5 min, separated by 5 min of recovery. We continuously measured blood flow using Doppler ultrasound and sampled venous blood for O2 content, Pco 2, pH, and lactate and potassium concentrations, and we calculated muscle O2uptake (V˙o 2). Forearm blood flow was elevated before the second exercise compared with the first and remained higher during the first 30 s of exercise (234 ± 18 vs. 187 ± 4 ml/min, P < 0.05). Flow was not different at 5 min. Arteriovenous O2 content difference was lower before the second bout (4.6 ± 0.9 vs. 7.2 ± 0.7 ml O2/dl) and higher by 30 s of exercise (11.2 ± 0.7 vs. 10.8 ± 0.7 ml O2/dl, P < 0.05). Muscle V˙o 2was unchanged before the start of exercise but was elevated during the first 30 s of the transition to the second exercise bout (26.0 ± 2.1 vs. 20.0 ± 0.9 ml/min, P < 0.05). Changes in venous blood Pco 2, pH, and lactate concentration were consistent with reduced reliance on anaerobic glycolysis at the onset of the second exercise bout. These data show that limitations of muscle blood flow can restrict the adaptation of oxidative metabolism at the onset of heavy muscular exertion.
Detrimental effects of complement activation in hemorrhagic shock
Authors: Younger John G. , Sasaki Nobuyoshi , Waite Michael D. , Murray Holt N. , Saleh Edward F. , Ravage Zachary A. , Hirschl Ronald B. , Ward Peter A. , Till Gerd O.
Published: December 2017

The complement system has been implicated in early inflammatory events and a variety of shock states. In rats, we measured complement activation after hemorrhage and examined the hemodynamic and metabolic effects of complement depletion before injury and worsening of complement activation after hemorrhage and resuscitation [with a carboxypeptidase N inhibitor (CPNI), which blocks the clearance of C5a]. Rats were bled to a mean arterial pressure of 30 mmHg for 50 min and were then resuscitated for 2 h. Shock resulted in significant evidence of complement consumption, with serum hemolytic activity being reduced by 33% ( P < 0.05). Complement depletion before injury did not affect hemorrhage volume (complement depleted = 28 ± 1 ml/kg, complement intact = 29 ± 1 ml/kg, P = 0.74) but improved postresuscitation mean arterial pressure by 37 mmHg ( P < 0.05) and serum bicarbonate levels (complement depleted = 22 ± 3 meq/ml, complement intact = 13 ± 8 meq/ml, P < 0.05). Pretreatment with CPNI was lethal in 80% of treated animals vs. the untreated hemorrhaged group in which no deaths occurred ( P < 0.05). In this model of hemorrhagic shock, complement activation appeared to contribute to progressive hypotension and metabolic acidosis seen after resuscitation. The lethality of CPNI during acute blood loss suggests that the anaphylatoxins are important in the pathophysiological events involved in hemorrhagic shock.
Tuning of pulmonary arterial circulation evidenced by MR phase mapping in healthy volunteers
Authors: Laffon Eric , Bernard Virginie , Montaudon Michel , Marthan Roger , Barat Jean-Louis , Laurent François
Published: December 2017

Magnetic resonance (MR) phase mapping was used to noninvasively assess both blood flow and cross-sectional area (CSA) in the main pulmonary artery (MPA) of 12 healthy volunteers. Flow and CSA patterns exhibited two positive peaks: high systolic and small diastolic. This finding can be explained using a simple “distributed” theoretical model that takes into account the role of a reflected pressure wave from pulmonary vascular impedance in generating a diastolic flow. The mean reflection coefficient of pressure wave, MPA input impedance, and pulmonary vascular impedance were assessed. We verified, in this series, that pressure wave velocity appears to be age-dependent. MR phase mapping has been used to observe the tuning (resonance) of the right cardiovascular system at rest under physiological conditions. MR phase mapping could be used to assess pathological modifications of the tuning that occurs in cases of pulmonary arterial hypertension.
Prolonged exercise suppresses antigen-specific cytokine response to upper respiratory infection
Authors: Kohut M. L. , Boehm G. W. , Moynihan J. A.
Published: December 2017

Fatiguing exercise has been associated with an increased susceptibility to infection. This study examined the antigen-specific T-helper (Th) type 1 and Th type 2 cytokine response to herpes simplex virus (HSV) infection after an acute bout of fatiguing exercise. Male BALB/cJ mice ran on a treadmill (Ex) until voluntary fatigue (∼2.5 h), and control mice were handled and remained next to the treadmill. Mice were infected with HSV 20 min after exercise. Mice were killed 2 or 7 days postinfection, and sera and spleens were taken for the determination of HSV-specific serum IgM, splenocyte cytokine production during culture with HSV, and splenocyte natural killer cell cytotoxicity. Both Th type 1 [interleukin (IL)-2, interferon-γ, IL-12] and Th type 2 (IL-10) cytokine production in spleen cell cultures, as well as natural killer cell cytotoxicity, decreased in Ex on day 2 postinfection. On day 7postinfection, there was no difference in HSV-specific serum IgM or cytokine production by cells from control and Ex mice, with the exception of decreased IL-12 in Ex mice. These findings suggest that fatiguing exercise may alter the kinetics of antigen-specific cytokine production.
Habitual exercise enhances neuromuscular transmission efficacy of rat soleus muscle in situ
Authors: Desaulniers Patrice , Lavoie Pierre-André , Gardiner Phillip F.
Published: December 2017

Rat motor nerve terminals and the endplates they interact with exhibit changes to varying patterns of use, as when exposed to increased activation in the form of endurance exercise training. The extent to which these changes affect neuromuscular transmission efficacy is uncertain. In this study, the effects of habitual exercise on the electrophysiological properties of neuromuscular transmission in rat soleus muscle were investigated using a novel in situ approach. Consistent with previous reports, miniature endplate potential frequency was enhanced by habitual exercise. Other passive properties, such as resting membrane potential, miniature endplate potential amplitude, and “giant” miniature endplate potential characteristics were unaltered by the training program. Full-size endplate potentials were obtained by blocking soleus muscle action potentials with μ-conotoxin GIIIb. Quantal content values were 91.5 and 119.9 for control and active groups, respectively ( P < 0.01). We also measured the rate and extent of endplate potential amplitude rundown during 3-s trains of continuous stimulation at 25, 50, and 75 Hz; at 50 and 75 Hz, we found both the rate and extent of rundown to be significantly attenuated (10–20%) in a specific population of cells from active rats ( P < 0.05). The results establish the degree of activity-dependent plasticity as it pertains to neuromuscular transmission in a mammalian slow-twitch muscle.
Impact of age on breathing and resistive pressure in people with and without sleep apnea
Authors: Browne Helen A. K. , Adams Lewis , Simonds Anita K. , Morrell Mary J.
Published: December 2017

We investigated the effect of age on breathing and total pulmonary resistance (Rl) during sleep by studying elderly (>65 yr) and young (25–38 yr) people without sleep apnea (EN and YN, respectively) matched for body mass index (BMI). To determine the impact of sleep apnea on age-related changes in breathing, we studied elderly and young apneic patients (EA and YA, respectively) matched for apnea and BMI. In all groups ( n = 11), breathing during periods of stable sleep was analyzed to evaluate the intrinsic variability of respiratory control mechanisms. In the absence of sleep apnea, the variability of the breathing was similar in the elderly and young [mean (± SD) coefficient of variation (CV) of tidal volume (Vt); wake: EN 21.0 ± 14.9%, YN 14.7 ± 5.5%; sleep: EN 14.0 ± 6.0%; YN 11.5 ± 6.4%]. In patients with sleep apnea, breathing during stable sleep was more irregular, but there were no age-related differences (CV of Vt; wake: EA 22.0 ± 11.6%, YA 16.7 ± 11.3%; sleep: EA 32.8 ± 24.9%, YA 25.2 ± 16.3%). In addition, EN tended to have a higher Rl( n = 6, Rl midinspiration, wake: EN 7.1 ± 3.0; YN 9.1 ± 6.4 cmH2O · l−1 · s, sleep: EN 17.5 ± 11.7; YN 9.8 ± 2.0 cmH2O · l−1 · s). We conclude that aging per se does not contribute to the intrinsic variability of respiratory control mechanisms, although there may be a lower probability of finding elderly people without respiratory instability.
Selected Contribution: IGF-I antibody prevents increases in protein synthesis in epitrochlearis muscles from refed, diabetic rats
Authors: Fedele Mark J. , Vary Thomas C. , Farrell Peter A
Published: December 2017

The purpose of this study was to examine whether immune neutralization of muscle-produced insulin-like growth factor I (IGF-I) would prevent an appropriate anabolic response to refeeding in diabetic rats. Male Sprague-Dawley rats were made diabetic by partial pancreatectomy and were randomly assigned to be either control-fed, fasted, or fasted-refed ( n = 7–8 per group). Diabetes decreased rates of protein synthesis and increased rates of protein degradation in incubated epitrochlearis muscles ( P < 0.05). In both groups of rats, fasting lowered protein synthesis and increased proteolysis and subsequent refeeding returned both parameters to near basal values ( P < 0.05). Neutralization of muscle IGF-I by the addition of IGF-I antibody to the incubation medium reduced protein synthesis an average of 22% for all groups ( P < 0.05). However, rates of protein degradation were not affected. In nondiabetic rats, refeeding increased protein synthesis in both control and antibody-treated muscles ( P < 0.05). Refeeding also increased protein synthesis in the control muscles from diabetic rats ( P < 0.01). In contrast, muscles from diabetic rats that were incubated with anti-IGF-I did not increase protein synthesis in response to refeeding. These data suggest that immune neutralization of muscle IGF-I in hypoinsulinemic rats negated the ability of endogenous IGF-I to promote protein synthesis and thereby prevented an appropriate anabolic response.
Effects of different durations of exercise on macrophage functions in mice
Authors: Sugiura Haruo , Sugiura Hiroko , Nishida Hiroyuki , Inaba Ryoichi , Mirbod S. M. , Iwata Hirotoshi
Published: December 2017

The effects of differing durations of daily exercise on macrophage functions in mice were studied. Male ICR mice aged 4 wk were divided into five groups: a nonexercise group (control) and four exercise groups with differing daily exercise durations of 15–120 min (Exr groups). The exercise applied was 5 days/wk treadmill running at 13 m/min for 12 wk. The potentiation of the phagocytosis function of the reticuloendothelial system and the glucose consumption of peritoneal macrophages in the Exr 30, 60, and 120 groups were significantly higher than those in the control group. Superoxide anion production of peritoneal macrophages in both the absence and the presence of phorbol 12-myristate 13-acetate in the Exr 60 and 120 groups was significantly higher than that in the control group. The acid phosphatase and β-glucuronidase activities of peritoneal macrophages in the Exr 30, 60, and 120 groups were significantly increased. These results suggest that treadmill running exercise for at least 30 min/day (30–120 min) effectively enhances macrophage functions in mice. These data provide preliminary evidence indicating that chronic exercise-induced increases in phagocytic activity exhibit a dose-dependent relationship with exercise duration.
Lipoprotein lipase activity in skeletal muscles of the rat: effects of denervation and tenotomy
Authors: Smol E. , Z˙ernicka E. , Czarnowski D. , Langfort J.
Published: December 2017

The effects of denervation, tenotomy, or tenotomy with simultaneous denervation on the activity of heparin-releasable and intracellular, residual lipoprotein lipase (LPL) and triacylglycerol (TG) content were examined in rat skeletal muscles. An influence of muscle electrostimulation on denervated and tenotomized muscles was also evaluated. Activity of both LPL fractions was decreased in denervated and/or tenotomized soleus and red portion of gastrocnemius muscles. It was accompanied by a slight elevation of the intracellular TG content. Electrostimulation increased activities of both fractions of LPL in red muscles from intact hindlimbs. In stimulated denervated muscles without or with simultaneous tenotomy, activity of two LPL fractions was also enhanced, but control values were reached only in denervated soleus muscle. Electrical stimulation had no pronounced effect on LPL activity in tenotomized muscles. In conclusion, denervation and/or tenotomy decreases LPL activity in red muscles, indicating reduction of the muscle potential to utilize circulating TG. Electrostimulation only partly restores the diminished LPL activity in denervated muscles, without any effect in tenotomized ones. Thus, to maintain LPL activity in resting muscle, intact innervation and tension are needed.
Muscimol dialysis in the rostral ventral medulla reduced the CO2 response in awake and sleeping piglets
Authors: Curran Aidan K. , Darnall Robert A. , Filiano James J. , Li Aihua , Nattie Eugene E.
Published: December 2017

Some victims of sudden infant death syndrome have arcuate nucleus abnormalities. The arcuate nucleus may be homologous with ventral medullary structures in the cat known to be involved in the control of breathing and the response to systemic hypercapnia. We refer to putative arcuate homologues in the piglet collectively as the rostral ventral medulla (RVM). We inhibited the RVM in awake and sleeping, chronically instrumented piglets by microdialysis of the GABAA receptor agonist muscimol. Muscimol dialysis (10 and 40 mM) had no effect on eupnea but caused a significant reduction in the response to hypercapnia during both wakefulness (34.8 ± 8.7 and 30.7 ± 10.1%, respectively) and sleep (36.7 ± 6.7 and 49.5 ± 8.9%, respectively). The effect of muscimol on the CO2 response was entirely via a reduction in tidal volume and appeared to be greater during non-rapid-eye-movement sleep. We conclude that the piglet RVM contains neurons of importance in the response to systemic CO2 during both wakefulness and non-rapid-eye-movement sleep. We hypothesize that dysfunction of homologous regions in the human infant could lead to impaired ability to respond to hypercapnia, particularly during sleep, which could potentially be involved in the pathogenesis of sudden infant death syndrome.
Effect of unilateral denervation on maximum specific force in rat diaphragm muscle fibers
Authors: Geiger Paige C. , Cody Mark J. , Macken Rebecca L. , Bayrd Megan E. , Sieck Gary C.
Published: December 2017

We hypothesize that 1) the effect of denervation (DNV) is more pronounced in fibers expressing fast myosin heavy chain (MHC) isoforms and 2) the effect of DNV on maximum specific force reflects a reduction in MHC content per half sarcomere or the number of cross bridges in parallel. Studies were performed on single Triton X-100-permeabilized fibers activated at a pCa (−log Ca2+ concentration) of 4.0. MHC content per half sarcomere was determined by densitometric analysis of SDS-PAGE gels and comparison to a standard curve of known MHC concentrations. After 2 of wk DNV, the maximum specific force of fibers expressing MHC2X was reduced by ∼40% (MHC2Bexpression was absent), whereas the maximum specific force of fibers expressing MHC2A and MHCslow decreased by only ∼20%. DNV also reduced the MHC content in fibers expressing MHC2X, with no effect on fibers expressing MHC2A and MHCslow. When normalized for MHC content per half sarcomere, force generated by DNV fibers expressing MHC2X and MHC2A was decreased compared with control fibers. These results suggest the force per cross bridge is also affected by DNV.
Hormonal regulation of PGE2and COX-2 production in rabbit uterine cervical fibroblasts
Authors: Sato T. , Michizu H. , Hashizume K. , Ito A.
Published: December 2017

Prostaglandins (PGs) cause uterine contraction to initiate labor at term. We investigated the effect of progesterone and 17β-estradiol on the production of PGE2in rabbit uterine cervical fibroblasts. When the cervical fibroblasts were treated with interleukin-1α (IL-1α), the level of PGE2was augmented in a time- and dose-dependent manner. The IL-1α-augmented PGE2level was almost completely suppressed by progesterone and 17β-estradiol at the physiological concentration (0.01 μM), whereas a slight decrease in the basal level of PGE2was observed in the cervical fibroblasts treated with both hormones at a pharmacological concentration (1 μM). In addition, the level of PGE2augmented by IL-1α was due to the increase of cyclooxygenase (COX) activity, which was inhibited by progesterone and 17β-estradiol as well as by indomethacin and a specific COX-2 inhibitor, NS-398, but not by the well-known COX-1 inhibitor, aspirin. Furthermore, progesterone and 17β-estradiol suppressed the IL-1α-augmented COX-2 production but not the constitutive production of COX-1 in rabbit uterine cervical fibroblasts. These results suggest that progesterone and 17β-estradiol prevent the initiation of labor by inhibiting PGE2production after the suppression of COX-2 production during pregnancy in the rabbit.
CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep
Authors: Nattie Eugene E. , Li Aihua
Published: December 2017

Central chemoreceptors are widespread within the brain stem. We hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produced focal acidification at single sites by means of microdialysis using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured under anesthesia, is equivalent to that observed with 63 Torr end-tidal Pco 2 and is limited to 600 μm. Focal acidification of the retrotrapezoid nucleus increased ventilation by 24% only in wakefulness via an increase in tidal volume (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In this study of the medullary raphe, the effect of such focal acidification was in sleep (defined by electroencephalographic and electromyographic criteria): ventilation and frequency increased by 15–20% in non-rapid eye movement sleep, and frequency increased by 15% in rapid eye movement sleep. There was no effect in wakefulness. Chemoreception in the medullary raphe appears to be responsive in sleep. Central chemoreceptors at two different locations appear to vary in effectiveness with arousal state.
Effects of smooth muscle activation on axial mechanical properties of excised canine bronchi
Authors: Shardonofsky Felix R. , Officer Todd M. , Boriek Aladin M. , Rodarte Joseph R.
Published: December 2017

This study tested the hypothesis that airway smooth muscle (ASM) activation produces an airway active axial force (AAAF). Bronchi ( n = 10) immersed in a tissue bath containing 95% O2-5% CO2-equilibrated Krebs solution were subjected to passive axial lengthening and shortening at 0–20 cmH2O of transmural pressure. ASM was relaxed with isoproterenol and activated with methacholine. Axial tensile (ε x), transverse compressive (ε y), and shear strains (ε xy) were computed from the displacements of four markers placed onto the specimen's surface. The AAAF was estimated by subtracting the control axial force (AF) values at a given ε x from those obtained after methacholine. ε x-AF relationships were curvilinear, with maximum ε x being approached at ∼15 g of AF. The ε ydecreased during bronchial lengthening. Cholinergic stimulation produced 1) a decrease of both ε x and ε y at a given AF relative to control, indicating ASM shortening, and 2) an AAAF that increased with increasing ε x and transmural pressure. A portion of the work of expanding the lungs is required to lengthen the airways; therefore, an AAAF would increase lung elastance and recoil.
A method of reconstruction of clinical gas-analyzer signals corrupted by positive-pressure ventilation
Authors: Farmery A. D. , Hahn C. E. W.
Published: December 2017

The use of sidestream infrared and paramagnetic clinical gas analyzers is widespread in anesthesiology and respiratory medicine. For most clinical applications, these instruments are entirely satisfactory. However, their ability to measure breath-by-breath volumetric gas fluxes, as required for measurement of airway dead space, oxygen uptake, and so on, is usually inferior to that of the mass spectrometer, and this is thought to be due, in part, to their slower response times. We describe how volumetric gas analysis with the Datex Ultima analyzer, although reasonably accurate for spontaneous ventilation, gives very inaccurate results in conditions of positive-pressure ventilation. We show that this problem is a property of the gas sampling system rather than the technique of gas analysis itself. We examine the source of this error and describe how cyclic changes in airway pressure result in variations in the flow rate of the gas within the sampling catheter. This results in the phenomenon of “time distortion,” and the resultant gas concentration signal becomes a nonlinear time series. This corrupted signal cannot be aligned or integrated with the measured flow signal. We describe a method to correct for this effect. With the use of this method, measurements required for breath-by-breath gas-exchange models can be made easily and reliably in the clinical setting.
Lactate removal is not enhanced in nonstimulated perfused skeletal muscle after endurance training
Authors: Sumida Ken D. , Donovan Casey M.
Published: December 2017

The effects of endurance training (running 40 m/min, 10% grade for 60 min, 5 days/wk for 8 wk) on skeletal muscle lactate removal was studied in rats by utilizing the isolated hindlimb perfusion technique. Hindlimbs were perfused (single-pass) with Krebs-Henseleit bicarbonate buffer, fresh bovine erythrocytes (hematocrit ∼30%), 10 mM lactate, and [U-14C]lactate (30,000 dpm/ml). Arterial and venous blood samples were collected every 10 min for the duration of the experiment to assess lactate uptake. During perfusions, no significant differences in skeletal muscle lactate uptake were observed between trained (7.31 ± 0.20 μmol/min) and control hindlimbs (6.98 ± 0.43 μmol/min). In support, no significant differences were observed for [14C]lactate uptake in trained (22,776 ± 370 dpm/min) compared with control hindlimbs (21,924 ± 1,373 dpm/min). Concomitant with these observations, no significant differences were observed between groups for oxygen consumption (4.93 ± 0.18 vs. 4.92 ± 0.13 μmol/min), net skeletal muscle glycogen synthesis (7.1 ± 0.4 vs. 6.5 ± 0.3 μmol · 40 min−1· g−1), or14CO2production (2,203 ± 185 vs. 2,098 ± 155 dpm/min), trained and control, respectively. These findings indicate that endurance training does not affect lactate uptake or alter the metabolic fate of lactate in quiescent skeletal muscle.
Evaluation of laser-Doppler perfusion imaging for measurement of blood flow in cortical bone
Authors: Shymkiw Roxane C. , Zernicke Ronald F. , Forrester Kevin R. , Bray Robert C.
Published: December 2017

Most techniques currently available to measure blood flow in bone are time consuming and require destruction of the tissue, but laser-Doppler technology offers a less invasive method. This study assessed the utility of laser-Doppler perfusion imaging (LDI) to measure perfusion in cortical bone. Twelve mature New Zealand White rabbits were assigned to one of three groups: normal control, constriction (norepinephrine), or dilatation (nitroprusside). The left and right medial tibiae were consecutively scanned at red (634-nm) and near-infrared (810-nm) wavelengths to examine the repeatability of LDI output. The pharmacological intervention groups were injected with the respective drug, and LDI measurements at 810 nm were obtained concurrently with colored microsphere-determined flow in all of the groups. LDI effectively quantified blood flow in cortical bone and detected physiologically induced changes in perfusion. A significant positive correlation was found between microsphere-determined flow and LDI output ( r = 0.6, P < 0.05). Repeatability of consecutive LDI measurements was within 5%. The effectiveness of LDI to measure perfusion in bone suggests this method has potential for investigating the role of blood flow in bone metabolism and remodeling.
Aged bone displays an increased responsiveness to low-intensity resistance exercise
Authors: Buhl Kathleen M. , Jacobs Christopher R. , Turner Russell T. , Evans Glenda L. , Farrell Peter A. , Donahue Henry J.
Published: December 2017

The ability of bone to respond to increased loading as a function of age was tested by use of three-point bending and histomorphometry. The hindlimbs of male Fischer 344 rats of three age groups (young = 4 mo, adult = 12 mo, and old = 22 mo; n = 10 per age group) were progressively overloaded by training the rats to depress a lever high on the side of a cage while wearing a weighted backpack. This squatlike movement required full extension of the hindlimbs. Exercised (Exer) rats performed 50 repetitions three times per week for 9 wk. Pack weight was gradually increased to 65% of body weight. Controls ( n = 10 per age group) performed the same exercise without additional weight. Neither the mechanical properties of the femur nor histomorphometry in the proximal tibia was significantly affected in young or adult rats. However, old Exer rats were found to have significantly smaller medullary areas and a decreased trabecular spacing than their age-matched controls. These results suggest a greater sensitivity to increased loading in aged rats.
Exercise-enhanced satellite cell proliferation and new myonuclear accretion in rat skeletal muscle
Authors: Smith Heather K. , Maxwell Linda , Rodgers Carol D. , McKee Nancy H. , Plyley Michael J.
Published: December 2017

The effects of increased functional loading on early cellular regenerative events after exercise-induced injury in adult skeletal muscle were examined with the use of in vivo labeling of replicating myofiber nuclei and immunocyto- and histochemical techniques. Satellite cell proliferation in the soleus (Sol) of nonexercised rats (0.4 ± 0.2% of fibers) was unchanged after an initial bout of declined treadmill exercise but was elevated after two (1.0 ± 0.2%, P ≤ 0.01), but not four or seven, daily bouts of the same task. Myonuclei produced over the 7-day period comprised 0.9–1.9% of myonuclei in isolated fibers of Sol, tibialis anterior, and vastus intermedius of nonexercised rats. The accretion of new myonuclei was enhanced ( P ≤ 0.05) in Sol and vastus intermedius by the initial exercise followed by normal activity (to 3.1–3.4% of myonuclei) and more so by continued daily exercise (4.2–5.3%). Observed coincident with a lower incidence of histological fiber injury and unchanged fiber diameter and myonuclei per millimeter, the greater new myonuclear accretion induced by continued muscle loading may contribute to an enhanced fiber repair and regeneration after exercise-induced injury.
Intermittent hypoxia increases ventilation and SaO2 during hypoxic exercise and hypoxic chemosensitivity
Authors: Katayama Keisho , Sato Yasutake , Morotome Yoshifumi , Shima Norihiro , Ishida Koji , Mori Shigeo , Miyamura Miharu
Published: December 2017

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (SaO2 ) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and SaO2 during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (V˙o 2), expired minute ventilation (V˙e), and SaO2 were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2(V˙e/V˙o 2) and SaO2 during submaximal exercise. There were significant correlations among the changes in HVR at rest and inV˙e/V˙o 2 and SaO2 during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.
Cardiac and respiratory activity at arousal from sleep under controlled ventilation conditions
Authors: Trinder John , Padula Marinella , Berlowitz David , Kleiman Jan , Breen Sibilah , Rochford Peter , Worsnop Christopher , Thompson Bruce , Pierce Robert
Published: December 2017

Arousal from sleep is associated with elevated cardiac and respiratory activity. It is unclear whether this occurs because of homeostatic mechanisms or a reflex activation response associated with arousal. Cardiorespiratory activity was measured during spontaneous arousals from sleep in subjects breathing passively on a ventilator. Under such conditions, homeostatic mechanisms are eliminated. Ventilation, end-tidal Pco2, mask pressure, diaphragmatic electromyograph, heart rate, and blood pressure were measured in four normal subjects under two conditions: assisted ventilation and a normal ventilation control condition. In the control condition, there was a normal, sleep-related fall in ventilation and rise in end-tidal Pco2. Subsequently, at an arousal, there was an increase in respiratory and cardiac activity. In the ventilator condition, a vigorous cardiorespiratory response to a spontaneous arousal from sleep remained. These results indicate that sleep-related respiratory stimuli are not necessary for the occurrence of elevated cardiorespiratory activity at an arousal from sleep and are consistent with the hypothesis that such activity is at least in part due to a reflex activation response.