bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical performance and soleus muscle fiber composition in wild-derived and laboratory inbred mouse strains
Authors: Totsuka Yoshikazu , Nagao Yasumitsu , Horii Takuro , Yonekawa Hiromichi , Imai Hiroshi , Hatta Hideo , Izaike Yoshiaki , Tokunaga Tomoyuki , Atomi Yoriko
Published: March 2015

We compared four inbred mouse strains in their physical performance, measured as a maximal treadmill running time, characteristics of soleus muscle, anatomic character, and growth. The strains used were Mus musculus domesticus [C57BL/6 (B6) and BALB/c], Mus musculus molossinus (MSM/Ms), and Mus spretus. Maximal running time was significantly different among these four mouse strains. Running time until exhaustion was highest in MSM/Ms and lowest in M. spretus. Maximal times for the laboratory mouse strains were nearly identical. Soleus muscle fiber type and cross-sectional area also differed significantly among the species. In particular, M. spretus was significantly different from the other inbred mouse strains. Growth in the wild-derived inbred mice appeared to be complete earlier than in the laboratory mice, and the body size of the wild strains was about half that of the laboratory strains. From these results, we propose that wild-derived inbred mouse strains are useful models for enhancing phenotypic variation in physical performance and adaptability.
George I. Finch and his pioneering use of oxygen for climbing at extreme altitudes
Authors: West John B.
Published: March 2015

George Ingle Finch (1888–1970) was the first person to prove the great value of supplementary oxygen for climbing at extreme altitudes. He did this during the 1922 Everest expedition when he and his companion, Geoffrey Bruce, reached an altitude of 8,320 m, higher than any human had climbed before. Finch was well qualified to develop the oxygen equipment because he was an eminent physical chemist. Many of the features of the 1922 design are still used in modern oxygen equipment. Finch also demonstrated an extraordinary tolerance to severe acute hypoxia in a low-pressure chamber experiment. Remarkably, despite Finch's desire to participate in the first three Everest expeditions in 1921–1924, he was only allowed to be a member of one. His rejection from the 1921 expedition was based on medical reports that were apparently politically biased. Then, following his record ascent in 1922, he was refused participation in the 1924 expedition for complex reasons related to his Australian origin, his forthright and unconventional views, and the fact that some people in the climbing establishment in Britain saw Finch as an undesirable outsider.
State and chemical drive modulate respiratory variability
Authors: BuSha Brett F. , Stella Martha H.
Published: March 2015

The quantification of respiratory variability may provide insight into the integrative control of breathing. To test the hypothesis that sleep and/or increased chemical drive modifies respiratory variability, six male adult Sprague-Dawley rats were instrumented with diaphragm electromyographic (EMG) electrodes and exposed to 0, 2.5, and 5.0% CO2 with a balance of room air during wakefulness and behaviorally determined sleep. Respiratory interval (Ttot), peak diaphragm EMG, and ventilation index (peak diaphragm EMG/Ttot) were calculated for 1,024 sequential breaths. The variability of breathing was quantified with a measurement of signal complexity, the approximate entropy, and two autocorrelation measurements, the autoregressive power spectrum slope and the detrended fluctuation analysis slope. Elevated chemical drive and/or sleep significantly modulated the variability of ventilation index and Ttot. There were also significant interactions between state and CO2 drive in all respiratory parameters. We conclude that state (sleep or wakefulness) and increased chemical drive affect respiratory variability differentially.
Older adults are less steady during submaximal isometric contractions with the knee extensor muscles
Authors: Tracy Brian L. , Enoka Roger M.
Published: March 2015

This study compared the steadiness of submaximal contractions with the knee extensor muscles in young and old adults. Twenty young and twenty old subjects underwent assessment of isometric maximum voluntary contraction (MVC), one-repetition maximum (1-RM) strength, and steadiness during isometric, concentric, and eccentric contractions with the knee extensor muscles. The old adults displayed 33% lower MVC force and a 41% lower 1-RM load. The coefficient of variation for force was significantly greater for the old adults during isometric contractions at 2, 5, and 10% of MVC but not at 50% MVC. The decline in steadiness at low forces experienced by the men was marginally greater than that experienced by the women. The steadiness of concentric and eccentric contractions was similar in young and old adults at 5, 10, and 50% of 1-RM load. Old subjects exhibited greater coactivation of an antagonist muscle compared with young subjects during the submaximal isometric and anisometric contractions. These results indicate that, whereas the ability to exert steady submaximal forces with the knee extensor muscles was reduced in old adults, fluctuations in knee joint angle during slow movements were similar for young and old adults.
Attenuated responses to sympathoexcitation in individuals with Down syndrome
Authors: Fernhall Bo , Otterstetter Mari
Published: March 2015

This study evaluated blood pressure and heart rate responses to exercise and nonexercise tasks as indexes of autonomic function in subjects with and without Down syndrome (DS). Twenty-four subjects (12 with and 12 without DS) completed maximal treadmill exercise, isometric handgrip (30% of maximum), and cold pressor tests, with heart rate and blood pressure measurements. Maximal heart rate and heart rate and blood pressure responses to the isometric handgrip and cold pressor tests were reduced in subjects with DS ( P < 0.05). Both early (first 30 s) and late (last 30 s) responses were reduced. Obesity did not appear to influence the results, as both obese and normal-weight subjects with DS exhibited similar responses, and controlling for body mass index did not alter the results between controls and subjects with DS. Individuals with DS, without congenital heart disease, exhibit reduced heart rate and blood pressure responses to isometric handgrip exercise and cold pressor testing, consistent with autonomic dysfunction. Autonomic dysfunction may partially explain chronotropic incompetence observed during maximal treadmill exercise in individuals with DS.
Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon
Authors: Nieman David C. , Henson Dru A. , McAnulty Steve R. , McAnulty Lisa , Swick Nathaniel S. , Utter Alan C. , Vinci Debra M. , Opiela Shannon J. , Morrow Jason D.
Published: March 2015

The purpose of this randomized study was to measure the influence of vitamin C ( n = 15 runners) compared with placebo ( n = 13 runners) supplementation on oxidative and immune changes in runners competing in an ultramarathon race. During the 7-day period before the race and on race day, subjects ingested in randomized, double-blind fashion 1,500 mg/day vitamin C or placebo. On race day, blood samples were collected 1 h before race, after 32 km of running, and then again immediately after race. Subjects in both groups maintained an intensity of ∼75% maximal heart rate throughout the ultramarathon race and ran a mean of 69 km (range: 48–80 km) in 9.8 h (range: 5–12 h). Plasma ascorbic acid was markedly higher in the vitamin C compared with placebo group prerace and rose more strongly in the vitamin C group during the race (postrace: 3.21 ± 0.29 and 1.28 ± 0.12 μg/100 μl, respectively, P < 0.001). No significant group or interaction effects were measured for lipid hydroperoxide, F2-isoprostane, immune cell counts, plasma interleukin (IL)-6, IL-10, IL-1-receptor antagonist, or IL-8 concentrations, or mitogen-stimulated lymphocyte proliferation and IL-2 and IFN-γ production. These data indicate that vitamin C supplementation in carbohydrate-fed runners does not serve as a countermeasure to oxidative and immune changes during or after a competitive ultramarathon race.
Hindlimb unloading rodent model: technical aspects
Authors: Morey-Holton Emily R. , Globus Ruth K.
Published: March 2015

Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30° head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.
Gasping and autoresuscitation in the developing rat: effect of antecedent intermittent hypoxia
Authors: Gozal David , Gozal Evelyne , Reeves Stephen R. , Lipton Andrew J.
Published: March 2015

Gasping is a critically important mechanism for autoresuscitation and survival during extreme tissue hypoxia. Evidence of antecedent hypoxia in sudden infant death syndrome suggests that intermittently occurring hypoxic episodes may modify gasping and autoresuscitation. To examine this issue, an intermittent hypoxia (IH) profile consisting of alternating room air and 10% O2-balance N2 every 90 s was applied to pregnant Sprague-Dawley rats (IHRA; n = 50) and to pups after a normal pregnancy (RAIH; n = 50) as well as to control pups (RARA; n = 50). At postnatal day 5, pups were exposed to 95% N2-5% CO2, and gasping and the ability to autoresuscitate were assessed. Compared with RARA, IHRA- and RAIH-exposed pups had a reduced number of gasps, decreased overall gasp duration, and were less likely to autoresuscitate on introduction of room air to the breathing mixture during the last phase of gasping ( P < 0.001 vs. RARA). We conclude that both prenatal and early postnatal IH adversely affect gasping and related survival mechanisms.
Preexercise hypervolemia does not affect arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise
Authors: Manohar Murli , Goetz Thomas E. , Hassan Aslam S.
Published: March 2015

It is reported that preexercise hyperhydration caused arterial O2 tension of horses performing submaximal exercise to decrease further by 15 Torr (Sosa-Leon L, Hodgson DR, Evans DL, Ray SP, Carlson GP, and Rose RJ. Equine Vet J Suppl 34: 425–429, 2002). Because hydration status is important to optimal athletic performance and thermoregulation during exercise, the present study examined whether preexercise induction of hypervolemia would similarly accentuate the arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise. Two sets of experiments (namely, control and hypervolemia studies) were carried out on seven healthy, exercise-trained Thoroughbred horses in random order, 7 days apart. In resting horses, an 18.0 ± 1.8% increase in plasma volume was induced with NaCl (0.30–0.45 g/kg dissolved in 1,500 ml H2O) administered via a nasogastric tube, 285–290 min preexercise. Blood-gas and pH measurements as well as concentrations of plasma protein, hemoglobin, and blood lactate were determined at rest and during incremental exercise leading to maximal exertion (14 m/s on a 3.5% uphill grade) that induced pulmonary hemorrhage in all horses in both treatments. In both treatments, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, acidosis, and hyperthermia developed during maximal exercise, but statistically significant differences between treatments were not found. Thus preexercise 18% expansion of plasma volume failed to significantly affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing maximal exercise. Although blood lactate concentration and arterial pH were unaffected, hemodilution caused in this manner resulted in a significant ( P < 0.01) attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O2 content gradient.
Maximal intermittent cycling exercise: effects of recovery duration and gender
Authors: Billaut François , Giacomoni Magali , Falgairette Guy
Published: March 2015

This study aimed to evaluate potential gender differences in recovery of power output during repeated all-out cycling exercise. Twenty men and thirteen women performed four series of two sprints (Sp1 and Sp2) of 8 s, separated by 15-, 30-, 60-, and 120-s recovery. Peak power (Ppeak), power at the 8th s, total mechanical work, and time to Ppeak were calculated for each sprint. Ppeak and mechanical work decreased significantly between Sp1 and Sp2 after 15-s recovery in both men (-6.4 and -9.4%, respectively) and women (-7.4 and -6.8%, respectively). Time to Ppeak did not change between recovery durations, but women reached their peak power more slowly than men (on average 5.15 ± 1.2 and 3.8 ± 1.2 s, respectively; P < 0.01). During Sp1 and Sp2, linear regressions from Ppeak to power at the 8th s showed a greater power decrease (%Ppeak) in women compared with men ( P < 0.05). In conclusion, patterns of power output recovery between two consecutive short bouts were similar in men and women, despite lower overall performance and greater fatigability during sprints in women.
Submandibular responses to stimulation of the parasympathetic innervation in anesthetized sheep
Authors: Edwards C. M. B. , Corkery P. P. , Edwards A. V.
Published: March 2015

Submandibular secretory and vascular responses to stimulation of the parasympathetic innervation and the output of vasoactive intestinal peptide (VIP) were investigated in anaesthetized sheep in the presence and absence of atropine (≥0.5 mg/kg). In the absence of atropine, parasympathetic stimulation caused an increase in the flow of saliva and a decrease in submandibular vascular resistance; the latter response persisted after the administration of atropine and was then significantly reduced at the lowest but not at the higher frequencies tested. The output of VIP from the gland was frequency dependent over the range of 10-20 Hz (continuously) and significantly increased after atropine ( P < 0.02). Furthermore, the fall in vascular resistance was linearly related to log VIP output after total muscarinic blockade. Intracarotid infusions of synthetic VIP produced dose-dependent falls in submandibular vascular resistance, together with a corresponding increase in submandibular blood flow. It is concluded that the atropine-resistant vasodilatation that occurs in this gland during parasympathetic stimulation is likely to be due largely, if not entirely, to the release of VIP.
Sequence variants in the FcεRI alpha chain gene
Authors: Shikanai Toshiki , Silverman Eric S. , Morse Brian W. , Lilly Craig M. , Inoue Hiroshi , Drazen Jeffrey M.
Published: March 2015

There is a relationship between IgE levels and expression of high-affinity IgE receptors (FcεRI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the FcεRI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the FcεRI alpha chain gene with genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by using single-stranded conformational polymorphism analysis. No nonsynonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A/C transversion at −770 from the translation start site; a G/A transition at −664; and a T/C transition at −335. No differences in allele frequencies were detected between asthmatic subjects and controls. Homozygosity for the C variant at locus −335 was more common in Caucasian asthmatic patients with IgE levels in the lower quartile than in the upper quartile ( P = 0.032). An analysis of highly polymorphic SNPs indicated that this association is unlikely to be due to population substructure. We conclude that homozygosity for the C allele of FcεRI alpha chain variant is associated with lower IgE levels.
Heat stress protection against mesenteric I/R-induced alterations in intestinal mucosa in rats
Authors: Fleming Sherry d. , Starnes Benjamin W. , Kiang Juliann G. , Stojadinovic Alexander , Tsokos George C. , Shea-Donohue Terez
Published: March 2015

Prior induction of heat shock protein 70 (HSP70) protects against ischemia-reperfusion (I/R) mucosal injury, but the ability of HSP70 to affect I/R-induced alterations in epithelial cell function is unknown. Rats subjected to whole body hyperthermia (41.5–42°C for 6 min) increased HSP70 and heat shock factor 1 mRNA expression, reaching a maximum 2 h after heat stress and declining thereafter. HSP70 production was maximally elevated at 4 h after heat stress and remained elevated until after 12 h. Heat stress alone had no effect on mucosal function except to enhance secretion in response to ACh. Heat stress provided complete morphological protection against I/R-induced mucosal injury but did not confer a similar protection against I/R-induced decreases in mucosal resistance, sodium-linked glucose absorption, or tachykinin-mediated chloride secretion. Heat stress, however, attenuated the I/R-induced suppression of ACh response, and this effect was dependent on enteric nerves. Thus induction of heat shock protein 70 is associated with the preservation of mucosal architecture and attenuation of some specific functional alterations induced by I/R.
Invited Review: Effect of oxygen deprivation on cell cycle activity: a profile of delay and arrest
Authors: Douglas R. M. , Haddad G. G.
Published: March 2015

One of the most fascinating fields that have emanated in the past few decades is developmental biology. This is not only the case from a research point of view but also from the angle of clinical care and treatment strategies. It is now well demonstrated that there are many diseases (some believe all diseases) that have their roots in embryogenesis or in early life, where nature and environment often team up to facilitate the genesis of disease. There is probably no better example to illustrate the interactions between nature and environment than in early life, as early as in the first several cell cycles. As will be apparent in this review, the cell cycle is a very regulated activity and this regulation is genetic in nature, with checkpoint proteins playing an important role in controlling the timing, the size, and the growth of daughter cells. However, it is also very clear, as will be discussed in this work, that the microenvironment of the first dividing cells is so important for the outcome of the organism. In this review, we will focus on the effect of one stress, that of hypoxia, on the young embryo and its cell division and growth. We will first review some of the cell cycle definitions and stages and then review briefly our current knowledge and its gaps in this area.
Selected Contribution: Hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis
Authors: Ning Xue-Han , Chen Shi-Han , Xu Cheng-Su , Li Linheng , Yao Lena Y. , Qian Kun , Krueger Julia J. , Hyyti Outi M. , Portman Michael A.
Published: March 2015

Hypothermia improves resistance to ischemia in the cardioplegia-arrested heart. This adaptive process produces changes in specific signaling pathways for mitochondrial proteins and heat-shock response. To further test for hypothermic modulation of other signaling pathways such as apoptosis, we used various molecular techniques, including cDNA arrays. Isolated rabbit hearts were perfused and exposed to ischemic cardioplegic arrest for 2 h at 34°C [ischemic group (I); n = 13] or at 30°C before and during ischemia [hypothermic group (H); n = 12]. Developed pressure, the maximum first derivative of left ventricular pressure, oxygen consumption, and pressure-rate product ( P < 0.05) recovery were superior in H compared with in I during reperfusion. mRNA expression for the mitochondrial proteins, adenine translocase and the β-subunit of F1-ATPase, was preserved by hypothermia. cDNA arrays revealed that ischemia altered expression of 13 genes. Hypothermia modified this response to ischemia for eight genes, six related to apoptosis. A marked, near fivefold increase in transformation-related protein 53 in I was virtually abrogated in H. Hypothermia also increased expression for the anti-apoptotic Bcl-2 homologue Bcl-x relative to I but decreased expression for the proapoptotic Bcl-2 homologue bak. These data imply that hypothermia modifies signaling pathways for apoptosis and suggest possible mechanisms for hypothermia-induced myocardial protection.
Psychrometric limits and critical evaporative coefficients for unacclimated men and women
Authors: Kenney W. Larry , Zeman Michael J.
Published: March 2015

Critical environmental limits, defined as those above which heat balance cannot be maintained for a given metabolic heat production, have not been determined for unacclimated subjects. To characterize critical environmental limits and to derive evaporative heat exchange coefficients ( K e′) for unacclimated young men ( n = 11) and women ( n = 10), subjects of average aerobic fitness walked at 30% maximal aerobic capacity in an environmental chamber. Critical environmental conditions were defined as the psychrometric loci of dry-bulb temperature and water vapor pressure at which core (esophageal) temperature was forced out of equilibrium (heat gain exceeded heat loss). Compared with the men in our study, the women had significantly higher critical environmental limits ( P < 0.001) in warm (34–38°C), humid (>60%) environments, a function of their lower absolute metabolic heat production at the fixed relative exercise intensity. Isotherms constructed from biophysical models closely fit the data in this range of environments but underestimated empirically determined critical limits in hotter, drier environments. Sex-specific values of K e′ were derived by partial calorimetry in the critical water vapor pressure environments, in which full skin wettedness occurred. There were no sex differences for K e′ (men = 17.4, 15.5, and 14.2 W · m−2 · Torr−1 and women = 16.8, 15.5, and 14.2 W · m−2 · Torr−1 at 34, 36, and 38°C, respectively). These K e′ values were lower than those previously published for fully heat-acclimated men (18.4 W · m−2 · Torr−1 at 36°C) and women (17.7 W · m−2 · Torr−1 at 36°C and 15.5 W · m−2 · Torr−1 at 38°C) and may be used to model heat balance responses for unacclimated men and women working in hot environments.
Postnatal alveolar development of the rabbit
Authors: Kovar Jana , Sly Peter D. , Willet Karen E.
Published: March 2015

Previous studies of alveolarization have used rats or lambs; however, neither closely reflects human alveolar development. We characterized alveolar development in rabbits ( n = 3–7 /group) at 28 days gestation (dg) to 9 mo to determine whether they followed the human pattern more closely. The right lung was made up of 30% alveolar and 50% duct space at 28 dg to 3 days and of 50 and 30%, respectively, at 14 days to 9 mo. Tissue fraction and alveolar wall thickness decreased by 40% 28 dg to birth. At birth, ∼4.5% of the number of alveoli seen at 9 mo were present, with alveolar number increasing progressively well into adulthood. The rate of alveolar formation was high around birth, decreasing progressively with age. Alveolar volume increased more than twofold (28 dg to birth) and continued to increase postnatally to 16 wk. Surface fraction decreased by 17% (28 dg to 3 days), after which it remained uniform. Our findings suggest that the timing of onset of alveolarization in humans and rabbits is similar and that rabbits may be used to model postnatal influences on alveolar development.
Afferent vagal pathways mediating respiratory reflexes evoked by ROS in the lungs of anesthetized rats
Authors: Ruan Ting , Ho Ching-Yin , Kou Yu Ru
Published: March 2015

We investigated the afferent vagal pathways mediating respiratory reflexes evoked by reactive oxygen species (ROS) in the lungs of anesthetized rats. Spontaneous inhalation of 0.2% aerosolized H2O2 acutely evoked initial bradypnea followed by delayed tachypnea, which was frequently mixed with delayed augmented inspiration. The initial response was abolished after perivagal capsaicin treatment (PCT), but was prolonged during vagal cooling (VC) to 7°C; PCT and VC are known to differentially block the conduction of unmyelinated C and myelinated fibers, respectively. The delayed responses were eliminated during VC but emerged earlier after PCT. Vagotomy, catalase (an antioxidant for H2O2), dimethylthiourea (an antioxidant for · OH), or deferoxamine (an antioxidant for · OH) largely or totally suppressed these reflexive responses, whereas sham nerve treatment, heat-inactivated catalase, saline vehicle, or iron-saturated deferoxamine failed to do so. These results suggest that 1) the H2O2-evoked initial and delayed airway reflexes are antagonistic and may result from stimulation of lung C fibers and rapidly adapting receptors, respectively, and 2) the reflex effects of H2O2 are, in part, due to the action of · OH on these afferents.
Cortical bone dynamics, strength, and densitometry after induction of emphysema in hamsters
Authors: Shea Jill E. , Miller Scott C. , Poole David C. , Mattson John P.
Published: March 2015

Recent evidence suggests that patients suffering from chronic obstructive pulmonary disease are also at an increased risk of developing osteoporosis. The pathophysiological mechanism(s) linking these progressive diseases is unknown. The goal of this investigation was to determine whether there were alterations in bone mineral density and content, cortical bone structure and strength, and indexes of bone formation and resorption in the elastase-induced emphysematous hamster. At 3 wk after induction of emphysema, the femoral bone mineral content was 8% less ( P = 0.026) and the femoral fracture strength was 6% less ( P = 0.032) in the emphysematous hamster than in controls. The cortical area was 8.4% less ( P = 0.013) and the periosteal mineral appositional rate was 27% less ( P = 0.05) than in controls. Additionally, the endocortical eroded surface in the emphysematous group was about twice that in the control group ( P = 0.003). Differences in some indexes of bone formation and resorption, paralleled by differences in bone structure and strength, were observed 3 wk after induction of emphysema. These differences in skeletal metabolism and strength may help explain some of the skeletal changes associated with chronic obstructive pulmonary disease in humans.
Selected Contribution: Effects of spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions
Authors: Pecaut Michael J. , Nelson Gregory A. , Peters Luanne L. , Kostenuik Paul J. , Bateman Ted A. , Morony Sean , Stodieck Louis S. , Lacey David L. , Simske Steven J. , Gridley Daila S.
Published: March 2015

There are several aspects of the spaceflight environment that may lead to changes in immunity: mission-related psychological stress, radiation, and changes in gravity. On December 5, 2001, the space shuttle Endeavor launched for a 12-day mission to examine these effects on C57BL/6 mice for the first time. On their return, assays were performed on the spleen, blood, and bone marrow. In response to flight, there were no significant differences in the general circulating leukocyte proportions. In contrast, there was an increase in splenic lymphocyte percentages, with a corresponding decrease in granulocytes. There was an overall shift in splenic lymphocytes away from T cells toward B cells, and a decrease in the CD4-to-CD8 ratios due to a decrease in T helpers. In contrast, there were proportional increases in bone marrow T cells, with decreases in B cells. Although the blast percentage and count were decreased in flight mice, the CD34+ population was increased. The data were more consistent with a shift in bone marrow populations rather than a response to changes in the periphery. Many of the results are similar to those using other models. Clearly, spaceflight can influence immune parameters ranging from hematopoiesis to mature leukocyte mechanisms.
Effect of bupropion on hippocampal neurotransmitters and on peripheral hormonal concentrations in the rat
Authors: Piacentini M. F. , Clinckers R. , Meeusen R. , Sarre S. , Ebinger G. , Michotte Y.
Published: March 2015

The purpose of the present study was to administer an acute dose of the dual dopamine norepinephrine reuptake blocker bupropion in freely moving rats and to monitor the extracellular neurotransmitter concentrations in the hippocampus via in vivo microdialysis and the peripheral hormonal concentrations via catheterization. A microdialysis probe was inserted in the hippocampus, and samples for serotonin, dopamine, and norepinephrine were collected every 20 min before and after the injection of 17 mg/kg of bupropion, for a total sampling time of 180 min. A catheter was placed in the vena femoralis of the second group of rats, and blood samples were collected before and after bupropion injection for quantification of growth hormone, prolactin, corticosterone, adrenocorticotropin hormone, and β-endorphins. All neurotransmitter levels (dopamine, norepinephrine, and serotonin) significantly increased after bupropion injection. This was accompanied by a significant decrease in prolactin concentrations, whereas the other hormones showed no statistically significant variation. It can, therefore, be concluded that, although bupropion has dual reuptake proprieties, the observed effects both at the central and at the peripheral level seem to be ruled by the dopaminergic system.
Postevent ventilation as a function of CO2 load during respiratory events in obstructive sleep apnea
Authors: Berger Kenneth I. , Ayappa Indu , Sorkin I. Barry , Norman Robert G. , Rapoport David M. , Goldring Roberta M.
Published: March 2015

Maintenance of eucapnia during sleep in obstructive sleep apnea (OSA) requires a balance between CO2 loading during apnea and CO2 elimination. This study examines individual respiratory events and relates magnitude of postevent ventilation to CO2 load during the preceding respiratory event in 14 patients with OSA (arterial Pco 2 42–56 Torr). Ventilation and expiratory CO2 and O2 fractions were measured on a breath-by-breath basis during daytime sleep. Calculations included CO2 load during each event (metabolic CO2 production − exhaled CO2) and postevent ventilation in the 10 s after an event. In 12 of 14 patients, a direct relationship existed between postevent ventilation and CO2 load during the preceding event ( P < 0.05); the slope of this relationship varied across subjects. Thus the postevent ventilation is tightly linked to CO2 loading during each respiratory event and may be an important mechanism that defends against development of acute hypercapnia in OSA. An inverse relationship was noted between this postevent ventilatory response slope and the chronic awake arterial Pco 2 ( r = 0.90, P < 0.001), suggesting that this mechanism is impaired in patients with chronic hypercapnia. The link between development of acute hypercapnia during respiratory events asleep and maintenance of chronic awake hypercapnia in OSA remains to be further investigated.
Spanish genetic admixture is associated with larger V̇o2 maxdecrement from sea level to 4,338 m in Peruvian Quechua
Authors: Brutsaert Tom D. , Parra Esteban J. , Shriver Mark D. , Gamboa Alfredo , Palacios Jose-Antonio , Rivera Maria , Rodriguez Ivette , León-Velarde Fabiola
Published: March 2015

Quechua in the Andes may be genetically adapted to altitude and able to resist decrements in maximal O2consumption in hypoxia (ΔV̇o2 max). This hypothesis was tested via repeated measures of V̇o2 max(sea level vs. 4,338 m) in 30 men of mixed Spanish and Quechua origins. Individual genetic admixture level (%Spanish ancestry) was estimated by using ancestry-informative DNA markers. Genetic admixture explained a significant proportion of the variability in ΔV̇o2 maxafter control for covariate effects, including sea level V̇o2 maxand the decrement in arterial O2saturation measured at V̇o2 max(ΔSpO2 max) ( R2for admixture and covariate effects ∼0.80). The genetic effect reflected a main effect of admixture on ΔV̇o2 max( P = 0.041) and an interaction between admixture and ΔSpO2 max( P = 0.018). Admixture predicted ΔV̇o2 maxonly in subjects with a large ΔSpO2 max( P = 0.031). In such subjects, ΔV̇o2 maxwas 12–18% larger in a subgroup of subjects with high vs. low Spanish ancestry, with least squares mean values (±SE) of 739 ± 71 vs. 606 ± 68 ml/min, respectively. A trend for interaction ( P = 0.095) was also noted between admixture and the decrease in ventilatory threshold at 4,338 m. As previously, admixture predicted ΔV̇o2 maxonly in subjects with a large decrease in ventilatory threshold. These findings suggest that the genetic effect on ΔV̇o2 maxdepends on a subject's aerobic fitness. Genetic effects may be more important (or easier to detect) in athletic subjects who are more likely to show gas-exchange impairment during exercise. The results of this study are consistent with the evolutionary hypothesis and point to a better gas-exchange system in Quechua.
Biophysical basis for inner ear decompression sickness
Authors: Doolette David J. , Mitchell Simon J.
Published: March 2015

Isolated inner ear decompression sickness (DCS) is recognized in deep diving involving breathing of helium-oxygen mixtures, particularly when breathing gas is switched to a nitrogen-rich mixture during decompression. The biophysical basis for this selective vulnerability of the inner ear to DCS has not been established. A compartmental model of inert gas kinetics in the human inner ear was constructed from anatomical and physiological parameters described in the literature and used to simulate inert gas tensions in the inner ear during deep dives and breathing-gas substitutions that have been reported to cause inner ear DCS. The model predicts considerable supersaturation, and therefore possible bubble formation, during the initial phase of a conventional decompression. Counterdiffusion of helium and nitrogen from the perilymph may produce supersaturation in the membranous labyrinth and endolymph after switching to a nitrogen-rich breathing mixture even without decompression. Conventional decompression algorithms may result in inadequate decompression for the inner ear for deep dives. Breathing-gas switches should be scheduled deep or shallow to avoid the period of maximum supersaturation resulting from decompression.
Cardiovascular variability after arousal from sleep: time-varying spectral analysis
Authors: Blasi Anna , Jo Javier , Valladares Edwin , Morgan Barbara J. , Skatrud James B. , Khoo Michael C. K.
Published: March 2015

We performed time-varying spectral analyses of heart rate variability (HRV) and blood pressure variability (BPV) recorded from 16 normal humans during acoustically induced arousals from sleep. Time-varying autoregressive modeling was employed to estimate the time courses of high-frequency HRV power, low-frequency HRV power, the ratio between low-frequency and high-frequency HRV power, and low-frequency power of systolic BPV. To delineate the influence of respiration on HRV, we also computed respiratory airflow high-frequency power, the modified ratio of low-frequency to high-frequency HRV power, and the average transfer gain between respiration and heart rate. During cortical arousal, muscle sympathetic nerve activity and heart rate increased and returned rapidly to baseline, but systolic blood pressure, the ratio between low-frequency and high-frequency HRV power, low-frequency HRV power, the modified ratio of low-frequency to high-frequency HRV power, and low-frequency power of systolic BPV displayed increases that remained above baseline up to 40 s after arousal. High-frequency HRV power and airflow high-frequency power showed concommitant decreases to levels below baseline, whereas the average transfer gain between respiration and heart rate remained unchanged. These findings suggest that 1) arousal-induced changes in parasympathetic activity are strongly coupled to respiratory pattern and 2) the sympathoexcitatory cardiovascular effects of arousal are relatively long lasting and may accumulate if repetitive arousals occur in close succession.
Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans
Authors: Halliwill John R. , Minson Christopher T.
Published: March 2015

We tested the hypothesis that acute hypoxia would alter the sensitivity of arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20–33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity by using the modified Oxford technique during both normoxia and hypoxia (12% O2). Compared with normoxia, hypoxia reduced arterial O2 saturation levels from 96.8 ± 0.3 to 80.7 ± 1.4% ( P < 0.001), increased heart rate from 59.8 ± 2.4 to 79.4 ± 2.9 beats/min ( P < 0.001), increased mean arterial pressure from 96.7 ± 2.5 to 105.0 ± 3.3 mmHg ( P = 0.002), and increased sympathetic activity 126 ± 58% ( P < 0.05). The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by hypoxia (heart rate: −1.02 ± 0.09 vs. −1.02 ± 0.11 beats · min−1 · mmHg−1; nerve activity: −5.6 ± 0.9 vs. −6.2 ± 0.9 integrated activity · beat−1 · mmHg−1; both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity.
Heterogeneous capillary recruitment among adjoining alveoli
Authors: Baumgartner William A. , Jaryszak Eric M. , Peterson Amanda J. , Presson Robert G. , Wagner Wiltz W.
Published: March 2015

Pulmonary capillaries recruit when microvascular pressure is raised. The details of the relationship between recruitment and pressure, however, are controversial. There are data supporting 1) gradual homogeneous recruitment, 2) sudden and complete recruitment, and 3) heterogeneous recruitment. The present study was designed to determine whether alveolar capillary networks recruit in a variety of ways or whether one model predominates. In isolated, pump-perfused canine lung lobes, fields of six neighboring alveoli were recorded with video microscopy as pulmonary venous pressure was raised from 0 to 40 mmHg in 5-mmHg increments. The largest group of alveoli (42%) recruited gradually. Another group (33%) recruited suddenly (sheet flow). Half of the neighborhoods had at least one alveolus that paradoxically derecruited when pressure was increased, even though neighboring alveoli continued to recruit capillaries. At pulmonary venous pressures of 40 mmHg, 86% of the alveolar-capillary networks were not fully recruited. We conclude that the pattern of recruitment among neighboring alveoli is complex, is not homogeneous, and may not reach full recruitment, even under extreme pressures.
β-Adrenergic signaling and thyroid hormones affect HSP72 expression during heat acclimation
Authors: Maloyan Alina , Horowitz Michal
Published: March 2015

Heat acclimation upregulates 72-kDa heat shock protein (HSP72) and predisposes to faster activation of the heat shock response (HSR). This study investigates the role played by β-adrenergic signaling and/or plasma thyroxine level in eliciting these features by using rats undergoing 1) heat acclimation (AC; 34°C, 2 and 30 days); 2) AC with β-adrenergic blockade; 3) AC-maintained euthyroid; 4) hypothyroid; 5) hyperthyroid; and 6) controls. The hsp72 mRNA (RT-PCR) and HSP72 levels (Western blot) were measured before and after heat stress (2 h, 41°C, rectal temperature monitored). β-Adrenergic blockade during AC abolished HSP72 accumulation, without disrupting HSR. Low thyroxine blunted the HSR at posttranscriptional level, whereas thyroxine administration in hyperthyroid and AC-maintained euthyroid rats arrested heat stress-evoked hsp72transcription. We conclude that β-adrenergic signaling contributes to the high HSP72 level characterizing the AC state. Thyroxine has two opposing effects: 1) direct repressive on rapid hsp72 transcription after heat stress; and 2) indirect stimulatory via β-adrenergic signaling. Low thyroxine could account for diminished HSP72 synthesis via lower heat production and thermoregulatory set point.
A mathematical model to detect inspiratory flow limitation during sleep
Authors: Mansour Khaled F. , Rowley James A. , Meshenish A. A. , Shkoukani Mahdi A. , Badr M. Safwan
Published: March 2015

The physiological significance of inspiratory flow limitation (IFL) has recently been recognized, but methods of detecting IFL can be subjective. We sought to develop a mathematical model of the upper airway pressure-flow relationship that would objectively detect flow limitation. We present a theoretical discussion that predicts that a polynomial function [F(P) = AP3 + BP2 + CP + D, where F(P) is flow and P is supraglottic pressure] best characterizes the pressure-flow relationship and allows for the objective detection of IFL. In protocol 1, step 1, we performed curve-fitting of the pressure-flow relationship of 20 breaths to 5 mathematical functions and found that highest correlation coefficients ( R 2) for quadratic (0.88 ± 0.10) and polynomial (0.91 ± 0.05; P < 0.05 for both compared with the other functions) functions. In step 2, we performed error-fit calculations on 50 breaths by comparing the quadratic and polynomial functions and found that the error fit was lowest for the polynomial function (3.3 ± 0.06 vs. 21.1 ± 19.0%; P < 0.001). In protocol 2, we performed sensitivity/specificity analysis on two sets of breaths (50 and 544 breaths) by comparing the mathematical determination of IFL to manual determination. Mathematical determination of IFL had high sensitivity and specificity and a positive predictive value (>99% for each). We conclude that a polynomial function can be used to predict the relationship between pressure and flow in the upper airway and objectively determine the presence of IFL.
Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans
Authors: Kellogg D. L. , Liu Y. , McAllister K. , Friel C. , Pérgola P. E.
Published: March 2015

To test the hypothesis that bradykinin effects cutaneous active vasodilation during hyperthermia, we examined whether the increase in skin blood flow (SkBF) during heat stress was affected by blockade of bradykinin B2 receptors with the receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for local delivery of drugs in eight healthy subjects. HOE-140 was dissolved in Ringer solution (40 μM) and perfused at one site, whereas the second site was perfused with Ringer alone. SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial pressure (MAP) was monitored from a finger, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control body temperature and evoke hyperthermia. After hyperthermia, both microdialysis sites were perfused with 28 mM nitroprusside to effect maximal vasodilation. During hyperthermia, CVC increased at HOE-140 (69 ± 2% maximal CVC, P < 0.01) and untreated sites (65 ± 2% maximal CVC, P < 0.01). These responses did not differ between sites ( P > 0.05). Because the bradykinin B2-receptor antagonist HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin does not mediate cutaneous active vasodilation.
Invited Review: Effects of heat and cold stress on mammalian gene expression
Authors: Sonna Larry A. , Fujita Jun , Gaffin Stephen L. , Lilly Craig M.
Published: March 2015

This review examines the effects of thermal stress on gene expression, with special emphasis on changes in the expression of genes other than heat shock proteins (HSPs). There are ∼50 genes not traditionally considered to be HSPs that have been shown, by conventional techniques, to change expression as a result of heat stress, and there are <20 genes (including HSPs) that have been shown to be affected by cold. These numbers will likely become much larger as gene chip array and proteomic technologies are applied to the study of the cell stress response. Several mechanisms have been identified by which gene expression may be altered by heat and cold stress. The similarities and differences between the cellular responses to heat and cold may yield key insights into how cells, and by extension tissues and organisms, survive and adapt to stress.
Time course of performance changes and fatigue markers during intensified training in trained cyclists
Authors: Halson Shona L. , Bridge Matthew W. , Meeusen Romain , Busschaert Bart , Gleeson Michael , Jones David A. , Jeukendrup Asker E.
Published: March 2015

To study the cumulative effects of exercise stress and subsequent recovery on performance changes and fatigue indicators, the training of eight endurance cyclists was systematically controlled and monitored for a 6-wk period. Subjects completed 2 wk of normal (N), intensified (ITP), and recovery training. A significant decline in maximal power output (N = 338 ± 17 W, ITP = 319 ± 17 W) and a significant increase in time to complete a simulated time trial (N = 59.4 ± 1.9 min, ITP = 65.3 ± 2.6 min) occurred after ITP in conjunction with a 29% increase in global mood disturbance. The decline in performance was associated with a 9.3% reduction in maximal heart rate, a 5% reduction in maximal oxygen uptake, and an 8.6% increase in perception of effort. Despite the large reductions in performance, no changes were observed in substrate utilization, cycling efficiency, and lactate, plasma urea, ammonia, and catecholamine concentrations. These findings indicate that a state of overreaching can already be induced after 7 days of intensified training with limited recovery.