bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the arousal response can impair performance on a simple motor task
Authors: Noteboom J. Timothy , Fleshner Monika , Enoka Roger M.
Published: December 2017

The purpose of this study was to determine the effect of arousal in men and women on the moment-to-moment performance of a simple motor task. We examined the control of a precision task in the presence and absence of imposed stressors. Twenty-nine subjects (14 men, 15 women; 18–44 yr) were randomly assigned to either a control group or one of two stressor groups, Mental Math or Electric Shock. Subjects presented with Math and Shock stressors, which lasted 10 min, experienced significant increases in cognitive and physiological arousal compared with baseline and control subjects. Heart rate, systolic blood pressure, and electrodermal activity were elevated 5–80% with presentation of the stressors, whereas diastolic blood pressure and salivary cortisol were unchanged. The greater levels of cognitive and physiological arousal were associated with reductions in steadiness of a pinch grip for the Shock subjects (∼130% reduction from baseline) but not for the subjects in the Math group, who experienced heightened arousal but no change in steadiness (10% reduction from baseline). Although women exhibited more of a reduction in steadiness than men, the effect was largely unrelated to the magnitude of the change in arousal.
Effects of exhaustive endurance exercise on pulmonary gas exchange and airway function in women
Authors: Wetter Thomas J. , St. Croix Claudette M. , Pegelow David F. , Sonetti David A. , Dempsey Jerome A.
Published: December 2017

Seventeen fit women ran to exhaustion (14 ± 4 min) at a constant speed and grade, reaching 95 ± 3% of maximal O2consumption. Pre- and postexercise lung function, including airway resistance [total respiratory resistance (Rrs)] across a range of oscillation frequencies, was measured, and, on a separate day, airway reactivity was assessed via methacholine challenge. Arterial O2saturation decreased from 97.6 ± 0.5% at rest to 95.1 ± 1.9% at 1 min and to 92.5 ± 2.6% at exhaustion. Alveolar-arterial O2difference (A-aDo2) widened to 27 ± 7 Torr after 1 min and was maintained at this level until exhaustion. Arterial Po2(PaO2) fell to 80 ± 8 Torr at 1 min and then increased to 86 ± 9 Torr at exhaustion. This increase in PaO2over the exercise duration occurred due to a hyperventilation-induced increase in alveolar Po2in the presence of a constant A-aDo2. Arterial O2saturation fell with time because of increasing temperature (+2.6 ± 0.5°C) and progressive metabolic acidosis (arterial pH: 7.39 ± 0.04 at 1 min to 7.26 ± 0.07 at exhaustion). Plasma histamine increased throughout exercise but was inversely correlated with the fall in PaO2at end exercise. Neither pre- nor postexercise Rrs, frequency dependence of Rrs, nor diffusing capacity for CO correlated with the exercise A-aDo2or PaO2. Although several subjects had a positive or borderline hyperresponsiveness to methacholine, this reactivity did not correlate with exercise-induced changes in Rrs or exercise-induced arterial hypoxemia. In conclusion, regardless of the degree of exercise-induced arterial hypoxemia at the onset of high-intensity exercise, prolonging exercise to exhaustion had no further deleterious effects on A-aDo2, and the degree of gas exchange impairment was not related to individual differences in small or large airway function or reactivity.
Modulation of laryngeal and respiratory pump muscle activities with upper airway pressure and flow
Authors: Stella M. H. , England S. J.
Published: December 2017

The hypothesis that upper airway (UA) pressure and flow modulate respiratory muscle activity in a respiratory phase-specific fashion was assessed in anesthetized, tracheotomized, spontaneously breathing piglets. We generated negative pressure and inspiratory flow in phase with tracheal inspiration or positive pressure and expiratory flow in phase with tracheal expiration in the isolated UA. Stimulation of UA negative pressure receptors with body temperature air resulted in a 10–15% enhancement of phasic moving-time-averaged posterior cricoarytenoid electromyographic (EMG) activity above tonic levels obtained without pressure and flow in the UA (baseline). Stimulation of UA positive pressure receptors increased phasic moving-time-averaged thyroarytenoid EMG activity above tonic levels by 45% from baseline. The same enhancement of posterior cricoarytenoid or thyroarytenoid EMG activity was observed with the addition of flow receptor stimulation with room temperature air. Tidal volume and diaphragmatic and abdominal muscle activity were unaffected by UA flow and/or pressure, whereas respiratory timing was minimally affected. We conclude that laryngeal afferents, mainly from pressure receptors, are important in modulating the respiratory activity of laryngeal muscles.
Chronic airway infection leads to angiogenesis in the pulmonary circulation
Authors: Hopkins Natalie , Cadogan Elaine , Giles Shay , McLoughlin Paul
Published: December 2017

In both pulmonary and systemic hypertension, the walls of the arteriolar vessels are thickened and the lumen size is reduced, leading to increased total vascular resistance. It has been reported previously that chronic airway infection and inflammation lead to increased wall thickness in the pulmonary vasculature, without the development of pulmonary hypertension. The aim of the present study was to examine quantitatively the remodeling of intra-acinar blood vessels in chronically infected rat lungs. Adult rats were anesthetized and inoculated intratracheally with Pseudomonas aeruginosa( n = 10) incorporated into agar beads to induce chronic airway infection. Control groups included rats inoculated with sterile agar beads ( n = 8) and rats that were not inoculated ( n = 6). Chronic infection caused vascular wall thickening without reduction in mean lumen radius. Furthermore, chronic infection led to increased total length of intra-acinar vessels and increased numbers of branch points, demonstrating that angiogenesis had occurred. Preservation of lumen size and formation of new parallel pathways in the vasculature of chronically infected lungs account for the maintenance of normal PVR despite vessel wall remodeling.
Automated quantification of sympathetic beat-by-beat activity, independent of signal quality
Authors: Hamner J. W. , Taylor J. Andrew
Published: December 2017

Sympathetic nerve activity (SNA) can provide critical information on cardiovascular regulation; however, in a typical laboratory setting, adequate recordings require assiduous effort, and otherwise high-quality recordings may be clouded by frequent baseline shifts, noise spikes, and muscle twitches. Visually analyzing this type of signal can be a tedious and subjective evaluation, whereas objective analysis through signal averaging is impossible. We propose a new automated technique to identify bursts through objective detection criteria, eliminating artifacts and preserving a beat-by-beat SNA signal for a variety of subsequent analyses. The technique was evaluated during both steady-state conditions (17 subjects) and dynamic changes with rapid vasoactive drug infusion (14 recordings from 5 subjects) on SNA signals of widely varied quality. Automated measures of SNA were highly correlated to visual measures of steady-state activity ( r = 0.903, P < 0.001), dynamic relation measures ( r= 0.987, P < 0.001), and measures of burst-by-burst variability ( r = 0.929, P < 0.001). This automated sympathetic neurogram analysis provides a viable alternative to tedious and subjective visual analyses while maximizing the usability of noisy nerve tracings.
Mortality after carotid body denervation in rats
Authors: Serra A. , Brozoski D. , Hedin N. , Franciosi R. , Forster H. V.
Published: December 2017

Carotid body denervation (CBD) in neonatal goats and piglets results in minimal irregular breathing and no fatalities. Redundancy and/or plasticity of peripheral chemosensitivity and a relatively mature ventilatory control system at birth may contribute to the paucity of CBD effects in these species. In the present study, we tested the hypothesis that CBD mortality would be greater in neonates of a less mature species such as the rat. We found that the mortality in rats denervated at 2–3 and 7–8 days of age was significantly higher ( P < 0.05) than in sham-CBD rats. In all surviving rats, pulmonary ventilation during hypoxia was lower in CBD than in sham operated rats 2 days after denervation. In surviving rats denervated during the 7th and 8th postnatal days, there was also reduced weight gain and pulmonary ventilation during eupnea, including apneas up to 20 s in duration. However, the effects of CBD were compensated within 3 wk after denervation. Local injections of NaCN indicated that aortic chemoreceptors might have been one of the sites of recovery of peripheral chemosensitivity. We concluded that CBD has higher mortality in newborn rats than in other mammals, possibly because of the relative immaturity of these animals at birth. Nonetheless, in survivors there was enough redundancy and plasticity in the control of breathing to eventually compensate for the consequences of CBD.
Humidity does not affect central nervous system oxygen toxicity
Authors: Arieli R. , Moskovitz Y.
Published: December 2017

Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of consciousness when hyperbaric oxygen is breathed in diving and hyperbaric medical therapy. Lin and Jamieson ( J Appl Physiol 75: 1980–1983, 1993) reported that humidity in the inspired gas enhances CNS oxygen toxicity. Because alveolar gas is fully saturated with water vapor, we could not see a cause and effect and surmised that other factors, such as metabolic rate, might be involved. Rats were exposed to 507- and 608-kPa O2 in dry (31 or 14%) or humid (99%) atmosphere until the appearance of the first electrical discharge preceding the clinical convulsions. Each rat served as its own control. A thermoneutral temperature (28 ± 0.4°C) yielded resting CO2 production of 0.81 ± 0.06 ml · g−1 · h−1. Latency to the first electrical discharge was not affected by humidity. At 507-kPa O2, latency was 23 ± 0.4 and 22 ± 0.7 min in dry and humid conditions, respectively, and, at 608-kPa O2, latency was 15 ± 4 and 14 ± 3 min in dry and humid conditions, respectively. When no effects of CO2 and metabolic rate are present, humidity does not affect CNS oxygen toxicity. Relevance of the findings to diving and hyperbaric therapy is discussed.
Distribution and colocalization of neurotransmitters and receptors in the pre-Bötzinger complex of rats
Authors: Liu Ying-Ying , Ju Gong , Wong-Riley Margaret T. T.
Published: December 2017

The pre-Bötzinger complex (PBC), thought to be the center of respiratory rhythm generation, is a cell column ventrolateral to the nucleus ambiguus. The present study analyzed its cellular and neurochemical composition in adult rats. PBC neurons were mainly oval, fusiform, or multipolar in shape and small to medium in size. Neurokinin-1 receptor, a marker of the PBC, was present in the plasma membrane of mostly medium and small neurons and their associated processes and boutons. Among neurons immunoreactive for different neurotransmitter or receptor candidates, various numbers were colocalized with neurokinin-1 receptor. The highest ratio was with nitric oxide synthase (52.72%), and the lowest was with glycine receptors (31.93%). Glutamic acid decarboxylase- and glycine transporter 2-immunoreactive boutons, as well as GABAA receptor-immunoreactive plasma membrane processes and boutons, were also identified in the PBC. PBC neurons exhibited different levels of cytochrome oxidase activity, indicating their various energy demands. Our results suggest that synaptic interactions within the PBC of adult rats involve a variety of neurotransmitter and receptor types and that nitric oxide may play an important role in addition to glutamate, GABA, glycine, and neurokinin.
Invited Review: The circle of life: cell cycle regulation in airway smooth muscle
Authors: Ammit Alaina J. , Panettieri Reynold A.
Published: December 2017

Severe asthma is characterized by increased airway smooth muscle (ASM) mass, due predominantly to ASM hyperplasia. Diverse stimuli, which include growth factors, plasma- or inflammatory cell-derived mediators, contractile agonists, cytokines, and extracellular matrix proteins, induce ASM proliferation. Mitogens act via receptor tyrosine kinase, G protein-coupled receptors, or cytokine receptors, to activate p21ras and stimulate two parallel signaling pathways in ASM cells, namely, the extracellular signal-regulated kinase (ERK) or the phosphatidylinositol 3-kinase (PI3K) pathways. ERK and PI3K regulate cell cycle protein expression and thus modulate cell cycle traversal. ERK activation and downstream effectors of PI3K, such as Rac1 and Cdc42, stimulate expression of cyclin D1, a key regulator of G1progression in the mammalian cell cycle. In addition, PI3K activates 70-kDa ribosomal S6 kinase, an enzyme that also regulates the translation of many cell cycle proteins, including the elongation factor E2F. The present review examines the mitogens and critical signal transduction pathways that stimulate ASM cell proliferation. Further study in this area may reveal new therapeutic targets to abrogate ASM hyperplasia in diseases such as asthma and chronic obstructive pulmonary disease.
Nitric oxide and neurally mediated regulation of skin blood flow during local heating
Authors: Minson Christopher T. , Berry Latoya T. , Joyner Michael J.
Published: December 2017

The mechanisms underlying the skin blood flow (SkBF) response to local heating are complex and poorly understood. Our goal was to examine the role of axon reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating protocol with different interventions, including blockade of the axon reflex (EMLA cream), antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS) inhibition (≥10 mM NG-nitro-l-arginine methyl ester; microdialysis). Appropriate controls were performed to verify the efficacy of the various blocks. Values are expressed as a percentage of maximal SkBF (SkBFmax; 50 mM sodium nitroprusside). At the initiation of local heating, SkBF rose to an initial peak, followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon reflex block decreased the initial peak from 75+3 to 32 ± 2% SkBFmax( P< 0.01 vs. control) but did not affect the plateau. NOS inhibition before and throughout local heating reduced the initial peak from 75 ± 3 to 56 ± 3% SkBFmax( P< 0.01) and the plateau from 87 ± 4 to 40 ± 5%. NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone. Antebrachial nerve block did not affect the local heating SkBF response. The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating: a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO.
Major role for neuronal NO synthase in curtailing choroidal blood flow autoregulation in newborn pig
Authors: Hardy P. , Lamireau D. , Hou X. , Dumont I. , Abran D. , Nuyt A.-M. , Varma D. R. , Chemtob S.
Published: December 2017

We examined whether nitric oxide (NO) generated from neuronal NO synthase (nNOS) contributes to the reduced ability of the newborn to autoregulate retinal blood flow (RBF) and choroidal blood flow (ChBF) during acute rises in perfusion pressure. In newborn pigs (1–2 days old), RBF (measured by microsphere) is autoregulated over a narrow range of perfusion pressure, whereas ChBF is not autoregulated. NG-nitro-l-arginine methyl ester (l-NAME) or specific nNOS inhibitors 7-nitroindazole, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethyl-phenyl)imidazole as well as ganglionic blocker hexamethonium, unveiled a ChBF autoregulation as observed in juvenile (4- to 6-wk old) animals, whereas autoregulation of RBF in the newborn was only enhanced byl-NAME. All NOS inhibitors and hexamethonium prevented the hypertension-induced increase in NO mediator cGMP in the choroid. nNOS mRNA expression and activity were three- to fourfold higher in the choroid of newborn pigs than in tissues of juvenile pigs. It is concluded that increased production of NO from nNOS curtails ChBF autoregulation in the newborn and suggests a role for the autonomic nervous system in this important hemodynamic function, whereas, for RBF autoregulation, endothelial NOS seems to exert a more important contribution in limiting autoregulation.
Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans
Authors: Cui Jian , Wilson Thad E. , Shibasaki Manabu , Hodges Nicole A. , Crandall Craig G.
Published: December 2017

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative ( P < 0.001) during posthandgrip muscle ischemia (−201.9 ± 20.4 units · beat−1 · mmHg−1) when compared with control conditions (−142.7 ± 17.3 units · beat−1 · mmHg−1). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.
Orthostasis fails to produce active limb venoconstriction in adolescents
Authors: Stewart Julian M. , Lavin Jean , Weldon Amy
Published: December 2017

Orthostasis is characterized by translocation of blood from the upper body and thorax into dependent venous structures. Although active splanchnic venoconstriction is known to occur, active limb venoconstriction remains controversial. Based on prior work, we initially hypothesized that active venoconstriction does occur in the extremities during orthostasis in response to baroreflex activation. We investigated this hypothesis in the arms and legs of 11 healthy volunteers, aged 13–19 yr, using venous occlusion strain gauge plethysmography to obtain the forearm and calf blood flows and to compute the capacitance vessel volume-pressure compliance relation. Subjects were studied supine and at −10, +20, and +35° to load the baroreflexes. With +20° of tilt, blood flow decreased and limb arterial resistance increased significantly ( P < 0.05) compared with supine. With +35° of tilt, blood flow decreased, limb arterial resistance increased, and heart rate increased, indicating parasympathetic withdrawal and sympathetic activation with arterial vasoconstriction. The volume-pressure relation was unchanged by orthostatic maneuvers. The results suggest that active venoconstriction in the limbs is not important to mild orthostatic response.
Muscle glycogen depletion and subsequent replenishment affect anaerobic capacity of horses
Authors: Lacombe Veronique A. , Hinchcliff Kenneth W. , Geor Ray J. , Baskin Carole R.
Published: December 2017

The purpose of this study was to determine the effect of muscle glycogen depletion and subsequent replenishment on anaerobic capacity of horses. In a blinded crossover study, seven fit horses performed glycogen-depleting exercise on two occasions. Horses were infused after glycogen-depleting exercise with either 6 g/kg body wt of glucose as a 13.5% solution in 0.9% NaCl (Glu) or with 0.9% NaCl (Sal) of equivalent volume. Subsequently, horses performed a high-speed exercise test (120% of maximal rate of oxygen consumption) to estimate maximum accumulated oxygen deficit. Replenishment of muscle glycogen was greater ( P < 0.05) in Glu [from 24.7 ± 7.2 (SE) to 116.5 ± 7 mmol/kg wet wt before and after infusion, respectively] than in Sal (from 23.4 ± 7.2 to 47.8 ± 5.7 mmol/kg wet wt before and after infusion, respectively). Run time to fatigue during the high-speed exercise test (97.3 ± 8.2 and 70.8 ± 8.3 s, P < 0.05), maximal accumulated oxygen deficit (105.7 ± 9.3 and 82.4 ± 10.3 ml O2equivalent/kg, P < 0.05), and blood lactate concentration at the end of the high-speed exercise test (11.1 ± 1.4 and 9.2 ± 3.7 mmol/l, P < 0.05) were greater for Glu than for Sal, respectively. We concluded that decreased availability of skeletal muscle glycogen stores diminishes anaerobic power generation and capacity for high-intensity exercise in horses.
Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats
Authors: Stupka Nicole , Tiidus Peter M.
Published: December 2017

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.
Selected Contribution: Gender differences in cardiovascular regulation during recovery from exercise
Authors: Carter Robert , Watenpaugh Donald E. , Smith Michael L.
Published: December 2017

Are women more susceptible to acute postexercise orthostatic hypotension compared with men? We hypothesized that decreases in arterial pressure during recovery from dynamic exercise are greater in women compared with men. We studied 8 men and 11 women during inactive and active recovery from cycling exercise. Heart rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during and after 3 min of exercise at 60% of calculated maximum heart rate. At 1 min after exercise, MAP decreased less ( P < 0.05) during inactive recovery in men (−18 ± 2 mmHg) compared with women (−30 ± 2 mmHg). This difference was due to greater decreases in SV and less increase in TPR during inactive recovery from exercise in women compared with men. These differences persisted for 5 min after exercise. MAP decreased less during active recovery in men compared with women. These findings suggest that women may have increased risk of postexercise orthostatic hypotension and that active recovery from exercise may reduce this risk.
Pulmonary arterial dilation by inhaled NO: arterial diameter, NO concentration relationship
Authors: Bentley Jason , Rickaby David , Haworth Steven T. , Hanger Christopher C. , Dawson Christopher A.
Published: December 2017

The objective of this study was to determine the nitric oxide (NO) concentration and vessel diameter dependence of the pulmonary arterial dilation induced by inhaled NO. Isolated dog lung lobes were situated between a microfocal X-ray source and X-ray detector and perfused with either blood or plasma. Boluses of radiopaque contrast medium were injected into the lobar artery under control conditions, when the pulmonary arteries were constricted by infusion of serotonin and when the serotonin infusion was accompanied by inhalation of from 30 to 960 parts/million NO. Arterial diameter measurements were obtained from X-ray images of vessels having control diameters in the 300- to 3,400-μm range. Serotonin constricted the vessels throughout the size range studied, with an average decrease in diameter of ∼20%. The fractional reversal of the serotonin-induced constriction by inhaled NO was directly proportional to inhaled NO concentration, inversely proportional to vessel size, and greater with plasma than with blood perfusion in vessels as large as 3 mm in diameter. The latter indicates that intravascular hemoglobin affected the bronchoalveolar-to-arterial luminal NO concentration gradient in fairly large pulmonary arteries. The data provide information regarding pulmonary arterial smooth muscle accessibility to intrapulmonary gas that should be useful as part of the database for modeling the communication between intrapulmonary gas and pulmonary arterial smooth muscle cells in future studies.
Sucrose diets increase glucose-6-phosphatase and glucose release and decrease glucokinase in hepatocytes
Authors: Bizeau Michael E. , Thresher Jeffrey S. , Pagliassotti Michael J.
Published: December 2017

A high-sucrose diet (SU) decreases insulin action in the liver (Pagliassotti MJ, Shahrokhi KA, and Moscarello M. Am J Physiol Regulatory Integrative Comp Physiol 266: R1637–R1644, 1994). The present study was conducted to characterize the effect of SU on glucagon action in isolated periportal (PP) and perivenous (PV) hepatocytes by measuring glucagon-stimulated glycogenolysis and glucose release. Male rats were fed a SU (68% sucrose) or starch diet (ST, 68% starch) for 1 wk, and hepatocytes were isolated from PP or PV regions ( n = 4/diet/cell population). Hepatocytes were incubated for 1 h in the presence of varying concentrations of glucagon (0–100 nM). In PP and PV cells, glucagon stimulation of glucose release and glycogenolysis (sum of glucose release and lactate accumulation) was not significantly different between SU and ST cells. However, in the SU PP cells, glucose release was increased compared with ST PP cells, both in the absence of glucagon (76.1 ± 4 vs. 54.8 ± 3 nmol · h−1· mg cell wet wt−1) and at all glucagon concentrations. In SU-fed PV cells, glucose release was increased compared with ST PV cells in the absence of glucagon (79.3 ± 5 vs. 56.4 ± 5 nmol · h−1· mg cell wet wt−1) and at low glucagon concentrations. Maximal glucose-6-phosphatase activity (in nmol · min−1· mg protein−1) was elevated in SU compared with ST cells (61.4 ± 3 vs. 37.5 ± 4 in PP and 37.5 ± 4 vs. 29.5 ± 3 in PV cells). In contrast, maximal glucokinase activity (in nmol · min−1· mg protein−1) was elevated in ST compared with SU cells (15.9 ± 2 vs. 12.1 ± 1 in PP and 19.4 ± 2 vs. 14.2 ± 1 in PV cells). These data demonstrate that SU increases the capacity for glucose release in both PP and PV hepatocytes, in part because of reciprocal changes in glucose-6-phosphatase and glucokinase.
Influence of aerobic fitness and body fatness on tolerance to uncompensable heat stress
Authors: Selkirk Glen A. , McLellan Tom M.
Published: December 2017

This study examined the independent and combined importance of aerobic fitness and body fatness on physiological tolerance and exercise time during weight-bearing exercise while wearing a semipermeable protective ensemble. Twenty-four men and women were matched for aerobic fitness and body fatness in one of four groups (4 men and 2 women in each group). Aerobic fitness was expressed per kilogram of lean body mass (LBM) to eliminate the influence of body fatness on the expression of fitness. Subjects were defined as trained (T; regularly active with a peak aerobic power of 65 ml · kg LBM−1 · min−1) or untrained (UT; sedentary with a peak aerobic power of 53 ml · kg LBM−1 · min−1) with high (High; 20%) or low (Low; 11%) body fatness. Subjects exercised until exhaustion or until rectal temperature reached 39.5°C or heart rate reached 95% of maximum. Exercise times were significantly greater in TLow(116 ± 6.5 min) compared with their matched sedentary (UTLow; 70 ± 3.6 min) or fatness (THigh; 82 ± 3.9 min) counterparts, indicating an advantage for both a high aerobic fitness and low body fatness. However, similar effects were not evident between THigh and UTHigh(74 ± 4.1 min) or between the UT groups (UTLow and UTHigh). The major advantage attributed to a higher aerobic fitness was the ability to tolerate a higher core temperature at exhaustion (the difference being as great as 0.9°C), whereas both body fatness and rate of heat storage affected the exercise time as independent factors.
Gender difference in cardiovagal baroreflex gain in humans
Authors: Beske Stacy D. , Alvarez Guy E. , Ballard Tasha P. , Davy Kevin P.
Published: December 2017

We tested the hypothesis that women would demonstrate lower cardiovagal baroreflex gain compared with men. If so, we further hypothesized that the lower cardiovagal baroreflex gain in women would be associated with their lower aerobic fitness and higher body fat percentage compared with men. To accomplish this, we measured cardiovagal baroreflex gain (modified Oxford technique) in sedentary, nonobese (body mass index < 25 kg/m2) men (age = 26.0 ± 2.1 yr, n = 11) and women (age = 26.9 ± 1.6 yr, n = 14). Resting R-R interval and diastolic blood pressure were similar in the two groups, but systolic blood pressure was lower ( P < 0.05) in the women. Cardiovagal baroreflex gain was significantly lower in the women compared with the men (13.3 ± 1.5 vs. 20.0 ± 2.8 ms/mmHg, P< 0.05). The lower cardiovagal baroreflex gain in the women was not related ( P > 0.05) to their lower aerobic fitness and was only marginally related to their higher body fat percentage ( r = −0.34, P < 0.05). There were no gender differences in the threshold and saturation, operating range, or operating point (all P > 0.05), although the operating point fell significantly to left (i.e., at a lower systolic blood pressure) compared with men. Therefore, the findings of this study suggest that the gain of the cardiovagal baroreflex is reduced whereas other parameters were similar in women compared with men. The mechanisms responsible for the reduced cardiovagal baroreflex gain remain unclear.
Invited Review: Gender issues related to spaceflight: a NASA perspective
Authors: Harm Deborah L. , Jennings Richard T. , Meck Janice V. , Powell Michael R. , Putcha Lakshmi , Sams Clarence P. , Schneider Suzanne M. , Shackelford Linda C. , Smith Scott M. , Whitson Peggy A.
Published: December 2017

This minireview provides an overview of known and potential gender differences in physiological responses to spaceflight. The paper covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction. Potential health and functional impacts associated with the various physiological changes during spaceflight are discussed, and areas needing additional research are highlighted. Historically, studies of physiological responses to microgravity have not been aimed at examining gender-specific differences in the astronaut population. Insufficient data exist in most of the discipline areas at this time to draw valid conclusions about gender-specific differences in astronauts, in part due to the small ratio of women to men. The only astronaut health issue for which a large enough data set exists to allow valid conclusions to be drawn about gender differences is orthostatic intolerance following shuttle missions, in which women have a significantly higher incidence of presyncope during stand tests than do men. The most common observation across disciplines is that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders. Individual characteristics usually outweigh gender differences per se.
Invited Review: Sex-based differences in gene expression
Authors: Ostrer Harry
Published: December 2017

Certain diseases are more prevalent among women than men. The reasons for this increased prevalence are unknown, but there could be a genetic basis. Increased expression of X-linked genes in females, protective effects of Y-linked genes in males, or sex-limited gene expression that is developmentally or hormonally regulated could all account for these differences. Analysis of individuals with and without genetic sex reversal provides a means for distinguishing between genetic and hormonal causes. This can be complemented by genetic linkage and gene expression profiling to aid in the identification of candidate genes.
Cervical spinal cord injury alters the pattern of breathing in anesthetized rats
Authors: Golder Francis J. , Reier Paul J. , Davenport Paul W. , Bolser Donald C.
Published: December 2017

The mechanisms by which chronic cervical spinal cord injury alters respiratory function and plasticity are not well understood. We speculated that spinal hemisection at C2would alter the respiratory pattern controlled by vagal mechanisms. Expired volume (Ve) and respiratory rate (RR) were measured in anesthetized control and C2-hemisected rats at 1 and 2 mo postinjury. C2hemisection altered the pattern of breathing at both postinjury time intervals. Injured rats utilized a higher RR and lower Ve to maintain the same minute ventilation as control rats. After bilateral vagotomy, the pattern of breathing in injured rats was not different from controls. The frequency of augmented breaths was higher in injured rats at 2 mo postinjury before vagotomy; however, the Ve of augmented breaths was not different between groups. In conclusion, C2hemisection alters the pattern of breathing at 1 and 2 mo postinjury via vagal mechanisms.
Supine position decreases the ability of the nose to warm and humidify air
Authors: Assanasen Paraya , Baroody Fuad M. , Naureckas Edward , Solway Julian , Naclerio Robert M.
Published: December 2017

We tested the hypothesis that decreasing nasal air volume (i.e., increasing nasal turbinate blood volume) improves nasal air conditioning. We performed a randomized, two-way crossover study on the conditioning capacity of the nose in six healthy subjects in the supine and upright position. Cold, dry air (CDA) was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before it entered and after it exited the nasal cavity. The total water gradient (TWG) across the nose was calculated and represents the nasal conditioning capacity. Nasal volume decreased significantly from baseline without changing the mucosal temperature when subjects were placed in the supine position ( P < 0.01). TWG in supine position was significantly lower than that in upright position ( P < 0.001). In the supine position, nasal mucosal temperature after CDA exposure was significantly lower than that in upright position ( P < 0.01). Our data show that placing subjects in the supine position decreased the ability of the nose to condition CDA compared with the upright position, in contrast to our hypothesis.
Airway response to deep inspiration: role of inflation pressure
Authors: Brown Robert H. , Mitzner Wayne
Published: December 2017

Deep inspirations (DIs) have been shown to have both bronchoprotective and bronchodilator effects in healthy subjects; however, the bronchodilator effects of a DI appear to be impaired in asthmatic compared with healthy subjects. Because the ability to generate high transpulmonary pressures at total lung capacity depends on both the lung properties and voluntary effort, we wondered how the response of airways to DI might be altered if the maneuver were done with less than maximal inflation. The present work was undertaken to examine the effects of varying the magnitude of lung inflation during the DI maneuver on subsequent airway caliber. In five anesthetized and ventilated dogs during methacholine infusion, changes in airway size after DIs of increasing magnitude were measured over the subsequent 5-min period using high-resolution computed tomography. Results show that the magnitude of lung inflation is extremely important, leading to a qualitative change in the airway response. A large DI (45 cmH2O airway pressure) caused subsequent airway dilation, whereas smaller DIs (≤35 cmH2O) caused bronchoconstriction. The precise mechanism underlying these observations is uncertain, but it seems to be related to an interaction between intrinsic properties of the contracted airway smooth muscle and the response to mild stretch.
Erythropoiesis in women during 11 days at 4,300 m is not affected by menstrual cycle phase
Authors: Reeves John T. , Zamudio Stacy , Dahms Thomas E. , Asmus Ingrid , Braun Barry , Butterfield Gail E. , McCullough Rosann G. , Muza Stephen R. , Rock Paul B. , Moore Lorna G.
Published: December 2017

Because the ovarian steroid hormones, progesterone and estrogen, have higher blood levels in the luteal (L) than in the follicular (F) phase of the menstrual cycle, and because of their known effects on ventilation and hematopoiesis, we hypothesized that less hypoxemia and less erythropoiesis would occur in the L than the F phase of the cycle after arrival at altitude. We examined erythropoiesis with menstrual cycle phase in 16 women (age 22.6 ± 0.6 yr). At sea level, 11 of 16 women were studied during both menstrual cycle phases, and, where comparison within women was available, cycle phase did not alter erythropoietin ( n= 5), reticulocyte count ( n = 10), and red cell volume ( n = 9). When all 16 women were taken for 11 days to 4,300-m altitude (barometric pressure = 462 mmHg), paired comparisons within women showed no differences in ovarian hormone concentrations at sea level vs. altitude on menstrual cycle day 3 or 10 for either the F ( n = 11) or the L ( n = 5) phase groups. Arterial oxygen saturation did not differ between the F and L groups at altitude. There were no differences by cycle phase on day 11 at 4,300 m for erythropoietin [22.9 ± 4.7 (L) vs. 18.8 ± 3.4 mU/ml (F)], percent reticulocytes [1.9 ± 0.1 (L) vs. 2.1 ± 0.3% (F)], hemoglobin [13.5 ± 0.3 (L) vs. 13.7 ± 0.3 g/100 ml (F)], percent hematocrit [40.6 ± 1.4 (L) vs. 40.7 ± 1.0% (F)], red cell volume [31.1 ± 3.6 (L) vs. 33.0 ± 1.6 ml/kg (F)], and blood ferritin [8.9 ± 1.7 (L) vs. 10.2 ± 0.9 μg/l (F)]. Blood level of erythropoietin was related ( r= 0.77) to arterial oxygen saturation but not to the levels of progesterone or estradiol. We conclude that erythropoiesis was not altered by menstrual cycle phase during the first days at 4,300-m altitude.
Methacholine versus histamine: paradoxical response of spirometry and ventilation distribution
Authors: Verbanck Sylvia , Schuermans Daniël , Noppen Marc , Vincken Walter , Paiva Manuel
Published: December 2017

We investigated the differential effect of histamine and methacholine on spirometry and ventilation distribution (where indexes S cond and S acin represent conductive and acinar ventilation heterogeneity; Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W. J Appl Physiol 83: 1807–1816, 1997). Thirty normal subjects were challenged with cumulative doses of 6.52 μmol histamine and, on a separate day, with either 6.67 μmol methacholine (equal-dose group; n = 15) or 13.3 μmol methacholine (double-dose group; n = 15). Largest average forced expiratory volume in 1 s (FEV1) decreases or S cond increases obtained in either group were −9% and +286%, respectively; S acin remained unaffected at all times. In the equal-dose group, a smaller FEV1 decline ( P= 0.002) after methacholine was paralleled by a smaller S cond increase ( P = 0.041) than with histamine. However, in the double-dose group, methacholine maintained a smaller FEV1 decline ( P = 0.009) while inducing a larger S cond increase ( P = 0.006) than did histamine. The differential action of histamine and methacholine is confined to the conductive airways, where histamine likely causes the greatest overall airway narrowing and methacholine induces the largest parallel heterogeneity in airway narrowing, probably at the level of the large and small conductive airways, respectively. The observed ventilation heterogeneities predict a risk for dissociation between ventilation-perfusion mismatch and spirometry, particularly after methacholine challenge.
Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes
Authors: Evans Joyce M. , Ziegler Michael G. , Patwardhan Abhijit R. , Ott J. Blaine , Kim Charles S. , Leonelli Fabio M. , Knapp Charles F.
Published: December 2017

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 ± 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after β- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after β- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be α-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited β-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.
Skeletal muscle intracellular Po2assessed by myoglobin desaturation: response to graded exercise
Authors: Richardson R. S. , Newcomer S. C. , Noyszewski E. A.
Published: December 2017

The relationship between skeletal muscle intracellular Po2(iPo2) and progressive muscular work has important implications for the understanding of O2transport and utilization. Presently there is debate as to whether iPo2falls progressively with increasing O2demand or reaches a plateau from moderate to maximal metabolic demand. Thus, using1H magnetic resonance spectroscopy of myoglobin (Mb), we studied cellular oxygenation during progressive single-leg knee extensor exercise from unweighted to 100% of maximal work rate in six active human subjects. In all subjects, the Mb peak at 73 ppm was not visible at rest, whereas the peak was small or indistinguishable from the noise in the majority of subjects during progressive exercise from unweighted to 50–60% of maximum work rate. In contrast, beyond this exercise intensity, a Mb peak of consistent magnitude was discernible in all subjects. When a Mb half saturation of 3.2 Torr was used, the calculated skeletal muscle Po2was variable before 60% of maximum work rate but in general was relatively high (>18 Torr, the measurable Po2with the poorest signal-to-noise ratio, in the majority of cases), whereas beyond this exercise intensity iPo2fell to a relatively uniform and invariant level of 3.8 ± 0.5 Torr across all subjects. These results do not support the concept of a progressive linear fall in iPo2across increasing work rates. Instead, this study documents variable but relatively high iPo2from rest to moderate exercise and again confirms that from 50–60% of maximum work rate iPo2reaches a plateau that is then invariant with increasing work rate.
Effects of stimulation frequencies and patterns on performance of repetitive, nonisometric tasks
Authors: Kebaetse Maikutlo B. , Turner Amanda E. , Binder-Macleod Stuart A.
Published: December 2017

The purpose of this paper was to determine the effects of stimulation pattern and frequency on repetitive human knee movements. Quadriceps femoris muscles were stimulated against a load equal to 10% of each subject's maximum voluntary isometric force. The main variable of interest was the number of repetitions in which the leg reached a target angle of 40° of knee extension. Sixteen different trains were tested, including 1) six constant-frequency trains with frequencies ranging from 9 to 100 Hz, 2) five variable-frequency trains with an initial 5-ms triplet and mean frequencies ranging from 11 to 35 Hz, and 3) five doublet-frequency trains, which used doublets (2 pulses with a 5-ms interpulse interval) to replace single pulses, with mean frequencies of 17–57 Hz. Testing was stopped when the subject failed to reach the target angle for three consecutive activations. Results showed that no single pattern was best for all subjects. The 33- and 100-Hz constant-frequency trains, 35-Hz variable-frequency trains, and 27- and 36-Hz doublet frequency trains each met the target the most times for some subjects. The results showed that, under our testing conditions, higher frequency trains were better suited for producing repetitive knee movements than lower frequency trains.