bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep
Authors: Zhou X. S. , Shahabuddin S. , Zahn B. R. , Babcock M. A. , Badr M. S.
Published: December 2017

We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25–35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21–43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (Vt) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal Pco 2(Pet CO2 ) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in Vt to 155 ± 29% (mean ± SD) and a reduction of Pet CO2 by −4.72 ± 0.57 Torr. In men, induction of a central apnea required an increase in Vt to 142 ± 13% and a reduction of Pet CO2 by −3.54 ± 0.31 Torr ( P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.
Forearm muscle metabolism studied using 31P-MRS during progressive exercise to fatigue after Acz administration
Authors: Kowalchuk John M. , Smith Shelly A. , Weening Brad S. , Marsh Greg D. , Paterson Donald H.
Published: December 2017

The effects of acetazolamide (Acz)-induced carbonic anhydrase inhibition (CAI) on muscle intracellular thresholds (T) for intracellular pH (pHi) and inorganic phosphate-to-phosphate creatine ratio (Pi/PCr) and the plasma lactate (La−) threshold were examined in nine adult male subjects performing forearm wrist flexion exercise to fatigue. Exercise consisted of raising and lowering (1-s contraction, 1-s relaxation) a cylinder whose volume increased at a rate of 200 ml/min. The protocol was performed during control (Con) and after 45 min of CAI with Acz (10 mg/kg body wt iv). TpHi and TPi /PCr, determined using 31P-labeled magnetic resonance spectroscopy (MRS), were similar in Acz (722 ± 50 and 796 ± 75 mW, respectively) and Con (855 ± 211 and 835 ± 235 mW, respectively). The pHi was similar at end-exercise (6.38 ± 0.10 Acz and 6.43 ± 0.22 Con), but pHirecovery was slowed in Acz. In a separate experiment, blood was sampled from a deep arm vein at the elbow for determination of plasma lactate concentration ([La−]pl) and TLa− . [La−]pl was lower ( P < 0.05) in Acz than Con (3.7 ± 1.7 vs. 5.0 ± 1.7 mmol/l) at end-exercise and in early recovery, but TLa− was higher (1,433 ± 243 vs. 1,041 ± 414 mW, respectively). These data suggest that the lower [La−]pl seen with CAI was not due to a delayed onset or rate of muscle La− accumulation but may be related to impaired La− removal from muscle.
Analysis of responses of garlic derivatives in the pulmonary vascular bed of the rat
Authors: Kaye Alan D. , De Witt Bracken J. , Anwar Muhammad , Smith Donald E. , Feng Chang J. , Kadowitz Philip J. , Nossaman Bobby D.
Published: December 2017

Allicin, an extract from garlic, has been shown to be a systemic and pulmonary arterial vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (10–100 μg), allyl mercaptan (0.3–1 mg), and diallyl disulfide (0.3–1 mg) were studied in the isolated lung of the rat under constant-flow conditions. When baseline tone in the pulmonary vascular bed of the rat was raised to a high-steady level with the thromboxane A2mimic U-46619, dose-related decreases in pulmonary arterial pressure were observed. In terms of the mechanism of action of allicin vasodilator activity in the rat, responses to allicin were not significantly different after administration of the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester, the KATP+channel antagonist U-37883A, or the cyclooxygenase inhibitor sodium meclofenamate, or when lung ventilation was interrupted. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the rat, whereas allyl mercaptan and diallyl disulfide produced no significant changes in pulmonary arterial perfusion pressure. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of nitric oxide, ATP-sensitive K+channels, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed of the rat.
Sprint training normalizes Ca2+transients and SR function in postinfarction rat myocytes
Authors: Zhang Lian-Qin , Zhang Xue-Qian , Ng Yuk-Chow , Rothblum Lawrence I. , Musch Timothy I. , Moore Russell L. , Cheung Joseph Y.
Published: December 2017

Previous studies have shown that myocytes isolated from sedentary (Sed) rat hearts 3 wk after myocardial infarction (MI) undergo hypertrophy, exhibit altered intracellular Ca2+concentration ([Ca2+]i) dynamics and abnormal contraction, and impaired sarcoplasmic reticulum (SR) function manifested as prolonged half-time of [Ca2+]idecline. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+regulation, the present study examined whether 6–8 wk of high-intensity sprint training (HIST) would restore [Ca2+]idynamics and SR function in MI myocytes toward normal. In MI rats, HIST ameliorated myocyte hypertrophy as indicated by significant ( P ≤ 0.05) decreases in whole cell capacitances [Sham-Sed 179 ±12 ( n = 20); MI-Sed 226 ± 7 ( n = 20); MI-HIST 183 ± 11 pF ( n = 19)]. HIST significantly ( P < 0.0001) restored both systolic [Ca2+]i[Sham-Sed 421 ± 9 ( n = 79); MI-Sed 350 ± 6 ( n = 70); MI-HIST 399 ± 9 nM ( n = 70)] and half-time of [Ca2+]idecline (Sham-Sed 0.197 ± 0.005; MI-Sed 0.247 ± 0.006; MI-HIST 0.195 ± 0.006 s) toward normal. Compared with Sham-Sed myocytes, SR Ca2+-ATPase expression significantly ( P < 0.001) decreased by 44% in MI-Sed myocytes. Surprisingly, expression of SR Ca2+-ATPase was further reduced in MI-HIST myocytes to 26% of that measured in Sham-Sed myocytes. There were no differences in calsequestrin expression among the three groups. Expression of phospholamban was not different between Sham-Sed and MI-Sed myocytes but was significantly ( P < 0.01) reduced in MI-HIST myocytes by 25%. Our results indicate that HIST instituted shortly after MI improves [Ca2+]idynamics in surviving myocytes. Improvement in SR function by HIST is mediated not by increased SR Ca2+-ATPase expression, but by modulating phospholamban regulation of SR Ca2+-ATPase activity.
PLA2dependence of diaphragm mitochondrial formation of reactive oxygen species
Authors: Nethery D. , Callahan L. A. , Stofan D. , Mattera R. , DiMarco A , Supinski G.
Published: December 2017

Contraction-induced respiratory muscle fatigue and sepsis-related reductions in respiratory muscle force-generating capacity are mediated, at least in part, by reactive oxygen species (ROS). The subcellular sources and mechanisms of generation of ROS in these conditions are incompletely understood. We postulated that the physiological changes associated with muscle contraction (i.e., increases in calcium and ADP concentration) stimulate mitochondrial generation of ROS by a phospholipase A2(PLA2)-modulated process and that sepsis enhances muscle generation of ROS by upregulating PLA2activity. To test these hypotheses, we examined H2O2generation by diaphragm mitochondria isolated from saline-treated control and endotoxin-treated septic animals in the presence and absence of calcium and ADP; we also assessed the effect of PLA2inhibitors on H2O2formation. We found that 1) calcium and ADP stimulated H2O2formation by diaphragm mitochondria from both control and septic animals; 2) mitochondria from septic animals demonstrated substantially higher H2O2formation than mitochondria from control animals under basal, calcium-stimulated, and ADP-stimulated conditions; and 3) inhibitors of 14-kDa PLA2blocked the enhanced H2O2generation in all conditions. We also found that administration of arachidonic acid (the principal metabolic product of PLA2activation) increased mitochondrial H2O2formation by interacting with complex I of the electron transport chain. These data suggest that diaphragm mitochondrial ROS formation during contraction and sepsis may be critically dependent on PLA2activation.
Effects of inspiratory flow on diaphragmatic motor output in normal subjects
Authors: Corne S. , Webster K. , Younes M.
Published: December 2017

Increasing inspiratory flow (V˙) has been shown to shorten neural inspiratory time (Ti n) in normal subjects breathing on a mechanical ventilator, but the effect of V˙ on respiratory motor output before inspiratory termination has not previously been studied in humans. While breathing spontaneously on a mechanical ventilator, eight normal subjects were intermittently exposed to 200-ms-duration positive pressure pulses of different amplitudes at the onset of inspiration. Based on the increase in V˙ above control breaths (ΔV˙), trials were grouped into small, medium, and large groups (mean ΔV˙: 0.51, 1.11, and 1.65 l/s, respectively). We measured Ti n, transdiaphragmatic pressure (Pdi), and electrical activity (electromyogram) of the diaphragm (EMGdi). Transient increases inV˙ caused shortening of Ti n from 1.34 to 1.10 (not significant), 1.55 to 1.11 ( P < 0.005), and 1.58 to 1.17 s ( P < 0.005) in the small, medium, and large ΔV˙ groups, respectively. EMGdi measured at end Ti n of the pulse breaths was 131 ( P < 0.05), 142, and 155% ( P < 0.05) of the EMGdi of the control breaths at an identical time point in the small, medium, and large trials, respectively. The latency of the excitation was 126 ± 42 (SD) ms, consistent with a reflex effect. Increasing V˙ had two countervailing effects on Pdi: 1) a depressant mechanical effect due primarily to the force-length (11.2 cmH2O/l) relation of the diaphragm, and 2) an increase in diaphragm activation. For the eight subjects, mean peak Pdi did not change significantly, but there was significant intersubject variability, reflecting variability in the strength of the excitation reflex. We conclude that increasing inspiratory V˙ causes a graded facilitation of EMGdi, which serves to counteract the negative effect of the force-length relation on Pdi.
Effects of high myoplasmic l-lactate concentration on E-C coupling in mammalian skeletal muscle
Authors: Posterino Giuseppe S. , Fryer Martin W.
Published: December 2017

The effects of high myoplasmic l-lactate concentrations (20–40 mM) at constant pH (7.1) were investigated on contractile protein function, voltage-dependent Ca2+ release, and passive Ca2+ leak from the sarcoplasmic reticulum (SR) in mechanically skinned fast-twitch (extensor digitorum longus; EDL) and slow-twitch (soleus) fibers of the rat. l-Lactate (20 mM) significantly reduced maximum Ca2+-activated force by 4 ± 0.5% ( n = 5, P < 0.05) and 5 ± 0.4% ( n = 6, P < 0.05) for EDL and soleus, respectively. The Ca2+ sensitivity was also significantly decreased by 0.06 ± 0.002 ( n = 5, P < 0.05) and 0.13 ± 0.01 ( n = 6, P < 0.001) pCa units, respectively. Exposure tol-lactate (20 mM) for 30 s reduced depolarization-induced force responses by ChCl substitution by 7 ± 3% ( n = 17, P < 0.05). This inhibition was not obviously affected by the presence of the lactate transport blocker quercetin (10 μM), or the chloride channel blocker anthracene-9-carboxylic acid (100 μM). l-Lactate (20 mM) increased passive Ca2+ leak from the SR in EDL fibers (the integral of the response to caffeine was reduced by 16 ± 5%, n = 9, P < 0.05) with no apparent effect in soleus fibers (100 ± 2%, n = 3). These results indicate that the l-lactate ion per se has negligible effects on either voltage-dependent Ca2+ release or SR Ca2+ handling and exerts only a modest inhibitory effect on muscle contractility at the level of the contractile proteins.
Response-time enhancement of a clinical gas analyzer facilitates measurement of breath-by-breath gas exchange
Authors: Farmery A. D. , Hahn C. E. W.
Published: December 2017

Tidal ventilation gas-exchange models in respiratory physiology and medicine not only require solution of mass balance equations breath-by-breath but also may require within-breath measurements, which are instantaneous functions of time. This demands a degree of temporal resolution and fidelity of integration of gas flow and concentration signals that cannot be provided by most clinical gas analyzers because of their slow response times. We have characterized the step responses of the Datex Ultima (Datex Instrumentation, Helsinki, Finland) gas analyzer to oxygen, carbon dioxide, and nitrous oxide in terms of a Gompertz four-parameter sigmoidal function. By inversion of this function, we were able to reduce the rise times for all these gases almost fivefold, and, by its application to real on-line respiratory gas signals, it is possible to achieve a performance comparable to the fastest mass spectrometers. With the use of this technique, measurements required for non-steady-state and tidal gas-exchange models can be made easily and reliably in the clinical setting.
Total body water and ECFV measured using bioelectrical impedance analysis and indicator dilution in horses
Authors: Forro Mariann , Cieslar Scott , Ecker Gayle L. , Walzak Angela , Hahn Jay , Lindinger Michael I.
Published: December 2017

The purposes of this study were 1) to determine the compartmentation of body water in horses by using indicator dilution techniques and 2) to simultaneously measure bioelectrical impedance to current flow at impulse current frequencies of 5 and 200 kHz to formulate predictive equations that could be used to estimate total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). Eight horses and ponies weighing from 214 to 636 kg had catheters placed into the left and right jugular veins. Deuterium oxide, sodium thiocyanate, and Evans blue were infused for the measurement of TBW, ECFV, and plasma volume (PV), respectively. Bioelectrical impedance was measured by using a tetrapolar electrode configuration, with electrode pairs secured above the knee and hock. Measured TBW, ECFV, and PV were 0.677 ± 0.022, 0.253 ± 0.006, and 0.040 ± 0.002 l/kg body mass, respectively. Strong linear correlations were determined among measured variables that allowed for the prediction of TBW, ECFV, ICFV, and PV from measures of horse length or height and impedance. It is concluded that bioelectrical impedance analysis (BIA) can be used to improve the predictive accuracy of noninvasive estimates of ECFV and PV in euhydrated horses at rest.
Relationship of interstitial fluid volume to alveolar fluid clearance in mice: ventilated vs. in situ studies
Authors: Fukuda Norimasa , Folkesson Hans G. , Matthay Michael A.
Published: December 2017

Our recent report (Garat C, Carter EP, and Matthay MA. J Appl Physiol 84: 1763–1767, 1998) described a new method to measure alveolar fluid clearance (AFC) in an in situ mouse preparation. However, in vivo preparations may be more suitable for studying alveolar fluid transport under some pathological conditions. Therefore, we developed a ventilated mouse model and compared AFC in the ventilated and the in situ mouse models. After 15 min, AFC was similar in both groups, but, after 30 min, AFC was 38% slower in the in situ mice ( P < 0.05). Bilateral adrenalectomy and propranolol did not inhibit AFC after 15 min. Amiloride inhibited 90% of AFC in both groups. To evaluate the mechanism for the slower AFC in the in situ mouse preparation, we measured the extravascular lung water and calculated interstitial fluid volume. Extravascular lung water and interstitial fluid volume were greater in the in situ mice than in the ventilated mice at 30 min ( P < 0.05). These results indicate that mouse AFC is fast, highly amiloride sensitive, and independent of endogenous catecholamines during the first 15 min. Accumulation of interstitial fluid probably plays an important role in slowing AFC in the in situ mouse lung model at later time intervals. These mouse models will be useful to quantify alveolar epithelial fluid transport under pathological conditions.
Maximum specific force depends on myosin heavy chain content in rat diaphragm muscle fibers
Authors: Geiger Paige C. , Cody Mark J. , Macken Rebecca L. , Sieck Gary C.
Published: December 2017

In the present study, myosin heavy chain (MHC) content per half sarcomere, an estimate of the number of cross bridges available for force generation, was determined in rat diaphragm muscle (Diam) fibers expressing different MHC isoforms. We hypothesize that fiber-type differences in maximum specific force [force per cross-sectional area (CSA)] reflect the number of cross bridges present per CSA. Studies were performed on single, Triton X-100-permeabilized rat Diamfibers. Maximum specific force was determined by activation of single Diamfibers in the presence of a high-calcium solution (pCa, −log Ca2+concentration of 4.0). SDS-PAGE and Western blot analyses were used to determine MHC isoform composition and MHC content per half sarcomere. Differences in maximum specific force across fast MHC isoforms were eliminated when controlled for half-sarcomere MHC content. However, the force produced by slow fibers remained below that of fast fibers when normalized for the number of cross bridges available. On the basis of these results, the lower force produced by slow fibers may be due to less force per cross bridge compared with fast fibers.
Dual effects of nitric oxide on cat carotid body chemoreception
Authors: Iturriaga Rodrigo , Villanueva Sandra , Mosqueira Matias
Published: December 2017

We studied the effects of nitric oxide (NO) released by NO donors on cat carotid body (CB) chemosensory activity during normoxia and hypoxia. CBs excised from pentobarbital sodium-anaesthetized cats were perfused with Tyrode at 38°C and pH 7.40. The frequency of chemosensory discharges (ƒx) was recorded from the carotid sinus nerve, and changes of NO concentration were measured by a chronoamperometric technique, with NO-selective carbon-fiber microelectrodes inserted in the CB. During steady chemosensory excitation induced by hypoxia, bolus injections of NO (ΔNO = 0.5–12 μM), released by S-nitroso- N-acetylpenicillamine (SNAP) and 6-(2-hydroxy-1-methyl-nitrosohydrazino)- N-methyl-1-hexanamine (NOC-9), transiently reduced ƒx in a dose-dependent manner. However, during normoxia, the same concentration of NO (ΔNO = 0.5–13 μM) released by the NO donors increased ƒx in a dose-dependent manner. The present results show a dual effect of NO on CB chemoreception that is dependent on the Po 2 levels. During hypoxia, NO is predominantly an inhibitor of chemoreception, whereas, in normoxia, NO increased ƒx. The mechanisms by which NO produces chemosensory excitation during normoxia remain to be determined.
Skeletal muscle oxidative capacity in young and older women and men
Authors: Kent-Braun Jane A. , Ng Alexander V.
Published: December 2017

It has been suggested that a decline in skeletal muscle oxidative capacity is a general consequence of aging in humans. However, previous studies have not always controlled for the effects of varying levels of physical activity on muscle oxidative capacity. To test the hypothesis that, when matched for comparable habitual physical activity levels, there would be no age-related decline in the oxidative capacity of a locomotor muscle, the postexercise recovery time of phosphocreatine was compared in the tibialis anterior muscle of young [ n = 19; 33.8 ± 4.8 (SD) yr] and older [ n = 18; 75.5 ± 4.5 yr] healthy women and men of similar, relatively low, activity levels. The intramuscular metabolic measurements were accomplished by using phosphorus magnetic resonance spectroscopy. The results indicate that there was no age effect on the postexercise recovery time of phosphocreatine recovery, thus supporting the stated hypothesis. These data suggest that there is no requisite decline in skeletal muscle oxidative capacity with aging in humans, at least through the seventh decade.
Denervation alters myosin heavy chain expression and contractility of developing rat diaphragm muscle
Authors: Sieck Gary C. , Zhan Wen-Zhi
Published: December 2017

We hypothesized that unilateral denervation (DNV) of the rat diaphragm muscle (Diam) in neonates at postnatal day 7 (D-7) alters normal transitions of myosin heavy chain (MHC) isoform expression and thereby affects postnatal changes in maximum specific force (Po) and maximum unloaded shortening velocity ( Vo). The relative expression of different MHC isoforms was analyzed electrophoretically. With DNV at D-7, expression of MHCneoin the Diampersisted, and emergence of MHC2Xand MHC2Bwas delayed. By D-21 and D-28, relative expression of MHC2Aand MHC2Bwas reduced in DNV compared with control (CTL) animals. Expression of MHCneoalso reappeared in adult Diamby 2–3 wk after DNV, and relative expression of MHC2Bwas reduced. At each age, Powas reduced and Vowas slowed by DNV, compared with CTL. In CTL Diam, postnatal changes in Poand Vowere associated with an increase in fast MHC isoform expression. In DNV Diam, no such association existed. We conclude that, in the Diam, DNV induces alterations in both MHC isoform expression and contractile properties, which are not necessarily causally linked.
Reduced strength after passive stretch of the human plantarflexors
Authors: Fowles J. R. , Sale D. G. , MacDougall J. D.
Published: December 2017

The purpose of this study was to assess strength performance after an acute bout of maximally tolerable passive stretch (PSmax) in human subjects. Ten young adults (6 men and 4 women) underwent 30 min of cyclical PSmax (13 stretches of 135 s each over 33 min) and a similar control period (Con) of no stretch of the ankle plantarflexors. Measures of isometric strength (maximal voluntary contraction), with twitch interpolation and electromyography, and twitch characteristics were assessed before (Pre), immediately after (Post), and at 5, 15, 30, 45, and 60 min after PSmax or Con. Compared with Pre, maximal voluntary contraction was decreased at Post (28%) and at 5 (21%), 15 (13%), 30 (12%), 45 (10%), and 60 (9%) min after PSmax( P < 0.05). Motor unit activation and electromyogram were significantly depressed after PSmax but had recovered by 15 min. An additional testing trial confirmed that the torque-joint angle relation may have been temporarily altered, but at Post only. These data indicate that prolonged stretching of a single muscle decreases voluntary strength for up to 1 h after the stretch as a result of impaired activation and contractile force in the early phase of deficit and by impaired contractile force throughout the entire period of deficit.
Acellular hemoglobin solution enters compressed lung capillaries more readily than red blood cells
Authors: Conhaim Robert L. , Rodenkirch Lance A. , Watson Kal E. , Harms Bruce A.
Published: December 2017

High lung inflation pressures compress alveolar septal capillaries, impede red cell transit, and interfere with oxygenation. However, recently introduced acellular hemoglobin solutions may enter compressed lung capillaries more easily than red blood cells. To test this hypothesis, we perfused isolated rat lungs with fluorescently labeled diaspirin cross-linked hemoglobin (DCLHb; 10%) and/ or autologous red cells (hematocrit, 20). Septal capillaries were compressed by setting lung inflation pressure above vascular pressures (zone 1). Examination by confocal microscopy showed that DCLHb was distributed throughout alveolar septa. Furthermore, this distribution was not affected by adding red blood cells to the perfusate. We estimated the maximum acellular hemoglobin mass within septa to be equivalent to that of 15 red blood cells. By comparison, we found an average of 2.7 ± 4.6 red cells per septum in zone 1. These values increased to 30.4 ± 25.8 and 50.4 ± 22.1 cells per septum in zones 2 and 3, respectively. We conclude that perfusion in zone 1 with a 10% acellular hemoglobin solution may increase the hemoglobin concentration per septum up to fivefold compared with red cell perfusion.
Selected Contribution: Measuring the response time of pulmonary capillary recruitment to sudden flow changes
Authors: Jaryszak Eric M. , Baumgartner William A. , Peterson Amanda J. , Presson Robert G. , Glenny Robb W. , Wagner Wiltz W.
Published: December 2017

To determine how rapidly pulmonary capillaries recruit after sudden changes in blood flow, we used an isolated canine lung lobe perfused by two pumps running in parallel. When one pump was turned off, flow was rapidly halved; when it was turned on again, flow immediately doubled. We recorded pulmonary capillary recruitment in subpleural alveoli using videomicroscopy to measure how rapidly the capillaries reached a new steady state after these step changes in blood flow. When flow was doubled, capillary recruitment reached steady state in <4 s. When flow was halved, steady state was reached in ∼8 s. We conclude that the pulmonary microcirculation responds rapidly to step changes in flow, even in the capillaries that are most distant from the hilum.
Selected Contribution: Redistribution of pulmonary perfusion during weightlessness and increased gravity
Authors: Glenny Robb W. , Lamm Wayne J. E. , Bernard Susan L. , An Dowon , Chornuk Myron , Pool Sam L. , Wagner Wiltz W. , Hlastala Michael P. , Robertson H. Thomas
Published: December 2017

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into ∼2 cm3 pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.
Differences in airway structure in immature and mature rabbits
Authors: Ramchandani R. , Shen X. , Elmsley C. L. , Ambrosius W. T. , Gunst S. J. , Tepper R. S.
Published: December 2017

Our laboratory has previously demonstrated that maximal bronchoconstriction produces a greater degree of airway narrowing in immature than in mature rabbit lungs (33). To determine whether these maturational differences could be related to airway structure, we compared the fraction of the airway wall occupied by airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to ASM, and the number of alveolar attachments to the airways, from mature and immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed at total lung capacity. The results demonstrate that the airway walls of immature rabbits had a greater percentage of smooth muscle, a lower percentage of cartilage, and fewer alveolar attachments compared with mature rabbit airways; however, we did not find maturational differences in the airway wall thickness relative to airway size. We conclude that structural differences in the airway wall may contribute to the greater airway narrowing observed in immature rabbits during bronchoconstriction.
Hypoxia inhibits amino acid uptake in human lung fibroblasts
Authors: Berk John L. , Hatch Christine A. , Goldstein Ronald H.
Published: December 2017

Hypoxia and amino acid deprivation downregulate expression of extracellular matrix genes in lung fibroblasts. We examined the effect of hypoxia on amino acid uptake and protein formation in human lung fibroblasts. Low O2tension (0% O2) suppressed incorporation of [3H]proline into type I collagen without affecting [35S]methionine labeling of other proteins. Initial decreases in intracellular [3H]proline incorporation occurred after 2 h of exposure to 0% O2, with maximal suppression of intracellular [3H]proline levels at 6 h of treatment. Hypoxia significantly inhibited the uptake of radiolabeled proline, 2-aminoisobutyric acid (AIB), and 2-(methylamino)isobutyric acid (methyl-AIB) while inducing minor decreases in leucine transport. Neither cycloheximide nor indomethacin abrogated hypoxia-related suppression of methyl-AIB uptake. Efflux studies demonstrated that hypoxia inhibited methyl-AIB transport in a bidirectional fashion. The downregulation of amino acid transport was not due to a toxic effect; function recovered on return to standard O2conditions. Kinetic analysis of AIB transport revealed a 10-fold increase in Kmaccompanied by a small increase in maximal transport velocity among cells exposed to 0% O2. These data indicate that low O2tension regulates the system A transporter by decreasing transporter substrate affinity.
Ischemic exercise and the muscle metaboreflex
Authors: Cornett Jacob A. , Herr Michael D. , Gray Kristen S. , Smith Michael B. , Yang Qing X. , Sinoway Lawrence I.
Published: December 2017

In exercising muscle, interstitial metabolites accumulate and stimulate muscle afferents. This evokes the muscle metaboreflex and raises arterial blood pressure (BP). In this report, we examined the effects of tension generation on muscle metabolites and BP during ischemic forearm exercise in humans. Heart rate (HR), BP, Pi, H2PO4 −, and pH (31P-NMR spectroscopy) data were collected in 10 normal healthy men (age 23 ± 1 yr) during rhythmic handgrip exercise. After baseline measurements, the subjects performed rhythmic handgrip for 2 min. At 2 min, a 250-mmHg occlusion cuff was inflated, and ischemic handgrip exercise was continued until near fatigue (Borg 19). Measurements were continued for an additional 30 s of ischemia. This protocol was performed at 15, 30, 45, and 60% of the subjects' maximum voluntary contraction (MVC) in random order. As tension increased, the time to fatigue decreased. In addition, mean arterial pressure and HR were higher at 60% MVC than at any of the other lower tensions. The NMR data showed significantly greater increases in H2PO4 −, Pi, and H+at 60% than at 15 and 30% MVC. Therefore, despite the subjects working to the same perceived effort level, a greater reflex response (represented by BP and HR data) was elicited at 60% MVC than at any of the other ischemic tensions. These data are consistent with the hypothesis that, as tension increases, factors aside from insufficient blood flow contribute to the work effect on muscle metabolites and the magnitude of the reflex response.
Alveolar epithelial integrity in athletes with exercise-induced hypoxemia
Authors: Edwards Michael R. , Hunte Garth S. , Belzberg Allan S. , Sheel A. William , Worsley Dan F. , McKenzie Donald C.
Published: December 2017

The effect of incremental exercise to exhaustion on the change in pulmonary clearance rate ( k) of aerosolized99mTc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) and the relationship between k and arterial Po 2 (PaO2 ) during heavy work were investigated. Ten male cyclists (age = 25 ± 2 yr, height = 180.9 ± 4.0 cm, mass = 80.1 ± 9.5 kg, maximal O2 uptake = 5.25 ± 0.35 l/min, mean ± SD) completed a pulmonary clearance test shortly (39 ± 8 min) after a maximal O2 uptake test. Resting pulmonary clearance was completed ≥24 h before or after the exercise test. Arterial blood was sampled at rest and at 1-min intervals during exercise. Minimum PaO2 values and maximum alveolar-arterial Po 2 difference ranged from 73 to 92 Torr and from 30 to 55 Torr, respectively. No significant difference between resting k and postexercise kfor the total lung (0.55 ± 0.20 vs. 0.57 ± 0.17 %/min, P > 0.05) was observed. Pearson product-moment correlation indicated no significant linear relationship between change in k for the total lung and minimum PaO2 ( r = −0.26, P > 0.05). These results indicate that, averaged over subjects, pulmonary clearance of99mTc-DTPA after incremental maximal exercise to exhaustion in highly trained male cyclists is unchanged, although the sampling time may have eliminated a transient effect. Lack of a linear relationship between k and minimum PaO2 during exercise suggests that exercise-induced hypoxemia occurs despite maintenance of alveolar epithelial integrity.
Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats
Authors: Wood John G. , Johnson Jennifer S. , Mattioli Leone F. , Gonzalez Norberto C.
Published: December 2017

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734–1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873–881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.
Electrical admittance for filling of the heart during lower body negative pressure in humans
Authors: Cai Yan , Holm Søren , Jenstrup Morten , Strømstad Morten , Eigtved Annika , Warberg Jørgen , Højgaard Liselotte , Friberg Lars , Secher Niels H.
Published: December 2017

To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (ThoraxICW), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during lower body negative pressure (LBNP) in humans. Changes in ThoraxICWwere compared with positron emission tomography-determined C15O-labeled erythrocytes over the heart. During −40 mmHg LBNP, the blood volume of the heart decreased by 21 ± 3% as the erythrocyte volume was reduced by 20 ± 2% and the plasma volume declined by 26 ± 2% ( P< 0.01; n = 8). Over the heart region, LBNP was also associated with a decrease in the technetium-labeled erythrocyte activity by 26 ± 4% and, conversely, an increase over the lower leg by 92 ± 5% ( P < 0.01; n = 6). For 15 subjects, LBNP increased thoracic impedance by 3.3 ± 0.3 Ω (1.5 kHz) and 3.0 ± 0.4 Ω (100 kHz), whereas leg impedance decreased by 9.0 ± 3.3 Ω (1.5 kHz) and 6.1 ± 3 Ω (100 kHz; P < 0.01). ThoraxICWwas reduced by 7.1 ± 1.9 S · 10−4( P < 0.01) and intracellular water in the leg tended to increase (from 37.8 ± 4.6 to 40.9 ± 5.0 S · 10−4; P = 0.08). The correlation between ThoraxICWand heart erythrocyte volume was 0.84 ( P < 0.05). The results suggest that thoracic electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans.
Effects of voluntary activity and genetic selection on muscle metabolic capacities in house miceMus domesticus
Authors: Houle-Leroy Philippe , Garland Theodore , Swallow John G. , Guderley Helga
Published: December 2017

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly ( P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome- c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome- c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.
Invited Review: Effects of flow on vascular endothelial intracellular calcium signaling of rat aortas ex vivo
Authors: Jen Chauying J. , Jhiang Shuo-Ju , Chen Hsiun-Ing
Published: December 2017

To study the effects of flow on in situ endothelial intracellular calcium concentration ([Ca2+]i) signaling, rat aortic rings were loaded with fura 2, mounted on a tissue flow chamber, and divided into control and flow-pretreated groups. The latter was perfused with buffer at a shear stress of 50 dyns/cm2for 1 h. Endothelial [Ca2+]iresponses to ACh or shear stresses were determined by ratio image analysis. Moreover, ACh-induced [Ca2+]ielevation responses were measured in a calcium-free buffer, or in the presence of SKF-96365, to elucidate the role of calcium influx in the flow effects. Our results showed that 1) ACh increased endothelial [Ca2+]iin a dose-dependent manner, and these responses were incremented by flow-pretreatment; 2) the differences in ACh-induced [Ca2+]ielevation between control and flow-pretreated groups were abolished by SKF-96365 or by Ca2+-free buffer; and 3) in the presence of 10−5M ATP, shear stress induced dose-dependent [Ca2+]ielevation responses that were not altered by flow-pretreatment. In conclusion, flow-pretreatment augments the ACh-induced endothelial calcium influx in rat aortas ex vivo.
Transplantation and its biology: from fantasy to routine
Authors: Tilney Nicholas L.
Published: December 2017

The replacement of diseased organs and tissues by the healthy ones of others has been a unique milestone in modern medicine. For centuries, transplantation remained a theme of fantasy in literature and the arts. Within the past five decades, however, it has developed from a few isolated attempts to salvage occasional individuals with end-stage organ failure to a routine treatment for many patients. In parallel with the progressive improvements in clinical results has come an explosion in immunology, transplantation biology, immunogenetics, cell and molecular biology, pharmacology, and other relevant biosciences, with knowledge burgeoning at a rate not dreamed of by the original pioneers. Indeed, there have been few other instances in modern medicine in which so many scientific disciplines have contributed in concert toward understanding and treating such a complex clinical problem as the failure of vital organs. The field has been a dramatic example of evolution from an imagined process to an accepted form of therapy.
Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs
Authors: Diaz Véronique , Arsenault Julie , Praud Jean-Paul ,   (With the Technical Assistance of Bruno Gagné)
Published: December 2017

The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO2rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.
Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans
Authors: Harmer Alison R. , McKenna Michael J. , Sutton John R. , Snow Rodney J. , Ruell Patricia A. , Booth John , Thompson Martin W. , Mackay Nadine A. , Stathis Chris G. , Crameri Regina M. , Carey Michael F. , Eager Diane M.
Published: December 2017

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac−) and H+ concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K+ and norepinephrine concentrations were reduced ( P < 0.05). In PostExh, time to exhaustion was 21% greater than PreExh ( P < 0.001); however, muscle Lac− accumulation was unchanged; muscle H+concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac−, norepinephrine, and H+ concentrations were higher ( P < 0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.
Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance
Authors: Greer F. , Friars D. , Graham T. E.
Published: December 2017

This two-part investigation compared the ergogenic and metabolic effects of theophylline and caffeine. Initially ( part A), the ergogenic potential of theophylline on endurance exercise was investigated. Eight men cycled at 80% maximum O2consumption to exhaustion 90 min after ingesting either placebo (dextrose), caffeine (6 mg/kg; Caff), or theophylline (4.5 mg/kg Theolair; Theo). There was a significant increase in time to exhaustion in both the Caff (41.2 ± 4.8 min) and Theo (37.4 ± 5.0 min) trials compared with placebo (32.6 ± 3.4 min) ( P < 0.05). In part B, the effects of Theo on muscle metabolism were investigated and compared with Caff. Seven men cycled for 45 min at 70% maximum O2consumption (identical treatment protocol as in part A). Neither methylxanthines (MX) affected muscle glycogen utilization ( P > 0.05). Only Caff increased plasma epinephrine ( P < 0.05), but both MX increased blood glycerol levels ( P < 0.05). Muscle cAMP was increased ( P < 0.05) by both MX at 15 min and remained elevated at 45 min with Theo. This demonstrates that both MX are ergogenic and that this can be independent of muscle glycogen.
Preexercise carbohydrate ingestion, glucose kinetics, and muscle glycogen use: effect of the glycemic index
Authors: Febbraio Mark A. , Keenan Justin , Angus Damien J. , Campbell Shannon E. , Garnham Andrew P.
Published: December 2017

Eight trained men cycled at 70% peak oxygen uptake for 120 min followed by a 30-min performance cycle after ingesting either a high-glycemic index (HGI), low-glycemic index (LGI), or placebo (Con) meal 30 min before exercise. Ingestion of HGI resulted in an elevated ( P < 0.01) blood glucose concentration compared with LGI and Con. At the onset of exercise, blood glucose fell ( P < 0.05) such that it was lower ( P < 0.05) in HGI compared with LGI and Con at 15 and 30 min during exercise. Plasma insulin concentration was higher ( P < 0.01) throughout the rest period after ingestion of HGI compared with LGI and Con. Plasma free fatty acid concentrations were lower ( P < 0.05) throughout exercise in HGI compared with LGI and Con. The rates of [6,6-2H]glucose appearance and disappearance were higher ( P < 0.05) at rest after ingestion and throughout exercise in HGI compared with LGI and Con. Carbohydrate oxidation was higher ( P < 0.05) throughout exercise, whereas glycogen use tended ( P = 0.07) to be higher in HGI compared with LGI and Con. No differences were observed in work output during the performance cycle when comparing the three trials. These results demonstrate that preexercise carbohydrate feeding with a HGI, but not a LGI, meal augments carbohydrate utilization during exercise but does not effect exercise performance.