bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebellar role in the load-compensating response of expiratory muscle
Authors: Xu F. , Frazier D. T.
Published: December 2017

The hypothesis that the cerebellum is involved in the load-compensating response of expiratory muscles to expiratory tracheal occlusion was tested in anesthetized cats. A continuous expiratory threshold load (ETL; 5 cmH2O) was applied to elicit consistent phasic baseline electromyographic activity in the transversus abdominis muscle (EMGab). Tracheal occlusion for single expirations (TOE) were applied, and the evoked responses were compared in the intact and decerebellate preparation. Cold blockade of the dorsal spinal column (C5-7) and bilateral vagal inactivation (cold blockade or transection) were employed to determine the role of afferents from the lung, airways, chest wall, and diaphragm in shaping the cerebellar involvement in the motor response. The results showed that 1) decerebellation increased the baseline amplitude of the integrated EMGab (fEMGab) activity (P < 0.05) with little change in expiratory duration, 2) TOE applied after decerebellation markedly increased the expiratory duration compared with the intact values (P < 0.05), with little effect on the peak fEMGab, 3) cooling the dorsal spinal columns (C5-7) did not significantly affect EMGab responses in the intact or decerebellate preparations, and 4) vagal inactivation in the intact or decerebellate preparation significantly eliminated the fEMGab responses to ETL and TOE. We conclude that the cerebellum is involved in the modulation of transversus abdominis activity during ETL and TOE. Vagal afferents provide the major sensory input for the cerebellar modulation of the expiratory loading response.
Capsaicin-activated bronchial- and alveolar-initiated pathways regulating tracheal ciliary beat frequency
Authors: Eljamal M. , Wong L. B. , Yeates D. B.
Published: December 2017

We questioned whether the prolonged stimulation of ciliary beat frequency (CBF) to a short exposure of low-dose capsaicin (Wong et al. J. Appl. Physiol. 68: 257–2580, 1990) could be due to the activation of indirect pathways involving neural reflexes initiated independently in the bronchi and alveoli. Tracheal CBF (CBFtr) was measured temporally in anesthetized groups of 10 dogs by means of heterodyne-mode correlation analysis laser light scattering. To elucidate the site of the afferent neural stimulation and the efferent mediators affecting the ciliated epithelium, capsaicin (3 nM) aerosol was delivered for 4 min, either predominantly to the bronchi or to the alveolar regions, with use of pulsed aerosol techniques. This resulted in 13 pg of bronchial (85%) and 10 pg of alveolar (96%) capsaicin deposited, which caused marked stimulation of CBFtr with maxima at 7 and 35 min, respectively. Prior administration of aerosolized indomethacin to the bronchi or aerosolized cromolyn to the alveoli inhibited the bronchial and alveolar responses, respectively. Prior administration of aerosolized hexamethonium to the tracheal lumen blocked the stimulatory CBFtr responses from both capsaicin challenges. Ipratropium or propranolol aerosols delivered to the tracheal lumen also inhibited these responses. It is proposed that these pathways comprise one set of sensitive mechanisms to ensure a prolonged stimulation of CBF to effect the removal of secretions and the irritant from the lungs.
Continuous negative airway pressure increases tonic activity in diaphragm and intercostal muscles in humans
Authors: Meessen N. E. , van der Grinten C. P. , Luijendijk S. C. , Folgering H. T.
Published: December 2017

The main objective of the present study was to quantify the increase in tonic inspiratory activity (delta TIA) in response to continuous negative airway pressure (CNAP) in humans. TIA represents the activity in inspiratory muscles at the end of expiration. In 20 subjects, electromyograms (EMGs) were recorded from the diaphragm and parasternal intercostal muscles (ICM) with surface electrodes during control and at three different levels of CNAP (-0.3, -0.6, and -0.9 kPa; 1 kPa approximately 10 cmH2O). From these recordings we determined delta TIA and the amplitudes of phasic EMG activities (EMGphas) during CNAP and control. To evaluate the effects of CNAP on functional residual capacity (FRC), respiratory frequency, tidal volume, and minute ventilation, the subjects were connected to a closed breathing circuit. When the pressure at the airway opening was -0.9 kPa, mean values of delta TIA were 53 and 49% of control EMGphas for the diaphragm and ICM, respectively. In addition, EMGphas at airway opening pressure of -0.9 kPa had increased to 195 and 162% of control EMGphas for the diaphragm and ICM, respectively. The concomitant decrease in FRC was on average 18.7% of predicted FRC. Minute ventilation had increased significantly (P < 0.05) at all levels of CNAP compared with control. We conclude that CNAP is a forceful stimulus to increase TIA in humans in both the diaphragm and the ICM.
TGF-beta 1 causes increased endothelial ICAM-1 expression and lung injury
Authors: Suzuki Y. , Tanigaki T. , Heimer D. , Wang W. , Ross W. G. , Murphy G. A. , Sakai A. , Sussman H. H. , Vu T. H. , Raffin T. A.
Published: December 2017

Neutrophil adherence to vascular endothelium is partially mediated by adhesion molecules, including intracellular adhesion molecule 1 (ICAM-1), on endothelial cells. We examined the effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of ICAM-1 in human umbilical vein endothelial cells (HUVEC). TGF-beta 1 (1 ng/ml) increased ICAM-1 and ICAM-1 mRNA expression in HUVEC, as assessed by flow cytometry and Northern blot analysis, respectively. In addition, we investigated whether exogenous recombinant TGF-beta 1 can cause neutrophil-mediated lung injury in guinea pigs. The plasma half-life of 125I-labeled TGF-beta 1 in guinea pigs was 4.6 +/- 0.1 min, and the 125I activity was 2.8 +/- 0.2% 8 h after injection. The ratio of 125I-labeled albumin concentration in lung tissue and bronchoalveolar lavage (BAL) fluid to that in plasma, lung wet-to-dry weight ratio, numbers of neutrophils in BAL fluid, and numbers of neutrophils per alveolus in fixed lung sections increased in guinea pigs that received a high dose of TGF-beta 1 (25 micrograms i.v. followed by 2 micrograms/h for 8 h) compared with the control group. These results suggest that TGF-beta 1 causes neutrophil-mediated lung injury, possibly through upregulation of ICAM-1 on endothelial cells, and might be important in the pathogenesis of lung injury.
Effects of NO synthase inhibition on the muscular blood flow response to treadmill exercise in rats
Authors: Hirai T. , Visneski M. D. , Kearns K. J. , Zelis R. , Musch T. I.
Published: December 2017

The functional role of nitric oxide (NO) release in regulating blood flow (BF) to exercising skeletal muscle was studied in conscious male Sprague-Dawley rats (603 +/- 28 g; n = 6). In this study, BF was measured using radiolabeled microspheres during treadmill exercise (10% grade, 20 m/min) before and after NO synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (30 mg/kg ia). After NOS inhibition, mean arterial blood pressure increased from resting baseline values and the duration of vasodilator responses to acetylcholine (ACh) injections (3.0 and 10.0 micrograms/kg ia) was diminished (P < 0.05), demonstrating reduced NOS function. During exercise, BF to the kidneys and organs of the gut was reduced after NOS inhibition. In addition, BF was reduced in 16 of the 28 individual hindquarter muscles or muscle parts. Moreover these reductions in BF were linearly correlated with the estimated sum of the percentage of fast-twitch oxidative glycolytic (FOG) and slow-twitch oxidative (SO) types of fibers found in each muscle [delta BF = -1.1 (%SO + %FOG) + 16.4; r = 0.88, P < 0.001]. These results suggest that NO-mediated vasodilation contributes to the BF responses within and among the muscles of the rat's hindquarters during exercise.
Effect of hematocrit on systemic O2 transport in hypoxic and normoxic exercise in rats
Authors: Gonzalez N. C. , Erwig L. P. , Painter C. F. , Clancy R. L. , Wagner P. D.
Published: December 2017

The effect of hematocrit (Hct) on O2 transport in hypoxic [inspired PO2 (PIO2) approximately 70 Torr] and normoxic (PIO2 approximately 145 Torr) exercise was studied in rats acclimatized to 3 wk of PIO2 at approximately 70 Torr (A rats) and in nonacclimatized littermates (NA rats). Isovolumic exchange transfusion of plasma or red blood cells was used to lower Hct in A rats from approximately 60 to 45% and to raise Hct of NA rats from 45 to 60%: Controls were A and NA rats exchange transfused with whole blood at constant Hct. Lowering Hct of A rats lowered the arterial O2 concentration (CaO2) and the arterial-mixed venous O2 difference and increased the maximal cardiac output (Qmax) without changes in maximal O2 uptake (VO2 max) or in the product of Qmax x CaO2, circulatory O2 convection at maximal exercise (TO2 max). Raising Hct in NA rats produced the opposite changes in CaO2, arterial-mixed venous O2 difference, and Qmax, but VO2 max and TO2 max increased significantly, both in hypoxia and normoxia, because of relatively small changes in Qmax. In NA rats, a steeper slope of the line relating VO2 max to calculated mean capillary PO2 at high Hct suggested a higher tissue O2 diffusing capacity with high Hct. For a given Hct and Qmax, systemic arterial pressure was higher in A rats. The data suggest that 1) the effect of Hct on systemic hemodynamics is different in A and NA rats, resulting in different effects on VO2 max; 2) factors in addition to Hct contribute to the high systemic vascular resistance of A rats; and 3) increased diffusive conductance for O2, as well as increased TO2 max, could be responsible for the effect of Hct on VO2 max of NA rats.
Endurance exercise training is associated with elevated basal sympathetic nerve activity in healthy older humans
Authors: Ng A. V. , Callister R. , Johnson D. G. , Seals D. R.
Published: December 2017

We tested the hypothesis that endurance training is associated with altered basal levels of muscle sympathetic nerve activity (MSNA) and responses to acute stress in healthy older adults. MSNA (peroneal microneurography) and plasma norepinephrine (NE) concentrations were measured during supine rest, a cold pressor test, and isometric handgrip (40% maximal voluntary force to exhaustion) in 16 older masters endurance athletes [10 men, 6 women; 66 +/- 1 (SE) yr] and 15 healthy normotensive untrained control subjects (9 men, 6 women; 65 +/- 1 yr). The athletes had higher levels of estimated daily energy expenditure and maximal oxygen uptake and lower levels of resting heart rate and body fat than the control subjects (all P < 0.05). MSNA during supine rest was elevated in the athletes whether expressed as burst frequency (43 +/- 2 vs. 32 +/- 3 bursts/min, respectively; P < 0.05) or burst incidence (75 +/- 4 vs. 52 +/- 5 bursts/100 heartbeats, respectively; P < 0.01). These whole group differences were due primarily to markedly higher levels of MSNA in the athletic vs. untrained women (48 +/- 4 vs. 25 +/- 3 bursts/min, 82 +/- 3 vs. 38 +/- 3 bursts/100 heartbeats, respectively, P < 0.001). In contrast, basal plasma NE concentrations were not significantly different in the athletes vs. control subjects. The MSNA and plasma NE responses to acute stress tended to be greater in the athletes. These findings indicate that vigorous regular aerobic exercise is associated with an elevated level of MSNA at rest and a tendency for an enhanced response to acute stress in healthy normotensive older humans.
Decline running produces more sarcomeres in rat vastus intermedius muscle fibers than does incline running
Authors: Lynn R. , Morgan D. L.
Published: December 2017

Unaccustomed eccentric exercise, in which a muscle is lengthened while generating tension, is well known to cause injury and pain. A rapid training effect has been demonstrated in a number of eccentric exercises. The mechanism for both the damage and the training has been unknown. Morgan proposed that the damage is caused by sarcomere length instabilities during operation on the descending limb of the sarcomere length-tension curve and that the training effect is an increase in the number of sarcomeres connected in series in a muscle fiber, thus avoiding the descending limb (Biophys. J. 57: 209–221, 1990). We tested this proposal by exercising rats on a treadmill set at either an incline or a decline of 16 degrees, an exercise that has previously been shown to cause damage in untrained rats and a training effect. The vastus intermedius muscles were fixed and were digested in acid, and the fiber and sarcomere lengths of representative fibers were measured. From these measurements, the mean number of sarcomeres per fiber was found for the different training regimes. A clear and repeatable difference was found, supporting Morgan's prediction of more sarcomeres after decline running, although with some differences in response that depended on the age of the rats.
Effect of elastase on oscillation mechanics of lung parenchymal strips
Authors: Moretto A. , Dallaire M. , Romero P. , Ludwig M.
Published: December 2017

Using isolated parenchymal strips from degassed rat lungs, we studied the contribution of the collagen-elastin network to lung tissue hysteretic behavior. Strips were suspended in an organ bath filled with Krebs solution (37 degrees C, pH 7.4) continuously bubbled with 95% O2–5% CO2. One end of the strip was attached to a force transducer and the other to a servo-controlled lever arm. Sinusoidal oscillations of 2.5% of resting length were applied at 1 Hz. Measurements were sampled under baseline conditions at different levels of stress (sigma = 10–26 g/cm). Porcine pancreatic elastase (0.05 IU.mg tissue-1.ml Krebs solution-1) was then added to the bath, and tension and length were measured continuously for 15 min at sigma = 15 g/cm. After washout, measurements were repeated at sigma = 10–26 g/cm. Elastance (E) and resistance (R) were calculated using the equation of motion. Hysteresivity (eta), the structural damping coefficient, was obtained using the following equation: eta = (R/E) pi 2f, where f is frequency. At baseline, we found that E and R were significantly dependent on sigma (P < 0.01), whereas eta was unchanged. During enzymatic digestion with elastase, there were significant decreases of tension, E, and R and no change in eta. Significant increases in E and R were found when these parameters were compared at the same sigma before and after treatment. Again, eta did not change. The constancy of eta after elastase suggests that disruption of the elastin-collagen network does not alter the coupling between elastic and dissipative processes in lung tissue.
Effect of regional circulation patterns on observed HbCO levels
Authors: Smith M. V. , Hazucha M. J. , Benignus V. A. , Bromberg P. A.
Published: December 2017

In an earlier experiment, we briefly exposed 15 young men to high levels of CO while simultaneously monitoring arterial and peripheral venous HbCO levels. The arterial HbCO levels were considerably higher than the venous levels during the CO exposure. Furthermore, great variation in the difference between arterial and venous HbCO levels was observed, with the maximal difference for each subject ranging from 2.3 to 12.1% HbCO. In the present paper, we suggest an explanation for the observed differences between arterial and venous HbCO on the basis of the regional circulation of the forearm, where both samples were taken. Because regional circulation patterns are known to vary with physical training, the differences in physical training between subjects may account for the observed variation. An expanded model was derived from the Coburn-Forster-Kane equation, which reflects the above hypothesis. Most of the parameter values for the expanded model were measured on individual subjects. Literature values were used for other parameters. Two parameters were estimated using five of the subjects and were then used in the predictions of the expanded model for the remaining subjects.
Induction of mixed apneas by inhalation of 100% oxygen in preterm infants
Authors: Alvaro R. , Alvarez J. , Kwiatkowski K. , Cates D. , Rigatto H.
Published: December 2017

Administration of 100% O2 to preterm infants induces an apnea that is usually central. We hypothesized that this apnea may be “mixed” at times with an obstructive component appearing late during the respiratory pause. In addition, we reasoned that obstruction would depend on the duration of the apnea. Thus, we gave 100% O2 to 61 healthy preterm infants. Group 1 was > or = 1,500 g [birth wt 1.8 +/- 0.1 (SE) kg, gestational age 32 +/- 1 wk, postnatal age 19 +/- 2 days, n = 26] and group 2 was < 1,500 g [birth wt 1.2 +/- 0.1 kg, gestational age 29 +/- 1 wk, postnatal age 30 +/- 4 days, n = 35]. Ventilation was measured using a flow-through system. Respiratory efforts in the absence of flow were detected using chest and abdominal displacements or diaphragmatic electromyography. In group 1, 19% of the central apneas became obstructive at 17 +/- 3 s, whereas in group 2, 34% did so at 12 +/- 2 s. Mixed apneas were longer than those without obstruction (28 +/- 3 vs. 12 +/- 1 s; P = 0.0001). The incidence of mixed apneas was 0, 14, and 66% in group 1 and 0, 27, and 69% in group 2 in apneas of 3–10, 11–20, and > 20 s, respectively. These findings suggest that 1) a percentage of the central apneas induced by inhaling 100% O2 became obstructive, 2) the incidence of the obstructive component increased with the duration of apnea, and 3) smaller infants became obstructed sooner and had a higher incidence of obstruction than larger infants.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of lung volume and surface forces on maximal airway smooth muscle shortening
Authors: James A. , Pearce-Pinto G. , Hillman D.
Published: December 2017

The effects of lung volume and surface forces on airway smooth muscle shortening were studied in isolated perfused rat lungs. The lungs were inflated via the trachea with gas or Krebs solution (n = 12 each) to volumes equivalent to gas inflation pressures of 5 (low), 15 (medium), and 25 (high) cmH2O (n = 4 each). At each volume, two of the four lungs were perfused with methacholine (10(-2) M) and then all were perfused with Formalin for fixation. The amount of smooth muscle shortening present in transverse sections of the airways was determined by comparing the observed outer perimeter of the smooth muscle layer with its calculated relaxed perimeter. In the control lungs, mean shortening was < or = 10% in all groups except the liquid-filled lungs at low lung volumes [33 +/- 12% (SD)]. In the methacholine-stimulated lungs, mean shortening was between 45 and 56% at medium and low lung volumes in gas- and liquid-filled lungs, respectively, and approximated the degree of shortening required to cause airway closure. At high lung volume, less shortening was observed in the methacholine-stimulated lungs, either liquid (34 +/- 17%) or gas filled (16 +/- 19%; P < 0.05 compared with liquid filled). The effects of lung volume in liquid-filled lungs and the differences in response between gas- and liquid-filled lungs demonstrate, respectively, that both lung tissue recoil and surface forces act to oppose shortening of maximally stimulated smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Capacity for red blood cell aggregation is higher in athletic mammalian species than in sedentary species
Authors: Popel A. S. , Johnson P. C. , Kameneva M. V. , Wild M. A.
Published: December 2017

The purpose of this study was to show that two rheological parameters, red blood cell (RBC) sedimentation rate and apparent blood viscosity at low shear rate, characterizing the degree of RBC aggregation, correlate significantly with the maximal mass-specific rate of oxygen consumption or aerobic capacity (VO2max). Comparisons were made within two groups of similarly sized athletic and sedentary species: group 1, pronghorn antelope, dog, goat, and sheep; and group 2, horse and cow. The pronghorn antelope (Antilocapra americana) is one of the most athletic mammals, and we have obtained data on the rheological properties of blood from this species for the first time. The values of apparent viscosity at hematocrit = 40% and shear rate = 0.277 s-1 measured in a rotational viscometer were 59.5, 42.6, and 9.1 cP for antelope, dog, and sheep blood, respectively, and 55.3 and 11.5 cP for horse and cow blood, respectively. The viscosity values for antelope, dog, and sheep blood can be correlated with aerobic capacity: ln viscosity = 4.48–106.3 VO2(-1)max (r2 = 0.998; P < 0.05). The values of RBC sedimentation rate at hematocrit = 40% were 12.8, 7.0, and 0 mm/h for antelope, dog, and sheep blood, respectively, and 45.3 and 0.1 mm/h for horse and cow blood, respectively. Therefore, the data showed that the athletic species exhibit a consistently higher degree of RBC aggregation than do the corresponding nonathletic species.
Sidestream cigarette smoke exposure and airway reactivity during early life
Authors: Lai Y. L. , Thacker A. , Gairola C. G.
Published: December 2017

We established a guinea pig model to investigate effects of in utero and neonatal exposure to sidestream cigarette smoke (SSCS) on bronchial reactivity during early life. Animals were divided into four groups: 1) room air/room air, 2) sham/sham, 3) SSCS/room air, and 4) SSCS/SSCS. Pregnant and neonatal animals of group 1 breathed room air and those of group 2 were sham treated. Pregnant animals of both groups 3 and 4 as well as neonates of group 4 were exposed to SSCS. SSCS exposure was limited to between days 28 and 55 of pregnancy and days 8 and 24 of the neonatal period. Bronchial response to acetylcholine (ACh) and substance P (SP) were determined in very young animals at 25 days of age. Maximal expiratory flow was used as an index of airway dimension. SP, but not ACh, induced a significantly larger decrease in peak maximal expiratory flow in group 4, indicating an important role of neonatal SSCS exposure in augmenting bronchial response to SP. To further investigate the role of tachykinins in cigarette smoke-induced changes in bronchial reactivity, four additional groups (the same as above) of neonates were pretreated with capsaicin to deplete tachykinins. In the SSCS/SSCS group, SP-induced airway hyperreactivity was abolished by capsaicin pretreatment. Furthermore, in all four groups, capsaicin pretreatment abolished the bronchial response to SP but not the response to ACh. In additional very young animals, acute SSCS caused a nonsignificant increase in bronchial response to SP. These results indicate that chronic neonatal SSCS exposure induces bronchial hyperreactivity to SP; this hyperreactivity is abolished by capsaicin pretreatment.
Evaluation of dynamic response of catheter-manometer systems for pulmonary arterial pressure
Authors: Kinefuchi Y. , Suzuki T. , Takiguchi M. , Yamasaki Y. , Yamamoto M.
Published: December 2017

To quantitatively evaluate the waveform distortions observed through a catheter-manometer system, the tolerance range of amplitude errors and that of phase errors are defined as both within +/- 5%, and the frequency bandwidth was calculated where the frequency characteristics of amplitude and those of phase difference satisfy the two tolerance ranges by use of a second-order kinetic equation. The results were expressed by three variables, composed of the natural frequency (fn), damping coefficient (zeta), and highest frequency (fh) corresponding to the frequency bandwidth; a chart was constructed with fn on the x-axis, zeta on the y-axis, and fh as parameter. Also on the chart, the propagation delay times (td's) determined by fn, zeta, and fh were plotted. We measured the frequency characteristics of two 7-Fr Swan-Ganz catheters with lengths of 75 and 110 cm. fn's and zeta's were found to be 13.9 and 10.1 Hz and 0.23 and 0.32, respectively. Referring to this chart, the maximal fh these catheters would be able to reproduce within the tolerance ranges and the propagation td's can be predicted to be 3.2 and 2.4 Hz and 7 and 12 ms, respectively. Suppression of resonance by use of Accudynamic improved the maximal fh's to 3.9 and 2.9 Hz, respectively, but resulted in the increased td's to 14 and 19 ms due to increased zeta.
Exercise-induced oxidative stress: glutathione supplementation and deficiency
Authors: Sen C. K. , Atalay M. , Hanninen O.
Published: December 2017

Glutathione (GSH) plays a central role in coordinating the synergism between different lipid- and aqueous-phase antioxidants. We documented 1) how exogenous GSH and N-acetylcysteine (NAC) may affect exhaustive exercise-induced changes in tissue GSH status, lipid peroxides [thiobarbituric acid-reactive substances (TBARS)], and endurance and 2) the relative role of endogenous GSH in the circumvention of exercise-induced oxidative stress by using GSH-deficient [L-buthionine-(S,R)-sulfoximine (BSO)-treated] rats. Intraperitoneal injection of GSH remarkably increased plasma GSH; exogenous GSH per se was an ineffective delivery agent of GSH to tissues. Repeated administration of GSH (1 time/day for 3 days) increased blood and kidney total GSH [TGSH; GSH+oxidized GSH (GSSG)]. Neither GSH nor NAC influenced endurance to exhaustion. NAC decreased exercise-induced GSH oxidation in the lung and blood. BSO decreased TGSH pools in the liver, lung, blood, and plasma by approximately 50% and in skeletal muscle and heart by 80–90%. Compared with control, resting GSH-deficient rats had lower GSSG in the liver, red gastrocnemius muscle, heart, and blood; similar GSSG/TGSH ratios in the liver, heart, lung, blood, and plasma; higher GSSG/TGSH ratios in the skeletal muscle; and more TBARS in skeletal muscle, heart, and plasma. In contrast to control, exhaustive exercise of GSH-deficient rats did not decrease TGSH in the liver, muscle, or heart or increase TGSH of plasma; GSSG of muscle, blood, or plasma; or TBARS of plasma or muscle. GSH-deficient rats had approximately 50% reduced endurance, which suggests a critical role of endogenous GSH in the circumvention of exercise-induced oxidative stress and as a determinant of exercise performance.
Effects of altered muscle activation on oxidative enzyme activity in rat alpha-motoneurons
Authors: Seburn K. , Coicou C. , Gardiner P.
Published: December 2017

Some controversy exists as to whether alpha-motoneurons adapt their oxidative metabolism to changes in chronic activity levels and to altered status of their end organs, as occurs in other neuron types in the central nervous system. We measured, using a personal computer-based image analysis system, succinate dehydrogenase (SDH) activity in rat hindlimb motoneurons under conditions of increased activity (daily voluntary exercise plus treadmill endurance training, the latter 2 h/day, 4 days/wk, for 12 wk) and in a condition of muscle disuse (tetrodotoxin-induced paralysis for 2 wk) in which muscle oxidative enzymes are reduced. Although exercise-trained medial gastrocnemius showed significant adaptations (increased mean SDH activity of type I and increased proportion and total SDH activity of type I and combined I + IIa fibers), SDH activity of innervating motoneurons (identified by retrograde tracing using fast blue) was unchanged. In addition, tetrodotoxin-induced disuse, which results in hindlimb atrophy and SDH decreases (30% decrease measured in medial gastrocnemius muscle homogenates), failed to alter soma SDH or size in unspecified lumbar motoneurons. These results, obtained over a wider range of activity levels than in previous reports, suggest that the oxidative enzymes of motoneurons do not change despite clear adaptations in the muscles they innervate.
Blood lactate and acid-base balance in graded neonatal hypoxia: evidence for oxygen-restricted metabolism
Authors: Torrance S. M. , Wittnich C.
Published: December 2017

This study examines the neonatal response to graded hypoxia and determines the arterial PO2 (PaO2) threshold for oxygen-restricted metabolism as confirmed by the development of lactic acidosis and altered oxygen handling. Anesthetized, intubated, and ventilated 3-day-old pigs (n = 56) were randomly assigned to one of five predetermined acute (120 min) graded hypoxia groups: normoxia (PaO2 = 80 Torr) or mild (60 Torr), moderate (40 Torr), moderately severe (30 Torr), or severe (20 Torr) hypoxia. In moderate hypoxia, lactate and acid-base homeostasis were unaltered due to a significant increase in oxygen extraction (P < 0.05) that was sufficient to maintain the arteriovenous oxygen content difference (oxygen uptake). In moderately severe hypoxia, increased arterial lactate and decreased HCO3- and base excess were evidence of anaerobic metabolism, yet pH was unaltered, indicating adequate buffering. In this group, despite the increase in oxygen extraction, oxygen uptake was reduced, indicating the onset of oxygen-restricted metabolism. The severe hypoxia group had significantly increased lactate (21.7 +/- 3.9 mmol/l), decreased pH (7.01 +/- 0.07) and base excess (-21.5 +/- 3.0 mmol/l), and depletion of HCO3- (9.7 +/- 1.6 mmol/l) (P < 0.0001). Here, increases in oxygen extraction were severely limited by availability, resulting in significantly reduced oxygen uptake, anaerobic metabolism, and profound lactic acidosis.
Glucocorticoids inhibit sulfur mustard-induced airway muscle hyperresponsiveness to substance P
Authors: Calvet J. H. , D'Ortho M. P. , Jarreau P. H. , Levame M. , Harf A. , Macquin-Mavier I.
Published: December 2017

To explore the mechanisms of airway hyperreactivity to aerosolized substance P observed in guinea pigs 14 days after intratracheal injection of sulfur mustard (SM), we studied the effects of epithelium removal and inhibition of neutral endopeptidase (NEP) activity on airway muscle responsiveness. Tracheal rings from SM-intoxicated guinea pigs expressed a greater contractile response to substance P than rings from nonintoxicated guinea pigs. After epithelium removal or incubation with the NEP inhibitor phosphoramidon, the contractile responses of tracheal rings to substance P did not differ in guinea pigs injected with SM or ethanol (SM solvent). Treatment of the guinea pigs with betamethasone for 7 days before measurement abolished the airway muscle hyperresponsiveness observed in untreated SM-intoxicated guinea pigs and partially restored tracheal epithelium NEP activity. In addition, the tracheal epithelium height and cell density of SM-intoxicated guinea pigs treated with betamethasone were significantly greater than in those without betamethasone. These results demonstrate that SM intoxication induces airway muscle hyperresponsiveness to substance P by reducing tracheal epithelial NEP activity and that glucocorticoids might inhibit this hyperresponsiveness by increasing this activity.
Effect of hyperbaric oxygen on tissue distribution of mononuclear cell subsets in the rat
Authors: Bitterman N. , Lahat N. , Rosenwald T. , Kinarty A. , Melamed Y. , Bitterman H.
Published: December 2017

In a previous study we found a significant temporary decrease in the ratio of CD4/CD8 (helper, inducer/suppressor, cytotoxic) T lymphocytes in the peripheral blood of healthy human volunteers after exposure to a single commonly used profile of hyperbaric oxygen (HBO). The transient nature of the changes suggested redistribution of T-cell subsets. The purpose of the present study was to verify such a redistribution and to locate possible target organs in an animal model. A single exposure of rats to HBO (0.28 MPa) induced a highly significant rapid decrease in the CD4/CD8 ratio in peripheral blood count (P < 0.0001), confirming our previous findings in humans. HBO also induced a significant increase in the CD4/CD8 ratio in the lungs and lymph nodes (P < 0.001) and a significant decrease in the ratio in the spleen (P < 0.01). Furthermore, exposure to HBO induced a significant increase in T cells bearing surface interleukin-2 receptors in the blood, spleen, lungs, and lymph glands (P < 0.001) and a significant decrease in T cells expressing alpha beta-receptors in the lungs (P < 0.001) and lymph glands (P < 0.05). Our findings suggest rapid T-cell activation after a brief exposure to HBO, with shifts of CD4 and CD8 subsets and variations in T-cell receptor type. These rapid changes in the parameters of cell-mediated immunity may represent the activation of protective mechanisms against the toxic effect of oxygen or the early stages of pulmonary oxygen toxicity.
Cardiopulmonary effects of granulocyte colony-stimulating factor in a canine model of bacterial sepsis
Authors: Eichacker P. Q. , Waisman Y. , Natanson C. , Farese A. , Hoffman W. D. , Banks S. M. , MacVittie T. J.
Published: December 2017

We investigated the effects of recombinant granulocyte colony-stimulating factor (G-CSF) in a canine model of septic shock. Awake 2-yr-old beagles were studied before and after intraperitoneal placement of an Escherichia coli-infected clot. Nine days before and until 3 days after clot placement, animals received daily high-dose (G-CSF (5 microgram/kg body wt; n = 17), low-dose G-CSF (0.1 microgram/kg body wt; n = 17), or a control protein (5 micrograms/kg body wt; n = 20). Survival rate was greater (P < 0.04, Wilcoxon test) in the high-dose G-CSF group (14/17) than in the low-dose G-CSF (10/17) and control (12/20) groups. High-dose G-CSF improved cardiovascular function, as evidenced by increased left ventricular ejection fraction (day 1 after clot; P < 0.001) and mean arterial pressure (day 2; P < 0.02) compared with low-dose G-CSF and control groups. High-dose G-CSF increased (P < 0.001) mean peripheral neutrophils before (-3 days) and after (2 h to 4 days) clot and produced a more rapid (P < 0.001) rise (day 2) and fall (day 4) in mean alveolar neutrophil numbers compared with the low-dose G-CSF and control groups. High-dose G-CSF decreased mean serum endotoxin (2–8 h; P < 0.002) and tumor necrosis factor (2 h; P < 0.02) levels and lowered blood bacteria counts (2–6 h; P < 0.04) compared with the low-dose G-CSF and control groups. Thus, in this canine model, G-CSF sufficient to increase peripheral neutrophils before and during peritonitis and septic shock enhances host defense, reduces cytokine (tumor necrosis factor) levels, and improves cardiovascular function and survival.
Effects of sprint cycle training on human skeletal muscle
Authors: Allemeier C. A. , Fry A. C. , Johnson P. , Hikida R. S. , Hagerman F. C. , Staron R. S.
Published: December 2017

Eleven men sprint trained two to three times per week for 6 wk to investigate possible exercise-induced slow-to-fast fiber type conversions. Six individuals served as controls. Both groups were tested at the beginning and end of the study to determine anaerobic performance and maximal oxygen consumption. In addition, pre- and postbiopsies were extracted from the vastus lateralis muscle and were analyzed for fiber type composition, cross-sectional area, and myosin heavy chain (MHC) content. No significant changes were found in anaerobic or aerobic performance variables for either group. Although a trend was found for a decrease in the percentage of type IIb fibers, high-intensity sprint cycle training caused no significant changes in the fiber type distribution or cross-sectional area. However, the training protocol did result in a significant decrease in MHC IIb with a concomitant increase in MHC IIa for the training men. These data appear to support previous investigations that have suggested exercise-induced adaptations within the fast fiber population (IIb-->IIa) after various types of training (endurance and strength).
Use of scaling theory to relate measurements of lung endothelial barrier permeability
Authors: Harris T. R. , Waters C. M. , Haselton F. R.
Published: December 2017

This work examined the relationships between lung microvascular permeability-surface area products (PS) for small solutes in animals of different size and for columns of endothelial-covered microcarrier beads. We assembled PS data (humans, sheep, lambs, and rabbits) for labeled sucrose, mannitol, urea, 1,2-propanediol, 1,3-propanediol, and 1,4-butanediol. In addition, PS for cell columns using sucrose, mannitol, and sodium fluorescein were evaluated. A new mathematical model for the analysis of cell columns that accounts for transit time variations was derived and compared with models neglecting this variation. Allometric relationships between PS and body weight or exchange surface (S) were examined. Permeability relative to diffusivity (P/D) correlated inversely with S for all animals. In addition, P/D for the cell columns fell near this regression line. The results suggest either that permeability for hydrophilic tracers is higher for smaller animals or that the indicator-dilution measurement is a fractal process dependent on scale. Furthermore, the P/D-S correlations may help relate cell column experiments to animal studies.
Sympathetic and parasympathetic indicators of heart rate control at altitude studied by spectral analysis
Authors: Hughson R. L. , Yamamoto Y. , McCullough R. E. , Sutton J. R. , Reeves J. T.
Published: December 2017

The adaptive responses of the cardiovascular system to altitude appear to be dominated by increased sympathetic neural activity. We investigated the combined roles of the sympathetic and parasympathetic nervous systems (SNS and PNS, respectively) in the early (days 4–5) and subsequent (days 11–12) phases of acclimatization on Pike's Peak, CO (4,300 m), by spectral analysis of heart rate variability. Male subjects were randomly assigned to groups receiving oral propranolol (240 mg/day; n = 6) or a matched placebo (n = 3). On ascent to altitude, the high-frequency, fractal, and total spectral powers were reduced in the placebo group during days 4–5 and 11–12. At altitude during days 4–5, all three placebo group subjects increased SNS and decreased PNS activities compared with at sea level, and during days 11–12 SNS decreased and PNS increased compared with days 4–5. Relative to the placebo group, propranolol caused lengthening of the R-R interval; increases in high-frequency power, total spectral power, and the PNS indicator; and a decrease in the SNS indicator. Total spectral power tended to decrease at altitude, but there were no effects of altitude on PNS and SNS indicators in the propranolol group. The data from the placebo and propranolol groups suggest that both the PNS and SNS are involved in the elevated heart rate during the early phase of altitude acclimatization. Changes in heart rate variability during days 11–12 at altitude must be considered in light of the possible reductions in sympathetic receptor number noted in previous studies.
Contribution of potassium to exercise-induced vasodilation in humans
Authors: Wilson J. R. , Kapoor S. C. , Krishna G. G.
Published: December 2017

It has been postulated that skeletal muscle release of potassium contributes to exercise-induced vasodilation of skeletal muscle arterioles. To determine whether potassium produces muscle arteriolar vasodilation in humans, we measured plethysmographic forearm blood flow and brachial venous potassium concentrations during brachial arterial infusion of potassium (0.6, 3, 6, 15, and 30 mueq.min-1.100 ml forearm volume-1) in nine normal subjects. Infusion of potassium decreased forearm vascular resistance, with an increase in brachial venous potassium of 1 meq/l decreasing forearm vascular tone by 25–30%. We then measured plasma potassium concentrations during forearm and upright bicycle exercise in 15 normal subjects. Forearm exercise at 0.6 W decreased forearm vascular resistance by 83%, whereas brachial venous potassium increased by only 0.5 +/- 0.2 meq/l (both P < 0.05). Maximal bicycle exercise increased systemic potassium concentrations by 1.2 +/- 0.2 meq/l. These findings indicate that potassium produces muscle arteriolar vasodilation in humans and therefore supports the hypothesis that potassium release from exercising muscle contributes to exercise-induced vasodilation. The relatively small change in venous potassium noted during forearm exercise despite marked forearm vasodilation suggests that local potassium release is only a small contributor to exercise-induced vasodilation. However, potassium release during maximal exercise may have significant vasodilatory effects on arterioles both in exercising and nonexercising tissues.
Training-related enhancement in the control of motor output in elderly humans
Authors: Keen D. A. , Yue G. H. , Enoka R. M.
Published: December 2017

The increase in motor unit force that occurs with aging has been hypothesized to cause a decline in the ability to maintain a constant submaximal force. To test this hypothesis, young and elderly subjects performed a 12-wk strength-training program that was intended to increase motor unit force. The training program caused similar increases (%initial) in the training load (137.4 +/- 17.2%), twitch force (23.1 +/- 7.4%), and maximum voluntary contraction force (39.2 +/- 6.8%) of the first dorsal interosseus muscle for the young and elderly subjects. The increase in strength was associated with a modest increase in muscle volume (7% of initial value) and a nonmonotonic increase in the surface-recorded electromyogram that was significant at week 8 but not at week 12. The elderly subjects reduced the variability in force at the lower target forces (2.5, 5.0, and 20.0% maximum voluntary contraction force). This improvement, however, was unrelated to changes in the distribution of motor unit forces, which was not consistent with the hypothesis that the greater coefficient of variation for the force fluctuations is due to increased motor unit forces.
Effect of hypercapnia on laryngeal airway resistance in normal adult humans
Authors: Kuna S. T. , Vanoye C. R. , Griffin J. R. , Updegrove J. D.
Published: December 2017

Laryngeal airway resistance (Rlar) was measured in eight normal adult humans during progressive hyperoxic hypercapnia. In most subjects, the translaryngeal pressure-flow relationship appeared linear under normocapnic conditions. During hypercapnia, the pressure-flow relationship on inspiration and expiration was curvilinear with increasing translaryngeal pressure associated with progressively smaller increments in flow. Translaryngeal pressure-flow relationships at different CO2 levels were compared over their common flow ranges by performing a least-squares linear regression on data throughout inspiration and expiration. During normocapnia, the mean slope, i.e., mean Rlar, was 0.50 +/- 0.21 (SD) cmH2O.l-1.s. A moderately significant decrease in Rlar was present at 9% end-tidal CO2 (P = 0.08). In a separate series of experiments, subjects breathed oxygen- and helium-based gas mixtures through a face mask attached to a pneumotachograph. Data analysis over the flow range present during normocapnia revealed no difference in Rlar between nose and mouth breathing and similar decreases in Rlar under hypercapnic conditions with the oxygen- and helium-based gas mixtures. The decrease in Rlar from normocapnic to hypercapnic conditions found over common, but relatively low, ranges of flow predicts that even greater increases in Rlar would occur at high flow rates in the absence of increasing glottic aperture.
Effect of acclimatization to high altitude (5,050 m) on motor unit activation pattern and muscle performance
Authors: Orizio C. , Esposito F. , Veicsteinas A.
Published: December 2017

This study evaluated the influence of acute and chronic hypoxia (up to 40 days at 5,050 m) on the muscle strength, fast-to-slow fiber motor unit (MU) ratio, and MU activation strategy. These factors were studied by measuring the maximal voluntary contraction (MVC) of the elbow flexors and analyzing surface electromyogram (EMG) and soundmyogram (SMG) of the isometrically contracting biceps brachii. From the time and frequency domain analysis of EMG and SMG, the root mean square and mean frequency of the spectra were calculated. SMG and EMG were recorded during 4-s exercises in the 20–100% MVC range before departure; after 2, 15, and 40 days at high altitude; and after the return to sea level. MVC or root mean square and mean frequency at all levels of effort were not significantly different among all experimental conditions. In the present study where optimal living conditions (i.e., food, physical activity, and environmental temperature) were ensured, acute and chronic hypoxia (at least up to 40 days) did not affect the maximal force output or fast-to-slow fiber MU ratio and MU activation pattern during isometric exercise.
Myocardial edema, left ventricular function, and pulmonary hypertension
Authors: Davis K. L. , Mehlhorn U. , Laine G. A. , Allen S. J.
Published: December 2017

Left ventricular dysfunction has been reported in both experimentally induced and clinical pulmonary hypertension. However, the mechanism by which pulmonary hypertension causes left ventricular dysfunction is unknown. We hypothesized that acute pulmonary hypertension causes left ventricular myocardial interstitial edema and that it is this edema that causes left ventricular dysfunction. In pulmonary artery-banded or sham-operated dogs, left ventricular diameter (septal-free wall axis) and pressure were measured using sonomicrometry crystals and a micromanometer, respectively. These measurements were used to calculate preload recruitable stroke work (PRSW), an index of contractility, and the rate of active relaxation (tau) to assess systolic and diastolic left ventricular function, respectively. After 3 h of pulmonary arterial hypertension or control, the dogs were killed and the left ventricles were excised to determine wet-to-dry weight ratios. The wet-to-dry weight ratios were significantly higher in the pulmonary artery-banded dogs (3.57 +/- 0.12) than in the sham-operated dogs (3.41 +/- 0.17). PRSW decreased to 56.8 +/- 30.3% of control after 3 h of pulmonary hypertension. tau Slowed significantly from 29.8 +/- 5.8 ms at baseline to 63.6 +/- 30.4 ms after 3 h of pulmonary arterial hypertension. There were no differences in PRSW or tau in the sham-operated dogs. We conclude that pulmonary hypertension causes left ventricular myocardial interstitial edema, which results in both systolic and diastolic left ventricular dysfunction.
Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release
Authors: Leikauf G. D. , Fink S. P. , Miller M. L. , Lockey J. E. , Driscoll K. E.
Published: December 2017

Refractory ceramic fiber has been developed for industrial processes requiring materials with high thermal and mechanical stability. To evaluate the biological activity of this fiber, rat alveolar macrophages were exposed for < or = 24 h to 0–1,000 micrograms/ml of refractory ceramic fiber, crocidolite asbestos, silica (fibrogenic particles), or titanium dioxide (a nonfibrogenic particle), and eicosanoid, tumor necrosis factor-alpha (TNF), and lactate dehydrogenase release were measured. Particle dimensions were determined by electron microscopy. Radioactivity coeluting with leukotriene B4 (LTB4) and immunoreactive LTB4 and TNF release increased after refractory ceramic fiber and were similar in magnitude after asbestos but less than after silica. For example, the total [3H]eicosanoid release increased 3.9-fold after refractory ceramic fiber, 4.6-fold after asbestos, and 8.7-fold after silica. Refractory ceramic fiber and asbestos also have similar particle dimensions (diameter, length, and surface area). Inasmuch as macrophage-derived LTB4 and TNF are potent mediators in inflammatory events, including migration and activation of neutrophils, these findings suggest that refractory ceramic fiber can activate macrophages in vitro to release mediators relevant to in vivo findings of inflammation and fibrotic lung disease in laboratory animals.