bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of expiratory flow limitation in determining lung volumes and ventilation during exercise
Authors: McClaran Steven R. , Wetter Thomas J. , Pegelow David F. , Dempsey Jerome A.
Published: December 2017

We determined the role of expiratory flow limitation (EFL) on the ventilatory response to heavy exercise in six trained male cyclists [maximal O2uptake = 65 ± 8 (range 55–74) ml ⋅ kg−1⋅ min−1] with normal lung function. Each subject completed four progressive cycle ergometer tests to exhaustion in random order: two trials while breathing N2O2(26% O2-balance N2), one with and one without added dead space, and two trials while breathing HeO2(26% O2-balance He), one with and one without added dead space. EFL was defined by the proximity of the tidal to the maximal flow-volume loop. With N2O2during heavy and maximal exercise, 1) EFL was present in all six subjects during heavy [19 ± 2% of tidal volume (Vt) intersected the maximal flow-volume loop] and maximal exercise (43 ± 8% of Vt), 2) the slopes of the ventilation (ΔV˙e) and peak esophageal pressure responses to added dead space (e.g., ΔV˙e/[Formula: see text], where [Formula: see text] is end-tidal[Formula: see text]) were reduced relative to submaximal exercise, 3) end-expiratory lung volume (EELV) increased and end-inspiratory lung volume reached a plateau at 88–91% of total lung capacity, and 4) Vt reached a plateau and then fell as work rate increased. With HeO2(compared with N2O2) breathing during heavy and maximal exercise, 1) HeO2increased maximal flow rates (from 20 to 38%) throughout the range of vital capacity, which reduced EFL in all subjects during tidal breathing, 2) the gains of the ventilatory and inspiratory esophageal pressure responses to added dead space increased over those during room air breathing and were similar at all exercise intensities, 3) EELV was lower and end-inspiratory lung volume remained near 90% of total lung capacity, and 4) Vt was increased relative to room air breathing. We conclude that EFL or even impending EFL during heavy and maximal exercise and with added dead space in fit subjects causes EELV to increase, reduces the Vt, and constrains the increase in respiratory motor output and ventilation.
Serum levels of total and free IGF-I and IGFBP-3 are increased and maintained in long-term training
Authors: Koziris L. P. , Hickson R. C. , Chatterton R. T. , Groseth R. T. , Christie J. M. , Goldflies D. G. , Unterman T. G.
Published: December 2017

The goals of this study were to determine whether the long-term training regimens experienced by competitive collegiate swimmers would result in altered levels of total and free serum insulin-like growth factor I (IGF-I) as well as IGF-binding proteins (BP) IGFBP-1 and -3. Two male (Teams 1M and 2M) and one female (Team 2F) teams were studied at the start of training, after 2 mo of training, after 4 mo (2–4 mo had the highest volume of training), after 5 mo (near the end of tapering; only for Team 1M), and several days after training was over. For Team 1M, total IGF-I concentrations were increased by 76% after 4 mo and were subsequently maintained at this level. Total IGF-I responses were more variable for Teams 2F and 2M. Free IGF-I levels were increased nearly twofold for all teams at 2 mo and were maintained or increased further with subsequent training. Only the levels of free IGF-I for Team 1M returned to pretraining values after training had ended. Training had little effect on IGFBP-1 levels. For all teams, serum IGFBP-3 was elevated by 4 mo of training (for Team 2F it was increased at 2 mo) by 30–97% and remained at these higher levels thereafter. The ratio of total IGF-I to IGFBP-3 was not increased by training in any group. These data indicate that serum levels of total and free IGF-I and total IGFBP-3 can be increased with intense training and maintained with reduced training (tapering). The findings show that changes in free IGF-I levels are not accounted for by alterations in the total IGF-I/IGFBP-3 complex or in IGFBP-3 levels and indicate that there are other important determinants of free IGF-I.
Red cell distribution and the recruitment of pulmonary diffusing capacity
Authors: Hsia Connie C. W. , Johnson Robert L. , Shah Dipen
Published: December 2017

The distribution of red blood cells in alveolar capillaries is typically nonuniform, as shown by intravital microscopy and in alveolar tissue fixed in situ. To determine the effects of red cell distribution on pulmonary diffusive gas transport, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of red blood cells. Red blood cells are spaced uniformly, randomly, or clustered without overlap within the capillary. Total CO diffusing capacity (Dl CO) and membrane diffusing capacity (DmCO) are calculated by a finite-element method. Results show that distribution of red blood cells at a fixed hematocrit greatly affects capillary CO uptake. At any given average capillary red cell density, the uniform distribution of red blood cells yields the highest DmCO and Dl CO, whereas the clustered distribution yields the lowest values. Random nonuniform distribution of red blood cells within a single capillary segment reduces diffusive CO uptake by up to 30%. Nonuniform distribution of red blood cells among separate capillary segments can reduce diffusive CO uptake by >50%. This analysis demonstrates that pulmonary microvascular recruitment for gas exchange does not depend solely on the number of patent capillaries or the hematocrit; simple redistribution of red blood cells within capillaries can potentially account for 50% of the observed physiological recruitment of Dl CO from rest to exercise.
Oxygenation of the cat primary visual cortex
Authors: Padnick Lissa B. , Linsenmeier Robert A. , Goldstick Thomas K.
Published: December 2017

Tissue [Formula: see text] was measured in the primary visual cortex of anesthetized, artificially ventilated normovolemic cats to examine tissue oxygenation with respect to depth. The method utilized 1) a chamber designed to maintain cerebrospinal fluid pressure and prevent ambient[Formula: see text] from influencing the brain, 2) a microelectrode capable of recording electrical activity as well as local[Formula: see text], and 3) recordings primarily during electrode withdrawal from the cortex rather than during penetrations. Local peaks in the [Formula: see text] profiles were consistent with the presence of numerous vessels. Excluding the superficial 200 μm of the cortex, in which the ambient[Formula: see text] may have influenced tissue[Formula: see text], there was a slight decrease (4.9 Torr/mm cortex) in [Formula: see text] as a function of depth. After all depths and cats were weighted equally, the average [Formula: see text] in six cats was 12.8 Torr, with approximately one-half of the values being ≤10 Torr. The kurtosis of the [Formula: see text] histogram, with all depths and cats weighted equally, was 3.61, and the skewness was 1.70.
Effect of ultrasonically nebulized distilled water on airway epithelial cell swelling in guinea pigs
Authors: Mochizuki Hiroyuki , Ohki Yasushi , Arakawa Hirokazu , Tokuyama Kenichi , Morikawa Akihiro
Published: December 2017

To investigate the pathogenesis of ultrasonically nebulized distilled water-induced airway narrowing, we studied the role of airway epithelial cells during a distilled water-inhalation challenge in an animal model of airway inflammation. Guinea pigs were divided into four groups: 1) a sham/saline (S/S) group: sham ozone followed by saline inhalation; 2) a sham/water (S/W) group: sham ozone followed by water inhalation; 3) an ozone/saline (O/S) group: ozone followed by saline inhalation; and 4) an ozone/water (O/W) group: ozone followed by water inhalation. After exposure to either 3.0 parts/million ozone or air at the same flow rate for 2 h, guinea pigs were anesthetized and tracheostomized, and then lung resistance (Rl) was measured. For morphometric assessment, tissues were fixed with formaldehyde, stained with hematoxylin and eosin, and cut into transverse sections. Airway dimensions were either measured directly or calculated from the internal perimeter, the external perimeter, and airway wall area. There were no statistical differences in the values of Rl before distilled water inhalation between the sham groups and the ozone groups. Rl increased significantly after 10 min of distilled water inhalation in both the S/W group and the O/W group. In the S/W group, epithelial cells were swollen, and intercellular spaces were wider, resulting in significant increase in epithelial wall thickness, but there was no significant infiltration by inflammatory cells. In the O/S group, the epithelium showed infiltration by inflammatory cells without change in cell volume. In the O/W group, the epithelium showed both infiltration and a greater increase in epithelial wall thickness compared with the S/W group. These results suggest that airway epithelial cell swelling, induced by inhaled distilled water, increases with Rl in guinea pigs and that this reaction may be accelerated by airway inflammation.
Effects of feeding frequency and voluntary salt intake on fluid and electrolyte regulation in athletic horses
Authors: Jansson Anna , Dahlborn Kristina
Published: December 2017

The effect of feeding frequency and voluntary sodium intake (VSI) on fluid shifts and plasma aldosterone concentration (PAC) were studied at rest and after exercise in six athletic horses. The horses were fed twice a day (2TD) and six times a day (6TD) for 25 days for each protocol, according to a changeover design. VSI was measured by weighing each horse’s salt block daily. Feeding 2TD or 6TD caused no major alterations in fluid shifts, but in the 2TD treatment there was a postprandial increase in plasma protein concentration and osmolality that lasted <1 h. PAC and VSI were not affected by feeding frequency. VSI ranged from 0 to 62 mg ⋅ kg body weight−1⋅ day−1and caused significant alterations in PAC. At VSI <26 mg ⋅ kg body weight−1⋅ day−1, a diurnal rhythm for PAC was noted. Water intake, fecal concentrations of sodium and potassium, and packed cell volume during exercise were influenced by VSI. The response to exercise did not differ between treatments. In conclusion, VSI, but not feeding frequency, has significant effects on fluid and electrolyte regulation in athletic horses.
Biophysical characterization and modeling of lung surfactant components
Authors: Ingenito E. P. , Mark L. , Morris J. , Espinosa F. F. , Kamm R. D. , Johnson M.
Published: December 2017

The present study characterizes the dynamic interfacial properties of calf lung surfactant (CLS) and samples reconstituted in a stepwise fashion from phospholipid (PL), hydrophobic apoprotein (HA), surfactant apoprotein A (SP-A), and neutral lipid fractions. Dipalmitoylphosphatidylcholine (DPPC), the major PL component of surfactant, was examined for comparison. Surface tension was measured over a range of oscillation frequencies (1–100 cycles/min) and bulk phase concentrations (0.01–1 mg/ml) by using a pulsating bubble surfactometer. Distinct differences in behavior were seen between samples. These differences were interpreted by using a previously validated model of surfactant adsorption kinetics that describes function in terms of 1) adsorption rate coefficient ( k1), 2) desorption rate coefficient ( k2), 3) minimum equilibrium surface tension (γ*), 4) minimum surface tension at film collapse (γmin), and 5) change in surface tension with interfacial area for γ < γ* ( m2). Results show that DPPC and PL have k1and k2values several orders of magnitude lower than CLS. PL had a γminof 19–20 dyn/cm, significantly greater than CLS (nearly zero). Addition of the HA to PL restored dynamic interfacial behavior to nearly that of CLS. However, m2remained at a reduced level. Addition of the SP-A to PL + HA restored m2to a level similar to that of CLS. No further improvement in function occurred with the addition of the neutral lipid. These results support prior studies that show addition of HA to the PL markedly increases adsorption and film stability. However, SP-A is required to completely normalize dynamic behavior.
Selective in vivo inhibition of inducible nitric oxide synthase in a rat model of sepsis
Authors: Scott J. A. , McCormack D. G.
Published: December 2017

Elevated production of nitric oxide (NO) by the inducible NO synthase (type II, iNOS) may contribute to the vascular hyporesponsiveness and hemodynamic alterations associated with sepsis. Selective inhibition of this isoenzyme is a possible therapeutic intervention to correct these pathophysiological alterations. Aminoguanidine has been shown to be a selective iNOS inhibitor and to correct the endotoxin-mediated vascular hypocontractility in vitro. However, to date aminoguanidine has not been shown to selectively block iNOS activity in vivo. The in vivo effects of aminoguanidine were assessed in the cecal ligation and perforation model of sepsis in rats. Aminoguanidine (1.75–175 mg/kg) was administered to septic and sham-operated rats for 3 h before euthanasia and harvest of tissues. NOS activities were determined in the thoracic aorta and lung from these animals. Aminoguanidine (17.5 mg/kg) did not alter the mean arterial pressure; however, it did inhibit induced iNOS (but not constitutive NOS) activity in the lung and thoracic aorta from septic animals. Only the higher dose of aminoguanidine (175 mg/kg) was able to increase the mean arterial pressure in septic and sham-operated animals. Thus selective inhibition of iNOS in vivo with aminoguanidine is possible, but our data suggest that other mechanisms, in addition to iNOS induction, are responsible for the loss of vascular tone characteristic of sepsis.
Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining
Authors: Katayama Keisho , Sato Yasutake , Morotome Yoshifumi , Shima Norihiro , Ishida Koji , Mori Shigeo , Miyamura Miharu
Published: December 2017

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (V˙o 2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitudeV˙o 2 max) in a hypobaric chamber.V˙o 2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups V˙o 2 maxincreased significantly after training, and a significant loss ofV˙o 2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.
A physiological model for predicting carboxyhemoglobin formation from exposure to carbon monoxide in rats
Authors: Kimmel Edgar C. , Carpenter Robert L. , Reboulet James E. , Still Kenneth R.
Published: December 2017

A time-dependent simulation model, based on the Coburn-Forster-Kane equation, was written in Advanced Continuous Simulation Language to predict carboxyhemoglobin (HbCO) formation and dissociation in F-344 rats during and after exposure to 500 parts/million CO for 1 h. Blood-gas analysis and CO-oximetry were performed on samples collected during exposure and off-gassing of CO. Volume displacement plethysmography was used to measure minute ventilation (V˙e) during exposure. CO diffusing capacity in the lung (Dl CO) was also measured. Other model parameters measured in the animals included blood pH, total blood volume, and Hb concentration. Comparisons between model predictions using values forV˙e, Dl CO, and the Haldane coefficient cited in the literature and predictions using measured V˙e, Dl CO, and calculated Haldane coefficient for individual animals were made. General model predictions using values for model parameters derived from the literature agreed with published HbCO values by a factor of 0.987 but failed to simulate experimental data. On average, the general model overpredicted measured HbCO level by nearly 9%. A specific model using the means of measured variables predicted HbCO concentration within a factor of 0.993. When experimentally observed parameter fluctuations were included, the specific model predictions reflected experimental effects on HbCO formation.
Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness
Authors: Gillis Heather L. , Lutchen Kenneth R.
Published: December 2017

Although airway remodeling and inflamation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflamation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction.
High-speed running performance is largely unaffected by hypoxic reductions in aerobic power
Authors: Weyand Peter G. , Lee Cherie S. , Martinez-Ruiz Ricardo , Bundle Matthew W. , Bellizzi Matthew J. , Wright Seth
Published: December 2017

We tested the importance of aerobic metabolism to human running speed directly by altering inspired oxygen concentrations and comparing the maximal speeds attained at different rates of oxygen uptake. Under both normoxic (20.93% O2) and hypoxic (13.00% O2) conditions, four fit adult men completed 15 all-out sprints lasting from 15 to 180 s as well as progressive, discontinuous treadmill tests to determine maximal oxygen uptake and the metabolic cost of steady-state running. Maximal aerobic power was lower by 30% (1.00 ± 0.15 vs. 0.77 ± 0.12 ml O2 ⋅ kg−1 ⋅ s−1) and sprinting rates of oxygen uptake by 12–25% under hypoxic vs. normoxic conditions while the metabolic cost of submaximal running was the same. Despite reductions in the aerobic energy available for sprinting under hypoxic conditions, our subjects were able to run just as fast for sprints of up to 60 s and nearly as fast for sprints of up to 120 s. This was possible because rates of anaerobic energy release, estimated from oxygen deficits, increased by as much as 18%, and thus compensated for the reductions in aerobic power. We conclude that maximal metabolic power outputs during sprinting are not limited by rates of anaerobic metabolism and that human speed is largely independent of aerobic power during all-out runs of 60 s or less.
Glucose production during exercise in humans: a-hv balance and isotopic-tracer measurements compared
Authors: Bergeron R. , Kjaer M. , Simonsen L. , Bülow J. , Galbo H.
Published: December 2017

The present study compared the arteriohepatic venous (a-hv) balance technique and the tracer-dilution method for estimation of hepatic glucose production during both moderate and heavy exercise in humans. Eight healthy young men (aged 25 yr; range, 23–30 yr) performed semisupine cycling for 40 min at 50.4 ± 1.5(SE)% maximal O2 consumption, followed by 30 min at 69.0 ± 2.2% maximal O2 consumption. The splanchnic blood flow was estimated by continuous infusion of indocyanine green, and net splanchnic glucose output was calculated as the product of splanchnic blood flow and a-hv blood glucose concentration differences. Glucose appearance rate was determined by a primed, continuous infusion of [3-3H]glucose and was calculated by using formulas for a modified single compartment in non-steady state. Glucose production was similar whether determined by the a-hv balance technique or by the tracer-dilution method, both at rest and during moderate and intense exercise ( P > 0.05). It is concluded that, during exercise in humans, determination of hepatic glucose production can be performed equally well with the two techniques.
Hormonal and metabolic responses to maintained hyperglycemia during prolonged exercise
Authors: MacLaren D. P. M. , Reilly T. , Campbell I. T. , Hopkin C.
Published: December 2017

We studied the effects of maintained hyperglycemia (12 mmol/l) on endurance exercise to determine the hormonal and metabolic responses, the maximal rate of glucose infusion (i.e., utilization), and the effects on muscle glycogen stores. Eight men undertook two trials during which they exercised on a cycle ergometer at an intensity of ∼70% peak O2uptake for 120 min. In the first trial ( trial A), subjects had their blood glucose concentration clamped at 12 mmol/l 30 min before exercise and throughout exercise. The same rate and volume of infusion of saline as had occurred for trial A were used in a placebo trial ( trial B). Maintained hyperglycemia resulted in significantly lowered plasma concentrations of nonesterified fatty acid, glycerol, 3-hydroxybutyrate, epinephrine, norepinephrine, and growth hormone ( P < 0.001) during exercise, whereas concentrations of plasma insulin were significantly elevated ( P < 0.001). Calculations of the rates of total carbohydrate oxidation showed that trial A resulted in significantly higher values when compared with trial B ( P < 0.01) and that the maximal rates of glucose infusion varied between 1.33 and 2.78 g/min at 100–120 min. Muscle glycogen concentrations were significantly depleted ( P < 0.01) after both trials ( trial A, 170.3 μmol/g dry wt decrease; trial B, 206 μmol/g dry wt decrease), although this apparent difference may be accounted for by storage of 22.6 g glucose during the 30-min prime infusion. The results from this study confirm that maintained hyperglycemia attenuates the hormonal response and promotes carbohydrate oxidation and utilization and that muscle glycogen may not be spared.
Role of AVP in mediating the altered core temperature response to a simulated open field in pregnant rats
Authors: Tang Patricia A. , Fewell James E. , Eliason Heather L.
Published: December 2017

Near the term of pregnancy, rats have an attenuated core temperature response on exposure to a novel environment (e.g., a simulated open field) compared with that observed early in pregnancy or in nonpregnant rats. The present experiments were carried out on 26 nonpregnant and 26 pregnant rats to test the hypothesis that arginine vasopressin, functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated core temperature response. Exposure to a simulated open field after intracerebroventricular (ICV) vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which were greater in the nonpregnant rats. In nonpregnant rats, exposure to a simulated open field after ICV vasopressin V1-receptor antagonist altered the pattern of the core temperature response but not the core temperature index compared with that observed on exposure to a simulated open field after ICV vehicle. In pregnant animals, ICV vasopressin V1-receptor antagonist did not alter the core temperature response to a simulated open field compared with that observed after ICV vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin attenuates the core temperature response to a simulated open field in rats near the term of pregnancy.
Mechanical loading attenuates bone loss due to immobilization and calcium deficiency
Authors: Inman Cynthia L. , Warren Gordon L. , Hogan Harry A. , Bloomfield Susan A.
Published: December 2017

Our purpose was to determine the effects of a mechanical loading intervention on mass, geometry, and strength of rat cortical bone during a period of disuse concurrent with calcium deficiency (CD). Adult female rats were assigned to unilateral hindlimb immobilization, immobilized-loaded, or control (standard chow, 1.85% calcium) treatments. Both immobilized groups were fed a CD rat chow (0.01% calcium) to induce high bone turnover. Three times weekly, immobilized-loaded rats were subjected to 36 cycles of 4-point bending of the immobilized lower leg. After 6 wk, the immobilized rats exhibited decreased tibial shaft bone mineral density (−12%), ultimate load (−19%), and stiffness (−20%; tested in 3-point bending to failure) vs. control rats. Loading prevented this decline in bone density and attenuated decreases in ultimate load and stiffness. Elastic modulus was unaffected by disuse or loading. Bone cross-sectional area in the immobilized-loaded rats was equivalent to that of control animals, even though endocortical resorption continued unabated. On the medial periosteum, percent mineralizing surface doubled vs. that in immobilized rats. This loading regimen stimulated periosteal mineralization and maintained bone mineral density, thereby attenuating the loss in bone strength incurred with disuse and concurrent calcium deficiency.
Ventilation and locomotion coupling in varsity male rowers
Authors: Siegmund Gunter P. , Edwards Michael R. , Moore Kelly S. , Tiessen Dale A. , Sanderson David J. , McKenzie Donald C.
Published: December 2017

Ventilation and locomotion coupling (entrainment) has been observed and described in rowers during incremental exercise protocols but not during simulated race conditions. The purpose of this descriptive study was to examine ventilation and locomotion entrainment on a breath-by-breath and stroke-by-stroke basis in varsity male rowers during a maximal 2,000-m ergometer test. Eight of eleven rowers entrained ventilation at integral multiples of stroke rate (1:1, 2:1, or 3:1) for at least 120 consecutive seconds, with a 2:1 entrainment pattern being most common. In all 2:1-entrained subjects, inspiration occurred at catch and finish and expiration occurred during the latter portions of drive and recovery. In entrained and unentrained breaths from all rowers, peak flow rates and tidal volumes varied depending on when the breath was initiated during the stroke cycle. Entrained rowers made use of these differences and breathed in a pattern by which they avoided initiating breaths that resulted in reduced tidal volumes. The present data indicated that ventilation was impaired at stroke finish and not at catch, as hypothesized by some previous researchers. Ventilation also appeared to be subordinate to consistent locomotive patterns under race conditions.
Tyrosine kinase inhibitors modulate the ventilatory response to hypoxia in the conscious rat
Authors: Czapla Marc A. , Simakajornboon Narong , Holt Gregory A. , Gozal David
Published: December 2017

Tyrosine kinases (TKs) exert multiple regulatory roles in neuronal activity and synaptic plasticity and could be involved in modulation of cardiovascular and respiratory control mechanisms within the dorsocaudal brain stem. To study this issue, the cardioventilatory responses to 1-μl microinjection within the dorsocaudal brain stem of either vehicle (Veh), the inactive TK inhibitor analog tyrphostin A1 (A1; 1 mM), or the active TK inhibitors genistein (Gen; 10 mM) and tyrphostin A25 (A25; 1 mM) were assessed by whole body plethysmography in unrestrained Sprague-Dawley adult rats. No changes in minute ventilation, heart rate, or mean arterial pressure occurred with Veh, A1, Gen, or A25 during room air breathing ( P not significant). However, Gen and A25 attenuated the peak hypoxic ventilatory responses (HVR) to 10% O2( P < 0.006 vs. Veh), whereas A1 did not modify HVR ( P not significant). HVR reductions by Gen and A25 were primarily due to diminished respiratory frequency enhancements ( P< 0.002). No changes in heart rate or mean arterial pressure responses occurred during hypoxia with TK inhibition. In addition, increases in tyrosine phosphorylation of the NR2A/B subunits, but not of the NR2C subunit, of the N-methyl-d-aspartate receptor occurred at 5, 30, and 60 min of hypoxia in the dorsocaudal brain stem and returned to baseline values at 120 min. We conclude that hypoxia induces tyrosine phosphorylation of the N-methyl-d-aspartate glutamate receptor, and TK inhibition within the dorsocaudal brain stem attenuates components of HVR in conscious rats.
Validity of the heart rate deflection point as a predictor of lactate threshold during running
Authors: Vachon John A. , Bassett David R. , Clarke Stephen
Published: December 2017

During an incremental run test, some researchers consistently observe a heart rate (HR) deflection at higher speeds, but others do not. The present study was designed to investigate whether differences in test protocols could explain the discrepancy. Additionally, we sought to determine whether the HR deflection point accurately predicts lactate threshold (LT). Eight trained runners performed four tests each: 1) a treadmill test for maximal O2uptake, 2) a Conconi test on a 400-m track with speeds increasing ∼0.5 km/h every 200 m, 3) a continuous treadmill run with speeds increasing 0.5 km/h every minute, and 4) a continuous LT treadmill test in which 3-min stages were used. All subjects demonstrated an HR deflection on the track, but only one-half of the subjects showed an HR deflection on the treadmill. On the track the shortening of stages with increasing speeds contributed to a loss of linearity in the speed-HR relationship. Additionally, the HR deflection point overestimated the LT when a continuous treadmill LT protocol was used. In conclusion, the HR deflection point was not an accurate predictor of LT in the present study.
Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia
Authors: Kitano Yoshihiro , Davies Paul , von Allmen Daniel , Adzick N. Scott , Flake Alan W.
Published: December 2017

Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death ( day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia.
Chronic hypoxia enhances the phrenic nerve response to arterial chemoreceptor stimulation in anesthetized rats
Authors: Dwinell M. R. , Powell F. L.
Published: December 2017

Chronic exposure to hypoxia results in a time-dependent increase in ventilation called ventilatory acclimatization to hypoxia. Increased O2 sensitivity of arterial chemoreceptors contributes to ventilatory acclimatization to hypoxia, but other mechanisms have also been hypothesized. We designed this experiment to determine whether central nervous system processing of peripheral chemoreceptor input is affected by chronic hypoxic exposure. The carotid sinus nerve was stimulated supramaximally at different frequencies (0.5–20 Hz, 0.2-ms duration) during recording of phrenic nerve activity in two groups of anesthetized, ventilated, vagotomized rats. In the chronically hypoxic group (7 days at 80 Torr inspired [Formula: see text]), phrenic burst frequency (fR, bursts/min) was significantly higher than in the normoxic control group with carotid sinus nerve stimulation frequencies >5 Hz. In the chronically hypoxic group, peak amplitude of integrated phrenic nerve activity ( ∫ Phr, percent baseline) or change in ∫ Phr was significantly greater at stimulation frequencies between 5 and 17 Hz, and minute phrenic activity ( ∫ Phr × fR) was significantly greater at stimulation frequencies >5 Hz. These experiments show that chronic hypoxia facilitates the translation of arterial chemoreceptor afferent input to ventilatory efferent output through a mechanism in the central nervous system.
Respiratory-related evoked potential elicited by expiratory occlusion
Authors: Hammond Carol Smith , Gaeta Helen , Sapienza Christine , Davenport Paul W.
Published: December 2017

Respiratory-related evoked potentials (RREPs) have been elicited by inspiratory loads in adults and children. The RREP was recorded over the somatosensory region of the cerebral cortex. It was hypothesized that a RREP could be recorded by using expiratory occlusion. Electroencephalographic activity was recorded in adults from 14 scalp locations, referenced to the linked earlobes. The occlusion was presented as an interruption of expiration. Epochs of electroencephalographic activity and mouth pressure were recorded for each expiratory occlusion presentation. There were two occlusion trials and a control trial of 100 presentations each. The epochs in each trial were averaged and examined for the presence of short-latency, occlusion-related peaks. RREP peaks were observed bilaterally with expiratory occlusion and were absent in control unoccluded averages. A positive peak, P34, was observed at central and postcentral sites. A negative peak, N53, was observed at frontal and central sites. A second positive peak, P95, was observed at frontal and central sites. These results demonstrate that expiratory occlusion elicits a RREP. This suggests that expiratory occlusion-related sensory information activates the cerebral cortex similar to that for inspiratory loads.
Comparison of the response to histamine challenge of the nose and the maxillary sinus: effect of loratadine
Authors: Baroody Fuad M. , Gungor Anil , deTineo Marcy , Haney Lauran , Blair Christopher , Naclerio Robert M.
Published: December 2017

To study the response of the maxillary sinus to histamine provocation, we performed a double-blind, randomized, crossover trial during which nonallergic subjects without symptoms of rhinitis ( n = 25) received either 10 mg loratadine or placebo once daily for a week and then underwent nasal challenge with histamine (3, 10, and 30 mg/ml) followed, 24 h later, by a maxillary sinus challenge while still receiving the medication. Nasal challenge with histamine led to significant increases in vascular permeability, reflex nasal secretions, sneezing, and other nasal symptoms. Sinus challenge resulted in significant increases in vascular permeability within the sinus cavity ( P < 0.01) and some nasal symptoms but no significant change in reflex nasal secretions. The response of the sinus mucosa to histamine was lower in magnitude than that of the nose. Treatment with loratadine resulted in a significant inhibition of the histamine-induced changes in both nasal and sinus cavities. Our data suggest the lack of a sinonasal reflex response to histamine provocation of the maxillary sinus of nonallergic individuals.
Reliability and validity of body composition measures in female athletes
Authors: Fornetti Willa C. , Pivarnik James M. , Foley Jeanne M. , Fiechtner Justus J.
Published: December 2017

The purpose of this investigation was to determine the reliability and validity of bioelectrical impedance (BIA) and near-infrared interactance (NIR) for estimating body composition in female athletes. Dual-energy X-ray absorptiometry was used as the criterion measure for fat-free mass (FFM). Studies were performed in 132 athletes [age = 20.4 ± 1.5 (SD) yr]. Intraclass reliabilities (repeat and single trial) were 0.987–0.997 for BIA (resistance and reactance) and 0.957–0.980 for NIR (optical densities). Validity of BIA and NIR was assessed by double cross-validation. Because correlations were high ( r = 0.969–0.983) and prediction errors low, a single equation was developed by using all 132 subjects for both BIA and NIR. Also, an equation was developed for all subjects by using height and weight only. Results from dual-energy X-ray absorptiometry analysis showed FFM = 49.5 ± 6.0 kg, which corresponded to %body fat (%BF) of 20.4 ± 3.1%. BIA predicted FFM at 49.4 ± 5.9 kg ( r = 0.981, SEE = 1.1), and NIR prediction was 49.5 ± 5.8 kg ( r = 0.975, SEE = 1.2). Height and weight alone predicted FFM at 49.4 ± 5.7 kg ( r = 0.961, SEE = 1.6). When converted to %BF, prediction errors were ∼1.8% for BIA and NIR and 2.9% for height and weight. Results showed BIA and NIR to be extremely reliable and valid techniques for estimating body composition in college-age female athletes.
Development of muscle strength in relation to training level and testosterone in young male soccer players
Authors: Hansen L. , Bangsbo J. , Twisk J. , Klausen K.
Published: December 2017

Isometric and functional strength of ninety-eight 11-yr-old male soccer players at an elite (E) and nonelite (NE) level were determined (3–4 times) through a 2-yr period, and the changes were related to growth and maturation. The initial isometric strength for extension with dominant leg [1,502 ± 35 (E) vs. 1,309 ± 39 (NE) N], extension with nondominant leg (1,438 ± 37 vs. 1,267 ± 45 N), extension with both legs (2,113 ± 76 vs. 1,915 ± 72 N), back muscles (487 ± 11 vs. 414 ± 10 N), abdominal muscles (320 ± 9 vs. 294 ± 8 N), and handgrip (304 ± 10 vs. 259 ± 8 N) increased by 15–40% during the period. Broad jump increased ( P < 0.05) by 15 (E) and 10% (NE). The E players had higher ( P< 0.05) initial isometric strength and broad jump performance compared with NE players, and differences were maintained throughout the period (multiple ANOVA for repeated measures) also when adjustment was made for age, dimensions, testosterone, and insulin-like growth factor I (generalized estimating equations analyses). The development of strength for both E and NE players together was significantly ( P < 0.001) related to changes in serum testosterone concentrations. The present data indicate that testosterone is important for development of strength in young boys and that, independent of serum testosterone concentration, E players have developed greater muscle strength compared with NE players.
Acute plasma volume expansion: effect on metabolism during submaximal exercise
Authors: Watt Matthew J. , Febbraio Mark A. , Garnham Andrew P. , Hargreaves Mark
Published: December 2017

To examine the effect of acute plasma volume expansion (PVE) on substrate selection during exercise, seven untrained men cycled for 40 min at 72 ± 2% peak oxygen uptake (V˙o 2 peak) on two occasions. On one occasion, subjects had their plasma volume expanded by 12 ± 2% via an intravenous infusion of the plasma substitute Haemaccel, whereas on the other occasion no such infusion took place. Muscle samples were obtained before and immediately after exercise. In addition, heart rate and pulmonary gas and venous blood samples were obtained throughout exercise. No differences in oxygen uptake or heart rate during exercise were observed between trials, whereas respiratory exchange ratio, blood glucose, and lactate were unaffected by PVE. Muscle glycogen and lactate concentrations were not different either before or after exercise. In addition, there was no difference in total carbohydrate oxidation between trials (control: 108 ± 2 g; PVE group: 105 ± 2 g). Plasma catecholamine levels were not affected by PVE. These data indicate that substrate metabolism during submaximal exercise in untrained men is unaltered by acute hypervolemia.
Impairment of transalveolar fluid transport and lung Na+-K+-ATPase function by hypoxia in rats
Authors: Suzuki Satoshi , Noda Masafumi , Sugita Makoto , Ono Sadafumi , Koike Kaoru , Fujimura Shigefumi
Published: December 2017

We examined whether hypoxic exposure in vivo would influence transalveolar fluid transport in rats. We found a significant decrease in alveolar fluid clearance of the rats exposed to 10% oxygen for 48 h. Terbutaline did not stimulate alveolar fluid clearance, and alveolar fluid cAMP levels were lower than those determined in normoxia experiment. Hypoxia did not influence the alveolar fluid lactate dehydrogenase levels, Evans blue dye fluid-to-serum concentration ratio, or lung wet-to-dry weight ratio, indicating no significant change in the permeability of alveolar-capillary barrier. Histological examination showed no significant fluid accumulation into the interstitium and the alveolar space. Hypoxia did not reduce lung ATP content; however, we found significant decrease in Na+-K+-ATPase hydrolytic activity in lung tissue preparations and isolated alveolar type II cells. Our data indicate that hypoxic exposure in vivo impairs transalveolar fluid transport, and this impairment is related to the decrease in alveolar epithelial Na+-K+-ATPase hydrolytic activity but is not secondary to the alteration of cellular energy source.
Relaxation of diaphragm muscle
Authors: Coirault Catherine , Chemla Denis , Lecarpentier Yves
Published: December 2017

Relaxation is the process by which, after contraction, the muscle actively returns to its initial conditions of length and load. In rhythmically active muscles such as diaphragm, relaxation is of physiological importance because diaphragm must return to a relatively constant resting position at the end of each contraction-relaxation cycle. Rapid and complete relaxation of the diaphragm is likely to play an important role in adaptation to changes in respiratory load and breathing frequency. Regulation of diaphragm relaxation at the molecular and cellular levels involves Ca2+removal from the myofilaments, active Ca2+pumping by the sarcoplasmic reticulum (SR), and decrease in the number of working cross bridges. The relative contribution of these mechanisms mainly depends on sarcomere length, muscle tension, and the intrinsic contractile function. Increased capacity of SR to take up Ca2+can arise from increased density of active SR pumping sites or in slow-twitch fibers from phosphorylation of phospholamban, whereas impaired coupling between ATP hydrolysis and Ca2+transport into the SR or intracellular acidosis reduces SR Ca2+pump activity. In experimental conditions of decreased contractile performance, slowed, enhanced, or unchanged relaxation rates have been reported in vitro. In vivo, a slowing in the rate of decline of the respiratory pressure is generally considered an early reliable index of respiratory muscle fatigue. Impaired relaxation rate may, in turn, favor mismatch between blood flow and metabolic demand, especially at high breathing frequencies.
Theoretical and experimental intravascular gas embolism absorption dynamics
Authors: Branger Annette B. , Eckmann David M.
Published: December 2017

Multifocal cerebrovascular gas embolism occurs frequently during cardiopulmonary bypass and is thought to cause postoperative neurological dysfunction in large numbers of patients. We developed a mathematical model to predict the absorption time of intravascular gas embolism, accounting for the bubble geometry observed in vivo. We modeled bubbles as cylinders with hemispherical end caps and solved the resulting governing gas transport equations numerically. We validated the model using data obtained from video-microscopy measurements of bubbles in the intact cremaster microcirculation of anesthetized male Wistar rats. The theoretical model with the use of in vivo geometry closely predicted actual absorption times for experimental intravascular gas embolisms and was more accurate than a model based on spherical shape. We computed absorption times for cerebrovascular gas embolism assuming a range of bubble geometries, initial volumes, and parameters relevant to brain blood flow. Results of the simulations demonstrated absorption time maxima and minima based on initial geometry, with several configurations taking as much as 50% longer to be absorbed than would a comparable spherical bubble.
A computer simulation of free-range exercise in the laboratory
Authors: Terblanche E. , Wessels J. A. , Stewart R. I. , Koeslag J. H.
Published: December 2017

We present a technique for simulating dynamic field (free-range) exercise, using a novel computer-controlled cycle ergometer. This modified cycle ergometer takes into account the effect of friction and aerodynamic drag forces on a 70-kg cyclist in a racing position. It also affords the ability to select different gear ratios. We have used this technique to simulate a known competition cycle route in Cape Town, South Africa. In an attempt to analyze the input stimulus, in this case the generated power output of each cyclist, eight subjects cycled for 40 min at a self-selected, comfortable pace on the first part of the simulated route. Our results indicate that this exercise input excites the musculocardiorespiratory system over a wide range of power outputs, both in terms of amplitude and frequency. This stimulus profile thereby complies with the fundamental requirement for nonlinear (physiological) systems analysis and identification. Through a computer simulation, we have devised a laboratory exercise protocol that not only is physiologically real but also overcomes the artificiality of most traditional laboratory exercise protocols.
Presinusoidal vessels predominantly contract in response to norepinephrine, histamine, and KCl in rabbit liver
Authors: Shibamoto Toshishige , Wang Hong-Gang , Miyahara Takashige , Tanaka Satoshi , Haniu Hisao , Koyama Shozo
Published: December 2017

In rabbit livers, it is not well known which segments of the hepatic vasculature are predominantly contracted by various vasoconstrictors. We determined effects of histamine, norepinephrine, and KCl on hepatic vascular resistance distribution in isolated rabbit livers perfused via the portal vein with 5% albumin-Krebs solution at a constant flow rate. Hepatic capillary pressure was measured by double vascular occlusion pressure (Pdo) and was used to determine portal (Rpv) and hepatic venous (Rhv) resistances. A bolus injection of either histamine or norepinephrine dose-dependently increased portal venous pressure but not Pdo, resulting in a dose-dependent increase in Rpv and no changes in Rhv. KCl (50 mM), when injected in anterogradely perfused livers, contracted the presinusoidal vessels selectively with liver weight loss. Although KCl significantly increased Rhv in retrogradely perfused livers, the increase in Rpv by 400% of baseline predominated over the increase in Rhv by 85% of baseline. In the retrogradely perfused livers, KCl produced an initial liver weight loss followed by a profound weight gain. We conclude that histamine and norepinephrine selectively contract the presinusoidal vessels. The results on KCl effects suggest that this selective presinusoidal constriction might be possibly due to predominant distribution of functionally active vascular smooth muscle in the presinusoidal vessels rather than the hepatic vein in rabbit livers.