bluuebunny/crossref_metadata_2025 huggingface dataset:
African runners exhibit greater fatigue resistance, lower lactate accumulation, and higher oxidative enzyme activity
Authors: Weston Adèle R. , Karamizrak O. , Smith A. , Noakes T. D. , Myburgh Kathryn H.
Published: December 2017

Nine African and eight Caucasian 10-km runners resident at sea level volunteered. Maximal O2consumption and peak treadmill velocity (PTV) were measured by using a progressive test, and fatigue resistance [time to fatigue (TTF)] was measured by using a newly developed high-intensity running test: 5 min at 72, 80, and 88% of individual PTV followed by 92% PTV to exhaustion. Skeletal muscle enzyme activities were determined in 12 runners and 12 sedentary control subjects. In a comparison of African and Caucasian runners, mean 10-km race time, maximal O2consumption, and PTV were similar. In African runners, TTF was 21% longer ( P < 0.01), plasma lactate accumulation after 5 min at 88% PTV was 38% lower ( P < 0.05), and citrate synthase activity was 50% higher (27.9 ± 7.5 vs. 18.6 ± 2.1 μmol ⋅ g wet wt−1⋅ min−1, P = 0.02). Africans accumulated lactate at a slower rate with increasing exercise intensity ( P < 0.05). Among the entire group of runners, a higher citrate synthase activity was associated with a longer TTF ( r= 0.70, P < 0.05), a lower plasma lactate accumulation ( r = −0.73, P = 0.01), and a lower respiratory exchange ratio ( r = −0.63, P < 0.05). We conclude that the African and Caucasian runners in the present study differed with respect to oxidative enzyme activity, rate of lactate accumulation, and their ability to sustain high-intensity endurance exercise.
Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension
Authors: Hill Laureen L. , Pearl Ronald G.
Published: December 2017

Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI2) produce selective reductions in pulmonary vascular resistance (PVR) through differing mechanisms. NO decreases PVR via cGMP, and PGI2 produces pulmonary vasodilation via cAMP. As a general pharmacological principle, two drugs that produce similar effects via different mechanisms should have additive or synergistic effects when combined. We designed this study to investigate whether combined inhaled NO and PGI2 therapy results in additive effects during chronic pulmonary hypertension in the rat. Monocrotaline injected 4 wk before study produced pulmonary hypertension in all animals. Inhaled NO (20 parts/million) reversibly and selectively decreased pulmonary artery pressure (Ppa) with a mean reduction of 18%. Four concentrations of PGI2were administered via inhalation (5, 10, 20, and 80 μg/ml), both alone and combined with inhaled NO. Inhaled PGI2 alone decreased Ppa in a dose-dependent manner with no change in mean systemic arterial pressure. Combined inhaled NO and PGI2 selectively and significantly decreased Ppa more did than either drug alone. The effects were additive at the lower concentrations of PGI2 (5, 10, and 20 μg/ml). The combination of inhaled NO and inhaled PGI2 may be useful in the management of pulmonary hypertension.
Gas supersaturation in the cecal wall of mice due to bacterial CO2production
Authors: Rasmussen Henrik , Kvarstein Gunnvald , Johnsen Helge , Dirven Hubert , Midtvedt Tore , Mirtaheri Peyman , Tønnessen Tor Inge
Published: December 2017

Pco2in the lumen and serosa of cecum and jejunum was measured in mice. The anesthetic used was a fentanyl-fluanisone-midazolam mixture.[Formula: see text] was recorded in vivo and postmortem. [Formula: see text] was 409 ± 32 Torr (55 ± 4 kPa) in the cecal lumen and 199 ± 22 Torr (27 ± 3 kPa) on the serosa in normal mice. Irrigation of the cecum resulted in serosal and luminal [Formula: see text]levels of 65–75 Torr. Cecal [Formula: see text]was significantly lower in germ-free mice (65 ± 5 Torr). Cecal[Formula: see text] increased significantly after introduction of normal bacterial flora into germ-free mice. Introduction of bacterial monocultures into germ-free mice had no effect. After the deaths of the mice, cecal[Formula: see text] increased rapidly in normal mice. The intestinal bacteria produced the majority of the cecal[Formula: see text], and the use of tonometry in intestinal segments with a high bacterial activity should be interpreted with caution. We propose that serosal[Formula: see text] levels >150–190 Torr (20–25 kPa) in the cecum of mice with a normal circulation may represent a state of gas supersaturation in the cecal wall.
Human muscle performance and PCr hydrolysis with varied inspired oxygen fractions: a31P-MRS study
Authors: Hogan Michael C. , Richardson Russell S. , Haseler Luke J.
Published: December 2017

The purpose of this study was to use31P-magnetic resonance spectroscopy to examine the relationships among muscle PCr hydrolysis, intracellular H+concentration accumulation, and muscle performance during incremental exercise during the inspiration of gas mixtures containing different fractions of inspired O2([Formula: see text]). We hypothesized that lower [Formula: see text]would result in a greater disruption of intracellular homeostasis at submaximal workloads and thereby initiate an earlier onset of fatigue. Six subjects performed plantar flexion exercise on three separate occasions with the only variable altered for each exercise bout being the [Formula: see text] (either 0.1, 0.21, or 1.00 O2in balance N2). Work rate was increased (1-W increments starting at 0 W) every 2 min until exhaustion. Time to exhaustion (and thereby workload achieved) was significantly ( P < 0.05) greater as[Formula: see text] was increased. Muscle phosphocreatine (PCr) concentration, Piconcentration, and pH at exhaustion were not significantly different among the three[Formula: see text] conditions. However, muscle PCr concentration and pH were significantly reduced at identical submaximal workloads (and thereby equivalent rates of respiration) above 4–5 W during the lowest[Formula: see text] condition compared with the other two [Formula: see text]conditions. These results demonstrate that exhaustion during all[Formula: see text] occurred when a particular intracellular environment was acheived and suggest that during the lowest [Formula: see text]condition, the greater PCr hydrolysis and intracellular acidosis at submaximal workloads may have contributed to the significantly earlier time to exhaustion.
Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and lipolysis in rats
Authors: Podolin Deborah A. , Wei Yuren , Pagliassotti Michael J.
Published: December 2017

The purpose of the present study was to determine the effects of diet composition and exercise on glycerol and glucose appearance rate (Ra) and on nonglycerol gluconeogenesis (Gneo) in vivo. Male Wistar rats were fed a high-starch diet (St, 68% of energy as cornstarch, 12% corn oil) for a 2-wk baseline period and then were randomly assigned to one of four experimental groups: St ( n = 7), high-fat (HF; 35% cornstarch, 45% corn oil; n = 8), St with free access to exercise wheels (StEx; n = 7), and HF with free access to exercise wheels (HFEx; n = 7). After 8 wk, glucose Rawhen using [3-3H]glucose, glycerol Rawhen using [2H5]glycerol (estimate of whole body lipolysis), and [3-13C]alanine incorporation into glucose (estimate of alanine Gneo) were determined. Body weight and fat pad mass were significantly ( P < 0.05) decreased in exercise vs. sedentary animals only. The average amount of exercise was not significantly different between StEx (3,212 ± 659 m/day) and HFEx (3,581 ± 765 m/day). The ratio of glucose to alanine enrichment and absolute glycerol Ra(μmol/min) were higher ( P < 0.05) in HF and HFEx compared with St and StEx rats. In separate experiments, the ratio of3H in C-2 to C-6 of glucose from3H2O (estimate of Gneo from pyruvate) was also higher ( P < 0.05) in HF ( n = 5) and HFEx ( n = 5), compared with St ( n = 5) and StEx ( n = 5) rats. Voluntary wheel running did not significantly increase estimated alanine or pyruvate Gneo or absolute glycerol Ra. Voluntary wheel running increased ( P< 0.05) glycerol Rawhen normalized to fat pad mass. These data suggest that a high-fat diet can increase in vivo Gneo from precursors that pass through pyruvate. They also suggest that changes in the absolute rate of glycerol Ramay contribute to the high-fat diet-induced increase in Gneo.
Dispersion of 0.5- to 2-μm aerosol in μG and hypergravity as a probe of convective inhomogeneity in the lung
Authors: Darquenne Chantal , West John B. , Prisk G. Kim
Published: December 2017

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (μG) and hypergravity (∼1.6 G). Boluses of 0.5-, 1-, and 2-μm-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-μm-diameter particles for which sedimentation velocity is low, the differences between dispersion in μG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between μG and 1 G.
Relationship between activity levels, aerobic fitness, and body fat in 8- to 10-yr-old children
Authors: Rowlands Ann V. , Eston Roger G. , Ingledew David K.
Published: December 2017

The relationships between children’s activity, aerobic fitness, and fatness are unclear. Indirect estimates of activity, e.g., heart rate (HR) and recall, may mask any associations. The purpose of this study was to assess these relationships by using the Tritrac-R3D, a pedometer, and heart rate. Thirty-four children, ages 8–10 yr, participated in the study. The Tritrac and pedometer were worn for up to 6 days. HR was measured for 1 day. Activity measured by Tritrac or pedometer correlated positively to fitness in the whole group (Tritrac, r = 0.66; pedometer, r = 0.59; P < 0.01) and in boys and girls separately ( P < 0.05) and correlated negatively to fatness in the whole group ( r = −0.42, P < 0.05). In contrast, HR did not correlate significantly to fitness, and HR of >139 beats/min correlated positively to fatness in girls ( r = 0.64, P < 0.05). This suggests that HR is misleading as a measure of activity. This study supports a positive relationship between activity and fitness and suggests a negative relationship between fatness and activity.
Exercise V˙eand physical performance at altitude are not affected by menstrual cycle phase
Authors: Beidleman Beth A. , Rock Paul B. , Muza Stephen R. , Fulco Charles S. , Forte Vincent A. , Cymerman Allen
Published: December 2017

We hypothesized that progesterone-mediated ventilatory stimulation during the midluteal phase of the menstrual cycle would increase exercise minute ventilation (V˙e; l/min) at sea level (SL) and with acute altitude (AA) exposure but would only increase arterial O2saturation ([Formula: see text], %) with AA exposure. We further hypothesized that an increased exercise[Formula: see text] with AA exposure would enhance O2transport and improve both peak O2uptake (V˙o2 peak; ml ⋅ kg−1⋅ min−1) and submaximal exercise time to exhaustion (Exh; min) in the midluteal phase. Eight female lowlanders [33 ± 3 (mean ± SD) yr, 58 ± 6 kg] completed aV˙o2 peakand Exh test at 70% of their altitude-specificV˙o2 peakat SL and with AA exposure to 4,300 m in a hypobaric chamber (446 mmHg) in their early follicular and midluteal phases. Progesterone levels increased ( P < 0.05) ∼20-fold from the early follicular to midluteal phase at SL and AA. PeakV˙e (101 ± 17) and submaximalV˙e (55 ± 9) were not affected by cycle phase or altitude. Submaximal[Formula: see text] did not differ between cycle phases at SL, but it was 3% higher during the midluteal phase with AA exposure. NeitherV˙o2 peaknor Exh time was affected by cycle phase at SL or AA. We conclude that, despite significantly increased progesterone levels in the midluteal phase, exercise V˙e is not increased at SL or AA. Moreover, neither maximal nor submaximal exercise performance is affected by menstrual cycle phase at SL or AA.
Effects of bilateral vestibular lesions on orthostatic tolerance in awake cats
Authors: Jian B. J. , Cotter L. A. , Emanuel B. A. , Cass S. P. , Yates B. J.
Published: December 2017

Previous experiments in anesthetized or decerebrate cats showed that the vestibular system participates in adjusting blood pressure during postural changes. The present experiments tested the hypothesis that removal of vestibular inputs in awake cats would affect orthostatic tolerance. Before the lesion, blood pressure typically remained within 10 mmHg of baseline values during nose-up-pitch body rotations of up to 60° in amplitude. In contrast, bilateral peripheral vestibular lesions altered the pattern of orthostatic responses in all animals, and blood pressure fluctuated >10 mmHg from baseline values during most 60° nose-up tilts in five of six animals. The deficit in correcting blood pressure was particularly large when the animal also was deprived of visual cues indicating position in space. During this testing condition, either a decrease or increase in blood pressure >10 mmHg in magnitude occurred in >80% of tilts. The deficit in adjusting blood pressure after vestibular lesions persisted for only 1 wk, after which time blood pressure remained stable during tilt. These data show that removal of vestibular inputs alters orthostatic responses and are consistent with the hypothesis that vestibular signals are one of several inputs that are integrated to elicit compensatory changes in blood pressure during movement.
Volume of ankle dorsiflexors and plantar flexors determined with stereological techniques
Authors: Gadeberg Paula , Andersen Henning , Jakobsen Johannes
Published: December 2017

The validity of the methods used for determination of muscle mass has not been evaluated previously. We determined muscle mass by estimating muscle volume with assumption-free stereological techniques applied to magnetic resonance imaging (MRI) in 18 healthy untrained subjects (6 women, 12 men) aged 41 yr (29–64 yr; median, range). Muscle mass was also estimated by measuring leg circumference and cross-sectional muscle areas (CSA) from MRIs at three predetermined levels. Power [peak torque (PT)] of the ankle dorsiflexors and plantar flexors was estimated by using isokinetic dynamometry. Dorsiflexor volume ( r2= 0.76, P < 5 × 10−6) and CSA ( r2= 0.73, P < 5 × 10−5) were related to PT, whereas circumference was not ( r2= 0.17, not significant). Correspondingly, a relationship to plantar PT was established for plantar flexor volume ( r2= 0.69, P < 5 × 10−5) and CSA ( r2= 0.46, P < 5 × 10−3) but not leg circumference ( r2= 0.15, not significant). SDs of the residuals were smaller for the relationship between dorsiflexor PT and volume than between PT and CSA (0.42 vs. 0.45) for plantar flexors (1.5 vs. 2.0). By using the Cavalieri method, six MRI sections and 15 min of point counting are sufficient to obtain a valid estimate of the volume of the muscles of the lower leg.
Acetylcholine-induced endothelium-derived contracting factor in hypoxic pulmonary hypertensive rats
Authors: Maruyama Junko , Yokochi Ayumu , Maruyama Kazuo , Nosaka Shoichiro
Published: December 2017

We determined the role of an endothelium-derived contracting factor in the impaired relaxation response to ACh of conduit pulmonary arteries (PAs) isolated from rats with hypoxic pulmonary hypertension (PH). A PGH2/thromboxane A2(TxA2)-receptor antagonist (ONO-3708) partially restored the impairment of ACh-induced relaxation, whereas TxA2synthase inhibitors (OKY-046 and CV-4151) did not affect the impaired relaxation in phenylephrine-precontracted hypertensive PAs. Endothelium-denuded hypertensive PA rings showed no difference in the response to ACh between preparations with and without ONO-3708. In both endothelium-denuded control and hypertensive PAs, exogenous PGH2induced contractions, and the magnitude of the contractions was greater in the control than in hypoxic PH preparations. An endothelin A-receptor antagonist (BQ-485), an endothelin B-receptor antagonist (BQ-788), and a superoxide anion scavenger (superoxide dismutase) did not restore the impaired response to ACh in hypertensive PAs. These findings suggest that PGH2produced from the conduit PAs of rats with chronic hypoxic PH may be the endothelium-derived contracting factor responsible for the impairment of ACh-mediated vasorelaxation.
Sympathetic responses to head-down rotations in humans
Authors: Hume Keith M. , Ray Chester A.
Published: December 2017

Muscle sympathetic nerve activity (MSNA) increases with head-down neck flexion (HDNF). The present study had three aims: 1) to examine sympathetic and vascular responses to two different magnitudes of HDNF; 2) to examine these same responses during prolonged HDNF; and 3) to determine the influence of nonspecific pressure receptors in the head on MSNA. The first experiment tested responses to two static head positions in the vertical axis [HDNF and intermediate HDNF (I-HDNF; ∼50% of HDNF)]. MSNA increased above baseline during both I-HDNF and HDNF (from 219 ± 36 to 301 ± 47 and from 238 ± 42 to 356 ± 59 units/min, respectively; P < 0.01). Calf blood flow (CBF) decreased and calf vascular resistance increased during both I-HDNF and HDNF ( P < 0.01). Both the increase in MSNA and the decrease in CBF were linearly related to the magnitude of the downward head rotations ( P < 0.01). The second experiment tested responses during prolonged HDNF. MSNA increased (from 223 ± 63 to 315 ± 79 units/min; P < 0.01) and CBF decreased (from 3.2 ± 0.4 to 2.6 ± 0.04 ml ⋅ 100 ml−1 ⋅ min−1; P < 0.01) at the onset of HDNF. These responses were maintained throughout the 30-min period. Mean arterial blood pressure gradually increased during the 30 min of HDNF (from 94 ± 4 to 105 ± 3 mmHg; P < 0.01). In a third experiment, head-down neck extension was performed with subjects in the supine position. Unlike HDNF, head-down neck extension did not affect MSNA. The results from these studies demonstrate that MSNA: 1) increases in magnitude as the degree of HDNF increases; 2) remains elevated above baseline during prolonged HDNF; and 3) responses during HDNF are not associated with nonspecific receptors in the head activated by increases in cerebral pressure.
Longitudinal distribution of chlorine absorption in human airways: comparison of nasal and oral quiet breathing
Authors: Nodelman Vladislav , Ultman James S.
Published: December 2017

The fraction of an inspired chlorine (Cl2) bolus absorbed during a single breath (Λ) was measured as a function of bolus penetration (VP) into the respiratory system of five male and five female nonsmokers during both nasal and oral breathing at a quiet respiratory flow of 250 ml/s. The correspondence between VPand specific anatomic landmarks was found for each subject by a combination of acoustic reflection and nitrogen washout measurements. For both nasal and oral breathing, Λ reached ∼0.95 at the distal end of the upper airways and reached 1.00 within the lower conducting airways. The values of a regional mass transfer parameter computed from the Λ-VPdata indicated that the resistance to Cl2diffusion in the airway mucosa was negligible compared with the diffusion resistance in the respired gas. Changing the peak inhaled Cl2concentration from 0.5 to 3.0 parts/million did not significantly affect the distribution of Cl2absorption, suggesting that the underlying mass transport and chemical reaction processes were linear with respect to Cl2concentration.
Role of nitric oxide in hypoxic hypometabolism in rats
Authors: Gautier Henry , Murariu Cristina
Published: December 2017

Because it has been recently suggested that nitric oxide (NO) may mediate the effects of hypoxia on body temperature and ventilation, the present study was designed to assess more completely the effects of a neuronal NO synthase inhibitor (7-nitroindazole, 25 mg/kg ip), at ambient temperature of 26 and 15°C, on the ventilatory (V˙), metabolic (O2 consumption), and thermal changes (colonic and tail temperatures) induced by ambient hypoxia (fractional inspired O2 of 11%) or CO hypoxia (fractional inspired CO of 0.07%) in intact, unanesthetized adult rats. At both ambient temperatures, 7-nitroindazole decreased oxygen consumption, colonic temperature, andV˙ in normoxia. The drug reduced ambient or CO hypoxia-induced hypometabolism and ventilatory response, but the hypothermia persisted. It is concluded that NO arising from neural NO synthase plays an important role in the control of metabolism andV˙ in normoxia. As well, it mediates, in part, the hypometabolic and the ventilatory response to hypoxia. The results are consistent with the notion that central nervous system hypoxia resets the thermoregulatory set point by decreasing brain NO.
Mechanisms of improvement in pulmonary gas exchange during isovolemic hemodilution
Authors: Deem Steven , Hedges Richard G. , McKinney Steven , Polissar Nayak L. , Alberts Michael K. , Swenson Erik R.
Published: December 2017

Severe anemia is associated with remarkable stability of pulmonary gas exchange (S. Deem, M. K. Alberts, M. J. Bishop, A. Bidani, and E. R. Swenson. J. Appl. Physiol. 83: 240–246, 1997), although the factors that contribute to this stability have not been studied in detail. In the present study, 10 Flemish Giant rabbits were anesthetized, paralyzed, and mechanically ventilated at a fixed minute ventilation. Serial hemodilution was performed in five rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; five rabbits were followed over a comparable time. Ventilation-perfusion (V˙a/Q˙) relationships were studied by using the multiple inert-gas-elimination technique, and pulmonary blood flow distribution was assessed by using fluorescent microspheres. Expired nitric oxide (NO) was measured by chemiluminescence. Hemodilution resulted in a linear fall in hematocrit over time, from 30 ± 1.6 to 11 ± 1%. Anemia was associated with an increase in arterial [Formula: see text] in comparison with controls ( P < 0.01 between groups). The improvement in O2exchange was associated with reducedV˙a/Q˙heterogeneity, a reduction in the fractal dimension of pulmonary blood flow ( P = 0.04), and a relative increase in the spatial correlation of pulmonary blood flow ( P = 0.04). Expired NO increased with anemia, whereas it remained stable in control animals ( P < 0.0001 between groups). Anemia results in improved gas exchange in the normal lung as a result of an improvement in overallV˙a/Q˙matching. In turn, this may be a result of favorable changes in pulmonary blood flow distribution, as assessed by the fractal dimension and spatial correlation of blood flow and as a result of increased NO availability.
Dexamethasone in resting and exercising men. II. Effects on adrenocortical hormones
Authors: Lac G. , Marquet P. , Chassain A. P. , Galen F. X.
Published: December 2017

This study presents the reactions of adrenocorticosteroids (cortisol and aldosterone) and sex steroids [testosterone, androstenedione, and dehydroepiandrosterone and its sulfate (DHAS)] 1) to a dexamethasone (Dex) treatment, which is expected to lower steroid levels via the ACTH blockade, and 2) to an exercise bout at maximal O2consumption, which is expected to increase steroid production via ACTH stimulation. Consistent with the decrease in ACTH, all steroids except testosterone reacted negatively to Dex, independently of the dose (0.5 and 1.5 mg administered twice daily for 4.5 days). After exercise, plasma ACTH rose to 600% of basal value, resulting in a significant increase in aldosterone and adrenal androgens, but cortisol and DHAS were unaffected. This apparently surprising result can be explained by differences in peripheral metabolism: a theoretical calculation predicted that after 15 min the increase in hormone concentration may only reach 12% for cortisol and 2% for DHAS. For cortisol and adrenal androgens, assays were carried out using plasma and saliva. The consistent results obtained from the two matrices allow us to consider salivary assays as a useful tool for steroid abuse detection.
Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation
Authors: Deshpande Prashant , Khurana Atul , Hansen Polly , Wilkins Davida , Thach Bradley T.
Published: December 2017

“Autoresuscitation” (AR) is the spontaneous recovery from hypoxic apnea by gasping. We examined aspects of heart function in two situations: 1) the maturationally acquired failure of AR that is characteristic of SWR, but not BALB/c, weanling mice and 2) AR failure in BALB/c mice induced by repeated exposures to anoxia. We determined maturational changes in heart and liver glycogen. Unlike liver glycogen levels, heart glycogen levels in SWR mice differed from those in BALB/c mice. They were consistently much lower throughout maturation and reached a nadir during the brief period when SWR weanling mice are vulnerable to AR failure. Also, rate of cardiac glycogen utilization in vulnerable SWR mice was lower than that of same-aged BALB/c mice and was nil during the latter one-half of the gasping stage when heart function is critical for AR success. Therefore, because glycogen utilization reflects cardiac work, heart failure could explain AR failure in SWR weanlings. Additionally, the increase in hypoxic heart rate that occurs with maturation is developmentally delayed in SWR mice, and this may contribute to their AR failure. Cardiac glycogen was not fully depleted in BALB/c mice during repeated anoxic exposures, indicating other reasons for AR failure. We view these findings as a potential model for the age-related peak in incidence of sudden infant death syndrome.
ICAM-1 and CD11b inhibition worsen outcome in rats withE. colipneumonia
Authors: Zeni Fabrice , Parent Chantal , Correa Rosaly , Natanson Charles , Freeman Bradley , Fontana Joseph , Quezado Marcello , Danner Robert L. , Fitz Yvonne , Richmond Steve , Gerstenberger Eric , Banks Steven M. , Eichacker Peter Q.
Published: December 2017

We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h × 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h × 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control ( P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly ( P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils ( P = 0.04–0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.
Influence of brief daily tendon vibration on rat soleus muscle in non-weight-bearing situation
Authors: Falempin Maurice , In-Albon Soumeya Fodili
Published: December 2017

The purpose of this study was to investigate whether tendon vibration could prevent soleus muscle atrophy during hindlimb unloading (HU). Mechanical vibrations with a constant low amplitude (0.3 mm) were applied (192 s/day) with constant frequency (120 Hz) to the Achilles tendon of the unloaded muscle during the 14-day HU period. Significant reductions in muscle mass (−41%), fiber size, maximal twitch (−54%), and tetanic tensions (−73%) as well as changes in fiber type and electrophoretic profiles and twitch-time parameters (−31% in the contraction time and −30% in the half relaxation time) were found after 14 days of HU when compared with the control soleus. Tendon vibration applied during HU significantly attenuated, but did not prevent, 1) the loss of muscle mass (17 vs. 41%); 2) the decrease in the fiber cross-sectional area of type IIA (−28 vs. −50%) and type IIC (−29 vs. −56%) fibers; and 3) the decrease in maximal twitch (−3 vs. −54%) and maximal tetanic tensions (−29 vs. −73%) and the half relaxation time (1 vs. −30%). Changes in the contraction time and in histological and electrophoretical parameters associated with HU were not counteracted. These findings suggest that tendon vibration can be used as a paradigm to counteract the atrophic process observed after HU.
Increased training load and the β-adrenergic-receptor system on human lymphocytes
Authors: Schaller K. , Mechau D. , Scharmann H. Grosse , Weiss M. , Baum M. , Liesen H.
Published: December 2017

The influence of increased training on the sympathoadrenergic system was investigated. Moderately trained male subjects ( n = 15) increased their training within 10 wk by 60%; eight of the subjects increased their training volume, and seven increased their training intensity. Before and after the training, an exhaustive treadmill exercise was carried out. Acute treadmill exercise increased β-adrenergic receptor number on mononuclear lymphocytes, isoproternol-stimulated cAMP production, and plasma catecholamine concentration. The increase of receptor number can at least partially be explained by a changed lymphocyte composition at rest and after exercise. After training, the exercise-induced increase of β-adrenergic receptor number was significantly blunted, and the exercise-induced increase of the isoproternol-stimulated cAMP production per β-receptor was enhanced. Subjects who experienced increased symptoms of physical discomfort and/or mood changes showed an enhanced cAMP production after training. These findings point to an altered regulation of the receptor and postreceptor mechanisms as an effect of a 10-wk period of hard training.
Cellular P O 2 as a determinant of maximal mitochondrial O2consumption in trained human skeletal muscle
Authors: Richardson R. S. , Leigh J. S. , Wagner P. D. , Noyszewski E. A.
Published: December 2017

Previously, by measuring myoglobin-associated [Formula: see text](PMb o 2) during maximal exercise, we have demonstrated that 1) intracellular[Formula: see text] is 10-fold less than calculated mean capillary [Formula: see text] and 2) intracellular[Formula: see text] and maximum O2 uptake (V˙o 2 max) fall proportionately in hypoxia. To further elucidate this relationship, five trained subjects performed maximum knee-extensor exercise under conditions of normoxia (21% O2), hypoxia (12% O2), and hyperoxia (100% O2) in balanced order. Quadriceps O2 uptake (V˙o 2) was calculated from arterial and venous blood O2concentrations and thermodilution blood flow measurements. Magnetic resonance spectroscopy was used to determine myoglobin desaturation, and an O2 half-saturation pressure of 3.2 Torr was used to calculate PMb o 2from saturation. Skeletal muscleV˙o 2 max at 12, 21, and 100% O2 was 0.86 ± 0.1, 1.08 ± 0.2, and 1.28 ± 0.2 ml ⋅ min−1 ⋅ ml−1, respectively. The 100% O2 values approached twice that previously reported in human skeletal muscle. PMb o 2values were 2.3 ± 0.5, 3.0 ± 0.7, and 4.1 ± 0.7 Torr while the subjects breathed 12, 21, and 100% O2, respectively. From 12 to 21% O2,V˙o 2 and PMb o 2were again proportionately related. However, 100% O2 increasedV˙o 2 max relatively less than PMb o 2, suggesting an approach to maximal mitochondrial capacity with 100% O2. These data 1) again demonstrate very low cytoplasmic [Formula: see text] atV˙o 2 max, 2) are consistent with supply limitation of V˙o 2 maxof trained skeletal muscle, even in hyperoxia, and 3) reveal a disproportionate increase in intracellular [Formula: see text] in hyperoxia, which may be interpreted as evidence that, in trained skeletal muscle, very high mitochondrial metabolic limits to muscleV˙o 2 are being approached.
Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading
Authors: Ingalls Christopher P. , Warren Gordon L. , Armstrong R. B.
Published: December 2017

The objective of this study was to determine whether altered intracellular Ca2+ handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice ( n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice ( n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice ( n = 10) that had normal cage activity. Maximum isometric tetanic force (Po) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca2+ concentration ([Ca2+]i), tetanic [Ca2+]i, and 4-chloro- m-cresol-induced [Ca2+]iwere measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca2+]iabove control by 36% and 24%, respectively. Although unloading reduced Po and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca2+]i. Po, specific force, and tetanic [Ca2+]iwere reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca2+]iwas not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca2+ homeostasis, changes in tetanic [Ca2+]ido not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca2+]i.
Appetite at “high altitude” [Operation Everest III (Comex-’97)]: a simulated ascent of Mount Everest
Authors: Westerterp-Plantenga Margriet S. , Westerterp Klaas R. , Rubbens Mira , Verwegen Christianne R. T. , Richelet Jean-Paul , Gardette Bernard
Published: December 2017

We hypothesized that progressive loss of body mass during high-altitude sojourns is largely caused by decreased food intake, possibly due to hypobaric hypoxia. Therefore we assessed the effect of long-term hypobaric hypoxia per se on appetite in eight men who were exposed to a 31-day simulated stay at several altitudes up to the peak of Mt. Everest (8,848 m). Palatable food was provided ad libitum, and stresses such as cold exposure and exercise were avoided. At each altitude, body mass, energy, and macronutrient intake were measured; attitude toward eating and appetite profiles during and between meals were assessed by using questionnaires. Body mass reduction of an average of 5 ± 2 kg was mainly due to a reduction in energy intake of 4.2 ± 2 MJ/day ( P < 0.01). At 5,000- and 6,000-m altitudes, subjects had hardly any acute mountain sickness symptoms and meal size reductions ( P < 0.01) were related to a more rapid increase in satiety ( P < 0.01). Meal frequency was increased from 4 ± 1 to 7 ± 1 eating occasions per day ( P < 0.01). At 7,000 m, when acute mountain sickness symptoms were present, uncoupling between hunger and desire to eat occurred and prevented a food intake necessary to meet energy balance requirements. On recovery, body mass was restored up to 63% after 4 days; this suggests physiological fluid retention with the return to sea level. We conclude that exposure to hypobaric hypoxia per se appears to be associated with a change in the attitude toward eating and with a decreased appetite and food intake.
Physiological effects of alveolar, tracheal, and “standard” pressure supports
Authors: Diehl Jean-Luc , Isabey Daniel , Desmarais Gilbert , Brochard Laurent , Harf Alain , Lofaso Frédéric
Published: December 2017

Pressure support (PS) is characterized by a pressure plateau, which is usually generated at the ventilator level (PSvent). We have built a PS device in which the pressure plateau can be obtained at the upper airway level (PSaw) or at the alveolar level (PSA). The effect of these different PS modes was evaluated in seven healthy men during air breathing and 5% CO2breathing. Minute ventilation during air breathing was higher with PSAthan with PSawand lower with PSvent(16 ± 3, 14 ± 3, and 11 ± 2 l/min, respectively). By contrast, there were no significant differences in minute ventilation during 5% CO2breathing (25 ± 5, 27 ± 7, and 23 ± 5 l/min, respectively). The esophageal pressure-time product per minute was lower with PSAthan with PSawand PSventduring air breathing (29 ± 26, 44 ± 44, and 48 ± 30 cmH2O ⋅ s, respectively) and 5% CO2breathing (97 ± 40, 145 ± 62, and 220 ± 41 cmH2O ⋅ s, respectively). In conclusion, during PS, moving the inspiratory pressure plateau from the ventilator to the alveolar level reduces pressure output, particularly at high ventilation levels.
Effect of hemodilution on RBC velocity, supply rate, and hematocrit in the cerebral capillary network
Authors: Hudetz Antal G. , Wood James D. , Biswal Bharat B. , Krolo Ines , Kampine John P.
Published: December 2017

The effect of isovolemic hemodilution on the circulation of red blood cells (RBCs) in the cerebrocortical capillary network was studied by intravital videomicroscopy with use of a closed-cranial-window technique in the rat. Velocity and supply rate of RBCs were measured by tracking the movement and counting the number of fluorescently labeled cells. Arterial blood was withdrawn in increments of 2 ml and replaced by serum albumin. Arterial blood pressure was maintained constant with an infusion of methoxamine. Both velocity and supply rate of RBCs increased, by approximately equal amounts, as arterial hematocrit was reduced from 44 to 15%. The maximum increase in RBC velocity was 4.6 and in RBC supply rate was 5.2 times the baseline value. Calculated lineal density of RBC, an index of capillary hematocrit, did not change with hemodilution. The results suggest that RBC flow and oxygen supply in the cerebral capillary network are maintained during isovolemic hemodilution. The “optimal hematocrit” is as low as 15%.
Intratracheal anti-tumor necrosis factor-α antibody attenuates ventilator-induced lung injury in rabbits
Authors: Imai Yumiko , Kawano Toshio , Iwamoto Sanju , Nakagawa Satoshi , Takata Masao , Miyasaka Katsuyuki
Published: December 2017

To evaluate the role of tumor necrosis factor (TNF)-α in the pathogenesis of ventilator-induced lung injury, we 1) measured TNF-α production in the lung caused by conventional mechanical ventilation (CMV) and 2) evaluated the protective effect of anti-TNF-α antibody (Ab) in saline-lavaged rabbit lungs. After they received saline lung lavage, rabbits were intratracheally instilled with 1 mg/kg of polyclonal anti-TNF-α Ab in the high-dose group ( n = 6), 0.2 mg/kg of anti-TNF-α Ab in the low-dose group ( n = 6), serum IgG fraction in the Ab control group ( n = 6), and saline in the saline control group ( n = 7). Animals then underwent CMV for 4 h. Levels of TNF-α in lung lavage fluid were significantly higher after CMV than before in both control groups. Pretreatment with intratracheal instillation of high and low doses of anti-TNF-α Ab improved oxygenation and respiratory compliance, reduced the infiltration of leukocytes, and ameliorated pathological findings. CMV led to TNF-α production in the lungs, and intratracheal instillation of anti-TNF-α Ab attenuated CMV-induced lung injury in this model.
Responses of group III and IV muscle afferents to distension of the peripheral vascular bed
Authors: Haouzi Philippe , Hill Janeen M. , Lewis Brock K. , Kaufman Marc P.
Published: December 2017

This study was undertaken to test the hypothesis that group III and IV afferents with endings in skeletal muscle signal the distension of the peripheral vascular network. The responses of these slowly conducting afferents to pharmacologically induced vasodilation and to acute obstruction of the venous drainage of the hindlimbs were studied in barbiturate-anesthetized cats. Afferent impulses arising from endings in the triceps surae muscles were recorded from the L7 and S1 dorsal roots. Fifteen of the 48 group IV and 3 of the 19 group III afferents tested were stimulated by intra-aortic injections of papaverine (2–2.5 mg/kg). Sixty-two percent of the afferents that responded to papaverine also responded to isoproterenol (50 μg/kg). Seven of the 36 group IV and 2 of the 12 group III afferents tested were excited by acute distension of the hindlimb venous system. Four of the seven group IV afferents responding to venous distension also responded to papaverine (57 vs. 13% for the nonresponding). Finally, we observed that most of the group IV afferents that were excited by dynamic contractions of the triceps surae muscles also responded either to venous distension or to vasodilatory agents. These results are consistent with the histological findings that a large number of group IV endings have their receptive fields close to the venules and suggest that they can be stimulated by the deformation of these vascular structures when peripheral conductance increases. Moreover, such a mechanism offers the possibility of encoding both the effects of muscle contraction through intramuscular pressure changes and the distension of the venular system, thereby monitoring the activity of the veno-muscular pump.
Postinspiratory activity of costal and crural diaphragm
Authors: Easton P. A. , Katagiri M. , Kieser T. M. , Platt R. S.
Published: December 2017

Because the first stage of expiration or “postinspiration” is an active neurorespiratory event, we expect some persistence of diaphragm electromyogram (EMG) after the cessation of inspiratory airflow, as postinspiratory inspiratory activity (PIIA). The costal and crural segments of the mammalian diaphragm have different mechanical and proprioceptive characteristics, so postinspiratory activity of these two portions may be different. In six canines, we implanted chronically EMG electrodes and sonomicrometer transducers and then sampled EMG activity and length of costal and crural diaphragm segments at 4 kHz, 10.2 days after implantation during wakeful, resting breathing. Costal and crural EMG were reviewed on-screen, and duration of PIIA was calculated for each breath. Crural PIIA was present in nearly every breath, with mean duration 16% of expiratory time, compared with costal PIIA with duration −2.6% of expiratory time ( P < 0.002). A linear regression model of crural centroid frequency vs. length, which was computed during the active shortening of inspiration, did not accurately predict crural EMG centroid frequency values at equivalent length during the controlled relaxation of postinspiration. This difference in activation of crural diaphragm in inspiration and postinspiration is consistent with a different pattern of motor unit recruitment during PIIA.
Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle
Authors: Robinson Tristan M. , Sewell Dean A. , Hultman Eric , Greenhaff Paul L.
Published: December 2017

We examined the effect of glycogen-depleting exercise on subsequent muscle total creatine (TCr) accumulation and glycogen resynthesis during postexercise periods when the diet was supplemented with carbohydrate (CHO) or creatine (Cr) + CHO. Fourteen subjects performed one-legged cycling exercise to exhaustion. Muscle biopsies were taken from the exhausted (Ex) and nonexhausted (Nex) limbs after exercise and after 6 h and 5 days of recovery, during which CHO (CHO group, n = 7) or Cr + CHO (Cr+CHO group, n = 7) supplements were ingested. Muscle TCr concentration ([TCr]) was unchanged in both groups 6 h after supplementation commenced but had increased in the Ex ( P < 0.001) and Nex limbs ( P < 0.05) of the Cr+CHO group after 5 days. Greater TCr accumulation was achieved in the Ex limbs ( P < 0.01) of this group. Glycogen was increased above nonexercised concentrations in the Ex limbs of both groups after 5 days, with the concentration being greater in the Cr+CHO group ( P = 0.06). Thus a single bout of exercise enhanced muscle Cr accumulation, and this effect was restricted to the exercised muscle. However, exercise also diminished CHO-mediated insulin release, which may have attenuated insulin-mediated muscle Cr accumulation. Ingesting Cr with CHO also augmented glycogen supercompensation in the exercised muscle.
Daytime blood pressure elevation after nocturnal hypoxia
Authors: Arabi Yaseen , Morgan Barbara J. , Goodman Brian , Puleo Dominic S. , Xie Ailiang , Skatrud James B.
Published: December 2017

The purpose of this study was to investigate whether nocturnal hypoxia causes daytime blood pressure (BP) elevation. We hypothesized that overnight exposure to hypoxia leads the next morning to elevation in BP that outlasts the hypoxia stimulus. We studied the effect on BP of two consecutive night exposures to hypobaric hypoxia in 10 healthy normotensive subjects. During the hypoxia nights, subjects slept for 8 h in a hypobaric chamber at a simulated altitude of 4,000 m (barometric pressure = 462 mmHg). Arterial O2saturation and electrocardiogram were monitored throughout the night. For 30 min before the nocturnal simulated ascent and for 4 h after return to baseline altitude the next morning, BP was measured every 5 min while the subject was awake. The same measurements were made before and after 2 normoxic nights of sleep in the hypobaric chamber at ambient barometric pressure (745 mmHg). Principal components analysis was applied to evaluate patterns of BP response after the second night of hypoxia and normoxia. A distinct pattern of diastolic BP (DBP) elevation was observed after the hypoxia night in 9 of the 10 subjects but in none after the normoxia night. This pattern showed a mean increase of 4 mmHg in DBP compared with the presleep-awake baseline in the first 60 min and a return to baseline by 90 min. We conclude that nocturnal hypoxia leads to a carryover elevation of daytime DBP.