bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of alae nasi activation on maximal nasal inspiratory airflow in humans
Authors: Gold Avram R. , Smith Philip L. , Schwartz Alan R.
Published: December 2017

The upper airway is a complicated structure that is usually widely patent during inspiration. However, on inspiration during certain physiological and pathophysiological states, the nares, pharynx, and larynx may collapse. Collapse at these locations occurs when the transmural pressure (Ptm) at a flow-limiting site (FLS) falls below a critical level (Ptm′). On airway collapse, inspiratory airflow is limited to a maximal level (V˙i max) determined by (−Ptm′)/Rus, where Rus is the resistance upstream to the FLS. The airflow dynamics of the upper airway are affected by the activity of its associated muscles. In this study, we examine the modulation ofV˙i maxby muscle activity in the nasal airway under conditions of inspiratory airflow limitation. Each of six subjects performed sniffs through one patent nostril (pretreated with an alpha agonist) while flaring the nostril at varying levels of dilator muscle (alae nasi) EMG activity (EMGan). For each sniff, we located the nasal FLS with an airway catheter and determinedV˙i max, Ptm′, and Rus. Activation of the alae nasi from the lowest to the highest values of EMGan increasedV˙i maxfrom 422 ± 156 to 753 ± 291 ml/s ( P < 0.01) and decreased Ptm′ from −3.6 ± 3.0 to −6.0 ± 4.7 cmH2O ( P < 0.05). Activation of the alae nasi had no consistent effect on Rus.V˙i maxwas positively correlated with EMGan, and Ptm′ was negatively correlated with EMGan in all subjects. Our findings demonstrate that alae nasi activation increasesV˙i maxthrough the nasal airway by decreasing airway collapsibility.
Rapid determination of glomerular filtration rate by single-bolus inulin: a comparison of estimation analyses
Authors: Sturgeon Cord , Sam Albert D. , Law William R.
Published: December 2017

Rapid measurement of glomerular filtration rate (GFR) by an inulin single-bolus technique would be useful, but its accuracy has been questioned. We hypothesized that reported inaccuracies reflect the use of inappropriate mathematical models. GFR was measured in 14 intact and 5 unilaterally nephrectomized conscious male Sprague-Dawley rats (mean weight 368 ± 12 g) by both single-bolus (25 mg/kg) and constant-infusion techniques (0.693 mg ⋅ kg−1⋅ min−1). The temporal decline in plasma inulin concentration was analyzed through biexponential curve fitting, which accounted for renal inulin loss before complete vascular and interstitial mixing. We compared our mathematical model based on empirical rationale with those of other investigators whose studies suggest inaccuracy of single-bolus methods. Our mathematical model yielded GFR values by single bolus that agreed with those obtained by constant infusion [slope = 0.94 ± 0.16 (SE); y intercept = 0.23 ± 0.64; r = 0.82]. In comparison to the data obtained by constant inulin infusion, this method yielded a very small bias of −0.0041 ± 0.19 ml/min. Two previously reported models yielded unsatisfactory values (slope = 1.46 ± 0.34, y intercept = 0.47 ± 1.5, r = 0.72; and slope = 0.17 ± 1.26, y intercept = 17.15 ± 5.14, r = 0.03). The biases obtained by using these methods were −2.21 ± 0.42 and −13.90 ± 1.44 ml/min, respectively. The data indicate that when appropriate mathematical models are used, inulin clearance after single-bolus delivery can be used to measure GFR equivalent to that obtained by constant infusion of inulin. Attempts to use methods of analysis for simplicity or expediency can result in unacceptable measurements relative to the clinical range of values seen.
Effects of caffeine on blood pressure, heart rate, and forearm blood flow during dynamic leg exercise
Authors: Daniels Jason W. , Molé Paul A. , Shaffrath James D. , Stebbins Charles L.
Published: December 2017

This study examined the acute effects of caffeine on the cardiovascular system during dynamic leg exercise. Ten trained, caffeine-naive cyclists (7 women and 3 men) were studied at rest and during bicycle ergometry before and after the ingestion of 6 mg/kg caffeine or 6 mg/kg fructose (placebo) with 250 ml of water. After consumption of caffeine or placebo, subjects either rested for 100 min (rest protocol) or rested for 45 min followed by 55 min of cycle ergometry at 65% of maximal oxygen consumption (exercise protocol). Measurement of mean arterial pressure (MAP), forearm blood flow (FBF), heart rate, skin temperature, and rectal temperature and calculation of forearm vascular conductance (FVC) were made at baseline and at 20-min intervals. Plasma ANG II was measured at baseline and at 60 min postingestion in the two exercise protocols. Before exercise, caffeine increased both systolic blood pressure (17%) and MAP (11%) without affecting FBF or FVC. During dynamic exercise, caffeine attenuated the increase in FBF (53%) and FVC (50%) and accentuated exercise-induced increases in ANG II (44%). Systolic blood pressure and MAP were also higher during exercise plus caffeine; however, these increases were secondary to the effects of caffeine on resting blood pressure. No significant differences were observed in heart rate, skin temperature, or rectal temperature. These findings indicate that caffeine can alter the cardiovascular response to dynamic exercise in a manner that may modify regional blood flow and conductance.
Long-term effects of clenbuterol on diaphragm morphology and contractile properties in emphysematous hamsters
Authors: Van Der Heijden H. F. M. , Dekhuijzen P. N. R , Folgering H. , Ginsel L. A. , Van Herwaarden C. L. A.
Published: December 2017

The aim of the present study was to investigate the effect of chronic long-term clenbuterol treatment (1 mg/kg subcutaneously twice a day for 12 wk) on diaphragm morphology and function in emphysematous (EH) and normal hamsters (NH). Clenbuterol increased body weight, diaphragm weight, and skeletal muscle weight in both EH and NH to a similar extent. In the diaphragm, clenbuterol significantly increased myosin heavy chain type I, IIa, and IIx muscle fiber cross-sectional areas by ∼35–55% in both EH and NH. This response to clenbuterol treatment was not significantly different between EH and NH diaphragm. In EH, twitch force (Pt), maximal tetanic force, and force-frequency curve were significantly reduced compared with NH. In EH, clenbuterol increased Pt by ∼10%, restoring Pt to NH level. A similar improvement was observed in the force-frequency characteristics. Clenbuterol did not alter contractile properties in NH. In conclusion, long-term clenbuterol treatment resulted in an increased size of all diaphragm muscle fiber types in both NH and EH. Clenbuterol completely abolished the reduced force generation induced by emphysema.
Airway-parenchymal interdependence after airway contraction in rat lung explants
Authors: Adler Andy , Cowley Elizabeth A. , Bates Jason H. T. , Eidelman David H.
Published: December 2017

The constriction of pulmonary airways is limited by the tethering effect exerted by parenchymal attachments. To characterize this tethering effect at the scale of intraparenchymal airways, we studied the pattern of parenchymal distortion due to bronchoconstriction in a rat lung explant system. First, we measured the elastic modulus under tension for 2% (wt/vol) agarose alone (37.6 ± 1.5 kPa) and for agarose-filled lung (5.7 ± 1.3 kPa). The latter is similar to the elastic modulus of air-filled lung at total lung capacity (4.5–6 kPa) (S. J. Lai-Fook, T. A. Wilson, R. E. Hyatt, and J. R. Rodarte. J. Appl. Physiol. 40: 508–513, 1976), suggesting that explants can be used as a model of lung tissue distortion. Subsequently, confocal microscopic images of fluorescently labeled 0.5-mm-thick explants prepared from agarose-filled rat lungs inflated to total lung capacity (48 ml/kg) were acquired. Images were taken before and after airway constriction was induced by direct application of 10 mM methacholine, and the pattern of parenchymal distortion was measured from the displacement of tissue landmarks identified in each image for 14 explants. The magnitude of the radial component of tissue displacement was calculated as a function of distance from the airway wall and characterized by a parameter, b, describing the rate at which tissue movement decreased with radial distance. The parameter b was 0.994 ± 0.19 (SE), which is close to the prediction of b = 1 of micromechanical modeling (T. A. Wilson. J. Appl. Physiol. 33: 472–478, 1972). There was significant variability in b, however, which was correlated with the fractional reduction in airway diameter ( r = 0.496). Additionally, parenchymal distortion showed significant torsion with respect to the radial direction. This torsion was similar in concentric zones around the airway, suggesting that it originates from inhomogeneity in the parenchyma rather than inhomogeneous airway constriction. Our results demonstrate the significance of the nonlinear mechanical properties of alveolar walls and the anisotropy of the parenchyma in determining the nature of airway-parenchymal interdependence.
Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus
Authors: Regensteiner Judith G. , Bauer Timothy A. , Reusch Jane E. B. , Brandenburg Suzanne L. , Sippel Jeffrey M. , Vogelsong Andria M. , Smith Susan , Wolfel Eugene E. , Eckel Robert H. , Hiatt William R.
Published: December 2017

Persons with type II diabetes mellitus (DM), even without cardiovascular complications have a decreased maximal oxygen consumption (V˙o2 max) and submaximal oxygen consumption (V˙o2) during graded exercise compared with healthy controls. We evaluated the hypothesis that change in the rate ofV˙o2in response to the onset of constant-load exercise (measured byV˙o2-uptake kinetics) was slowed in persons with type II DM. Ten premenopausal women with uncomplicated type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had aV˙o2 maxtest. On two separate occasions, subjects performed 7-min bouts of constant-load bicycle exercise at workloads below and above the lactate threshold to enable measurements of V˙o2kinetics and heart rate kinetics (measuring rate of heart rate rise).V˙o2 maxwas reduced in subjects with type II DM compared with both lean and overweight controls ( P < 0.05). Subjects with type II DM had slowerV˙o2and heart rate kinetics than did controls at constant workloads below the lactate threshold. The data suggest a notable abnormality in the cardiopulmonary response at the onset of exercise in people with type II DM. The findings may reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.
Red blood cells do not contribute to removal of K+ released from exhaustively working forearm muscle
Authors: Maassen N. , Foerster M. , Mairbäurl H.
Published: December 2017

K+ released from exercising muscle via K+ channels needs to be removed from the interstitium into the blood to maintain high muscle cell membrane potential and allow normal muscle contractility. Uptake by red blood cells has been discussed as one mechanism that would also serve to regulate red blood cell volume, which was found to be constant despite increased plasma osmolality and K+ concentration ([[Formula: see text]]). We evaluated exercise-related changes in [[Formula: see text]], pH, osmolality, mean cellular Hb concentration, cell water, and red blood cell K+ concentration during exhaustive handgrip exercise. Unidirectional86Rb+(K+) uptake by red blood cells was measured in media with elevated extracellular K+, osmolarity, and catecholamines to simulate particularly those exercise-related changes in plasma composition that are known to stimulate K+ uptake. During exercise [[Formula: see text]] increased from 4.4 ± 0.7 to 7.1 ± 0.5 mmol/l plasma water and red blood cell K+ concentration increased from 137.2 ± 6.0 to 144.6 ± 4.6 mmol/l cell water ( P ≤ 0.05), but the intracellular K+-to-mean cellular Hb concentration ratio did not change.86Rb+uptake by red blood cells was increased by ∼20% on stimulation, caused by activation of the Na+-K+pump and Na+-K+-2Cl−cotransport. Results indicate the K+ content of red blood cells did not change as cells passed the exhaustively exercising forearm muscle despite the elevated [[Formula: see text]]. The tendency for an increase in intracellular K+ concentration was due to a slight, although statistically not significant, decrease in red blood cell volume. K+ uptake, although elevated, was too small to move significant amounts of K+ into red blood cells. Our results suggest that red blood cells do not contribute to the removal of K+ released from muscle and do not regulate their volume by K+uptake during exhaustive forearm exercise.
Reduced leg blood flow during dynamic exercise in older endurance-trained men
Authors: Proctor David N. , Shen Peter H. , Dietz Niki M. , Eickhoff Tamara J. , Lawler Lori A. , Ebersold Ethan J. , Loeffler Darrell L. , Joyner Michael J.
Published: December 2017

It is currently unclear whether aging alters the perfusion of active muscles during large-muscle dynamic exercise in humans. To study this issue, direct measurements of leg blood flow (femoral vein thermodilution) and systemic arterial pressure during submaximal cycle ergometry (70, 140, and 210 W) were compared between six younger (Y; 22–30 yr) and six older (O; 55–68 yr) chronically endurance-trained men. Whole body O2uptake, ventilation, and arterial and femoral venous samples for blood-gas, catecholamine, and lactate determinations were also obtained. Training duration (min/day), estimated leg muscle mass (dual-energy X-ray absorptiometry; Y, 21.5 ± 1.2 vs. O, 19.9 ± 0.9 kg), and blood hemoglobin concentration (Y, 14.9 ± 0.4 vs. O, 14.7 ± 0.2 g/dl) did not significantly differ ( P > 0.05) between groups. Leg blood flow, leg vascular conductance, and femoral venous O2 saturation were ∼20–30% lower in the older men at each work rate (all P < 0.05), despite similar levels of whole body O2 uptake. At 210 W, leg norepinephrine spillover rates and femoral venous lactate concentrations were more than twofold higher in the older men. Pulmonary ventilation was also higher in the older men at 140 (+24%) and 210 (+39%) W. These results indicate that leg blood flow and vascular conductance during cycle ergometer exercise are significantly lower in older endurance-trained men in comparison to their younger counterparts. The mechanisms responsible for this phenomenon and the extent to which they operate in other groups of older subjects deserve further attention.
Thermogenesis in newborn rats after prenatal or postnatal hypoxia
Authors: Mortola Jacopo P. , Naso Lina
Published: December 2017

Oxygen consumption (V˙o 2) was measured in normoxia as ambient temperature (Ta) was lowered from 40 to 15°C, at the rate of 0.5°C/min (thermoneutrality ∼33°C). In 2-day-old rats born in hypoxia after hypoxic gestation, the Ta-V˙o 2relationship was as in controls; their interscapular brown adipose tissue (IBAT) was hypoplastic (less proteins and DNA), with lower concentration of the mitochondrial uncoupling protein thermogenin. In 8-day-old rats exposed to hypoxia postnatally ( day 2 to day 8), at any Ta below thermoneutralityV˙o 2 was higher than in controls; also, in this group IBAT was hypoplastic with decreased thermogenin. Additional measurements under various experimental conditions indicated that the increased thermogenic capacity was not explained by the smaller body mass and increased blood oxygen content or by the eventuality of intermittent cold stimuli during the chronic hypoxia. On the other hand, chronic hypercapnia (3% CO2 in normoxia, from day 2 to day 8) also resulted in increased normoxic thermogenesis. We conclude that chronic hypoxia in the perinatal period 1) reduces IBAT mass and thermogenin concentration and 2) can increase the newborn’s thermogenic capacity because of stress-related mechanisms not specific to hypoxia.
Bed rest decreases mechanically induced myofiber wounding and consequent wound-mediated FGF release
Authors: Clarke Mark S. F. , Bamman Marcas M. , Feeback Daniel L.
Published: December 2017

Using a terrestrial model of spaceflight (i.e., bed rest), we investigated the amount of myofiber wounding and fibroblast growth factor (FGF) release that occurs during unloading. Myofiber wounding was determined by serum levels of the creatine kinase MM (CKMM) isoform before and after bed rest. Serum levels of both acidic FGF (aFGF) and basic FGF were also determined. A second group of subjects was treated in an identical fashion except that they underwent a resistive exercise program during bed rest. Bed rest alone caused significant ( P < 0.05; n = 7) reductions in post-bed-rest serum levels of both CKMM and aFGF, which were paralleled by a significant ( P < 0.05; n = 7) decrease in myofiber size. In contrast, bed rest plus resistive exercise resulted in significant ( P < 0.05; n = 7) increases in post-bed-rest serum levels of both CKMM and aFGF, which were paralleled by inhibition of the atrophic response. These results suggest that mechanically induced, myofiber wound-mediated FGF release may play an important role in the etiology of unloading-induced skeletal muscle atrophy.
Lactate efflux from exercising human skeletal muscle: role of intracellular P O 2
Authors: Richardson Russell S. , Noyszewski Elizabeth A. , Leigh John S. , Wagner Peter D.
Published: December 2017

It remains controversial whether lactate formation during progressive dynamic exercise from submaximal to maximal effort is due to muscle hypoxia. To study this question, we used direct measures of arterial and femoral venous lactate concentration, a thermodilution blood flow technique, phosphorus magnetic resonance spectroscopy (MRS), and myoglobin (Mb) saturation measured by 1H nuclear MRS in six trained subjects performing single-leg quadriceps exercise. We calculated net lactate efflux from the muscle and intracellular[Formula: see text] with subjects breathing room air and 12% O2. Data were obtained at 50, 75, 90, and 100% of quadriceps maximal O2 consumption at each fraction of inspired O2. Mb saturation was significantly lower in hypoxia than in normoxia [40 ± 3 vs. 49 ± 3% (SE)] throughout incremental exercise to maximal work rate. With the assumption of a[Formula: see text] at which 50% of Mb-binding sites are bound with O2 of 3.2 Torr, Mb-associated [Formula: see text] averaged 3.1 ± 0.3 and 2.3 ± 0.2 Torr in normoxia and hypoxia, respectively. Net blood lactate efflux was unrelated to intracellular[Formula: see text] across the range of incremental exercise to maximum ( r = 0.03 and 0.07 in normoxia and hypoxia, respectively) but linearly related to O2 consumption ( r = 0.97 and 0.99 in normoxia and hypoxia, respectively) with a greater slope in 12% O2. Net lactate efflux was also linearly related to intracellular pH ( r = 0.94 and 0.98 in normoxia and hypoxia, respectively). These data suggest that with increasing work rate, at a given fraction of inspired O2, lactate efflux is unrelated to muscle cytoplasmic [Formula: see text], yet the efflux is higher in hypoxia. Catecholamine values from comparable studies are included and indicate that lactate efflux in hypoxia may be due to systemic rather than intracellular hypoxia.
Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance
Authors: Kovacs Eva M. R. , Stegen Jos H. C. H. , Brouns Fred
Published: December 2017

The effect of addition of different dosages of caffeine (Caf) to a carbohydrate-electrolyte solution (CES) on metabolism, Caf excretion, and performance was examined. Subjects ( n = 15) ingested 8 ml/kg of water placebo (Pla-W), 7% CES (Pla-CES), or 7% CES with 150, 225, and 320 mg/l Caf (CES-150, CES-225, and CES-320, respectively) during a warm-up protocol (20 min) and 3 ml/kg at one-third and two-thirds of a 1-h time trial. Performance was improved with Caf supplementation: 62.5 ± 1.3, 61.5 ± 1.1, 60.4 ± 1.0, 58.9 ± 1.0, and 58.9 ± 1.2 min for Pla-W, Pla-CES, CES-150, CES-225, and CES-320, respectively. The postexercise urinary Caf concentration (range 1.3–2.5 μg/ml) was dose dependent and always far below the doping level of the International Olympic Committee (12 μg/ml) in all subjects. Sweat Caf excretion during exercise exceeded postexercise early-void urinary Caf excretion. Caffeinated CES did not enhance free fatty acid availability, ruling out the fact that performance improvement resulted from enhanced fat oxidation. It is concluded that addition of relatively low amounts of Caf to CES improves performance and that postexercise urinary Caf concentration remained low.
Central venous pressure and cardiac function during spaceflight
Authors: White Ronald J. , Blomqvist C. Gunnar
Published: December 2017

Early in spaceflight, an apparently paradoxical condition occurs in which, despite an externally visible headward fluid shift, measured central venous pressure is lower but stroke volume and cardiac output are higher, and heart rate is unchanged from reference measurements made before flight. This paper presents a set of studies in which a simple three-compartment, steady-state model of cardiovascular function is used, providing insight into the contributions made by the major mechanisms that could be responsible for these events. On the basis of these studies, we conclude that, during weightless spaceflight, the chest relaxes with a concomitant shape change that increases the volume of the closed chest cavity. This leads to a decrease in intrapleural pressure, ultimately causing a shift of blood into the vessels of the chest, increasing the transmural filling pressure of the heart, and decreasing the central venous pressure. The increase in the transmural filling pressure of the heart is responsible, through a Starling-type mechanism, for the observed increases in heart size, left ventricular end-diastolic volume, stroke volume, and cardiac output.
Epidermal growth factor increases lung liquid clearance in rat lungs
Authors: Sznajder Jacob I. , Ridge Karen M. , Yeates Donovan B. , Ilekis John , Olivera Walter
Published: December 2017

Epidermal growth factor (EGF) has been reported to stimulate the proliferation of epithelial cells and increase Na+flux and Na+-K+-ATPase function in alveolar epithelial cell monolayers. Increases in Na+-K+-ATPase in alveolar type II cells (AT2) have been associated with increased active Na+transport and lung edema clearance across the rat alveolar epithelium in a model of proliferative lung injury. Thus we tested whether administration of aerosolized EGF to rat lungs would increase active Na+transport and lung liquid clearance. Sixteen adult Sprague-Dawley male rats were randomized to three groups. To a group of six rats, an aerosol generated from 20 μg of EGF in saline was delivered to the lungs, to a second group of five rats only aerosolized saline was delivered, and a third group of five rats without treatment served as the control. Forty-eight hours postaerosolization of rat lungs with EGF there was an ∼40% increase in active Na+transport and lung liquid clearance compared with control rats, in the absence of changes in22Na+, [3H]mannitol, and albumin permeabilities. The Na+-K+-ATPase activity in AT2 cells harvested from these lungs was increased in rats that received aerosolized EGF compared with AT2 cells from both control rats and rats receiving aerosolized saline. These results support the hypothesis that in vivo delivery of EGF aerosols upregulates alveolar epithelial Na+-K+-ATPase and increases lung liquid clearance in rats.
Effects of NaHCO3loading on acid-base balance, lactate concentration, and performance in racing greyhounds
Authors: Kesl Lyle D. , Engen Richard L.
Published: December 2017

This investigation examined the effects of NaHCO3loading on lactate concentration ([La]), acid-base balance, and performance for a 603.5-m sprint task. Ten greyhounds completed a NaHCO3(300 mg/kg body weight) and control trial in a crossover design. Results are expressed as means ± SE. Presprint differences ( P < 0.05) were found for NaHCO3vs. control, respectively, for blood pH (7.47 ± 0.01 vs. 7.42 ± 0.01), [Formula: see text] (28.4 ± 0.4 vs. 23.5 ± 0.3 meq/l), and base excess (5.0 ± 0.3 vs. 0.2 ± 0.3 meq/l). Peak blood [La] increased ( P < 0.05) in NaHCO3vs. control (20.4 ± 1.6 vs. 16.9 ± 1.3 mM, respectively). Relative to control, NaHCO3produced a greater ( P < 0.05) reduction in blood base excess (−18.5 ± 1.4 vs. −14.1 ± 0.8 meq/l) and[Formula: see text] (−17.4 ± 1.2 vs. −12.8 ± 0.7 meq/l) from presprint to postexercise. Postexercise peak muscle H+concentration ([H+]) was higher ( P < 0.05) in NaHCO3vs. control (158.8 ± 8.8 vs. 137.0 ± 5.3 nM, respectively). Muscle [H+] recovery half-time (7.2 ± 1.6 vs. 11.3 ± 1.6 min) and time to predose values (22.2 ± 2.4 vs. 32.9 ± 4.0 min) were reduced ( P < 0.05) in NaHCO3vs. control, respectively. No differences were found in blood [H+] or blood [La] recovery curves or performance times. NaHCO3increased postexercise blood [La] but did not reduce the muscle or blood acid-base disturbance associated with a 603.5-m sprint or significantly affect performance.
Mechanism of leg stiffness adjustment for hopping on surfaces of different stiffnesses
Authors: Farley Claire T. , Houdijk Han H. P. , Van Strien Ciska , Louie Micky
Published: December 2017

When humans hop in place or run forward, leg stiffness is increased to offset reductions in surface stiffness, allowing the global kinematics and mechanics to remain the same on all surfaces. The purpose of the present study was to determine the mechanism for adjusting leg stiffness. Seven subjects hopped in place on surfaces of different stiffnesses (23–35,000 kN/m) while force platform, kinematic, and electromyographic data were collected. Leg stiffness approximately doubled between the most stiff surface and the least stiff surface. Over the same range of surfaces, ankle torsional stiffness increased 1.75-fold, and the knee became more extended at the time of touchdown (2.81 vs. 2.65 rad). We used a computer simulation to examine the sensitivity of leg stiffness to the observed changes in ankle stiffness and touchdown knee angle. Our model consisted of four segments (foot, shank, thigh, head-arms-trunk) interconnected by three torsional springs (ankle, knee, hip). In the model, an increase in ankle stiffness 1.75-fold caused leg stiffness to increase 1.7-fold. A change in touchdown knee angle as observed in the subjects caused leg stiffness to increase 1.3-fold. Thus both joint stiffness and limb geometry adjustments are important in adjusting leg stiffness to allow similar hopping on different surfaces.
Deterioration of cerebral autoregulation during orthostatic stress: insights from the frequency domain
Authors: Zhang Rong , Zuckerman Julie H. , Levine Benjamin D.
Published: December 2017

To determine whether dynamic cerebral autoregulation is impaired during orthostatic stress, cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler) and mean arterial pressure (MAP; Finapres) were measured continuously in 12 healthy subjects during ramped maximal lower body negative pressure (LBNP) to presyncope. Velocity and pressure were averaged over 6-min periods of stable data at rest and during LBNP to examine steady-state cerebral hemodynamics. Beat-to-beat variability of velocity and pressure were quantified by a “variation index” (oscillatory amplitude/steady-state mean value) and by power spectral analysis. The dynamic relationship between changes in pressure and velocity was evaluated by the estimates of transfer and coherence function. The results of the study were as follows. Steady-state MAP remained relatively constant during LBNP, whereas CBF velocity decreased progressively by 6, 15, and 21% at −30, −40, and −50 mmHg LBNP, respectively ( P < 0.05 compared with baseline). At the maximal level of LBNP (30 s before presyncope) MAP decreased by 9.4% in association with a prominent reduction in velocity by 24% ( P < 0.05 compared with baseline). The variation index of pressure increased significantly from 3.8 ± 0.3% at baseline to 4.5 ± 0.6% at −50 mmHg LBNP in association with an increase in the variation index of velocity from 6.0 ± 0.6 to 8.4 ± 0.7% ( P < 0.05). Consistently, the low- (0.07–0.20 Hz) and high-frequency (0.20–0.30 Hz) power of variations in pressure and velocity increased significantly at high levels of LBNP ( P < 0.05) in association with an increase in transfer function gain (24% at −50 mmHg, P < 0.05). We conclude that the damping effects of autoregulation on variations in CBF velocity are diminished during orthostatic stress in association with substantial falls in steady-state CBF velocity. We suggest that these changes may contribute in part to the development of presyncope.
Laryngeal-receptor responses to phasic CO2 in anesthetized cats
Authors: Bradford A. , McKeogh D. , O’Regan R. G.
Published: December 2017

We compared the effects of CO2 applied continuously and during expiration on laryngeal-receptor activity in paralyzed, artificially ventilated and nonparalyzed, spontaneously breathing cats by using an isolated larynx, artificially ventilated to approximate a normal respiratory cycle. The majority of quiescent negative-pressure and all cold receptors were excited by 5 and 9% CO2 applied both continuously and during expiration. In general, quiescent positive-pressure, tonic negative-pressure, and tonic positive-pressure receptors were inhibited by 5 and 9% CO2 applied continuously and during expiration. There were no significant differences between responses to 5 and 9% CO2 or to continuous and expired CO2 or between paralyzed and nonparalyzed preparations. In conclusion, laryngeal receptors respond to changes in CO2 concentration occurring during a normal respiratory cycle. Because laryngeal-receptor stimulation exerts reflex effects on ventilation and upper airway muscle activity, these results suggest that airway CO2 plays a role in reflex regulation of breathing and upper airway patency.
Nitric oxide and cutaneous active vasodilation during heat stress in humans
Authors: Kellogg D. L. , Crandall C. G. , Liu Y. , Charkoudian N. , Johnson J. M.
Published: December 2017

Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions,l-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38–38.5°C, internal temperature rose from 36.66 ± 0.10 to 37.34 ± 0.06°C ( P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 ± 2 to 44 ± 5% of maximum, but only rose from 13 ± 2 to 30 ± 5% of maximum at l-NAME-treated sites ( P < 0.05 between sites) during heat stress. l-NAME had no effect on sweat rate ( P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.
Prolonged exercise increases peripheral plasma ACTH, CRH, and AVP in male athletes
Authors: Inder W. J. , Hellemans J. , Swanney M. P. , Prickett T. C. R. , Donald R. A.
Published: December 2017

We wished to determine whether the increased ACTH during prolonged exercise was associated with changes in peripheral corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP). Six male triathletes were studied during exercise: 1 h at 70% maximal oxygen consumption, followed by progressively increasing work rates until exhaustion. Data obtained during the exercise session were compared with a nonexercise control session. Venous blood was sampled over a 2-h period for cortisol, ACTH, CRH, AVP, renin, glucose, and plasma osmolality. There were significant increases by ANOVA on log-transformed data in plasma cortisol ( P = 0.002), ACTH ( P < 0.001), CRH ( P < 0.001), and AVP ( P < 0.03) during exercise compared with the control day. A variable increase in AVP was observed after the period of high-intensity exercise. Plasma osmolality rose with exercise ( P < 0.001) and was related to plasma AVP during submaximal exercise ( P < 0.03) but not with the inclusion of data that followed the high-intensity exercise. This indicated an additional stimulus to the secretion of AVP. The mechanism by which ACTH secretion occurs during exercise involves both CRH and AVP. We hypothesize that high-intensity exercise favors AVP release and that prolonged duration favors CRH release.
Activity of respiratory pump and upper airway muscles during sleep onset
Authors: Worsnop Christopher , Kay Amanda , Pierce Robert , Kim Young , Trinder John
Published: December 2017

Ventilation decreases at sleep onset. This change is initiated abruptly at α-θ electroencephalographic transitions. The aim of this study was to determine the contributions of reduced activity in respiratory pump muscles and upper airway dilator muscles to this change. Surface electromyograms over the diaphragm (Di) and intercostal muscles and fine-wire intramuscular electrodes in genioglossus (GG) and tensor palatini (TP) muscles were recorded in nine healthy young men. It was shown that phasic Di and both phasic and tonic TP activities were lower during θ than during α activity. Breath-by-breath analysis of the changes at α-θ transitions during the sleep-onset period showed a number of changes. At α-θ transitions, phasic activity of Di, intercostal, and GG muscles fell and rose again, and phasic and tonic activities of TP fell and remained at low levels during θ. With a state transition from θ to α, the phasic and tonic activities of the Di, GG, and TP increased dramatically. It is now clear that the fall in ventilation that occurs with sleep is related to a fall in activities of both upper airway dilator muscles and respiratory pump muscles.
Vascular resistance and the efficacy of red cell substitutes in a rat hemorrhage model
Authors: Winslow Robert M. , Gonzales Armando , Gonzales Maria L. , Magde Michael , McCarthy Michael , Rohlfs Ronald J. , Vandegriff Kim D.
Published: December 2017

We have compared polyethylene glycol-modified bovine hemoglobin (PEG-Hb; high O2affinity, high viscosity, high oncotic pressure) and human hemoglobin cross-linked between the α-chains (αα-Hb; low O2affinity, low viscosity, low oncotic pressure) with a non-O2-carrying plasma expander (pentastarch, high viscosity and oncotic pressure) after a 50% (by volume) exchange transfusion followed by a severe (60% of blood volume) hemorrhage. Mean arterial pressure and systemic vascular resistance rose significantly in the αα-Hb but not in the PEG-Hb animals. Two-hour survival was greater in the PEG-Hb animals (93%) than in control (35%), pentastarch (8%), or αα-Hb (6%) animals. In the PEG-Hb animals, there was no disturbance of acid-base balance, significantly less accumulation of lactic acid, and higher cardiac output than in the other groups. The data suggest that the rise in vascular resistance that follows αα-Hb exchange transfusion offsets the additional O2transport provided by the cell-free hemoglobin. When resistance does not rise, as with PEG-Hb, even relatively small amounts of cell-free hemoglobin appear to be a very effective blood replacement.
Effects of hyperchloremia on blood oxygen binding in healthy calves
Authors: Cambier C. , Detry B. , Beerens D. , Florquin S. , Ansay M. , Frans A. , Clerbaux T. , Gustin P.
Published: December 2017

Three different levels of hyperchloremia were induced in healthy Friesian calves to study the effects of chloride on blood oxygen transport. By infusion, the calves received either 5 ml/kg of 0.9% NaCl (low-level hyperchloremia; group A), 5 ml/kg of 7.5% NaCl (moderate hyperchloremia; group B), or 7.5 ml/kg of 7.5% NaCl (high-level hyperchloremia; group C). Blood was sampled from the jugular vein and the brachial artery. Chloride concentration, hemoglobin content, arterial and venous pH, [Formula: see text], and[Formula: see text] were determined. At each time point (0, 15, 30, 60, and 120 min), the whole blood oxygen equilibrium curve (OEC) was measured under standard conditions. In groups B and C, hyperchloremia was accompanied by a sustained rightward shift of the OEC, as indicated by the significant increase in the standard [Formula: see text] at 50% hemoglobin saturation. Infusion of hypertonic saline also induced relative acidosis. The arterial and venous OEC were calculated, with body temperature, pH, and [Formula: see text] values in arterial and venous blood taken into account. The degree of blood desaturation between the arterial and the venous compartments [O2exchange fraction (OEF%)] and the amount of oxygen released at tissue level by 100 ml of bovine blood (OEF vol%) were calculated from the arterial and venous OEC combined with the [Formula: see text] and hemoglobin concentration. The chloride-induced rightward shift of the OEC was reinforced by the relative acidosis, but the altered[Formula: see text] values combined with the lower hemoglobin concentration explained the absence of any significant difference in OEF (% and vol%). We conclude that infusion of hypertonic saline induces hyperchloremia and acidemia, which can explain the OEC rightward shift observed in arterial and peripheral venous blood.
Endothelial modulation of neural sympathetic vascular tone in canine skeletal muscle
Authors: King-VanVlack C. E. , Curtis S. E. , Mewburn J. D. , Cain S. M. , Chapler C. K.
Published: December 2017

The effect of nitric oxide synthase (NOS) inhibition and endothelin-A (ETA)-receptor blockade on neural sympathetic control of vascular tone in the gastrocnemius muscle was examined in anesthetized dogs under conditions of constant flow. Muscle perfusion pressure (MPP) was measured before and after NOS inhibition ( Nω-nitro-l-arginine methyl ester; l-NAME) and ETA-receptor blockade [ cyclo-(d-Trp- d-Asp-Pro-d-Val-Leu); BQ-123]. Zero and maximum sympathetic nerve activities were achieved by sciatic nerve cold block and stimulation, respectively. In group 1( n = 6), MPP was measured 1) before nerve cold block, 2) during nerve cold block, and 3) during nerve stimulation. Measurements under these conditions were repeated afterl-NAME and then BQ-123. The same protocol was followed in group 2( n = 6) except that the order ofl-NAME and BQ-123 was reversed. MPP and muscle vascular resistance (MVR) increased afterl-NAME and then decreased to control values after BQ-123. MVR decreased after BQ-123 alone and, with the addition of l-NAME, increased to a level not different from that observed during the control period. MVR fell during nerve cold block. This response was not affected by administration ofl-NAME followed by BQ-123, but it was attenuated by administration of BQ-123 beforel-NAME. The constrictor response during sympathetic nerve stimulation was enhanced byl-NAME; no further effect was observed with BQ-123, nor was the response affected when BQ-123 was given first. These findings indicate that endothelin contributes to 1) basal vascular tone in skeletal muscle and 2) the increase in skeletal muscle vascular resistance after NOS inhibition. Finally, nitric oxide “buffers” the degree of constriction in skeletal muscle vasculature during maximal sympathetic stimulation.
Chemo- and baroresponses differ in African-Americans and Caucasians in sleep
Authors: Crisostomo Isabel , Zayyad Adel , Carley David W. , Abubaker Jawed , Önal Ergün , Stepanski Edward J. , Lopata Melvin , Basner Robert C.
Published: December 2017

To determine sleep effects on baro- and ventilatory responses to transient chemo- and barostimulation in African-Americans and Caucasians, 26 nonobese normotensive young subjects (13 African-Americans and 13 Caucasians) were studied awake and in non-rapid-eye movement (NREM) and rapid-eye-movement sleep during induced transient hypoxemia (N2), hypertension (phenylephrine, PE), and concomitant hypoxemia and hypertension (N2+ PE). Arterial blood pressure was recorded by plethysmographic volume clamp, minute ventilation by pneumotachograph, and arterial O2saturation by pulse oximeter. For all subjects, chronotropic baroresponse (Δpulse interval/Δsystolic blood pressure, where Δ is change) increased with NREM sleep ( P = 0.007). Baroresponse slope was greater in Caucasians than in African-Americans (ANOVA, P = 0.02). Hypoxemic ventilatory response (Δminute ventilation/Δarterial O2saturation) was greater in African-Americans than in Caucasians in NREM sleep ( P = 0.01), as was hypoxemic attenuation of baroresponse (N2+ PE, P = 0.03). These data suggest sleep-related differences in arterial chemo- and baroreceptor responses in normal young African-Americans and Caucasians, which may have implications concerning development of systemic hypertension.
Effect of urokinase on disseminated intravascular coagulation
Authors: Vasquez Yvonne , Williams Charles H. , Hardaway Robert M.
Published: December 2017

Our study evaluated the possible therapeutic effect of urokinase in treating the microthrombiotic effects of disseminated intravascular coagulation by assisting the activation of endogenous plasminogen. Twenty-six pigs were anesthetized, intubated, mechanically ventilated, and surgically catheterized. Septic shock was induced in all 26 pigs by an intravenous infusion of heat-killed Escherichia coli. The pigs were divided into two sets of experiments: in experiment 2( n = 14), one-half received an intravenous dose of urokinase 1 h after heat-killed E. coli infusion and in experiment 3 ( n = 12) one-half received an intravenous bolus dose and a continuous drip of urokinase 2 h after heat-killed E. coli infusion. The untreated pigs served as controls. Hemodynamic parameters, blood chemistries, and blood gases were analyzed. Urokinase given 1 h after bacterial toxin infusion significantly restored blood flow, resulting in an increase in cardiovascular and pulmonary function and improved survival rate (43% control vs. 100% treated, 24-h experimental period). Treatment given after 2 h showed some significant effect on pulmonary function; however, within 10 h of E. coli infusion, mortality rates in control and treated groups were 100 and 83%, respectively. Early administration of urokinase after onset of disseminated intravascular coagulation restored blood flow and helped resolve organ damage.
Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea
Authors: Berry Richard B. , Asyali Musa A. , McNellis Michael I. , Khoo Michael C. K.
Published: December 2017

We studied the within-night variability of the maximum esophageal pressure deflection before apnea termination (DPmax) in nine patients with severe obstructive sleep apnea as an index of the arousal threshold and the mean electroencephalogram (EEG) delta power for each 30 s as an index of the timing of sleep cycles. Periodicity in the time variation of delta power and DPmaxwas analyzed by determining their power spectral density and their relationship determined by cross correlation. DPmaxand delta power varied cyclically and in phase with a major periodicity (major peak in power spectral density) of 117.6 ± 8.8 (SE) min. The correlation between the values of DPmaxand delta power was significant ( P < 0.001) in each subject (mean r = 0.47 ± 0.03), and the coherence between DPmaxand delta power at their dominant frequency was high. Within cycles of non-rapid-eye-movement sleep, DPmaxand delta power increased, reaching peak values on average at or after midcycle. These findings suggest that the arousal threshold to airway occlusion in patients with obstructive sleep apnea varies cyclically during the night synchronous to the underlying cycles of sleep.
Stimulation of breathing by activation of pulmonary peripheral afferents in rabbits
Authors: Yu J. , Zhang J. F. , Fletcher E. C.
Published: December 2017

Respiratory response to selective activation of vagal afferents in the peripheral airways was investigated in anesthetized, open-chest, and artificially ventilated rabbits. Phrenic activity was used as an index of central respiratory drive before and after injection of hypertonic saline (8.1%, 0.1 ml) into the periphery of the lung to stimulate the afferents. The amplitude of “integrated” phrenic activity and phrenic burst rate increased by 19 ± 3.4 and 53.7 ± 12.7% ( n = 23; P < 0.001), respectively. The response peaked at 5.5 ± 1.6 s and returned to the baseline at 7 min (median) after the injection. The magnitude of the response was positively related to the concentration of injected NaCl. The response could not be elicited by injection of normal saline and was abolished by vagotomy. Because artificial ventilation caused phrenic activity to be entrained with the ventilator, respiratory drive was further assessed after the ventilator was stopped. Again, neural hyperpnea and tachypnea were observed. Because activation of a small fraction of the pulmonary peripheral afferents resulted in vigorous stimulation of respiratory drive, we speculate that initiation of this reflex may contribute to hyperpnea and tachypnea under both physiological and pathophysiological conditions.
Letters to the Editor
Authors: Ferretti Guido
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter:

Koga, Shunsaku, Tomoyuki Shiojiri, Narihiko Kondo, and Thomas J. Barstow. Effect of increased muscle temperature on oxygen uptake kinetics during exercise. J. Appl. Physiol. 83(4): 1333–1338, 1997.—To test whether increased muscle temperature (Tm) would improve O2 uptake (V˙o 2) kinetics, seven men performed transitions from rest to a moderate work rate [below the estimated lactate threshold (LTest)] and a heavy work rate (V˙o 2 = 50% of the difference between LTest and peakV˙o 2) under conditions of normal Tm (N) and increased Tm (H), produced by wearing hot water-perfused pants before exercise. Quadriceps Tm was significantly higher in H, but rectal temperature was similar for the two conditions. There were no significant differences in the amplitudes of the fast component ofV˙o 2 or in the time constants of the on and off transients for moderate and heavy exercise between the two conditions. The increment inV˙o 2 between the 3rd and 6th min of heavy exercise was slightly but significantly smaller for H than for N. These data suggest that elevated Tm before exercise onset, which would have been expected to increase O2delivery and off-loading to the muscle, had no appreciable effect on the fast exponential component ofV˙o 2 kinetics (invariant time constant). These data further suggest that elevated Tm does not contribute to the slow component ofV˙o 2 during heavy exercise.