bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between fructose 2,6-bisphosphate and lactate production in skeletal muscle
Authors: Jones J. P. , MacLean P. S. , Winder W. W.
Published: December 2017

The epinephrine-induced production of lactate in nonexercising muscles may be due in part to allosteric activation of 6-phosphofructo-1-kinase by fructose 2,6-bisphosphate (F-2,6-P2). To determine if a correlation exists between F-2,6-P2 and lactate production in skeletal muscle, isolated rat hindlimbs were perfused for 30 min with a medium containing epinephrine at concentrations varying between 1.7 +/- 0.5 and 72.4 +/- 4.2 nM. In comparison to control values, hindlimbs perfused with 72.4 +/- 4.2 nM epinephrine had a two- to threefold increase in F-2,6-P2 and a fourfold increase in muscle lactate production. Hindlimb lactate production was highly correlated to gastrocnemius adenosine 3′,5′-cyclic monophosphate (r = 0.80), fructose 6-phosphate (r = 0.87), and F-2,6-P2 (r = 0.81). The adenosine 3′,5′-cyclic monophosphate-mediated increase in glycogenolysis with consequent increase in fructose 6-phosphate (substrate for 6-phosphofructo-1-kinase and 6-phosphofructo-2-kinase) is likely important for induction of lactate production by inactive muscle. The high correlation between muscle F-2,6-P2 and muscle lactate production at varying concentrations of epinephrine supports the hypothesis that the epinephrine-induced activation of glycolysis and lactate production in nonexercising muscle is mediated in part by increases in F-2,6-P2 levels.
Dimethyl sulfoxide depresses skeletal muscle contractility
Authors: Reid M. B. , Moody M. R.
Published: December 2017

Dimethyl sulfoxide (DMSO) is commonly used in studies of skeletal muscle as a selective antioxidant (DMSO preferentially scavenges hydroxyl radicals) or as a solvent for drugs. The present experiments tested DMSO for direct effects on diaphragm contractile properties. Fiber bundles were removed from anesthetized rats, mounted in vitro at optimal length (37 degrees C), curarized, and stimulated directly. Protocol 1 tested for contractile depression and dose dependence by comparing bundles treated with DMSO (0.6–640 mM) with time- and stimulus-matched controls. Protocol 2 tested reversibility of 220 mM DMSO effects by using each bundle as its own control. DMSO decreased the relative forces developed during twitch and submaximal tetanic (30- and 60-Hz) contractions, shifting the force-frequency relationship down and to the right. These effects were strongly dose dependent and were reversed by DMSO washout. DMSO had no detectable effect on the forces developed during maximal tetany (200 Hz). DMSO depresses contractile function of diaphragm fibers by reversible dose-dependent inhibition of excitation-contraction coupling.
In situ arterial and brain tissue PCO2 responses to acetazolamide in cats
Authors: Kohshi K. , Konda N. , Kinoshita Y. , Tsuru E. , Yokota A.
Published: December 2017

We have studied how in situ arterial (PaCO2) and brain tissue PCO2 (PbCO2) responses to acetazolamide (AZ) are affected by respiratory patterns. Sixteen cats were anesthetized with ketamine. Group 1 cats (n = 7) breathed air spontaneously. Group 2 cats (n = 6) were paralyzed and ventilated mechanically to maintain PaCO2 at 37 +/- 1 Torr before AZ administration; the respiratory rate and depth did not change during the course of measurements. Two CO2 sensors to measure in situ PaCO2 and PbCO2 continuously were used. One was placed through a burr hole into the cerebral white matter 15 mm in depth, and another was inserted into the femoral artery. After intravenous administration of AZ (20 mg/kg), PaCO2 decreased, after a significant transient rise, and then returned gradually to the baseline in group 1, but it increased gradually and reached a new steady state in group 2. PbCO2 and the PbCO2-PaCO2 gradient increased remarkably in the two groups immediately after administration. We conclude that AZ resulted in a large increase in both PbCO2 and the PbCO2-PaCO2 gradient and that there are two distinct in situ PaCO2 responses to AZ in spontaneously breathing vs. mechanically ventilated animals. The mechanisms for these observations are discussed.
Effect of training and growth hormone suppression on insulin-like growth factor I mRNA in young rats
Authors: Zanconato S. , Moromisato D. Y. , Moromisato M. Y. , Woods J. , Brasel J. A. , Leroith D. , Roberts C. T. , Cooper D. M.
Published: December 2017

The growth hormone (GH)-insulin-like growth factor I (IGF-I) axis plays a role in the adaptation to exercise training, but IGF-I gene expression in response to exercise training and GH suppression has not been studied. Twenty female rates underwent a 4-wk treadmill training program begun in the prepubertal period (day 14 of life). In 10 of the training rats, GH production was suppressed by anti-GH-releasing hormone antibodies (GH suppressed). IGF-I mRNA and protein levels were measured in liver and hindlimb skeletal muscle. GH suppression reduced IGF-I mRNA expression in the liver to a much greater extent than in the muscle. In the GH control rats, training induced significant increases in hepatic exon 1-derived IGF-I mRNA (mean increase 30%; P < 0.05) and muscle exon 2-derived mRNA (mean increase 35%; P < 0.05). In the GH-suppressed rats, only muscle exon 1-derived transcripts were significantly increased by training (55%; P < 0.05) and this was associated with a significant increase in muscle IGF-I protein levels (P < 0.05). We speculate that the anabolic response to training may involve both GH-dependent increases in IGF-I mRNA in the liver and GH-independent increases in the muscle.
Investigation of computer lung model-predicted DLCO during single-breath maneuvers
Authors: Brenner M. , Babusis A. , Tran V. , Bellusa L. , Pinderski E. , Chen C. , Boyajian J. , Guich S. , Wilson A. F.
Published: December 2017

A computer model based on the theoretical gas absorption equations of Martonen and Wilson (J. Math. Biol. 14: 203–220, 1982) was developed to predict changes in single-breath diffusing capacity of the lung for carbon monoxide (DLCO) with alterations in anatomic dead space, alveolar volume, and inspiratory time. The computer model predictions were compared with results obtained from normal subjects performing DLCO maneuvers under correspondingly altered conditions to assess the validity of the Martonen-Wilson equations. In normal subjects, a theoretical “ideal” single-breath DLCO was derived from measured DLCO and adjusted to instantaneous inspiratory and expiratory times with this three-phase computer model. Clinical single-breath DLCO measurements with increased external dead space and inspiratory and expiratory times in normal subjects correlated well with our mathematical model predictions (all r > 0.80, P < 0.001) but did not correlate closely with the predicted effects of alveolar volume on DLCO. This study demonstrates that uniform gas absorption equations of Martonen and Wilson closely predict changes in observed DLCO with systematic variation of inspiratory and expiratory time in normal subjects at full lung volume and appear to be a reasonable estimation of normal physiological events during single-breath carbon monoxide absorption.
Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats
Authors: Sun D. , Huang A. , Koller A. , Kaley G.
Published: December 2017

We aimed to test the hypothesis that as a consequence of short-term daily bouts of exercise the control of arteriolar smooth muscle by endothelium is altered. Rats ran on a treadmill once a day, 5 days/wk, for 2–4 wk (with gradually increasing intensity, up to 26 min at 22 m/min at a 1% grade by the beginning of the 3rd wk and up to 38 min at 28 m/min at a 2% grade by the beginning of the 4th wk) while a control group remained sedentary (SED). Cannulated and pressurized arterioles of rat gracilis muscle developed spontaneous myogenic tone, which was slightly enhanced in exercised (EX) compared with SED rat arterioles. At 80 mmHg pressure, the passive (Ca(2+)-free solution) and active diameters of SED and EX rat arterioles were 105.4 +/- 3.8 and 55.1 +/- 2.3 microns and 107.1 +/- 3.4 and 50.2 +/- 2.2 microns, respectively. Dose-dependent dilations to sodium nitroprusside (10(-8)-10(-6) M) and constrictions to norepinephrine (10(-8)-10(-6) M) were not affected in EX arterioles, whereas dilations to adenosine (10(-6)-10(-4) M) were significantly reduced. In contrast, dose-dependent dilations to acetylcholine (ACh; 5 x 10(-9)-10(-7) M) and L-arginine [precursor of nitric oxide (NO); 10(-4)-10(-3) M] were significantly enhanced (by 33–78 and 57–75%, respectively) in arterioles of EX compared with those of SED rats. Responses of arterioles to sodium nitrite were not different in SED and EX groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Tracheal vascular response to hypertonic and hypotonic solutions
Authors: Prazma J. , Coleman C. C. , Shockley W. W. , Boucher R. C.
Published: December 2017

One of the major roles of the upper respiratory mucosa is to humidify inspired air. This function requires the coordinated activity of respiratory epithelium and mucosal vasculature. It has been difficult to study this relationship in vivo. In the present study, we investigated the effects of osmolarity on the vessel diameter of mucosal vessels via a specially constructed chamber that allows direct visualization of the rat trachea microvasculature. With use of an anesthetized and instrumented rat preparation, the luminal surface of the dorsal wall of the trachea was superfused with physiological solutions at 37 degrees C. The osmolarities were varied by removing or adding NaCl or mannitol (200, 290, and 500 mosM). The mucosal vessels dilated when the airway surface was superfused with hypertonic solutions and constricted when superfused with hypotonic solution. The largest changes occurred in the arterioles (51 +/- 5.6 microns diam), which constricted by 10 +/- 2.18 microns (P = 0.0001) when exposed to a 200 mosM solution and dilated by 11 +/- 1.55 microns (P = 0.0001) when exposed to a 500 mosM NaCl-enriched solution. Smaller changes of similar pattern were seen in venules. The changes in vessel diameter were readily reversible upon replacement of the hypo- or hypertonic solutions by an isotonic solution. We conclude that increase or decrease of solution osmolarity on the epithelial surface of the trachea can regulate diameter of mucosal blood vessels.
Effect of training on interaction between insulin and exercise in human muscle
Authors: Dela F. , Mikines K. J. , Sonne B. , Galbo H.
Published: December 2017

Exercise adds to the effect of maximal insulin on whole body glucose uptake. Training increases contraction-induced glucose transport measured in vitro but not glucose utilization in human muscle exercising during normoinsulinemia. We studied whether exercise adds to the effect of maximal insulin in human muscle and whether trained (T) and untrained (UT) muscle differ. Six healthy men [23 +/- 0.4 (SE) yr] trained one leg for 10 wk, 6 days/wk, 30 min/day at 70% of one-legged maximal O2 uptake while keeping the other leg sedentary. At 16 h after the last training bout, both femoral veins and a radial artery were catheterized and 150-min hyperinsulinemic (480 mU.min-1.m-2) euglycemic clamp was performed. During the final 30 min, subjects performed two-legged bicycling at 76 +/- 0.3% of maximal heart rate. During exercise, blood flow (597 +/- 45 vs. 572 +/- 37 ml.min-1.kg-1), O2 uptake (74 +/- 6 vs. 68 +/- 6 ml O2.min-1.kg-1), and carbohydrate oxidation (88 +/- 10 vs. 81 +/- 7 mg.min-1.kg-1) increased similarly (P > 0.05) in T and UT legs, respectively. Arteriovenous glucose difference decreased (P < 0.05) during exercise but tended to remain higher in T (0.47 +/- 0.04) than in UT (0.41 +/- 0.05 mol/l) (P < 0.1). Glucose uptake increased with exercise, the increase being higher in T than in UT (change: 28 +/- 5 vs. 23 +/- 5 mg.min-1.kg-1; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Behavior of motor units in human biceps brachii during a submaximal fatiguing contraction
Authors: Garland S. J. , Enoka R. M. , Serrano L. P. , Robinson G. A.
Published: December 2017

The activity of 50 single motor units was recorded in the biceps brachii muscle of human subjects while they performed submaximal isometric elbow flexion contractions that were sustained to induce fatigue. The purposes of this study were to examine the influence of fatigue on motor unit threshold force and to determine the relationship between the threshold force of recruitment and the initial interimpulse interval on the discharge rates of single motor units during a fatiguing contraction. The discharge rate of most motor units that were active from the beginning of the contraction declined during the fatiguing contraction, whereas the discharge rates of most newly recruited units were either constant or increased slightly. The absolute threshold forces of recruitment and derecruitment decreased, and the variability of interimpulse intervals increased after the fatigue task. The change in motor unit discharge rate during the fatigue task was related to the initial rate, but the direction of the change in discharge rate could not be predicted from the threshold force of recruitment or the variability in the interimpulse intervals. The discharge rate of most motor units declined despite an increase in the excitatory drive to the motoneuron pool during the fatigue task.
Systemic acidosis after controlled hypotension activates catechol activity in the vasomotor center
Authors: Bruandet N. , Quintin L.
Published: December 2017

Activation of the catechol metabolism, assessed with in vivo voltammetry, in the vasopressor area of the vasomotor center was investigated during systemic acidosis occurring after controlled hypotension. Rats anesthetized with halothane were mechanically ventilated. Sodium nitroprusside lowered mean arterial pressure to 55 mmHg for > or = 20 min. Arterial blood gases allowed us to group rats according to whether they showed symptoms of metabolic acidosis (pH < or = 7.34) immediately after controlled hypotension. To assess the effect of systemic acidosis independently of the progressive decline in pressure observed during the recovery period after controlled hypotension, we used phenylephrine infusion to maintain mean arterial pressure at baseline pressure during the recovery period after controlled hypotension in two groups of animals. Systemic acidosis increased the catechol signal in a prolonged manner [nitroprusside with acidosis (n = 7) vs. nitroprusside without acidosis (n = 5); P < 0.0001]. This catechol activation was greater when pressure was restored after hypotension [nitroprusside with acidosis plus phenylephrine (n = 5) vs. nitroprusside with acidosis over the whole interval (from -30 to +150 min); P < 0.05]. When the nitroprusside with acidosis group and nitroprusside with acidosis plus phenylephrine group were compared, hypercapnia had an involvement in the larger increase of the catechol signal observed in the nitroprusside with acidosis plus phenylephrine group [arterial PCO2: nitroprusside with acidosis vs. nitroprusside with acidosis plus phenylephrine over the whole interval (from -30 to +150 min) and at +30 and +60 min; all P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)
Doppler evaluation of cardiac filling and ejection properties in humans during parabolic flight
Authors: Johns J. P. , Vernalis M. N. , Karemaker J. M. , Latham R. D.
Published: December 2017

The cardiac filling and ejection properties of seven normal human subjects were examined during microgravity created on a National Aeronautics and Space Administration aircraft during parabolic flight. Doppler echocardiography was used to measure intracardiac velocities in sitting and supine subjects during three phases of flight: hypergravity (phase I), early microgravity (phase III), and late microgravity (phase IV). Heart rate declined 6% (P < 0.001) and right ventricular inflow velocities rose (46%, early; 26%, mean; P < 0.01) between phase I and phases III or IV in the sitting position only. Peak left ventricular outflow velocities rose 12% and inflow velocities rose (13%, early; 20%, mean) between phases I and IV while subjects were in the supine position (P < 0.05). A 14% rise in early velocities alone was seen between phases I and IV while subjects were in the sitting position (P < 0.05). In subjects entering microgravity while sitting, right heart chambers can accept additional venous return. When microgravity was entered while subjects were supine, however, venous augmentation was not observed. Left heart filling was more prominently enhanced when microgravity was entered while subjects were supine, suggesting a shift of fluid within the pulmonary vasculature.
Probabilistic model of altitude decompression sickness based on mechanistic premises
Authors: Van Liew H. D. , Conkin J. , Burkard M. E.
Published: December 2017

To develop a predictive equation and to test ideas about the mechanisms involved in hypobaric decompression sickness, we performed statistical analyses on published results of 7,023 exercising O2-breathing men subjected to one-step decompressions in altitude chambers. The dependent variable was signs or symptoms so severe that the person's trial was terminated (forced descent). The three independent variables were 1) duration of 100% O2 breathing at ground level (prebreathing), 2) atmospheric pressure after ascent, and 3) exposure duration. The best model, chosen from trial-and-error combinations of premises about bubble behavior, indicates that decompression sickness outcome depends on 1) prebreathing time, but with an unexpectedly long washout half time for N2; 2) time at altitude, as if bubbles grow; and 3) the estimated difference, raised to the fifth power, between the partial pressure of N2 in tissue before and that in bubbles after decompression, perhaps an index of the number of bubbles generated. We expect the model to provide accurate predictions for decompressions matching those of the bulk of the data; the mechanistic cues should be considered hypotheses for further investigation.
Maximal skin blood flow is decreased in elderly men
Authors: Rooke G. A. , Savage M. V. , Brengelmann G. L.
Published: December 2017

When subjected to total body heating and exercise, skin blood flow does not increase as much in elderly as in young subjects. It is not known whether this age-related decline is due to the autonomic dysfunction that develops in the elderly or to changes at the level of the blood vessels of the skin. We used local heating of the forearm to quantify the intrinsic ability of the cutaneous vasculature to dilate in seven young men (avg age 31 yr) and seven elderly men (avg age 71 yr). A water spray was used to maintain a neutral skin temperature of 32–35 degrees C for > 10 min, followed by 60 min of a 42 degrees C skin temperature to induce maximal skin blood flow. Forearm blood flow was measured by venous occlusion plethysmography with a mercury-in-Silastic circumference gauge. At the neutral skin temperature, forearm blood flows in the elderly subjects were comparable to those in the young subjects: 3.0 +/- 0.5 vs. 2.8 +/- 1.0 ml.min-1 x 100 ml-1. During the last 10 min of heating, however, blood flows were much lower in the elderly than in the young subjects: 11.1 +/- 2.7 vs. 19.9 +/- 5.2 ml.min-1 x 100 ml-1 (P = 0.002). We conclude that aging results in a reduction of the maximal conductance of the cutaneous vasculature.
Force and contractile characteristics after stretch overload in quail anterior latissimus dorsi muscle
Authors: Alway S. E.
Published: December 2017

Stretch overload has been shown to increase muscle mass by increasing fiber size and fiber number in the anterior latissimus dorsi (ALD) of adult Japanese quail. However, the functional significance of these changes is not known. The purpose of this study was to determine if stretch-induced hypertrophy alters function of the ALD. A tube weight corresponding to 12% of the bird's body mass was added to one wing of 12 Japanese quail for 30 days. This increased muscle mass corrected for the increase in non-muscle tissue by 121 +/- 3%. In vitro contractile measures were made at 25 degrees C by direct stimulation of the ALD. Fiber hypertrophy accounted for only 60% of the 95% increase in maximal force in stretched muscles. Specific tension was similar in control (11.1 +/- 0.2 mN/mm2) and experimental muscles (9.2 +/- 0.3 mN/mm2). Stretch-enlarged muscles had significantly greater twitch half-relaxation time (161.9 +/- 7.4 vs. 187.7 +/- 9.7 ms) relative to control muscles. The maximal velocity of loaded shortening decreased from 2.6 +/- 0.4 muscle lengths/s in control muscles to 1.1 +/- 0.1 muscle lengths/s in stretched muscles. The maximal velocity of unloaded shortening decreased from 4.2 +/- 0.6 to 2.6 muscle lengths/s in stretched muscles. These data indicate that 1) twitch duration and shortening velocity are slowed in stretch hypertrophied muscle and 2) new fibers contribute to force production after 30 days of stretch overload.
Calcitonin gene-related peptide modulates pulmonary vascular reactivity in isolated rat lungs
Authors: Janssen P. L. , Tucker A.
Published: December 2017

The role of calcitonin gene-related peptide (CGRP) in modulating hypoxic pulmonary vasoconstriction was assessed. The effects of CGRP and its antagonist [CGRP-(8–37)] on responses to acute hypoxia (3% O2) and angiotensin II (ANG II; 0.4 microgram) were studied in isolated lungs of male Sprague-Dawley rats perfused with a salt solution. Rats with pulmonary hypertension, induced by simulated altitude exposure, were also used to determine the actions of CGRP in a remodeled pulmonary vascular bed. In normotensive (NT) and altitude-exposed (AE) lungs, CGRP injections (10 nM), given after stable pressor responses were attained, attenuated (P < 0.05) subsequent hypoxic pressor responses. Pretreatment with CGRP-(8–37) (10 nM) enhanced (P < or = 0.05) initial ANG II-induced pressor responses in both AE and NT lungs. CGRP-(8–37) pretreatment (10 nM) had little influence on the hypoxic pressor responses in either NT or AE lungs. Results indicate that CGRP modulates hypoxic pulmonary vasoconstriction and that CGRP-(8–37) enhances pressor responses to ANG II in NT and AE rat lungs.
Chloride and inorganic phosphate modulate binding of oxygen to bovine red blood cells
Authors: Gustin P. , Detry B. , Cao M. L. , Chenut F. , Robert A. , Ansay M. , Frans A. , Clerbaux T.
Published: December 2017

The influence of Pi and Cl on the equilibrium of oxygen binding to bovine red blood cells was assessed by plotting the whole blood oxygen dissociation curve measured under standard conditions with and without added KCl and K2HPO4. Both salts shifted the oxygen dissociation curve to the right. This effect was more marked at the highest saturation levels. At a given saturation level, the anion-induced shift was linearly related to the concentration of salt added to the blood. Cl had a greater effect than Pi. The relationship between changes in Po2 at 50% hemoglobin saturation (in Torr) and concentrations of ions added (in mmol/l) was equal to 0.0515[Cl] + 0.0302[Pi] (r2 = 0.94; P < 0.001). These changes were not due to the hyperosmolality induced by salt addition, since sucrose added in place of salts was without effect on the measured parameters. The oxygen exchange fraction expressed as percentage of saturation, i.e., the difference in hemoglobin saturation when Po2 decreases from 130 to 40 Torr, was linearly correlated to added anion concentration (in mmol/l) (= 0.102[Cl] + 0.059[Pi] (r2 = 0.95; P < 0.001)). No significant interaction between the anions was observed; their effects were purely additive. This original mechanism of controlling the oxygen affinity of bovine blood may have clinical relevance: Cl and Pi could be used to increase oxygen transport efficiency in hypoxic animals.
Effect of growth hormone administration and treadmill exercise on the body composition of rats
Authors: Yeh J. K. , Aloia J. F. , Chen M. , Sprintz S.
Published: December 2017

The aim of this study was to compare the effects of growth hormone administration and treadmill exercise on bone mass, body fat mass, and fat-free mass. Forty female rats aged 14 mo were divided into control, ovine growth hormone administration (0.5 mg.kg-1.day-1; GH), treadmill exercise (17 m/min, 60 min/day; EX), and EX + GH groups. Noninvasive total body electrical conductivity and dual X-ray absorptiometry techniques were used to assess the body fat content, fat-free mass, and tibial and L4 vertebral bone mineral content of each experimental animal at weeks 0, 9, and 16. The age-related increase in body fat mass was suppressed in the GH group, and the fat-free mass and L4 bone mass were higher in the GH group than in the control group. Conversely, in the EX group there was no gain in body fat mass and no significant change in fat-free mass or vertebral bone mass. The tibial bone mass increased in both the GH and EX groups; however, the time response to the two interventions appeared to differ. In the EX + GH group there was no further enhancement of the anabolic effect on the tibial bone mass. The effect of growth hormone administration on body fat content and bone mass is distinct from that of treadmill exercise.
Effect of step length optimization on the aerobic demand of running
Authors: Morgan D. , Martin P. , Craib M. , Caruso C. , Clifton R. , Hopewell R.
Published: December 2017

To assess whether distance runners displaying uneconomical freely chosen step lengths (FCSL) could be trained to shift FCSL toward a more optimal setting, six males and three females who exhibited uneconomical FCSL [mean optimal step length (OSL) = -9.81% of leg length from FCSL; mean change in oxygen uptake (VO2) (FCSL - OSL) = 1.46 ml.kg-1.min-1] comprised an experimental group that completed 15 treadmill sessions (30 min/day, 5 days/wk, 3 wk) of OSL training at individually determined running velocities (2.87–3.74 m/s). Training sessions featured alternating 5-min periods of combined audio and visual feedback matching OSL and no feedback. A control group of three subjects with uneconomical FCSL (2 males, 1 female) performed 3 wk of treadmill running without feedback. The extent of step length optimization was evaluated by comparing pre- and posttraining differences between FCSL and OSL and between pre- and posttraining VO2. Compared with the control group, the experimental group demonstrated a significantly (P < or = 0.05) greater relative shift in FCSL toward OSL and a marked reduction in FCSL VO2. Taken together, these results suggest that short-term audiovisual feedback training can be effective in optimizing step length and producing a decrease in aerobic demand among distance runners exhibiting uneconomical FCSL.
Airway and tissue mechanics during physiological breathing and bronchoconstriction in dogs
Authors: Lutchen K. R. , Suki B. , Zhang Q. , Petak F. , Daroczy B. , Hantos Z.
Published: December 2017

In five open-chest dogs and with four to five alveolar capsules we used an optimal ventilator waveform (OVW) to follow frequency and tidal volume (VT) dependence of lung, airway, and tissue resistance (R) and elastance (E) before and during constant infusion of histamine (16 micrograms.kg-1.min-1). OVW contains sufficient flow energy between 0.234 and 4.7 Hz, avoids nonlinear harmonic interactions, and simultaneously ventilates with physiological VT. Each OVW breath permits a smooth estimate of frequency dependence of R and E for the whole lung. A constant-phase model analysis provided estimates of purely viscous resistance (Rvis), which represents the sum of airway resistance (Raw) and any purely newtonian component of tissue resistance (Rti), and parameters G and H, which govern frequency dependence of Rti and tissue elastance (Eti), respectively. Tissue structural damping (eta) is calculated as G/H. This model was applied to the whole lung and tissue impedance as estimated from each capsule. We found a small but inconsequential purely newtonian component of Rti, even during constriction. Four dogs showed a peak response at approximately 4 min in lung Rvis coupled (in time) to initial increases in G, H, eta, and airway inhomogeneities. In two of these dogs the response was severe. Tissue properties estimated from whole lung impedance (G, H, and eta) were nearly identical to values estimated from unobstructed capsules throughout infusion. By using a technique independent of alveolar capsules, our results indicate that a major if not dominant response to a constrictive agonist occurs in lung tissues, resulting in a large increase in Rti and Eti. With severe constriction, significant increases occur in Raw and airway inhomogeneities as well. Finally, separation of airway and tissue properties using input impedance estimated from the frequency-rich OVW avoids use of alveolar capsules and may prove an effective tool for partitioning airway and tissue properties in humans.
Serial distribution of airway mechanical properties in dogs: effects of histamine
Authors: Habib R. H. , Suki B. , Bates J. H. , Jackson A. C.
Published: December 2017

We measured respiratory input impedance (Zin; 8–2,048 Hz) in five dogs (anesthetized, tracheostomized, vagotomized, and mechanically ventilated) during 80 s of apnea after a bolus intravenous injection of saline or histamine (5.0 mg). In the control case, three antiresonances in Zin were found in four of the dogs, whereas in the remaining dog only two were found. The magnitude and frequency of these antiresonances were significantly altered after bronchoconstriction. To interpret Zin, a model incorporating detailed airway geometry, asymmetrical branching, and nonrigid airway walls was developed. The model fit both the saline and histamine Zin data well and predicted a serial distribution of bronchoconstriction consistent with known effects of histamine; i.e., the diameters of the most peripheral airways were reduced (26% of their control values), whereas tracheal diameters were not significantly affected. The model provided estimates of tracheal diameters that were well correlated (r = 0.92) with direct measurements. Control estimates of soft tissue viscosity (1.63 +/- 0.42 cmH2O.s) and Young's modulus (406 +/- 125 cmH2O) compared closely with values in the literature. These results indicate that bronchoconstriction induced by histamine results in significant changes in Zin over this frequency range and that by using this data analysis approach definitive physiological parameters relative to airway geometry and wall mechanical properties can be obtained from measurements made at the airway opening.
Surface activity of rabbit pulmonary surfactant subfractions at different concentrations in a captive bubble
Authors: Putz G. , Goerke J. , Clements J. A.
Published: December 2017

This study investigates the surface activity of rabbit pulmonary surfactant subfractions at different concentrations in a new pressure-driven captive bubble surfactometer, which provides more rigorous testing conditions than heretofore applied to this material. Subfractions were separated by centrifugation of lavage return into a third (P3; 1,000 x average g, 20 min), a fourth (P4; 60,000 x average g, 60 min), and a fifth (P5; 100,000 x average g, 16 h) pellet. At 2.0 mg phospholipid/ml, P3 and P4 demonstrated more rapid adsorption, lower minimum surface tensions on first and subsequent compressions, and lower monolayer compressibilities than did P5. This surface activity of P3 and P4 increased with concentration between 0.1 and 2.0 mg phospholipid/ml. Adsorption rate constants were approximately 10,000 times faster than desorption constants. We conclude that, in a normal lung, components of P3 and P4 determine alveolar surface tension. We speculate that under special circumstances even the less surface active P5 could have an important influence at the air-water interface.
Gender-related differences in the baroreceptor reflex control of heart rate in normotensive humans
Authors: Abdel-Rahman A. R. , Merrill R. H. , Wooles W. R.
Published: December 2017

The present study investigates the baroreceptor reflex control of heart rate (HR) of normotensive male and female human volunteers under two conditions: bolus- and infusion-evoked elevations of blood pressure by intravenous administration of phenylephrine. Average age and blood pressure were similar in both sexes, but females had a significantly lower heart period (HP; higher HR). A major difference existed between the two sexes when the blood pressure was elevated by the bolus method. Females had a significantly (50%) smaller baroreflex sensitivity (regression coefficient), which inferred a gender-related difference in baroreceptor reflex control of HR. However, because a positive correlation existed between basal HP and baroreflex sensitivity, it was important to investigate whether this difference was related to the significantly lower basal HP in females. This possibility was ruled out because a similar difference still existed when the data were collected from another group of females who had basal HP values similar to those of males. This gender-related difference in baroreceptor reflex control of HR seems to depend on the pattern by which the pressor stimulus is evoked. The baroreceptor HP response to a slowly developing pressor response that was maintained at a steady-state level was very similar in both sexes. Because the HP response to abrupt (bolus-evoked) pressor stimuli mainly reflects the activity of the vagal component, our findings suggest that the cardiac vagal component seems to play a substantially smaller role in the baroreflex-mediated bradycardia in females.
Exercise O2 transport model assuming zero cytochrome PO2 at VO2 max
Authors: Severinghaus J. W.
Published: December 2017

An analogy is drawn between cytochrome aa3 function and a polarographic cathode at which the potential of -0.6 V captures all O2 diffusing to the surface, achieving maximal O2 consumption (VO2max) by eliminating O2 backpressure and outward diffusion from the surface, defined herein as zero surface PO2. The relationship of O2 consumption (as %VO2max) to muscle venous, myoglobin, and cytochrome PO2 is modeled assuming that cytochrome aa3 PO2 reaches zero at VO2max, incorporating published data on the profile of leg venous PO2, pH, and blood lactate vs. work. Equations describe hemoglobin and myoglobin O2 dissociation and the Bohr effect of acid on O2 unloading. The O2 gradient from capillary blood to cytochrome aa3 is assumed to be proportional to O2 consumption. The model suggests that 1) to extract 75% of the O2 from myoglobin at VO2max, myoglobin must lie 90% down the O2 gradient from capillary to cytochrome; 2) the Bohr effect adds 15–30% to VO2max and keeps venous PO2 almost constant as work rises from 60 to 100% of VO2max; and 3) in steady heavy work, the rising arterial lactate may impede lactate excretion from muscle, reduce anaerobic ATP generation, and shift the energy balance toward aerobic metabolism. The zero PO2 hypothesis facilitates modeling and may be the key to understanding the physiological limitation of work.
Higher exercise performance and lower VO2max in Tibetan than Han residents at 4,700 m altitude
Authors: Ge R. L. , Chen Q. H. , Wang L. H. , Gen D. , Yang P. , Kubo K. , Fujimoto K. , Matsuzawa Y. , Yoshimura K. , Takeoka M. , et al.
Published: December 2017

To examine the hypothesis that the pathway of adaptation to high altitude in natives differs considerably from that in newcomers, we measured maximal O2 uptake (VO2max), minute ventilation, anaerobic threshold (AT), blood lactate, and blood gases during maximal exercise in 17 lifelong Tibetan residents and 14 acclimatized Han Chinese newcomers living at the altitude of 4,700 m. The two groups were similar in age, height, and weight, and the subjects were nonathletes. Although VO2max was significantly lower in the Tibetans than in the Hans (30.4 +/- 1.5 vs. 36.0 +/- 1.9 ml.min-1.kg-1 STPD; P < 0.05), at maximal exercise effort the exercise workload was greater (167.7 +/- 4.2 vs. 150.0 +/- 5.9 W; P < 0.05). The mean AT values (in % VO2max) in the Tibetan and Han subjects were 84.1 and 61.6%, respectively (P < 0.01). Minute ventilation at maximal exercise was significantly lower in the Tibetans than in the Hans (68.4 +/- 3.4 vs. 79.7 +/- 4.1 l/min BTPS; P < 0.05), whereas heart rate at maximal effort was equivalent in the two groups. The Tibetans showed lower blood lactate value than did the Hans both before and at the end of exercise. We conclude that the Tibetan natives have higher exercise performance and AT but lower VO2max and blood lactate concentration than do acclimatized Han newcomers. These results may reflect the effects of genetic or peripheral adaptation factors in the Tibetan natives.
Vascular impedance analysis in dog lung with detailed morphometric and elasticity data
Authors: Gan R. Z. , Yen R. T.
Published: December 2017

On the basis of experimentally measured morphometric and elasticity data and model-derived mean pressure-flow conditions, we attempt a theoretical modeling of pulsatile flow in the whole lung. In the model we use the "elastic tube" for arteries and veins, and the vascular impedance in arteries and veins follows Womersley's theory and electric analogue. We employ the “sheet-flow” theory to describe the flow in the capillaries and to obtain the microvascular impedance matrix. The characteristic impedance of each order along the vascular tree, the input impedance at the capillary entrance and exit, and the pulmonary arterial input impedance at the main pulmonary artery are computed under certain physiological conditions. Using the pulsatile flow model, we investigate the effects of arterial vascular obstruction on pulmonary vascular impedance. The model-derived data are compared with the available experimental results in the literature.
Diameters of juxtacapillary venules determined by oil-drop method in rat lung
Authors: Sadurski R. , Tsukada H. , Ying X. , Bhattacharya S. , Bhattacharya J.
Published: December 2017

We report a new method for precise quantification of lung microvascular diameter. Isolated blood-perfused rat lungs (500-g Sprague-Dawley rats) at constant inflation pressure [alveolar pressure (PA)] and stopped blood flow were viewed by microscopy and video. Subpleural venules of the second and third postcapillary generations were microinjected with oil colored with Sudan Black. Vascular pressure (Pvas) was varied in steps, and at each step the horizontal diameter (DH) and the length of the oil-filled segment were determined by microcaliper measurements of the replayed video image. At PA = 5 cmH2O, a decrease in Pvas from 25 to 0 cmH2O decreased DH in the second-generation venules from 55 +/- 2 (SE) to 41 +/- 1 microns (n = 13) and in the third-generation venules from 96 +/- 6 to 73 +/- 6 microns (n = 6). The constant-volume oil-filled segment conformed to the cylinder formula in that decreases in DH correlated linearly with 1/ square root of length, thereby indicating that at all Pvas values venular geometry was constant and probably circular in cross section. The decrease in Pvas to -5 cmH2O did not further decrease DH. At Pvas = 10–25 cmH2O, an increase in PA to 15 cmH2O did not significantly increase DH, although the increase in PA did diminish the slope (compliance) of the DH-Pvas relationship in second- but not third-generation venules. We conclude that 1) lung expansion decreases compliance of juxtacapillary venules, 2) venules retain circular cross sections at Pvas between -5 and 25 cmH2O, and 3) venules are patent at subzero Pvas.
Magnesium attenuates pulmonary hypertension due to hypoxia and group B streptococci
Authors: Anderson M. E. , Burnette T. M. , Geiser D. R. , Janjindamai W.
Published: December 2017

We investigated whether hypermagnesemia alleviates hypoxic or group B streptococcal (GBS) pulmonary hypertension (PH). Hypoxic PH was induced and maintained in 14 lambs by continuous ventilation with 12% oxygen. GBS PH was induced and maintained in 16 lambs by the continuous infusion of 5–10 x 10(8) colony-forming units.kg-1.h-1 of GBS. After the onset of PH, lambs were randomized to receive either magnesium sulfate (MgSO4, intermittent boluses of 0.38 mmol/kg, with a continuous infusion of 0.15 mmol.kg-1.h-1) or a similar volume of normal saline. Hypermagnesemia lowered pulmonary arterial pressure (PAP) and delayed the fall in systemic arterial pressure and stroke volume index seen in the control animals (each P < 0.05). At a serum magnesium concentration ([Mg]) of 2.75 +/- 0.25 mmol/l, PAP was 27 +/- 3 compared with 40 +/- 4 Torr in the control animals ([Mg] = 0.87 +/- 0.06 mmol/l; P < 0.05). In the GBS PH trial, hypermagnesemia prevented the continued increase in PAP seen in the control animals. At [Mg] = 2.15 +/- 0.07 mmol/l, PAP fell 2 +/- 1 Torr from prerandomization values, whereas it rose 4 +/- 2 Torr in the control animals ([Mg] = 0.59 +/- 0.07 mmol/l; P < 0.05). However, during the same time the systemic arterial pressure fell further in the magnesium-treated animals (-19 +/- 1 vs. -2 +/- 5 Torr). MgSO4 attenuates PH in both models but may cause systemic hypotension in sepsis.
Lung volume specificity of inspiratory muscle training
Authors: Tzelepis G. E. , Vega D. L. , Cohen M. E. , McCool F. D.
Published: December 2017

We examined the extent to which training-related increases of inspiratory muscle (IM) strength are limited to the lung volume (VL) at which the training occurs. IM strength training consisted of performing repeated static maximum inspiratory maneuvers. Three groups of normal volunteers performed these maneuvers at one of three lung volumes: residual volume (RV), relaxation volume (Vrel), or Vrel plus one-half of inspiratory capacity (Vrel + 1/2IC). A control group did not train. We constructed maximal inspiratory pressure-VL curves before and after a 6-wk training period. For each group, we found that the greatest improvements in strength occurred at the volume at which the subjects trained and were significantly greater for those who trained at low (36% for RV and 26% for Vrel) than at high volumes (13% for Vrel + 1/2IC). Smaller increments in strength were noted at volumes adjacent to the training volume. The range of vital capacity (VC) over which strength was increased was greater for those who trained at low (70% of VC) than at high VL (20% of VC). We conclude that the greatest improvements in IM strength are specific to the VL at which training occurs. However, the increase in strength, as well as the range of volume over which strength is increased, is greater for those who trained at the lower VL.
Hypoxia increases glucose transport at blood-brain barrier in rats
Authors: Harik S. I. , Behmand R. A. , LaManna J. C.
Published: December 2017

Prolonged hypoxia causes several adaptive changes in systemic physiology and tissue metabolism. We studied the effects of hypobaric hypoxia on glucose transport at the blood-brain barrier (BBB) in the rat. We found that hypoxia increased the density of brain microvessels seen on immunocytochemical stains using an antibody to the glucose transporting protein GLUT. In addition, we found that hypoxia increased the density of GLUT in isolated cerebral microvessels as determined by specific cytochalasin B binding. The higher GLUT density in isolated cerebral microvessels was evident after 1 wk of hypoxia and was associated with decreased activity of gamma-glutamyltranspeptidase. Consistent with these findings, we also demonstrated that 3 wk of hypobaric hypoxia caused increased unidirectional transport of glucose at the BBB in several brain regions in vivo, as determined by the doubly labeled single-pass indicator-fractionation atrial bolus injection method in anesthetized rats. We conclude that chronic hypobaric hypoxia is associated with increased glucose transport at the BBB.
Lower limit of body fat in healthy active men
Authors: Friedl K. E. , Moore R. J. , Martinez-Lopez L. E. , Vogel J. A. , Askew E. W. , Marchitelli L. J. , Hoyt R. W. , Gordon C. C.
Published: December 2017

We examined body composition changes in 55 normal young men during an 8-wk Army combat leadership training course involving strenuous exercise and low energy intake, with an estimated energy deficit of 5.0 +/- 2.0 MJ/day and a resultant 15.7 +/- 3.1% weight loss. Percent body fat (BF) measured by dual-energy X-ray absorptiometry (DEXA) averaged 14.3% (range 6–26%) and 5.8 +/- 1.8% (range 4–11%) at the beginning and end of the course, respectively. Men who achieved a minimum percent BF (4–6%) by 6 wk demonstrated only small additional total and subcutaneous fat losses in the final 2 wk and sacrificed increasingly larger proportions of fat-free mass. Percent BF estimated from skinfold thicknesses reflected relative changes in fat mass, although actual percent BF was overestimated. Instead of reaching a plateau after fat stores were substantially depleted, abdominal, hip, and thigh girths continued to decline with body weight loss. Final percent BF for the leanest men was similar to that observed after a 25% body weight reduction in the 1950 Minnesota study (5.2% by underwater weighting), and height-corrected final fat mass was the same (1.0 +/- 0.2 vs. 0.9 +/- 0.7 kg fat/m2), suggesting that these values represent a minimal body fat content in healthy men and that weight loss subsequent to achieving this level is contributed from the fat-free mass. Our results suggest that 4–6% BF or approximately 2.5 kg fat represents the lower limit for healthy men, as assessed by DEXA or by underwater weighing.
Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume
Authors: Hsia C. C. , Herazo L. F. , Ramanathan M. , Johnson R. L.
Published: December 2017

Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6–12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar-capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135–142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of > 50% of lung.