bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring circulating cytokines
Authors: Cannon J. G. , Nerad J. L. , Poutsiaka D. D. , Dinarello C. A.
Published: December 2017

Cytokines, i.e., regulatory proteins derived primarily (but not exclusively) from cells of the immune system, are receiving increasing attention for their influences on physiological processes. This paper outlines several of the unique characteristics of cytokines and discusses the pitfalls encountered when measuring them in biological fluids. At present, each available assay has a combination of advantages and drawbacks; therefore, investigators must be aware of the trade-offs and choose the assay that best addresses their needs. The factors that affect cytokine measurement also influence cytokine activity in vivo; thus they are important from a physiological as well as methodological standpoint. Moreover, the absolute concentration of a single cytokine is probably less important than the balance between that cytokine and its natural antagonists.
Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid secretion
Authors: Cassin S. , Perks A. M.
Published: December 2017

The effects of arginine vasopressin (AVP) and amiloride were studied in 16 unanesthetized fetal sheep (129–135 days of age) with indwelling catheters. Secretion was measured by an impermeant tracer technique. Control fetuses showed no change in lung liquid secretion over a 5-h period with an average secretion rate of 3.6 +/- 0.31 ml.kg-1.h-1. Infusion of AVP (23.4 +/- 2.23 mU.kg-1.min-1) in seven fetuses (134–140 days of age) produced significant decreases (from control) in the secretion rate over a 5-h period: the secretion rate decreased by 68% in the last hour. Amiloride placed in the lung liquid during infusion of AVP, but after AVP effects had taken place, reversed the AVP-induced decrease in lung liquid secretion. AVP in conjunction with other hormones that are elevated during the stress of birth (epinephrine and cortisol) may be important in the removal of lung fluid at birth.
Spreading of exogenous surfactant in an airway
Authors: Espinosa F. F. , Shapiro A. H. , Fredberg J. J. , Kamm R. D.
Published: December 2017

Using a theoretical model, we studied spreading of a bolus of insoluble surfactant deposited on a thin liquid layer of a model airway. Applications include instillation of exogenous surfactant as a treatment for neonatal respiratory distress syndrome, the use of surfactant carriers to deliver drugs via the lung, and the movement of liquid along the airway tree due to naturally occurring gradients of surface tension. The time-dependent governing equations were solved numerically for longitudinal axisymmetric surfactant spreading. We examined the influences of the resident liquid layer (thickness, viscosity, endogenous surfactant, airway radius), of the bolus (volume and surfactant content), and of gravity. The gradient in surface tension drives the flow toward the region of higher surface tension, ultimately creating a shocklike wave of nearly twice the initial lining thickness. Pressure gradients due to interfacial curvature (capillarity) have little effect on the rate of surfactant spread. The presence of an endogenous resident surfactant greatly augments the rate of spreading while inhibiting development of the shock. In all cases studied, the effect of circumferential curvature was negligible, indicating that the liquid layer can be treated as if it were spreading over a flat surface. Our results reveal that the surfactant spreads as time to the one-third power. Accordingly, a surfactant deposited in the trachea of a neonate would spread to the periphery in approximately 12 s.
Volume changes in the legs of paraplegic subjects during arm exercise
Authors: Hopman M. T. , Verheijen P. H. , Binkhorst R. A.
Published: December 2017

The purpose of this study was to examine the inability of paraplegic (P) subjects to redistribute fluid below the spinal cord lesion during arm exercise, with emphasis on the role of the sympathetic system in this redistribution failure. Fifteen male P and 15 male able-bodied [control (C)] subjects performed arm cranking exercise, and volume changes in the calf were measured by strain gauge plethysmography before, during, and after exercise. Muscle pump activity in the legs of C subjects was eliminated. The rate of calf volume decrease at the beginning and halfway points of the exercise period, the total volume decrease during exercise, and the volume increase during recovery were significantly lower in P than in C subjects. Whereas completeness of the lesion had no influence on leg volume changes, the rate of calf volume decrease at the beginning of exercise and the total volume decrease during exercise were significantly correlated with the level of the spinal cord lesion. This study confirms that P subjects are unable to redistribute fluid effectively below the spinal cord injury during arm exercise, which is partly caused by a loss of sympathetically induced vasoconstriction and which appears to be independent of the completeness of the lesion but dependent on its level.
Modulation of the QT interval: effects of graded exercise and reflex cardiovascular stimulation
Authors: Arrowood J. A. , Kline J. , Simpson P. M. , Quigg R. J. , Pippin J. J. , Nixon J. V. , Mohanty P. K.
Published: December 2017

During exercise, as heart rate (HR) increases, the QT interval of the electrocardiogram shortens. The mechanism(s) involved in this QT shortening has not been clearly defined. To distinguish the influence of increased circulating catecholamines from myocardial efferent stimulation, the relationship between HR and QT interval was investigated during exercise and cardiovascular reflex stimulation in cardiac transplant patients and normal control subjects. Because of cardiac denervation, increases in HR in these patients are solely due to circulating catecholamines and thus allow isolation of their effect on the QT interval. Twenty-one cardiac transplant patients were studied and compared with 16 normal control subjects. The QT-HR relationship was determined according to an exponential model during treadmill exercise in both groups [QT = 0.12 + 0.492e(-0.008.HR) and QT = 0.12 + 0.459e(-0.007.HR) in normal subjects and transplant patients, respectively] and was statistically similar between groups, suggesting similar QT interval shortening in both groups. During cold pressor and Valsalva maneuvers, HR increased significantly in normal subjects only, whereas QT interval changed minimally in both groups. These results suggest that during exercise the QT interval is influenced predominantly by increases in circulating catecholamines rather than by neurally mediated reflex autonomic changes.
Generation and transit pathway of H+ is critical for inhibition of palmar sweating by iontophoresis in water
Authors: Sato K. , Timm D. E. , Sato F. , Templeton E. A. , Meletiou D. S. , Toyomoto T. , Soos G. , Sato S. K.
Published: December 2017

Passing galvanic current across the skin (known as "tap water iontophoresis" or TWI) inhibits sweating; however, its mechanism of action is unclear. Using improved methods, we confirmed that anodal current has more of an inhibitory effect than cathodal current, water is superior to saline, and the inhibitory effect is a function of the amperage used. To address the importance of current flowing through the pores, a layer of silicone grease was placed on the skin to reduce the shunt pathway across the epidermis. With silicone, total skin conductance decreased 60% without the sweat pores being occluded, swelling of the stratum corneum and collapse of the poral lumen was prevented, and current-induced inhibition of sweating was enhanced, most likely because of an increase in current density in the pores. The pH of anodal water, but not of saline, dropped to 3, whereas that of cathodal water increased to 10 during passage of current through the skin. Acidified anodal water was superior to alkaline water. Sweat glands isolated from TWI-induced anhidrotic palmar skin responded to methacholine in vitro, but the sweat rate and pharmacological sensitivity were slightly lowered. Thus the strong acidity generated by hydrolysis of water in the anodal bath and the further accumulation of H+ in the sweat duct by anodal current may be responsible for TWI-induced inhibition of sweating due to an unknown lesion(s) in the duct or sweat pore. The secretory coil function may also be altered because of exposure to intense acidity during TWI. The importance of H+ movement into the sweat pore for inhibition of sweating could be further exploited to develop new strategies for the control of sweating.
Central effects of somatostatin and atrial natriuretic peptide on tracheal tone
Authors: Haxhiu M. A. , Deal E. C. , Van Lunteren E. , Cherniack N. S.
Published: December 2017

The effects of somatostatin and atrial natriuretic peptide applied topically to the ventral surface of the medulla (VMS) on tracheal tone and phrenic nerve activity (Phr) were studied in chloralose-anesthetized and paralyzed cats artificially ventilated with 7% CO2 in O2. Surface application of drugs to the chemosensitive areas of the VMS significantly decreased tracheal tension measured by changes in pressure in a balloon placed in a bypassed segment of the trachea (Ptseg). Application of somatostatin (9 cats) caused a mean decrease in Ptseg from 17.3 +/- 1.8 (SE) to 4.3 +/- 1.4 cmH2O (P < 0.01) and a reduction in Phr from 24.9 +/- 3.4 to 10.3 +/- 3.4 units (P < 0.05). Like somatostatin, application of atrial natriuretic peptide to the VMS (5 cats) produced tracheal relaxation (Ptseg decreased from 19.3 +/- 2.6 to 9.9 +/- 1.3 cmH2O, P < 0.01), but in contrast there was an insignificant reduction in Phr (from 18.5 +/- 3.6 to 16.1 +/- 3.8 units, P > 0.05). When parasympathetic activity was abolished by atropine methylnitrate and tracheal tone was restored with 5-hydroxytryptamine, somatostatin and atrial natriuretic peptide applied on the VMS had no effect on tracheal pressure, suggesting that observed changes were not caused by direct action of peptides on tracheal smooth muscle via the bloodstream or by facilitation of inhibitory pathways. Both somatostatin and atrial natriuretic peptide applications were associated with a slight but significant decrease in arterial blood pressure. These data suggest that somatostatin and atrial natriuretic peptide acting on the chemosensitive structure of the VMS may play significant roles in modulating para-sympathetic outflow to airway smooth muscle.
Mutant hemoglobins (alpha 119-Ala and beta 55-Ser): functions related to high-altitude respiration in geese
Authors: Weber R. E. , Jessen T. H. , Malte H. , Tame J.
Published: December 2017

The unusually high blood-O2 affinity in the bar-headed and Andean geese is a necessary adaptation for migration across high mountain ranges. The amino acid residues alpha-119 and beta-55, which form an alpha 1 beta 1 contact in human hemoglobin (Hb), are altered in bar-headed and Andean geese, respectively, which suggests that loss of this contact increases O2 affinity. Two mutant human Hbs with equivalent mutations at these sites prepared by site-directed mutagenesis show the same increase in O2 affinity compared with Hb A, which indicates that these mutations are responsible for the changes in the protein. The intrinsic affinity difference compared with native Hb A is amplified by organic phosphates. Whereas the recombinant and native Hbs displayed similar sensitivities to pH, chloride, and 2,3-diphosphoglycerate, the oxygenation heat of the alpha-chain mutant decreased in the presence of 2,3-diphosphoglycerate. O2 association constants for the deoxygenated state of the alpha-mutant were about three times those for Hb A. The mutant Hb analogously exhibited higher affinity constants for binding the first three O2 molecules. Calculated heme-heme interaction energies indicated that loss of a single contact, resulting in destabilization of the deoxy (tense) structure, underlies the increased O2 affinity. Adaptations securing Hb-O2 binding at extreme altitude are discussed.
Influence of nitroglycerin on splanchnic capacity and splanchnic capacity-cardiac output relationship
Authors: Morse M. A. , Rutlen D. L.
Published: December 2017

It has been postulated, but not tested directly, that nitroglycerin's venodilatory effects attenuate cardiac output. Thus, the present study examined the importance of changes in splanchnic capacity, as assessed by scintigraphy, in the regulation of cardiac output during nitroglycerin administration in 16 anesthetized pigs under conditions of carotid sinus denervation and cervical vagotomy. With nitroglycerin administration (0.5 mg/min i.v.) for 5 min, systemic arterial pressure decreased from 115 +/- 7 to 95 +/- 7 mmHg (P < 0.0001), portal vein pressure decreased from 9.0 +/- 0.5 to 8.5 +/- 0.5 mmHg (P < 0.0001), portal flow increased from 637 +/- 49 to 668 +/- 60 ml/min (P = 0.09), and transhepatic resistance decreased from 7.5 +/- 1.5 to 6.5 +/- 1.0 mmHg.min.l-1 (P < 0.01), but cardiac output was unchanged (1,929 +/- 126 to 1,890 +/- 138 ml/min). Total splanchnic intravascular volume (VI) increased 1.6 +/- 1.0% (P < 0.05, 14 +/- 10 ml). This increase was due to an increment in extrahepatosplenic (mesenteric) VI (12.9 +/- 1.9%, P < 0.0001), since splenic VI decreased (9.6 +/- 2.8%, P < 0.0001) and hepatic VI did not change. After splenectomy, nitroglycerin infusions at doses of 0.5 and 2 mg/min were associated with increases in total splanchnic VI of 3.7 +/- 1.2% (P < 0.0001, 30 +/- 10 ml) and 7.6 +/- 1.7% (P < 0.001, 59 +/- 10 ml) due entirely to increases in mesenteric volume of 9.9 +/- 2.7% (P < 0.0001) and 16.5 +/- 1.9% (P < 0.0001), respectively, but cardiac output was unchanged at the end of infusion at either dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Very large range of baroreflex sympathetic control of vascular resistance in human skeletal muscle and skin
Authors: Lundvall J. , Edfeldt H.
Published: December 2017

We analyzed in the forearm of “comfortably warm” male volunteers 1) reflex sympathetic vascular resistance changes evoked by short-term graded [1.5-min exposure to 15, 40, 55, and 70 mmHg and high and barely tolerated (77–95 mmHg)] lower body negative pressure (LBNP) and 2) resistance changes evoked by abolition of control sympathetic vasoconstrictor tone (anesthetic axillary nerve block). Graded LBNP caused graded neurogenic vasoconstriction with pronounced average flow decline at high LBNP from 3.7 to 0.8 ml.min-1 x 100 ml-1 (77 +/- 2% decrease), corresponding to a drastic resistance increase from 25.4 to 127 mmHg.ml-1 x min x 100 ml (352 +/- 27% rise above control). Axillary nerve block caused marked increases in forearm blood flow from 4.3 +/- 0.4 to 15.7 +/- 1.4 ml.min-1 x 100 ml-1 [> 3-fold flow increase equivalent to an average resistance decline from 19.7 to 6.3 mmHg.ml-1 x min x 100 ml (72 +/- 5%)], reflecting a surprisingly high resting constrictor fiber vascular tone. The overall results indicate that the sympathetic skeletal muscle and skin resistance vessel control in men allows very large (almost 20-fold) alterations in blood flow and vascular resistance from complete inhibition of neurogenic vascular tone to maximal reflex nerve activation. This range of sympathetic control was clearly greater than that revealed in comparative experiments on the cat lower leg.
Do canine scalene and sternomastoid muscles play a role in breathing?
Authors: De Troyer A. , Cappello M. , Brichant J. F.
Published: December 2017

To assess the respiratory function of the scalene and sternomastoid muscles in the dog, we studied the effect of graded increases in inspiratory airflow resistance and single-breath airway occlusion on the electrical activity of these muscles in 18 supine anesthetized spontaneously breathing animals. The sternomastoids never showed any activity, and the scalenes showed some inspiratory activity during occlusion in only two animals. The adoption of the prone position and bilateral cervical vagotomy did not affect this pattern. Hypercapnia also did not elicit any sternomastoid activity and induced scalene inspiratory activity during occlusion in only four of nine animals. On microscopic examination, however, both muscles were found to contain large numbers of spindles, suggesting that they have the capacity to respond to stretch. In addition, with increases in inspiratory resistance, both the sternum and ribs were displaced in the caudal direction. As a result, the scalenes demonstrated a gradual inspiratory lengthening and the normal inspiratory lengthening of the sternomastoids was accentuated. Additional studies in three unanesthetized animals showed consistent activity in the scalene and sternomastoid muscles during movements of the trunk and neck but no activity during breathing, including occluded breathing. These observations thus indicate that the alpha-motoneurons of the scalene and sternomastoid muscles in the dog have very small central respiratory drive potentials with respect to their critical firing threshold. In this animal, these muscles do not have a significant respiratory function.
Increased dependence on blood glucose in smokers during rest and sustained exercise
Authors: Colberg S. R. , Casazza G. A. , Horning M. A. , Brooks G. A.
Published: December 2017

To evaluate the hypothesis that smoking increases the dependence on blood glucose as a fuel, seven male smokers [28.7 +/- 1.7 (SE) yr. 77.7 +/- 4.3 kg] and seven nonsmokers (NS; 29.1 +/- 0.9 yr, 78.7 +/- 5.3 kg) were studied in the postabsorptive condition. NS received a primed continuous infusion of [6,6–2H]glucose and [1–13C]glucose during 90 min of rest and 60 min of exercise at 49.7 +/- 0.8% of peak O2 consumption on one occasion; chronic smokers continued their overnight abstinence from smoking (CS) for one trial but, on another occasion, acutely smoked (AS) two cigarettes immediately before resting measurements and another cigarette before exercise. Plasma glucose levels were similar among all groups at all times during the trials; however, the glucose rates of appearance (Ra) at rest in CS (1.96 +/- 0.14 mg.kg-1 x min-1) and AS (2.02 +/- 0.14) were higher than in NS (1.41 +/- 0.15, P < 0.05). With exercise, the glucose Ra values rose in all groups above resting values but were significantly greater in CS (4.76 +/- 0.50) and AS (4.71 +/- 0.53) than in NS (3.31 +/- 0.16). Glucose oxidation during exercise was elevated in smokers (2.31 +/- 0.37 mg.kg-1 x min-1 in CS and 2.18 +/- 0.34 in AS) compared with NS (1.09 +/- 0.18, P < 0.05). Nicotine levels correlated with the glucose Ra in AS (r = 0.93, P < 0.01). In conclusion, the results indicate that long-term smoking, independent of acute smoking, increases the dependence on blood glucose as a fuel during rest and sustained submaximal exercise.
Heterogeneous regional behavior during forced expiration before and after histamine inhalation in dogs
Authors: McNamara J. J. , Castile R. G. , Ludwig M. S. , Glass G. M. , Ingram R. H. , Fredberg J. J.
Published: December 2017

We studied the evolution of alveolar pressure (PA) heterogeneity during the course of forced expiration in the lungs of six anesthetized open-chest dogs. Using an alveolar capsule technique, we measured PA simultaneously in six lung regions during full maximal forced deflations before and after administering aerosolized histamine. Flow was measured plethysmographically with volume obtained by flow integration. Heterogeneity was expressed as the coefficient of variation (CV) of regional PA after 25% of the vital capacity had been expired from total lung capacity. The CV in in vivo open-chest canine lungs (21.3%) was significantly greater than that we measured previously in excised lungs (8.7%) (P < 0.02). Inhalation of aerosolized solutions of histamine produced significant increases in interregional heterogeneity (CV = 35.5 and 38.8% after 3 and 10 mg/ml of histamine, respectively; P < 0.025). After histamine, the vital capacity was reduced and the configuration of the flow-volume curve demonstrated some shortening of the flow plateau commonly observed in dogs. Changes in the flow-volume relationship failed, however, to reflect well the marked degree of heterogeneity of PA after histamine administration. These findings may be reconciled on the basis of interdependence of regional expiratory flows. Reductions in flow from obstructed regions appear to be compensated by increases in flow from unobstructed regions and thus mask upstream nonuniformities. These mechanisms may explain in part why the maximal expiratory flow-volume curve has been a relatively insensitive tool for the detection of early nonuniform airway disease.
Pulsatile and nonpulsatile pressure-flow relationships in zone 3 excised rabbit lungs
Authors: Saito O. , Lamm W. J. , Hildebrandt J. , Albert R. K.
Published: December 2017

We compared the effects of pulsatile vs. nonpulsatile flow (Q) on pulmonary arterial pressure (Ppa)-Q relationships in zone 3 over wide ranges of pulse rate, stroke volume (SV), and Q. Excised left lungs of rabbits (n = 15) were perfused with tris(hydroxymethyl)aminomethane-buffered Tyrode solution containing 4% dextran, 1% albumin, and 10 mg/l of indomethacin and were ventilated with room air. Pulsatile Q was generated by a diaphragm pump delivering SV of 0.5, 1, or 2 ml (representing approximately 0.3, 0.6, and 1.2 times, respectively, the normal resting SV for rabbit left lung) and adjusting the pump frequency. Nonpulsatile Q was generated by raising an arterial reservoir to the required height. Mean pulmonary arterial (Ppa) and left atrial pressures were measured at end exhalation (positive end-expiratory pressure = 2.5 cmH2O) near the tips of the perfusion cannulas and were referenced to the lung base. Left atrial pressure was held constant at 7 cmH2O.Q was alternated between pulsatile and nonpulsatile, increasing Q stepwise from 100 to 600 ml/min (Q from approximately 0.3 to 2 times the normal resting Q for rabbit left lung), after which Q was reduced stepwise back to initial values. For the smallest SV there were no differences between Ppa-Q curves under pulsatile and nonpulsatile conditions. At the largest SV, Ppa was greater during pulsatile than nonpulsatile Q at Q > 100 ml/min. The slopes of the Ppa-Q curves were greater during pulsatile Q at the two larger SV values. These results can be explained by increasing Q turbulence and less ideal velocity profiles at higher peak Q resulting from the effects of rapidly changing inertial forces.
Central chemosensitivity affects respiratory muscle responses to laryngeal stimulation in the piglet
Authors: Litmanovitz I. , Dreshaj I. , Miller M. J. , Haxhiu M. A. , Martin R. J.
Published: December 2017

Stimulation of laryngeal afferent fibers triggers reflex apnea, which can be very long in the neonatal period. The purpose of this study was twofold: 1) to determine the effect of superior laryngeal nerve (SLN) stimulation on expiratory as well as inspiratory muscle activity and 2) to compare the respiratory response to SLN stimulation under conditions that would appear to alter the level of central chemosensitivity in anesthetized spontaneously breathing piglets. In protocol 1, we measured electromyogram (EMG) responses from the diaphragm (DIA), triangularis sterni, and transversus abdominis muscles to graded SLN stimulation; in protocol 2, we compared the DIA response to different levels of SLN stimulation during normocapnia, hypercapnia, and cooling of the ventrolateral medullary surface (VMS). SLN stimulation performed during normocapnia caused significantly greater inhibition of both expiratory muscles (triangularis sterni and transversus abdominis) than of the DIA. During hypercapnia, laryngeal stimulation-induced inhibition of all three muscles was significantly diminished, and the degree of inhibition for the three muscles became equivalent. Inhibition of the DIA EMG was significantly greater with SLN stimulation during VMS cooling than with a VMS temperature of 38 degrees C. We conclude that the magnitude of respiratory inhibition induced by laryngeal stimulation during early postnatal life is inversely related to the level of central chemical input and speculate that functional deficiency of structures located in the VMS may contribute to potentially life-threatening apnea in infants.
Muscle metabolism during exercise and heat stress in trained men: effect of acclimation
Authors: Febbraio M. A. , Snow R. J. , Hargreaves M. , Stathis C. G. , Martin I. K. , Carey M. F.
Published: December 2017

Exercise metabolism was examined in 13 endurance athletes who exercised on three occasions for 40 min at 70% of maximal O2 uptake in an environmental chamber at either 20 degrees C and 20% relative humidity (RTT) or 40 degrees C and 20% relative humidity before (PRE ACC) or after (POST ACC) 7 days of acclimation. Exercise in the heat resulted in a lower (P < 0.05) mean O2 uptake (0.13 l/min) and higher (P < 0.01) heart rate and respiratory exchange ratio. Acclimation resulted in a lower (P < 0.01) mean heart rate and respiratory exchange ratio. Postexercise rectal temperature, muscle temperature, muscle and blood lactate, and blood glucose were higher (P < 0.01) in the PRE ACC than in the RTT trial, but all were reduced (P < 0.01) in the POST ACC compared with the PRE ACC trial. Muscle glycogenolysis and percentage of type I muscle fibers showing glycogen depletion were greater (P < 0.05) in the PRE ACC than in the RTT trial. Muscle glycogenolysis was unaffected by acclimation during exercise in the heat, although the percentage of depleted type I fibers was higher (P < 0.05) in the unacclimated state. Plasma epinephrine was higher (P < 0.01) during exercise in the heat in the unacclimated individual relative to RTT but was lower (P < 0.01) in the POST ACC than in the PRE ACC trial. The greater reliance on carbohydrate as a fuel source during exercise in the heat appears to be partially reduced after acclimation. These alterations are consistent with the observed changes in plasma epinephrine concentrations.
Influence of hypoxia and carotid sinus nerve stimulation on abdominal muscle activities in the cat
Authors: Fregosi R. F.
Published: December 2017

Experiments were designed to test two hypotheses regarding the influence of isocapnic hypoxia on the expiratory activity of the abdominal muscles: 1) brain hypoxia attenuates the increased drive to the abdominal muscles that is elicited by hypoxic stimulation of peripheral chemoreceptor afferents, and 2) activation of the abdominal muscles in hypoxia requires vagal afferent feedback. The measurements included inspired ventilation (VI) and the electromyogram (EMG) of the external and internal oblique and transversus abdominis muscles in 12 supine cats that were anesthetized with chloralose (50 mg/kg) and breathed spontaneously. Changes in respiratory drive were evoked with isocapnic hypoxia or electrical stimulation of a carotid sinus nerve. Although both stimuli increased abdominal motor output, carotid sinus nerve stimulation evoked a significantly greater increase in the external and internal oblique EMG than hypoxia when comparisons were made at an equivalent level of VI. Neither stimulus changed the abdominal EMG significantly after bilateral cervical vagotomy. Separate experiments revealed that, at a given level of VI, hypercapnia evoked a significantly greater increase in abdominal activity than isocapnic hypoxia. The results suggest that the increased drive to the abdominal muscles elicited by stimulation of the peripheral and central chemoreceptors can be antagonized by an inhibitory input that is triggered by brain hypoxia. Moreover the decrease in expiratory motor activity often observed during hypoxia in vagotomized animals is due to the removal of an excitatory mechanism that is mediated by vagal afferent feedback.
Beta-adrenergic blockade does not prevent the lactate response to exercise after acclimatization to high altitude
Authors: Mazzeo R. S. , Brooks G. A. , Butterfield G. E. , Cymerman A. , Roberts A. C. , Selland M. , Wolfel E. E. , Reeves J. T.
Published: December 2017

We examined the extent to which epinephrine influences blood lactate adjustments to exercise during both acute (AC) and chronic (CH) high-altitude exposure. Eleven male sea level residents were divided into a control group (n = 5) receiving a placebo or a drug group (n = 6) receiving 240 mg/day of propranolol. All subjects were studied at rest and during 45 min of submaximal exercise (approximately 50% of sea level maximal O2 uptake) at sea level (SL) and within 4 h of exposure to and after 3 wk residence at 4,300 m (summit of Pikes Peak). Blood samples were collected from the femoral artery for epinephrine and lactate concentration. Exercising blood lactate concentration was significantly different across all altitude conditions such that AC > CH > SL (P < 0.05). For a given arterial O2 saturation, mean exercising blood lactates were lower for the beta-blocked group compared with controls; however, both groups demonstrated similar patterns across all conditions. Epinephrine levels during exercise followed a similar pattern to that of lactate, averaging 0.67, 0.43, and 0.29 ng/ml for AC, CH, and SL, respectively. The correlation between lactate and epinephrine was 0.93 and 0.84 for control and beta-blocked subjects, respectively. Whereas during exercise epinephrine was consistently higher for the beta-blocked group than controls, this difference was only significant during CH exposure. The epinephrine response was related to the extent of hypoxia in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Permeability of parietal pleura to liquid and proteins
Authors: Negrini D. , Venturoli D. , Townsley M. I. , Reed R. K.
Published: December 2017

The permselectivity of the parietal pleura was determined in spontaneously breathing anesthetized rabbits and dogs. In rabbits, we injected intrapleurally 5 ml of 1-g/dl albumin solution containing 100 microCi of 131I-labeled albumin plus 100 microCi of either lactate dehydrogenase (LDH) or alpha 2–125I-macroglobulin. Dogs received 100 ml of 1-g/dl albumin solution containing 100 microCi of 131I-albumin plus 100 microCi of alpha 2–125I-macroglobulin. A transpleural pressure gradient was set, lowering the intracapsular pressure to -30 cmH2O. The solvent drag reflection coefficients (sigma f) were calculated as the ratio between tracer concentrations in capsular and pleural liquid collected at 60–180 min. In rabbits sigma f was 0.44 +/- 0.2 (SD) for albumin, 0.84 +/- 0.1 for LDH, and 0.93 +/- 0.05 for alpha 2-macroglobulin. In dogs sigma f was 0.30 +/- 0.19 for albumin and 0.53 +/- 0.15 for alpha 2-macroglobulin. The hydraulic conductivity of the parietal pleura was 2.18 +/- 1.54 microliters.h-1.cmH2O-1.cm-2 in rabbits and 1.22 +/- 1.13 microliters.h-1.cmH2O-1.cm-2 in dogs. The parietal pleura could be modeled by two pore populations with radii of 83–89 and 156-222 A. The permeability coefficient averaged 0.08–0.21 x 10(-6) cm/s for albumin, 0.06–0.09 x 10(-6) cm/s for LDH, and 0.01-0.03 x 10(-6) cm/s for alpha 2-macroglobulin.
Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass
Authors: Kayser B. , Narici M. , Binzoni T. , Grassi B. , Cerretelli P.
Published: December 2017

Exhaustive dynamic exercise with large muscle groups in chronic hypobaric hypoxia may be limited by central (nervous) rather than peripheral (metabolic) fatigue. Six males [32 +/- 4 (SD) yr] at sea level (SL) and after 1-mo acclimatization at 5,050 m (HA) performed exhaustive dynamic forearm exercise at a constant absolute load, requiring regional maximum aerobic power at SL, and exhaustive cycle exercise at prevailing maximal O2 uptake (HA approximately equal to 80% SL). Exhaustion time (t(ex)), blood O2 saturation (SaO2), and heart rate (HR) were measured during each exercise bout. Before and after both arm and leg exercise, lactate concentration ([La]), PO2, PCO2, and pH were measured in arterialized blood samples. Integrated electromyogram activity (IEMG) and mean (MPF) and centroid (CPF) power frequencies of the EMG power spectrum during exercise were calculated for forearm flexors and vastus lateralis muscle. t(ex) for forearm exercise at the same absolute load was the same at SL and HA. Similar increases of IEMG (+214% at SL vs. +172% at HA) and decreases of CPF (-13% at SL vs. -16% at HA) and MPF (-22% at SL vs. -21% at HA) were observed. By contrast, at HA, for similar t(ex), leg exercise had to be performed at the same relative (i.e., prevailing maximal O2 uptake) but lower absolute load (approximately equal to 80% of SL).(ABSTRACT TRUNCATED AT 250 WORDS)
Successive time courses of strength development and steroid hormone responses to heavy-resistance training
Authors: Hickson R. C. , Hidaka K. , Foster C. , Falduto M. T. , Chatterton R. T.
Published: December 2017

Subjects (5 males, 5 females) performed heavy-resistance exercise at a constant stimulus 3 days/wk for 8 wk. Work rates were then increased to higher but constant levels for an additional 8 wk. Half times of the first training period were 14 and 10 days for the bench press and parallel squat, respectively. The second time course resulted in only one-third of the overall magnitude of strength increases for both exercises as the first, and the kinetics were slower in the parallel squat but similar in the bench press (half time 13 days). Skeletal muscle fiber area was significantly increased (19%) in fast-twitch fibers by the end of the second training period. Postexercise elevations in serum cortisol and prolactin were seen only in the male subjects. Because the males trained at considerably higher work loads than the females, these results imply that absolute amounts of resistance may be an essential requirement for inducing certain hormonal responses. Serum cortisol levels in males after exercise were blunted by the 5th wk of the first time course. For serum testosterone, neither resting nor higher post-exercise concentrations were different at any point of the training periods for either sex. We conclude that the strength time course results are not inconsistent with current thought on factors contributing to strength accumulation. The absence of a specific serum androgenic response with strength development may be related to the fact that the constant exercise stimulus is not conducive to establishing clear-cut hormone-strength relationships.
Plasma extravasation induced in rat trachea by 6-OHDA is mediated by sensory nerves, not by sympathetic nerves
Authors: Sulakvelidze I. , Baluk P. , McDonald D. M.
Published: December 2017

6-Hydroxydopamine (6-OHDA) stimulates the release of catecholamines from sympathetic nerves. This stimulation has been proposed as the basis of the 6-OHDA-induced increase in vascular permeability in the rat knee joint. We sought to determine whether 6-OHDA increases vascular permeability in the rat trachea through a similar mechanism. We also sought to determine whether sympathetic nerves contribute to the plasma extravasation caused by stimulating sensory nerves with capsaicin. In anesthetized rats, an intratracheal infusion of 6-OHDA caused more Monastral blue extravasation than did an infusion of vehicle (area density, 23 +/- 3% vs. 9 +/- 1%). Chemical sympathectomy, which reduced the number of tyrosine hydroxylase-immunoreactive nerves by 98%, did not reduce the amount of extravasation induced by 6-OHDA. However, pretreatment with capsaicin, which reduced the number of substance P-immunoreactive nerves by 95%, reduced the Monastral blue extravasation induced by 6-OHDA by 98%. Extravasation induced by stimulating sensory nerves with capsaicin was not significantly different in tracheae with or without sympathetic nerves. We conclude that in the rat trachea infusion of 6-OHDA causes plasma extravasation by stimulating sensory nerves, not by stimulating sympathetic nerves. Furthermore, sympathetic nerves are not essential for the plasma extravasation induced by capsaicin.
Structure and function in fibrosing alveolitis
Authors: Verbeken E. K. , Cauberghs M. , Lauweryns J. M. , Van de Woestijne K. P.
Published: December 2017

Lung volumes, maximal expiratory volume and flows, elastic recoil pressure, and impedances at various levels of the bronchial tree, as well as tissue impedance, were measured in 13 human lungs that demonstrated generalized fibrosis at autopsy. After fixation, mean internal chord of air spaces (Lma), transsection length of the alveolar walls (Lmw), and internal diameter (d) and density of membraneous bronchioles (n/cm2) were determined in the same lungs by use of morphometric techniques. The results of functional and structural measurements were correlated and compared with measurements obtained similarly in 10 normal lungs. This study shows that the functional alterations typical for fibrosing alveolitis can be attributed to the replacement of part of the parenchyma by fibrous tissue and to modifications of the mechanical properties of still-functional units. The lungs were characterized structurally by an increase of Lmw and d. In addition, in three lungs, an increase of Lma and a decrease of n/cm2 were observed. Functionally, these lungs demonstrated a pattern compatible with a mixture of fibrosis and emphysema.
Effect of endurance training on activators of glycolysis in muscle during exercise
Authors: Duan C. , Winder W. W.
Published: December 2017

Endurance training attenuates exercise-induced increases in blood lactate at the same submaximal work rate. Three intramuscular compounds that influence muscle lactate production were measured in fasted non-trained (NT) and endurance-trained (T) rats. The T rats were subjected to a progressive endurance-training program. At the end of the program (11 wk), they were running 2 h/day at 31 m/min up a 15% grade 5 days/wk. NT and T rats were fasted for 24 h and then anesthetized (pentobarbital, iv) at rest or after running for 30 min at 21 m/min (15% grade). Blood lactate levels were significantly lower in the T rats than in the NT rats after 30 min of running (2.3 +/- 0.2 vs. 3.9 +/- 0.2 mM). The lower blood lactate concentration was accompanied by lower plasma epinephrine (2.8 +/- 0.4 vs. 6.0 +/- 0.8 nM), adenosine 3′, 3′,5′-cyclic monophosphate (0.36 +/- 0.02 vs. 0.50 +/- 0.03 pmol/mg), mg), glucose 1,6-diphosphate (26 +/- 2 vs. 40 +/- 5 pmol/mg), and fructose 2,6-diphosphate (3.2 +/- 0.2 vs. 4.3 +/- 0.3 pmol/mg) in white quadriceps muscle in T than in NT rats. Red quadriceps muscle glucose 1,6-diphosphate and adenosine 3′,5′-cyclic monophosphate were also lower in T than in NT rats. These adaptations may be responsible in part for the lower exercise-induced blood lactate in fasted rats as a consequence of endurance training.
Respective oxidation of exogenous glucose and fructose given in the same drink during exercise
Authors: Adopo E. , Peronnet F. , Massicotte D. , Brisson G. R. , Hillaire-Marcel C.
Published: December 2017

We computed the respective amounts of exogenous glucose (G) and fructose (F), which are oxidized during exercise when ingested simultaneously, with the use of 13C labeling. Six subjects exercised for 2 h at 60.7 +/- 2.9% of maximal O2 uptake on a cycle ergometer while ingesting 50 or 100 g of G or F or a mixture of 50 g each of G and F in 500 ml of water. The amount of exogenous G oxidized increased from 37.8 +/- 2.2 to 58.3 +/- 8.1 g when the total amount ingested increased from 50 to 100 g. The amount of F oxidized was significantly lower (32.2 +/- 1.2 and 45.8 +/- 2.6 g for the 50 and 100 g ingested, respectively). When 50 g each of G and F were simultaneously ingested in the same drink, the amounts oxidized (39.5 +/- 4.8 and 34.1 +/- 1.5 g, respectively) were similar to those observed when 50 g of G or F were ingested separately. The cumulative amount of exogenous hexoses oxidized (73.6 +/- 6.6 g) was 21% larger than when 100 g of G were ingested. This finding could be due to the fact that the routes for absorption and metabolism of exogenous G and F are at least partly different, resulting in less competition for oxidation when a mixture of these two hexoses is ingested than when an isocaloric amount of G is ingested. From a practical point of view, these data may provide experimental support for using mixtures of carbohydrates in the energy supplements for endurance athletes.
Time course of erythropoietin, triiodothyronine, thyroxine, and thyroid-stimulating hormone at 2,315 m
Authors: Gunga H. C. , Kirsch K. , Rocker L. , Schobersberger W.
Published: December 2017

Erythropoietin (EPO), triiodothyronine, thyroxine, thyroid-stimulating hormone (TSH), hemoglobin (Hb), reticulocytes, packed cell volume, and plasma volume changes were studied in 29 male Austrian mountain rescue soldiers before and several days after an ascent from 744 to 2,315 m in the Alps. EPO concentrations showed a remarkable increase 48 h after the ascent (P < 0.01). No significant changes were found in triiodothyronine, thyroxine, and TSH. Reticulocytes increased only slightly. Hb decreased during the week (P < 0.01). Packed cell volume did not change, whereas plasma volume showed a slight decrease for 48 h after the ascent but then increased constantly (P < 0.01). It seems that thyroid hormones, TSH, and Hb play only a minor role in the regulation of EPO production and release under mild hypobaric-hypoxic conditions (2,315 m).
Modifications of glucose and lipid metabolism in cold-acclimated lean and genetically obese rats
Authors: Bobbioni-Harsch E. , Assimacopoulos-Jeannet F. , Jeanrenaud B.
Published: December 2017

Glucose turnover rate, 2-deoxy-D-[3H]glucose (2-DG) uptake, lipid synthesis in liver, white adipose tissue, and brown adipose tissue (BAT) were measured in lean FA/FA and genetically obese fa/fa rats either kept at 21 degrees C or acclimated to a cold environment (4 degrees C). After 10 days at 4 degrees C, lean rats increased their glucose turnover rate; 2-DG uptake as well as lipid synthesis in BAT were markedly stimulated. After cold acclimation, obese rats also increased glucose turnover; however, BAT glucose utilization was only slightly stimulated. Basal hyperinsulinemia and muscle insulin resistance of the obese group (as assessed by reduced 2-DG uptake in the soleus muscle) were present at room temperature and persisted at 4 degrees C. Total BAT lipid synthesis was increased to the same extent as in lean rats. Obese rat liver lipid synthesis, already much higher than normal at 21 degrees C, was further increased by cold exposure. We conclude that obese cold-acclimated fa/fa rats do not improve their muscle insulin resistance and barely improve BAT glucose utilization. We further suggest that an additional activation of hepatic lipid synthesis and oxidation thereof could participate in the heat production needed by the cold-acclimated obese rats.
Relationships between regional ventilation and vascular and extravascular volume in supine humans
Authors: Brudin L. H. , Rhodes C. G. , Valind S. O. , Jones T. , Jonson B. , Hughes J. M.
Published: December 2017

With the use of positron emission tomography, alveolar ventilation (VA), lung density, and pulmonary blood volume (VB) were measured regionally in eight nonsmokers in the supine posture and one nonsmoker in the prone posture during quiet breathing in a transaxial thoracic section at midheart level. Regional values of alveolar volume (VA) and extravascular tissue volume (VEV) were derived from the inherent relationships between different compartments in the lung. Ratios proportional to gas volume (VA/VEV) and ventilation (VA/VEV) per alveolar unit, respectively, were calculated. No differences between right and left lung were found. Variations in the vertical direction could explain approximately 65% of the total within-group variation in VA, VB, and ln (VA), whereas the corresponding value for horizontal variation was only 3–9% (right lung, supine subjects). Similar gravitational gradients were found in the single prone subject. There was a significant linear correlation between VA and ln (VA). When VA and VA are related to a given number of alveolar units (VEV), the data are consistent with a linear relationship between VA/VEV and VA/VEV, indicating that ventilation might be explained by the elastic properties of lung tissue according to Salazar and Knowles (J. Appl. Physiol. 19: 97–104, 1964). Regional VB was closely associated with the gradient of regional alveolar volume (VA/VEV) (by virtue of weight of blood and competition for space) and therefore, indirectly, closely associated with the vertical gradient of ventilation.
Thyroarytenoid muscle activity during hypocapnic central apneas in awake nonsedated lambs
Authors: Kianicka I. , Leroux J. F. , Praud J. P.
Published: December 2017

In this study, we examined whether the glottis is open or closed during central apnea and the effect of arterial PO2 (PaO2) on this control. We hyperventilated nine 11- to 30-day-old awake nonsedated lambs via a tracheostomy for 1 min to induce central apnea. Four gas mixtures (8, 15, 21, and 30% O2) were used. At the end of the hyperventilation period, the lambs were allowed to breathe spontaneously through intact upper airways. Using a pneumotachograph attached to a face mask, we measured airflow, and we continuously recorded electromyographic (EMG) activity of the thyroarytenoid (TA), the main glottic adductor muscle. We also studied the lateral cricoarytenoid muscle (LCA, laryngeal adductor), the posterior cricoarytenoid muscle (PCA, laryngeal abductor), the cricothyroid muscle (CT), and the diaphragm. We found that hyperventilation consistently induced hypocapnic central apnea in all nine lambs in hyperoxic conditions [30% inspiratory fraction of O2 (FIO2)], in eight of nine lambs in normoxia or mild hypoxia (15 and 21% FIO2), and in four of seven lambs in hypoxia (8% FIO2). During baseline room air breathing, there was no glottic adductor muscle expiratory EMG activity or expiratory airflow braking. Continuous TA EMG activity began early during hyperventilation and continued throughout the central apnea, regardless of PaO2. The first subsequent breathing efforts were marked by expiratory flow braking and expiratory activity of the TA. The LCA and the TA demonstrated the same EMG activity pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
Release of creatine kinase and prostaglandin E2 from regenerating skeletal muscle fibers
Authors: McArdle A. , Edwards R. H. , Jackson M. J.
Published: December 2017

To study the effect of regeneration on the release of creatine kinase (CK) and prostaglandin E2 from muscle, extensor digitorum longus muscles of mice were injected with 50 microliters of BaCl2 solution in saline (1.2% wt/vol). Injected muscles showed almost complete degeneration at 3 days postinjection but had regenerated to approximately the same fiber cross-sectional area as contralateral control muscles by 12 days postinjection. These muscles released reduced amounts of intracellular CK compared with contralateral control muscles in response to excessive isometric contractile activity or treatment with the calcium ionophore A-23187 (20 microM) in vitro. However, regenerating muscles contained a lower total CK activity than contralateral control muscles, which accounted for the reduced CK efflux after experimental damage. Regenerating muscles released an increased amount of prostaglandin E2 compared with control muscles after both damaging stimuli. We conclude that regenerated muscles show no reduced susceptibility to contraction-induced damage (as assessed by CK release) but show an elevated release of prostaglandin E2 in response to contractile activity or an increase in intracellular calcium.