bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of airway smooth muscle shortening in excised canine lobes
Authors: Okazawa M. , Vedal S. , Verburgt L. , Lambert R. K. , Pare P. D.
Published: December 2017

There is marked heterogeneity of airway narrowing in intraparenchymal airways in response to bronchoconstricting stimuli. We hypothesized that this heterogeneity results from variations in the structure of the airway wall. Freshly excised dog lung lobes were inflated to transpulmonary pressures (PL) of between 5 and 15 cmH2O, and an aerosol containing a high concentration of carbachol was administered. The lobes were fixed and processed for light-microscopic examination and morphometric analysis of membranous airway dimensions. The relationships of smooth muscle shortening to PL and airway dimensions were analyzed using multiple linear regression. The results show that airway smooth muscle shortening was greater at lower PL and in airways with larger internal perimeter and a greater number of folds per internal perimeter and that it was less in airways with greater inner wall area. We conclude that the magnitude and variability of airway smooth muscle shortening and airway narrowing in response to maximal constricting stimuli are influenced by mechanical factors related to airway wall geometry.
Training and muscle ammonia and amino acid metabolism in humans during prolonged exercise
Authors: Graham T. E. , Turcotte L. P. , Kiens B. , Richter E. A.
Published: December 2017

We studied the responses of NH3 and amino acids (AA) to prolonged exercise (3 h) in trained (Tr; n = 6) and untrained (Utr; n = 6) men. Each subject exercised the knee extensor muscles of one leg at 60% of maximum capacity. Thigh blood flow and femoral arteriovenous differences (0, 30, 60, 120, 150, and 180 min) as well as muscle biopsies (0, 120, and 180 min) were taken for NH3 and AA measurements. In both groups, muscle Glu decreased (P < 0.05) and Asp increased (P < 0.05), but the intramuscular AA pool, including the essential AA, remained constant despite a total AA efflux of 22.4 +/- 8.3 and 24.4 +/- 6.8 mmol/kg wet wt in Tr and Utr, respectively. Tr had greater (P < 0.05) muscle Tau, Phe, Ala, and Glu. Both groups had a large Glu uptake and effluxes of NH3, Gln, and Ala as well as essential AA. The latter implies that there was a net protein catabolism. The efflux of NH3 and Gln was much greater than that expected from AMP deamination, suggesting that deamination of AA was occurring. Many of the AA responses use Glu, and Tr maintained the intramuscular Glu pool at a higher concentration (P < 0.05), implying that they derived more Glu from protein catabolism and/or AA transaminations. Under these conditions, prolonged dynamic knee extensor exercise is associated with a large release of alpha-amino moieties both as NH3 and as Gln as well as a net protein catabolism; these responses are similar in Tr and Utr.
Multifrequency bioelectrical impedance fails to quantify sequestration of abdominal fluid
Authors: Cha K. , Hill A. G. , Rounds J. D. , Wilmore D. W.
Published: December 2017

Multifrequency bioelectrical impedance analysis (MFBIA) was used to determine the intracellular (ICW) and extracellular water (ECW) compartments in rats. Resistance and reactance were measured on various body segments with frequencies ranging from 1 KHz to 1 MHz. After initial measurements, 0.9% NaCl was injected intravenously or intraperitoneally, and changes in ECW and ICW were estimated by MFBIA. Important differences were found between segments. In the leg, estimated ECW increased in proportion to the volume of intravenous fluid infused, whereas estimated ICW changed minimally. However, in the trunk region, both estimated ECW and ICW were increased with intravenous and intraperitoneal injections. Our findings indicate that MFBIA has important limitations for quantifying fluid compartments in the trunk and thus in whole body, especially when applied to ill patients in whom sequestration of fluid in the trunk region frequently occurs.
Catecholaminergic effects of prolonged head-down bed rest
Authors: Goldstein D. S. , Vernikos J. , Holmes C. , Convertino V. A.
Published: December 2017

Prolonged head-down bed rest (HDBR) provides a model for examining responses to chronic weightlessness in humans. Eight healthy volunteers underwent HDBR for 2 wk. Antecubital venous blood was sampled for plasma levels of catechols [norepinephrine (NE), epinephrine, dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid] after supine rest on a control (C) day and after 4 h and 7 and 14 days of HDBR. Urine was collected after 2 h of supine rest during day C, 2 h before HDBR, and during the intervals 1–4, 4–24, 144–168 (day 7), and 312–336 h (day 14) of HDBR. All subjects had decreased plasma and blood volumes (mean 16%), atriopeptin levels (31%), and peripheral venous pressure (26%) after HDBR. NE excretion on day 14 of HDBR was decreased by 35% from that on day C, without further trends as HDBR continued, whereas plasma levels were only variably and nonsignificantly decreased. Excretion rates of dihydroxyphenylglycol and dihydroxyphenylalanine decreased slightly during HDBR; excretion rates of epinephrine, dopamine, and dihydroxyphenylacetic acid and plasma levels of catechols were unchanged. The results suggest that HDBR produces sustained inhibition of sympathoneural release, turnover, and synthesis of NE without affecting adrenomedullary secretion or renal dopamine production. Concurrent hypovolemia probably interferes with detection of sympathoinhibition by plasma levels of NE and other catechols in this setting. Sympathoinhibition, despite decreased blood volume, may help to explain orthostatic intolerance in astronauts returning from spaceflights.
Exercise training alters the Ca2+ and contractile responses of coronary arteries to endothelin
Authors: Bowles D. K. , Laughlin M. H. , Sturek M.
Published: December 2017

We tested the hypothesis that alterations in myoplasmic free Ca2+ (Ca(m)) regulation in coronary smooth muscle after exercise training (Ex) underlie changes in vasomotor function. Yucatan miniature pigs were endurance trained by treadmill running for 16-20 wk. Simultaneous determination of Ca(m) (fura-2 microfluorometry) and contraction during endothelin exposure in coronary arteries were then performed. Endothelin (10(-9) to 10(-7) M) was administered either cumulatively or as a single concentration. Ex significantly attenuated the Ca(m) response to 10(-9) and 10(-8) M endothelin. Developed tension was significantly diminished at 10(-8) M endothelin in Ex pigs, producing a rightward shift in the concentration-developed tension response. Attenuated Ca(m) and contractile response to 10(-8) M endothelin were present after Ex whether endothelin was applied cumulatively or as a single concentration. The developed tension-Ca(m) relationship showed an increased Ca(m) sensitivity of contraction with Ex. Endothelin (10(-8) M)-induced Ca2+ influx, estimated by Ba2+ influx in low-Na+ solution, was increased threefold in coronary arteries from Ex pigs. The decreased Ca(m) in the presence of increased divalent cation (i.e., Ca2+) influx during 10(-8) M endothelin suggests a greatly enhanced sarcolemmal Ca2+ cycling in coronary arteries from Ex pigs.
Effect of RBC shape and deformability on pulmonary O2 diffusing capacity and resistance to flow in rabbit lungs
Authors: Betticher D. C. , Reinhart W. H. , Geiser J.
Published: December 2017

Isolated rabbit lungs were perfused with washed and resuspended human red blood cells (RBCs) in the presence of drugs known to change the shape and deformability of RBCs. With sodium salicylate (0.5–2 g/l), which causes echinocytosis and increases RBC deformability, lung diffusing capacity for O2 (DLO2) increased by 21%. When chlorpromazine, which induces stomatocytosis and stiffens RBCs, was given (50 mg/l), DLO2 decreased by 18%. With sodium salicylate, the mean pulmonary artery pressure dropped by 14% from control values, whereas it increased by 18% under chlorpromazine. Comparative experiments with hemoglobin solutions did not reveal any effect of those two drugs either on DLO2 or on pulmonary arterial pressure, which indicates that the effects of sodium salicylate and chlorpromazine were due to changes in RBC shape and deformability. It is concluded that RBC shape and deformability affect pulmonary artery pressure and oxygen diffusing capacity, which may have an influence on oxygen transfer to tissue and hence be of clinical relevance.
Exogenous surfactant function in very preterm lambs with and without fetal corticosteroid treatment
Authors: Chen C. M. , Ikegami M. , Ueda T. , Polk D. H. , Jobe A. H.
Published: December 2017

We have asked whether the function of a bovine source surfactant frequently used clinically (Survanta) could be enhanced after exposure to the very preterm lung when the surfactant was subsequently tested in vivo in preterm surfactant-deficient rabbits. We also evaluated whether there would be effects resulting from fetal treatment with 0.5 mg/kg betamethasone given 48 h before delivery of lambs at 121 days gestational age. The fetal corticosteroid treatment significantly improved gas exchange, increased compliance, increased functional residual capacity, decreased vascular-to-alveolar protein leak, and increased static lung volumes. However, surfactant from both groups of lambs, recovered by alveolar wash and subsequently fractionated to recover the large-aggregate functional surfactant, was equivalent in function to the Survants given to the lambs when tested in preterm surfactant-deficient rabbits. Addition of plasma to Survanta resulted in high minimum surface tensions in vitro, and this inhibition could be prevented by supplementation of the Survanta with 5 or 10% sheep surfactant. No activation occurred with treatment of the very preterm lung, a result consistent with the lung being too immature to contribute components to the surfactant used for treatment. Fetal corticosteroid treatment had no effect on surfactant function at this gestational age.
Stability of evoked parasternal intercostal muscle electromyogram at increased end-expiratory lung volume
Authors: Road J. D. , Osborne S. , Cairns A.
Published: December 2017

The diaphragmatic electromyogram has been measured as an index of the level of diaphragmatic activation. The diaphragmatic electromyogram, however, even when measured by intramuscular electrodes, can be artifactually altered by a change in lung volume (A. Brancatisano, S. M. Kelly, A. Tully, S. H. Loring, and L. A. Engel. J. Appl. Physiol. 66: 1699–1705, 1989) or by a change in body position. The parasternal intercostal muscle may be less subject to the mechanisms that are believed to produce this artifactual change. We asked whether the parasternal intercostal electromyographic activity could be reliable when lung volume changes. Six supine rabbits were anesthetized with ketamine and xylazine. Fine bipolar copper wires, with their tips exposed, were inserted into the left parasternal intercostal muscle in the third interspace. A stimulus that was three times maximal was applied to the corresponding intercostal nerve, and the resulting action potential (AP) was photographed. Parasternal intercostal muscle length was measured by sonomicrometry over the vital capacity range. There were small nonsignificant changes in the AP from functional residual capacity (FRC) to total lung capacity. From FRC to residual volume there was variation in the AP. The AP was also quite stable when regional conductivity was altered but showed variation when the parasternal intercostal muscle length change was accentuated by traction on the rib cage. We conclude that the parasternal intercostal electromyographic activity can be reliably used to measure inspiratory motoneuron output to it over the range of lung volumes from FRC to total lung capacity.
Role of vagal feedback from the lung in hypoxic-induced tachycardia in humans
Authors: Simon P. M. , Taha B. H. , Dempsey J. A. , Skatrud J. B. , Iber C.
Published: December 2017

We assessed the cardiovascular responses to systemic normocapnic hypoxia in five normal subjects, five double lung transplant patients with lung denervation and intact hearts, and five patients with denervated hearts. Progressive normocapnic hypoxia was induced over 10–15 min and maintained for 2–3 min each at 90, 87, 84, and 80% arterial O2 saturation (SaO2). Normal subjects showed the most pronounced mean increase in heart rate (dHR/dSaO2 = 0.86 +/- 0.13 beat/min per 1% SaO2). Three lung-denervated subjects had normal tachycardiac responses (1.6, 0.9, and 0.69 beats/min per 1%), whereas the other two had distinctly lower responses (0.34 and 0.39 beat/min per 1%). Most of the lung-denervated subjects also showed a significant tachycardia with even mild hypoxia; none showed a bradycardiac response to any level of hypoxia. In the heart-denervated group, hypoxic tachycardia was significantly lower than normal (0.29 +/- 0.13 beat/min per 1%). We conclude that vagal feedback from the lungs is not required for the normal chronotropic response to hypoxia in humans; however, this mechanism may contribute significantly to the marked variability in hypoxic-induced tachycardia found among human subjects. These data in humans contrast with the progressive bradycardiac response to hypoxia reported in vagally denervated (or nonhyperpneic) dogs and cats.
Pathophysiological response of bovine diaphragm function to gastric distension
Authors: Desmecht D. , Linden A. , Lekeux P.
Published: December 2017

Because of the anatomic association of an exceptionally bulky stomach with a striking compartmentation of the chest wall, leading to the most cranial insertion of the diaphragm among mammals, gastric overdistension in the bovine species offers a unique pathophysiological condition for the diaphragm. The purpose of the present study was to determine whether increased intragastric pressure (Pga) (1, 2, 3, 4, and 5 kPa) leads to perturbations of respiratory and diaphragm function in calves. Changes in diaphragmatic strength and inspiratory action followed a biphasic pattern: 1) transdiaphragmatic pressure (Pdi) in response to constant bilateral maximal phrenic nerve stimulation at 30 Hz increased with moderate gastric distension and then fell abruptly as Pga continued to rise and 2) the magnitude of the ratio of the fall in pleural pressure to total Pdi was maintained up to a Pga amounting to 2 kPa but declined at higher pressures. We conclude that gastric distension in the bovine species provokes physiologically significant alterations of the diaphragm excitation-to-pressure generation coupling as well as of its capacity to convert Pdi into useful inspiratory pleural pressure. We suggest that these perturbations resulted from the combination of 1) altered tension-generating capacity due to compromised perfusion, 2) altered diaphragm geometry capable of altering tension-to-pressure generation coupling, and 3) modified coupling of the diaphragm with the chest wall that reduced its ability to drive inspiration.
Effects of raising carotid sinus pressure on upper airway resistance and EEG frequency in sleeping dogs
Authors: Saupe K. W. , Smith C. A. , Henderson K. S. , Dempsey J. A.
Published: December 2017

The purpose of this study was to determine whether acutely raising carotid sinus pressure (Pcs) causes changes in upper airway resistance and/or electroencephalographic (EEG) frequency during wakefulness and non-rapid-eye-movement (NREM) sleep. Five dogs were chronically instrumented so that breathing, tracheal pressure, mouth pressure, EEG, and electrooculogram could be measured while pressure in the vascularly isolated carotid sinus was rapidly increased between 40 and 150 mmHg via an extracorporeal perfusion circuit. Dogs were studied during both wakefulness and NREM sleep. Multiple trials of increased Pcs were conducted in each dog. We observed that increasing Pcs 40–150 mmHg caused not only a reflex cardiovascular response but also a 15–40% decrease in minute ventilation. Raising Pcs caused no physiologically significant changes in upper airway resistance over the range of airway pressures and flow rates encountered during inspiration and expiration. Even dogs that demonstrated moderate to substantial sleep-induced increases in airway resistance did not consistently increase resistance during superimposed baroreceptor stimulation. Small increases in airway resistance were sometimes observed during baroreceptor stimulation, but this was not a consistent finding. Acute increases in Pcs did not cause measurable changes in EEG frequency during wakefulness or NREM sleep. We conclude that acute stimulation of the carotid sinus baroreceptors does not cause physiologically meaningful changes in upper airway resistance or EEG activity in awake or sleeping dogs.
Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology and biochemistry
Authors: Huang Y. C. , Sane A. C. , Simonson S. G. , Fawcett T. A. , Moon R. E. , Fracica P. J. , Menache M. G. , Piantadosi C. A. , Young S. L.
Published: December 2017

Prolonged exposure to O2 causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O2 exposure in primates. Sixteen healthy male baboons (10–15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O2 (n = 6) or 100% O2 plus aerosolized artificial surfactant (Exosurf; n = 5). A third group of animals (n = 5) was ventilated with an inspired fraction of O2 of 0.21 to control for the effects of sedation and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution (VA/Q) was measured daily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH2O and was intermittently raised to 10 cmH2O for 30 min to obtain additional measurements of VA/Q. After the experiments, lungs were obtained for biochemical and histological assessment of injury. O2 exposures altered hemodynamics, progressively worsened VA/Q, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturated phosphatidylcholine in lavage fluid and improved intrapulmonary shunt, arterial PO2, and lung edema. Surfactant also enhanced the shunt-reducing effect of positive end-expiratory pressure. We conclude that an aerosolized protein-free surfactant decreased the progression of pulmonary O2 toxicity in baboons.
Artificial surfactant attenuates hyperoxic lung injury in primates. II. Morphometric analysis
Authors: Piantadosi C. A. , Fracica P. J. , Duhaylongsod F. G. , Huang Y. C. , Welty-Wolf K. E. , Crapo J. D. , Young S. L.
Published: December 2017

Diffuse lung injury from hyperoxia is accompanied by low compliance and hypoxemia with disruption of endothelial and alveolar epithelial cell layers. Because both function and content of surfactant in diffuse lung injury decrease in animals and in humans, changes in the extent of injury during continuous hyperoxia were evaluated after treatments with a protein-free surfactant in primates. Ten baboons were ventilated with 100% O2 for 96 h and five were intermittently given an aerosol of an artificial surfactant (Exosurf). Physiological and biochemical measurements of the effects of the surfactant treatment are presented in a companion paper (Y.-C. T. Huang, A. C. Sane, S. G. Simonson, T. A. Fawcett, R. E. Moon, P. J. Fracica, M. G. Menache, C. A. Piantadosi, and S. L. Young. J. Appl. Physiol. 78: 1823–1829, 1995.) After O2 exposures, lungs were fixed and processed for electron microscopy. The cellular responses to O2 included epithelial and endothelial cell injuries, interstitial edema, and inflammation. Morphometry was used to quantitate changes in lungs of animals treated with the artificial surfactant during O2 exposure and to compare them with the untreated animals. The surfactant decreased neutrophil accumulation, increased fibroblast proliferation, and decreased changes in the volume of type I epithelial cells. Surfactant-treated animals also demonstrated better preservation of endothelial cell integrity. These responses indicate ameliorating effects of the surfactant on the pulmonary response to hyperoxia, including protection against epithelial and endothelial cell destruction. Significant interstitial inflammation and fibroblast proliferation remained, however, in surfactant-treated lungs exposed to continuous hyperoxia.
Increased prostacyclin production during exercise in untrained and trained men: effect of low-dose aspirin
Authors: Boger R. H. , Bode-Boger S. M. , Schroder E. P. , Tsikas D. , Frolich J. C.
Published: December 2017

The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in untrained and trained subjects before and after low-dose aspirin administration (50 mg/day, 7 days). 2,3-Dinor-TxB2 excretion was significantly higher in the athletes at rest (P < 0.05). Submaximal exercise selectively increased 2,3-dinor-6-keto-PGF1 alpha excretion without affecting 2,3-dinor-TxB2 or prostaglandin E2 excretion rates or platelet aggregation. Low-dose aspirin inhibited platelet aggregation and 2,3-dinor-TxB2 excretion but reduced 2,3-dinor-6-keto-PGF1 alpha by only 24% in the untrained and by 51% in the trained subjects (P < 0.05). After low-dose aspirin administration, the selective stimulatory effect of submaximal exercise on urinary 2,3-dinor-6-keto-PGF1 alpha excretion was even more pronounced than before. The ratio of 2,3-dinor-6-keto-PGF1 alpha to 2,3-dinor-TxB2 was increased by exercise; this effect was significantly enhanced by low-dose aspirin (P < 0.05). Our results suggest that the stimulatory effect of submaximal exercise on prostacyclin production is mostly due to an activation of prostacyclin synthesis from endogenous precursors rather than the result of an enhanced endoperoxide shift from activated platelets to the endothelium. This effect is potentiated by low-dose aspirin pretreatment, indicating that 50 mg/day of aspirin do not impair exercise-induced endothelial prostacyclin production.
Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults
Authors: McClaran S. R. , Babcock M. A. , Pegelow D. F. , Reddan W. G. , Dempsey J. A.
Published: December 2017

We retested 18 healthy, active, and highly fit [maximal O2 consumption (VO2max) 201 +/- 12% of predicted] older adults over a 6-yr period (mean age 67-->73 yr) to determine the longitudinal effects of aging on lung function at rest and during exercise. In the 6-yr period, total lung capacity (TLC), functional residual capacity, and diffusion capacity did not change; vital capacity, forced expiratory volume in 1 s, and maximal volitional flow rates decreased; and residual volume and closing capacity/TLC increased 11-13%, all of which were greater than predicted from cross-sectional data. At maximum exercise over the 6-yr period, VO2max fell 11.2 +/- 3.4% (45.0-->40.3 ml.kg-1.min-1), six (of 18) subjects showed significant arterial hypoxemia (arterial O2 saturation < or = 92%), and maximum heart rate and minute ventilation-to-O2 consumption ratio (VF/VO2) were unchanged. At any given submaximal work rate, VE and breathing frequency were higher, the degree of expiratory flow limitation increased, and end-expiratory and end-inspiratory lung volumes were unchanged but remained significantly higher relative to young adults. We conclude that in contrast to implications from cross-sectional data, our longitudinal findings demonstrate that habitual physical activity and high aerobic capacity modify neither the normal deterioration in resting lung function nor the increased levels of ventilatory work during exercise that occur with healthy aging over the sixth and seventh decades of life.
Role of vagal afferents in the acute ventilatory responses to inhaled wood smoke in rats
Authors: Kou Y. R. , Wang C. Y. , Lai C. J.
Published: December 2017

Spontaneous inhalation of wood smoke (approximately 6 ml) via tracheostomy immediately evoked either a slowing of respiration (SR) or an augmented inspiration (AI) in each of the 76 anesthetized Sprague-Dawley rats studied. The SR was abolished after perineural capsaicin treatment of both cervical vagi (PCT; n = 20) but persisted during cooling of both vagi to 6.7 degrees C (VGC, n = 12); PCT selectively blocked the conduction of unmyelinated C fibers, whereas VGC differentially blocked the conduction of myelinated fibers. In contrast, the AI was eliminated during VGC (n = 10) but was unaffected by PCT (n = 5). Furthermore, after the SR was abolished in rats with PCT, an AI became the dominant immediate response to inhaled wood smoke. Conversely, after the AI was eliminated in rats receiving VGC, a SR was instantly evoked by inhaled wood smoke. Removal of smoke particulates did not affect the SR (n = 17) but did prevent the AI in 5 of the 12 rats studied. These results suggest the following: 1) the SR is a reflex resulting from stimulation of bronchopulmonary C-fiber nerve endings by the gas-phase smoke; 2) the AI results from excitation of lung irritant receptors by the gas-phase and/or smoke particulates; and 3) in intact animals, both types of vagal bronchopulmonary afferents are probably activated by inhaled wood smoke.
Effect of coingestion of fat and protein with carbohydrate feedings on muscle glycogen storage
Authors: Burke L. M. , Collier G. R. , Beasley S. K. , Davis P. G. , Fricker P. A. , Heeley P. , Walder K. , Hargreaves M.
Published: December 2017

Dietary guidelines for achieving optimal muscle glycogen storage after prolonged exercise have been given in terms of absolute carbohydrate (CHO) intake (8-10 g.kg-1.day-1). However, it is of further interest to determine whether the addition of fat and protein to carbohydrate feedings affects muscle glycogen storage. Eight well-trained triathletes [23.1 +/- 2.0 (SE) yr; 74.0 +/- 3.4 kg; peak O2 consumption = 4.7 +/- 0.4 l/min] undertook an exercise trial (2 h at 75% peak O2 consumption, followed by four 30-s sprints) on three occasions, each 1 wk apart. For 24 h after each trial, the subjects rested and were assigned to the following diets in randomized order: control (C) diet (high glycemic index CHO foods; CHO = 7 g.kg-1.day-1), added fat and protein (FP) diet (C diet + 1.6 g.kg-1.day-1 fat + 1.2 g.kg-1.day-1 protein), and matched-energy diet [C diet + 4.8 g.kg-1.day-1 additional CHO (Polycose) to match the additional energy in the FP diet]. Meals were eaten at t = 0, 4, 8, and 21 h of recovery. The total postprandial incremental plasma glucose area was significantly reduced after the FP diet (P < 0.05). Serum free fatty acid and plasma triglyceride responses were significantly elevated during the FP trial (P < 0.05). There were no differences between trials in muscle glycogen storage over 24 h (C, 85.8 +/- 2.7 mmol/kg wet wt; FP, 80.5 +/- 8.2 mmol/kg wet wt; matched-energy, 87.9 +/- 7.0 mmol/kg wet wt).(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatic anion flux during acute endotoxemia
Authors: Kellum J. A. , Bellomo R. , Kramer D. J. , Pinsky M. R.
Published: December 2017

We sought to determine the role the liver might play in the regulation of anion-cation balance during both stable baseline conditions and acute endotoxemia. Ten pentobarbital sodium-anesthetized dogs were instrumented at laparotomy with ultrasonic flow probes around the left renal artery, portal vein, and hepatic artery, and catheters were inserted into the hepatic vein, portal vein, pulmonary artery, left renal vein, and abdominal aorta. Measurements were obtained from each site at baseline and 30-45 min after the intravenous infusion of endotoxin. The total anion flux across the liver was calculated from the strong-ion difference. At baseline, the liver removed anions from the circulation (-0.34 meq/min). With early endotoxemia, however, the liver switched to the release of anions (0.12 meq/min; P = 0.0046). After endotoxin administration, the gut, which was neutral at baseline, began to take up anions (-0.47 meq/min; P = 0.008). Anion flux across the lung and kidney was unchanged. We conclude that in the dog the liver, which removes anions at baseline, switches to release anions during early endotoxemia and may be a major site of acid production in early sepsis.
Brain glucose metabolism in hypobaric hypoxia
Authors: Harik S. I. , Lust W. D. , Jones S. C. , Lauro K. L. , Pundik S. , LaManna J. C.
Published: December 2017

Hypobaric hypoxia at one-half atmospheric pressure for 3 wk was reported to increase the brain capillary density and glucose transport at the blood-brain barrier in the adult rat. We examined the metabolic concomitants of these alterations in rats subjected to the same hypoxic insult. Hypoxic rats increased brain glucose and lactate concentrations and decreased brain glycogen. However, hypoxia had no significant effects on regional brain levels of ATP and phosphocreatine or on intracellular pH, indicating successful adaptation to the hypoxic insult. 2-Deoxyglucose studies showed that hypoxia increased the regional metabolic rate for glucose by 10–40%. These results indicate increased glycolysis in the hypoxic rat brain, which probably underlies the increased density of glucose transporters in brain microvessels and the increased blood-to-brain glucose influx in hypoxia.
Effects of muscle fiber type and size on EMG median frequency and conduction velocity
Authors: Kupa E. J. , Roy S. H. , Kandarian S. C. , De Luca C. J.
Published: December 2017

This paper describes an in vitro method for comparing surface-detected electromyographic median frequency (MF) and conduction velocity (CV) parameters with histochemical measurements of muscle fiber type composition and cross-sectional area (CSA). Electromyographic signals were recorded during electrically elicited tetanic contractions from rat soleus, extensor digitorum longus, and diaphragm muscles placed in an oxygenated Krebs bath. Fibers were typed as slow oxidative, fast oxidative glycolytic, and fast glycolytic based on histochemical enzyme stains. Muscles with a greater percentage of fast glycolytic and fast oxidative glycolytic fibers exhibited greater initial values of MF and CV as well as a greater reduction in these variables over the course of the contraction. Regression indicated that fiber type composition could be predicted based on two MF parameters. A weighted measure of muscle fiber CSA was found to be linearly related to both initial MF and CV. The results of this study suggest that MF and CV parameters recorded during a muscular contraction are related to muscle fiber type composition and muscle fiber CSA.
Maximal skin vascular conductance in subjects aged 5-85 yr
Authors: Martin H. L. , Loomis J. L. , Kenney W. L.
Published: December 2017

This study examined maximal forearm skin vascular conductance (FVCmax) as a function of age in 74 healthy male and female subjects ranging in age from 5 to 85 yr. The skin temperature of the left forearm was uniformly clamped at 42 degrees C by spraying a fine mist of water over the surface. Forearm blood flow (FBF) was measured by venous occlusion plethysmography (Hg-in-Silastic strain gauge). After 60 min of heating, a reactive hyperemia maneuver was performed to verify that forearm skin blood flow was maximal by using laser Doppler flowmetry to isolate the skin component of FBF. The maximal FBF of each subject was then divided by mean arterial pressure to yield FVCmax (in ml.100 ml-1.min-1.100 mmHg-1), i.e., minimal resistance. The model that best fits the data was curvilinear, as described by FVCmax = 13.1 + 86.9 (age-0.75) (r2 = 0.52, P < 0.001). The exclusion of subjects younger than 18 yr of age simplified the model to a linear fit with a slope of -0.16 conductance units/yr for adults. Interindividual variability remained constant across the entire age span. Once the age effect was considered, there were no significant effects of gender, adiposity, resting blood pressure, physical activity level, or body surface area on FVCmax.
Effect of multiple denervations on the exercise hyperpnea in awake ponies
Authors: Pan L. G. , Forster H. V. , Wurster R. D. , Brice A. G. , Lowry T. F.
Published: December 2017

In three previously reported studies, we had documented that the normal exercise hyperventilation in ponies is accentuated by carotid body denervation (CBD), not affected by hilar nerve pulmonary vagal denervation (HND), and mildly attenuated by spinal cord ablation of the dorsal lateral columns at L2 (SA). In the present study, we hypothesized that if redundancy of control existed in exercising ponies, then multiple denervations of theoretically important pathways in the same animal might attenuate the ventilatory response to exercise in a way not predictable by the individual lesion experiments alone. There were three major findings in the various combinations of CBD, HND, and SA in ponies during treadmill exercise. First, the combination of CBD with HND or SA resulted generally in an accentuation of the hypocapnia during exercise that was predictable on the basis of CBD alone. However, in one pony that showed a hypercapnic exercise response after SA alone, CBD subsequently caused a greater exercise hypercapnia. Second, HND in a CBD or SA pony did not affect the exercise arterial PCO2 response, which is consistent with previous data showing the lack of an HND effect in otherwise intact ponies. Third, in ponies with all three denervations together, the predominant response was an increase, not a decrease, in the exercise hyperventilation; this increase was greater than that predicted from the individual lesions. We conclude that these data do not provide evidence of redundancy in mechanism for the exercise hyperpnea other than instances of carotid chemoreceptor error sensing when hypercapnia occurs during exercise.
Dynamic viscoelastic nonlinearity of lung parenchymal tissue
Authors: Navajas D. , Maksym G. N. , Bates J. H.
Published: December 2017

To investigate the contribution of nonlinear tissue viscoelasticity to the dynamic behavior of lung, time and frequency responses of isolated parenchymal strips of degassed dog lungs were investigated. The strips were subjected to loading and unloading stretch steps for 60 s and to sinusoidal oscillations (0.03–3 Hz) of different stretch amplitudes (delta lambda = 0.05, 0.1, and 0.2) and at different operating stresses (T(o) = 0.5, 1, and 2 kPa). Elastance (E) increased linearly with the logarithm of frequency (approximately 10% per frequency decade), and resistance (R) decreased hyperbolically with frequency. Both E and R varied little with delta lambda but they increased proportionally with T(o). Hysteresivity (eta = R x 2 pi x frequency/E) ranged from 0.07 to 0.10. In agreement with the frequency response, the magnitude of the unit step response increased with T(o) and was higher when loading than when unloading, and the stress relaxation ratio (approximately 0.10) did not vary greatly with T(o) or with delta lambda. The time and frequency behavior of the strips were interpreted in terms of the quasilinear viscoelastic model of Navajas et al. (J. Appl. Physiol. 73:2681–2692, 1992). The model explains most of the dependencies of step and oscillatory responses on the measurement conditions, in particular the proportional dependence of E and R on T(o). According to the model, about two-thirds of energy dissipated during oscillation arises from tissue viscoelasticity. The remaining dissipated energy could be accounted for by plasticity. Thus the effect of nonlinear elasticity on the dynamic behavior of lung tissue can be empirically described by a simple quasilinear model characterized by only two parameters.
Effect of altitude on uterine artery blood flow during normal pregnancy
Authors: Zamudio S. , Palmer S. K. , Droma T. , Stamm E. , Coffin C. , Moore L. G.
Published: December 2017

To determine whether uterine blood flow was reduced and indexes of pelvic blood flow distribution altered in normotensive pregnancy at high (3,100 m) compared with low altitude (1,600 m), we measured uterine, common iliac, and external iliac artery blood flow velocities and diameters in women during pregnancy and again postpartum. Pregnancy increased uterine artery diameter, blood flow velocity, and volumetric flow at both altitudes. Uterine artery blood flow velocity was greater (69.0 +/- 2.2 vs. 59.4 +/- 3.0 cm/s; P < 0.005) but diameter was smaller at 3,100 m than at 1,600 m (2.5 +/- 0.3 mm vs. 3.4 +/- 0.2 mm; P < 0.005), resulting in volumetric flow that was one-third lower at week 36 of pregnancy (203 +/- 48 vs. 312 +/- 22 ml/min, respectively; P < 0.01). Pregnancy increased common iliac blood flow velocity and decreased external iliac artery blood flow velocity at both altitudes. The uterine artery received a smaller percent of common iliac flow at 3,100 than at 1,600 m (46 +/- 7 vs. 74 +/- 6%; P < 0.005). Gestational age was similar but birth weight was lower at 3,100 m than at 1,600 m. Among subjects at 1,600 m, variation in uterine blood flow velocity correlated positively with infant birth weight. We concluded that reduced uterine blood flow and altered pelvic blood flow distribution during pregnancy at high altitude likely contributed to the altitude-associated reduction in infant birth weight.
Hypoxic ventilatory decline: site of action
Authors: Robbins P. A.
Published: December 2017

Although superficially similar, HVD appears to arise from different mechanisms in the awake animal as compared with the anesthetized animal. Consequently, the good evidence supporting a central site of action for hypoxia in the genesis of HVD in the anesthetized animal cannot be used as evidence for a central site of action for hypoxia in the awake animal. In their paper on HVD in the awake cat, Long et al. (10) conclude: “The striking similarity between feline and human ventilatory responses to moderate hypoxia illustrated by this and previous experiments leads us to believe that it is likely similar mechanisms apply to both species. Thus it seems probable that working out the mechanisms of the ventilatory response to hypoxia in the awake cat will go a long way toward solving the same problems in humans.” This activity should not neglect a consideration of whether adaptation at the carotid body during sustained hypoxia may be involved in the genesis of HVD in the awake state.
Hypothetical roles of angiogenesis, osmotic swelling, and ischemia in high-altitude cerebral edema
Authors: Severinghaus J. W.
Published: December 2017

High-altitude cerebral edema (HACE) has been tentatively attributed to either cellular ion pump failure from ATP depletion or high cerebral blood flow inducing high capillary pressure. These hypotheses are inadequate because 1) ATP decrease occurs only after anoxia has silenced neuronal activity and 2) prolonged hypercapnic hyperemia generates only minor transcapillary protein leakage localized to the less hyperemic brain regions. In connection with this review of HACE and its causes, three other hypothetical mechanisms that might contribute are presented. 1) Osmotic cell swelling: cellular and mitochondrial osmotic pressure may rise 30 mosmol in ischemia or anoxia (potentially a 7–10% expansion). Smaller rises caused by hypoxia may be significant in the closed calvarium. 2) Focal ischemia: this may result from intracranial hypertension from hyperemia and osmotic swelling. 3) Angiogenesis: cellular hypoxia initially attracts and activates macrophages that express vascular endothelial growth factor and other cytokines, dissolving capillary basement membranes and degrading extracellular matrix, resulting in capillary leakage. In HACE, petechial hemorrhages are seen in the nerve cell layers of the retina, and similar changes have been described throughout the brain. Evidence linking HACE to angiogenesis is that dexamethasone, an effective inhibitor of angiogenesis, has demonstrated unique success in preventing and treating HACE.
Central effects of endothelin on respiratory output during development
Authors: Dreshaj I. A. , Miller M. J. , Ernsberger P. , Haxhiu-Poskurica B. , Martin R. J. , Haxhiu M. A.
Published: December 2017

Both endothelin-1 protein and endothelin-1 specific binding sites have been identified in areas of the medulla oblongata involved in respiratory control. We examined whether endothelin acting centrally affects respiratory output during early postnatal life. We initially examined the effect of intracisternally administrated endothelin on respiratory output in 10 2- to 18-day-old piglets. Endothelin-1 administration at 50 nmol to 1 mumol caused respiratory inhibition. We subsequently examined whether this response is mediated through chemosensitive areas of the ventral medulla. Endothelin-1 was microinjected into specific ventral or dorsal medullary regions in 31 14- to 22-day-old piglets. Microinjection of endothelin-1 (10 fmol to 0.1 pmol) just above the hypoglossal roots, lateral to the pyramids, and within 1 mm from the surface (n = 24) attenuated respiratory output, and complete apnea occurred with 1 pmol in all animals. However, microinjection of endothelin-1 3 mm below the ventral surface (n = 5) and into the dorsal medulla (n = 3) had no inhibitory effect. Comparable doses of angiotensin II (n = 5) and norepinephrine (n = 5) microinjected into the endothelin-1 sensitive area also did not influence respiratory output. These effects of endothelin-1 were not altered by prior endothelin-B receptor blockade (IRL-1038) but could be reversed by endothelin-A receptor blockade (BQ-610). These results suggest that endothelin-1 release may cause ventilatory depression mediated through endothelin-A receptors located in the chemosensitive areas of the ventrolateral medulla.
Effect of microgravity on forearm subcutaneous vascular resistance in humans
Authors: Gabrielsen A. , Norsk P. , Videbaek R. , Henriksen O.
Published: December 2017

To test the hypothesis that the subcutaneous vascular constrictor response to an orthostatic stress in humans is augmented after exposure to microgravity, the following experiment was performed. Four male astronauts underwent a standardized stepwise lower body negative pressure (LBNP) profile 5 mo before and between 24 and 40 h after completion of the 10-day Spacelab D2 mission (STS-55). Forearm subcutaneous blood flow was continuously measured during LBNP by the 133Xe washout technique, and forearm subcutaneous vascular resistance (FSVR) was estimated by dividing mean arterial pressure by forearm subcutaneous blood flow. Relative to the pre-LBNP level, FSVR increased to 169 +/- 42 (P < 0.05), 176 +/- 12 (P < 0.05) and 158 +/- 27% during postflight LBNP of -11 (20 min), -23 (5 min), and -30 (7.5 min) mmHg, respectively. During the same LBNP levels of the same durations preflight, FSVR increased to 121 +/- 11 (not significant), 139 +/- 12 (P < 0.05), and 135 +/- 13% (P < 0.05), respectively. Thus, FSVR increased more promptly and, in three of the four subjects, was more pronounced during postflight than during preflight LBNP. In conclusion, the FSVR response was more prompt and tended to be accentuated after 1–2 days after exposure to 10 days of microgravity and could act as a defense mechanism to alleviate decreased orthostatic tolerance.
Cold dry air-induced rhinitis: effect of inhalation and exhalation through the nose
Authors: Naclerio R. M. , Proud D. , Kagey-Sobotka A. , Lichtenstein L. M. , Thompson M. , Togias A.
Published: December 2017

Ten subjects with a history of cold air-induced nasal symptoms participated in a randomized two-period crossover study to evaluate the occurrence and magnitude of the reaction induced by inhalation and exhalation of cold dry air through the nose. The protocol involved breathing of either warm moist or cold dry air for 45 min at resting breathing rates. The nasal response was quantified by determining the amount of produced secretions as well as by measuring histamine and N-alpha-p-tosyl-L-arginine methyl (TAME) esterase activities in recovered nasal lavage fluids. Symptom scores were obtained. Warm moist air did not increase symptoms nor did it result in any significant changes in secretions or mediator levels. Compared with baseline, cold dry air induced significant rhinorrhea and increased both secretion weights (9.6 +/- 1.3 vs. 28.1 +/- 6.5 mg; P = 0.01) and the levels of histamine (3.9 +/- 1.2 vs. 10.6 +/- 2.7 ng/ml; P = 0.02) and TAME esterase activity (3.1 +/- 0.8 vs. 7.0 +/- 2.0 counts.min-1.10(-3); P = 0.01). We conclude that bidirectional nasal breathing of cold dry air results in a reaction that is qualitatively similar to that induced when air is only inhaled through the nose and exhaled through the mouth.
Application of a cervical stimulating apparatus for bilateral transcutaneous phrenic nerve stimulation
Authors: Eastwood P. R. , Panizza J. A. , Hillman D. R. , Finucane K. E.
Published: December 2017

Transcutaneous bilateral phrenic nerve stimulation (tPNS) is frequently used to assess diaphragmatic function in humans. Commonly, stimulation is performed with hand-held electrodes; however, these are unsuitable for studies requiring repeated PNS and where recruitment of rib cage and neck muscles may shift the probes in relation to the nerves. In this study we describe the design of a cervical neck brace and electrode probes that maintain stimulating electrodes in constant position relative to the phrenic nerves and facilitates studies requiring repeated maximal PNS. The effectiveness of the apparatus was examined by 1) reviewing the reproducibility of the transdiaphragmatic pressure response to 0.1 ms tPNS (PdiT) at relaxed functional residual capacity in four subjects studied on 25 +/- 8 (SD) occasions (> or = 24 h apart) over a 4-yr period, and 2) measuring peak-to-peak amplitude of the left and right diaphragmatic compound muscle action potentials (surface electrodes) during two prolonged studies (38 +/- 9 min) in each subject, when tPNS was performed during repeated submaximal and maximal inspiratory efforts. PdiT was reproducible in each subject when measured repeatedly within a single study [coefficient of variation (CV) of 3.8 +/- 0.8%] and over separate days (CV of 11.5 +/- 3.5%). The peak-to-peak amplitudes of the left and right compound muscle action potentials were also reproducible (CV of 8.4 +/- 4.3 and 8.4 +/- 2.9%, respectively) and independent of the degree of effort. The apparatus appears effective for the maintenance of maximal stimulation under varied conditions for long periods and provides reproducible measurements of PdiT both within and between studies.