bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptations in the elbow flexors of elderly males after heavy-resistance training
Authors: Roman W. J. , Fleckenstein J. , Stray-Gundersen J. , Alway S. E. , Peshock R. , Gonyea W. J.
Published: December 2017

The structural and functional characteristics of the elbow flexors in five elderly males were studied before and after 12 wk of heavy-resistance training. Muscle volume and cross-sectional area of two of the elbow flexor (biceps brachii and brachialis) muscles were determined by magnetic resonance imaging. Mean muscle fiber area, percent fiber distribution, and collagen and noncontractile tissue densities were determined on histological sections from needle biopsies. Isokinetic strength of the elbow flexors was measured at velocities between 60 and 300 degrees/s. Muscle volume and cross-sectional area of the biceps brachii and brachialis significantly increased by 13.9 and 22.6%, respectively, after the training program. A preferential hypertrophy of type II fibers (37.2%) was observed. Significant increases in peak torque were observed at all the tested velocities. The amount of work a subject could perform during a 25-repetition test at 240 degrees/s increased by 41% after training. These results demonstrate that the skeletal muscles of elderly individuals can adapt to heavy-resistance exercise and do so by increases in both muscle size and strength.
Enhanced gluconeogenesis from lactate in perfused livers after endurance training
Authors: Sumida K. D. , Urdiales J. H. , Donovan C. M.
Published: December 2017

The effects of endurance training (running 90 min/day at 30 m/min, 10% grade) on hepatic gluconeogenesis were studied in 24-h-fasted rats with use of the isolated liver perfusion technique. After isolation, the liver was perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes (hematocrit 22–24%) with no added substrate. Subsequent to the "washout" period, the reservoir was elevated with various concentrations of lactate and [U-14C]lactate (10,000 dpm/ml) to assess hepatic glucose production. Relative flow rates were not significantly different between trained (1.94 +/- 0.05 ml/g liver) and control livers (1.91 +/- 0.05 ml/g liver). Furthermore, no significant differences were observed in perfusate pH, hematocrit, bile production, or serum alanine aminotransferase effluxing from trained or control livers. At saturating arterial lactate concentrations (> 2 mM), the maximal rate (Vmax) for hepatic glucose production was significantly higher for trained (0.91 +/- 0.04 mumol.min-1 x g liver-1) than for control livers (0.73 +/- 0.02 mumol.min-1 x g liver-1). That this reflected increased gluconeogenesis is supported by a significant elevation in the Vmax for [14C]glucose production from trained (13,150 +/- 578 dpm.min-1 x g liver-1) compared with control livers (10,712 +/- 505 dpm.min-1 x g liver-1). Significant increases were also observed in the Vmax for lactate uptake (25%), O2 consumption (19%), and 14CO2 production (23%) from endurance-trained livers. The Km for hepatic glucose output, approximately 1.05 mM lactate, was unchanged after endurance training. These findings demonstrate that chronic physical activity results in an elevated capacity for hepatic gluconeogenesis, as assessed in situ at saturating lactate concentrations.
Blood glutathione status during exercise: effect of carbohydrate supplementation
Authors: Ji L. L. , Katz A. , Fu R. , Griffiths M. , Spencer M.
Published: December 2017

Blood glutathione status and activities of antioxidant enzymes have been investigated during prolonged exercise with or without carbohydrate (CHO) supplementation. Eight subjects cycled at approximately 70% of maximal oxygen uptake to fatigue [134 +/- 19 (SE) min] on the first occasion (control, CON) and at the same work load and duration on the second occasion but with CHO ingestion during exercise. Blood reduced glutathione (GSH) concentration increased from 0.55 +/- 0.05 mM at rest to 0.77 +/- 0.09 mM after 120 min of exercise during CON (P < 0.01) but remained constant during CHO exercise. Blood glutathione disulfide (GSSG) levels were unchanged during CON and CHO exercise. Blood GSH + GSSG content and GSH/GSSG ratio were also significantly (P < 0.05) elevated during CON but not during CHO exercise. The increases in GSH and GSH + GSSG in CON were associated with decreases in plasma glucose and insulin levels. Activities of blood GSH peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase were significantly increased during the CHO exercise, whereas only GSSG reductase activity was elevated during the CON ride. It is concluded that blood GSH increases during prolonged exercise and that CHO supplementation may prevent blood GSH increase possibly because of its inhibitory effects on hepatic hormonal releases, which stimulate GSH output.
Ventilatory response to moderate hypoxia in awake chemodenervated cats
Authors: Long W. Q. , Giesbrecht G. G. , Anthonisen N. R.
Published: December 2017

In humans and cats the ventilatory response to 30 min of moderate hypoxia (arterial PO2 40–55 Torr) is biphasic: ventilation increases sharply for the first 5 min and then declines. In humans there is evidence that the decline is dependent on the initial increase. We therefore examined ventilatory responses to moderate isocapnic hypoxia in awake cats with and without carotid body denervation. Cats underwent denervation or a sham operation. Then they were studied in a Drorbaugh-Fenn plethysmograph while ventilation, arterial PO2, and end-tidal PO2 and PCO2 were measured. Three sham-operated and four denervated cats were studied with room air as the control. Sham animals demonstrated a biphasic response: ventilation rose to 211% of control at 5 min and fell to 114% of control at 25 min. Denervated animals showed neither the initial increase nor the subsequent decrease in ventilation. Three sham-operated and three denervated cats were studied with 2% CO2 added to the inspirate. Results were similar: intact cats showed a biphasic response to hypoxia, whereas denervated cats showed neither an increase nor a decrease in ventilation. Preliminary experiments showed that hypoxia was not associated with changes in CO2 output or systemic blood pressure in either denervated or intact animals. We conclude that depression of ventilation does not occur in awake denervated cats in response to moderate hypoxia and that the decline in ventilation that occurs in intact cats is in some way dependent on peripheral chemoreceptor output.
Intratracheal E. coli lipopolysaccharide induces platelet-dependent bronchial hyperreactivity
Authors: Vincent D. , Lefort J. , Chatelet F. , Bureau M. F. , Dry J. , Vargaftig B. B.
Published: December 2017

Bronchial hyperresponsiveness (BHR) characterizes asthma and accompanies respiratory infections. Because endotoxin [lipopolysaccharide (LPS)] induces either hyper- or hyporesponsiveness of the guinea pig airways and protects against bronchopulmonary anaphylaxis in sensitized guinea pigs, we compared the effects of the intratracheal administration of Escherichia coli LPS on bronchopulmonary responsiveness to intravenous serotonin or acetylcholine in sensitized and nonsensitized guinea pigs. LPS (1 mg) induced BHR within 1–2 h, with a threefold increase in the bronchial response after serotonin challenge in both groups (n = 6; P < 0.005) and a marked influx of neutrophils into the perivascular and peribronchial connective tissue and the bronchoalveolar lavage fluid. This BHR was not leukocyte dependent, since it was still observed in animals depleted of circulating leukocytes with vinblastine and was not modified by antineutrophil serum, unless platelet counts were < 100,000/mm3. This suggested that LPS-induced BHR involves platelets, and indeed antiplatelet serum, which depleted platelets, or prostacyclin, which inhibited platelets, was effective in suppressing BHR. Neither aspirin, mepyramine, nor the platelet-activating factor antagonist WEB 2170, administered before LPS instillation, prevented BHR, whereas the association of methysergide, mepyramine, and aspirin was effective, without modifying platelet and leukocyte counts. This association has been shown to prevent the release of ATP by ex vivo platelets. Our results suggest that platelets or a platelet-derived product mediates LPS-induced BHR.
Weight-training-induced attenuation of the circulatory response of older males to weight lifting
Authors: McCartney N. , McKelvie R. S. , Martin J. , Sale D. G. , MacDougall J. D.
Published: December 2017

We examined the effects of 12 wk of dynamic strength training on the heart rate (HR) and blood pressure of older male subjects during 10 repetitions of single-arm curl and single- and double-leg press at 60 and 80% of both the pre- and posttraining maximum capacities and during single maximum lifts (1 RM). The circulatory responses were greater at 80% of 1 RM than at 60% and increased with active muscle mass. After training, the 1 RMs increased by 24 (legs) to 54% (arms) and there was a marked attenuation of HR and arterial pressure during exercise when subjects lifted the same absolute load. Greatest reductions in HR (108 +/- 4 to 94 +/- 2 beats/min), systolic blood pressure (BPs, 247 +/- 14 to 206 +/- 9 Torr), diastolic pressure (156 +/- 9 to 116 +/- 5 Torr), mean arterial pressure (143 +/- 6 to 131 +/- 5 Torr), and rate-pressure product (268 +/- 22 to 196 +/- 12 HR.BPs/100) occurred during double-leg press at 80% of the pretraining 1 RM. After training, during lifting at 60, 80, and 100% of the posttraining 1 RMs, the HRs and arterial pressures were the same as those during pretraining testing when the same relative, but lighter, absolute loads were used. These observations are consistent with a significant part of the circulatory response to weight lifting being mediated by a feedforward "central command" mechanism coupled to the relative intensity rather than to the absolute level of force.
Caffeine attenuates the exercise-induced increase in plasma [K+] in humans
Authors: Lindinger M. I. , Graham T. E. , Spriet L. L.
Published: December 2017

This study examined the dose-response effects of caffeine on plasma K+ balance during prolonged exercise. Two series of experiments were performed. In series A, 1 h after ingestion of 9 mg/kg dextrose (placebo) or 9 mg/kg caffeine, eight subjects cycled at 78% of peak O2 consumption until exhaustion; in series B, in four trials, 1 h after ingestion of 0, 3, 6, or 9 mg/kg caffeine, eight subjects ran on a treadmill at 85% of peak O2 consumption until exhaustion. Blood was sampled from an antecubital vein for analysis of hematocrit, plasma concentrations of epinephrine ([Epi]) and norepinephrine, and [K+]. The change in plasma volume was calculated from hematocrit. During exercise, there was a net addition of K+ to and a net loss of fluid from the plasma compartment. Caffeine had no effect on plasma volume and norepinephrine concentration during exercise. In series A and B 9 mg/kg caffeine and in series B 6 mg/kg caffeine resulted in a significant attenuation of the increase in plasma [K+] with exercise. In series A increases in plasma [Epi] were 1.4- to 2-fold greater during exercise with caffeine than with placebo. At exhaustion, plasma [Epi] was twofold higher with caffeine (10.1 +/- 2.3 nM) than with placebo (5.3 +/- 0.8 nM), whereas plasma [K+] was only 4.88 +/- 0.18 meq/l with caffeine compared with 5.37 +/- 0.14 meq/l with placebo. It is concluded that caffeine attenuates the increase in plasma [K+] during exercise by stimulation (via one of its metabolites or by increased [Epi]) of tissue Na-K pump activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary interstitial pressure in intact in situ lung: transition to interstitial edema
Authors: Miserocchi G. , Negrini D. , Del Fabbro M. , Venturoli D.
Published: December 2017

In anesthetized rabbits (n = 25) subject to slow intravenous saline loading (0.4 ml.min-1.kg-1) for 3 h, we measured pulmonary interstitial pressure (Pip) in intact in situ lungs with glass micropipettes inserted directly into the lung parenchyma via a "pleural window." Measurements were done in apneic animals at the end-expiratory volume with O2 delivered in the trachea. Pip was -10 +/- 1.5 (SD) cmH2O in control and increased to 0.6 +/- 3.8 and 5.7 +/- 3.3 cmH2O at 66 and 180 min, respectively. The wet-to-dry weight ratio (W/D) of the lung was 5.04 +/- 0.2 in the control group and 5.34 +/- 0.7 at 180 min (+6%); the corresponding W/D for intercostal muscles were 3.25 +/- 0.03 and 4.19 +/- 0.5 (+28%). Pulmonary interstitial compliance was 0.47 ml.mmHg-1.100 g wet wt-1. Pulmonary arterial and left atrial pressures were 18.4 +/- 2 and 3 +/- 1 cmH2O in control and increased to 19.5 +/- 2.9 and 4.6 +/- 1.7 cmH2O at 180 min, respectively. Aortic flow (cardiac output) increased from 103 +/- 35 to 131 +/- 26 ml/min; pulmonary resistance fell from 0.17 +/- 0.06 to 0.14 +/- 0.05 cmH2O.min.ml-1 (-18%), suggesting that the increase in Pip did not limit blood flow. The pulmonary capillary-to-interstitium filtration pressure gradient decreased sharply from a control value of 10 cmH2O to 0 cmH2O within 60 min because of the increase in Pip and remained unchanged for < or = 180 min. Data suggest that the pulmonary interstitial matrix can withstand fluid pressures above atmospheric, preventing the development of pulmonary alveolar flooding.
Body fluid compartments, renal blood flow, and hormones at 6,000 m in normal subjects
Authors: Anand I. S. , Chandrashekhar Y. , Rao S. K. , Malhotra R. M. , Ferrari R. , Chandana J. , Ramesh B. , Shetty K. J. , Boparai M. S.
Published: December 2017

We previously described a syndrome of congestive heart failure occurring in healthy young men at extreme altitude (Anand et al. Lancet 335: 561–565, 1990). The pathogenesis of this condition is unclear. We therefore measured body fluid compartments, renal blood flow, and a variety of plasma hormones in 10 asymptomatic young men staying above 6,000 m for > 10 wk and compared the results with controls at sea level. Body compartments were measured with isotope dilution techniques and renal blood flow with o-[125I]iodohippurate sodium. There was a marked expansion of all the fluid spaces: total body sodium was 14% above normal (P < 0.05), total body water was 18% above normal (P < 0.05), plasma volume was 33% above normal (P < 0.05), and blood volume was 84.5% above normal (P < 0.001). The effective renal plasma flow was lower than normal by 55% (P < 0.001), but the reduction in the effective renal blood flow was 37% below normal (P < 0.001) because the hematocrit was high (41.6% above normal). Plasma norepinephrine was nearly 3 times normal (P < 0.01), cortisol 3 times normal (P < 0.001), and growth hormone 18 times normal (P < 0.01). Aldosterone was twice normal (P < 0.03). Plasma epinephrine, atrial natriuretic peptide, and plasma renin activity were unchanged. The degree of fluid retention in these normal subjects was similar to that in patients with severe untreated congestive heart failure (Anand et al. Circulation 80: 299–305, 1989), whereas sodium retention and reduction in effective renal blood flow were less.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant
Authors: Lewis J. F. , Tabor B. , Ikegami M. , Jobe A. H. , Joseph M. , Absolom D.
Published: December 2017

Adult sheep (35 +/- 3 kg) underwent saline lung lavage and 1.5 h of mechanical ventilation to induce acute lung injury. Animals received 100 mg lipid/kg body wt of tracheally instilled surfactant (Inst Surf) or either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) and were killed 3 h later. Inst Surf and Neb Surf groups had significant improvements in oxygenation (P < 0.01) and peak inspiratory pressures (PIP) (P < 0.05) compared with pretreatment values. Improvements in oxygenation and PIP for Inst Surf animals were significantly greater than for Neb Surf animals (P < 0.05). Volumes of maximal pressure of quasi-static pressure-volume curves measured at the time the animals were killed were significantly greater for Inst Surf and Neb Surf animals than for animals given Neb Saline (P < 0.05). Alveolar recovery of exogenous surfactant was 100 times greater for Inst Surf animals (1,732 +/- 70 mg) than for Neb Surf animals (15.3 +/- 2.9 mg) at the time they were killed. Although there were no differences in exogenous surfactant distribution patterns at the lobar level between the two surfactant-treated groups, distribution histograms calculated for 10-g lung pieces revealed the Neb Surf animals had significantly more pieces within 25% of the mean value of 1.0 (42.7 +/- 6.9%) than did Inst Surf animals (20.8 +/- 5.5%) (P < 0.01). Exogenous surfactant therapy improved lung function with significantly different quantities of surfactant deposited in lung tissue for the two delivery methods evaluated.
Protein kinase C-mediated pulmonary vasoconstriction in rabbit: role of Ca2+, AA metabolites, and vasodilators
Authors: Michael J. R. , Yang J. , Farrukh I. S. , Gurtner G. H.
Published: December 2017

We studied the effects of three chemically distinct protein kinase C activators on pulmonary vascular tone in the buffer-perfused isolated rabbit lung. The three activators, 12-deoxyphorbol 13-isobutyrate (12,13-phorbol), mezerein, and 1-oleoyl-2-acetyl-sn-glycerol, produce concentration-dependent increases in pulmonary arterial pressure, whereas the inactive compound 4 alpha-phorbol 12,13-dibutyrate does not affect pulmonary arterial pressure. Reducing calcium availability with verapamil, a calcium-free buffer, or a chelator of intracellular calcium significantly decreases the response to 12,13-phorbol or mezerein. Pretreatment with phloretin, an inhibitor of protein kinase C, has no affect on the vasoconstriction caused by infusion of a KCl bolus, but it does inhibit in a dose-dependent manner the response to 12,13-phorbol and mezerein. 12,13-Phorbol at a concentration of 2.5 microM, but not of 1 microM, stimulates prostacyclin and thromboxane synthesis by the isolated lung. Because inhibitors of thromboxane synthesis significantly decrease the response, thromboxane likely contributes to the vasoconstriction produced by higher concentrations of 12,13-phorbol and mezerein. Pretreatment with isoproterenol or nitroprusside reduces the increase in pulmonary arterial pressure caused by the protein kinase C activators but does not reverse vasoconstriction, even though subsequent treatment with verapamil does. In summary, activating protein kinase C in the isolated rabbit lung causes long-lasting pulmonary vasoconstriction, reducing calcium availability decreases the response, part of the increase in pulmonary arterial pressure appears secondary to thromboxane generation, and pretreatment with isoproterenol or nitroprusside prevents the vasoconstriction, but posttreatment with these vasodilators is ineffective.
Inhibition of antigen-induced airway and cutaneous responses by heparin: a pharmacodynamic study
Authors: Ahmed T. , Syriste T. , Lucio J. , Abraham W. , Robinson M. , D'Brot J.
Published: December 2017

We have previously shown that heparin attenuates the acute bronchoconstrictor response and immediate cutaneous reaction (ICR) to antigen in allergic sheep. In the present investigation, we studied the pharmacodynamics of the antiallergic action of heparin. Specific lung resistance (sRL) was measured in eight sheep, allergic to Ascaris suum antigen, before and 5 min after inhalation challenge with the antigen. On different experiment days, antigen challenge was repeated after pretreatment with 1) aerosol heparin (1,000 U/kg) administered < or = 20 min, 6 h, 12 h, and 24 h and 2) intravenous heparin (1,000 U/kg) administered < or = 20 min, 1 h, 6 h, and 12 h before antigen challenge. sRL increased by 374 +/- 116% (SE) above baseline with antigen alone. Both aerosol and intravenous heparin attenuated the antigen effects on sRL in a time-dependent fashion. Prolonging the lag time between pretreatment and antigen challenge decreased the inhibitory effect of aerosol heparin; delta sRL was 31 +/- 29, 99 +/- 38, 142 +/- 40, and 306 +/- 60% for < or = 20-min, 6-h, 12-h, and 24-h pretreatment protocols, respectively. In contrast, prolonging the lag time increased the inhibitory effect of intravenous heparin: delta sRL was 246 +/- 64, 66 +/- 26, and 76 +/- 32% for < or = 20 min, 1 h, and 6 h, respectively. In seven additional sheep pretreatment with intravenous heparin (1,000 U/kg) attenuated the ICR also in a time-dependent manner; the inhibitory effect of heparin on ICR to antigen was enhanced 60% by increasing the heparin pretreatment interval from 20 to 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Oxygen dependence of redox state of copper in cytochrome oxidase in vitro
Authors: Hoshi Y. , Hazeki O. , Tamura M.
Published: December 2017

To obtain quantitative information about tissue oxygenation from near-infrared signals, the oxygen dependencies of the redox states of both heme a+a3 and copper in cytochrome oxidase of isolated mitochondria were determined at low oxygen concentrations (10(-6)-10(-9) M) using leghemoglobin as an oxygen indicator. The maximum absorbance changes caused by the aerobic-anaerobic transition measured at 830–760 nm of copper in state 3, state 4, and the uncoupled state were 10, 17, and 5% of those at 605–620 nm of heme a+a3, respectively. Thus the relative absorbance ratio of copper to heme a+a3 could be used as a sensitive indicator for the mitochondrial energy state. The oxygen concentrations required for the half-maximal reduction of heme a+a3 varied with the energy state and the respiratory rate and were 7.8 x 10(-8) and 1.6 x 10(-7) M in state 4 and state 3, respectively. In contrast, that of copper was 7.5 x 10(-8) M and was independent of both the energy state and the respiratory rate. The relationship between the percent oxidation of heme a+a3 and copper in the aerobic-anaerobic transition did not show a straight-line relationship. This was referred to as the difference in oxygen affinity between these two chromophores. The deviation from the straight line was larger in state 3 than in state 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise
Authors: Naeije R. , Melot C. , Niset G. , Delcroix M. , Wagner P. D.
Published: December 2017

Almitrine, a peripheral chemoreceptor agonist, has been reported to increase arterial O2 saturation (SaO2) without changing minute ventilation (VE) during hypoxic exercise (Giesbrecht et al. J. Appl. Physiol. 70: 1770–1774, 1991). To explain this finding, we studied pulmonary hemodynamics (right heart catheterization) and gas exchange (multiple inert gas elimination technique) in six healthy volunteers at rest and during heavy exercise in normobaric normoxia (fractional concentration of O2 in inspired air 0.21) or hypoxia (fractional concentration of O2 in inspired air 0.125), before and after 75 mg of almitrine taken orally. During normoxic exercise, at a mean O2 uptake (VO2) of 4.0 l/min, almitrine increased arterial PO2 (PaO2) (P < 0.05), SaO2 (P < 0.01), and VE (P < 0.05) and decreased arterial PCO2 (P < 0.01), without affecting pulmonary hemodynamics or ventilation-perfusion distributions. During hypoxic exercise, at a mean VO2 of 3.0 l/min, almitrine increased SaO2 (P < 0.01) and VE (P < 0.01) and decreased arterial PCO2 (P < 0.05), with no effect on PaO2 or on ventilation-perfusion distributions and with a slight pulmonary vasoconstriction (P < 0.01). Almitrine during hypoxia did not affect cardiac output or calculated O2 diffusing capacity, but it did increase the slope of the VE/VO2 relationship (P < 0.01). We conclude that during hypoxic exercise, a pharmacological stimulation of the peripheral chemoreceptors improves SaO2 but not PaO2 by means of increased ventilation and an associated leftward shift of the oxyhemoglobin dissociation curve.
PtiO2 and CMRO2 changes in cortex and hippocampus of aging gerbil brain
Authors: Buerk D. G. , Nair P.
Published: December 2017

Tissue O2 partial pressure (PtiO2) and O2 disappearance rates (dPO2/dt) after bilateral carotid artery occlusion were measured with recessed cathode O2 microelectrodes (tips < 3 microns) in gerbil brains (n = 38) from three age groups: young (Y, 3–6 mo), mature (M, 10–12 mo), and older (O, 18–21 mo). Mean PtiO2 values were 18.4 +/- 1.2 (SE), 14.0 +/- 0.8 (P < 0.005), and 21.2 +/- 1.0 (NS) Torr for Y, M, and O groups, respectively, in the cortex and 14.1 +/- 0.8, 15.6 +/- 0.8 (NS), and 16.1 +/- 0.8 (NS) Torr in the hippocampus (Mann-Whitney comparisons with Y). In the cortex, mean dPO2/dt declined significantly with age: -19.2 +/- 1.1, -14.2 +/- 0.9 (P < 0.001), and -12.4 +/- 0.5 (P < 0.001) Torr/s for Y, M, and O, respectively (ANOVA comparisons with Y). In the hippocampus, the respective mean dPO2/dt values were -16.4 +/- 0.8, -15.6 +/- 1.9, and -13.9 +/- 2.2 Torr/s. Although the time trend for dPO2/dt was significant (P < 0.05), mean hippocampal differences compared by ANOVA were not. In Y, mean PtiO2 and dPO2/dt were lower in the hippocampus than in the cortex (P < 0.05). Apparent Michaelis-Menten constants for O2 were estimated from the O2 disappearance curves. These constants were significantly higher for the O group in the hippocampus (5.1 +/- 0.8 Torr) than in the cortex (2.7 +/- 0.6 Torr, P < 0.05).
Cognitive performance and event-related brain potentials under simulated high altitudes
Authors: Kida M. , Imai A.
Published: December 2017

The effects of hypobaric hypoxia on cognitive processing in humans were studied by recording event-related potentials (ERPs) from the scalp in a go/no-go reaction time (RT) paradigm under various simulated high altitudes. Most subjects indicated abrupt impairment of RT at high altitudes. RTs lengthened in association with changes in latency and amplitude of the N2-P3 components, reflecting sensory discrimination and evaluation processes. Some subjects did not suffer any changes in RT up to an extremely high altitude of 6,000 m. In the latter case, although the N2-P3 components did not undergo any changes, the P3 component was followed by a sequence of negative on-going (frontal maximum) and positive on-going (parietal maximum) slow waves. The amplitudes of these slow waves increased as altitude increased. Although these same waves appeared in the ERPs of subjects who demonstrated the increase in RTs at high altitudes, when the subjects failed in the RT task, both of the slow waves either disappeared or diminished. Such slow waves may be associated with attempts to maintain RTs against the deteriorative effects of hypobaric hypoxia.
Exercise reduces muscle glucose transport protein (GLUT-4) mRNA in type 1 diabetic patients
Authors: Koivisto V. A. , Bourey R. E. , Vuorinen-Markkola H. , Koranyi L.
Published: December 2017

We examined the effect of acute exercise on muscle glucose transporter (GLUT-4) protein and mRNA concentrations in nine male type 1 diabetic patients (age 31 +/- 3 yr, body mass index 23.6 +/- 0.7 kg/m2, insulin dose 44 +/- 4 U/day, glycosylated hemoglobin 7.8 +/- 0.4%) and in nine healthy control subjects (34 +/- 1 yr, 25.3 +/- 0.8 kg/m2). Three hours of cycle ergometer exercise was performed after an overnight fast. A needle biopsy (100–150 mg) was taken from the quadriceps femoris 40 min before and immediately after the end of exercise. During exercise, plasma glucose, insulin, cortisol, and growth hormone concentrations were higher in the diabetic patients than in the control subjects. In the basal state, GLUT-4 protein and mRNA concentrations were similar in the two groups. During exercise, GLUT-4 mRNA concentration decreased by 30–45% in the diabetic patients but remained unchanged in the control subjects. GLUT-4 protein content remained unchanged in both groups. These data suggest an abnormal GLUT-4 mRNA production or degradation or both in type 1 diabetic patients during physical exercise.
Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin
Authors: Hess J. R. , MacDonald V. W. , Brinkley W. W.
Published: December 2017

Human hemoglobin (Hb) and Hb cross-linked between the alpha subunits with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) were used to treat hemorrhagic shock in water-deprived swine. Water was withheld for 48 h to induce a 10% loss of body mass, and 25 ml/kg of blood were removed in 1 h to produce circulatory shock. Swine were resuscitated with 1) Hb, 2) alpha alpha Hb, 3) human serum albumin, or 4) Ringer lactate. Mild high-output renal failure was observed in the non-cross-linked Hb-treated animals but not in other groups of animals. Swine treated with Hb and alpha alpha Hb had increases in plasma creatine kinase and lactate dehydrogenase activity that were resolved within 7 days. Both Hb- and alpha alpha Hb-treated swine displayed marked elevations of mean blood pressure in the systemic (39 +/- 6 Torr) and pulmonary (20 +/- 6 Torr) circulations that continued for 3 h and were associated with reduced cardiac output and a doubling of the systemic and pulmonary vascular resistances. Oxygen delivery was equivalent, and the rate of correction of the lactic acidosis was equal in all groups.
ARDS-like lung injury produced by endotoxin in platelet-activating factor-primed rats
Authors: Rabinovici R. , Bugelski P. J. , Esser K. M. , Hillegass L. M. , Vernick J. , Feuerstein G.
Published: December 2017

We recently reported that the combined administration of lipopolysaccharide (LPS) and platelet-activating factor (PAF) in rats, at doses that are completely devoid of any effect when given alone, caused lung injury characterized by neutrophil adhesion to lung capillaries and postcapillary venules, neutrophil accumulation in the lung parenchyma, platelet-fibrin deposits in postcapillary venules, and pulmonary edema. A marked increase in lung myeloperoxidase activity and an elevation of serum tumor necrosis factor-alpha and thromboxane B2, along with leukopenia and thrombocytopenia, were also noticed. The present study aimed to examine whether repeated LPS-PAF stimulus can cause progressive lung injury reminiscent of adult respiratory distress syndrome (ARDS). A second LPS-PAF challenge, 4 h (n = 11) after the original challenge, induced mortality (69% at 24 h, P < 0.01) and some of the pathological changes seen in clinical ARDS, including severe pulmonary edema, alveolar proteinaceous exudates, monocytic infiltration, and a further increase in lung myeloperoxidase activity (700%, P < 0.01). Repeated LPS-PAF dosing also resulted in sustained increased serum tumor necrosis factor-alpha levels (1,610 +/- 470 pg/ml, P < 0.01) and further exacerbation of the leukopenia (-68 +/- 6%, P < 0.01) and thrombocytopenia (-65 +/- 8%, P < 0.01). These data suggest that repeated LPS-PAF actions are sufficient to elicit pathophysiology of ARDS-like lung injury.
Influence of NREM sleep on respiratory-related cortical evoked potentials in normal humans
Authors: Wheatley J. R. , White D. P.
Published: December 2017

Sleep substantially alters respiratory system responses to a variety of ventilatory stimuli. This could, to some extent, be a product of a sleep-induced decrement in respiratory afferent traffic to the cortex or cortical influences on central respiratory neurons. To investigate this, we determined the effect of non-rapid-eye-movement (NREM) sleep on cortical evoked potentials produced by rapid-onset inspiratory negative-pressure generations in the airway of seven normal subjects. Mean electroencephalographic activity at Cz-C3 and Cz-C4 for each subject was obtained by signal averaging. For Cz-C3, four respiratory-related cortical evoked potentials (P1, N1, P2, N2) occurred during wakefulness with latencies of 72 +/- 8, 128 +/- 9, 231 +/- 12, and 340 +/- 15 ms and amplitudes of 2.7 +/- 1.1, -3.2 +/- 1.1, 3.0 +/- 0.9, and -2.1 +/- 1.0 microV, respectively. During sleep, amplitudes of N1 and P2 were much greater (-9.4 +/- 1.3 and 14.1 +/- 1.7 microV, respectively; P < 0.05) and the latencies of P1, N1, and P2 (116 +/- 16, 244 +/- 24, and 664 +/- 75 ms, respectively) were substantially prolonged (P < 0.05). We conclude that respiratory-related cortical evoked potentials produced by negative-pressure generations in the airway during wakefulness are profoundly altered by NREM sleep. Their latencies are prolonged, magnitudes are increased, and the waveform is altered to resemble a K-complex. This altered sensory processing may impair respiratory responses during NREM sleep.
Pulmonary and systemic vascular responsiveness to TNF-alpha in conscious rats
Authors: Stevens T. , Morris K. , McMurtry I. F. , Zamora M. , Tucker A.
Published: December 2017

Endotoxin decreases pulmonary vascular reactivity. Because tumor necrosis factor-alpha (TNF-alpha) is a primary mediator of endotoxemia, we tested whether TNF-alpha altered pulmonary vascular reactivity in conscious adult female rats. Osmotic pumps were implanted intraperitoneally, and low-dose TNF-alpha (62 micrograms, TNF62; n = 7), high-dose TNF-alpha (> or = 250 micrograms, TNF250; n = 5), or saline (n = 5) was administered for 2 wk. Pulmonary pressor responses to 14% O2 and angiotensin II (ANG II, 0.0206 micrograms/min for 10 min) were measured without (day 13) or after (day 14) administration of nitro-L-arginine (4.4 mg/kg iv), an inhibitor of endothelium-derived relaxing factor (EDRF). TNF-alpha administration slightly decreased (P < or = 0.08) baseline pulmonary arterial pressure in TNF250 rats and decreased (P < or = 0.05) hypoxia- and ANG II-induced constrictions in TNF62 and TNF250 rats. Whereas nitro-L-arginine potentiated (P < or = 0.05) pressure responses in control rats, it had no effect on hypoxic responses in TNF-alpha-treated rats. Nitro-L-arginine increased (P < or = 0.05) ANG II-induced vasoconstriction in TNF-alpha-treated rats, but the pulmonary arterial pressure response was still lower (P < or = 0.05) in TNF250 than in control and TNF62 rats. These results suggest that chronic TNF-alpha decreases 1) pulmonary vascular reactivity in the intact rat, 2) hypoxic pulmonary vasoconstriction by a mechanism that is independent of EDRF, and 3) ANG II-induced constriction by a mechanism that is partly EDRF dependent.
Ventilatory response to oxygen after eucapnic hypoxia in conscious dogs
Authors: Cao K. Y. , Berthon-Jones M. , Sullivan C. E. , Zwillich C. W.
Published: December 2017

In humans the ventilatory [minute ventilation (VI)] response to sustained hypoxia is biphasic: an initial brisk increase followed by a decline is usually seen. However, in adult dogs, the ventilatory response to a similar stimulus shows no decline. To evaluate if central ventilatory drive is altered by sustained hypoxia, we measured the lowest ventilation (nadir) as the lowest moving average of seven sequential breaths within 200 s after transition to hyperoxia (100% O2) after 3 different exposures: room air, 4-min (brief) eucapnic hypoxia (arterial O2 saturation = approximately 80%), and 12-min (prolonged) eucapnic hypoxia. The nadir hyperoxic VI after brief hypoxia (2.7 +/- 0.2 l/min) was similar to that after room air (2.6 +/- 0.2 l/min; P > 0.05), with both less than prior room air mean VI (P < 0.05). The nadir after prolonged hypoxia (3.5 +/- 0.3 l/min) was significantly greater than that after brief hypoxia (P < 0.05). This suggests that central ventilatory drive increases in conscious dogs after sustained eucapnic hypoxia. The reason for the difference in central ventilatory response to hypoxia between conscious dogs and adult humans is unexplained.
Cerebellar control of expiratory activities of medullary neurons and spinal nerves
Authors: Huang Q. , Zhou D. , St John W. M.
Published: December 2017

Expiratory-related activities of spinal nerves are augmented after stimulation of the infracerebellar nucleus of the cerebellum. These stimulations alter neither inspiratory spinal neural activities nor inspiratory and expiratory laryngeal neural activities. It was hypothesized that efferents from the infracerebellar nucleus impinge on spinal motoneurons by a pathway that bypasses the medulla. In decerebrate, paralyzed, and vagotomized cats, phrenic and expiratory triangularis sterni activities and activities of medullary respiratory neurons were recorded. During infracerebellar stimulation, activities increased for expiratory bulbospinal neurons and neurons with tonic discharge patterns. After unilateral ablation of the infracerebellar nucleus by kainic acid, triangularis sterni discharge was eliminated and activities of expiratory bulbospinal neurons continued at reduced frequencies. Stimulations of the anterior interposed nucleus caused both inspiratory and expiratory activities to increase, whereas no systematic changes followed stimulations of the vermis. Results establish that at least a portion of the changes in expiratory activities of spinal motoneurons after perturbations of the infracerebellar nucleus occurs secondarily to changes in activities of medullary neurons. The possibility of separate cerebellar projections to medullary and spinal neurons is discussed.
Contribution of left ventricular diastolic function to exercise capacity in normal subjects
Authors: Vanoverschelde J. J. , Essamri B. , Vanbutsele R. , d'Hondt A. , Cosyns J. R. , Detry J. R. , Melin J. A.
Published: December 2017

Previous studies have established that most of the heterogeneity in exercise capacity seen with sedentariness, aging, or physical training can be accounted for by individual differences in the maximal rate of total body oxygen consumption (VO2 max) during dynamic exercise. However, the factors that limit VO2 max in normal subjects remain disputed. To test the hypothesis that differences in left ventricular diastolic performance contribute to the heterogeneity of VO2 max seen in healthy subjects, 57 normal sedentary volunteers (36 +/- 13 yr, range 20–76 yr) and 9 endurance athletes (37 +/- 8 yr, range 26–51 yr) were studied. Aerobic capacity was estimated as VO2 max during a multistage dynamic cycle exercise protocol, whereas resting left ventricular systolic and diastolic function was assessed by two-dimensional and Doppler echocardiography. The relationship of the left ventricular functional indexes with VO2 max was investigated by stepwise multiple regression analysis. VO2 max ranged from 25 to 58 ml.kg-1 x min-1 in sedentary subjects and from 44 to 60 ml.kg-1 x min-1 in athletes. With univariate analysis, significant correlations were observed between VO2 max and age (r = -0.60), maximal heart rate (r = 0.48), maximal work load (r = 0.80), left ventricular volumes at both end diastole (r = 0.51) and end systole (r = 0.62), peak early transmitral filling velocities (r = 0.80), and the ratio of early to late transmitral filling velocities (r = 0.87).
Effect of selective diaphragmatic paralysis on the inspiratory motor drive
Authors: Teitelbaum J. , Borel C. O. , Magder S. , Traystman R. J. , Hussain S. N.
Published: December 2017

Using alpha-chloralose-anesthetized mechanically ventilated vagotomized dogs, we assessed the effects of selective diaphragmatic paralysis on the inspiratory motor drive. Diaphragmatic paralysis was accomplished by a bolus injection of vecuronium, a neuromuscular junction blocker, into the left phrenic artery of an in situ vascularly isolated and innervated left diaphragm. The inspiratory motor drive during spontaneous breathing attempts was assessed by measuring peak integrated electromyographic (EMG) activities of the left and right diaphragms and parasternal and alae nasi muscles. Respiratory timing parameters were measured from the integrated EMG signals of the diaphragm. Three groups of dogs were studied. In group 1 (n = 9), vecuronium was injected into the phrenic artery with the left diaphragmatic length adjusted at the functional residual capacity. Vecuronium injection (0.2 mg) resulted in a significant decline in left diaphragmatic tension and integrated EMG. Breathing frequency increased by 24% of the baseline value, whereas right diaphragm, parasternal, and alae nasi EMG activities rose to 136, 227, and 165% of their respective baseline values a few seconds after the vecuronium injection. In group 2 (n = 6), vecuronium injection in left phrenectomized animals did not alter the EMG activities of the inspiratory muscles (left EMG signal was abolished) nor did it alter respiratory timing. In group 3 (n = 4), the left diaphragm was placed in a flaccid position. Vecuronium injection in this group did not produce any changes in the EMG activities or respiratory timing. We conclude that selective diaphragmatic paralysis elicits a significant rise in the inspiratory motor drive. This effect is likely to be mediated through the inhibition of diaphragmatic Golgi tendon organ activity.
Strength training increases regional bone mineral density and bone remodeling in middle-aged and older men
Authors: Menkes A. , Mazel S. , Redmond R. A. , Koffler K. , Libanati C. R. , Gundberg C. M. , Zizic T. M. , Hagberg J. M. , Pratley R. E. , Hurley B. F.
Published: December 2017

To determine the effects of strength training (ST) on bone mineral density (BMD) and bone remodeling, 18 previously inactive untrained males [mean age 59 +/- 2 (SE) yr] were studied before and after 16 wk of either ST (n = 11) or no exercise (inactive controls; n = 7). Total, spinal (L2-L4), and femoral neck BMD were measured in nine training and seven control subjects before and after the experimental period. Serum concentrations of osteocalcin, skeletal alkaline phosphatase isoenzyme, and tartrate-resistant acid phosphatase were measured before, during, and after the experimental program in all subjects. Training increased muscular strength by an average of 45 +/- 3% (P < 0.001) on a three-repetition maximum test and by 32 +/- 4% (P < 0.001) on an isokinetic test of the knee extensors performed at 60 degrees/s. BMD increased in the femoral neck by 3.8 +/- 1.0% (0.900 +/- 0.05 vs. 0.933 +/- 0.05 g/cm2, P < 0.05) and in the lumbar spine by 2.0 +/- 0.9% (1.180 +/- 0.06 vs. 1.203 +/- 0.06 g/cm2, P < 0.05). However, changes in lumbar spine BMD were not significantly different from those in the control group. There was no significant change in total body BMD. Osteocalcin increased by 19 +/- 6% after 12 wk of training (P < 0.05) and remained significantly elevated after 16 wk of training (P < 0.05). There was a 26 +/- 11% increase in skeletal alkaline phosphatase isoenzyme levels (P < 0.05) after 16 wk of training.
Interaction of various mechanical activity models in regulation of myosin heavy chain isoform expression
Authors: Diffee G. M. , McCue S. , LaRosa A. , Herrick R. E. , Baldwin K. M.
Published: December 2017

The purpose of this study was to determine the effects of a novel combination of mechanical activity paradigms on the isomyosin distribution in rat hindlimb muscles. Thirty female Sprague-Dawley rats were divided into five experimental groups as follows: normal control, functional overload (OV) of the plantaris, OV in conjunction with hindlimb suspension (OV-S), and a combination of OV-S and either static standing weight-bearing activity (OV-SS) or high-incline treadmill exercise (OV-SE). OV of the plantaris resulted in significant hypertrophy and significant fast-to-slow isomyosin shifts. These changes were completely inhibited by the addition of hindlimb suspension (OV-S). Also, neither of the two weight-bearing regimes (OV-SS and OV-SE) was able to attenuate the suspension-induced atrophy. In the vastus intermedius and vastus lateralis, however, OV-SS was able to partially retard the atrophy associated with suspension. In both the plantaris and vastus intermedius, only OV-SS was able to partially reverse the slow-to-fast isomyosin transitions associated with suspension. These results suggest that the type of mechanical activity is important in determining adaptation to altered loading conditions, with OV-SS appearing more effective than OV-SE in reversing the effects of unweighting.
Expiratory flow limitation and regulation of end-expiratory lung volume during exercise
Authors: Pellegrino R. , Brusasco V. , Rodarte J. R. , Babb T. G.
Published: December 2017

To investigate the impact of expiratory flow limitation (FL) on breathing pattern and end-expiratory lung volume (EELV), we imposed a small expiratory threshold load for a few breaths during exercise in nine volunteers (29–62 yr): six were healthy and three had mild-to-moderate airflow obstruction (67–71% predicted forced expiratory volume in 1 s). Six subjects showed evidence of FL, i.e., tidal expiratory flow impinging on maximal forced expiratory flow, at one or more exercise levels. Whenever an expiratory threshold load was imposed, mean expiratory flow decreased (P < 0.02) in association with an increased expiratory time (TE; P < 0.05). When the load was imposed during non-FL conditions, TE increased less than expiratory flow decreased and EELV tended to increase. In contrast, during FL, with the load, TE increased more than expiratory flow decreased, subjects did not achieve maximal expiratory flow until a lower volume, and EELV decreased (P < 0.001). Under both FL and no-FL conditions, unloading reversed the changes associated with loading. These data indicate that the increase in EELV during exercise is linked to the occurrence of FL. We suggest that compression of airways downstream from the flow-limiting segment may elicit a reflex mechanism that influences breathing pattern by terminating expiration prematurely, thus increasing EELV.
Computation of aortic flow from pressure in humans using a nonlinear, three-element model
Authors: Wesseling K. H. , Jansen J. R. , Settels J. J. , Schreuder J. J.
Published: December 2017

We computed aortic flow pulsations from arterial pressure by simulating a nonlinear, time-varying three-element model of aortic input impedance. The model elements represent aortic characteristic impedance, arterial compliance, and systemic vascular resistance. Parameter values for the first two elements were computed from a published, age-dependent, aortic pressure-area relationship (G. J. Langewouters et al. J. Biomech. 17:425–435, 1984). Peripheral resistance was predicted from mean pressure and model mean flow. Model flow pulsations from aortic pressure showed the visual aspects of an aortic flow curve. For evaluation we compared model mean flow from radial arterial pressure with thermodilution cardiac output estimations, 76 times, in eight open heart surgical patients. The pooled mean difference was +7%, the SD 22%. After using one comparison per patient to calibrate the model, however, we followed quantitative changes in cardiac output that occurred either during changes in the state of the patient or subsequent to vasoactive drugs. The mean deviation from thermodilution cardiac output was +2%, the SD 8%. Given these small errors the method could monitor cardiac output continuously.