bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of aerosol methacholine and histamine on airways and lung parenchyma in healthy humans
Authors: Pellegrino R. , Violante B. , Crimi E. , Brusasco V.
Published: December 2017

To investigate whether histamine (His) and methacholine (MCh) have different effects on airways and lung parenchyma, 11 healthy subjects were given aerosol MCh until a response plateau was obtained and then two doses of His. At the plateau, forced expiratory volume in 1 s and forced expiratory flow at 40% of vital capacity from partial flow-volume curves were reduced by 19 +/- 3 (SE) and 80 +/- 4%, respectively. Aerosol His decreased forced expiratory volume in 1 s by an additional 12 +/- 1% but left partial forced expiratory flow unchanged. The bronchodilator effect of deep inhalation, as inferred from the ratio of forced expiratory flow from maximal to that from partial flow-volume curves, increased after MCh and plateaued but decreased after His. Quasi-static transpulmonary pressure-volume area determined in seven subjects was unchanged after MCh but was increased by 57 +/- 10% after His. We conclude that adding His after the response to MCh plateaued does not increase the maximal degree of bronchoconstriction but may increase parenchymal hysteresis, thus blunting the bronchodilator effect of deep inhalation. These results suggest that His and MCh have similar effects on airway smooth muscle but different effects on lung tissue properties.
Effect of insulin on adipocyte lipolysis in exercise-trained rats
Authors: Suda K. , Izawa T. , Komabayashi T. , Tsuboi M. , Era S.
Published: December 2017

The effect of exercise training on the antilipolytic action of insulin was studied in rat adipocytes. Exercise training enhanced lipolysis induced by norepinephrine. Insulin dose dependently inhibited norepinephrine- (1 microM) stimulated lipolysis in both groups. Its inhibition rate was significantly greater in the trained than in the control group. Thus, exercise training enhanced the antilipolytic action of insulin. In the control group, insulin (1,000 microU/ml) reduced the displacement rate of [3H]CGP-12177 binding to adipocytes by low concentrations of (-)-norepinephrine. The slope factor without insulin was 0.76, whereas that with insulin was 0.95. In the trained group, insulin did not affect the competition binding of (-)-norepinephrine for [3H]CGP-12177. The displacement rate of [3H]CGP-12177 binding from adipocytes by low concentrations of (-)-norepinephrine was significantly greater in the trained than in the control group. The number of surface beta-adrenergic receptors per adipocyte was smaller in the trained than in the control group. Cilostamide, which blocks the antilipolytic action of insulin, restored lipolysis in both groups. The recovery rate was significantly greater in the trained than in the control group. These findings suggest that the enhanced antilipolytic action by insulin in the trained group occurs at a site distal to the binding of norepinephrine to beta-adrenergic receptors and that it is due to the increased activity of particulate low-Michaelis constant phosphodiesterase.
Apnea threshold and breathing rhythmicity in newborn lambs
Authors: Canet E. , Praud J. P. , Laberge J. M. , Blanchard P. W. , Bureau M. A.
Published: December 2017

This study was designed to determine the effect of the removal of chemical stimuli on breathing rhythmicity in awake newborn lambs; it was also designed to define the chemical threshold below which breathing would stop [arterial PCO2 (PaCO2) apnea threshold]. We used a technique of graded extracorporeal CO2 removal with apneic oxygenation in three groups of animals according to age and carotid body (CB) integrity: < 2 days, CB intact (n = 5); 12 days, CB intact (n = 7); and 12 days, CB denervated (CBD; n = 5). In all animals, whatever their age and CB status, suppression of the chemical drive resulted in sustained apnea. The study, performed at four constant levels of oxygenation (hyperoxia, normoxia, moderate hypoxia, and severe hypoxia), allowed precise determination of the PaCO2 apnea threshold. We found that this PaCO2 apnea threshold depended on the degree of postnatal maturation (it was higher in the younger lambs), the level of arterial oxygenation (it was lowered by hypoxia), and CB status (it was higher in CBD animals). Moreover, we found that the 12-day-old CBD lambs breathe at a level of PaCO2 set close to the point of apnea.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanics of respiratory system in healthy anesthetized humans with emphasis on viscoelastic properties
Authors: Jonson B. , Beydon L. , Brauer K. , Mansson C. , Valind S. , Grytzell H.
Published: December 2017

The classic model of the respiratory system (RS) is comprised of a Newtonian resistor in series with a capacitor and a viscoelastic unit including a resistor and a capacitor. The flow interruption technique has often been used to study the viscoelastic behavior under constant inspiratory flow rate. To study the viscoelastic behavior of the RS during complete respiratory cycles and to quantify viscoelastic resistance (Rve) and compliance (Cve) under unrestrained conditions, we developed an iterative technique based on a differential equation. We, as others, assumed Rve and Cve to be constant, which concords with volume and flow dependency of model behavior. During inspiration Newtonian resistance (R) was independent of flow and volume. During expiration R increased. Static elastic recoil showed no significant hysteresis. The viscoelastic behavior of the RS was in accordance with the model. The magnitude of Rve was 3.7 +/- 0.7 cmH2O.l-1 x s, i.e., two times R. Cve was 0.23 +/- 0.051 l/cmH2O, i.e., four times static compliance. The viscoelastic time constant, i.e., Cve.Rve, was 0.82 +/- 0.11s. The work dissipated against the viscoelastic system was 0.62 +/- 0.13 cmH2O x 1 for a breath of 0.56 liter, corresponding to 32% of the total energy loss within the RS. Viscoelastic recoil contributed as a driving force during the initial part of expiration.
Sprint training increases human skeletal muscle Na(+)-K(+)-ATPase concentration and improves K+ regulation
Authors: McKenna M. J. , Schmidt T. A. , Hargreaves M. , Cameron L. , Skinner S. L. , Kjeldsen K.
Published: December 2017

This study investigated the effects of sprint training on muscle Na(+)-K(+)-adenosinetriphosphatase (ATPase) concentration, plasma [K+] regulation, muscle performance, and fatigue during severe intermittent exercise. Six untrained male subjects underwent intensive cycle-sprint training for 7 wk. Muscle biopsies were taken at rest from the vastus lateralis muscle before and after 7 wk of training and were assayed for Na(+)-K(+)-ATPase concentration using vanadate-facilitated [3H]ouabain binding to intact samples. Before and after the training period, subjects performed four maximal 30-s exercise bouts (EB) on a cycle ergometer, each separated by a 4-min recovery. Arterialized venous blood samples were drawn immediately before and after each sprint bout and were analyzed for plasma [K+]. The work output was significantly elevated (11%) across all four EBs after training. The muscle [3H]ouabain binding site concentration was significantly increased (16%) from 333 +/- 19 to 387 +/- 15 (SE) pmol/g wet wt after training but was unchanged in muscle obtained from three control subjects. Plasma [K+] rose by 1–2 mmol/l with each EB and declined rapidly by the end of each recovery period. The increases in plasma [K+] resulting from each EB were significantly lower (19%) after training. The ratios of rise in plasma [K+] relative to work output during each EB were also significantly lower (27%) after training. The increased muscle [3H]ouabain binding site concentration and the reduced ratio of rise in [K+] relative to work output with exercise are both consistent with improved plasma and skeletal muscle K+ regulation after sprint training.
Augmentation of muscle sympathetic nerve activity during fatiguing isometric leg exercise
Authors: Ray C. A. , Mark A. L.
Published: December 2017

Recent studies have shown a lack of an increase in muscle sympathetic nerve activity (MSNA) during leg exercise. Experiments using isometric knee extension (IKE) have shown a biphasic response in MSNA with a decrease during the 1st min and a return of MSNA to control levels during the 2nd min of IKE. Moreover, MSNA was not augmented during postexercise muscle ischemia (PEMI) of the exercising leg, suggesting that the muscle metaboreflex may have not been engaged in these experiments. The purpose of the present study was 1) to examine MSNA during IKE performed to fatigue to determine whether MSNA could be increased with leg exercise and 2) to determine whether increases in MSNA during fatiguing IKE were associated with an augmented MSNA response during PEMI. IKE was initially performed to fatigue at 30% of maximal voluntary contraction in the sitting position (n = 7; trial 1). IKE elicited a marked increase in mean arterial pressure and heart rate (P < 0.01). Total MSNA (burst frequency x mean burst amplitude; units) in the contralateral leg increased 96 +/- 40% (P < 0.01) above control levels during the final 30 s of IKE (207 +/- 23 s). Subjects (n = 8) then performed IKE to fatigue followed by PEMI (trial 2). MSNA in the contralateral leg increased 107 +/- 50% (P < 0.01) above control levels during the final 30 s of IKE (169 +/- 12 s) and remained significantly elevated during PEMI (83 +/- 40% above control), indicating that the muscle metaboreflex was engaged during fatiguing IKE.(ABSTRACT TRUNCATED AT 250 WORDS)
Protective effects of E5, an antiendotoxin monoclonal antibody, in the ovine pulmonary circulation
Authors: Chen T. Y. , Zapol W. M. , Greene E. , Robinson D. R. , Rubin R. H.
Published: December 2017

The cross-protective effects of a murine immunoglobulin M monoclonal antilipid A antibody (E5 MAb) were tested by challenging awake sheep with mixtures of in vitro incubated E5 MAb (0.02 mg/kg) with lipopolysaccharide (LPS, 0.02 micrograms/kg) derived from Escherichia coli O111:B4, E. coli O55:B5, or Serratia marcescens. Intravenous infusion of these LPS preparations without antibody into awake sheep produced a similar pattern of fever, leukopenia, plasma thromboxane B2 (TxB2) release, and acute pulmonary vasoconstriction with pulmonary hypertension. The addition of MAb E5 to LPS from E. coli O111:B4 reduced these responses to the LPS in a fashion comparable to that achieved with an MAb specific to the E. coli O111:B4 O-side chain. Incubation of LPS derived from E. coli O55:B5 with the E5 MAb only slightly diminished acute pulmonary hypertension, the delayed temperature increase, and the degree of leukopenia (all P = NS) but reduced the mean peak TxB2 at 60 min (P < 0.05) compared with a control infusion of E. coli O55:B5 LPS. We were unable to demonstrate any protective effects on the pulmonary circulation from incubating E5 with LPS derived from S. marcescens. Preincubation of B55 MAb (a murine immunoglobulin M MAb directed against a human milk fat globulin), the control antibody, with LPS from E. coli 0111:B4 decreased the mean peak TxB2 but had no effect on the other parameters. We conclude that incubating E5 with LPS protects the pulmonary circulation of sheep from challenge with LPS derived from the parent E. coli strain. There were trends toward protection by E5 against LPS from 055:B5 E. coli, but these did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Cigarette smoke extract potentiates bradykinin-induced increases in microvascular permeability
Authors: Mayhan W. G. , Rubinstein I.
Published: December 2017

The first goal of this study was to determine whether cigarette smoke extract (CSE) increases microvascular permeability of the hamster cheek pouch in vivo. The second goal was to determine whether CSE potentiates bradykinin-induced increases in vascular permeability in the hamster cheek pouch. Using intravital microscopy, we examined the permeability of the hamster cheek pouch to fluorescein isothiocyanate-dextran (mol wt 70,000). Increases in permeability were quantitated by counting the number of postcapillary venular leaky sites per 0.11 cm2. Superfusion of CSE (1, 5, and 10%) did not produce venular leaky sites and, thus, did not alter macromolecular permeability. Superfusion of bradykinin (0.1, 0.5, and 1.0 microM) produced a dose-related increase in the number of venular leaky sites. Formation of leaky sites in response to bradykinin was potentiated by CSE. To determine whether potentiation of bradykinin-induced leaky site formation by CSE was related to products released via the cyclooxygenase pathway, we examined the effects of pretreatment with indomethacin (10 mg/kg i.v.). Indomethacin did not alter the potentiating effect of CSE on bradykinin-induced leaky site formation. These findings suggest that CSE does not alter basal permeability of the hamster cheek pouch microcirculation in vivo. However, CSE potentiates bradykinin-induced increases in microvascular permeability. The mechanism of CSE-induced potentiation of microvascular permeability does not appear to be related to substances produced via the cyclooxygenase pathway.
Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts
Authors: Whyte M. K. , Hughes J. M. , Jackson J. E. , Peters A. M. , Hempleman S. C. , Moore D. P. , Jones H. A.
Published: December 2017

The majority of patients with intrapulmonary right-to-left shunting due to pulmonary arteriovenous malformations-exhibit good maximum exercise capacity (> 70% predicted) despite profound arterial oxygen desaturation. We studied seven such patients to assess tissue oxygen delivery during steady-state exercise. From rest to exercise [50 +/- 7 (SE) W] arterial saturation fell from 80 +/- 3 to 74 +/- 3%, and mean right-to-left shunt increased slightly from 31 +/- 4 to 34 +/- 5% (P = NS). Minute ventilation was high for oxygen uptake, and the ventilatory equivalent was raised (174 +/- 19% predicted) and was correlated with shunt size (r = 0.93). The majority of the patients maintained pulmonary alveolar blood flow within the predicted range for their power output, but total cardiac output was increased to 142 +/- 11% predicted due to flow through the shunt. Consequently, on exercise, oxygen delivery per unit oxygen consumption [2.3–3.3 (normal range 1.6–2.4)] and calculated mixed venous oxygen tension (27.0 +/- 0.8 Torr) were preserved. Arterial PCO2 rose on exercise by 2.8 +/- 1.2 Torr, in proportion to the ratio of flow through the shunt to total cardiac output (r = 0.73), but remained low (33.1 +/- 1.4 Torr) in absolute terms. The high cardiac output on exercise may be facilitated by a low pulmonary vascular resistance (0.33 +/- 0.08 mmHg.1–1.min, measured at rest), which may explain why exercise performance is better in these patients than in patients with equivalent hypoxemia from other causes.
Analysis of responses to serotonin in the pulmonary vascular bed of the cat
Authors: McMahon T. J. , Hood J. S. , Nossaman B. D. , Kadowitz P. J.
Published: December 2017

Pulmonary vascular responses to serotonin (5-hydroxytryptamine; 5-HT) were investigated in the intact-chest cat under constant-flow conditions. Injections of 5-HT into the perfused lobar artery in doses of 1–30 micrograms caused dose-related increases in lobar arterial pressure and, at doses of 3–30 micrograms, decreases in systemic arterial pressure. Left atrial pressure was not changed, and responses to 5-HT were not altered by a thromboxane receptor blocking agent. Responses to 5-HT were blocked by ketanserin in doses that did not alter responses to agonists that increase pulmonary vascular resistance by various mechanisms. The ketanserin-induced blockade was not surmountable and at a dose of 0.5 mg/kg iv persisted for > 4 h. Prazosin and yohimbine, selective alpha 1- and alpha 2-adrenoceptor antagonists, were without effect on the pressor response to 5-HT, and ketanserin did not reduce responses to norepinephrine or the alpha 1-agonists, phenylephrine and methoxamine. 5-HT and the thromboxane mimic, U-46619, produced large increases in pulmonary vascular resistance; however, U-46619 was 300 times more potent than 5-HT. 5-HT increased lobar arterial pressure when the lung was perfused with dextran, and increases in lobar arterial pressure in response to 5-HT were not diminished when lobar ventilation was interrupted but were enhanced by N omega-nitro-L-arginine methyl ester and to a small extent by meclofenamate. The present data suggest that increases in pulmonary vascular resistance in the cat in response to 5-HT are due to activation of an S2 receptor in undefined "resistance vessel elements." These data suggest that pulmonary vasoconstrictor responses to 5-HT may be modulated to a small extent by release of a vasodilator prostaglandin and endothelium-derived nitric oxide but are not dependent on activation of thromboxane receptors, changes in bronchomotor tone, and interaction with alpha 1-receptors or with formed elements in blood.
Myocardial substrate uptake in lambs with and without aortopulmonary shunts during strenuous exercise
Authors: Gratama J. W. , Dalinghaus M. , Meuzelaar J. J. , Gerding A. M. , Koers J. H. , Zijlstra W. G. , Kuipers J. R.
Published: December 2017

Increased myocardial fatty acid uptake during acute exercise could adversely affect myocardial O2 consumption in lambs with left-to-right shunts, which would be unfavorable in view of their decreased coronary blood flow reserve. Therefore, we studied myocardial substrate uptake (glucose, lactate, pyruvate, free fatty acids, triglycerides, beta-hydroxybutyrate, and acetoacetate) in 10 7-wk-old lambs with an aortopulmonary left-to-right shunt [61 +/- 3% (SE) of left ventricular output] and 9 control lambs during strenuous treadmill exercise. The hemodynamic reaction to exercise was similar in shunt and control lambs. The peripheral metabolic response to exercise was also similar in the two groups: glucose free fatty acids, and, most prominently, lactate concentrations increased. Myocardial O2 consumption increased but less in shunt than in control lambs because of a smaller increase in heart rate. In both groups myocardial lactate uptake increased substantially at the cost of other substrates, providing the heart with 40% of its oxidative metabolism. Fatty acid uptake was not different between the two groups. In conclusion, our data reveal no essential differences in myocardial substrate uptake between shunt and control lambs during a substantial circulatory load.
Bifurcations of the respiratory pattern associated with reduced lung volume in the rat
Authors: Sammon M. , Romaniuk J. R. , Bruce E. N.
Published: December 2017

Rats with intact vagal reflexes exhibit patterns of breathing that contain greater degrees of freedom than those seen after vagotomy. To determine how alterations in end-expiratory volume modify the respiratory pattern, continuous positive (CPAP) and negative (CNAP) airway pressure was applied to tracheal openings of nine urethan-anesthetized vagi-intact rats (+3 to -9 cmH2O). Phase portraits (e.g., volume vs. flow curves), power spectra, correlation integral curves, and inspiratory-to-expiratory duration (TI/TE) ratios are used to interpret the vagal-dependent responses to changes in mean tracheal pressure (Ptr). With CPAP, respiratory oscillation was highly periodic and one dimensional, with TI/TE near 1.0. As Ptr was reduced in a stepwise manner, transient bursts of inspiratory airflow developed local to the expiratory-inspiratory transition, with amplitude increasing proportionally with the level of CNAP. These oscillatory "expiratory interrupts" (doubling TI/TE in five of nine cases) produced highly variable and asymmetric respiratory patterns. Progressive increases in correlation dimension (maximum = 1.8–3.0) and tendencies toward broadband power spectra were seen as Ptr was lowered. The irregular phase-switching dynamics seen with CNAP (which disappeared after vagotomy) are consistent with onset of low-dimensional chaos, probably correlated with activation of feedback mechanisms responsive to lung deflation.
Contribution of in vivo microvascular PO2 in the cat carotid body chemotransduction
Authors: Lahiri S. , Rumsey W. L. , Wilson D. F. , Iturriaga R.
Published: December 2017

To understand the interplay between microcirculatory control and carotid body (CB) function, we simultaneously measured carotid body microvascular PO2 (CBM PO2) and chemosensory activity in the cat in vivo under several experimental conditions. Cats were anesthetized with pentobarbital sodium, paralyzed, and artificially ventilated. CBs were exposed, and steady-state CBM PO2 was measured by the O2-dependent quenching of the phosphorescence of Pd-meso-tetra-(4-carboxyphenyl)porphine, which was administered intravenously. A few fibers of the carotid sinus nerve were used to record chemosensory discharges. At arterial PO2 (PaO2) of 103.4 +/- 4.1 Torr, CBM PO2 was 52.5 +/- 3.6 Torr (n = 9). Graded lowering of PaO2 from 160 to 50 Torr resulted in nearly proportional decreases in CBM PO2, but at lower PaO2 the decrease in CBM PO2 became more substantial. As PaO2 decreased, chemosensory discharge increased in parallel with CBM PO2. Hypercapnia and hypocapnia did not significantly change the relationship between PaO2 and CBM PO2, although the chemosensory discharge responded significantly. CBM PO2 and chemosensory discharge were not affected by hemorrhagic hypotension until arterial blood pressure fell below approximately 50 Torr and then CBM PO2 decreased and chemosensory discharge increased. The lack of a significant effect of hemorrhagic hypotension indicated that O2 delivery to CB was almost independent of the systemic blood pressure. Taken together, the observations suggest that CB microcirculation and PO2 are subject to control by intrinsic mechanisms and that CBM PO2 is compatible with oxidative metabolism playing a role in O2 chemoreception during hypoxia.
Importance of prostanoids in calcium chelator-induced airway constriction
Authors: Lindeman K. S. , Downey N. , Liu M. C. , Hubbard W. C. , Kagey-Sobotka A. , Hirshman C. A.
Published: December 2017

To elucidate the mechanism of calcium chelator-induced airway constriction, we examined the relationship between prostanoids and histamine in bronchoalveolar lavage (BAL) fluid and the magnitude of airway constriction in peripheral airways of anesthetized Basenji-Greyhound dogs. A wedged bronchoscope technique was used to measure collateral system resistance (Rcs) before and after aerosol challenges. Sublobar segments were challenged either with acetylcholine or with Na2EDTA in the presence or absence of meclofenamate sodium (3 mg/kg iv) or methylprednisolone (2 mg.kg-1.day-1). After measurements of Rcs, BAL was performed, and the fluid was analyzed for prostanoids with the use of gas chromatography-mass spectrometry. Sublobar segments challenged with Na2EDTA showed increased concentrations of prostaglandin (PG) D2 but no increases in PGE2, PGF2 alpha, 9 alpha,11 beta-PGF2, 6-keto-PGF1 alpha, thromboxane B2, or histamine. There was a strong relationship (r = 0.84, P = 0.005) between changes in Rcs after Na2EDTA and concentrations of PGD2 in BAL fluid. Acetylcholine, which increased Rcs to a similar degree as Na2EDTA did, produced no significant increase in prostanoid concentrations. Changes in Rcs after Na2EDTA and concentrations of PGD2 were reduced in the presence of meclofenamate or methylprednisolone. These data support the idea that the mechanism of calcium chelator-induced bronchoconstriction involves the release of bronchoconstricting prostanoids.
Cardiovascular responses to voluntary and treadmill exercise in rats
Authors: Yancey S. L. , Overton J. M.
Published: December 2017

Male Sprague-Dawley rats (n = 12) were housed in activity wheels and familiarized with treadmill running 2 wk before they were instrumented with Doppler flow probes and a carotid catheter. Mean arterial pressure (MAP), heart rate (HR), mesenteric blood flow (BFmes), and iliac blood flow were determined during bouts of voluntary and treadmill exercise. One voluntary exercise bout (speed = 33 +/- 2 m/min, duration = 26 +/- 5 s) from each rat was selected to compare with 30 s of treadmill exercise at 30 m/min. Voluntary exercise produced increases in MAP (7 +/- 3 mmHg) and HR (63 +/- 7 beats/min) that were significantly less than the increases of 21 +/- 5 mmHg and 95 +/- 9 beats/min, respectively, with treadmill exercise. Voluntary exercise caused an immediate reduction in BFmes of 32 +/- 6%, whereas treadmill exercise produced a significantly greater reduction of 57 +/- 4%. Voluntary and treadmill exercise caused similar increases in iliac blood flow of 112 +/- 15 and 169 +/- 31%, respectively. The patterns of cardiovascular adjustments to the initiation of voluntary exercise are similar to those observed at the initiation of treadmill exercise; however, MAP, HR, and BFmes responses were significantly greater with treadmill exercise.
Sulfide toxicity: mechanical ventilation and hypotension determine survival rate and brain necrosis
Authors: Baldelli R. J. , Green F. H. , Auer R. N.
Published: December 2017

Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause "knockdown" (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, we sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilated rats given high-dose sulfide (a dose that was lethal in > or = 50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to < or = 35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. We conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect.
Effect of acute resistance exercise on postexercise energy expenditure and resting metabolic rate
Authors: Melby C. , Scholl C. , Edwards G. , Bullough R.
Published: December 2017

Two separate experiments were performed to determine the effect of acute resistive exercise on postexercise energy expenditure in male subjects previously trained in resistive exercise. In experiment 1, after measurement of their resting metabolic rate (RMR) at 0700 h and their ingestion of a standardized meal at 0800 h, seven subjects (age range 22–40 yr) beginning at 1400 h completed a 90-min weight-lifting protocol. Postexercise metabolic rate (PEMR) was measured continuously for 2 h after exercise and compared with a preexercise baseline. RMR was measured the following morning 15 h after completion of the workout. In experiment 2, six different men (age range 20–35 yr) completed a similar experimental protocol as well as a control condition on a separate day in which metabolic rate was measured for 2 h after a period of quiet sitting. For both experiments, PEMR remained elevated for the entire 2-h measured recovery period, with the average oxygen consumption for the last 6 min elevated by 11–12%. RMR measured the morning after exercise was 9.4% higher in experiment 1 and 4.7% higher in experiment 2 than on the previous day. In experiment 2, the postabsorptive respiratory exchange ratio was significantly lower the morning after the exercise bout. Strenuous resistive exercise may elevate PEMR for a prolonged period and may enhance postexercise lipid oxidation.
Validation of a volumeless breath-by-breath method for measurement of respiratory quotient
Authors: Hoffman G. M. , Torres A. , Forster H. V.
Published: December 2017

Measurement of respiratory quotient (RQ) is useful as an indicator of changes in CO2 equilibrium or metabolism. Because of technical difficulties when volumetric or mixed expired methods are applied to clinical practice, we sought to validate a method of volumeless breath-by-breath RQ measurement based on real-time analysis of inspired and alveolar concentrations of O2, CO2, and N2 alone. We derived our volumeless method from a modified three-compartment lung model and tested the validity of the model by comparing it with a standard volumetric open-circuit method. Data from 1,736 breaths from 25 healthy adult volunteers for a total of 78 epochs were collected. Inspired, end-tidal, and mixed expired gas compositions were analyzed by Raman spectroscopy, and RQ values from 0.6 to 2.4 were obtained. Linear regression of the volumeless breath-by-breath method against the open-circuit method yielded a line with a slope of 1.002 (95% confidence interval 0.928 to 1.076) and an intercept of 0.066 (95% confidence interval -0.008 to 0.146) with an R2 of 0.91 (P < 0.001). We analyzed agreement by several methods and used mathematical modeling to predict precision with variations in epoch length and breath volume, which were verified by Monte Carlo techniques. We demonstrated that RQ can be measured reliably and easily using this volumeless breath-by-breath technique.
Comparison of thoracoabdominal calibration methods in normal human subjects
Authors: Sartene R. , Dartus C. , Bernard J. L. , Mathieu M. , Goldman M. D.
Published: December 2017

In 19 normal subjects in the supine posture, we compared accuracy and precision of calibration methods that utilized different ranges of tidal volumes and thoracoabdominal partitioning: spontaneous quiet breathing (QB), isovolume maneuvers, and voluntary efforts to breathe with variable tidal volume and thoracoabdominal partitioning. Thoracic and abdominal movements were measured with the respiratory area fluxometer. Calibration methods utilizing one or more types of respiratory efforts were applied to three measurement situations: QB, variable breathing (volume and thoracoabdominal partitioning), and simulated obstructive apnea (isovolume efforts). Qualitative diagnostic calibration (QDC) included QB data only. The isovolume method (ISOCAL) included isovolumetric efforts at end expiration (functional residual capacity) and QB. Multilinear regression analyses were performed on data sets that included 1) voluntary efforts to breathe with variable volume and thoracoabdominal partitioning (CAL 1), 2) QB in addition to variable volume and partitioning (CAL 2), and 3) isovolume maneuvers in addition to QB and variable volume and partitioning efforts (CAL 3). When calibration data included a wide range of tidal volume, variable thoracoabdominal partitioning, and isovolume efforts (CAL 3), a stable calibration with small bias and scatter during all respiratory patterns was obtained. Excluding isovolume maneuvers (CAL 2) and QB (CAL 1) did not diminish accuracy. Limiting data to isovolume efforts at functional residual capacity plus QB (ISO-CAL) caused a significant increase in scatter during variable breathing patterns. Limiting calibration data to that portion of QB with small variation in the uncalibrated sum of thoracic and abdominal movements (QDC) caused significant increases in scatter in both isovolume efforts and variable breathing.
Metabolic basis for inspiratory muscle fatigue in normal humans
Authors: Mannix E. T. , Sullivan T. Y. , Palange P. , Dowdeswell I. R. , Manfredi F. , Galassetti P. , Farber M. O.
Published: December 2017

Inspiratory muscle fatigue, a common event in patients in the intensive care unit, is under multifactorial control. To test the hypothesis that systemic oxygenation is a factor in this event, we subjected five healthy males (age 42 +/- 3 yr) to continuous inspiratory pressure (75% of maximal inspiratory pressure, -95 +/- 5 cmH2O) with the use of a controlled breathing pattern while they breathed normoxic (21% O2), hyperoxic (30% O2), and hypoxic (13% O2) mixtures. Inspiratory muscle endurance (IME; time that pressure could be maintained) and other cardiorespiratory parameters were monitored. Room air IME (3.3 +/- 0.4 min) was shortened (P < 0.05) during 13% O2 breathing (1.6 +/- 0.4 min) but was unaffected during 30% O2 breathing (4.0 +/- 0.6 min). Inspiratory loading lowered the respiratory exchange ratio (RER) during the 21 and 30% O2 trials (1.02 +/- 0.01 to 0.80 +/- 0.03% and 1.05 +/- 0.05 to 0.69 +/- 0.01%, respectively) but not during the 13% O2 trials (1.03 +/- 0.03 to 1.06 +/- 0.07%). At the point of fatigue during the 13% O2 trials, RER was lower compared with the same time point during the 21 and 30% O2 trials. A significant relationship was observed between IME and RER (r = -0.73, P = 0.002) but not between IME and any of the other measured variables. We conclude that 1) hypoxemia impairs the ability of the inspiratory muscles to sustain a mechanical challenge and 2) substrate utilization of the respiratory muscles shifts toward a greater reliance on lipid metabolism when O2 is readily available; this shift was not observed when the O2 supply was reduced.
Mechanical determinants of isotonic relaxation in isolated diaphragm muscle
Authors: Coirault C. , Chemla D. , Pery N. , Suard I. , Lecarpentier Y.
Published: December 2017

Determinants of lengthening velocity have not been investigated in the diaphragm muscle. This study was undertaken to define the mechanical determinants of isotonic relaxation rate over the entire load continuum in isolated rat diaphragm (n = 30). We tested the hypothesis that the determinants of lengthening could include loading conditions, namely, preload and afterload; abrupt changes of load during the contraction phase; end-shortening muscle length (ESL); extent of shortening (delta L); time; stimulation mode; and stimulation frequency. In afterloaded contractions preloaded at optimal initial length and stimulated in tetanus at 30 Hz, peak lengthening velocity (+dL/dtmax) was linearly related to delta L, ESL, and/or total load. Varying initial muscle length, ESL, afterload, or the load imposed on the muscle during the isotonic lengthening process did not modify +dL/dtmax vs. delta L relationship, whereas +dL/dtmax vs. load and +dL/dtmax vs. ESL relationships were modified by these procedures. For a given delta L, +dL/dtmax could be modified when lengthening was delayed by reversing the relaxation sequence and when twitch and tetanus modes were compared. In conclusion, our results demonstrate that in isolated diaphragm muscle, delta L is the main determinant of +dL/dtmax over a wide range of loads and under various experimental conditions, independent of ESL and initial muscle length and independent of the load imposed on the muscle during the lengthening process. Time and stimulation mode were also shown to modulate the lengthening rate in diaphragm muscle.
Function of skeletal muscle sarcoplasmic reticulum vesicles with exercise
Authors: Belcastro A. N. , Gilchrist J. S. , Scrubb J.
Published: December 2017

In this study the response of sarcoplasmic reticulum (SR) to prolonged moderate-intensity exercise was examined in highly purified native vesicles isolated from rat gastrocnemius muscle. Maximal Ca(2+)-dependent ATP hydrolysis was reduced by 12.6% within 2 min after the onset of exercise. The reduction in Ca(2+)-dependent adenosinetriphosphatase activity progressed to 18% at 30 min of exercise and was maintained throughout the subsequent 90–100 min of exercise. Oxalate stimulation of unidirectional Ca2+ transport (Ca2+ loading) was unaffected by exercise. However, in the absence of anion stimulation, steady-state Ca2+ uptake (bidirectional flux) was 51.2 +/- 7.3 nmol Ca2+/mg SR after exercise compared with 36.2 +/- 2.5 nmol Ca2+/mg SR for the control period (P < 0.05). Anion-induced Ca2+ release increased from a control value of 33.9 +/- 4.3 to 55.9 +/- 9.8 nmol Ca2+/mg SR after exercise (P < 0.05). The mechanistic basis for the increase in apparent Ca(2+)-ATP coupling is unclear, although the early onset of the changes suggests the potential for functional adaptation for the SR in response to increased contractile activity.
Optimal frequency range to analyze respiratory transfer impedance with six-element model
Authors: Tomalak W. , Peslin R. , Duvivier C. , Gallina C.
Published: December 2017

The aim of this investigation was to assess the optimal frequency range for analyzing respiratory transfer impedance (Ztr) in terms of tissue and airway mechanical properties using the six-element model of DuBois et al. (J. Appl. Physiol. 8:587–594, 1956). Ztr was measured in nine healthy subjects from 2 to 64 Hz by studying the relationship between airway flow and pseudorandom pressure oscillations applied around the chest. The measurements were performed with and without two mechanical loads placed at the mouth: an added inertance of 1.4 Pa.s2.l-1 and an added resistance of 1.65 hPa.s.l-1. The data were corrected for the shunt effect of upper airway walls. The changes in Ztr induced by the loads were very consistent up to 56 Hz with the T-network topology assumed in DuBois's model; the agreement deteriorated at higher frequencies, presumably due to the difficulty of obtaining a homogeneous pressure field around the chest. The fit of the model to the data also worsened sharply at above 56 Hz. In the 2- to 56-Hz frequency range, similar values of the tissue and airway coefficients were obtained with and without the loads. In that frequency range the confidence intervals of the coefficients were better than 10%. We conclude that DuBois's model is valid from 2 to 56 Hz in healthy subjects and allows accurate partitioning of airways and tissue properties. In addition, we present evidence that the upper airway shunt negligibly influences Ztr data and the derived coefficients provided airway flow is measured with a low-impedance pneumotachograph.
Role of fetal breathing movements in control of fetal lung distension
Authors: Miller A. A. , Hooper S. B. , Harding R.
Published: December 2017

Our aim was to determine the role of fetal breathing movements (FBM) in the maintenance of fetal lung liquid volume. Experiments were performed in 14 chronically catheterized fetal sheep. FBM were selectively abolished for 48 h by the infusion of tetrodotoxin (TTX) onto the phrenic nerves of five fetuses. Lung liquid volumes and secretion rates were measured before each treatment, 46–48 h after the start of the TTX infusion, and 22–24 h after the end of the infusion. Blockade of the phrenic nerves reduced fetal lung liquid volumes from 27.6 +/- 1.9 to 21.8 +/- 2.6 ml/kg and increased lung liquid secretion rates from 3.8 +/- 0.6 to 6.2 +/- 1.1 ml.h-1.kg-1. Control experiments confirmed the lack of effect of TTX infused intravenously and saline infused intrapleurally on changes in fetal lung liquid volume and secretion rate. To measure the static relaxation volume of the fetal lung, in six fetuses we combined skeletal muscle paralysis with bypass of the upper airway for 48 h. This reduced fetal lung liquid volume from 39.1 +/- 3.1 to 23.0 +/- 2.5 ml/kg and increased lung liquid secretion rates from 4.1 +/- 0.7 to 5.8 +/- 0.9 ml.h-1.kg-1. This experiment demonstrates that the fetal lung is normally maintained at a level of expansion that is much greater than its static relaxation volume. We conclude that the volume of luminal liquid in the fetal lungs is dependent on the diaphragmatic contractions associated with FBM. Their effect is to resist the elastic recoil of the fetal lungs, thereby reducing the loss of liquid from the lungs via the trachea.
Nasal airway geometry: comparison between acoustic reflections and magnetic resonance scanning
Authors: Hilberg O. , Jensen F. T. , Pedersen O. F.
Published: December 2017

To evaluate the accuracy of the acoustic reflection (AR) technique for determination of nasal cavity cross-sectional areas, the area-distance function of both sides of the nose was determined in 10 subjects and compared with magnetic resonance imaging (MRI). Interindividual variation for the correlation between MRI and AR was seen, but in general the areas from 1 to 6 cm into the nasal cavity measured by AR were larger than areas measured by MRI, especially where the surface was most convoluted. The total volume for this region was 6.47 +/- 1.83 (SD) cm3 for AR and 5.65 +/- 1.34 cm3 for MRI. It was demonstrated that this could be due to errors in calculation of the areas on the basis of MRI and AR. In the posterior part of the nasal cavity and the epipharynx, there was a convincingly higher correlation between acoustic measurements and a scan perpendicular to the assumed geometrical axis of the epipharynx than between acoustic measurements and coronal scanning. This indicates that the sound axis roughly follows the geometrical axis. In a model of two tubes (nasal cavities) joined in a larger tube (the epipharynx), closure of the posterior part of the latter revealed that the contralateral nasal cavity is likely to cause overestimation of the posterior part of the epipharynx during AR compared with MRI.
Cardiovascular reactivity in isometric exercise and mental arithmetic in children
Authors: Verhaaren H. A. , Schieken R. M. , Schwartz P. , Mosteller M. , Matthys D. , Maes H. , Beunen G. , Vlietinck R. , Derom R.
Published: December 2017

In children, we studied noninvasively the cardiovascular stress responses, including changes over time of systolic blood pressure (SBP), heart rate (HR), and stroke volume (SV) in isometric handgrip (IHG) and mental arithmetic. Specifically, we asked whether 1) these cardiovascular stress responses were different for the two stress conditions in children, 2) these responses differed in boys and girls, and 3) the anthropometric variables related to these stress responses. SV differed significantly between IHG and mental arithmetic over the entire stress period. This may reflect higher systemic vascular resistance during IHG. HR in boys was lower than in girls over the entire period of stress in both stress tests. This observation cannot be attributed to differences in conditioning, because this should not influence responses to isometric or mental stress. A larger left ventricular mass was related to higher SVs. A marked relationship was found between HR and SBP and between HR and SV. No relationship was found between SBP and SV.
Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction
Authors: Demling R. , Lalonde C. , Heron P. , Picard L. , Blanchard J. , Brain J.
Published: December 2017

We determined the effect of a graded increase in lung exposure to a toxic smoke by increasing smoke tidal volume (VT) or the number of smoke breaths. Sheep were anesthetized and then insufflated with cooled cotton toweling smoke; VT was 5, 10, or 20 ml/kg, and smoke breaths were varied from 12 to 48. The smoke had a uniform particle size (3 +/- 0.4 microns diam). Peak carboxyhemoglobin levels varied from 8 +/- 2 to 45 +/- 4% in the lowest to highest exposure groups, respectively. Animals were monitored unanesthetized for 24 h, and then they were killed. Oxygenation (ratio of arterial PO2 to fraction of inspire O2) decreased from 480 +/- 21 to 200 Torr, and compliance decreased by approximately 50% in the highest smoke exposure groups, whereas only a modest decrease in oxygenation and no compliance changes were seen with lesser exposures. A moderate tracheobronchitis, some atelectasis, and no alveolar edema were noted in the lower smoke exposure groups, whereas severe tracheobronchitis, airway edema, and alveolar atelectasis were observed in the highest exposure group. Only modest alveolar flooding was noted. Impaired oxygenation and anatomic injury correlated best with the total smoke delivered (r = 0.59). Increasing VT from 5 to 20 ml/kg did not increase airway or alveolar injury if the total smoke mass delivered was maintained constant. The degree of impaired oxygenation did not correlate with measured lung water (r = 0.27) or lung lymph flow (r = 0.31).
Inhibitory nerve distribution and mediation of NANC relaxation by nitric oxide in horse airways
Authors: Yu M. , Wang Z. , Robinson N. E. , Leblanc P. H.
Published: December 2017

The distribution of inhibitory nerves and the mediator of the inhibitory nonadrenergic noncholinergic (iN-ANC) nervous system were investigated in smooth muscle preparations from seven regions of equine airways. In tissues incubated with atropine and precontracted with histamine, electrical field stimulation produced frequency-dependent relaxation, and the magnitude of the relaxation decreased from trachea to central bronchi and was absent in peripheral airways. The degree of relaxation in bronchi was not simply a function of bronchial size or generation. Propranolol inhibited part of the relaxation only in the cranial trachealis. After propranolol, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, eliminated the remaining relaxation in all preparations. This effect was reversed by L-arginine, the NO precursor, but not by D-arginine. Exogenous NO concentration dependently relaxed trachealis. These results indicate that: 1) adrenergic innervation is limited to cranial trachealis, 2) iNANC nerves supply the trachea and central bronchi, and 3) NO mediates iNANC function.
Influence of hypoxia and serotonin on small pulmonary vessels
Authors: al-Tinawi A. , Krenz G. S. , Rickaby D. A. , Linehan J. H. , Dawson C. A.
Published: December 2017

X-ray angiograms obtained from isolated perfused dog lungs were used to measure changes in the internal diameter of small intraparenchymal pulmonary arteries (150–1,600 microns) and veins (200–1,000 microns) in response to hypoxia or intra-arterial serotonin [5-hydroxytryptamine (5-HT)] infusion. The diameter changes in response to the two stimuli were measured over a range of stimulus-induced increases (delta Pa) in the total arteriovenous pressure drop. When the resulting delta Pa was small, all arteries in the diameter range studied constricted in response to either stimuli. The maximum decrease in diameter was approximately 25% with hypoxia and 36% with 5-HT. However, when delta Pa was large, arteries with a control diameter larger than approximately 800 microns distended with hypoxia. On the other hand, 5-HT constricted all the arteries in the size range studied regardless of the resulting magnitude of delta Pa. Hypoxia caused a small (approximately 9%) constriction in all veins in the diameter range studied independent of diameter or the magnitude of delta Pa, whereas in the concentration range studied 5-HT had no significant influence on these veins. An analysis of the potential impact of these vessels on total pulmonary vascular resistance suggested that although vessels in the size range studied contributed significantly to the total response to these two stimuli, vessels smaller than those studied also made a major contribution to the total response.