bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferences on passive diaphragm mechanics from gross anatomy
Authors: Boriek A. M. , Rodarte J. R.
Published: December 2017

The diaphragm is a relatively thin curved structure that is categorized in mechanics as a membrane. Tension in the membrane is given by the product of muscle thickness and stress parallel to the fiber bundles. If all muscle fibers were cylindrical and extended from origin to insertion, the ratio of thickness near the chest wall (CW) to thickness near the central tendon (CT) would vary inversely with the ratio of CW to CT perimeters. In freshly excised diaphragms of 36 mongrel dogs, the ratios of the perimeters (CT/CW) in the right and left costal diaphragm were 0.63 +/- 0.04 and 0.62 +/- 0.04, respectively. The means of the ratio of thickness near CW to that near CT in the right and left costal regions were 0.96 +/- 0.07 and 0.95 +/- 0.05, respectively, consistent with a nearly constant relationship between costal diaphragm membrane tension and muscle stress in the direction of the fibers. In the crural diaphragm, the average ratio of the perimeters of the insertions on CT to CW was 1.16 +/- 0.10. The average ratio of thickness of crural CW to CT was 1.25 +/- 0.11. The discrepancy between the perimeter ratio and thickness ratio in the costal diaphragm is incompatible with the muscle consisting of uniform fibers extending from CW to CT. Our data suggest that muscle fibers are either in series with a smaller number along the smaller perimeter or that they terminate by tapering within the muscle bundle. Both arrangements are consistent with previous anatomic studies (Gordon et al. J. Morphol. 201: 131–143, 1989). Having a nonuniform number of fibers mechanically in series is compatible with uniform stress in the fibers if the membrane is sufficiently curved as in a domed structure.
Vitamin E does not prevent exercise-induced increase in pulmonary clearance
Authors: Lorino A. M. , Paul M. , Cocea L. , Scherrer-Crosbie M. , Dahan E. , Meignan M. , Atlan G.
Published: December 2017

It has been observed that sustained exercise results in a prolonged increase in alveolar epithelial permeability, as assessed by the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (Lorino et al. J. Appl. Physiol. 67: 2055–2059, 1989). The involvement of lipid peroxidation in this increased permeability was tested in seven nonsmoking volunteers by comparing the exercise-induced increases in pulmonary 99mTc-diethylenetriaminepentaacetate clearance before and after a 3-wk supplementation with oral vitamin E (1,000 IU/day), according to a protocol designed as a single-blind crossover study. The 60-min exercise was performed on a treadmill at a constant load corresponding to 80% of maximal O2 uptake. Administration of vitamin E, a very important antioxidant, did not reduce the exercise-induced increase in lung clearance, suggesting that the exercise-induced increase in lung epithelial permeability does not primarily result from the occurrence of lipid peroxidation in the alveolar membrane. This result thus corroborates the hypothesis of an alteration of the intercellular tight junctions due to the mechanical effects of hyperventilation.
Forearm compression during exercise increases sympathetic nerve traffic
Authors: McClain J. , Hardy J. C. , Sinoway L. I.
Published: December 2017

Previously, we showed that forearm venous congestion augmented muscle sympathetic nerve activity (MSNA) during static exercise. We postulated that venous congestion increased interstitial pressure, sensitizing mechanoreceptor afferents that led to a greater sympathoexcitation during exercise. In this study, we tested the hypothesis that forearm compression (FC) would increase interstitial pressure and selectively stimulate mechanically sensitive afferents. We measured MSNA during 2 min of ischemic static exercise (40% maximal voluntary contraction) and 2 min of posthandgrip circulatory arrest. Exercise was performed again after 5 min of FC induced by inflation of a forearm cuff to 90 mmHg (n = 6) and 110 mmHg (n = 7). FC without exercise had no effect on any of the hemodynamic variables. MSNA and mean arterial blood pressure responses were not augmented when exercise was performed with FC at 90 mmHg. However, static exercise coupled with FC at 110 mmHg did augment the reflex responses to static exercise (changes in MSNA before and after FC were 277 +/- 58 and 503 +/- 82 arbitrary units, respectively, P < 0.02; changes in mean arterial pressure before and after FC were 35 +/- 4 and 41 +/- 5 mmHg, respectively, P < 0.003). These responses were probably not due to greater metaboreceptor stimulation, since posthandgrip circulatory arrest responses were unaffected by FC. We postulate that FC sensitizes mechanoreceptors, leading to greater sympathoexcitation during exercise.
Dose dependency of perceived breathlessness on hypoventilation during exercise in normal subjects
Authors: Harty H. R. , Adams L.
Published: December 2017

To determine whether a dose-dependent relationship exists between the subjective sensation of breathlessness and hypoventilation during steady-state exercise, we measured breathlessness at six levels of volitionally suppressed ventilation. To achieve this, subjects targeted their breathing at 0, 5, 10, 15, 20, and 25% below their spontaneous exercise level. All 12 subjects were successful in hypoventilating in a graded manner. However, in general, the degree of hypoventilation achieved was less than that of the target level set; this discrepancy was greatest at the higher target levels. Volitional hypoventilation at target levels of > or = 10% caused significant decreases in ventilation and significant increases in end-tidal PCO2. All levels of volitional hypoventilation caused increased ratings of breathlessness, reaching statistical significance at a set target level of 15%. Significant increases in breathlessness intensity were associated with increases in end-tidal PCO2 of 2–3 Torr. We conclude that, during steady-state exercise, there appears to be a dose-dependent relationship between breathlessness and volitionally induced inappropriately low ventilation. The need to minimize such subjective sensations of breathlessness may play a role in the increased ventilation observed during exercise.
Bronchomotor responses to hypoxia and hypercapnia in decerebrate cats
Authors: Iscoe S. , Fisher J. T.
Published: December 2017

Decerebrate animals are often used in investigations of the control of breathing because anesthesia-induced depression of respiratory reflexes is absent. We therefore investigated the level of tone and responsiveness of airway smooth muscle in seven decerebrate, paralyzed, and ventilated cats. Specifically, we measured the changes in pulmonary resistance (RL) and dynamic pulmonary compliance (CLdyn) in response to hypoxia and hypercapnia. All cats responded to hypoxia (approximately 10% O2 in N2) with significant increases (mean 49%, range 5–156%) in RL from a mean control value of 0.0197 +/- 0.0081 (SD) cmH2O.ml-1.s. During inhalation of 5% CO2 in O2, RL increased significantly (mean 59%, range 16–135%) from a mean control value of 0.0190 +/- 0.0056 cmH2O.ml-1.s. Decreases in CLdyn during hypoxia and hypercapnia were much smaller, averaging -9 and -11%, respectively. After atropine was administered, average control RL fell 50%, from 0.0269 to 0.0134 cmH2O.ml-1.s (P < 0.05; n = 4). Hypoxic and hypercapnic gas mixtures did not affect pulmonary mechanics after atropine was administered. In three cats, oscillations of RL were synchronized to phrenic activity but only at low respiratory frequencies (approximately 12 cycles/min), indicating that airway smooth muscle responded slowly to vagal input. Pentobarbital sodium, like atropine, reduced control RL in three cats. These cats lost their bronchoconstrictor response to hypercapnia but had augmented responses to hypoxia compared with preanesthetic responses. We conclude that decerebrate cats possess resting bronchomotor tone and retain their responsiveness to hypoxia and hypercapnia. Thus the decerebrate cat is a useful model for studying the control of tracheobronchial smooth muscle.
Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep
Authors: Sasaki F. , Pare P. , Ernest D. , Bai T. , Verburgt L. , March R. , Baile E.
Published: December 2017

To test whether endogenous endothelial nitric oxide (NO) influences baseline bronchial vascular tone and mediates acetylcholine (ACh)-induced bronchial vascular dilation and/or modulates bronchoconstriction in ovine airways, we studied anesthetized ventilated open-chest sheep and measured bronchial blood flow (Qbr) and pulmonary resistance (RL). In six sheep we measured the response of Qbr and RL to the dose of ACh required to produce 50% of the maximal increase in Qbr at baseline during infusion of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; 10(-2) M). Infusion of L-NNA decreased both the baseline Qbr (28 +/- 13 to 8 +/- 2 ml/min, P < 0.01) and the change in Qbr (delta Qbr) from the baseline value (84 +/- 42 to 33 +/- 18 ml/min, P < 0.05). There was no difference in baseline RL or in the response of RL to ACh at any time. In another six sheep, phenylephrine (5 x 10(-6) to 5 x 10(-7) M) decreased baseline Qbr (22 +/- 6 to 10 +/- 3 ml/min, P < 0.05) but not delta Qbr (62 +/- 13 to 66 +/- 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Qbr to a similar extent (11 +/- 5 ml/min) and also decreased delta Qbr (42 +/- 16 ml/min, P < 0.05). We conclude that endogenous endothelial NO influences baseline vascular tone and ACh-induced vasodilation of the ovine bronchial vasculature but has no effect on baseline RL or ACh-induced bronchoconstriction.
Natural killer cell response to exercise in humans: effect of hypoxia and epidural anesthesia
Authors: Klokker M. , Kjaer M. , Secher N. H. , Hanel B. , Worm L. , Kappel M. , Pedersen B. K.
Published: December 2017

For the response of immunologically competent blood cells to exercise, the importance of afferent nerve impulses was evaluated. On separate days, seven males cycled in a recumbent position approximately 60% of maximal O2 uptake with and without sensory nerve blockade by lumbar epidural anesthesia. Blood samples were collected after 60 min of rest, 20 min of exercise, and 120 min postexercise. Subsequently, on each day, the subjects were exposed to 11.5% O2–88.5% N2 for 10 min. This was followed by 20 min of hypoxic exercise at the same work rate, and a final blood sample was obtained. The concentrations of lymphocytes expressing the cluster designation (CD) cell-surface antigens CD3, CD4, CD8, and CD14 became elevated during exercise, and these responses were enhanced by hypoxia (P < or = 0.01). The most pronounced changes were within the concentrations of CD16+ and CD56+ natural killer cells, which increased twofold during normoxic and fivefold during hypoxic exercise (P < or = 0.01). Sensory nerve blockade decreased the number of CD3+ and CD4+ cells and increased the percentage of CD16+ cells, independent of exercise and hypoxia (P < or = 0.05). Sensory nerve blockade caused minor enhancement in the increase of unstimulated natural killer cell activity during exercise (P = 0.07) and enhanced the interferon-alpha-stimulated activity at normoxia (P < or = 0.05), whereas no effect was detected at hypoxia. The results demonstrate that the responses of immunological competent cells to normoxic and hypoxic exercise are not abolished by blockade of nerve impulses from active muscle.
Ozone-induced airway hyperresponsiveness: role of superoxide anions, NEP, and BK receptors
Authors: Tsukagoshi H. , Haddad E. B. , Sun J. , Barnes P. J. , Chung K. F.
Published: December 2017

We investigated the role of reactive oxygen species in ozone-induced airway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiveness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were measured in vivo. Neutral endopeptidase (NEP) activity assay and measurement of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-generating NADPH oxidase, was administered perorally 30 min before a 3- or 6-h exposure to 3 ppm of ozone, and the animals were studied 18–24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the increase in airway responsiveness to BK but not to ACh without affecting the neutrophil counts in BALF. The antioxidants allopurinol and deferoxamine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors in vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK receptors in lungs from rats treated with or without apocynin. We conclude that superoxide anions released from inflammatory cells in the airway may be involved in ozone-induced AHR. Inactivation of NEP or upregulation of BK receptors do not appear to be involved, but the possibility of localized changes cannot be excluded.
Complement activation in divers after repeated air/heliox dives and its possible relevance to DCS
Authors: Hjelde A. , Bergh K. , Brubakk A. O. , Iversen O. J.
Published: December 2017

Plasma levels of the anaphylatoxin C5a were measured in 19 divers performing repeated air dives. Blood samples were collected immediately before the first dive and 2 h after the first and the second or third dive. Serum obtained at the same times was subjected to complement activation in vitro by air bubbles. Six divers developed symptoms of decompression sickness (DCS). Most intravascular bubbles were observed in divers with the lowest plasma levels of C5a. Postdive plasma levels of C5a did not increase compared with predive levels, nor were postdive levels significantly different after two or three dives compared with the first dive. Repeated dives did not influence the amounts of C5a generated in vitro. Neither plasma levels of C5a nor C5a generated in vitro were significantly different in divers who experienced symptoms of DCS vs. divers without symptoms of DCS. We conclude that plasma level of C5a and measurement of C5a generation in vitro cannot be used to predict DCS.
Circulating palmitate uptake and oxidation are not altered by glycogen depletion in contracting skeletal muscle
Authors: Turcotte L. P. , Hespel P. , Richter E. A.
Published: December 2017

The extent to which muscle glycogen depletion affects plasma free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were glycogen depleted (GD) or supercompensated (SC) by swimming exercise and diet treatment 24 h before perfusion of their isolated hindquarters at rest and during electrically induced muscle contractions. After 20 min of equilibration with glucose (6 mM), palmitate (2,000 microM), and [1–14C]palmitate, palmitate uptake and oxidation were found to be similar between groups at rest and during electrical stimulation. Palmitate uptake increased by 55% during electrical stimulation and averaged 2.75 +/- 0.56 mumol.g-1.h-1. Resting palmitate oxidation averaged 0.14 +/- 0.03 mumol.g-1.h-1 and increased to 0.53 +/- 0.06 and 0.47 +/- 0.08 mumol.g-1.h-1 during electrical stimulation in GD and SC, respectively. Glucose uptake was significantly higher in GD than in SC at rest and during electrical stimulation and significantly increased in both groups during electrical stimulation to reach values of 11.8 +/- 1.2 and 7.6 +/- 1.4 mumol.g-1.h-1, respectively. Lactate release was lower in GD than in SC at rest and during electrical stimulation and was highest after 2 min of stimulation in both groups. Additional experiments at perfusate palmitate concentrations of 600–900 microM yielded similar results. These results show that, in contracting perfused skeletal muscle, muscle glycogen depletion increases glucose utilization but does not affect total plasma FFA oxidation, suggesting that regulation within pathways of carbohydrate metabolism takes precedence over regulation between pathways of lipid and carbohydrate metabolism.
Changes in total pulmonary resistance and PCO2 between wakefulness and sleep in normal human subjects
Authors: Morrell M. J. , Harty H. R. , Adams L. , Guz A.
Published: December 2017

We investigated the possible role of an increase in total pulmonary resistance in the sleep-related hypoventilation that occurs in healthy subjects. Eight nonsnoring volunteers were studied during quiet wakefulness and stage IV sleep. Airflow was measured via a nasal mask with a low dead space, and breathing pattern, end-tidal PCO2 (PETCO2), and a continuous estimate of total pulmonary resistance were estimated. From wakefulness to sleep, mean inspiratory resistance increased from 5.5 +/- 2.4 (SD) to 8.1 +/- 4.3 cmH2O.l–1.s, PETCO2 increase from 38.7 +/- 3.0 to 40.7 +/- 3.5 Torr, and ventilation decreased from 7.12 +/- 1.15 to 6.47 +/- 1.68 l/min. In five of the eight subjects, low levels of continuous positive airway pressure were applied during stage IV sleep to reverse any increase in resistance. In these subjects, continuous positive airway pressure reduced mean inspiratory resistance from 9.3 +/- 4.3 +/- 3.0 cmH2O.l–1.s but had little effect on mean PETCO2 (from 39.8 +/- 4.0 to 39.6 +/- 4.0 Torr) and mean ventilation (from 6.79 +/- 1.93 to 6.91 +/- 1.80 l/min). These findings suggest that in nonsnoring subjects reductions in alveolar ventilation cannot be accounted for by an increase in airway resistance.
Effect of hypoxia on reflex responses of tracheal submucosal glands
Authors: Hejal R. , Strohl K. P. , Erokwu B. , Cherniack N. S. , Haxhiu M. A.
Published: December 2017

The effects of moderate sustained normocapnic hypoxia on tracheal submucosal gland reflex responses were studied. Experiments were performed in anesthetized, paralyzed, and mechanically ventilated dogs. The changes in the number of secreting glands and volume of secreted fluid in the subsequent period of time were recorded after 15–30 min of controlled ventilation with room air [arterial PO2 (PaO2) 86 +/- 3 Torr], hypoxic gas mixture (PaO2 49 +/- 4 Torr), or 100% O2 (PaO2 339 +/- 39 Torr), under isocapnic and isohydric conditions. The hillocks method was used to quantify the changes in submucosal gland secretion. The changes in secretion 30 s after stimulation of pulmonary C-fiber receptors by right atrial injection of capsaicin (10 micrograms/kg; n = 10) were markedly lower during moderate hypoxia than in normoxia or hyperoxia. Differences in the number of liquid droplets and the volume of secreted fluid were statistically significant (P < 0.05 and P < 0.001, respectively). Stimulation of airway rapidly adapting receptors by lung deflation increased airway secretion; the number of “hillocks” and the volume of secreted fluid were lower in hypoxic than in hyperoxic state. Differences between response curves for the number of glands activated and secreted volume were statistically significant (P < 0.05 and P < 0.001). The number of glands activated by substance P given locally by arterial infusion was not affected by the state of oxygenation, but the calculated volume of secreted fluid was lower during the hypoxic state than under hyperoxic condition (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptations of rat lateral gastrocnemius motor units in response to voluntary running
Authors: Seburn K. L. , Gardiner P.
Published: December 2017

This study investigated the effects of 12 wk of voluntary wheel running on motor units from rat lateral gastrocnemius. Motor units were isolated via ventral root splitting (L5) from active or sedentary rats and were classified into slow, fast-fatigue-resistant, and fast-fatigable (FF) units. An overall increase in mean motor unit tetanic tension (35%) was accompanied by a decrease in mean motor unit fatigue resistance (-10%). These adaptations were localized in the fast unit population but varied among fast motor unit subtypes. The overall increase in tetanic force was due primarily to increases in fast-fatigue-resistant units (300%), whereas changes in fatigue resistance (-43%) were confined to FF units. However, the changes seen with activity may have been partly obscured by classifying fast motor units based on fatigability, since a significant increase in tetanic force accompanied by a decreased twitch one-half relaxation time was apparent in units falling in the midrange of the tetanic force continuum and included a number of FF units. These data provide direct demonstration of nonuniform motor unit adaptations subsequent to increases in normal functional activity.
Myosin heavy chain isoforms of human muscle after short-term spaceflight
Authors: Zhou M. Y. , Klitgaard H. , Saltin B. , Roy R. R. , Edgerton V. R. , Gollnick P. D.
Published: December 2017

The influence of microgravity on the myosin phenotype of skeletal muscle fibers in the vastus lateralis of eight crew members was studied before and after 5-day (n = 3) and 11-day (n = 5) spaceflights (space shuttle flights: STS-32, -33 and -34). Single-fiber electrophoresis analyses showed that the proportion of fibers expressing only slow (type I) myosin heavy chain (MHC) in the vastus lateralis was significantly lower after than before 11 days of spaceflight. Although the family of type II MHC isoforms was elevated post- compared with preflight, the distribution among the isoforms of type II MHC was not statistically different. Based on monoclonal and polyclonal antibodies specific for three adult MHC isoforms and single-fiber electrophoresis, approximately 3% of the fibers analyzed coexpressed all three adult MHC isoforms. The results from immunohistochemical staining with two different sets of antibodies indicate a reduction in the percentage of fibers expressing type I MHC as a result of spaceflight. The mean difference, however, was significant only when the fibers were categorized simply as type I or II. These changes appeared to be highly individualized among the astronauts. These results suggest that a rapid change in MHC isoform expression can occur in some muscle fibers after a relatively brief exposure to spaceflight.
Pressure-volume relationships in equine midcarpal joint
Authors: Hardy J. , Bertone A. L. , Muir W. W.
Published: December 2017

The effects of joint angle, fluid infusion, history-dependence, and time dependence on the pressure-volume (PV) relationships of normal equine midcarpal joints were determined. Horses (n = 24 and 48 midcarpal joints) were anesthetized and placed in dorsal recumbency, and the four midcarpal joint pouches were cannulated for intra-articular pressure (IAP) measurements and recording. Fluid (synovial fluid or saline) was infused or withdrawn through the dorsal joint capsule. The PV curves were sigmoid and best described by IAP = A x e(B x volume) - C, where B is the fractional change in pressure per unit change of volume, and A and C are constants. Compartmentation was not observed. Elastance was greater at sub- than supra-atmospheric pressures, at 90 degrees than 135 degrees angles, and with saline than synovial fluid. Hysteresis was greater at 90 degrees than 135 degrees angle, and with synovial fluid than saline. Elastance progressively increased with sequential distention at high IAPs. IAP relaxation was a positive logarithmic relationship of IAP. These findings suggest an important role of synovial fluid in articular PV relationships and emphasize the role of joint angle, prior distention cycles, and decay of IAP with time in future studies investigating these phenomena.
Effects of manganese superoxide dismutase on lung fluid balance after smoke inhalation
Authors: Nguyen T. T. , Cox C. S. , Herndon D. N. , Biondo N. A. , Traber L. D. , Bush P. E. , Zophel A. , Traber D. L.
Published: December 2017

There is evidence of increased oxygen free radical activity after smoke inhalation with and without concomitant burn injury. We determined the effects of manganese superoxide dismutase (Mn SOD) on lung fluid balance as measured by lung microvascular permeability coefficient (sigma), filtration coefficient (Kf), and lymph flow. Merino breed ewes (n = 6/group) were surgically prepared. The SOD group (SOD) received Mn SOD (9,000 U/kg) as an intravenous bolus and was insufflated with smoke. The control group (CON) received saline and smoke. sigma and Kf were determined 24 h before and 24 h after smoke injury. Lymph flow, arterial O2-to-inspired O2 fraction ratio, systemic hemodynamics, and pulmonary arterial and capillary pressures were measured. The sigma was significantly (P < 0.05) higher after smoke insufflation in SOD compared with CON (0.71 +/- 0.03 vs. 0.53 +/- 0.05). Kf was significantly lower after smoke insufflation in SOD compared with CON (0.038 +/- 0.010 vs. 0.061 +/- 0.010). Lymph flows were significantly lower during the 24 h after smoke insufflation in SOD compared with CON (33 +/- 7 vs. 55 +/- 8 ml/h at 24 h). Arterial O2-to-inspired O2 fraction ratio was significantly improved at 6 and 12 h after smoke insufflation in SOD compared with CON at the same time points. Mn SOD meliorates the lung microvascular permeability changes associated with smoke inhalation injury.
Oxygen effect on O2 deficit and VO2 kinetics during exercise in obstructive pulmonary disease
Authors: Palange P. , Galassetti P. , Mannix E. T. , Farber M. O. , Manfredi F. , Serra P. , Carlone S.
Published: December 2017

We evaluated the effect of supplemental O2 on energy metabolism of hypoxemic humans by measuring O2 uptake (VO2) kinetics and other cardiorespiratory parameters in nine male chronic obstructive pulmonary disease (COPD) patients and seven age-matched control subjects (on air and on 30% O2) at rest and during moderate cycle ergometer exercise. Heart rate, ventilation, VO2, CO2 output, respiratory exchange ratio, O2 cost of work, and work efficiency were measured with a computerized metabolic cart; O2 deficit and VO2 time courses were calculated. In COPD patients, 30% O2 breathing resulted in 1) reduction of O2 deficit (from 488 +/- 34 ml in air to 398 +/- 27 ml in O2; P < 0.05) and phase 2 VO2 time constant (from 116 +/- 13 s in air to 74 +/- 12 s in O2; P < 0.05); 2) a smaller steady-state increment in CO2 output than in room air (315 +/- 17 ml/min in O2 vs. 358 +/- 27 ml/min in air; P < 0.02), which resulted in a lower exercise respiratory exchange ratio (0.75 +/- 0.02 in O2 vs. 0.80 +/- 0.02 in air; P < 0.02); and 3) reduced steady-state ventilation (22.6 +/- 1.0 l/min in O2 vs. 25.4 +/- 1.1 l/min in air; P < 0.05). In conclusion, 30% O2 breathing accelerated exercise VO2 kinetics in mildly hypoxemic COPD patients. The observed VO2 kinetics improvement with O2 supplementation is consistent with an enhancement of aerobic metabolism in skeletal muscles during moderate exercise.
Renal and endocrine responses in humans to isotonic saline infusion during microgravity
Authors: Norsk P. , Drummer C. , Rocker L. , Strollo F. , Christensen N. J. , Warberg J. , Bie P. , Stadeager C. , Johansen L. B. , Heer M. , et al.
Published: December 2017

It was the purpose of this study to investigate how the endocrine and renal mechanisms of fluid volume control in humans (n = 4) adapt to microgravity by applying an intravenous isotonic saline infusion. The acute ground-based supine (Sup) and seated (Seat) positions were chosen as references. During microgravity, renal sodium excretion (UNaV) was doubled during the second and third hours after infusion compared with during Seat (P < 0.05) but blunted during the first hour after infusion compared with during Sup, leading to a reduction in cumulative UNaV (59 +/- 15 vs. 108 +/- 12 mmol/5 h; P < 0.05). Plasma norepinephrine (NE) attained the highest value 3 h after infusion during microgravity (31 +/- 5 x 10(-2) ng/ml vs. 19 +/- 1 and 13 +/- 3 x 10(-2) ng/ml for Seat and Sup, respectively; P < 0.05). Inflight levels of plasma renin and aldosterone were very similar to levels during Seat. In conclusion, 1) the microgravity-adapted renal responses to infusion reflected a condition in between that of ground-based Seat and Sup, respectively, and 2) the plasma levels of NE, renin, and aldosterone were elevated inflight and not related to the changes in UNaV and urinary flow rate. These observations are in contrast to results of ground-based simulation experiments and might partly have been caused by a prior inflight reduction in extracellular fluid volume. The high levels of NE during microgravity warrant further investigation.
Human temperature regulation during subanesthetic levels of nitrous oxide-induced narcosis
Authors: Cheung S. S. , Mekjavic I. B.
Published: December 2017

The present study investigated whether nitrous oxide (N2O) attenuates shivering thermogenesis during cold water immersion in a dose-dependent manner. Seven male subjects were immersed to the neck for 60 min in 20 degrees C water on five separate occasions while breathing either air (AIR) or a normoxic mixture of 10, 15, 20, or 25% N2O balanced with N2. All N2O concentrations investigated caused a significant (P < 0.02) reduction in shivering thermogenesis compared with AIR. Despite similar heat flux from the skin, the relative changes in esophageal temperature from resting preimmersion levels were significantly greater (P < 0.05) during the N2O trials compared with AIR, with no significant difference among the N2O conditions. A dose-dependent trend in the perception of thermal comfort was observed for the N2O conditions. It is concluded that shivering thermogenesis, and thus thermal balance, is affected to the same degree for the range of inspired N2O concentrations investigated, with no discernable dose-dependent effect.
Changes in serum lipids and apolipoproteins after exercise in men with high cholesterol: influence of intensity
Authors: Crouse S. F. , O'Brien B. C. , Rohack J. J. , Lowe R. C. , Green J. S. , Tolson H. , Reed J. L.
Published: December 2017

The purpose of this study was to characterize the short-term changes in blood lipid and apolipoprotein concentrations in healthy hypercholesterolemic men after high-intensity [80% maximal O2 uptake (VO2max); n = 20] or moderate-intensity (50% VO2max; n = 19) cycle ergometer exercise balanced for caloric expenditure (350 kcal). The men's age, height, weight, %fat, and VO2max were 46 +/- 2 yr, 173 +/- 7 cm, 82.7 +/- 2.2 kg, 28 +/- 1%, and 31.1 +/- 1.0 ml O2.kg-1.min-1, respectively. Blood samples were drawn before exercise, immediately after exercise, then 24 and 48 h later, and concentrations of all variables were adjusted for changes in plasma volume. Significant changes (P < 0.0016) were as follows: total and low-density lipoprotein cholesterol fell by 4% immediately after exercise and then rose by 5–8% by 48 h. Triglycerides were 18 and 15% lower at 24 and 48 h, respectively. HDL-cholesterol, high-density lipoprotein3-cholesterol, and apolipoprotein B rose 8–9% by 24 h and remained elevated. High-density lipoprotein2-cholesterol rose by 27% by 48 h after exercise, but this change was not significant. Apolipoprotein A-I did not change with exercise. The response patterns were not affected by exercise intensity. These data show that a single session of exercise performed by untrained hypercholesterolemic men alters blood lipid and apolipoprotein concentrations. Furthermore, the postexercise response patterns are not influenced by exercise intensity, as long as caloric expenditure is held constant.
Cytokine-induced neutrophil chemoattractant is necessary for interleukin-1-induced lung leak in rats
Authors: Koh Y. , Hybertson B. M. , Jepson E. K. , Cho O. J. , Repine J. E.
Published: December 2017

Because interleukin-1 (IL-1) is not a potent chemoattractant intrinsically, our goal was to determine whether cytokine-induced neutrophil chemoattractant (CINC) mediates neutrophil accumulation and leak that occur in lungs of rats given IL-1 intratracheally. We found that rats given IL-1 intratracheally had increased lung lavage CINC concentrations, lung myeloperoxidase (MPO) activity, lung lavage neutrophil numbers, and lung leak compared with saline-treated control rats. In parallel, rats given increasing doses of anti-CINC antibody along with IL-1 intratracheally had progressively decreased lung lavage CINC concentrations, lung lavage neutrophil numbers, and lung leak, but the same lung MPO activity, as did rats given only IL-1 intratracheally. In addition, lavage CINC concentrations correlated with lavage neutrophil numbers in rats. Because CINC is a chemoattractant in vitro and because anti-CINC antibody decreased lung leak induced by IL-1, CINC was then given alone intratracheally. Rats given only CINC intratracheally had the same lung MPO activity, lung lavage neutrophil numbers, and lung leak as did saline-treated control rats. These observations suggest that instilling IL-1 intratracheally induces lung leak via a CINC-dependent pathway but that administering CINC alone in concentrations exceeding the levels measured in lung lavages from IL-1-treated rats is not sufficient to cause lung neutrophil accumulation and lung leak.
Sarcolemmal disruption in reloaded atrophic skeletal muscle
Authors: Kasper C. E.
Published: December 2017

The purpose of this study was to determine whether reloading of atrophied skeletal muscle after 28 days of hind-limb unloading (HU) would produce significant sarcolemmal membrane disruption before frank necrosis. Soleus and plantaris muscles were atrophied by HU. Adult female Wistar rats (N = 13) were killed at 28 days of unloading and 4 and 7 days of reloading after HU. Rat serum albumin was used as a marker for muscle fiber disruption. Dark intracellular staining with horseradish peroxidase-conjugated anti-rat serum albumin antibody was interpreted as evidence of membrane rupture. There was a significantly different time course of disruption between plantaris and soleus muscles, with a negative correlation between cell size and occurrence of disruption. Fourteen percent of plantaris fibers were wounded after HU, peaking at day 4 of reloading (20% of cross-sectional area). Soleus demonstrated disruption only on reloading peaking in severity at day 7 (14% of fibers). It was demonstrated that sarcolemmal disruption due to atrophy and reloading does not always progress to necrosis and degeneration by the 7th day of recovery.
An anatomic and physiological model of hepatic vascular system
Authors: Fine D. R. , Glasser D. , Hildebrandt D. , Esser J. , Lurie R. E. , Chetty N.
Published: December 2017

Hepatic function can be characterized by the activity/time curves obtained by imaging the aorta, spleen, and liver. Nonparametric deconvolution of the activity/time curves is clinically useful as a diagnostic tool in determining organ transit times and flow fractions. The use of this technique is limited, however, because of numerical and noise problems in performing deconvolution. Furthermore, the interaction of part of the tracer with the spleen and gastrointestinal tract, before it enters the liver, further obscures physiological information in the deconvolved liver curve. In this paper, a mathematical relationship is derived relating the liver activity/time curve to portal and hepatic behavior. The mathematical relationship is derived by using transit time spectrum/residence time density theory. Based on this theory, it is shown that the deconvolution of liver activity/time curves gives rise to a complex combination of splenic, gastrointestinal, and liver dependencies. An anatomically and physiologically plausible parametric model of the hepatic vascular system has been developed. This model is used in conjunction with experimental data to estimate portal, splenic, and hepatic physiological blood flow parameters for eight normal volunteers. These calculated parameters, which include the portal flow fraction, the splenic blood flow fraction, and blood transit times are shown to adequately correspond to published values. In particular, the model of the hepatic vascular system identifies the portal flow fraction as 0.752 +/- 0.022, the splenic blood flow fraction as 0.180 +/- 0.023, and the liver mean transit time as 13.4 +/- 1.71 s. The model has also been applied to two portal hypertensive patients. The variation in some of the model parameters is beyond normal limits and is consistent with the observed pathology.
Critique of conceptual basis of diffusing capacity estimates: a finite element analysis
Authors: Hsia C. C. , Chuong C. J. , Johnson R. L.
Published: December 2017

We present a simple geometric model of a pulmonary capillary segment containing a variable number of red blood cells. The pattern of CO transfer from alveolar air to capillary red blood cells in this model is accurately computed by a finite element method and used to explore conceptual flaws in the Roughton-Forster (RF) and morphometric methods of estimating pulmonary diffusing capacity for CO. The CO uptakes calculated by the finite element method at two alveolar O2 tensions are introduced into the RF model to determine whether the anatomically defined membrane component of diffusing capacity for CO (DmCO) and pulmonary capillary blood volume (Vc) are recovered. The same capillary model is also subjected to standard morphometric analysis. Results are compared at different levels of capillary hematocrit (Hct). The RF method accurately recovers DmCO and Vc at a low Hct but modestly overestimates DmCO and underestimates Vc at higher Hct; errors arise because conductance of the tissue-plasma membrane for CO varies with alveolar O2 tension. The morphometric method seriously overestimates DmCO because the true tissue-plasma resistance to diffusion is underestimated and the effective membrane utilized for diffusion is overestimated; these errors are accentuated by a low Hct.
Metabolic availability of medium-chain triglycerides coingested with carbohydrates during prolonged exercise
Authors: Jeukendrup A. E. , Saris W. H. , Schrauwen P. , Brouns F. , Wagenmakers A. J.
Published: December 2017

The present study examined the metabolic response to medium-chain triglycerides (MCTs) ingestion with or without carbohydrates (CHOs). Eight well-trained athletes cycled 4 x 180 min at 50% maximal work rate (57% maximal O2 consumption). Subjects drank a bolus of 4 ml/kg at the start and 2 ml/kg every 20 min during exercise of either a 15% (214 g) CHO solution (CHO trial), an equicaloric 149 g CHO-29 g MCT suspension (CHO+MCT trial), 214 g CHO [high CHO (HCHO)]-29 g MCT suspension (HCHO+MCT trial) or 29 g MCT solution (MCT trial). Exogenous MCT oxidation was measured by adding a [1,1,1–13C]trioctanoate tracer to the MCT oil. 13CO2 enrichment of breath samples were measured every 15 min. During the second hour (60- to 120-min period), the amount of MCT oxidized was 72% of the amount ingested during the CHO+MCT trial, whereas during the MCT trial only 33% was oxidized. The rate of MCT oxidation increased more rapidly during the HCHO+MCT and CHO+MCT trials compared with the MCT trial, yet in all three cases the oxidation rate stabilized at 0.12 g/min during 120–180 min of exercise. It is concluded that more MCTs are oxidized when ingested in combination with CHOs. Data do confirm the hypothesis that oral MCTs might serve as an energy source in addition to glucose during exercise because the metabolic availability of MCTs was high during the last hour of exercise, with oxidation rates being approximately 70% of the ingestion rate.
Neurochemical control of tissue resistance in piglets
Authors: Martin R. J. , Dreshaj I. A. , Miller M. J. , Haxhiu M. A.
Published: December 2017

Lung resistance may be influenced by chemoreceptor activity and modulated by inspiratory neural output; however, it is unknown whether the contractile elements of lung tissue participate in these changes during early development. In anesthetized paralyzed open-chest piglets, we measured phrenic electroneurogram, lung resistance (RL), and tissue resistance utilizing alveolar capsules to partition the hypercapnic and hypoxic responses of RL into tissue (Rti) and airway resistance (Raw) components. Inhalation of 7% CO2 significantly increased RL (7.4 +/- 0.5 to 11.3 +/- 0.6 cmH2O.l-1.s), Rti (5.2 +/- 0.5 to 6.9 +/- 0.5 cmH2O.l-1.s), and Raw (2.2 +/- 0.2 to 4.4 +/- 0.4 cmH2O.l-1.s). Inhalation of 12% O2 caused more modest increases in RL, Rti, and Raw. Oscillations in tracheal and alveolar pressures appeared in synchrony with phrenic activity in response to both chemoreceptor stimuli. Cholinergic blockade eliminated these oscillations and significantly reduced the hypercapnic and hypoxic responses of RL, Rti, and Raw. These data demonstrate for the first time that hypercapnia and hypoxia elicit a cholinergically mediated increase in Rti which, just like the airway component of RL, is modulated by inspiratory neural output and is present during early development. Such coordination in neural function throughout the respiratory system may serve to optimize gas exchange during early postnatal life.
Glibenclamide does not reverse attenuated vasoreactivity to acute or chronic hypoxia
Authors: Eichinger M. R. , Resta T. C. , Balderrama D. S. , Herrera G. M. , Richardson L. A. , Resta J. M. , Walker B. R.
Published: December 2017

Recent studies from our laboratory have shown that acute and chronic hypoxic exposures are associated with attenuated systemic vasoreactivity in conscious rats. The present studies examined the role of adenosine triphosphate-sensitive potassium channels (KATP channels) in modulating the pressor and vasoconstrictor responses to phenylephrine (PE) in conscious instrumented rats 1) during acute hypoxia or 2) after chronic hypoxic exposure. Mean arterial pressure, mean cardiac output, and total peripheral resistance were assessed before and after graded infusions of PE in both groups of rats under normoxic or hypoxic conditions. Additionally, the role of KATP channels in attenuating vasoreactivity was determined by administration of glibenclamide (KATP channel blocker) before PE infusions. Acute hypoxia (12% O2) was associated with reduced pressor and constrictor responses to PE in control animals. Furthermore, acute return to room air did not restore the pressor and constrictor responses in the chronically hypoxic rats. Glibenclamide infusion did not influence the pressor or vasoconstrictor responses to PE in either group of animals during normoxia or acute hypoxia. Therefore, our data suggest that opening of KATP channels is not involved in the attenuated vasoreactivity associated with acute and chronic hypoxia in the conscious rat.
Pulmonary vasodilator drugs decrease lung liquid production in fetal sheep
Authors: Cummings J. J.
Published: December 2017

To examine a potential relationship between pulmonary vasodilatation and fetal lung liquid production, I measured lung liquid production in 20 fetal sheep at 130 +/- 4 days gestation while using several agents known to increase pulmonary blood flow. Thirty-two studies were done in which left pulmonary arterial flow (Qlpa) was measured by an ultrasonic Doppler flow probe and net lung luminal liquid production (Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabeled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. Qlpa and Jv were measured during a 1- to 2-h baseline period and then during a 1- to 2-h infusion period in which the fetuses received either an intravenous infusion of acetylcholine (n = 8), prostaglandin D2 (n = 10), or the leukotriene blocker FPL-55712 (n = 7). These vasodilators work by different mechanisms, each mechanism having been implicated in the decrease in pulmonary vascular resistance seen at birth. Control (saline) infusions (n = 7) caused no change in either Qlpa or Jv over 4 h. All vasodilator agents significantly increased pulmonary blood flow and decreased Jv. Pulmonary arterial pressure did not change significantly in either the control, acetylcholine, prostaglandin, or leukotriene-blocker studies, indicating that pulmonary vascular resistance decreased. Thus agents that increase pulmonary blood flow by mechanisms that occur at birth also decrease lung liquid production in fetal lambs.
Computerized tomography and pulmonary diffusing capacity in highly trained athletes after performing a triathlon
Authors: Caillaud C. , Serre-Cousine O. , Anselme F. , Capdevilla X. , Prefaut C.
Published: December 2017

We investigated the computerized tomographies (CTs) of the thorax and the pulmonary diffusing capacity for CO (DLCO) in eight male athletes before and after a triathlon. DLCO and alveolar volume (VA) were simultaneously measured during 9 s of breath holding. The transfer coefficient (KCO = DLCO/VA) was then calculated. CT scanning was performed during breath holding with the subjects in the supine position. Scanner analysis was done by 1) counting the linear and polygonal opacities (index of interstitial fluid accumulation) and 2) calculating the physical mean lung density and the mean slice mass. Results showed a significant reduction in DLCO (44.9 +/- 2.3 vs. 42.9 +/- 1.7 ml.min-1.mmHg-1; P < 0.05) and KCO (6.0 +/- 0.3 vs. 5.6 +/- 0.3 ml.min-1.mmHg-1.l of VA-1; P < 0.05) after the triathlon and an increase in mean lung density (0.21 +/- 0.009 vs. 0.25 +/- 0.01 g/cm3; P < 0.0001). The number of polygonal and linear opacities increased after the race (P < 0.001). This study confirmed that DLCO and KCO decrease in elite athletes after a long-distance race and showed a concomitant increase in CT lung density and in the number of opacities.
Neural drive to nasal dilator muscles: influence of exercise intensity and oronasal flow partitioning
Authors: Fregosi R. F. , Lansing R. W.
Published: December 2017

Our aim was to test the following hypotheses: 1) neural drive to the muscles of the alae nasi (AN) is proportional to nasal airflow and is independent of the overall level of central respiratory drive, and 2) the switch from nasal to oronasal breathing corresponds to the onset of marked flow turbulence in the nasal airway. Total and nasal inspired ventilation rates (VI) and the electromyogram (EMG) of the AN muscles were measured in seven subjects during progressive-intensity bicycling exercise. In separate experiments in six subjects the nasal VI corresponding to the transition from laminar to turbulent airflow was determined by measuring the pressure-flow relationship of the nasal airway with anterior rhinomanometry. Nasal VI accounted for 70 +/- 11% of total VI at rest and 27 +/- 8% (SE) at 90% of the maximal attainable power (max). Nasal VI and integrated AN EMG activities increased linearly with exercise intensity up to 60% of the max power, but both variables plateaued at this level even though total VI (and central respiratory drive) began to increase exponentially as exercise intensity increased to 90% max. The onset of the exponential rise in total VI was associated with a sharp increase in oral VI and with the onset of marked flow turbulence in the nasal airway. The results suggest that during incremental exercise 1) changes in AN EMG activities are highly correlated with changes in nasal VI, 2) turbulent flow in the nose may be the stimulus for the switch to oronasal breathing so that total pulmonary resistance is minimized, and 3) the correlation between nasal airflow and neural drive to the AN muscles is probably mediated by mechanisms that monitor airway resistance. Although these mechanisms were not identified, the most likely possibilities are receptors in the upper and/or lower airways that are sensitive to negative transmural pressure, or to effort sensations leading to greater corollary motor discharge to nasal dilator muscle motoneurons.