bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative capacity and capillary density of diaphragm motor units
Authors: Enad J. G. , Fournier M. , Sieck G. C.
Published: December 2017

Motor units in the cat diaphragm (DIA) were isolated in situ by microdissection and stimulation of C5 ventral root filaments. Motor units were classified based on their isometric contractile force responses and fatigue indexes (FI). The muscle fibers belonging to individual units (i.e., the muscle unit) were identified using the glycogen-depletion method. Fibers were classified as type I or II based on histochemical staining for myofibrillar adenosine triphosphatase (ATPase) after alkaline preincubation. The rate of succinate dehydrogenase (SDH) activity of each fiber was determined using a microphotometric procedure. The location of capillaries was determined from muscle cross sections stained for ATPase after acid (pH = 4.2) preincubation. The capillarity of muscle unit fibers was determined by counting the number of capillaries surrounding fibers and by calculating the number of capillaries per fiber area. A significant correlation was found between the fatigue resistance of DIA units and the mean SDH activity of muscle unit fibers. A significant correlation was also observed between DIA unit fatigue resistance and both indexes of muscle unit fiber capillarity. The mean SDH activity and mean capillary density of muscle unit fibers were also correlated. We conclude that DIA motor unit fatigue resistance depends, at least in part, on the oxidative capacity and capillary density of muscle unit fibers.
Diaphragmatic displacement measured by fluoroscopy and derived by Respitrace
Authors: Verschakelen J. A. , Deschepper K. , Jiang T. X. , Demedts M.
Published: December 2017

In eight healthy volunteers we simultaneously measured the axial diaphragmatic motion by fluoroscopy and the cross-sectional area changes of the rib cage (RC) and abdomen (ABD) by Respitrace (RIP) during semistatic vital capacities (VC). We found that, if the fluoroscopic axial displacement of the posterior part of the diaphragm between residual volume (RV) and total lung capacity (TLC) is considered equal to 100%, the movement of the middle part is 90%, whereas that of the anterior part is only approximately 60%; the ratio of the axial displacements to mouth volume, furthermore, decreases at high lung volumes, especially for the anterior part. The RIP signal is nearly linearly related to mouth volume, but the contribution of the RC (delta RC) progressively increases (and is approximately 80% RIP at TLC), whereas the volume contribution of the ABD (delta ABD) levels off (to 20% RIP at TLC). The diaphragmatic volume displacement calculated from the theoretical analysis described by Mead and Loring also levels off at high volumes similarly as the ABD but is approximately 50% RIP at TLC. Finally, the axial movements of the three parts of the diaphragm are linearly related to the RC and ABD cross-sectional-area changes (r 0.91–0.97) and are even significantly better correlated with the “calculated” diaphragmatic volume displacement.
Cerebral blood flow during submaximal and maximal dynamic exercise in humans
Authors: Thomas S. N. , Schroeder T. , Secher N. H. , Mitchell J. H.
Published: December 2017

Cerebral blood flow (CBF) in humans was measured at rest and during dynamic exercise on a cycle ergometer corresponding to 56% (range 27–85) of maximal O2 uptake (VO2max). Exercise bouts were performed by 16 male and female subjects, lasted 15 min each, and were carried out in a semisupine position. CBF (133Xe clearance) was expressed as the initial slope index (ISI) and as the first compartment flow (F1). CBF at rest [ISI, 58 (range 45–73); F1, 76 (range 55–98) ml.100 g-1.min-1] increased during exercise [ISI to 79 (57–94) and F1 to 118 (75–164) ml.100 g-1.min-1, P less than 0.01]. CBF did not differ significantly between work loads from 32 (24–33) to 86% (74–96) of VO2max (n = 10). During exercise, mean arterial pressure increased from 84 (60–100) to 101 (78–124) Torr (P less than 0.01) and PCO2 remained unchanged [5.1 (4.6–5.6) vs. 5.4 (4.4–6.3) kPa, n = 6]. These results demonstrate a median increase of 31% (0–87) in CBF by ISI and a median increase of 58% (0–133) in CBF by F1 during dynamic exercise in humans.
Interactive effects of anemia and muscle oxidative capacity on exercise endurance
Authors: Gregg S. G. , Willis W. T. , Brooks G. A.
Published: December 2017

We used endurance training and acute anemia to assess the interactions among maximal oxygen consumption (VO2max), muscle oxidative capacity, and exercise endurance in rats. Animals were evaluated under four conditions: untrained and endurance-trained with each group subdivided into anemic (animals with reduced hemoglobin concentrations) and control (animals with unchanged hemoglobin concentrations). Anemia was induced by isovolemic plasma exchange transfusion. Hemoglobin concentration and hematocrit were decreased by 38 and 41%, respectively. Whole body VO2max was decreased by 18% by anemia regardless of training condition. Anemia significantly reduced endurance by 78% in untrained rats but only 39% in trained animals. Endurance training resulted in a 10% increase in VO2max, a 75% increase in the distance run to exhaustion, and 35, 45, and 58% increases in skeletal muscle pyruvate-malate, alpha-ketoglutarate, and palmitylcarnitine oxidase activities, respectively. We conclude that endurance is related to the interactive effects of whole body VO2max and muscle oxidative capacities for the following reasons: 1) anemic untrained and trained animals had similar VO2max but trained rats had higher muscle oxidative capacities and greater endurance; 2) regardless of training status, the effect of acute anemia was to decrease VO2max and endurance; and 3) trained anemic rats had lower VO2max but had greater muscle oxidative capacity and greater endurance than untrained controls.
Edema from cyclooxygenase products of endogenous arachidonic acid in isolated lung
Authors: Littner M. R. , Lott F. D.
Published: December 2017

We infused A23187, a calcium ionophore, into the pulmonary circulation of dextran-salt-perfused isolated rabbit lungs to release endogenous arachidonic acid. This led to elevations in pulmonary arterial pressure and to pulmonary edema as measured by extravascular wet-to-dry weight ratios. The increase in pressure and edema was prevented by indomethacin, a cyclooxygenase enzyme inhibitor, and by 1-benzylimidazole, a selective inhibitor of thromboxane (Tx) A2 synthesis. Transvascular flux of 125I-albumin from vascular to extravascular spaces of the lung was not elevated by A23187 but was elevated by infusion of oleic acid, an agent known to produce permeability pulmonary edema. We confirmed that A23187 leads to elevations in cyclooxygenase products and that indomethacin and 1-benzylimidazole inhibit synthesis of all cyclooxygenase products and TxA2, respectively, by measuring perfusate levels of prostaglandin (PG) I2 as 6-ketoprostaglandin F1 alpha, PGE2, and PGF2 alpha and TxA2 as TxB2. We conclude that release of endogenous pulmonary arachidonic acid can lead to pulmonary edema from conversion of such arachidonic acid to cyclooxygenase products, most notably TxA2. This edema was most likely from a net hydrostatic accumulation of extravascular lung water with an unchanged permeability of the vascular space, since an index of permeability-surface area product (i.e., transvascular albumin flux) was not increased.
Bronchial artery ligation modifies pulmonary edema after exposure to smoke with acrolein
Authors: Hales C. A. , Barkin P. , Jung W. , Quinn D. , Lamborghini D. , Burke J.
Published: December 2017

Pulmonary edema can follow smoke inhalation and is believed to be due to the multiple chemical toxins in smoke, not the heat. We have developed a synthetic smoke composed of aerosolized charcoal particles to which one toxin at a time can be added to determine whether it produces pulmonary edema. Acrolein, a common component of smoke, when added to the synthetic smoke, produced a delayed-onset pulmonary edema in dogs in which the extravascular lung water (EVLW) as detected by a double-indicator technique began to rise after 42 +/- 2 (SE) min from 148 +/- 16 to 376 +/- 60 ml at 165 min after smoke exposure. The resulting pulmonary edema was widespread macroscopically but appeared focal microscopically with fibrin deposits in alveoli adjacent to small bronchi and bronchioles. Bronchial vessels were markedly dilated and congested. Monastral blue B when injected intravenously leaked into the walls of the bronchial vessels down to the region of the small bronchioles (less than or equal to 0.5 mm ID) of acrolein-smoke-exposed dogs but not into the pulmonary vessels. Furthermore, ligation of the bronchial arteries delayed the onset of pulmonary edema (87 +/- 3 min, P less than 0.05) and lessened the magnitude (232 +/- 30 ml, P less than 0.05) at 166 +/- 3 min after acrolein-smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Abrupt changes in mixed venous blood gas composition after the onset of exercise
Authors: Casaburi R. , Daly J. , Hansen J. E. , Effros R. M.
Published: December 2017

It has been assumed that increases in both O2 uptake and ventilation occurring within the first few seconds after the onset of exercise cannot be the result of changes in blood gas composition reaching the central circulation because of the circulatory delay from the exercising limbs (A. Krogh and J. Lindhard, J. Physiol. Lond. 42: 112–136, 1913). We sought to validate this assumption by measuring the time course of pulmonary arterial blood gases during the transition from rest to exercise. Six healthy men underwent pulmonary arterial catheterization and then performed transitions from rest to moderate cycle ergometer exercise. An anaerobic sampling manifold withdrew 19 samples of blood during the rest-to-exercise transition; sampling interval was usually 4 s. Blood gas analysis showed that, on average, from rest-to-steady-state exercise, O2 saturation (Svo2) fell from 71 to 41% and mixed venous PCO2 (PvCO2) rose from 42 to 59 Torr. Contrary to our expectations, Svo2 decreased and PvCO2 increased with no discernible latency after exercise onset (by 10% and 2 Torr, respectively, within 6 s). The half time for the Svo2 decrease was 32 s, whereas for the PvCO2 increase it was 80 s. The time course of superior vena cava blood gas composition was determined in several experiments; no rapid changes after exercise onset were found. We conclude that at exercise onset there is a rapid fall in Svo2 and rise in PvCO2 well in advance of arrival of blood produced by exercising legs.(ABSTRACT TRUNCATED AT 250 WORDS)
Lateral pontine lesions affect central chemosensitivity in unanesthetized fetal lambs
Authors: Johnston B. M. , Gluckman P. D.
Published: December 2017

The mechanisms underlying the apnea associated with both hypoxia and high-voltage electrocortical activity (HV ECOG) in the fetal lamb are not clearly understood. We have previously shown that lesions in the rostral lateral pons change the depressive response to hypoxia to one of stimulation. We now present evidence that lesions in this area also affect the fetal response to H+/CO2. Lactic acidemia and 5–6% hypercapnia both caused almost continuous breathing throughout both HV and low-voltage (LV) ECOG in seven of eight fetuses with lesions that reversed the depressive response to hypoxia. In five intact control fetuses and seven fetuses with lesions that did not affect the response to hypoxia, neither CO2 nor lactic acidemia induced continuous breathing. We conclude that the lateral pontine area, which is involved in the hypoxic depression of breathing in the fetus, is also involved in the inhibitory mechanisms operating during HV ECOG. Furthermore the inhibition of breathing during HV ECOG appears to be related to a raised threshold for fetal breathing, which is sensitive to H+/CO2.
Autosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine
Authors: Levitt R. C. , Mitzner W.
Published: December 2017

We have previously reported that airway hyperresponsiveness to acetylcholine (ACh) is inherited as an autosomal recessive trait in A/J and C3H/HeJ mice and the progeny of crosses between them (FASEB J. 2: 2605–2608, 1988). In the present report, we have extended these studies by evaluating the biological variability in the airway response to 5-hydroxytryptamine (5-HT) and ACh among multiple genetically standardized inbred strains of mice. The pattern of airway responsiveness to ACh differed significantly from that of 5-HT in nine inbred strains of mice. A/J mice showed nonspecific airway hyperresponsiveness to both 5-HT and ACh. DBA/2J mice were hyperresponsive to 5-HT but not to ACh. An airway phenotype that resembled these inbred strains is termed HYPERREACTIVE. The C3H/HeJ and C57BL/6J inbred strains were minimally reactive to either ACh or 5-HT. Airway phenotypes that resembled these minimally reactive strains are termed HYPOREACTIVE. The frequency of HYPERRACTIVE and HYPOREACTIVE offspring from crosses between A/J and C3H/HeJ mice or DBA/2J and C57BL/6J mice is consistent with a single autosomal recessive gene, primarily determining airway hyperresponsiveness to 5-HT. We report linkage studies which suggest that these genes are not closely linked and that 5-HT and ACh airway hyperresponsiveness is inherited independently. The results of these studies suggest that murine nonspecific airway hyperresponsiveness is determined by multiple genes.
Breathing during sleep with mild hypoxia
Authors: Chin K. , Ohi M. , Hirai M. , Kuriyama T. , Sagawa Y. , Kuno K.
Published: December 2017

To investigate ventilatory response to mild hypoxia during non-rapid-eye-movement sleep, we administered approximately 16% O2 (which corresponds to concentrations found in commercial high altitude air craft) to 12 normal subjects by using a Venturi mask, which did not alter the breathing pattern during this study. Under mild hypoxia, inspiratory minute ventilation during sleep showed an initial rapid increase (P less than 0.001) but then declined significantly (P less than 0.001) and stabilized. Stable levels differed among individuals and, compared with those measured before hypoxia, were significantly lower in some subjects, higher in one, and essentially unchanged in the others. The initial rapid increase in minute ventilation after mild hypoxia during sleep correlated with the respective values of hypoxic ventilatory response during the awake state (P less than 0.01), but the final lowered levels did not. We conclude that the ventilatory response after mild hypoxia during sleep is biphasic and hypoxic depression exerts considerable influence on ventilation under mild hypoxia during sleep. So we should take hypoxic depression into consideration to evaluate the response to hypoxia during sleep.
A comparison of the dose-response behavior of canine airways and parenchyma
Authors: Ludwig M. S. , Romero P. V. , Bates J. H.
Published: December 2017

We compared the histamine responsiveness of canine airways and parenchymal tissues in six anesthetized paralyzed open-chest mongrel dogs, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue viscance (Vti). Pressure was measured during tidal breathing (frequency was 0.3 Hz) at the trachea and in three alveolar regions by use of alveolar capsules. Measurements were taken before and after the delivery of increasing concentrations of aerosolized histamine (0.1–30 mg/ml). We found that Vti accounted for 78 +/- 8% of RL under base-line conditions; this proportion remained relatively constant throughout the histamine concentration-response curve. There was a significant correlation between percent change in Vti and percent change in Raw at all levels of histamine-induced constriction (P less than 0.001). Moreover, the sensitivity of the tissues and airways (defined as the concentration of histamine required to double resistance) was remarkably similar. We conclude that, at this frequency of ventilation, Vti accounts for the major portion of RL both under base-line conditions and after histamine-induced constriction. Although increases in RL cannot be attributed solely to events occurring in the airways, the close correlation between changes in Raw and Vti and the similar sensitivities of the two support the use of indexes reflecting changes in airway caliber as an indicator of overall lung histamine responsiveness.
Muscarinic receptor reserve and beta-adrenergic sensitivity in tracheal smooth muscle
Authors: Gunst S. J. , Stropp J. Q. , Flavahan N. A.
Published: December 2017

The possibility that differences in beta-adrenergic sensitivity among canine trachealis muscles contracted with different contractile agonists are related to differences in the receptor-occupancy characteristics of the contractile agonists was investigated. Relaxation to isoproterenol was compared in muscles contracted with the muscarinic agonists McN-A-343 and acetylcholine (ACh). The apparent dissociation constant (pKB) values for the M1-antagonist, pirenzepine, against ACh (6.96 +/- 0.18) and McN-A-343 (6.84 +/- 0.08) were similar. The pKB values for the M3-antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) against ACh (8.76 +/- 0.13) and McN-A-343 (8.71 +/- 0.10) were also similar, suggesting that these agonists were activating the same subtype of muscarinic receptor, probably M3. However, the contractile response to ACh was associated with a greater receptor reserve than that for McN-A-343. Isoproterenol relaxed muscles contracted with McN-A-343 much more effectively than those contracted with an equieffective concentration of ACh. The results suggest that the relative resistance of ACh-induced contractions to relaxation by isoproterenol may not be an inherent quality of muscarinic receptor stimulation. The large receptor reserve available to ACh may act to buffer the contractile response from the inhibitory effects of beta-adrenergic stimulation. Alternatively, ACh may be able to initiate subcellular mechanisms that are unavailable to agonists of lower efficacy.
Sympathetic nerve activity related to local fatigue sensation during static contraction
Authors: Saito M. , Mano T. , Iwase S.
Published: December 2017

The relationship between autonomic nervous activity and psychophysical responses was studied during static exercise in humans. Muscle sympathetic nerve activity (MSNA) recorded by a direct method of microneurography and the intensity of fatigue sensation in working muscles [levels of fatigue sensation (LFS) scale 0–10] were analyzed in 11 male subjects during static handgrip (SHG). SHG was exerted at a tension of 25% of maximal voluntary contraction until the given tension could no longer be sustained. MSNA, represented as total activity (burst number x mean burst amplitude), and LFS increased in a time-dependent process till the end of the SHG. At the termination of the static exercise MSNA had increased an average of 480% of the resting value. In the simple exponential curve, Y = A expBX, where X was LFS and Y was MSNA. The constants A and B estimated from the total experiments were 84.5 and 0.161, respectively. The correlation between LFS and MSNA was statistically significant. There was a large difference in the value of constant B (0.089–0.278) among the subjects, and a relatively small difference in the value of constant A (37.5–133.8). The increases in both MSNA and LFS during SHG may be mainly related to the same afferent volley from working skeletal muscles. The results indicate that the response of the muscle sympathetic nerve to SHG relates to the psychological feelings of fatigue in the working muscles.
Measurement of lung fluid volumes and albumin exclusion in sheep
Authors: Pou N. A. , Roselli R. J. , Parker R. E. , Clanton J. A. , Harris T. R.
Published: December 2017

A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125I- and/or 131I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99mTc-labeled DTPA and 51Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1–3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99mTc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h.
Effect of inert gas switching at depth on decompression outcome in rats
Authors: Lillo R. S. , MacCallum M. E.
Published: December 2017

The present investigation was performed to determine whether inert gas sequencing at depth would affect decompression outcome in rats via the phenomenon of counterdiffusion. Unanesthetized rats (Rattus norvegicus) were subjected to simulated dives in either air, 79% He-21% O2, or 79% Ar-21% O2; depths ranged from 125 to 175 feet of seawater (4.8–6.3 atmospheres absolute). After 1 h at depth, the dive chamber was vented (with depth held constant) over a 5-min period with the same gas as in the chamber (controls) or one of the other two inert gas-O2 mixtures. After the gas switch, a 5- to 35-min period was allowed for gas exchange between the animals and chamber atmosphere before rapid decompression to the surface. Substantial changes in the risk of decompression sickness (DCS) were observed after the gas switch because of differences in potencies (He less than N2 less than Ar) for causing DCS and gas exchange rates (He greater than Ar greater than N2) among the three gases. Based on the predicted gas exchange rates, transient increases or decreases in total inert gas pressure would be expected to occur during these experimental conditions. Because of differences in gas potencies, DCS risk may not directly follow the changes in total inert gas pressure. In fact, a decline in predicted DCS risk may occur even as total inert gas pressure in increasing.
Inspiratory action of separate external and parasternal intercostal muscle contraction
Authors: Budzinska K. , Supinski G. , DiMarco A. F.
Published: December 2017

We have previously shown that electrical stimulation of the thoracic spinal cord produces near maximal activation of the inspiratory intercostal muscles. In the present investigation, we used this technique to evaluate the relative capacity of separate external (EI) and parasternal intercostal (PA) muscle contraction to produce changes in airway pressure and inspired volume. Studies were performed in 23 anesthetized phrenicotomized dogs. Electrical stimuli were applied to the spinal cord after hyperventilation-induced apnea, before and after sequentially severing either the PA or EI muscles from the first through sixth intercostal spaces. During spinal cord stimulation (SCS), measurements were made of inspired volume (delta V) with the airway open and negative airway pressure (delta P) during tracheal occlusion. Compared with control values, sectioning of the PA muscles resulted in a 40.9% reduction in delta P and 35.7% reduction in delta V during SCS. In other animals, initial sectioning of the EI muscles produced reductions in delta P and delta V of 67.4 and 63.0, respectively, during SCS. After subsequent section of the PA muscles, SCS produced only negligible inspired volumes and changes in airway pressure. We conclude that 1) the EI and PA muscles are each capable of generating substantial changes in airway pressure and large inspired volumes and 2) the ventilatory capacity of the EI muscles exceeds that of the PA muscles.
Lung volumes after an increase in lung distension in pneumonectomized ferrets
Authors: McBride J. T.
Published: December 2017

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3–6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2–3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3–5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.
Bronchoalveolar lavage in interstitial lung disease: effect of volume of fluid infused
Authors: Helmers R. A. , Dayton C. S. , Floerchinger C. , Hunninghake G. W.
Published: December 2017

To evaluate the effect of varying infusate volume on the results of bronchoalveolar lavage (BAL) in patients with interstitial lung disease, 55 patients underwent 58 BAL during which both a 100- and 250-ml lavage was performed in the same lobe of the lung. Although the percent of the fluid that was returned and the total numbers of cells were greater in the 250- vs. the 100-ml lavage, there were no significant differences in cell differentials or numbers of cells per milliliter between the 100- and 250-ml BAL. We conclude that infusate volume does not affect cell differentials or numbers of cells per milliliter of bronchoalveolar lavage fluid in patients with interstitial lung disease.
Decreased exercise muscle lactate release after high altitude acclimatization
Authors: Bender P. R. , Groves B. M. , McCullough R. E. , McCullough R. G. , Trad L. , Young A. J. , Cymerman A. , Reeves J. T.
Published: December 2017

Blood lactate concentration during exercise decreases after acclimatization to high altitude, but it is not clear whether there is decreased lactate release from the exercising muscle or if other mechanisms are involved. We measured iliac venous and femoral arterial lactate concentrations and iliac venous blood flow during cycle exercise before and after acclimatization to 4,300 m. During hypoxia, at a given O2 consumption the venous and arterial lactate concentrations, the venous and arterial concentration differences, and the net lactate release were lower after acclimatization than during acute altitude exposure. While breathing O2-enriched air after acclimatization at a given O2 consumption the venous and arterial lactate concentrations and the venous and arterial concentration differences were significantly lower, and the net lactate release tended to be lower than while breathing ambient air at sea level before acclimatization. We conclude that the lower lactate concentration in venous and arterial blood during exercise after altitude acclimatization reflected less net release of lactate by the exercising muscles, and that this likely resulted from the acclimatization process itself rather than the hypoxia per se.
Virus induces airway hyperresponsiveness to tachykinins: role of neutral endopeptidase
Authors: Dusser D. J. , Jacoby D. B. , Djokic T. D. , Rubinstein I. , Borson D. B. , Nadel J. A.
Published: December 2017

We examined the effects of viral respiratory infection by Sendai virus on airway responsiveness to tachykinins in guinea pigs. We measured the change in total pulmonary resistance induced by substance P or capsaicin in the presence or absence of the neutral endopeptidase inhibitor, phosphoramidon, in infected and in noninfected animals. In the absence of phosphoramidon, the bronchoconstrictor responses to substance P and to capsaicin were greater in infected than in noninfected animals. Phosphoramidon did not further potentiate the responses to substance P and to capsaicin in the infected animals, whereas it did so in noninfected animals. Studies performed in vitro showed that nonadrenergic noncholinergic bronchial smooth muscle responses to electrical field stimulation were also increased in tissues from infected animals and that phosphoramidon increased the response of tissues from noninfected animals greatly but increased the responses of tissues from infected animals only slightly. Responses to acetylcholine were unaffected by viral infection. Neutral endopeptidase activity was decreased by 40% in the tracheal epithelial layer of the infected animals. We suggest that respiratory infection by Sendai virus causes enhanced airway responsiveness to tachykinins by decreasing neutral endopeptidase-like activity in the airway epithelium.
Bradykinin produces pulmonary vasodilation in fetal lambs: role of prostaglandin production
Authors: Frantz E. , Soifer S. J. , Clyman R. I. , Heymann M. A.
Published: December 2017

Bradykinin produces pulmonary vasodilation and also stimulates production of other pulmonary vasodilators, including prostaglandin I2 (PGI2) and endothelial-derived relaxing factor. In 12 chronically instrumented fetal lambs, we therefore investigated potential mediation of the bradykinin response by PGI2 or other cyclooxygenase products. A 15-min infusion of bradykinin (approximately 1 microgram/kg estimated fetal wt/min) increased fetal pulmonary blood flow by 522% (P less than 0.05) and decreased pulmonary vascular resistance by 86% (P less than 0.05); plasma 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentration also increased (P less than 0.05). After cyclooxygenase inhibition by indomethacin (3 mg), bradykinin increased pulmonary blood flow by only 350% (P less than 0.05) and decreased pulmonary vascular resistance by 83% (P less than 0.05); plasma 6-keto-PGF1 alpha concentrations did not increase. The increase in pulmonary blood flow produced by bradykinin was greater before administration of indomethacin than after (P less than 0.05). These studies demonstrate that bradykinin produces fetal pulmonary vasodilation by at least two mechanisms, one dependent on and the other independent of PGI2 production, the latter mechanism predominating.
A new technique to demonstrate flow limitation in partial expiratory flow-volume curves in infants
Authors: Ratjen F. , Zinman R. , Wohl M. E.
Published: December 2017

Partial expiratory flow-volume (PEFV) curves in infants are generated by applying a compressive pressure over the chest wall with an inflatable jacket. This study addresses two issues: pressure transmission to and across the chest wall and whether flow limitation can be identified. Eleven infants sedated with chloral hydrate were studied. Pressure transmission to the chest wall, measured with neonatal blood pressure cuffs placed on the infant's body surface, was 72 +/- 4% of jacket pressure during compression maneuvers. The pressure transmission to the air spaces, determined by measuring airway pressure during a compression maneuver against an occluded airway, was 56 +/- 6% of jacket pressure. A significant amount of the applied pressure is therefore lost across both the jacket and chest wall. Rapid pressure oscillations (RPO) were superimposed on static jacket pressures while expiratory flow was measured. Absence of associated oscillations of flow measured at the mouth was taken to indicate that flow was independent of driving pressure and therefore limited. Flow limitation was demonstrable with the RPO technique in all infants for jacket pressures greater than 50 cmH2O; however, it was evident at jacket pressures less than 30 cmH2O jacket pressure in four infants with obstructive airway disease. The RPO technique is a useful adjunct to the compression maneuver utilized to generate PEFV curves in infants because it facilitates the recognition of expiratory flow limitation.
Sustained maximal ventilation after endurance exercise in athletes
Authors: Anholm J. D. , Stray-Gundersen J. , Ramanathan M. , Johnson R. L.
Published: December 2017

Although impaired respiratory muscle performance that persists up to 5 min after exercise is stopped has been demonstrated during exhaustive exercise in normal young men, it is not known whether impaired respiratory muscle function follows endurance exercise to exhaustion in highly trained athletes. To study the effects of exercise on sustained maximal voluntary ventilation immediately after exercise, eight elite cross-country skiers performed a 4-min maximal sustained ventilation (MSV) test before and immediately after exhaustive exercise. Subjects were encouraged to maintain maximal ventilation (VE) throughout the MSV test. To encourage greater effort, rapid visual feedback of VE was provided on a computer terminal along with a target VE based on their 12-s maximum voluntary ventilation (MVV). The subjects (7 males, 1 female) were 18.5 +/- 0.9 yr old (mean +/- SD) and exercised for 62.5 +/- 16.7 min at 77 +/- 5% of their maximum oxygen consumption during which average VE was 106.7 +/- 24.2 l/min BTPS. The mean MVV was 196.0 +/- 29.9 l/min or 107% of their age- and height-predicted MVV. Before exercise the MSV was 86% of the MVV or 176.7 +/- 30.5 l/min, whereas after exercise the MSV was 90% of the MVV or 180.3 +/- 28.9 l/min (P = NS). The total volume of gas expired during the 4-min MSV was 706.7 +/- 121.9 liters before and 721.2 +/- 115.5 liters after exercise (P = NS). In this group of athletes, exhaustive exercise produced no deleterious effects on the ability to perform a 4-min MSV test immediately after exercise.
Influence of muscle mass on sympathetic neural activation during isometric exercise
Authors: Seals D. R.
Published: December 2017

The primary purpose of this study was to determine whether the sympathetic neural activation induced by isometric exercise is influenced by the size of the contracting muscle mass. To address this, in nine healthy subjects (aged 19-27 yr) we measured heart rate, systolic arterial blood pressure, and muscle sympathetic nerve activity in the leg (MSNA; peroneal nerve) before (control) and during 2.5 min of isometric handgrip exercise (30% of maximal voluntary force). Exercise was performed with the right and left arms separately and with both arms simultaneously (random order). During exercise, heart rate, systolic pressure, and MSNA increased above control under all conditions (P less than 0.05). For each variable, the magnitudes of the increases from control to the end of exercise were significantly greater when exercise was performed with two arms compared with either arm alone (P less than 0.05). In general, the increases in heart rate, systolic pressure, and MSNA elicited during two-arm exercise were significantly less than the simple sums of the responses evoked during exercise of each arm separately. These findings indicate that the magnitude of the sympathetic neural activation evoked during isometric exercise in humans is determined in part by the size of the active muscle mass. In addition, our results suggest that the sympathetic cardiovascular adjustments elicited during exercise of separate limbs are not simply additive but instead exhibit an inhibitory interaction (i.e., neural occlusion).
Blood flow distribution in rat muscles during preexercise anticipatory response
Authors: Armstrong R. B. , Hayes D. A. , Delp M. D.
Published: December 2017

Previous work has suggested that preexercise “anticipatory” blood flow distribution in the muscles of rats is influenced by the intensity of the preceding conditioning or training program. The purpose of this study was to carefully control the conditioning programs for control, low-speed conditioned, and high-speed conditioned rats to determine the respective effects on preexercise mean arterial pressure (Pa), heart rate (HR), and blood flow distribution in muscles and other organs. Control (daily placement on treadmill, no exercise), low-speed conditioned (daily treadmill walking up a 12 degree incline at 15 m/min), and high-speed conditioned (daily treadmill galloping up a 12 degree incline at 50 m/min) rats were conditioned for 2-4 wk in their respective programs. On the experimental day, the circulatory variables were measured immediately before exercise by using the same preexercise regimen as during the conditioning sessions. Pa, HR, and blood flow distribution were the same in control and low-speed conditioned rats (P greater than 0.05). However, in high-speed conditioned rats, HR (+9%), Pa (+7%), and white gastrocnemius muscle (+46%) blood flow were higher than in controls (P less than 0.05). The higher white muscle flow was the result of the higher Pa and lower resistance to flow. These data demonstrate that specific changes in preexercise anticipatory blood flow distribution among muscles occur during exercise conditioning programs and that the changes are dependent on the intensity of the conditioning regimen. The mechanisms responsible for the adaptations are not known.
Distribution of elastin and collagen in canine lung alveolar parenchyma
Authors: Oldmixon E. H. , Hoppin F. G.
Published: December 2017

We have quantified the fibrous collagen (predominantly type I) and elastin in four locations of perceived mechanical importance: one quasi-planar feature, the alveolar septum or wall (W), and three linear features, the junction (J) of three septa, the free edges (E) of septa, and the line along which two septa join at a distinct angle or bend (B). The frequencies of these four features on light micrographs and the areas of transections through collagen and elastin seen on electron micrographs were combined to give the volumes of collagen and elastin within each feature. We find that E and B have similar compositions and contain most (4/5) of the parenchymal elastin in their relatively heavy cables. The E and B are interconnected and similar in location and composition, and they may constitute a functional entity in which elastin provides tension over a range of lung volumes, opposing septal tensions. In J and W, elastin is typically sparse and fine. Calculations, however, suggest it contributes the dominant portion of septal tension at lower lung volumes. Elastin may be essential to stabilizing septal configuration. Collagen, on the other hand, is distributed relatively evenly throughout E, B, J, and W, consistent with the role of protecting all components against rupture.
Hemodynamic responses to acute hypoxia, hypobaria, and exercise in subjects susceptible to high-altitude pulmonary edema
Authors: Kawashima A. , Kubo K. , Kobayashi T. , Sekiguchi M.
Published: December 2017

To verify the presence of the constitutional abnormality implicated in the pathogenesis of high-altitude pulmonary edema (HAPE), we evaluated the hemodynamic responses to hypoxia, hypobaria, and exercise in HAPE-susceptible subjects (HAPE-S). HAPE-S were five males with a history of HAPE. Five healthy volunteers who had repeated experiences of mountain climbing without any history of altitude-related problems served as controls. HAPE-S showed much greater increase in pulmonary vascular resistance index (PVRI) than the control subjects, resulting in a much higher level of pulmonary arterial pressure (Ppa), under both acute hypoxia of 15% O2 (Ppa = 29.0 +/- 2.8 vs. 17.8 +/- 0.3 Torr, P less than 0.05) and acute hypobaria of 515 Torr (32.3 +/- 2.8 vs. 19.1 +/- 0.8 Torr, P less than 0.05). Also, PVRI in HAPE-S exhibited a tendency to increase even during light exercise with supine bicycle ergometer (50 W), whereas PVRI in the control subjects significantly decreased, so that HAPE-S showed a greater increase in Ppa (delta Ppa = 16.0 +/- 1.5 vs. 4.9 +/- 1.1 Torr, P less than 0.001) and a greater decrease in arterial oxygen tension (17.8 +/- 4.7 vs. 5.6 +/- 1.7 Torr, P less than 0.05). We thus conclude that HAPE-S have a constitutional abnormality, which can be evaluated at low altitude, in the pulmonary circulatory responses to possible causative factors of HAPE such as hypoxia, hypobaria, and exercise.
Species dependence of baroreceptor effects on ventilation in the cat and the dog
Authors: Maass-Moreno R. , Katona P. G.
Published: December 2017

Reflex respiratory responses to brief carotid baroreceptor stimuli in vagotomized pentobarbital-anesthetized cats were characterized and compared with those reported previously for chloralose-anesthetized dogs. To eliminate effects due to the anesthetic choice, dogs were reexamined under pentobarbital. Stimuli were applied to the isolated carotid sinus (CS) of both animals within a single respiratory phase. The stimuli were either steps triggered after one of four delays (5, 25, 50, and 75% of the control phase duration) and terminated at the end of the phase or pulses lasting 300-500 ms. In cats, 80-mmHg steps during inspiration shortened inspiratory duration by 23.2*, 25.0*, 20.4*, and 4.1% (*P less than 0.01) at the above four delays, respectively; inspired volume decreased by 21.4*, 18.0*, 8.0*, and 2.2%. Steps during expiration lengthened expiration by 38.4*, 37.1*, 21.9*, and 3.4%; expired volume changed less than 4%. Qualitatively, similar responses were obtained with steps 40 mmHg in amplitude. In dogs, 40-mmHg stimuli lengthened both inspiration (by 12.8*, 8.9*, -1.2, and -2.5%) and expiration (by 75.2*, 57.9*, 54.0*, and 61.4*%) but tidal volume did not change. Similar differences were observed when pulses were used. Selective baroreceptor denervation in the cat and occipital arterial occlusion in the dog confirmed that the responses were not chemoreceptor mediated. We conclude that although CS baroreceptor activity inhibits ventilation in both cats and dogs, the pattern of the responses is strongly species dependent.
Airway level at which edema liquid enters the air space of isolated dog lungs
Authors: Conhaim R. L.
Published: December 2017

To identify lung units associated with liquid leakage into the air space in high-pressure pulmonary edema, we perfused air-inflated dog lung lobes with albumin solution to fill the loose peribronchovascular interstitium. Next, we perfused the lobes for 90 s with fluorescent albumin solution then froze the lobes in liquid nitrogen. This procedure confined the fluorescent perfusate to the liquid flux pathway between the circulation and the air space and eliminated the previously filled peribronchovascular cuffs as a source of the fluorescence that entered the air space. We divided each frozen lobe into three horizontal layers and prepared fluorescence-microscopic sections of each layer. In the most apical layers where alveolar flooding was minimal, 10.6 +/- 21.0% (SD) of alveolar ducts were either fluorescence filled or air filled and continuous with fluorescence-filled alveoli. In the same layers, 11.0 +/- 19.0% of respiratory bronchioles were similarly labeled. No terminal bronchioles in these layers were fluorescence labeled. This suggested that the fluorescent albumin entered the air space across the epithelium of respiratory bronchioles, alveolar ducts, or their associated alveoli. To simulate an alternative explanation, i.e., that fluorescence first entered central airways then flowed into peripheral air spaces, we prepared two additional lobes that we first partially inflated with fluorescent albumin then filled to capacity with air. This pushed the fluorescent solution along the airways into the lung periphery. In these lobes the ciliary lining of bronchi and terminal bronchioles was fluorescence coated. By comparison, cilia in fluorescence-perfused lobes were not coated. We conclude that alveolar flooding in hydrostatic pulmonary edema occurs across the epithelium of alveolar ducts, respiratory bronchioles, or their associated alveoli.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of vagal C-fibers alters timing and distribution of respiratory motor output in cats
Authors: Holmes H. R. , Remmers J. E.
Published: December 2017

Pulmonary vascular congestion or pulmonary embolism in humans produces shallow tachypnea, and indirect experimental evidence suggests that this characteristic breathing pattern may result from activation of vagal unmyelinated afferents from the lung. We have investigated, in decerebrate cats, reflex changes in breathing pattern and in the activation of the diaphragm, posterior cricoarytenoid, and thyroarytenoid muscles caused by activating C-fiber afferents in the vagus nerve. The right vagus nerve was sectioned distal to the origin of the recurrent laryngeal nerve, eliminating vagal afferent traffic although preserving motor innervation of the larynx on that side. The left cervical vagus was stimulated electrically, and efferent activation of the laryngeal muscles was avoided by cutting the left recurrent laryngeal nerve. Transmission to the brain of vagal afferent traffic resulting from this stimulation was controlled by graded cold block of the nerve cranial to the site of application of the stimulus. Activation of C-fibers, when A-fibers were blocked, significantly decreased respiratory period and amplitude of diaphragm inspiratory burst. In addition, this selective activation of vagal C-fibers augmented postinspiratory activity of the diaphragm and recruited phasic expiratory bursts in the thyroarytenoid. We conclude that, in unanesthetized decerebrate cats, afferent traffic of vagal C-fibers initiates a pontomedullary reflex that increases respiratory frequency, decreases tidal volume, and augments braking of expiratory airflow.
Amino acid exchange between plasma and erythrocytes in vivo in humans
Authors: Darmaun D. , Froguel P. , Rongier M. , Robert J. J.
Published: December 2017

To study amino acid exchange between plasma and erythrocytes in vivo, 4-h primed, continuous intravenous infusions of L-[1-13C]leucine, [15N]glycine, and L-[15N]alanine were administered to five healthy young men in the postabsorptive state. Stable isotope enrichments and amino acid levels were determined by gas chromatography-mass spectrometry in both plasma and whole blood and estimated (using hematocrit) in erythrocytes. A high concentration gradient across the erythrocyte membrane was consistently found for glycine (552 +/- 268 microM in erythrocytes vs. 155 +/- 35 microM in plasma), but not for leucine or alanine. A steady-state isotopic enrichment was observed in whole blood as well as plasma for each amino acid in every subject. Steady-state [13C]leucine enrichment in erythrocytes did not differ from plasma enrichment at steady state, the ratio of erythrocyte to plasma enrichment being 1.03 +/- 0.20 (95% confidence limits = 0.78-1.28); in contrast, this ratio reached only 0.23 +/- 0.04 and 0.59 +/- 0.09 (confidence limits 0.18-0.28 and 0.48-0.70) for [15N]glycine and [15N]alanine at steady state, respectively. These results suggest that most of erythrocyte leucine is exchangeable with plasma, whereas only a fraction of erythrocyte glycine and alanine is involved in exchange with plasma in vivo.