bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased leukotriene C4 in ethchlorvynol-induced acute lung injury in dogs
Authors: Stephenson A. H. , Sprague R. S. , Dahms T. E. , Lonigro A. J.
Published: December 2017

We investigated whether ethchlorvynol (ECV)-induced acute lung injury (ALI) is associated with an increase in leukotriene C4 (LTC4) production. In six pentobarbital sodium-anesthetized dogs, ECV (15 mg/kg iv) introduced into the pulmonary circulation resulted in a 164 +/- 31% increase in extravascular lung water 120 min after ECV administration. Concomitantly, the mean (+/- SE) concentration of LTC4 in arterial plasma measured by radioimmunoassay following 80% EtOH precipitation, XAD-7 extraction and high-pressure liquid chromatography purification was 5.0 +/- 1.3 pg/ml, unchanged from control (pre-ECV) values. In contrast, in pulmonary edema fluid 120 min post-ECV, the LTC4 concentration was 35.2 +/- 10.8 pg/ml, sevenfold greater than those values found in the arterial plasma (P less than 0.01). In six additional dogs, 120 min after unilateral ALI had been induced with ECV (9 mg/kg iv), LTC4 in the bronchoalveolar lavage (BAL) of the uninjured lung was 12.1 +/- 1.5 pg/ml, unchanged from pre-ECV values, whereas, LTC4 in the BAL of the injured lung increased from a control value of 10.2 +/- 1.6 to 24.2 +/- 3.5 pg/ml (P less than 0.01) 120 min after ECV administration. These results demonstrate that, in ECV-induced acute lung injury, LTC4 concentrations in pulmonary edema fluid are considerably greater than those found in arterial plasma in the case of bilateral acute lung injury and significantly greater in the BAL of the injured lung compared with the uninjured lung in the case of unilateral acute lung injury. The results are a necessary first step in support of the hypothesis that leukotrienes participate in the altered permeability of ECV-induced acute lung injury.
Micropuncture measurement of alveolar liquid pressure in excised dog lung lobes
Authors: Raj J. U. , Conhaim R. L. , Bhattacharya J.
Published: December 2017

We have investigated the mechanism of alveolar liquid filling in pulmonary edema. We excised, degassed, and intrabronchially filled 14 dog lung lobes from nine dogs with 75, 150, 225, or 350 ml of 5% albumin solution, and then air inflated the lobes to a constant airway pressure of 25 cmH2O. By use of micropipettes, we punctured subpleural alveoli to measure alveolar liquid pressure by the servo-null technique. Alveolar liquid pressure was constant in all lobes despite differences in lobe liquid volume and averaged 10.6 +/- 1.3 cmH2O. Thus, in all lobes a constant pressure drop of 14.4 cmH2O existed from airway to alveolar liquid across the air-liquid interface. We attribute this finding, on the basis of the Laplace equation, to an air-liquid interface of constant radius in all the lobes. In fact, we calculated from the Laplace equation an air-liquid interface radius which equalled morphological estimates of alveolar radius. We conclude that in the steady state, alveoli that contained liquid have a constant radius of curvature of the air-liquid interface possibly because they are always completely liquid filled.
Neither anticoagulant nor nonanticoagulant heparin affects monocrotaline lung injury
Authors: Fasules J. W. , Stenmark K. R. , Henson P. M. , Voelkel N. F. , Reeves J. T.
Published: December 2017

The administration of monocrotaline to rats causes pulmonary vascular leak within 1 wk followed in 2–3 wk by perivascular proliferation and fatal pulmonary hypertension. Possibly blocking the proliferation might block the pulmonary hypertension, providing insight into its mechanism. Because heparin, given as an antiproliferative agent, reduced hypoxic pulmonary hypertension in mice, it might also block monocrotaline-induced pulmonary hypertension. Alternatively, anticoagulation could worsen the lung injury. We found that heparin (300 and 600 U/kg sc twice daily) inhibited clotting in rats given monocrotaline but did not change the vascular leak, the right ventricular pressure, the right ventricular hypertrophy, the increased medial thickness of the pulmonary arterioles, or the production of a slow-reacting substance of anaphylaxis-like material by the lungs. A nonanticoagulant heparin fragment (2 mg/kg sc twice daily), given to avoid anticoagulation also did not influence the monocrotaline injury. Thus neither anticoagulant nor nonanticoagulant heparin either attenuated or worsened the measured effects of monocrotaline.
Medullary inspiratory activity: influence of intercostal tendon organs and muscle spindle endings
Authors: Bolser D. C. , Lindsey B. G. , Shannon R.
Published: December 2017

Studies were conducted to determine the effects of intercostal muscle spindle endings (MSEs) and tendon organs (TOs) on medullary inspiratory activity in decerebrate and allobarbital-anesthetized cats. Impeded muscle contractions, elicited by electrical stimulation of the peripheral cut end of the T6 ventral root, were used to stimulate external and internal intercostal TOs without MSEs. Impeded contractions of either the external or internal intercostal muscles reduced phrenic and medullary inspiratory neuronal activities. Vibration was used to selectively stimulate external or internal intercostal MSEs (90 and 40 micron amplitude, respectively). Selective stimulation of either external or internal intercostal MSEs did not change phrenic or medullary inspiratory neuronal activities. It is concluded that both external and internal intercostal TOs have a generalized inhibitory effect on medullary inspiratory activity and intercostal MSEs have no effect on medullary inspiratory activity.
Menstrual cycle phase dissociation of blood glucose homeostasis during exercise
Authors: Lavoie J. M. , Dionne N. , Helie R. , Brisson G. R.
Published: December 2017

The purpose of this investigation was to evaluate the effects of 24-h carbohydrate-poor diet on metabolic and hormonal responses induced by prolonged exercise in both follicular (FP) and luteal (LP) phases of the menstrual cycle. At mid-FP and at mid-LP, seven eumenorrheic young women [means +/- SE; chronological age, 21.1 +/- 0.6 yr; O2 uptake (VO2) peak, 43.7 +/- 2.0 ml X kg-1 X min-1; body fat, 19.2 +/- 2.0%] were subjected to a 90-min bicycle exercise period at an intensity representing 63% of their measured VO2 peak. Venous blood samples obtained before and during exercise were analyzed for levels of substrates (glucose, lactate, free fatty acids, glycerol) and hormones (luteinizing hormone, progesterone, estradiol, insulin, glucagon, cortisol, catecholamines). Contrary to FP, a significant (P less than 0.01) decrease in blood glucose concentration was observed after 70 and 90 min of exercise during LP. Significant phase differences were also observed for blood lactate (highest in FP), cortisol (highest in LP), and progesterone (highest in LP). Although not significantly different, tendencies for menstrual phase dissociations were noticed for some of the other measured variables. Hence, a menstrual phase dissociation in circulating glucose level, unmasked by a prolonged exercise performed after a 24-h carbohydrate-poor diet, suggests to the authors a specific metabolic involvement for gonadotrophic and/or gonadal hormones.
Effect of a dopamine antagonist on ventilation during sustained hypoxia in mice
Authors: Olson L. G. , Saunders N. A.
Published: December 2017

To test the hypothesis that dopamine accumulated in the carotid body limits hyperventilation during acclimatization to sustained hypoxia, we administered the dopamine antagonist droperidol to mice undergoing acclimatization to an inspired O2 fraction (FIo2) of 0.1. Twelve mice were exposed to hypoxia for 10 days and ventilation in 10% O2 and in 7% CO2 in air were measured daily by a plethysmographic method. Under both conditions ventilation increased during acclimatization to hypoxia: ventilation in 10% O2 increased from 39.4 +/- 3.8 (mean +/- SE) ml/min before exposure to sustained hypoxia to 72.2 +/- 4.2 ml/min after 3 days of continuous hypoxia, and ventilation in 7% CO2 in air at the same time increased from 113.2 +/- 5.4 ml/min to 140.0 +/- 5.6 ml/min. Twelve mice were exposed to FIo2 of 0.1 for 10 days and received droperidol (300 micrograms/kg intraperitoneally) before exposure to sustained hypoxia and on the 2nd, 4th, and 8th days of continuous hypoxia. Before exposure to sustained hypoxia, droperidol increased ventilation in 10% O2 from 40.1 +/- 2.5 ml/min to 72.5 +/- 5.2 ml/min, but after 2, 4, and 8 days of continuous hypoxia droperidol caused an acute fall in ventilation (ventilation in 10% O2 after droperidol on day 2: 49.1 +/- 3.1 ml/min, on day 4: 44.4 +/- 3.7 ml/min, and on day 8: 27.8 +/- 3.4 ml/min). Two days after the animals were returned to room air, ventilation in 10% O2 again increased in response to droperidol. We conclude that dopamine in the carotid body does not limit ventilatory responses to hypoxia during acclimatization to sustained hypoxia.
Ventilation-perfusion inequality during constant-flow ventilation
Authors: Schumacker P. T. , Sznajder J. I. , Nahum A. , Wood L. D.
Published: December 2017

Previous work by Lehnert et al. (J. Appl. Physiol. 53:483–489, 1982) has demonstrated that adequate alveolar ventilation can be maintained during apnea in anesthetized dogs by delivering a continuous stream of inspired ventilation through cannulas aimed down the main-stem bronchi. Because an asymmetric distribution of ventilation might introduce ventilation-perfusion (VA/Q) inequality, we compared gas exchange efficiency in nine anesthetized and paralyzed dogs during constant-flow ventilation (CFV) and conventional ventilation (intermittent positive-pressure ventilation, IPPV). Gas exchange was assessed using the multiple inert gas elimination technique. During CFV at 3 l X kg-1 X min-1, lung volume, retention-excretion differences (R-E*) for low- and medium-solubility gases, and the log standard deviation of blood flow (log SD Q) increased, compared with the findings during IPPV. Reducing CFV flow rate to 1 l X kg-1 X min-1 at constant lung volume improved R-E* and log SD Q, but significant VA/Q inequality compared with that at IPPV remained and arterial PCO2 rose. Comparison of IPPV and CFV at the same mean lung volume showed a similar reversible deterioration in gas exchange efficiency during CFV. We conclude that CFV causes significant VA/Q inequality which may be due to nonuniform ventilation distribution and a redistribution of pulmonary blood flow.
Differences in brain cytochrome responses to carbon monoxide and cyanide in vivo
Authors: Piantadosi C. A. , Sylvia A. L. , Jobsis-Vandervliet F. F.
Published: December 2017

Cytochrome oxidation-reduction responses to two mitochondrial electron transport inhibitors, carbon monoxide (CO) and cyanide (CN), were studied in the intact brains of fluorocarbon-circulated rats. In vivo reflectance spectrophotometry indicated that cortical b-type cytochromes (564 nm) were highly resistant to reduction by CN in the presence of O2 but showed reduction responses to the administration of 1–5% CO in 90% O2. In contrast, cyanide-sensitive cytochromes aa3 (605 nm) and c + c1 (551 nm) did not increase their reduction levels during exposure to 5% CO in 90% O2. The in vivo CO-mediated b-cytochrome reduction responses did not occur after pretreatment with the cytochrome b inhibitor, antimycin A. Transmission spectrophotometry of superfused hemoglobin-free rat brain slices confirmed cortical b-type cytochromes to be CN-resistant in the presence of O2. Another cytochrome absorbing at 445 nm also was resistant to reduction by 1-mM cyanide in vitro, but it could be reduced anaerobically. The reduced 445-nm cytochrome bound CO in the presence of cyanide. We postulate that this CN-resistant CO binding component might account for in vivo cytochrome aa3-CO interactions and directly or indirectly modulate cytochrome b reduction responses to CO. In any event, the spectral data indicate different primary tissue target sites for CO and CN in living rat brain and also suggest different bioenergetic consequences of exposure to the two agents.
Effect of aging on tracheal mucociliary clearance in beagle dogs
Authors: Whaley S. L. , Muggenburg B. A. , Seiler F. A. , Wolff R. K.
Published: December 2017

Tracheal mucous velocity measurements were made in 24 beagle dogs in five age groups, using a gamma camera to detect movement of instilled 99mTc-macroaggregated albumin. Age groups were defined as immature (9–10 mo), young adult (2.8–3.0 yr), middle aged (6.7–6.9 yr), mature (9.6–9.8 yr), and aged dogs (13.6–16.2 yr). Mean velocities were 3.6 +/- 0.4 (SE) mm/min in the immature dogs, 9.7 +/- 0.6 mm/min in the young adults, 6.9 +/- 0.5 mm/min in the middle-aged dogs, 3.5 +/- 0.8 mm/min in the mature dogs, and 2.9 +/- 0.5 mm/min in the aged dogs. Tracheal mucous velocity was significantly (P less than 0.05) greater in the young adult and middle-aged groups compared with the immature, mature, and aged dogs. This pattern of age-related changes was noted to be similar to age-related changes described for certain pulmonary function measurements.
Lung epithelial permeability to aerosolized solutes: relation to position
Authors: Meignan M. , Rosso J. , Robert R.
Published: December 2017

The lung epithelial permeability to inhaled solutes is primarily attributed to the degree of distension of the interepithelial junctions and thus of the alveolar volume. To assess this hypothesis, a submicronic aerosol of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) was inhaled by eight normal subjects in left lateral decubitus (LLD). The regional lung clearance of 99mTc-DTPA was measured in LLD, then in right lateral decubitus (RLD) to reverse the relative distension of the alveoli. Although in LLD the deposition of the aerosol is the greatest in the gravity-dependent regions of the left lung, their 99mTc-DTPA clearances are significantly lower than those of the nondependent regions of the right lung (0.7 +/- 0.3 vs. 2 +/- 0.8%/min, P less than 0.001). In RLD, these regions placed in opposite positions significantly reversed their clearances (1.6 +/- 0.8 vs. 0.6 +/- 0.2%/min, P less than 0.001). Results indicate in lateral decubitus a gravity gradient of 99mTc-DTPA clearances independent of the aerosol deposition. This gradient of epithelial permeability to solutes appears to be influenced by the gradient of alveolar volume.
Substrate utilization and enzymes in skeletal muscle of extremely endurance-trained men
Authors: Jansson E. , Kaijser L.
Published: December 2017

Substrate utilization during exercise at 65% of maximal O2 uptake (VO2 max) and biochemical characteristics of vastus lateralis were compared between five endurance-trained (T) and five untrained subjects (U). The oxidative enzyme activities were 100% greater in T than in U, and VO2 max was 50% higher. A greater proportion of ATP regeneration occurred through oxidative processes in T than in U (smaller leg lactate release and smaller muscle lactate accumulation). The respiratory exchange ratio together with the local leg respiratory quotient indicated a greater contribution of fat to oxidative metabolism in T than U (53 vs. 33%). No difference, however, in the ratio of plasma free fatty acid extraction to O2 extraction by the working legs was found between T and U. Thus it could be calculated that a greater fraction of fat oxidation would have been covered by intramuscular triglycerides in T than in U (34 vs. 15%, P less than 0.05). T in comparison to U were further characterized by a smaller glycogen breakdown and a smaller glucose uptake, which may have been one contributing factor that prevented the blood glucose level from falling in T. The greater leg muscle citrate concentration in T could have been one factor mediating a lower carbohydrate utilization as a response to an increase in the relative proportion of fat oxidation.
Longitudinal elastic wave propagation in pulmonary parenchyma
Authors: Butler J. P. , Lehr J. L. , Drazen J. M.
Published: December 2017

Consideration of the lung as an elastic continuum led us to investigate the possible propagation of elastic waves. Here the relevant stiffness and density are given by the Lame constants and density of the parenchyma. To test this hypothesis, we measured propagation velocities (c) in dog lobes by recording transit times of a velocity impulse on one side of the lobe and the subsequent arrival on the other side. We compared our measured values of c with elastic longitudinal wave velocities (c long) predicted by values of elastic moduli given by Lai-Fook et al. (J. Appl. Physiol. 40: 508–513, 1976) as a function of translobar pressure (PL) and our measured densities. Good agreement was found between c and c long. Typical values of c ranged from 250–1,500 cm/s as PL ranged from 2–20 cmH2O. No systematic difference in the c-c long relation was found between inflation and deflation, suggesting that the elastic moduli of lungs are essentially a function of pressure. No significant effect was observed by changing the physical properties of the gas within the lobe [air vs. He vs. sulfur hexafluoride (SF6)], suggesting that indeed we were observing waves associated with the coupling of parenchymal density to parenchymal stiffness.
Lung mechanics and connective tissue proteins in diabetic Bio-Breeding/Worcester Wistar rats
Authors: Sahebjami H. , Denholm D.
Published: December 2017

We studied lungs of spontaneously diabetic Bio-Breeding/Worcester (BB/W) Wistar rats which resemble human insulin-dependent diabetes mellitus. Compared with the age-matched control group, the body weight of the diabetic rats tended to be smaller and lung wet and dry weight were similar, but lung dry weight, relative to body weight and to lung wet weight, was significantly larger. Both air and saline lung volumes were reduced in the diabetic rats, and volume-pressure (V-P) curves expressed as a percent of maximal lung volume were significantly shifted downward and to the right of those in the control group over the midportion. Total DNA and RNA contents were similar in both groups, whereas protein content and concentration and protein/DNA and RNA/DNA ratios were significantly reduced in the diabetic rats. In contrast, content and concentration of 4-hydroxy-L-proline, elastin, and crude connective tissue were significantly higher in the diabetic group. We conclude that the increase in connective tissue proteins in the BB/W rats is most likely responsible for the shift in the V-P curves.
Cationic neutrophil proteins increase transendothelial albumin movement
Authors: Peterson M. W. , Stone P. , Shasby D. M.
Published: December 2017

Neutrophils play a role in the development of pulmonary edema in many models of the adult respiratory distress syndrome, but the mechanism of their action is not completely understood. We asked whether two neutrophil secretory products, human neutrophil cationic protein (NCP) and human neutrophil elastase (HNE), would nonenzymatically alter the movement of albumin across a cultured endothelial monolayer. Both enzymes were inactivated by heating before use. HNE was additionally enzymatically inactivated with a chloromethylketone oligopeptide (CMK) inhibitor and with alpha 1-proteinase inhibitor (alpha 1-PI). Heated NCP, heated HNE, and CMK-complexed HNE all increased transendothelial albumin transfer. The cation protamine also increased albumin transfer across the endothelium and this increase was blocked by heparin. Alpha 1-PI and fetal bovine serum also prevented the cationic proteins from increasing albumin transfer. Using the release of lactate dehydrogenase as a marker of cytotoxicity, heated HNE was toxic to endothelial cells, heated NCP had only minimal toxicity, and protamine had no toxicity. Changes in endothelial cell shape with gap formation was seen after exposure to both heated HNE and heated NCP. Both the cytotoxicity associated with heated HNE and the cell shape changes associated with heated NCP and heated HNE could be blocked by heparin. These results suggest that in addition to neutrophil proteases and reactive O2 molecules, neutrophil-derived cationic proteins can directly and nonenzymatically contribute to edema formation during acute inflammation.
Changes in lung volume and breathing pattern during exercise and CO2 inhalation in humans
Authors: Cha E. J. , Sedlock D. , Yamashiro S. M.
Published: December 2017

Lung volume changes during CO2 inhalation and exercise were compared in seven human subjects. Expiratory reserve volume (ERV) normalized by vital capacity (VC) was used as an index of end-expiratory lung volume (EELV). Work loads tried were 30, 60, and 90 W and inspired CO2 concentrations were 3.5 and 5.0%. Exercise at 30 W led to a significant decrease in EELV, by 7% VC (P less than 0.005), with no further change at higher levels of exercise (P greater than 0.1). Both 3.5 and 5.0% CO2 inhalation resulted in an increase in EELV that was not statistically significant (3% VC, P greater than 0.1). A possible linkage of this different EELV behavior to breathing pattern was tested. The tidal volume-inspiratory duration curve shifted to a higher volume region during exercise compared with CO2 inhalation. Consequently, the volume-time threshold characteristic was better described by an end-inspiratory lung volume-inspiratory duration plot, resulting in a common relationship under these two different stimuli. These results suggest that the depth and rate of breathing in humans can be affected by not only phasic but also tonic components. A decrease in functional residual capacity or EELV was peculiar to exercise and should be associated with increased mechanical efficiency compared with CO2 inhalation. Theoretical predictions based on work of breathing optimization via a decreased EELV seemed to be capable of explaining isocapnic exercise hyperpnea in conjunction with proportional control of arterial CO2 tension.
Leukotriene inhibitors do not block hypoxic pulmonary vasoconstriction in dogs
Authors: Schuster D. P. , Dennis D. R.
Published: December 2017

We studied whether intravenously administered inhibitors of leukotriene synthesis (diethylcarbamazine, DEC) or end-organ effect (FPL-55712) would change the distribution of regional pulmonary blood flow (rPBF) caused by left lower lobe (LLL) alveolar hypoxia in dogs. Both drugs failed to alter rPBF. In addition, the pressor response to whole-lung hypoxia was not blocked by an FPL-55712 infusion. On the other hand, nitroprusside, as a nonspecific vasodilator also administered intravenously, was able to partially reverse the effects of LLL hypoxia on rPBF. Thus our data do not support a role for leukotriene mediation of hypoxic pulmonary vasoconstriction in dogs.
Beta-blockade reduces tidal volume during heavy exercise in trained and untrained men
Authors: Joyner M. J. , Jilka S. M. , Taylor J. A. , Kalis J. K. , Nittolo J. , Hicks R. W. , Lohman T. G. , Wilmore J. H.
Published: December 2017

The effects of beta-blockade on tidal volume (VT), breath cycle timing, and respiratory drive were evaluated in 14 endurance-trained [maximum O2 uptake (VO2max) approximately 65 ml X kg-1 X min-1] and 14 untrained (VO2max approximately 50 ml X kg-1 X min-1) male subjects at 45, 60, and 75% of unblocked VO2max and at VO2max. Propranolol (PROP, 80 mg twice daily), atenolol (ATEN, 100 mg once a day) and placebo (PLAC) were administered in a randomized double-blind design. In both subject groups both drugs attenuated the increases in VT associated with increasing work rate. CO2 production (VCO2) was not changed by either drug during submaximal exercise but was reduced in both subject groups by both drugs during maximal exercise. The relationship between minute ventilation (VE) and VCO2 was unaltered by either drug in both subject groups due to increases in breathing frequency. In trained subjects VT was reduced during maximal exercise from 2.58 l/breath on PLAC to 2.21 l/breath on PROP and to 2.44 l/breath on ATEN. In untrained subjects VT at maximal exercise was reduced from 2.30 l/breath on PLAC to 1.99 on PROP and 2.12 on ATEN. These observations indicate that 1) since VE vs. VCO2 was not altered by beta-adrenergic blockade, the changes in VT and f did not result from a general blunting of the ventilatory response to exercise during beta-adrenergic blockade; and 2) blockade of beta 1- and beta 2-receptors with PROP caused larger reductions in VT compared with blockade of beta 1-receptors only (ATEN), suggesting that beta 2-mediated bronchodilation plays a role in the VT response to heavy exercise.
Partitioning of pulmonary resistance in calves
Authors: Gustin P. , Lomba F. , Bakima J. , Lekeux P. , Van de Woestijne K. P.
Published: December 2017

Nine right apical lobes of healthy Friesian calves and 10 right apical lobes of double-muscled calves of Belgian White and Blue (BWB) breed were suspended in an airtight box, inflated at a constant transpulmonary pressure (Ptp), and subjected to quasi-sinusoidal pressure changes (amplitude: 0.5 kPa) at a frequency of 30 cycles/min. Lobar resistance (RL) was partitioned at six different lung volumes into three components: central airway resistance (Rc), small airway resistance (Rp), and tissue resistance (Rt). Pressure in small airways (2–3 mm ID) was measured with a retrograde catheter. Alveolar pressure was sampled in capsules glued onto the punctured pleural surface. RL was minimal at values of Ptp comprised between 0.5 and 0.7 kPa and increased at higher and lower values of Ptp. At a Ptp of 0.5 kPa, Rc, Rp, and Rt represented 30, 15, and 55% of RL, respectively, in Friesian calves and 25, 25, and 50% in BWB calves. Rp increased markedly at low lung volumes. Rt was responsible for the increase of RL at high Ptp. Rc tended to decrease at high Ptp. The significantly higher values of Rp in BWB calves (P less than 0.05) might explain the sensitivity of this breed to severe bronchopneumonia.
Effect of endogenous prostaglandins on acetylcholine release from dog trachealis muscle
Authors: Shore S. , Collier B. , Martin J. G.
Published: December 2017

We used a radioenzymatic technique to measure effects of the prostaglandin synthesis inhibitor indomethacin and of exogenous prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) on acetylcholine (ACh) efflux from canine tracheal smooth muscle (TSM) during sustained electrical field stimulation (EFS; 2 Hz, 2 ms pulse duration, 50 V for 15 min). ACh efflux from indomethacin (INDO, 10(-6) M)-pretreated and control TSM increased with consecutive stimulations. However, efflux of ACh was greater in INDO-treated than control muscles. INDO increased the tension produced by TSM in response to EFS. Neither PGE2 (10(-8) M) nor PGI2 (10(-6) M) had any effect on ACh efflux from INDO-pretreated TSM during the first of three periods of EFS. However, PGI2 and PGE2 prevented the progressive increase in ACh efflux observed on subsequent stimulations. PGE2 but not PGI2 decreased contractions of TSM caused by EFS. Our results demonstrate that endogenous prostaglandins, probably PGE2, do inhibit EFS-evoked ACh release from canine TSM in vitro, but suggest that these prostaglandins modulate EFS-evoked contractions predominantly by postsynaptic mechanisms.
Concentration-dependent interaction of theophylline with d-tubocurarine
Authors: Fuke N. , Martyn J. , Kim C. S. , Basta S.
Published: December 2017

The interaction of theophylline with d-tubocurarine chloride (dTC) was examined in rabbits. After steady-state subtherapeutic (less than 10 mg/l), therapeutic (10–20 mg/l), and toxic (greater than 20 mg/l) concentrations of theophylline, dose-response curves for dTC were determined and compared with controls that received no theophylline. At therapeutic concentrations of theophylline the effective dose for 50% inhibition of twitch (ED50) for dTC (mean +/- SE, 0.115 +/- 0.016 mg/kg) was significantly shifted to the left in comparison with the control (0.165 +/-0.008 mg/kg). The ED50 of dTC for the subtherapeutic group was 0.143 +/- 0.011 mg/kg, which was less than the control but not of statistical significance (P = 0.1). The ED50 for the toxic theophylline group was 0.168 +/- 0.003 mg/kg, which was not significantly different from controls but significantly different from the theophylline therapeutic and subtherapeutic groups. Thus, toxic concentrations of theophylline reversed the potentiating effects of therapeutic and subtherapeutic concentrations of dTC dose-response curves. Therefore, depending on concentration, theophylline exhibits a biphasic interaction with dTC. Surgical patients on theophylline may require less dTC intraoperatively. More importantly, the use of theophylline in the postoperative period to reverse anesthetic effects may result in recurarization.
Longitudinal study of ventilation threshold and maximal O2 uptake in athletic boys
Authors: Paterson D. H. , McLellan T. M. , Stella R. S. , Cunningham D. A.
Published: December 2017

Ventilation threshold (VET) and peak O2 uptake (VO2max) were determined annually from ages 11 to 15 yr in 18 athletic boys. The treadmill protocol consisted of a constant-run speed with grade increments every second minute. Ventilation, VO2, and CO2 production were measured using online open-circuit spirometry. Coefficients of variation for determination of VO2max and VET were 3.4 and 5.6%, respectively. VO2max increased across age 11–15 yr, from 60.8 to 68.0 ml X kg-1 X min-1. VET at 11 yr was 34.4 and at 15 yr 41.9 ml X kg-1 X min-1, thus increasing from 56 to 62% of VO2max. Previous studies of children have shown a decline of VET relative to VO2max across age; however, in the present study the increase may have been due to the training of the boys in competitive athletics. However, the trained youth did not achieve the high relative threshold of trained adults. Across age, both VO2max and VET scaled to weight to the power 1 (in a log-log transformation). The increase in VO2max (l/min) showed greatest increments corresponding to gains in size (a growth curve), whereas increases of VET were consistent year to year. Thus VET was altered independently of VO2max. Factors other than size (and presumably muscle mass) such as the maturation of an enzymatic profile of fast glycolytic fibers might have an important influence on the threshold during youth.
Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2
Authors: Tilden S. J. , Underwood D. C. , Cowen K. H. , Wegmann M. J. , Graybar G. B. , Hyman A. L. , McNamara D. B. , Kadowitz P. J.
Published: December 2017

The influence of OKY 1581, a thromboxane synthase inhibitor, on airway responses to arachidonic acid and endoperoxide, [prostaglandin (PG) H2], were investigated in anesthetized, paralyzed, mechanically ventilated cats. Intravenous injections of arachidonic acid and PGH2 caused dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic and static compliance. OKY 1581 significantly decreased airway responses to arachidonic acid but not to PGH2. Sodium meclofenamate, a cyclooxygenase inhibitor, abolished airway responses to arachidonic acid but had no effect on airway responses to PGH2. OKY 1581 or meclofenamate has no effect on airway responses to PGF2 alpha, PGD2, or U 46619, a thromboxane mimic. In microsomal fractions from the lung, OKY 1581 inhibited thromboxane formation without decreasing prostacyclin synthesis or cyclooxygenase activity. These studies show that OKY 1581 is a selective thromboxane synthesis inhibitor in the cat lung and suggest that a substantial part of the bronchoconstrictor response to arachidonic acid is due to thromboxane A2 formation. Moreover, the present data suggest that airway responses to endogenously released and exogenous PGH2 are mediated differently and that a significant part of the response to exogenous PGH2 may be due to activation of an endoperoxide/thromboxane receptor, since responses to PGH2 are blocked by the thromboxane receptor antagonist SQ 29548.
Relationship between intracellular pH and energy metabolism in dog brain as measured by 31P-NMR
Authors: Nioka S. , Chance B. , Hilberman M. , Subramanian H. V. , Leigh J. S. , Veech R. L. , Forster R. E.
Published: December 2017

The relationships between pHi (intracellular pH) and phosphate compounds were evaluated by nuclear magnetic resonance (NMR) in normo-, hypo-, and hypercapnia, obtained by changing fractional inspired concentration of CO2 in dogs anesthetized with 0.75% isoflurane and 66% N2O. Phosphocreatine (PCr) fell by 2.02 mM and Pi (inorganic phosphate) rose by 1.92 mM due to pHi shift from 7.10 to 6.83 during hypercapnia. The stoichiometric coefficient was 1.05 (r2 = 0.78) on log PCr/Cr against pHi, showing minimum change of ADP/ATP and equilibrium of creatine kinase in the pH range of 6.7 to 7.25. [ADP] varied from 21.6 +/- 4.1 microM in control (pHi = 7.10) to 26.8 +/- 6.3 microM in hypercapnia (pHi = 6.83) and 24.0 +/- 6.8 microM in hypocapnia (pHi = 7.17). ATP/ADP X Pi decreased from 66.4 +/- 17.1 mM-1 during normocapnia to 25.8 +/- 6.3 mM-1 in hypercapnia. The ADP values are near the in vitro Km; thus ADP is the main controller. The velocity of oxidative metabolism (V) in relation to its maximum (Vmax) as calculated by a steady-state Michaelis-Menten formulation is approximately 50% in normocapnia. In acidosis (pH 6.7) and alkalosis (pH 7.25), V/Vmax is 10% higher than the normocapnic brain. This increase of V/Vmax is required to maintain cellular homeostasis of energy metabolism in the face of either inhibition at extremes of pH or higher ATPase activity.
Lactate as substrate for glycogen resynthesis after exercise
Authors: Stevenson R. W. , Mitchell D. R. , Hendrick G. K. , Rainey R. , Cherrington A. D. , Frizzell R. T.
Published: December 2017

Muscle glycogen levels in the perfused rat hemicorpus preparation were reduced two-thirds by electrical stimulation plus exposure to epinephrine (10(-7) M) for 30 min. During the contraction period muscle lactate concentrations increased from a control level of 3.6 +/- 0.6 to a final value of 24.1 +/- 1.6 mumol/g muscle. To determine whether the lactate that had accumulated in muscle during contraction could be used to resynthesize glycogen, glycogen levels were determined after 1–3 h of recovery from the contraction period during which time the perfusion medium (flow-through system) contained low (1.3 mmol/l) or high (10.5 or 18 mmol/l) lactate concentrations but no glucose. With the low perfusate lactate concentration, muscle lactate levels declined to 7.2 +/- 0.8 mumol/g muscle by 3 h after the contraction period and muscle glycogen levels did not increase (1.28 +/- 0.07 at 3 h vs. 1.35 +/- 0.09 mg glucosyl U/g at end of exercise). Lactate disappearance from muscle was accounted for entirely by output into the venous effluent. With the high perfusate lactate concentrations, muscle lactate levels remained high (13.7 +/- 1.7 and 19.3 +/- 2.0 mumol/g) and glycogen levels increased by 1.11 and 0.86 mg glucosyl U/g, respectively, after 1 h of recovery from exercise. No more glycogen was synthesized when the recovery period was extended. Therefore, it appears that limited resynthesis of glycogen from lactate can occur after the contraction period but only when arterial lactate concentrations are high; otherwise the lactate that builds up in muscle during contraction will diffuse into the bloodstream.
Respiratory depressant effects of GABA alpha- and beta-receptor agonists in the cat
Authors: Taveira da Silva A. M. , Hartley B. , Hamosh P. , Quest J. A. , Gillis R. A.
Published: December 2017

The aim of this study was to evaluate the cardiorespiratory effects of intravenously administered gamma-aminobutyric acid (GABA) alpha-(4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, THIP) and beta-(baclofen) receptor agonists and to locate the site of action of these drugs in the brain. THIP and baclofen were administered to alpha-chloralose-anesthetized cats while minute ventilation (VE), arterial blood pressure (AP), and heart rate were monitored. THIP, in doses of 0.5 to 2 mg/kg decreased VE, tidal volume (VT), and AP. No changes in respiratory rate (f) or inspiratory (TI) or expiratory (TE) duration were observed. Baclofen, in doses of 0.5 to 4 mg/kg, decreased VE, f, and AP. VT and TI increased and an “apneustic” breathing pattern was seen. THIP (9.5 micrograms), applied bilaterally to the glycine-sensitive area of the ventral medulla, reproduced the effects seen with intravenous administration. Application of 10 micrograms of bicuculline bilaterally to this area reversed the effects of intravenous THIP but not those of baclofen. Baclofen (5.6-56 micrograms), administered by the intracisternal route, produced the same respiratory effects seen with intravenous administration. We conclude that activation of GABA alpha- and beta-receptors produces cardiorespiratory depression. However, this is accomplished by different mechanisms and by actions exerted at different central nervous system sites.
Lymph flow from edematous dog lungs
Authors: Drake R. E. , Allen S. J. , Williams J. P. , Laine G. A. , Gabel J. C.
Published: December 2017

We measured the flow rate (QLV) from cannulated lung lymph vessels in anesthetized dogs. Low-resistance lymph cannulas were used and the vessels were cannulated at the lung hilus. When we increased left atrial pressure to 42.9 +/- 5.7 (SD) cmH2O (base line = 6.6 +/- 4.6 cmH2O), the lungs became edematous and QLV increased from a base line of 20.4 +/- 21.5 microliters/min to 388 +/- 185 microliters/min. QLV plateaued at the higher level. We also measured the relationship between lymph flow rate and the height of the outflow end of the lymph cannula. From this relationship, determined at the end of the period of elevated left atrial pressure, we calculated the effective resistance and pressure driving lymph from the lungs. We also cannulated lymph vessels in the downstream direction and estimated the effective resistance and pressure opposing flow into the part of the lymphatic system between the lung hilus and the veins (extrapulmonary lymph vessels). We found that the effective resistance of the extrapulmonary part of the lymph system (0.042 +/- 0.030 (SD) cmH2O X min X microliter-1) was large compared with the resistance of the lymph vessels from the lungs (0.026 +/- 0.027). These data indicate that the resistance of the extrapulmonary part of the lung lymph system limits the maximum flow of lymph from edematous lungs.
Blood pressure and hemodynamic responses after exercise in older hypertensives
Authors: Hagberg J. M. , Montain S. J. , Martin W. H.
Published: December 2017

Recently, systolic and diastolic blood pressure have been reported to be significantly lower for several hours after exercise than when measured at rest before exercise in individuals with essential hypertension. We sought to determine the hemodynamic mechanism underlying this reduction in blood pressure. Twenty-four men and women 60–69 yr of age with persistent essential hypertension completed one of the following protocols: exercise at 50% of maximum O2 consumption (VO2 max) followed by 1 h of recovery, exercise at 70% of VO2 max followed by 3 h of recovery, or a 4-h control study. Systolic pressure was significantly lower during recovery after both intensities of exercise, but diastolic pressure was unchanged. The lower blood pressure was primarily due to a reduction in cardiac output, since total peripheral resistance was increased throughout both recovery periods. Cardiac output was reduced in recovery because of a reduction in stroke volume. Heart rate was above, or no different from, that at rest before exercise. Changes in plasma volume could not entirely account for the reduction in stroke volume. Therefore, other mechanisms altering venous return and/or myocardial contractility appear to be responsible for the reduction in systolic blood pressure evident after a single bout of submaximal exercise in individuals with essential hypertension.
Rib cage versus abdominal displacement in rabbits during forced oscillations to 30 Hz
Authors: Boynton B. R. , Fredberg J. J. , Buckley B. G. , Frantz I. D.
Published: December 2017

We measured relative displacement of the rib cage (RC) and abdomen (ABD) in 12 anesthetized rabbits during forced oscillations. Sinusoidal volume changes were delivered through a tracheostomy at frequencies from 0.5 to 30 Hz and measured by body plethysmography. Displacements of the RC and ABD were measured by inductive plethysmography. During oscillation at fixed tidal volume (VT = 1.3 ml/kg) the ratio ABD/RC, normalized to unity at 0.5 Hz, was 0.88 +/- 0.06 at 2 Hz and increased to 1.28 +/- 0.13 at 6 Hz (P less than 0.01). As frequency increased further ABD/RC fell sharply but between 20 and 30 Hz reached a plateau of 0.17 +/- 0.02 (P less than 0.001). Displacements of RC and ABD were nearly synchronous from 0.5 to 2 Hz, but as frequency increased ABD lagged RC progressively, reaching a phase difference of 90 degrees between 6 and 8 Hz and 180 degrees between 16 and 20 Hz. In six additional rabbits we measured chest wall displacements while varying VT from 0.5 to 3.7 ml/kg. ABD/RC was independent of VT at low frequencies (less than or equal to 6 Hz) but fell sharply with increasing VT at the higher frequencies. We interpreted these findings using a chest wall model having an RC compartment whose displacements are governed primarily by a nonlinear compliance, in parallel with an ABD compartment whose displacements are governed by a series resistance, inertance, and in addition a nonlinear compliance. The experimental findings are in large measure accounted for by such a model if the degree of nonlinearity of ABD and RC compliances are comparable.(ABSTRACT TRUNCATED AT 250 WORDS)
Substrate utilization in leg muscle of men after heat acclimation
Authors: Kirwan J. P. , Costill D. L. , Kuipers H. , Burrell M. J. , Fink W. J. , Kovaleski J. E. , Fielding R. A.
Published: December 2017

Eight men were heat acclimated (39.6 degrees C and 29.2% rh) for 8 days to examine changes in substrate utilization. A heat exercise test (HET), (cycling for 60 min; 50% maximal O2 consumption) was performed before (UN-HET) and after (ACC-HET) the acclimation period. Muscle glycogen utilization (67.0 vs. 37.6 mmol/kg wet wt), respiratory exchange ratio (0.85 +/- 0.002 vs. 0.83 +/- 0.001), and calculated rate of carbohydrate oxidation (75.15 +/- 1.38 vs. 64.80 +/- 1.52 g/h) were significantly reduced (P less than 0.05) during the ACC-HET. Significantly lower (P less than 0.05) femoral venous glucose (15, 30, and 45 min) and lactate (15 min) levels were observed during the ACC-HET. No differences were observed in plasma free fatty acid (FFA) and glycerol concentrations or glucose, lactate and glycerol arteriovenous uptake/release between tests. A small but significant increase (P less than 0.05) above resting levels in FFA uptake was observed during the ACC-HET. Leg blood flow was slightly greater (P greater than 0.05) during the ACC-HET (4.64 +/- 0.13 vs. 4.80 +/- 0.13 l/min). These findings indicate a reduced use of muscle glycogen following heat acclimation. However, the decrease is not completely explained by a shift toward greater lipid oxidation or increased blood flow.
Liposome-entrapped antioxidant enzymes prevent lethal O2 toxicity in the newborn rat
Authors: Tanswell A. K. , Freeman B. A.
Published: December 2017

Newborn rat pups delivered and maintained in greater than 95% O2 had a lethal time for 50% of population (LT50) of 13 days. Daily intraperitoneal injection per se did not alter the mortality due to inhalation of O2. Survival after 13.5 days of exposure increased from 40 +/- 7% of pups that received buffered saline only to 95 +/- 4% of pups that received liposomes containing superoxide dismutase and catalase. Daily injection of control liposomes containing no enzymes also caused a less dramatic, though significant, increase in survival from 40 +/- 7 to 71 +/- 7% of O2-exposed pups, indicating that the lipid vehicle, as well as the liposome-entrapped antioxidant enzymes, contributed to the protective effect. The component of the protective effect that could be attributed to the antioxidant enzymes was lost if inactive catalase was used in liposome preparation.
Hyperoxia increases H2O2 production by brain in vivo
Authors: Yusa T. , Beckman J. S. , Crapo J. D. , Freeman B. A.
Published: December 2017

Hyperoxia and hyperbaric hyperoxia increased the rate of cerebral hydrogen peroxide (H2O2) production in unanesthetized rats in vivo, as measured by the H2O2-mediated inactivation of endogenous catalase activity following injection of 3-amino-1,2,4-triazole. Brain catalase activity in rats breathing air (0.2 ATA O2) decreased to 75, 61, and 40% of controls due to endogenous H2O2 production at 30, 60, and 120 min, respectively, after intraperitoneal injection of 3-amino-1,2,4-triazole. The rate of catalase inactivation increased linearly in rats exposed to 0.6 ATA O2 (3 ATA air), 1.0 ATA O2 (normobaric 100% O2) and 3.0 ATA O2 (3 ATA 100% O2) compared with 0.2 ATA O2 (room air). Catalase inactivation was prevented by pretreatment of rats with ethanol (4 g/kg), a competitive substrate for the reactive catalase-H2O2 intermediate, compound I. This confirmed that catalase inactivation by 3-amino-1,2,4-triazole was due to formation of the catalase-H2O2 intermediate, compound I. The linear rate of catalase inactivation allows estimates of the average steady-state H2O2 concentration within brain peroxisomes to be calculated from the formula: [H2O2] = 6.6 pM + 5.6 ATA-1 X pM X [O2], where [O2] is the concentration of oxygen in ATA that the rats are breathing. Thus the H2O2 concentration in brains of rats exposed to room air is calculated to be about 7.7 pM, rises 60% when O2 tension is increased to 100% O2, and increases 300% at 3 ATA 100% O2, where symptoms of central nervous system toxicity first become apparent. These studies support the concept that H2O2 is an important mediator of O2-induced injury to the central nervous system.
Blood collection and processing for measurement of catecholamines in exercising rats
Authors: Winder W. W. , Yang H. T.
Published: December 2017

We have studied the time course of the decline in plasma catecholamines in the postexercise period in rats. Male Sprague-Dawley rats were run on the treadmill for 5 min at 31 m/min up a 15% grade. At the end of the exercise the rats were quickly anesthetized by intravenous injection of pentobarbital. Blood samples were collected as soon as possible (average of 43 s), at 2 and 7 min postexercise. Plasma epinephrine decreased from 0.79 +/- 0.09 ng/ml to 0.51 +/- 0.05 after 2 min and to 0.35 +/- 0.09 after 7 min. Plasma norepinephrine decreased from 0.89 +/- 0.16 ng/ml to 0.61 +/- 0.05 after 2 min and to 0.50 +/- 0.07 after 7 min. We also studied the effect of time of centrifugation with respect to time of blood collection on plasma catecholamines. If blood samples were kept on ice no significant change in plasma epinephrine occurred over a period of 1 h. A small (14%) but significant decrease in norepinephrine was observed after 15 and 60 min. These studies emphasize the importance of collecting rat blood samples as quickly as possible after the end of exercise. Catecholamines decline very quickly in the rat after intravenous pentobarbital anesthesia.