bluuebunny/crossref_metadata_2025 huggingface dataset:
PMA-induced pulmonary edema: mechanisms of the vasoactive response
Authors: Johnson A.
Published: December 2017

We investigated the effect of phorbol myristate acetate (PMA) in isolated guinea pig lungs perfused with phosphate-buffered Ringer solution. Pulmonary arterial pressure (Ppa), pulmonary capillary pressure (Ppc), and change in lung weight were recorded at 0, 10, 25, 40, and 70 min. The capillary filtration coefficient (Kf), an index of vascular permeability, was measured at 10 and 70 min. The perfusion of PMA (0.5 x 10(-7) M) increased Ppa, Ppc, and lung weight at 70 min. The ratio of arterial-to-venous vascular resistance (Ra/Rv) decreased and the Kf did not change with PMA. The perfusion of the lung with 4 alpha-phorbol didecanoate (inactive toward the protein kinase C analogue of PMA) did not affect the lung. The inhibition of TxA2 synthase with dazoxiben inhibited the response to PMA. The inhibition of the 5-lipoxygenase with U-60257 and the SRS-A receptor antagonist FPL 55712 also prevented the response to PMA. The addition of superoxide dismutase (SOD), catalase, or SOD plus catalase (the enzymes that remove O.2 H2O2, and OH., respectively) did not prevent the PMA effect or the release of TxA2; however, dimethylthiourea (DMTU), a scavenger of OH., did prevent the response to PMA. The data indicate that PMA causes a neutrophil-independent increase in lung weight due to increases in Ppc mediated by TxA2 and SRS-A. The protective effect of DMTU may be due to the inhibition of TxA2 generation.
Endogenous hormones subtly alter women's response to heat stress
Authors: Carpenter A. J. , Nunneley S. A.
Published: December 2017

The thermoregulatory responses of menstruant women to exercise in dry heat (dry-bulb temperature/wet-bulb temperature = 48/25 degrees C) were evaluated at three times during the menstrual cycle: menstrual flow (MF), 3-5 days during midcycle including ovulation (OV), and in the middle of the luteal phase (LU). Serum concentrations of estradiol-17 beta (E2), progesterone (Pg), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured by radioimmunoassay, and these values were used to determine the dates of OV (peak LH and FSH) and LU (peak postovulatory Pg). After heat acclimation, subjects received heat stress tests (HST) consisting of a 2-h cycle-ergometer exercise at 30% of maximal O2 consumption in the heat. Rectal (Tre) and mean skin (Tsk) temperatures, heart rate (HR), and sweat rate on the chest and thigh were recorded continuously. Total sweat loss (Msw), as indicated by weight loss, was recorded every 20 min, and equivalent water replacement was given. Steady-state exercise metabolic rate (M) was measured at 45 and 110 min. Seven of eight subjects had ovulatory cycles during experimental months. At rest, Tre was lowest at OV and significantly higher at LU. During steady-state exercise both Tre and Tsk were lowest at OV and significantly higher at LU. There were no differences between phases in Msw, sweat rate on the chest and thigh or M. Despite higher Tre and Tsk at LU, all subjects were able to complete the 2-h of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Behavioral activity during prolonged hypoxemia in fetal sheep
Authors: Bocking A. D. , Gagnon R. , Milne K. M. , White S. E.
Published: December 2017

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.
Parenchymal interdependence and airway response to methacholine in excised dog lobes
Authors: Gunst S. J. , Warner D. O. , Wilson T. A. , Hyatt R. E.
Published: December 2017

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.
BCNU-induced protection from hyperbaric hyperoxia: role of glutathione metabolism
Authors: Jenkinson S. G. , Jordan J. M. , Lawrence R. A.
Published: December 2017

To explore the role of the glutathione oxidation-reduction cycle in altering the sensitivity of rats to the effects of hyperbaric hyperoxia, we administered N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) to decrease tissue glutathione reductase activity. We then exposed these animals and their matched vehicle-treated controls to 100% O2 at 4 ATA. Animals that received BCNU and were immediately exposed to hyperbaric O2 showed enhanced toxicity by seizing earlier in the exposure than controls. Animals that received BCNU 18 h before the hyperbaric O2 exposure were paradoxically protected from the effects of the exposure with a prolongation of their time to initial seizure and a marked increase in their survival time during the exposure. Tissue glutathione concentrations were also measured in the various groups and the hyperbaric O2 exposure produced marked decreases in hepatic glutathione levels in all control animals. In animals treated with BCNU 18 h before exposure, hepatic glutathione concentrations also decreased, but the concentrations had significantly increased during the 18-h waiting period, allowing these animals to maintain hepatic levels in the normal range even during their hyperbaric exposures. We conclude that treatment of rats with BCNU 18 h before exposure to hyperbaric hyperoxia results in enhanced protection of the animals during the exposure.
Operation Everest II: muscle energetics during maximal exhaustive exercise
Authors: Green H. J. , Sutton J. , Young P. , Cymerman A. , Houston C. S.
Published: December 2017

To investigate the metabolic basis for the reduction in peak blood lactate concentration that occurs with maximal exercise after acclimatization to altitude, eight male subjects [maximal O2 uptake of 51.2 +/- 3.0 (SE) ml.kg-1.min-1] were acclimated to progressive hypobaria over a 40-day period. Before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) the subjects performed progressive cycle exercise to exhaustion. Analysis of muscle samples obtained from the vastus lateralis before exercise and at exhaustion indicated a pronounced reduction (P less than 0.05) in muscle lactate concentration (mmol/kg dry wt) at 282 Torr (39.2 +/- 11) compared with SL-1 (113 +/- 9.7), 380 Torr (94.6 +/- 18), and SL-2 (92.7 +/- 22). For the other glycolytic intermediates studied (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate) only the increase in glucose 1-phosphate, glucose 6-phosphate, and fructose 6-phosphate were blunted (P less than 0.05) at 282 Torr. The reduction in muscle glycogen concentration during exercise was similar (P less than 0.05) for all environmental conditions. Although exercise resulted in reductions (P less than 0.05) in ATP and creatine phosphate averaging 30 and 51%, respectively, the magnitude of the change was not dependent on the degree of hypobaria. Inosine monophosphate was elevated (P less than 0.05) approximately 11-fold with exercise at both SL-1 and SL-2. These findings support the hypothesis that the lower lactate concentration observed at 282 Torr after exhaustive exercise is due to a reduction in anaerobic glycolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics
Authors: Kreit J. W. , Gross K. B. , Moore T. B. , Lorenzen T. J. , D'Arcy J. , Eschenbacher W. L.
Published: December 2017

To compare the responses of asthmatic and normal subjects to high effective doses of ozone, nine asthmatic and nine normal subjects underwent two randomly assigned 2-h exposures to filtered, purified air and 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (minute ventilation = 30 l.min-1.m-2). Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms were recorded. Ozone exposure was associated with a statistically significant decrease in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), percent FEV1 (FEV1%), and forced expired flow at 25–75% FVC (FEF25–75) in both normal and asthmatic subjects. However, comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater percent decrease in FEV1, FEV1%, and FEF25–75 in the asthmatic subjects. The effect of ozone on FVC and symptom scores did not differ between the two groups. In both normal and asthmatic subjects, exposure to ozone was accompanied by a significant increase in bronchial responsiveness. We conclude that exposure to a high effective ozone dose produces 1) increased bronchial responsiveness in both normal and asthmatic subjects, 2) greater airways obstruction in asthmatic than in normal subjects, and 3) similar symptoms and changes in lung volumes in the two groups.
Exercise alters the distribution of ammonia and lactate in blood
Authors: Harris R. T. , Dudley G. A.
Published: December 2017

Six subjects (3 males, 3 females) worked for 4 min on a cycle ergometer at 115% of peak O2 uptake (VO2). Venous samples drawn before, directly after, and 15 min after exercise were analyzed for ammonia (NH3) and lactate concentrations of plasma, whole blood, and erythrocytes (RBCs) to examine the effect of exercise on blood NH3 and lactate distribution. Exercise increased (P less than 0.05) the [NH3] of plasma and RBCs, with the larger (P less than 0.05) change in plasma (1.8- vs. 0.7-fold). This reduced (P less than 0.05) the RBC-to-plasma [NH3] ratio of 2.4 at rest to 1.3. The plasma-to-RBC [lactate] gradient (P less than 0.05) at rest (0.5 mmol/l) increased (P less than 0.05) 16-fold immediately after exercise (8.7 mmol/l), reflecting the greater increase (P less than 0.05) in plasma than RBCs [lactate] (15.5 vs. 7.5 mmol/l). [Lactate] and [NH3] did not decrease (P greater than 0.05) immediately after to 15 min after exercise. Plasma and whole blood [NH3] or [lactate] were correlated (r greater than 0.93, P less than 0.01) at all sample times, but the slopes of the relations for [NH3] (immediately after vs. 15 min after exercise) or for [lactate] (before and immediately after vs. 15 min after exercise) differed (P less than 0.05). The results indicate that supramaximal exercise alters the distribution of NH3 and lactate between plasma and RBC, thus changing the relations between plasma and whole-blood concentrations of these metabolites. The alteration of NH3 distribution may reflect changes in the pH gradient between plasma and RBCs.
Prolonged whole-body cold water immersion: fluid and ion shifts
Authors: Deuster P. A. , Smith D. J. , Smoak B. L. , Montgomery L. C. , Singh A. , Doubt T. J.
Published: December 2017

To characterize fluid and ion shifts during prolonged whole-body immersion, 16 divers wearing dry suits completed four whole-body immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 msw. One immersion was conducted at 1000 (AM) and one at 2200 (PM) so that diurnal variations could be evaluated. Fifty-four hours separated the immersions, which lasted up to 6 h; 9 days separated each air saturation dive. Blood was collected before and after immersion; urine was collected for 12 h before, during, and after immersion for a total of 24 h. Plasma volume decreased significantly and to the same extent (approximately 17%) during both AM and PM immersions. Urine flow increased by 236.1 +/- 38.7 and 296.3 +/- 52.0%, urinary excretion of Na increased by 290.4 +/- 89.0 and 329.5 +/- 77.0%, K by 245.0 +/- 73.4 and 215.5 +/- 44.6%, Ca by 211.0 +/- 31.4 and 241.1 +/- 50.4%, Mg by 201.4 +/- 45.9 and 165.3 +/- 287%, and Zn by 427.8 +/- 93.7 and 301.9 +/- 75.4% during AM and PM immersions, respectively, compared with preimmersion. Urine flow and K excretion were significantly higher during the AM than PM. In summary, when subjects are immersed in cold water for prolonged periods, combined with a slow rate of body cooling afforded by thermal protection and enforced intermittent exercise, there is diuresis, decreased plasma volume, and increased excretions of Na, K, Ca, Mg, and Zn.
Extracellular matrix proteoglycan degradation by human alveolar macrophages and neutrophils
Authors: McGowan S. E. , Thompson R. J.
Published: December 2017

Degradation and restructuring of the elastin fiber network of the lung is a pivotal process in the pathogenesis of emphysema. Alveolar macrophages and neutrophils are probably directly involved in elastin degradation, but they may also indirectly influence elastin structure and function by altering other extracellular matrix components such as proteoglycans. In this study the mechanisms of proteoglycan degradation by human alveolar macrophages and neutrophils have been explored. Macrophages appear to utilize plasminogen in solubilizing 35SO4-labeled proteoglycans in extracellular matrix produced by neonatal rat vascular smooth muscle cells. Proteoglycan degradation by macrophages is significantly augmented in the presence of 1% human serum. In contrast, neutrophils apparently utilize intrinsic proteinases to solubilize extracellular matrix proteoglycans, and serum inhibits proteoglycan degradation by these cells. Persistent inflammation in the terminal airways of cigarette smokers may produce proteoglycan degradation and influence elastin fiber architecture where the earliest physiological and anatomic evidence of emphysema appears.
Effect of swim exercise training on human muscle fiber function
Authors: Fitts R. H. , Costill D. L. , Gardetto P. R.
Published: December 2017

This study examined the effect of a typical collegiate swim-training program and an intensified 10-day training period on the peak tension (Po), negative log molar Ca2+ concentration (pCa)-force, and maximal shortening speed (Vmax) of the slow-twitch type I and fast-twitch type II fibers of the deltoid muscle. Over a 10-wk period, the swimmers averaged 4,266 +/- 264 m/day swimming intermittent bouts of front crawl, kicking, or pulling. The training program induced an almost twofold increase in the mitochondrial marker enzyme citrate synthase. Po of the single fibers was not altered by either the training or 10-day intensive training programs, and no significant differences were observed in the Po (kg/cm2) of type I compared with the type II fibers. The type II fiber diameters were significantly larger than the type I fibers (94 +/- 4 vs. 80 +/- 2 microns), and although fiber diameters were unaffected by the training, the 10-day intensive training significantly reduced the type II fiber diameter. The type I fibers from the trained swimmers showed pCa-force curves shifted to the right such that higher free Ca2+ levels were required to elicit a given percent of Po (for values less than 0.5 Po). The activation threshold (pCa) for the onset of tension and the pCa required to elicit one-half maximal tension were not altered by the training in either fiber type. Fiber Vmax (measured by the slack test) was fivefold higher in type II compared with type I fibers (4.85 +/- 0.50 vs. 0.86 +/- 0.04 fiber lengths/s). The exercise-training program significantly increased and decreased the Vmax of the slow and fast fibers, respectively. The 10 days of intensified training produced a further significant decrease in the Vmax of the type II fibers. After a period of detraining, the Vmax of both fiber types returned to the control level. The force-velocity relation was not significantly altered in either fiber type by the swim training; however, the intensified training significantly depressed the velocity of the type II fiber at all loads studied. The Vmax changes with exercise training are likely explained by an exercise-induced expression of fast myosin in slow fibers and slow myosin in fast fibers.
A prototype gas exchange monitor for exercise stress testing aboard NASA Space Station
Authors: Orr J. A. , Westenskow D. R. , Bauer A.
Published: December 2017

A monitor was developed to track weightlessness deconditioning aboard the National Aeronautics and Space Administration (NASA) Space Station by measuring the O2 uptake (VO2) and CO2 production (VCO2) and calculating maximum VO2 and anaerobic threshold during an exercise stress test. The system uses two flowmeters in series to achieve a completely automatic flow calibration, and it uses breath-by-breath compensation for sample line transport delay. The accuracy of the system was measured over the range of VO2 and VCO2 from 100 to 800 ml/min by means of simulation. Accuracy was 0.54% for VO2 and 2.9% for VCO2. The system was further evaluated using two laboratory methods, the first method being comparison with a breath-by-breath system. As volunteers performed a maximum effort on a cycle ergometer, the mean difference in readings between the two systems was 17 ml/min for VO2 and 8.0 ml/min for VCO2. The correlation coefficient squared was greater than 0.96 for both. The second laboratory test was to use the system for 2 mo in a Human Performance Laboratory. Readings of maximum VO2 (VO2max) and anaerobic threshold were repeatable and consistent with the individual's activity level. The accuracy and convenience of operation will make this a valuable instrument aboard the Space Station.
Endothelin produces pulmonary vasoconstriction and systemic vasodilation
Authors: Lippton H. L. , Hauth T. A. , Summer W. R. , Hyman A. L.
Published: December 2017

Endothelin is a newly described polypeptide derived from endothelial cells. The effects of porcine endothelin on the pulmonary vascular bed and systemic vascular bed were investigated in the anesthetized, intact-chest cat under conditions of constant pulmonary blood flow and left atrial pressure. Intralobar bolus injections of porcine endothelin (100–1000 ng) produced a mild vasoconstrictor response in the pulmonary vascular bed. The pulmonary vasoconstrictor response to endothelin was not altered when pulmonary vasomotor tone was increased by infusion of U46619. In contrast to this mild pulmonary vasoconstrictor response, endothelin decreased systemic arterial pressure. Moreover, injections of porcine endothelin into the right and left atria produced similar reductions in aortic pressure as well as similar increases in cardiac output and decreases in systemic vascular resistance. The systemic vasodilator response to porcine endothelin was not affected by beta 2-adrenoceptor blockade. The present data suggest that endothelin does not undergo significant first-pass pulmonary metabolism. The pulmonary vasoconstrictor response to bolus injections of porcine endothelin is not altered by changes in pulmonary vasomotor tone. In contrast, endothelin markedly dilated the systemic vascular bed independently of activation of beta 2-adrenoceptors. The present study provides the first report of the activity of endothelin on pulmonary and systemic hemodynamics in vivo. Moreover, the potent vasodilator activity of endothelin in the systemic vascular bed and its weak effect on pulmonary vessels suggest that endothelin may be more important in the regulation of peripheral vasomotor tone than the pulmonary vascular bed.
Both acute and chronic exercise enhance in vivo ethanol clearance in rats
Authors: Ardies C. M. , Morris G. S. , Erickson C. K. , Farrar R. P.
Published: December 2017

Rates of ethanol clearance were measured at rest and with acute exercise in four groups of female Sprague-Dawley rats. Two groups were trained to run on a motor-driven rodent treadmill at 27 m/min, 1 h/day, 5 days/wk and were given a nutritionally balanced liquid diet; one of these groups received 35% calories as ethanol whereas in the other, sucrose was isocalorically substituted for the ethanol. Appropriate sedentary and nonethanol controls were also used. Clearance of a 1.75-g/kg ethanol dose injected intraperitoneally was determined by measuring ethanol levels in the blood each hour and utilizing these values in the Widmark equation (R. Teschke, F. Moreno, and A. Petrides, Biochem. Pharmacol. 30: 1745–1751, 1981) for calculating whole-body ethanol clearance. Rates of ethanol clearance were determined for each rat at 4 and 7 wk of training. The clearance tests at 4 wk included a 60-min period of running exercise, whereas the tests 3 wk later were conducted at rest. The results indicate that both acute exercise and exercise training can increase rates of in vivo ethanol clearance. In addition, the chronic exercise appeared to increase in vitro ethanol metabolism by hepatic microsomes without altering in vitro hepatic alcohol dehydrogenase activity.
Effect of dichloroacetate on lactate concentration in exercising humans
Authors: Carraro F. , Klein S. , Rosenblatt J. I. , Wolfe R. R.
Published: December 2017

The precise mechanism responsible for the increase in plasma lactate concentration during exercise in humans is not known. We have used dichloroacetate to test the hypothesis that a limitation in pyruvate dehydrogenase activity is responsible for the rise in plasma lactate. Dichloroacetate stimulates the activity of pyruvate dehydrogenase, which is normally the regulatory enzyme in the oxidation of glucose when tissue oxygenation is adequate. Six subjects were studied twice according to a randomized, crossover protocol, involving one test with saline infusion and another with dichloroacetate infusion. Exercise load on a bicycle ergometer was increased progressively until exhaustion. Blood samples were drawn each minute throughout exercise and periodically throughout 120 min of recovery. Dichloroacetate significantly lowered the lactate concentration during exercise performed at less than 80% of the average maximal O2 consumption. The peak concentration of lactate at exhaustion was not affected by dichloroacetate treatment, but dichloroacetate did lower lactate concentration throughout recovery. These results suggest that a limitation in pyruvate dehydrogenase activity contributes to the increase in plasma lactate during submaximal exercise and recovery.
Combined effects of female hormones and metabolic rate on ventilatory drives in women
Authors: Regensteiner J. G. , Woodard W. D. , Hagerman D. D. , Weil J. V. , Pickett C. K. , Bender P. R. , Moore L. G.
Published: December 2017

Increased resting ventilation (VE) and hypoxic and hypercapnic ventilatory responses occur during pregnancy in association with elevations in female hormones and metabolic rate. To determine whether increases in progestin, estrogen, and metabolic rate produced a rise in VE and hypoxic ventilatory response (HVR) similar in magnitude to that observed at full-term pregnancy, we studied 12 postmenopausal women after 1 wk of treatment with placebo, progestin (20 mg tid medroxyprogesterone acetate), estrogen (1.25 mg bid conjugated equine estrogens), and combined progestin and estrogen. Progestin alone or with estrogen raised VE at rest and decreased end-tidal PCO2 (PETCO2) by 3.9 +/- 0.8 and 3.3 +/- 0.6 Torr, respectively (both P less than 0.05), accounting for approximately one-fourth of the rise in VE and three-fourths of the PETCO2 reduction seen at full-term pregnancy. The addition of mild exercise sufficient to raise metabolic rate by 33–36% produced the remaining three-fourths of the rise in VE but no further decline in PETCO2. Combined progestin and estrogen raised HVR and hypercapnic ventilatory response more consistently than progestin alone and could account for one-half of the increase in HVR seen at full-term pregnancy. Mild exercise alone did not raise HVR, but when exercise was combined with progestin and estrogen administration, HVR rose by amounts equal to that seen at full-term pregnancy. We concluded that female hormones together with mild elevation in metabolic rate were likely responsible for the pregnancy-associated increases in VE and HVR.
Cyclooxygenase blockers inhibit ethanol-induced pulmonary vasoconstriction in lambs
Authors: Drummond W. H. , Carter R. L.
Published: December 2017

We investigated the mechanism of ethanol-induced pulmonary vasoconstriction in lambs, by a pharmacological approach. We chronically instrumented 28 lambs to determine whether phentolamine (alpha-block), propranolol (beta-block), promethazine and cimetidine (H1- and H2-block), high-dose indomethacin, or low- and high-dose meclofenamate (cyclooxygenase block) altered the vasoconstriction. Ethanol alone increased pulmonary vascular resistance from 0.14 to 0.49 Torr.ml-1.kg-1.min (U). Only indomethacin (7–8 mg/kg po) and high-dose meclofenamate (7–8 mg/kg iv) abolished the pulmonary vascular response to ethanol infusion. Pulmonary vascular resistance was 0.14 U after ethanol plus indomethacin and was 0.2 U after ethanol plus high-dose meclofenamate (P = NS vs. base line). Low-dose meclofenamate (2 mg/kg) attenuated the vasoconstrictor response. Systemic vascular resistance increased moderately after ethanol and had a similar pattern of inhibition by cyclooxygenase blockade. Cardiac output and heart rate decreased nearly significantly after ethanol (P less than 0.06), a tendency that was also ablated by cyclooxygenase inhibition. Thus the acute cardiocirculatory response to ethanol involves an intact prostaglandin synthase system in lambs. To our knowledge, these data are the first documentation that cyclooxygenase enzyme blockade can eliminate the acute cardiac and vascular effects of ethanol in a whole-animal system.
Effect of exercise on insulin action in human skeletal muscle
Authors: Richter E. A. , Mikines K. J. , Galbo H. , Kiens B.
Published: December 2017

The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2 consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp even though indirect estimates indicated net glycogen synthesis. In contrast, in exercised muscle estimated and biopsy-verified increases in muscle glycogen concentration agreed. Local contraction-induced increases in insulin sensitivity and responsiveness play an important role in postexercise recovery of human skeletal muscle.
Effects of lung volume, volume history, and methacholine on lung tissue viscance
Authors: Kariya S. T. , Thompson L. M. , Ingenito E. P. , Ingram R. H.
Published: December 2017

We examined the effects of lung volume change and volume history on lung resistance (RL) and its components before and during induced constriction. Eleven subjects, including three current and four former asthmatics, were studied. RL, airway resistance (Raw), and, by subtraction, tissue viscance (Vtis) were measured at different lung volumes before and after a deep inhalation and were repeated after methacholine (MCh) aerosols up to maximal levels of constriction. Vtis, which average 9% of RL at base line, was unchanged by MCh and was not changed after deep inhalation but increased directly with lung volume. MCh aerosols induced constriction by increasing Raw, which was reversed by deep inhalation in inverse proportion to responsiveness. such that the more responsive subjects reversed less after a deep breath. Responsiveness correlated directly with the degree of maximal constriction, as more responsive subjects constricted to a greater degree. These results indicate that in humans Vtis comprises a small fraction of overall RL, which is clearly volume-dependent but unchanged by MCh-induced constriction and unrelated to the degree of responsiveness of the subject.
Alveolar hyperoxic injury in rabbits receiving exogenous surfactant
Authors: Loewen G. M. , Holm B. A. , Milanowski L. , Wild L. M. , Notter R. H. , Matalon S.
Published: December 2017

We have previously demonstrated that instillation of a calf lung surfactant extract (CLSE) in rabbits after exposure to 100% O2 for 64 h mitigates the progression of lung pathology after return to room air (J. Appl. Physiol. 62: 756–761, 1987). In the present study, we investigated whether we could prevent or reduce the onset and development of hyperoxic lung injury by sequential instillations of CLSE during the hyperoxic exposure. Rabbits were exposed to 100% O2. CLSE (125 mg, approximately 170 mumol of phospholipid) was suspended in 10 ml of sterile saline and instilled intratracheally into their lungs, starting at 24 h in O2, a time at which no physiological or biochemical injury was detected, and at 24-h intervals thereafter. Control rabbits breathed 100% O2 and received either equal volumes of saline or no instillations at all. CLSE-instilled rabbits had higher arterial PO2 (Pao2) values throughout the exposure period and survived longer when compared with saline controls [120 +/- 4 vs. 102 +/- 4 (SE) h; n greater than or equal to 10; P less than 0.05]. At 72 h in O2, CLSE-instilled rabbits had significantly higher lavageable alveolar phospholipid levels (12.5 +/- 1.5 vs. 5 +/- 1 mumol/kg) and total lung capacities (41 +/- 2 vs. 25 +/- 3.5 ml/kg) and lower levels of alveolar protein (24 +/- 3 vs. 52 +/- 8 mg/kg), minimum surface tension (2 +/- 1 vs. 26.1 dyn/cm), and lung wet-to-dry weights (5.9 +/- 0.2 vs. 6.5 +/- 0.3). After 72 h in O2, lungs from both CLSE- and saline-instilled rabbits showed evidence of diffuse hyperoxic injury. However, atelectasis was less prominent in the former. We concluded that instillation of CLSE limits the onset and development of hyperoxic lung injury to the alveolar epithelium of rabbits.
Pharyngeal fluid clearance and aspiration preventive mechanisms in sleeping infants
Authors: Pickens D. L. , Schefft G. L. , Thach B. T.
Published: December 2017

We sought to characterize ventilatory and airway protective responses to pharyngeal stimulation in young infants during sleep. We studied the various responses with respect to frequency of occurrence, effect of increased stimulus intensity, and relation of stimulus fluid to laryngeal structures. Two groups of infants were studied: healthy full-term infants (n = 5) and preterm infants with a history of prolonged apnea (n = 9). We used a nasopharyngeal catheter to deliver small boluses of warm saline (0.02–0.35 ml) to the oropharynx. Responses repeatedly observed in both infant groups included swallows, obstructed respiratory efforts, brief apnea, prolonged apnea, and cough. In both infant groups, swallows and obstructed breaths occurred frequently and cough and prolonged apnea infrequently. The functional significance of some response patterns was clear, whereas that of others was obscure. Larger stimulus volumes yielded more frequent responses (P less than 0.01), and preterm infants responded much more frequently than full-term infants (P less than 0.01). Prolonged apnea was a composite of the other responses and was much more common in preterm than full-term infants (P less than 0.01). The stimulus technique was performed under direct visualization of the airway in two deceased infants. The findings suggested that the relation of the piriform fossae to the interarytenoid notch is important in determining response frequency. Implications for regulation of the removal of upper airway secretions during sleep are discussed.
Cellular uptake and processing of surfactant lipids and apoprotein SP-A by rat lung
Authors: Young S. L. , Wright J. R. , Clements J. A.
Published: December 2017

The intracellular pathways and the kinetics of metabolism of surfactant apoprotein and lipid, which may be recycled from the alveolar space, are largely unknown. We used a lipid-apoprotein complex made from liposomes of pure lipids in a ratio found in mammalian pulmonary surfactant plus surfactant apoprotein (SP-A, Mr = 26,000–36,000) to test some possible relationships in the recycling of these major surfactant components between intrapulmonary compartments. After intratracheal instillation of 80 microliters of an apoprotein-liposome mixture with separate radiolabels in the lipid and the apoprotein, rats were killed at times from 8 min to 4 h later. The lungs were lavaged with saline, and subcellular fractions were isolated on discontinuous sucrose density gradients. Both the [14C]lipid radiolabel and the 125I-apoprotein radiolabel demonstrated a time-dependent increase in radioactivity recovered in a lamellar body-enriched fraction. Uptake of the radiolabels into other subcellular fractions did not exhibit a clear-cut time dependence; more of the protein than the lipid radiolabel was found in the Golgi-rich and microsomal fractions. We conclude that both the lipid and apoprotein portions of lung surfactant are taken up by lung cells and are incorporated into secretory granules of the cells.
Mechanical arrangement of the parasternal intercostals in the different interspaces
Authors: De Troyer A. , Farkas G. A.
Published: December 2017

When the parasternal intercostal in a single interspace is selectively denervated in dogs with diaphragmatic paralysis, it continues to shorten during both quiet and occluded inspiration. In the present studies, we have tested the hypothesis that this passive parasternal inspiratory shortening is due to the action of the other parasternal intercostals. Changes in length of the denervated third right parasternal were measured in eight supine phrenicotomized animals. We found that 1) the inspiratory muscle shortening increased after denervation of the third left parasternal but gradually decreased with denervation of the parasternals situated in the second, fourth, and fifth interspaces; 2) the muscle, however, always continued to shorten during inspiration, even after denervation of all the parasternals; 3) stimulating selectively the third left parasternal caused a muscle lengthening; and 4) bilateral stimulation of the parasternals in the second or the fourth interspace produced a muscle shortening. We conclude that 1) the two parasternals situated in the same interspace on both sides of the sternum are mechanically arranged in series, whereas the parasternals located in adjacent interspaces are mechanically arranged in parallel; and 2) if a denervated parasternal continues to shorten during inspiration, this is in part because of the action of the parasternals in the adjacent interspaces and in part because of other inspiratory muscles of the rib cage, possibly the external intercostals and the levator costae.
Human recombinant tumor necrosis factor alpha infusion mimics endotoxemia in awake sheep
Authors: Johnson J. , Meyrick B. , Jesmok G. , Brigham K. L.
Published: December 2017

The macrophage-derived cytokine tumor necrosis factor alpha (TNF alpha) has been proposed as the major mediator of endotoxin-induced injury. To examine whether a single infusion of human recombinant TNF alpha (rTNF alpha) reproduces the pulmonary effects of endotoxemia, we infused rTNF alpha (0.01 mg/kg) over 30 min into six chronically instrumented awake sheep and assessed the ensuing changes in hemodynamics, lung lymph flow and protein concentration, and number of peripheral blood and lung lymph leukocytes. In addition, levels of thromboxane B2, 6-ketoprostaglandin F1 alpha, prostaglandin E2, and leukotriene B4 were measured in lung lymph. Pulmonary arterial pressure (Ppa) peaked within 15 min of the start of rTNF alpha infusion [base-line Ppa = 22.0 +/- 1.5 (SE) cmH2O; after 15 min of rTNF alpha infusion, Ppa = 54.2 +/- 5.4] and then fell toward base line. The pulmonary hypertension was accompanied by hypoxemia and peripheral blood and lung lymph leukopenia, both of which persisted throughout the 4 h of study. These changes were followed by an increase in protein-rich lung lymph flow (base-line lymph protein clearance = 1.8 +/- 0.4 cmH2O; 3 h after rTNF alpha infusion, clearance = 5.6 +/- 1.2), consistent with an increase in pulmonary microvascular permeability. Cardiac output and left atrial pressure did not change significantly throughout the experiment. Light-microscopic examination of lung tissue at autopsy revealed congestion, neutrophil sequestration, and patchy interstitial edema. We conclude that rTNF alpha induces a response in awake sheep remarkable similar to that of endotoxemia. Because endotoxin is a known stimulant of TNF alpha production, TNF alpha may mediate endotoxin-induced lung injury.
Central venous O2 saturation and rate of arterial desaturation during obstructive apnea
Authors: Fletcher E. C. , Kass R. , Thornby J. I. , Rosborough J. , Miller T.
Published: December 2017

We examined the rate of fall of arterial O2 saturation (dSao2/dt) after apnea onset in four spontaneously breathing adult male baboons. We postulated that a lower mixed venous O2 saturation (Svo2) would steepen dSao2/dt by more rapid depletion of alveolar O2. Single isolated (NREP) and five or more sequential repetitive apneas (REP) were created by clamping an indwelling cuffed endotracheal tube at end expiration. Fiberoptic catheters were used for continuous monitoring of Sao2, Svo2, and cardiac output. The mean dSao2/dt for all duration NREP apneas was 0.60%/s. Mean dSao2/dt increased above base line for each consecutive REP apnea and was higher in 60 s than in 45 and 30 s REP apnea series. The increase in dSao2/dt corresponded closely with the fall in preapneic Svo2. Preapneic arterial O2 content fell during successive REP apneas but the maximal decrement from base line (1.3 ml/dl) was much less than the maximal decrement in preapneic mixed venous O2 content of 5.1 ml/dl. Preapneic cardiac output for NREP apneas and nadir cardiac output for REP apneas remained constant. Nadir cardiac output for NREP apneas showed higher values for longer duration apneas. We concluded that dSao2/dt is inversely related to preapneic Svo2.
Protective role of epithelium in the guinea pig airway
Authors: Munakata M. , Huang I. , Mitzner W. , Menkes H.
Published: December 2017

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466–471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.
Medullary expiratory activity during opossum development
Authors: Farber J. P.
Published: December 2017

Medullary expiration-phased action potentials were obtained from 5-sec-butyl-5-ethyl-2-thiobarbituric acid- (Inactin) anesthetized suckling opossums from approximately 30 days of age to near weaning (80–90 days of age). The medulla was explored for expiratory neuronal action potentials during positive pressure breathing (PPB) (approximately 3 cmH2O) because many expiratory cells had little or no discharge during spontaneous breathing off load. After finding an expiratory unit, the response of the cell to removal (30–60 s) and reinstatement of PPB was measured. Projections to the spinal cord were also examined, and position of the cell was assessed. Results were compared with those obtained from rostral and caudal medullary expiratory neurons in adult opossums. Mean discharge rate of expiratory cells during PPB increased as a function of age. Discharge started with a delay after the cessation of inspiration; this delay decreased as a function of age. Cells averaged 7.5 spikes/breath during PPB and 2.2 spikes/breath off load. Forty-four percent of cells discharged less than once per breath when PPB was removed. Of cells becoming completely silent off load, 73% lost their discharge within the first two unloaded breaths. Only 5% of caudal and 15% of rostral medullary expiratory cells in adult opossums became silent after the end-expiratory transpulmonary pressure was reduced to normal. Neurons in sucklings were most often bulbospinal as were caudal medullary cells in adults; neurons were found in the region of the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS)
Development of O2 tolerance in rabbits with no increase in antioxidant enzymes
Authors: Baker R. R. , Holm B. A. , Panus P. C. , Matalon S.
Published: December 2017

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.
Calcium channel currents in isolated smooth muscle cells from human bronchus
Authors: Marthan R. , Martin C. , Amedee T. , Mironneau J.
Published: December 2017

An electrophysiological study was carried out on smooth muscle cells that were enzymatically dissociated from bundles of muscle fibers dissected out of human bronchi obtained at thoracotomy. These cells that retain the contractile properties of intact bundles were voltage-clamped by means of the whole-cell patch-clamp technique. Upon voltage steps from a holding potential of -60 mV to more positive levels, the initial inward current was followed by large outward currents that inactivated slowly. These were subsequently reduced by substituting Cs+ for K+ in the internal solution and by using Ba2+ instead of Ca2+ as a charge carrier in the external solution. Under these conditions, the inward current did not completely inactivate in the course of 300-ms voltage steps. Inward current measured after leak subtraction was activated at a membrane potential of -25.8 +/- 5 mV, was maximum at +18 +/- 4 mV, and had an apparent reversal potential of +52.5 +/- 5.5 mV (n = 5). The potential at which steady-state inactivation was half-maximum was -28 mV (n = 5). This inward current was identified as a calcium current on the following basis: 1) it was not altered by 10 microM tetrodotoxin (TTX) or by lowering to 10 mM external Na+ concentration; 2) it was blocked by 2.5 mM Co2+ or 1 microM PN 200–110; 3) it was enhanced by 1 microM BAY K 8644, which in addition suppressed the PN 200–110 blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Breathing route influences upper airway muscle activity in awake normal adults
Authors: Basner R. C. , Simon P. M. , Schwartzstein R. M. , Weinberger S. E. , Weiss J. W.
Published: December 2017

Both nasal obstruction and nasal anesthesia result in disordered breathing during sleep in humans, and bypassing the nasal route during tidal breathing in experimental animals produces decreased electromyographic activity of upper airway (UA) dilating muscles. To investigate UA responses to breathing route in normal awake humans, we studied eight healthy males (ages 21–38 yr) during successive trials of voluntary nose breathing (N), voluntary mouth breathing (M), and mouth breathing with nose occluded (MO). We measured genioglossus electromyographic activity (EMGgg) with perorally inserted bipolar electrodes, alae nasi (EMGan) and diaphragm EMG activity (EMGdi) with surface electrodes, and minute ventilation (VE) with a pneumotachograph. Mean phasic inspiratory EMG activity of both UA muscles was significantly greater during N than during M or MO, even when a 2.5-cmH2O.l-1.s inspiratory resistance was added to MO (P less than 0.01). In contrast, neither EMGdi nor VE was consistently affected by breathing route. EMGgg during N was significantly decreased after selective topical nasal anesthesia (P less than 0.002); a decrease in EMGan did not achieve statistical significance. These data suggest that peak UA dilating muscle activity may be modulated by superficial receptors in the nasal mucosa sensitive to airflow.