bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic smoke with acrolein but not HCl produces pulmonary edema
Authors: Hales C. A. , Barkin P. W. , Jung W. , Trautman E. , Lamborghini D. , Herrig N. , Burke J.
Published: December 2017

The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in concentrations of 0.1-6 N when added to heated carbon (120 degrees C) and cooled to 39 degrees C produced airway damage but no pulmonary edema. Acrolein, in contrast, produced airway damage but also pulmonary edema, whereas capillary wedge pressures remained stable. Low-dose acrolein smoke (less than 200 ppm) produced edema in two of five animals with a 2- to 4-h delay. Intermediate-dose acrolein smoke (200-300 ppm) always produced edema at an average of 147 ± 57 min after smoke, whereas high-dose acrolein (greater than 300 ppm) produced edema at 65 ± 16 min after smoke. Thus acrolein but not HCl, when presented as a synthetic smoke, produced a delayed-onset, noncardiogenic, and peribronchiolar edema in a roughly dose-dependent fashion.
Ventilatory muscle training in the elderly
Authors: Belman M. J. , Gaesser G. A.
Published: December 2017

To test the hypothesis that declining ventilatory function in the elderly impairs exercise capacity, we tested maximal exercise capacity and ventilatory function before and after a program of ventilatory muscle training in 25 elderly subjects (ages 65-75 yr). Ventilatory muscle training was performed by means of isocapnic hyperpnea for 30 min/day, 4 days/wk for 8 wk. Before and after the training, we measured maximal exercise capacity by means of an incremental exercise test (IET) and ventilatory muscle endurance by means of the maximum sustained ventilatory capacity (MSVC). Ratings of perceived exercise (RPE) for breathlessness and leg effort were evaluated each minute by means of a modified Borg scale during both the IET and a 12-min single-stage exercise test (SST) performed at approximately 70% of the maximal exercise capacity. The trained group showed a significant increase in the MSVC, from 71.9 ± 26.4 to 86.9 ± 20.9 l/min (P less than 0.01), whereas the control group showed no change (66.3 ± 22.5 to 65.1 ± 22.1 l/min). In addition, the maximal voluntary ventilation increased in the trained group, from 115 ± 41 to 135 ± 36 l/min (P less than 0.01). Neither the trained nor the control group showed an increase in maximum O2 uptake, maximum CO2 consumption, or maximum minute ventilation during the IET. Evaluation of the RPE during both the IET and SST showed that although there was a small decrease in RPE for breathing and leg discomfort, changes between the control and treated groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Catalase prevents increased lung vascular permeability during air emboli in unanesthetized sheep
Authors: Flick M. R. , Milligan S. A. , Hoeffel J. M. , Goldstein I. M.
Published: December 2017

We studied the effects of bovine catalase on increased lung vascular permeability to fluid and protein during air emboli in unanesthetized sheep. Pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, lymph and plasma protein concentrations, arterial PO2, and numbers of arterial leukocytes were measured in paired experiments in which each sheep served as its own control. We found an increase in protein-rich lung lymph flow during embolization in untreated sheep, indicating an increase in microvascular permeability. When sheep were pretreated with intraperitoneal injections of catalase (50 mg/kg divided over the 24 h before air infusion), vascular pressures, arterial PO2, and leukocyte counts were not different from when the sheep were untreated, but the expected increases in transvascular fluid and protein flow during emboli were significantly attenuated (by approximately 50%). This effect required catalase enzyme activity, as demonstrated by the failure of enzymatically inactivated catalase (by reaction in vitro with aminotriazole in the presence of H2O2) or catalase vehicle (0.1% thymol in water) to affect the lung lymph response to air emboli. We conclude that H2O2 plays a role in the pathogenesis of the acute lung injury caused by intravenous air infusions into unanesthetized sheep. Because both catalase and superoxide dismutase have protected sheep lungs from air emboli-induced increased vascular permeability, a possible specific cause of microvascular barrier injury could be hydroxyl radicals formed from reactions between H2O2 and superoxide anion.
Postexercise dose-response relationship between plasma glucose and insulin secretion
Authors: Mikines K. J. , Farrell P. A. , Sonne B. , Tronier B. , Galbo H.
Published: December 2017

To investigate whether exertion changes beta-cell reactivity to glucose stimulation and to characterize the beta-cell response to glucose in humans, we performed four sequential 90-min hyperglycemic clamps (7, 11, 20, and 35 mM). Concentrations of hormones and metabolites involved in glucoregulation were measured. Metabolic rate and substrate utilization were studied by indirect calorimetry. Studies were performed without prior exercise, as well as 2 and 48 h after 60 min of bicycle exercise at 150 W. We found 1) a progressive increase in insulin concentrations reaching 1,092 ± 135 microU/ml with increasing glucose levels, 2) linear relationships between glucose concentrations and concentrations of C-peptide (r = 0.931 ± 0.008) and proinsulin (r = 0.952 ± 0.009),3) increased glucose oxidation with increasing glucose uptake, 4) increased plasma norepinephrine, O2 uptake, and beta-hydroxybutyrate at greater than or equal to 20 mM glucose, and 5) no change in beta-cell response or glucose-induced thermogenesis after one bout of exercise despite no compensating changes in plasma concentrations of hormones or metabolites. We conclude that the beta-cell has a very large secretory potential. Secretion of the beta-cell increases linearly with prolonged, graded hyperglycemia. The processing of proinsulin is unchanged during prolonged beta-cell stimulation. In addition, hyperglycemia and sympathetic nervous activity induced by hyperinsulinemia enhance metabolic rate and ketone body production. Finally, a single bout of exercise does not influence either the beta-cell response to intravenous glucose or glucose-induced thermogenesis.
Operation Everest II: oxygen transport during exercise at extreme simulated altitude
Authors: Sutton J. R. , Reeves J. T. , Wagner P. D. , Groves B. M. , Cymerman A. , Malconian M. K. , Rock P. B. , Young P. M. , Walter S. D. , Houston C. S.
Published: December 2017

A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 ±0.20 l/min at sea level to 1.17 ± 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 ± 1 Torr and PCO2 = 11 ± 1 Torr, with a marked reduction in mixed venous PO2 [14.8 ± 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.
Epinephrine infusion enhances muscle glycogenolysis during prolonged electrical stimulation
Authors: Spriet L. L. , Ren J. M. , Hultman E.
Published: December 2017

To determine the effects of epinephrine (EPI) infusion on muscle glycogenolysis and force production, the quadriceps muscles of both legs in six subjects were intermittently stimulated for 30 min. Contractions lasted 1.6 s (20 Hz) and were separated by 1.6 s of rest. EPI was infused (approximately 0.14 micrograms.kg body wt-1.min-1) in one leg during the last 15 min and the vastus lateralis was biopsied at rest (control leg only) and after 15, 18 (EPI leg only), and 30 min of stimulation. EPI infusion doubled the mole fraction of phosphorylase a (22.5 ± 4.1 to 44.8 ± 9.0%) and glycogenolysis (2.16 ± 0.72 to 5.45 ± 0.81 mmol glucosyl U.kg dry muscle wt-1.min-1) during stimulation. Muscle glucose 6-phosphate increased from 3.04 ± 0.17 to 6.43 ± 0.20 mmol/kg dry muscle wt, and lactate increased from 25.8 ± 4.4 to 34.3 ± 4.6 mmol/kg after 3 min of EPI infusion. Isometric force production was unaltered by EPI infusion. These results demonstrate a strong glycogenolytic effect of EPI infusion during prolonged electrical stimulation and suggest that the extra pyruvate formed was converted mainly to lactate. Exclusive anaerobic metabolism of the extra substrate would provide only a 10% increase in total ATP production, possibly accounting for the lack of improvement in force production. We suggest that the decrease in force production during prolonged electrical stimulation is related to decreased excitation of the contractile mechanism rather than inhibition of cross-bridge turnover caused by a shortage of energy or accumulation of hyproducts.
Ventilatory response to sustained hypoxia after pretreatment with aminophylline
Authors: Easton P. A. , Anthonisen N. R.
Published: December 2017

During sustained hypoxia the decline in ventilation that occurs in normal adult humans may be related to central accumulation of a neurochemical with net inhibitory effect. Recent investigations have shown that the putative neurotransmitter adenosine can effect a prolonged respiratory inhibition. Therefore we evaluated the possible role of adenosine in the hypoxia ventilatory decline by employing aminophylline as an adenosine blocker. We evaluated the ventilatory response to 25 min of sustained hypoxia (80% arterial O2 saturation), in eight young adults after pretreatment with either intravenous saline or aminophylline. With a mean serum aminophylline level of 15.7 mg/l, over 25 min of sustained hypoxia, peak hypoxic ventilation decreased by only 12.8% compared with 24.8% with saline, a significant difference. However, the ventilatory decline during sustained hypoxia was not abolished by the aminophylline pretreatment. Unlike the usual tidal volume-dependent attenuation of hypoxic ventilation exhibited after saline, after aminophylline the ventilatory decline was achieved predominantly through alterations in respiratory timing. Thus aminophylline pretreatment did alleviate the hypoxic ventilatory decline, although the associated alterations in breathing pattern were uncharacteristic. We conclude that adenosine may play a contributing role in the hypoxic ventilatory decline.
Exercise thermoregulation after prolonged wakefulness
Authors: Kolka M. A. , Stephenson L. A.
Published: December 2017

The effect of 33 h of wakefulness on the control of forearm cutaneous blood flow and forearm sweating during exercise was studied in three men and three women. Subjects exercised for 30 min at 60% peak O2 consumption while seated behind a cycle ergometer (Ta = 35 degrees C, Pw = 1.0 kPa). We measured esophageal temperature (Tes), mean skin temperature, and arm sweating continuously and forearm blood flow (FBF) as an index of skin blood flow, twice each minute by venous occlusion plethysmography. During steady-state exercise, Tes was unchanged by sleep loss. The sensitivity of FBF to Tes was depressed an average of 30% (P less than 0.05) after 33 h of wakefulness with a slight decrease (-0.15 degrees C, P less than 0.05) in the core temperature threshold for vasodilatory onset. Sleep loss did not alter the Tes at which the onset of sweating occurred; however, sensitivity of arm sweating to Tes tended to be lower but was not significant. Arm skin temperature was not different between control and sleep loss experiments. Reflex cutaneous vasodilation during exercise appeared to be reduced by both central and local factors after 33 h of wakefulness
Effect of normobaric hyperoxia on airways of normal subjects
Authors: Beckett W. S. , Wong N. D.
Published: December 2017

Airway responsiveness to inhaled cholinergic agonist during the early stage of pulmonary O2 toxicity was examined to determine whether normobaric hyperoxia alters airway function. Eight healthy nonsmoking males with moderate base-line methacholine responsiveness breathed normobaric O2 (greater than or equal to 95%) over 12 h and on another occasion breathed air in an identical protocol. Vital capacity, expiratory flow, airway responsiveness to methacholine, and respiratory symptoms were measured at 0, 4, 8, and 12 h while subjects breathed O2 and 12 h afterwards. After 12 h, forced vital capacity was significantly decreased with O2 breathing but not with air breathing. At 4, 8, or 12 h of exposure and 12 h after exposure, there was no difference in methacholine sensitivity or reactivity between O2 and air-exposure trials. The earliest manifestations of pulmonary normobaric O2 toxicity in normal adults include diminished vital capacity and the onset of respiratory symptoms, but early O2 toxicity does not produce altered responsiveness to inhaled methacholine.
Increased lung volume limits endurance of inspiratory muscles
Authors: Tzelepis G. , McCool F. D. , Leith D. E. , Hoppin F. G.
Published: December 2017

We examined the influence of lung volume on the ability of normal subjects to sustain breathing against inspiratory resistive loading. Four normal subjects breathed on a closed circuit in which inspiration was loaded by a flow resistor. Subjects were assigned a series of breathing tasks over a range of pressures and flows. In each task there was a specified resistor and also targets for either mean esophageal or airway opening pressure, respiratory frequency, and duty cycle. Endurance was assessed as the length of time to failure of the assigned task. The prime experimental variable was lung volume, which was increased by approximately 1 liter during some tasks; 8 cmH2O continuous positive airway pressure was applied to increase lung volume without increasing elastic load. As previously shown (McCool et al.J. Appl. Physiol. 60: 299–303, 1986), for tasks that could be sustained for the same time, there was an inverse linear relationship of mean esophageal pressure with inspiratory flow rate. This trade-off of pressure and flow was apparent both with and without the increase of lung volume. Comparable tasks, however, could not be sustained as long at the higher lung volumes. This effect of volume on endurance was greater for tasks characterized by high inspiratory pressures and low flow rates than for tasks that could be sustained for the same time but that had lower inspiratory pressures and higher flow rates. This is probably due to the effects of shortening of the sarcomere on fatiguability. Increased lung volume, per se, may contribute to respiratory failure because of increased inspiratory muscle fatiguability by mechanisms independent of elastic load.
Nonadrenergic bronchodilator mechanisms in normal human subjects in vivo
Authors: Lammers J. W. , Minette P. , McCusker M. T. , Chung K. F. , Barnes P. J.
Published: December 2017

In seven normal subjects we investigated whether a nonadrenergic bronchodilator nervous system is demonstrable in humans in vivo. After inhalation of leukotriene D4 (LTD4), respiratory resistance (Rrs) increased by 115 +/- 11% (SE). Subsequent inhalation of 2 nmol of capsaicin induced coughing and a fall in Rrs of 22.1 +/- 2% (P less than 0.01). However, inhalation of the diluent of capsaicin, 10% saline-ethanol, decreased Rrs similarly. These bronchodilator responses were not altered by inhaled ipratropium bromide (120 micrograms) and oral propranolol (80 mg). After ipratropium and propranolol, voluntary coughing alone decreased Rrs by 25 +/- 3% (P less than 0.05). We next investigated whether these bronchodilator responses could be blocked by anesthesia of the airways with inhaled lidocaine. After inhalation of lidocaine and LTD4, capsaicin aerosol induced coughing and a transient increase in Rrs of 18 +/- 6% (P less than 0.05) but no bronchodilation. Inhalation of saline-ethanol (n = 4) and a deep inhalation (n = 6) decreased Rrs by 18 +/- 4% (P less than 0.05) and 34 +/- 3% (P less than 0.001), respectively. We conclude that in normal subjects a nonadrenergic, noncholinergic bronchodilator mechanism exists, which can be activated by inhalation of capsaicin and inhibited by local anesthesia.
Modulation by endogenous opioids of pulmonary vasoconstrictor response to acute lung injury
Authors: Scardella A. T. , Neubauer J. A. , Edelman N. H. , Santiago T. V.
Published: December 2017

The effects of endogenously generated opioids on distribution of pulmonary perfusion (as assessed by radiolabeled microspheres) and overall gas exchange in acute acid-induced lung injury were studied. In 14 anesthesized dogs, sufficient acid was given to one lung to double shunt fraction (Qs/Qt) from 14.2 +/- 0.8 to 32.4 +/- 2.6% (SE). This resulted in a significant decrease in Po2 from 495 +/- 9 to 136 +/- 21 Torr, cardiac output from 2.47 +/- 0.27 to 1.46 +/- 0.15 1/min, and blood pressure from 139 +/- 3 to 116 +/- 5 mmHg and a significant rise in pulmonary arterial pressure from 9.6 +/- 0.8 to 14.9 +/- 0.8 mmHg. After acid instillation, microsphere distribution to the injured lung segments decreased to 50% of the base-line value. At the same time, microsphere distribution in the normal segments increased to 160% of base line. In 7 of the 14 dogs the effects of naloxone (1 mg/kg) given after lung injury were compared with the other 7 animals that were given saline. Naloxone administration caused a significant redistribution of regional pulmonary perfusion such that microsphere distribution in the injured lung segments increased by a factor of 2 at 35 min compared with the animals given saline. Consistent with this finding, Qs/Qt in the naloxone group increased to 34.7 +/- 5.0% at 35 min, whereas that of the saline group decreased to 28.2 +/- 2.5%. The difference between the two groups was significant at 35 min. These changes occurred without further alterations in cardiac output, pulmonary arterial pressure, or systemic blood pressure in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of fasting on carbohydrate and fat metabolism during rest and exercise in men
Authors: Knapik J. J. , Meredith C. N. , Jones B. H. , Suek L. , Young V. R. , Evans W. J.
Published: December 2017

Metabolic effects of an overnight fast (postabsorptive state, PA) or a 3.5-day fast (fasted state, F) were compared in eight healthy young men at rest and during exercise to exhaustion at 45% maximum O2 uptake. Glucose rate of appearance (Ra) and disappearance (Rd) were calculated from plasma glucose enrichment during a primed, continuous infusion of [6,6–2H]glucose. Serum substrates and insulin levels were measured and glycogen content of the vastus lateralis was determined in biopsies taken before and after exercise. At rest, whole-body glucose flux (determined by the deuterated tracer) and carbohydrate oxidation (determined from respiratory exchange ratio) were lower in F than PA, but muscle glycogen levels were similar. During exercise, glucose flux, whole-body carbohydrate oxidation, and the rate of muscle glycogen utilization were significantly lower during the fast. In the PA state, glucose Ra and Rd increased together throughout exercise. However, in the F state Ra exceeded Rd during the 1st h of exercise, causing an increase in plasma glucose to levels similar to those of the PA state. The increase in glucose flux was markedly less throughout F exercise. Lower carbohydrate utilization in the F state was accompanied by higher circulating fatty acids and ketone bodies, lower plasma insulin levels, and the maintenance of physical performance reflected by similar time to exhaustion.
Recycling of surfactant in black and beige mice: pool sizes and kinetics
Authors: Gross N. J. , Barnes E. , Narine K. R.
Published: December 2017

Lung disaturated phosphatidylcholine (DSPC) turnover was investigated in normal C57 black and mutant beige mice; the latter have been postulated to have microtubular defects. Turnover experiments were performed on 117 black and 74 beige mice that were assayed for lamellar body-rich fraction (LB) and alveolar lavage fluid (AF) DSPC from 0.5 to 100 h after injection of [3H]glycerol. The data were analyzed by a program that derived the best-fit rate constants for an operator-chosen compartmental model. For black mice, a simple model with bidirectional exchange of DSPC between LB and AF compartments fitted the data almost as well as more complex models. This model yielded a turnover time of 5.9 h, a biological half-life of 16 h, and recycling of AF DSPC into LB of 47%. There was some evidence to suggest that DSPC might be degraded rather than recycled as a unit. For beige mice, the DSPC turnover time was 4.8 h, and its biological half-life was 40 h. The AF DSPC pool was smaller than in black mice, but the LB pool was larger. The bidirectional flux of DSPC between AF and LB was much greater than in black mice, the percent of recycling being 85. These data do not support a microtubular defect in beige mice, but the calculations for beige mice are based on a model of questionable validity.
Velocity-length-time relations in canine tracheal smooth muscle
Authors: Seow C. Y. , Stephens N. L.
Published: December 2017

Zero-load velocity (V0) as a function of the length of canine tracheal smooth muscle was obtained by applying zero-load clamps to isotonically contracting muscle under various loads. The load clamps were applied at a specific time after onset of contraction. The magnitude of the isotonic load therefore determines the length of the muscle at the moment of release or at the moment the unloaded shortening velocity was measured. A family of such V0-muscle length (L) curves was obtained at 1-s intervals in the time course of contraction. The V0-L curve was fitted by a parabolic function with satisfactory goodness of fit. The maximum shortening velocity at optimum muscle length varied with time, but the minimum length at which V0 diminished to zero was time independent.
Assessment of maximal expiratory pressure in healthy adults
Authors: Rubinstein I. , Slutsky A. S. , Rebuck A. S. , McClean P. A. , Boucher R. , Szeinberg A. , Zamel N.
Published: December 2017

Maximal static expiratory pressure developed at the mouth (PEmax) provides a useful clinical index of expiratory muscle function; however, the range of normal values among laboratories shows considerable variation. We examined the hypothesis that the wide variability could be attributable to the differences in technique among laboratories. We measured PEmax at functional residual capacity (PEmax FRC) in 28 healthy subjects using the following five techniques: 1) using a scuba-type mouthpiece with the cheeks supported by the hands ("hands on"), 2) without supporting the cheeks ("no hands"), 3) using a rigid, circular mouthpiece (2.8 cm ID, "tube"), 4) using the scuba-type mouthpiece but with the cheeks supported by an observer ("other hands"), and 5) using a large-bore circular mouthpiece (4.1 cm ID, "new tube"). Mean PEmax FRC obtained with hands on was significantly higher than no-hands and tube methods. PEmax FRC values obtained by the other-hands and new-tube maneuvers were similar to the hands-on maneuver. We conclude that the technique used to measure PEmax FRC can significantly affect the results and suggest that it should be measured using a large-bore circular mouthpiece or a scuba-diving mouthpiece with the cheeks supported.
Effect of metabolic products of muscular contraction on discharge of group III and IV afferents
Authors: Rotto D. M. , Kaufman M. P.
Published: December 2017

Static muscular contraction has been firmly established to reflexly increase cardiovascular and ventilatory function. Although group III and IV fibers with endings in muscle have been shown to comprise the afferent arm of this reflex arc, little is known about the nature of the contraction-induced stimulus causing the activation of these fibers. This stimulus has often been suggested to be a metabolic product of muscular contraction. We have therefore recorded the impulse activity of group III and IV afferents with endings in the triceps surae muscles of barbiturate-anesthetized cats while we injected into the femoral artery substances believed to be metabolic products of muscular contraction. We found that lithium and sodium lactate (400 mM; 1 ml) had little or no effect on the discharge of group III and IV afferents. Likewise, monobasic sodium phosphate (20 and 400 mM; 1 ml) and 2-chloroadenosine (50–100 micrograms) had only trivial effects on the discharge of these afferents. By contrast, lactic acid (25 and 400 mM; 1 ml) and arachidonic acid (0.5–2.0 mg) caused significant increases in the activity of group III and IV afferents. Most of the excitatory effect of arachidonic acid on the discharge of the afferents was prevented by indomethacin, a cyclooxygenase inhibitor. We conclude that of the substances tested in our experiments, lactic acid and some cyclooxygenase products, such as prostaglandins and thromboxanes, are the most likely to be responsible for any metabolic stimulation of group III and IV afferents during muscular contraction.
Influenza infection causes airway hyperresponsiveness by decreasing enkephalinase
Authors: Jacoby D. B. , Tamaoki J. , Borson D. B. , Nadel J. A.
Published: December 2017

Ferret tracheal segments were infected with human influenza virus A/Taiwan/86 (H1N1) in vitro. After 4 days, the smooth muscle contractile responses to acetylcholine and to substance P were measured. The response to substance P was markedly accentuated, with a threefold increase in force of contraction at a substance P concentration of 10(-5) M, the highest concentration tested. In contrast, the response to acetylcholine was not affected by viral infection. Histological examination of tissues revealed extensive epithelial desquamation. Activity of enkephalinase (neutral metallo-endopeptidase, EC.3.4.24.11), an enzyme that degrades substance P, was decreased by 50% in infected tissues. Inhibiting enkephalinase activity by pretreating with thiorphan (10(-5) M) increased the response to substance P to the same final level in both infected and control tissues. Inhibiting other substance P-degrading enzymes including kininase II (angiotensin-converting enzyme), serine proteases, and aminopeptidases did not affect the response to substance P. Inhibiting cyclooxygenase and lipoxygenase activity using indomethacin and BW 755c did not affect hyperresponsiveness to substance P. Pretreating tissues with antagonists of alpha-adrenoceptors, beta-adrenoceptors, and H1 histamine receptors (phentolamine 10(-5) M, propranolol 5 X 10(-6) M, and pyrilamine 10(-5) M, respectively) had no effect on substance P-induced contraction. These results demonstrate that infection of ferret airway tissues with influenza virus increases the contractile response of airway smooth muscle to substance P. This effect is caused by decreased enkephalinase activity in infected tissues.
Sympathoadrenal response to repetitive exercise in normal and asthmatic subjects
Authors: Gilbert I. A. , Lenner K. A. , McFadden E. R.
Published: December 2017

To explore the role of catecholamine release in the pathogenesis of exercise-induced asthma, we had seven asthmatic and seven normal subjects undergo three hourly exercise challenges that were matched for inspired air temperature, minute ventilation, and relative work loads. Pulmonary mechanics and plasma epinephrine and norepinephrine were measured before, at end exercise, and serially after each challenge. There were no differences in the pattern of sympathoadrenal response of asthmatic and normal subjects, and both groups released sufficient quantities of epinephrine and norepinephrine into the peripheral circulation to allow these compounds to function as circulating hormones. As the catecholamines rose with repetitive exercise, progressive bronchodilation occurred in the asthmatics at the end of the work load, thus decreasing the apparent magnitude of the obstructive response. In addition to their effects on airway smooth muscle, the alpha-adrenergic actions of both catecholamines may have reduced airway wall hyperemia and edema. These data demonstrate that asthmatics do not have a defect in catecholamine release during exercise and that the physiological expression of exercise-induced asthma can be modulated by the sympathoadrenal epiphenomena that are associated with physical exertion.
Surfactant therapy of newborn rabbits impairs lung macrophage bactericidal activity
Authors: Sherman M. P. , D'Ambola J. B. , Aeberhard E. E. , Barrett C. T.
Published: December 2017

Because in vitro studies indicate that pulmonary alveolar macrophages (PAM's) filled with phospholipid vesicles have depressed microbicidal capacity, we tested the intrapulmonary bactericidal activity of newborn PAM's after surfactant treatment. Term newborn rabbits received intratracheally either homologous surfactant or one of two artificial phospholipid vesicle preparations followed by pulmonary aerosol infection with group B streptococci (GBS). Four hours after lung infection, phagocytic killing of GBS was reduced by 70-90% in animals treated with the homologous and one of the artificial surfactants compared with untreated animals or animals that received intrapulmonary injections of the surfactant vehicle (P less than 0.02). The other artificial phospholipid preparation decreased intrapulmonary inactivation of GBS by 30-40% compared with the controls. The phospholipid vesicles in the three preparations were avidly ingested and processed by newborn PAM's. The diminished in vivo killing of GBS was not attributed to decreased viability or phagocytic behavior of the PAM's toward GBS. The bactericidal defect that was evident in the newborn PAM's appeared related to the uptake of large phospholipid vesicles in the preparations rather than to the phospholipid content of the surfactants themselves. When in vitro conditions that stimulated the alveolar environment were used, the natural surfactant preparation promoted GBS proliferation, whereas the artificial preparations did not. Our findings indicate that surfactant administration reduces the bactericidal activity of neonatal PAM's. We conclude that additional investigations are needed to ascertain the effect of surfactant replacement therapy on lost defenses of the lung.
Physiological and biochemical correlates of increased work in trained iron-deficient rats
Authors: Willis W. T. , Dallman P. R. , Brooks G. A.
Published: December 2017

We investigated physiological and biochemical factors associated with the improved work capacity of trained iron-deficient rats. Female 21-day-old rats were assigned to one of four groups, two dietary groups (50 and 6 ppm dietary iron) subdivided into two levels of activity (sedentary and treadmill trained). Iron deficiency decreased hemoglobin (61%), maximal O2 uptake. (VO2max) (40%), skeletal muscle mitochondrial oxidase activities (59-90%), and running endurance (94%). In contrast, activities of tricarboxylic acid (TCA) cycle enzymes in skeletal muscle were largely unaffected. Four weeks of mild training in iron-deficient rats resulted in improved blood lactate homeostasis during exercise and increased VO2max (15%), TCA cycle enzymes of skeletal muscle (27-58%) and heart (29%), and liver NADH oxidase (34%) but did not affect any of these parameters in the iron-sufficient animals. In iron-deficient rats training affected neither the blood hemoglobin level nor any measured iron-dependent enzyme pathway of skeletal muscle but substantially increased endurance (230%). We conclude that the training-induced increase in endurance in iron-deficient rats may be related to cardiovascular improvements, elevations in liver oxidative capacity, and increases in the activities of oxidative enzymes that do not contain iron in skeletal and cardiac muscle.
Involvement of sodium retention hormones during rehydration in humans
Authors: Nose H. , Mack G. W. , Shi X. R. , Nadel E. R.
Published: December 2017

We investigated the relation between involuntary dehydration and the mechanisms affecting Na+ retention in the body, focusing on the renin-angiotensin-aldosterone system. Six adult males were dehydrated to 2.3% of their body weight by an exercise-heat regimen, followed by rehydration (180 min) with tap water (H2O-R) or 0.45% NaCl solution (Na-R). We measured plasma renin activity (PRA) and aldosterone levels (PA) before dehydration (control), after dehydration, and at 60, 120, and 180 min of rehydration. During the 3-h rehydration period, subjects, restored 51% of the water lost during H2O-R and 71% during Na-R (P less than 0.05). Plasma volume was reduced by an average of 4.5% after dehydration. After 180 min of rehydration, plasma volume restoration during Na-R was to 174% of that lost, and during H2O-R it was to 78% of that lost. We found significant correlations between the change in plasma volume and PRA (r = -0.70, P less than 0.001) and between PRA and PA (r = 0.71, P less than 0.001). In both recovery conditions, PRA increased significantly after dehydration (P less than 0.05) and decreased almost to the control level by 180 min of rehydration, at which time the plasma volume deficit was restored. The change in PA paralleled that in PRA. The rate of sodium excretion was correlated with PA levels in both groups (r = -0.58, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Venous occlusion pressure and vascular permeability in the dog lung after air embolization
Authors: Hall J. E. , Hofman W. F. , Ehrhart I. C.
Published: December 2017

Pulmonary edema has frequently been associated with air embolization of the lung. In the present study the hemodynamic effects of air emboli (AE) were studied in the isolated mechanically ventilated canine right lower lung lobe (RLL), pump perfused at a constant blood flow. Air was infused via the pulmonary artery (n = 7) at 0.6 ml/min until pulmonary arterial pressure (Pa) rose 250%. While Pa rose from 12.4 +/- 0.6 to 44.6 +/- 2.0 (SE) cmH2O (P less than 0.05), venous occlusion pressure remained constant (7.0 +/- 0.5 to 6.8 +/- 0.6 cmH2O; P greater than 0.05). Lobar vascular resistance (RT) increased from 2.8 +/- 0.3 to 12.1 +/- 0.2 Torr.ml-1.min.10(-2) (P less than 0.05), whereas the venous occlusion technique used to determine the segmental distribution of vascular resistance indicated the increase in RT was confined to vessels upstream to the veins. Control lobes (n = 7) administered saline at a similar rate showed no significant hemodynamic changes. As an index of microvascular injury the pulmonary filtration coefficient (Kf) was obtained by sequential elevations of lobar vascular pressures. The Kf was 0.11 +/- 0.01 and 0.07 +/- 0.01 ml.min-1.Torr-1.100 g RLL-1 in AE and control lobes, respectively (P less than 0.05). Despite a higher Kf in AE lobes, total lobe weight gains did not differ and airway fluid was not seen in the AE group. Although air embolization caused an increase in upstream resistance and vascular permeability, venous occlusion pressure did not increase, and marked edema did not occur.
Divergent effects of silica on lymphocyte proliferation and immunoglobulin production
Authors: Moseley P. L. , Monick M. , Hunninghake G. W.
Published: December 2017

Silicosis is an interstitial lung disorder that is frequently associated with hypergammaglobulinemia and increased numbers of lymphocytes at sites of disease. To determine the effect of silica on the generation of immunoglobulin-secreting cells, mononuclear cells were stimulated with antigens or mitogens and placed into 1) high-density cultures (2.5 X 10(6) cells/ml) that were not exposed to silica, in which pokeweed mitogen (PWM)-induced generation of immunoglobulin-secreting cells was suppressed by the presence of monocytes; or 2) low-density cultures (0.5 X 10(6) cells/ml) that were not exposed to silica, in which PWM-induced generation of immunoglobulin-secreting cells was not suppressed. Silica added to PWM-stimulated high-density cultures significantly increased the numbers of immunoglobulin-secreting cells. Silica also significantly increased the numbers of immunoglobulin-secreting cells in high-density cultures stimulated with purified protein derivative and tetanus toxoid and augmented the proliferation of phytohemagglutinin-stimulated mononuclear cells (P less than 0.05). In contrast to high-density cultures, silica added with PWM to low-density cultures reduced the numbers of immunoglobulin-secreting cells. These studies suggest that silica can have potent regulatory effects on various cellular immune processes that are relevant to the lung.
Extrathoracic and intrathoracic removal of O3 in tidal-breathing humans
Authors: Gerrity T. R. , Weaver R. A. , Berntsen J. , House D. E. , O'Neil J. J.
Published: December 2017

We measured the efficiency of O3 removal from inspired air by the extrathoracic and intrathoracic airways in 18 healthy, nonsmoking, young male volunteers. Removal efficiencies were measured as a function of O3 concentration (0.1, 0.2, and 0.4 ppm), mode of breathing (nose only, mouth only, and oronasal), and respiration frequency (12 and 24 breaths/min). Subjects were placed in a controlled environmental chamber into which O3 was introduced. A small polyethylene tube was then inserted into the nose of each subject, with the tip positioned in the posterior pharynx. Samples of air were collected from the posterior pharynx through the tube and into a rapidly responding O3 analyzer yielding inspiratory and expiratory O3 concentrations in the posterior pharynx. The O3 removal efficiency of the extrathoracic airways was computed with the use of the inspiratory concentration and the chamber concentration, and intrathoracic removal efficiency was computed with the use of the inspiratory and expiratory concentrations. The mean extrathoracic removal efficiency for all measurements was 39.6 +/- 0.7% (SE), and the mean intrathoracic removal efficiency was 91.0 +/- 0.5%. Significantly less O3 was removed both extrathoracically and intrathoracically when subjects breathed at 24 breaths/min compared with 12 breaths/min (P less than 0.001). O3 concentration had no effect on extrathoracic removal efficiency, but there was a significantly greater intrathoracic removal efficiency at 0.4 ppm than at 0.1 ppm (P less than 0.05). Mode of breathing significantly affected extrathoracic removal efficiency, with less O3 removed during nasal breathing than during either mouth breathing or oronasal breathing (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of acetazolamide on cerebral acid-base balance
Authors: Bickler P. E. , Litt L. , Banville D. L. , Severinghaus J. W.
Published: December 2017

Acetazolamide (AZ) inhibition of brain and blood carbonic anhydrase increases cerebral blood flow by acidifying cerebral extracellular fluid (ECF). This ECF acidosis was studied to determine whether it results from high PCO2, carbonic acidosis (accumulation of H2CO3), or lactic acidosis. Twenty rabbits were anesthetized with pentobarbital sodium, paralyzed, and mechanically ventilated with 100% O2. The cerebral cortex was exposed and fitted with thermostatted flat-surfaced pH and PCO2 electrodes. Control values (n = 14) for cortex ECF were pH 7.10 +/- 0.11 (SD), PCO2 42.2 +/- 4.1 Torr, PO2 107 +/- 17 Torr, HCO3- 13.8 +/- 3.0 mM. Control values (n = 14) for arterial blood were arterial pH (pHa) 7.46 +/- 0.03 (SD), arterial PCO2 (PaCO2) 32.0 +/- 4.1 Torr, arterial PO2 (PaO2) 425 +/- 6 Torr, HCO3- 21.0 +/- 2.0 mM. After intravenous infusion of AZ (25 mg/kg), end-tidal PCO2 and brain ECF pH immediately fell and cortex PCO2 rose. Ventilation was increased in nine rabbits to bring ECF PCO2 back to control. The changes in ECF PCO2 then were as follows: pHa + 0.04 +/- 0.09, PaCO2 -8.0 +/- 5.9 Torr, HCO3(-)-2.7 +/- 2.3 mM, PaO2 +49 +/- 62 Torr, and changes in cortex ECF were as follows: pH -0.08 +/- 0.04, PCO2 -0.2 +/- 1.6 Torr, HCO3(-)-1.7 +/- 1.3 mM, PO2 +9 +/- 4 Torr. Thus excess acidity remained in ECF after ECF PCO2 was returned to control values. The response of intracellular pH, high-energy phosphate compounds, and lactic acid to AZ administration was followed in vivo in five other rabbits with 31P and 1H nuclear magnetic resonance spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
Automated temperature control system for vagal cooling
Authors: Cha E. J. , Chow E. , Vega D. M. , Yamashiro S. M.
Published: December 2017

An automated cooling system for vagal cold blockade was developed. A simple electronic circuit is described that enabled regulation of the steady-state nerve or circulant temperature to within +/- 0.1 degree C by alternating the cold circulant between low and high flows (10 and 350 ml/min, respectively). The 90% rise time ranged from 15 to 40 s depending on the desired steady state and the surrounding temperatures. The present apparatus can be conveniently and safely used, especially for differential vagal cold blockade.
Regulation of lactic acid production during exercise
Authors: Katz A. , Sahlin K.
Published: December 2017

Cortisol has minimal effects on lung maturation in fetal sheep before 130 days gestation. To test whether there is enhancement of cortisol action by other hormones, cortisol (F), triiodothyronine (T3), epinephrine (E), prolactin (PRL), and epidermal growth factor (EGF), alone or in combination, were infused into fetal sheep for 84 h between 124 and 128 days gestation. A mixture of F + T3 + PRL, but not any combination of two hormones, increased both distensibility [1.71 +/- 0.12 (SE) ml of air/g wet wt at 40 cmH2O, V40] and stability (1.16 +/- 0.09 ml of air per g wet wt at 5 cmH2O, V5) to near full-term values, above values resulting from treatment with F alone (0.91 +/- 0.12 and 0.43 +/- 0.09 ml/g, P less than 0.01). Only F had an effect when given alone, V40 increasing (P less than 0.05). Treatment with F + T3 (0.81 +/- 0.18 ml/g) and F + E (0.77 +/- 0.07 ml/g) increased V5 above values obtained with F alone (P less than 0.05). Alveolar saturated phosphatidylcholine (SPC) was higher after treatment with F + T3 (161 +/- 52 micrograms/g), F + T3 + PRL (156 +/- 53 micrograms/g, P less than 0.05), and F + E (113 +/- 40 micrograms/g, P = 0.07) than after F (12 +/- 3 micrograms/g). We conclude that F, T3, and PRL have a synergistic effect on the development of distensibility and stability of the ovine fetal lung.
Body composition response to exogenous GH during training in highly conditioned adults
Authors: Crist D. M. , Peake G. T. , Egan P. A. , Waters D. L.
Published: December 2017

The effects of biosynthetic methionyl-human growth hormone (met-hGH) on body composition and endogenous secretion of growth hormone (GH) and insulin-like growth factor I (IGF-I) were studied in eight well-trained exercising adults between 22 and 33 yr of age. By the use of double-blind procedures, met-hGH (2.67 mg/0.5 ml diluent, 3 days/wk) and bacteriostatic water (placebo, 0.5 ml, 3 days/wk) were administered in a repeated-measures design that counterbalanced treatment order. Duration of each treatment was 6 wk. Subjects trained with progressive resistance exercise throughout and were maintained on a high-protein diet monitored by extensive compositional analyses of daily dietary intake records. Hydrodensitometry revealed that met-hGH significantly decreased percent body fat (%fat) and increased fat-free weight (FFW) and FFW/fat weight (FW), whereas the placebo treatment did not change any of these measures. Changes in FFW/FW correlated with the relative dose of met-hGH but did not correlate with either the peak GH response to L-dopa/arginine stimulation or IGF-I levels obtained after treatment with placebo. There were no differences between treatments in the dietary intakes of total kilocalories, protein, carbohydrates, and fat. Mean IGF-I levels were elevated after treatment with met-hGH compared with postplacebo levels. After treatment with met-hGH, five of seven subjects had a suppressed GH response to stimulation from either L-dopa/arginine or submaximal exercise. We conclude that supraphysiological doses of met-hGH will alter body composition in exercising adults in a relative dose-dependent manner and that such treatment may suppress endogenous release of GH in some individuals.
Alveolar liquid and protein clearance from normal dog lungs
Authors: Berthiaume Y. , Broaddus V. C. , Gropper M. A. , Tanita T. , Matthay M. A.
Published: December 2017

To determine whether liquid and protein clearance from the air spaces and lungs of anesthetized and unanesthetized dogs is the same as in sheep, we quantified these variables at three different time periods (4, 8, and 12 h) by instilling heparinized plasma (3 ml/kg) labeled with 125I-albumin into one lower lobe. Protein clearance, measured from the residual 125I-albumin in the lung homogenate, was slow and monoexponential (approximately 1%/h), similar to our previous data for protein clearance from the lungs in sheep. Lung liquid clearance in dogs, however, was 50% less than in previous experiments in sheep. Residual lung liquid (as percent of instilled) was 88.7 +/- 7.0 at 4 h, 70.5 +/- 9.1 at 8 h, and 64.0 +/- 5.8 at 12 h. At each time period, alveolar protein concentration increased by 0.6 +/- 0.4 g/dl at 4 h, 1.3 +/- 1.2 g/dl at 8 h, and 2.1 +/- 0.8 g/dl at 12 h. This increase in alveolar protein concentration was proportional to the volume of liquid removed from the lungs. beta-Adrenergic agonist therapy with terbutaline (10(-5) M mixed with the instilled plasma) doubled the volume of liquid cleared from the lungs over 4 h, and the alveolar protein concentration increased proportionally. However, lung liquid clearance in dogs that were treated with beta-agonists was proportionally (50%) less than in sheep treated with beta-agonists. The slower liquid clearance in dogs compared with sheep cannot be explained by differences in hemodynamics, pulmonary blood flow, anesthesia, mode of ventilation, or alveolar surface area.(ABSTRACT TRUNCATED AT 250 WORDS)