bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbohydrate metabolism in fructose-fed and food-restricted running rats
Authors: Sonne B. , Galbo H.
Published: December 2017

In chronically catheterized rats hepatic glycogen was increased by fructose (approximately 10 g/kg) gavage (FF rats) or lowered by overnight food restriction (FR rats). [3-3H]- and [U-14C]glucose were infused before, during, and after treadmill running. During exercise the increase in glucose production (Ra) was always directly related to work intensity and faster than the increase in glucose disappearance, resulting in increased plasma glucose levels. At identical work-loads the increase in Ra and plasma glucose as well as liver glycogen breakdown were higher in FF and control (C) rats than in FR rats. Breakdown of muscle glycogen was less in FF than in C rats. Incorporation of [14C]glucose in glycogen at rest and mobilization of label during exercise partly explained that 14C estimates of carbohydrate metabolism disagreed with chemical measurements. In some muscles glycogen depletion was not accompanied by loss of 14C and 3H, indicating futile cycling of glucose. In FR rats a postexercise increase in liver glycogen was seen with 14C/3H similar to that of plasma glucose, indicating direct synthesis from glucose. In conclusion, in exercising rats the increase in glucose production is subjected to feedforward regulation and depends on the liver glycogen concentration. Endogenous glucose may be incorporated in glycogen in working muscle and may be used directly for liver glycogen synthesis rather than after conversion to trioses. Fructose ingestion may diminish muscular glycogen breakdown. The [14C]glucose infusion technique for determination of muscular glycogenolysis is of doubtful value in rats.
Thromboxane A2 and prostacyclin do not modulate pulmonary hemodynamics during exercise in sheep
Authors: Newman J. H. , Butka B. J. , Brigham K. L.
Published: December 2017

The purpose of this study was to determine the role of thromboxane and prostacyclin in modulating pulmonary hemodynamics during maximal cardiopulmonary stress in the healthy lung. We studied 11 yearling sheep in paired studies during progressive maximal treadmill exercise with and without meclofenamate (n = 5), ibuprofen (n = 6), or UK38485 (n = 2). We also studied five sheep during hypoxia and hypoxic exercise, and six sheep during prolonged steady-state treadmill exercise for 45-60 min with and without drug treatment. We measured the metabolites of thromboxane A2 (thromboxane B2, TxB2) and prostacyclin (6-ketoprostaglandin F1 alpha, 6-keto-PGF1 alpha) in blood plasma and lung lymph in each protocol. We found that progressive exercise significantly reduced pulmonary vascular resistance but that cyclooxygenase or thromboxane synthesis blockade did not alter the change. Plasma TxB2 rose minimally but significantly during maximal exercise, but 6-keto-PGF1 alpha did not change. During continuous hypoxia, exercise reduced pulmonary vascular resistance nearly to base-line levels, but the degree of reduction was also unchanged by drug treatment. There were also no significant changes in lymph or plasma TxB2 or 6-keto-PGF1 alpha during 45-60 min of continuous moderate exercise. We conclude that neither TxB2 nor prostacyclin modulate pulmonary hemodynamics in the normal lung during maximal exercise, prolonged moderate exercise, or exercise-induced reductions in vascular resistance during hypoxia.
Arterial elasticity and physical working capacity in young men
Authors: Eugene M. , Vandewalle H. , Bertholon J. F. , Teillac A.
Published: December 2017

We have tested the hypothesis that there is a positive relation between arterial elasticity and physical working capacity (PWC) at a given age. The subjects were 28 young men, 16–18 yr old. Arterial elasticity was evaluated by measuring the carotid to femoral pulse-wave velocity (c) at rest. The slope, S(c) of the relation between c and the diastolic blood pressure was studied during a cold pressor test to test vascular reactivity. The relationship between heart rate (HR) and work load was determined using a cycle ergometer; the variables measured were the slope of this relation S(PWC) and the power output at a HR of 170 min-1 (PWC170). The PWC170 ranged from 1.8 to 4.6 W/kg, and values of c ranged from 3.9 to 6.8 m/s. A strong inverse linear relation was found between c and PWC170 (r = -0.76), whereas the HR at rest was positively related to both c (r = 0.68) and PWC170 (r = 0.74). There was no relationship between HR at rest and the slopes S(c) and S(PWC); the latter two variables depend mainly on the sympathetic response. These results show the importance of the intrinsic mechanical properties of the cardiovascular system, particularly arterial elasticity, in human adaptations to muscular exercise.
Increased lung vascular permeability after arachidonic acid and hydrostatic challenge
Authors: Seeger W. , Walmrath D. , Menger M. , Neuhof H.
Published: December 2017

Arachidonic acid (AA) metabolites are known to be potent vasoactive substances in the pulmonary circulation, whereas their influence on lung vascular permeability is still uncertain. We investigated the effect of AA bolus injection on the capillary filtration coefficient (Kf,C) of isolated rabbit lungs, recirculatingly perfused with Krebs-Henseleit albumin (1%) buffer. Kf,C was measured using repetitive sudden venous pressure elevations (7.5 Torr) and time zero extrapolation of the slope of the weight gain curve. It ranged from 1.3 to 2.4 cm3 X s-1 X Torr-1 X g-1 X 10(-4) in control lungs. Pulmonary arterial injection of AA (100 microM; in presence of 20 microM indomethacin to suppress pulmonary arterial pressure rise) during an acute hydrostatic challenge, but not at zero venous pressure, caused a greater than 10-fold increase in Kf,C. Vascular compliance was not altered. Additional experiments, performed under zero-flow conditions to avoid any ambiguity in microvascular pressure, corroborated the severalfold increase in vascular permeability, detectable within 3 min after AA application during acute hydrostatic challenge.
Lymph flow and lung weight in isolated sheep lungs
Authors: Mitzner W. , Sylvester J. T.
Published: December 2017

To study the relationship between lung weight and lymph flow, we used an in situ, isolated sheep lung preparation that allowed these two variables to be measured simultaneously. All lungs were perfused for 4.5 h at a constant rate of 100 ml X min-1 X kg-1. In control lungs, the left atrial pressure (Pla) was kept at atmospheric pressure. In experimental lungs, Pla was kept atmospheric except for a 50-min elevation to 18 mmHg midway through the perfusion. During this period of left atrial hypertension, pulmonary arterial pressure rose from 18 to 31 mmHg, lymph flow rose from 3 to 12 ml/h, and the lymph-to-plasma oncotic pressure ratio (pi L/pi P) fell from 0.7 to 0.48. After left atrial pressure was returned to control, pulmonary arterial pressure, lymph flow, and pi L/pi P all returned to control levels. The rate of weight gain after the return of left atrial pressure to control was also the same as that in the control group. However, during the period of left atrial hypertension 135 ml of fluid were filtered into the lung, and this large increase in lung weight remained after the pressure was lowered. The presence of this substantial excess lung water despite control values for vascular pressures, lymph flow, rate of weight gain, and pi L/pi P suggests that the absolute amount of lung water has little influence on the dynamic aspects of lung fluid balance. These results are consistent with a two-compartment model of the interstitial space, where only one of the compartments is readily drained by the lymphatics.
Effects of dextran-bound inhibitors on carbonic anhydrase activity in isolated rat lungs
Authors: Heming T. A. , Geers C. , Gros G. , Bidani A. , Crandall E. D.
Published: December 2017

Effects of macromolecular Prontosil-dextran inhibitors (PD) on carbonic anhydrase (CA) activity in isolated rat lungs were studied. Isolated lungs were perfused with Krebs-Ringer bicarbonate (KRB) solutions containing no inhibitor, PD 100,000 (mol wt 100,000), PD 5,000 (mol wt 5,000), or low-molecular-weight inhibitors (Prontosil or acetazolamide). The time course of effluent perfusate pH equilibration was measured in a stop-flow pH electrode apparatus. Pulmonary CO2 excretion (Vco2) was monitored by continuously recording expired CO2 concentration. The lungs were ventilated with room air and perfused at 37 degrees C with KRB prebubbled with 5% CO2- 20% O2- 75% N2. The results obtained show that both the low-molecular-weight inhibitors and PD′s caused postcapillary pH disequilibria (delta pH) in effluent perfusate. However, only acetazolamide and Prontosil caused a reduction in Vco2. These results suggest that there is an intravascular CA, presumably associated with endothelial cell membranes, that is accessible to all inhibitors used and is responsible in part for equilibration of the CO2- HCO3- -H+ reactions in the perfusate but, under the conditions used, does not affect CO2 excretion; and there is an extravascular (possibly intracellular) CA that can be inhibited by low-molecular-weight inhibitors, is primarily responsible for enhanced CO2 transfer across the alveolar-capillary barrier (perhaps via facilitation of CO2 diffusion), and is in part responsible for pH equilibration.
Increased vasoreactivity and chronic pulmonary hypertension following thoracic irradiation in sheep
Authors: Perkett E. A. , Brigham K. L. , Meyrick B.
Published: December 2017

Six chronically catheterized sheep were exposed to 1,500-rad whole-lung irradiation and followed for a four-week period. Pulmonary arterial, left atrial and systemic arterial pressures, cardiac output, arterial blood gases, and pH were measured at base line and biweekly following radiation. Pulmonary vasoreactivity to 12% O2, 100% O2, and an analogue of prostaglandin H2 (PGH2-A) was also assessed. Five nonirradiated sheep served as controls. By the 2nd wk following irradiation, pulmonary vascular resistance had doubled. Final pulmonary arterial pressure was increased 50% over the base-line value (base line = 14 +/- 1 cm H2O; final 22 +/- 2; mean +/- SE; P less than 0.05). Arterial PO2 was decreased to approximately 70 Torr throughout the study. In addition, pulmonary vasoreactivity to PGH2-A, but not to breathing 12 or 100% O2, was significantly increased above base line in the irradiated animals (P less than 0.05). Morphometric techniques applied to the lungs in which the pulmonary arterial circulation was distended with barium gelatin mixture, showed extension of muscle into the distal intra-acinar arteries, and a reduction in both the external diameter and the number of barium-filled peripheral arteries in the irradiated animals. Thus thoracic irradiation results in functional and structural changes of chronic pulmonary hypertension and increased pulmonary vasoreactivity to PGH2-A. The structural changes in the peripheral pulmonary arterial bed may contribute to the increased pulmonary vascular reactivity following thoracic irradiation.
Fetal and uteroplacental heat production in sheep
Authors: Gilbert R. D. , Power G. G.
Published: December 2017

To separate heat production of the fetus from that of the placenta, endometrium, and uterine muscle, we measured total uterine heat production first with the fetus intact and then after the umbilical cord was snared and the fetus killed. Heat production was measured with the Fick principle using thermistors chronically implanted in a maternal artery and major uterine vein and a flowmeter placed on the common internal iliac artery. In nine ewes, carrying lambs weighing 4.46 +/- 0.42 (SE) kg, total uterine heat production fell from 10.6 to 2.9 W after fetal death. Uterine blood flow fell progressively to 90% of control levels during the first hour after death. The caloric equivalent for O2 averaged 4.1 cal/ml O2 for the uterus, 2.2 for the uteroplacenta, and 4.6 for the fetus per se. It was not possible to explain these results using a simple model of maternal-fetal heat transfer. Rather, it was necessary to assume an additional pathway for heat transfer between small uterine veins on the surface of the uterus and cooler structures in the maternal abdomen, presumably the ventral abdominal wall.
Late pulmonary responses induced by Ascaris allergen in conscious squirrel monkeys
Authors: Hamel R. , McFarlane C. S. , Ford-Hutchinson A. W.
Published: December 2017

This study presents an antigen-dependent model of biphasic pulmonary changes to Ascaris suum in conscious squirrel monkeys. Animals with strong positive skin reactivity towards A. suum were trained to sit quietly in chairs and to breathe through face masks. Dynamic compliance (Cdyn) and pulmonary resistance (RL) were measured in these conscious animals before and for a period of 11 h after administration of an aerosol of Ascaris or ragweed antigen. The aerosol of Ascaris antigen induced reproducible increases (42%) in RL (P less than 0.001) and decreases (17%) in Cdyn (P less than 0.01) that peaked respectively 5 and 35 min after antigen challenge and lasted 60–90 min. After recovery, a second bronchoconstriction began between 2 and 8 h and peaked between 4 and 10 h after antigen challenge. Decreases in Cdyn (41%) were significantly greater (P less than 0.003) whereas mean increases in RL (44%) were similar during the late phase as compared with the first phase. The mean Cdyn decreases lasted a minimum of 2 h, whereas RL increases lasted less than 60 min. The time course of the responses varied from animal to animal but changes in individual animals were reproducible over a period of 6 mo. No significant correlation was observed between the cutaneous and the pulmonary responses to Ascaris and the late response was not reversed by aerosol administration of salbutamol (1.0 mg/ml). As a negative control animals were exposed to an aerosol of ragweed extract after which no immediate or late pulmonary response were observed. The results suggest that this primate model may be useful to study the pathophysiology of asthma in humans.
Effects of indomethacin on estradiol-induced attenuation of hypoxic vasoconstriction in lamb lungs
Authors: Gordon J. B. , Wetzel R. C. , McGeady M. L. , Adkinson N. F. , Sylvester J. T.
Published: December 2017

To determine whether cyclooxygenase products mediated the attenuation of hypoxic pulmonary vasoconstriction induced by estradiol, we measured pulmonary arterial pressure at a flow of 50 ml X min-1 X kg-1 (Ppa50) during steady-state exposures to inspired O2 tensions (PIO2) between 0 and 200 Torr in isolated lungs of juvenile ewes. Intramuscular estradiol (10 mg) 44–60 h before study significantly decreased perfusate concentrations of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of the pulmonary vasodilator, prostacyclin, but did not significantly affect the stimulus-response relationship between PIO2 and Ppa50. Estradiol (20 mg) 3–5 days before study increased 6-keto-PGF1 alpha concentrations and decreased Ppa50 at PIO2 of 10, 30, and 50 Torr. Indomethacin added to the perfusate of these lungs reduced 6-keto-PGF1 alpha to undetectable levels and altered the estradiol-induced attenuation, increasing Ppa50 at PIO2 of 10 and 30 Torr, but decreasing Ppa50 at PIO2 of 200 Torr. Despite these effects, Ppa50 remained lower than the values measured in lungs not treated with estradiol. These results suggest that the estradiol-induced attenuation of the hypoxic stimulus-response relationship was mediated only in part by cyclooxygenase products, the net effects of which were vasodilation at PIO2 of 10 and 30 Torr, but vasoconstriction at PIO2 of 200 Torr.
Permeability of barriers to albumin flux in lungs of sheep resuscitated from hemorrhagic shock
Authors: Gorin A. B. , Mendiondo G.
Published: December 2017

We assessed pulmonary endothelial and epithelial permeability and lung lymph flow in nine adult sheep under base-line conditions and after resuscitation from profound hemorrhagic shock. Animals were mechanically ventilated and maintained on 1% halothane anesthesia while aortic pressure was held at 40 Torr for 3 h. Systemic heparin was not used. After reinfusion of shed blood, sheep recovered from anesthesia and we measured lung lymph flow (QL), lymph-to-plasma concentration ratio for proteins, and time taken to reach half-equilibrium concentration of intravenous tracer albumin in lymph (t1/2). Twenty-four hours after bolus injection of radio-albumin we lavaged subsegments of the right upper lobe and determined fractional equilibration of the tracer in the alveolar luminal-lining layer. In each sheep we had measured these parameters 7 days earlier under base-line conditions. Animals were killed, and the lungs were used for gravimetric determination of extravascular lung water (gravimetric extravascular lung water-to-dry weight ratio) 24 h after resuscitation from shock. Pulmonary endothelial injury after resuscitation was evidenced by marked increase in QL, without fall in lymph-to-plasma ratio. Time taken to reach half-equilibrium concentration fell from 169 +/- 47 (SD) min in base-line studies to 53 +/- 33 min after shock. There was no evidence of lung epithelial injury. Gravimetric extravascular lung water-to-dry weight ratio was significantly increased in these animals killed 24 h after resuscitation (4.94 +/- 0.29) compared with values in our laboratory controls (4.13 +/- 0.09, mean +/- SD). These data demonstrate a loss of lung endothelial integrity in sheep after resuscitation from profound hemorrhagic shock.
Methacholine-induced airway reactivity of inbred rats
Authors: Wang C. G. , DiMaria G. , Bates J. H. , Guttmann R. D. , Martin J. G.
Published: December 2017

Dose-response curves to inhaled aerosolized methacholine chloride (MCh) were obtained in anesthetized spontaneously breathing rats. Thirty rats (10/strain), randomly selected from highly inbred ACI, Lewis (L), and Brown Norway (BN) strains and 40 rats (20/strain) from similarly inbred Wistar-Furth (WF) and Buffalo (Buf) strains were studied. Airway responses were quantitated from changes in pulmonary resistance (RL) and airway reactivity was calculated as the dose of MCh required to increase RL to 150% (ED150RL) and 200% (ED200RL) of base line. There were no statistically significant differences in ED150RL and ED200RL among the five rat strains. Large interindividual variability was present as evidenced by 128-fold differences in ED150RL and ED200RL between the least and most sensitive animal of the same strain. In contrast, seven animals studied repeatedly on different days had values of ED150RL that differed by an average of only 2.9-fold (range 1.6–5.3). Thirteen rats that were studied on two occasions separated by an interval of 3 mo showed no systematic changes in airway reactivity. We conclude that airway reactivity to inhaled methacholine in anesthetized nose-breathing rats is not strain related, and despite animals of a given strain being genetically identical, the variability in airway reactivity within strains suggests that environmental rather than genetic factors are the major determinants of that reactivity.
Changes in flow-volume curve configuration with bronchoconstriction and bronchodilation
Authors: O'Donnell C. R. , Castile R. G. , Mead J.
Published: December 2017

Changes in the configuration of maximum expiratory flow-volume (MEFV) curves following mild degrees of bronchodilation or bronchoconstriction were studied in five normal and five asthmatic subjects. In a volume-displacement plethysmograph, MEFV curves were performed before and after inhalation of aerosolized isoproterenol (I) or histamine (H). Five filtered MEFV curves were averaged, and slope ratio vs. volume (SR-V) plots were obtained from averaged curves. Following I, maximal flows at 75% of the vital capacity (VC) were decreased in asthmatics but not in normal subjects. Flows at 50 and 25% of the VC increased in normal subjects and asthmatics, whereas VC′s were unchanged. In asthmatics, sudden large decreases in flow (bumps) occurred at lower lung volumes following I. H reduced flows over the entire VC, with greater reductions occurring in asthmatics than in normals, particularly at low lung volumes. In asthmatics, VC was slightly reduced, and bumps in MEFV curve configuration occurred at higher lung volumes or were abolished entirely following H. A reduction in the amount of configurational detail appreciable in MEFV curves following histamine in asthmatics was best seen in SR-V plots. Following H, SR′s decreased regularly with decreasing lung volume in all the asthmatics but in none of the normals. This was the single most striking finding of this study. Mild I- and H-induced perturbations of airway bronchomotor tone produced small but consistent changes in MEFV curve configuration.(ABSTRACT TRUNCATED AT 250 WORDS)
Finite difference analysis of respiratory heat transfer
Authors: Ingenito E. P. , Solway J. , McFadden E. R. , Pichurko B. M. , Cravalho E. G. , Drazen J. M.
Published: December 2017

A numerical computer model of heat and water transfer within the tracheobronchial tree of humans was developed based on an integral formulation of the first law of thermodynamics. Simulation results were compared with directly measured intraluminal airway temperature profiles previously obtained in normal human subjects, and a good correlation was demonstrated. The model was used to study aspects of regional pulmonary heat transfer and to predict the outcomes of experiments not yet performed. The results of these simulations show that a decrease in inspired air temperature and water content at fixed minute ventilation produces a proportionately larger increase in heat loss from extrathoracic airways relative to intrathoracic, whereas an increase in minute ventilation at fixed inspired air conditions produces the opposite pattern, with cold dry air penetrating further into the lung, and that changes in breathing pattern (tidal volume and frequency) at fixed minute ventilation and fixed inspiratory-to-expiratory (I/E) ratio do not affect local air temperature profiles and heat loss, whereas changes in I/E ratio at fixed minute ventilation do cause a significant change.
Effect of ozone on breathing in dogs: vagal and nonvagal mechanisms
Authors: Sasaki K. , Nadel J. A. , Hahn H. L.
Published: December 2017

We exposed two awake dogs with a chronic tracheostomy and the cervical vagus nerves exteriorized in skin loops to 1.0 ppm of ozone (O3) for 2 h at intervals of 4 wk. We measured ventilatory variables before and after O3 exposure during rest and exercise before and after vagal block. We compared the effects of vagal blockade, exercise, and O3 on the primary determinants of breathing pattern (VT/TI, VT/TE, TI, and TE) in each of three conditions: base line (steady state), during hypercapnia, and after inhalation of 1% histamine. Under base-line conditions, O3 increased respiratory rate and decreased tidal volume (VT) by shortening time of expiration (TE) and time of inspiration (TI) without affecting VT/TI, an indicator of the neural drive to breathing. During progressive hypercapnia, O3 shortened TE and TI by effects both on tonic (nonvolume-related) and on phasic (volume-related) vagal inputs, and only the latter were prevented completely by cooling of the vagus nerves. Histamine-induced tachypnea was increased by O3 and was totally blocked by cooling the vagus nerves. We conclude that O3 shortens the timing of respiration without increasing ventilatory drive, shortens TI and TE through vagal and nonvagal pathways, increases tonic nonvagal and phasic vagal inputs, and stimulates more than one vagal fiber type.
Dynamics of chest wall in preterm infants
Authors: Heldt G. P. , McIlroy M. B.
Published: December 2017

The chest wall of the preterm infant has visible paradoxical movement during breathing, because of its greater flexibility than those of older children and adults. We studied the dynamics of the chest wall in 10 preterm infants to describe the interaction of the chest wall volume, as partitioned by the inductance plethysmograph, and the transthoracic and abdominal pressures. There was considerable hysteresis between the chest wall volume and the transthoracic pressure, and it had linear pressure-volume behavior during airway occlusion, late inspiration, and early expiration. The slope of this pressure-volume relationship, or the instantaneous chest wall compliance, averaged 0.89 +/- 0.16 and 0.94 +/- 0.18 ml/cmH2O for the respiratory effort during airway occlusion and early expiration, respectively. The dynamic compliance was considerably greater, averaging 7.8 +/- 2.3 ml/cmH2O. This resistive pressure-volume behavior was not related to the absolute value of or the rate of development of the esophageal or abdominal pressures. This additional degree of freedom of motion of the chest wall suggests that its linkage to the diaphragm is flexible, which provides a braking force for expiration and allows free movement of the diaphragm for breathing movements before birth.
Histamine release and circulating cells after antigen inhalation in allergic dogs
Authors: Chung K. F. , Osborne M. L. , Corrales R. J. , Evans T. W. , McCabe L. , Frick O. L. , Nadel J. A. , Gold W. M.
Published: December 2017

Histamine can be recovered from the blood of ragweed-sensitized dogs after aerosol antigen challenge, although its source is unknown. Neutrophils and eosinophils have been recovered from bronchoalveolar lavage fluid (BALF) obtained under identical conditions. We investigated the time course of changes in histamine levels in plasma and BALF taken from ragweed-sensitized dogs after aerosol challenge. Changes in the numbers of circulating neutrophils, eosinophils, lymphocytes, monocytes, and platelets were also studied. After 3 min, total pulmonary resistance (RL) was maximally increased and systolic blood pressure was maximally decreased. Histamine levels in plasma and BALF were increased and circulating eosinophils and neutrophils were decreased. After 15 min, platelet numbers were reduced. By 90 min, changes in RL, blood pressure, plasma and BALF histamine concentrations, and circulating neutrophils and eosinophils had returned to base-line values, but platelet numbers remained significantly decreased. Sham challenge caused no significant changes in any of these variables. Intravenous administration of histamine in doses large enough to attain plasma levels comparable with those achieved after aerosol antigen challenge resulted in no concomitant rise in BALF histamine levels. We conclude that antigen challenge in sensitized dogs causes increases in BALF and plasma histamine levels and is associated with a reduction in circulating neutrophils, eosinophils, and platelets. It is likely that antigen causes airway mast cells to release mediators that move down a concentration gradient from the airways to the pulmonary circulation.
A modeling approach to the estimation of CO diffusing capacity
Authors: Prisk G. K. , McKinnon A. E.
Published: December 2017

Standard methods of measuring the diffusing capacity of the lung for CO are susceptible to inhomogeneity and to errors in the performance of a breathing maneuver by the subject. A mathematical model of CO uptake from a single alveolar lung is developed and used as the basis for an estimation procedure to measure both lung volume and diffusing capacity during a rebreathing maneuver. Because this estimator-model uses the exact flow generated by the subject, errors in such factors as breath-hold times or depth of inspiration do not result. The estimator-model was tested using simulated data from uniformly and nonuniformly ventilated models and was found to be insensitive to noise and inhomogeneity, in contrast to the diffusing capacity of the lungs for CO (exhaled). The estimator-model makes greater use of the available data than traditional methods by utilizing both the slope of the alveolar plateaus for CO and the relative heights of such plateaus in a rebreathing experiment.
Pharmacological modification of pulmonary vascular injury: possible role of cAMP
Authors: Farrukh I. S. , Gurtner G. H. , Michael J. R.
Published: December 2017

Experiments were designed to test the hypothesis that drugs which increase adenosine 3′,5′-cyclic monophosphate (cAMP) in the lung would prevent the pulmonary hypertension and the increase in vascular permeability caused by the infusion of the oxidant lipid peroxide, tert-butyl hydroperoxide (t-bu-OOH), in isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pretreatment with indomethacin or verapamil was also studied, since these drugs block the increase in pulmonary arterial pressure caused by t-bu-OOH. Indomethacin or verapamil prevented the pulmonary hypertension but did not prevent the increase in permeability caused by t-bu-OOH. Consequently, indomethacin or verapamil treatment partially reduced the gain in lung weight caused by t-bu-OOH. In contrast, pretreatment with isoproterenol, prostaglandin E1, or a cAMP analogue not only prevented the pulmonary hypertension but also inhibited the increase in vascular permeability caused by t-bu-OOH. Consequently, these drugs completely blocked the gain in lung weight caused by t-bu-OOH. Posttreatment with aminophylline or the cAMP analogue also significantly reduced the gain in lung weight caused by t-bu-OOH. These results indicate that pharmacological therapy can reduce the pulmonary hypertension and the increase in vascular permeability caused by the infusion of a lipid hydroperoxide. Since isoproterenol, aminophylline, prostaglandin E1, and a cAMP analogue all had similar effects, the results suggest that the likely common mechanism for their protective effect is an increase in cAMP.
Magnesium homeostasis during high-intensity anaerobic exercise in men
Authors: Deuster P. A. , Dolev E. , Kyle S. B. , Anderson R. A. , Schoomaker E. B.
Published: December 2017

This study was conducted to determine whether short-term, high-intensity anaerobic exercise alters Mg homeostasis. Thirteen men performed intermittent bouts of treadmill running at 90% of their predetermined maximum O2 uptake until exhaustion on one occasion during a week in which all men were consuming a standard diet (115 mg Mg/1,000 kcal). Plasma and erythrocyte Mg concentrations and peripheral blood mononuclear cell Mg content were measured before and after the exercise. Complete 24-h urine collections were obtained on control days, on the day of exercise, and on the day after exercise. Exercise induced a transient but significant decrease in plasma Mg content (-6.8%; P less than 0.01); over 85% of the loss could be accounted for by a shift to the erythrocytes. Significant increases in urinary excretion of Mg were observed on the day of exercise (131.5 +/- 6.8 mg/day) compared with control days (108 +/- 6.6 mg/day), with the percent increase correlating with postexercise blood lactate concentration (r = 0.68; P less than 0.01) and oxygen consumption during recovery (r = 0.84; P less than 0.001). The data indicate that high-intensity anaerobic exercise induces intercompartmental Mg shifts in blood that return to preexercise values within 2 h and urinary losses on the day of exercise that return to base line the day after exercise. It is postulated that the exercise-induced increase in Mg excretion may depend on the intensity of the exercise, and the relative contribution of anaerobic metabolism to the total energy expended during exercise.
Effects of airway pressure on bronchial blood flow
Authors: Wagner E. M. , Mitzner W. A. , Bleecker E. R.
Published: December 2017

We studied the effects of increased airway pressure caused by increasing levels of positive end-expiratory pressure (PEEP) on bronchial arterial pressure-flow relationships. In eight alpha-chloralose-anesthetized mechanically ventilated sheep (23–27 kg), the common bronchial artery, the bronchial branch of the bronchoesophageal artery, was cannulated and perfused with a pump. The control bronchial blood flow (avg 12 +/- 1 ml/min or 0.48 ml X min-1 X kg-1) was set to maintain mean bronchial arterial pressure equal to systemic blood pressure. Pressure-flow curves of the bronchial circulation were measured by making step changes in bronchial blood flow, and changes in these curves were analyzed with measurements of the pressure at zero flow and the slope of the linearized curve. The zero-flow pressure represents the effective downstream pressure, and the slope represents the resistance through the bronchial vasculature. At a constant bronchial arterial pressure of 100 mmHg, an 8 mmHg increase in mean airway pressure caused a 40% reduction in bronchial blood flow. Under constant flow conditions, increases in mean airway pressure with the application of PEEP caused substantial increases in bronchial arterial pressure, averaging 4.6 mmHg for every millimeters of mercury increase in mean airway pressure. However, bronchial arterial pressure at zero flow increased approximately one-for-one with increases in mean airway pressure. Thus the acute sensitivity of the bronchial artery to changes in mean airway pressure results primarily from changes in bronchovascular resistance and not downstream pressure.
Mechanical function of hyoid muscles during spontaneous breathing in cats
Authors: van Lunteren E. , Haxhiu M. A. , Cherniack N. S.
Published: December 2017

We assessed the mechanical behavior of the geniohyoid and sternohyoid muscles during spontaneous breathing using sonomicrometry in anesthetized cats. When the animals breathed O2, the hyoid muscles either became longer or did not change length (but never shortened) during inspiration. During progressive hyperoxic hypercapnia, transient increases in geniohyoid muscle inspiratory lengthening occurred in many animals; however, at high PCO2 the geniohyoid invariably shortened during inspiration (mean 4.9% of resting length at the end of CO2 rebreathing; P less than 0.001). The PCO2 at which geniohyoid inspiratory lengthening changed to inspiratory shortening was significantly higher than the CO2 threshold for the onset of geniohyoid electrical activity (P less than 0.01). For the sternohyoid muscle, hypercapnia caused inspiratory lengthening in 13 of 17 cats and inspiratory shortening in 4 of 17 cats; on average the sternohyoid lengthened by 1.6% of resting length at the end of CO2 rebreathing (P less than 0.01). Sternohyoid lengthening occurred in spite of this muscle being electrically active. These results suggest that the relationship between hyoid muscle electrical activity and respiratory changes in length is very complex, so that the presence of hyoid muscle electrical activity does not necessarily indicate muscle shortening, and among the geniohyoid and sternohyoid muscles, the geniohyoid has a primary role as a hypopharyngeal dilator in the spontaneously breathing cat, with the sternohyoid muscle acting in an accessory capacity.
Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women
Authors: Viswanathan M. , Van Dijk J. P. , Graham T. E. , Bonen A. , George J. C.
Published: December 2017

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.
Neutrophil collagenase in rheumatoid interstitial lung disease
Authors: Weiland J. E. , Garcia J. G. , Davis W. B. , Gadek J. E.
Published: December 2017

Ten patients with rheumatoid arthritis were evaluated by bronchoalveolar lavage. Five patients (group I) had interstitial lung disease by physiological and radiographic criteria, whereas five (group II) had no evidence of lung disease. Lavage fluid from four of the five group I patients contained an active collagenase which by inhibitory profile and substrate specificity appeared to be of neutrophil origin. None of the group II patients demonstrated lavage fluid collagenase. Treatment of lavage fluid with trypsin failed to uncover latent collagenase activity in either group, suggesting that the collagenase is present entirely in an active form. These findings parallel those observed in idiopathic pulmonary fibrosis and suggest a potential pathogenetic role for collagenase in rheumatoid interstitial lung disease.
Density dependence of maximal flow is lung volume dependent during bronchoconstriction
Authors: Greville H. W. , Arnup M. E. , Mink S. N.
Published: December 2017

We examined the changes in maximum expiratory flow (Vmax) and the density dependence of maximum expiratory flow (delta Vmax) during histamine-induced bronchoconstriction in dogs. Histamine acid phosphate solution was nebulized into the airways of six dogs to produce predominantly peripheral airway obstruction. Vmax air, Vmax with the dogs breathing 80% He-20% O2 (delta Vmax), and airway sites of flow limitation (choke points) were examined at four lung volumes (VL), which ranged from 51 to 23% of the control vital capacity (VC). The findings were interpreted in terms of the wave-speed theory of flow limitation. At all VL, Vmax air decreased during bronchoconstriction by approximately 30% compared with the control value. Resistances peripheral to a 0.3-cm-diam airway were increased about threefold with histamine, whereas resistances between 0.6-cm-diam bronchi and main-stem bronchi increased just slightly. Airway diameters were measured in the air-dried lung at 20 cmH2O transpulmonary pressure. Our results showed that only at 44% VC did delta Vmax decrease in all experiments after histamine to indicate peripheral obstruction (mean: 68.5 to 45%). At 23% VC, delta Vmax increased slightly, from 22 to 28%. At 23 and 36% VC, substantial differences in the wave-speed variables between air and HeO2 were present before bronchoconstriction, so that delta Vmax was low in some dogs, although peripheral airway obstruction was not evident. When bronchoconstriction was produced, delta Vmax at 23% VC could not be decreased further and even increased in four of six dogs. Thus changes in delta Vmax at given lung volume may not reflect the predominant site of airflow obstruction during bronchoconstriction.
Length-tension relationship of abdominal expiratory muscles: effect of emphysema
Authors: Arnold J. S. , Thomas A. J. , Kelsen S. G.
Published: December 2017

The present study examined the active and passive length-tension relationship of the abdominal expiratory muscles in vitro during electrically stimulated contractions. Studies were performed on isolated strips of transverse abdominis and external oblique muscle from nine adult hamsters with normal lung function. The effect of chronic hyperinflation on the two muscles was assessed in eight hamsters with elastase-induced emphysema. In normal animals the maximal active tension per cross-sectional area (Po) was equal in the two muscles. The absolute muscle fiber length at which Po occurred (Lo) was less for the external oblique than the transverse abdominis and the length-tension curve operated at shorter fiber lengths. However, the change in tension produced by an increase or decrease in muscle length expressed in relative terms (i.e., as %Lo) was greater for the transverse abdominis than the external oblique. Mean total lung capacity of emphysematous animals was 198% of control. Po of the transverse abdominis and external oblique were the same in emphysematous and control animals. However, Lo and the length-tension curve of the transverse abdominis occurred at shorter fiber lengths in emphysematous animals because of a reduction in the number of sarcomeres in series along the fiber. The length-tension curve and the number of sarcomeres in the external oblique was the same in emphysematous and control animals. These results in normal animals indicate that the magnitude of the change in active and passive tension produced by a change in muscle length differs in the transverse abdominis and external oblique. Moreover, chronic hyperinflation of the thorax produced by elastase injection alters the length-tension relationships of some but not all the expiratory muscles.
Regional surface areas of spontaneously hypertensive and Wistar-Kyoto rats
Authors: Lyzak W. A. , Hunter W. S.
Published: December 2017

Regional skin surface area and region-specific weighting factors for calculating mean skin temperature have not been determined for the rat. Therefore, measurements were made of total skin surface area segmented into five regions of 12 spontaneously hypertensive (SHR) and 12 normotensive Wistar-Kyoto (WKY) rats. SHR's were selected because chronically elevated core temperature and reduced ability of SHR's to withstand heat stress make them of interest for thermoregulatory studies. Area was determined by coating the skin with rubber base dental impression material, then measuring the area of the coating. The relationship between total skin surface area and mass of SHR's was not different from that of WKY's and is described by the equation SA = 8.62 M0.67. However, the ears of SHR's had larger surface area and their tails smaller surface area than those of WKY's. For the combined groups, the proportion of total surface area of the regions was as follows: ears, 0.022; front feet, 0.017; hind feet, 0.040; tail, 0.100; central skin, 0.826. These data provide a basis for calculating skin surface area, mean skin temperature, and related values for SHR and WKY rats.
Lung lymph flow after bone marrow injection into goats was reduced by indomethacin
Authors: Winn R. , Maunder R. , Harlan J.
Published: December 2017

We examined the pulmonary response to bone marrow embolism in untreated and indomethacin-treated goats. Pulmonary arterial pressure increased by 15 cmH2O after bone marrow infusion, reaching a peak of 37.2 then stabilizing at greater than 30 cmH2O in the control group. In the treated group it increased by 4.3 cmH2O from a base line of 18.5 cmH2O but had returned to base line by 6 h. Lymph flow increased in the control group from a base line of 7.3 ml/h to a peak of 22.4 ml/h and remained near that level. It increased from a base line of 6.4 ml/h to a peak of 9.8 ml/h in the treated group and remained close to that value. The lymph-to-plasma protein ratio was little changed throughout the experiment. Cardiac output decreased by 1.2 l/min in the control group but was unchanged from base line in the treated group. Systemic arterial pressure was similar in both groups of animals. We conclude that indomethacin prevents the pulmonary hypertension seen after bone marrow infusion and protects against some of the increased permeability.
Prejunctional beta 1-adrenoceptors inhibit cholinergic transmission in canine bronchi
Authors: Danser A. H. , van den Ende R. , Lorenz R. R. , Flavahan N. A. , Vanhoutte P. M.
Published: December 2017

The aim of the present study was to determine in canine bronchi the effects produced by norepinephrine (released from adrenergic nerve terminals) on cholinergic neurotransmission. Electrical stimulation of canine bronchi activates cholinergic and adrenergic nerve fibers. The adrenergic neuronal blocker, bretylium tosylate, inhibited the increase in [3H]norepinephrine overflow evoked by electrical stimulation but did not prevent that caused by the indirect sympathomimetic tyramine. During blockade of the exocytotic release of norepinephrine with bretylium, the pharmacological displacement of the sympathetic neurotransmitter by tyramine significantly decreased the contractions evoked by electrical stimulation but did not affect contractions caused by exogenous acetylcholine. Metoprolol, a beta 1-adrenergic antagonist, abolished and propranolol significantly reduced the effect of tyramine during electrical stimulation. alpha 2-Adrenergic blockade, beta 2-adrenergic blockade, or removal of the epithelium did not significantly affect the response to tyramine. These results suggest that norepinephrine when released from sympathetic nerve endings can activate prejunctional inhibitory beta 1-adrenoceptors to depress cholinergic neurotransmission in the bronchial wall.
Respiratory phase detection and delay determination for breath-by-breath analysis
Authors: Boutellier U. , Kundig T. , Gomez U. , Pietsch P. , Koller E. A.
Published: December 2017

The delay between air flow and gas concentration signals is generally assumed to be constant within a breath as well as from breath to breath, but it was not possible to examine the constancy of the delay with the delay determination techniques so far available. Thus we developed new methods for respiratory phase detection and delay determination. The presented algorithm for the detection of the start of inspiration and expiration (phase detection) replaces the generally used valve assembly with two pneumotachographs. Now, the pneumotachograph is used in a bidirectional mode, but with a volume criterion for phase detection replacing the less reliable threshold criterion. To measure the delay between flow and gas concentration signals, a test gas is periodically injected as a marker. This test gas contains less N2 than ambient air. Therefore, the delay is determined as time between the moment of injection and the drop of N2. These two methods rendered it possible to examine delay variations and their consequences. The investigation of various breathing patterns demonstrated that the usually assumed errors caused by delay uncertainty are underestimated. We suggest reliance on a breath-by-breath delay determination to account for delay variations.
Transient changes in expiratory time during hypercapnia in premature infants
Authors: Noble L. M. , Carlo W. A. , Miller M. J. , DiFiore J. M. , Martin R. J.
Published: December 2017

The transient ventilatory responses to hypercapnia were studied in nine healthy preterm infants. We administered 4% CO2 in air for at least 7 min during quiet sleep and measured frequency (f), inspiratory time (TI), expiratory time (TE), tidal volume (VT), and minute ventilation (VI). Frequency increased over the first 2 min of CO2 inhalation (P less than 0.05) and then decreased to control values (P less than 0.05). This response was secondary to changes in TE, which decreased over the first 2 min (P less than 0.05) and then returned to control values, whereas TI did not change. The late increase in TE was associated with an increased percent of breaths exhibiting retardation of expiratory flow (braking) (P less than 0.05). These breaths had longer TE than the breaths without braking (P less than 0.05). Exponential curves made to fit the increases in VI and VT revealed that only 67% of the infants reached 90% of steady state for both VI and VT over the 7-min study period. The time to 90% of steady state was always shorter for VI than VT (P less than 0.05) due to the transient changes in f. The results indicate that the transient changes of f in response to hypercapnia are secondary to changes in TE, which appear unique to human infants. We speculate that the expiratory braking that develops during the course of CO2 inhalation increases lung volume, resulting in prolongation of TE via mechanoreceptor-mediated reflexes.