bluuebunny/crossref_metadata_2025 huggingface dataset:
Density dependence of maximal flow in dogs with central and peripheral obstruction
Authors: Castile R. G. , Pedersen O. F. , Drazen J. M. , Ingram R. H.
Published: December 2017

In 12 anesthetized, tracheotomized, vagotomized, open-chested, mongrel dogs we measured end and side hole airway pressures during forced expiration using a Pitot static probe. Volume was obtained as the integral of flow from a dog plethysmograph with frequency response adequate to 20 Hz. Equal pressure points (EPPs) and choke points (CPs) were located with dogs breathing air or a mixture of 80% helium-20% oxygen (HeO2) before and after partial obstruction of the trachea and intravenous histamine and propranolol. At 50% of vital capacity (VC) the CP was in the trachea in 11 of 12 dogs. Partial obstruction of the trachea decreased flow during the plateau of the maximum expiratory flow-volume curve (MEFVC) with the CP remaining in the trachea. The MEFVC plateau was extended to a lower lung volume. At 50% of VC the EPP moved downstream and density dependence remained high. Histamine and propranolol caused EPPs and CPs to move towards the periphery and density dependence to decrease. The shape of the MEFVC changed as the plateau was shortened and, in some instances, abolished. A plateau on the MEFVC could be regenerated by partial obstruction of the trachea. This was accompanied by return of the CP to the trachea and an increase in density dependence. Changes in density dependence were found to be a result of both the relocation of sites of flow limitation and differences in local CP areas with HeO2 and air.
Contractile force of canine airway smooth muscle during cyclical length changes
Authors: Gunst S. J.
Published: December 2017

Strips of tonically contracted canine tracheal and bronchial airway smooth muscles (AWSM) were studied in vitro to compare dynamic muscle force during stretch-retraction cycles with static isometric muscle force at various length points within the cycling range. At any particular rate, a characteristic force-length loop was obtained by cycling over a given range of lengths. Dynamic muscle force dropped well below static isometric muscle force at lengths short of the peak length at all rates of cycling. When stretch or retraction of the muscle was stopped at any point along either path of the cycle, muscle force rose to approach the isometric force at that length. Dynamic force at the peak length of the cycle remained close to, or slightly greater than, the static isometric force. The results suggest that the velocity of shortening of tonically contracted AWSM is very slow relative to the rates of cycling employed. A slow rate of shortening of AWSM relative to the rate of change in airway caliber during breathing could account for well-known effects of volume history on airway tone.
Acute effects of intratracheal administration of platelet-activating factor in baboons
Authors: Denjean A. , Arnoux B. , Masse R. , Lockhart A. , Benveniste J.
Published: December 2017

The bronchomotor effect of intratracheal administration of PAF-acether (60 micrograms X kg -1) was investigated in 37 curarized baboons mechanically ventilated with constant volume and frequency. PAF-acether caused an immediate bronchoconstriction as assessed by a marked increase in peak inspiratory pressure with no change in static pulmonary compliance and chest X-rays. There was a concomitant fall in arterial PO2 and a significant increase in ventilated unperfused lung zones. A decrease of circulating platelets and leucocytes was also observed. Local anesthesia with lidocaine and atropine did not prevent PAF-acether-induced bronchoconstriction although both markedly reduced the bronchial response to histamine. Albuterol significantly reduced the bronchial response to PAF-acether. Pretreatment with aspirin (80 mg X kg -1 iv) did not prevent the bronchoconstriction caused by PAF-acether, and intravenous or intratracheal arachidonic acid caused no bronchial response. Thus the role of cyclooxygenase metabolites of arachidonic acid in PAF-acether-induced bronchoconstriction is unlikely. In conclusion, an acute bronchoconstriction probably not triggered by stimulation of irritant receptors of the airways and associated with aggregation of platelet takes place subsequent to intratracheal administration of PAF-acether. These data suggest that PAF-acether might play a role in the pathogenesis of human asthma.
Ozone and high ventilation effects on pulmonary function and endurance performance
Authors: Adams W. C. , Schelegle E. S.
Published: December 2017

Ozone (O3) toxicity is potentiated by exercise-induced expired minute ventilation (VE) for a given exposure, which may also impair endurance performance. Ten healthy, well-trained long-distance runners were exposed on six occasions for 1 h to O3 concentrations of 0, 0.20, or 0.35 parts per million (ppm), during exercise simulating either training or competition, with mean VE = 77.5 1 X min -1. Standard pulmonary function tests, subjective symptoms, and periodic observations of exercise ventilatory response and respiratory metabolism were obtained. Statistical analyses revealed no significant exercise mode effect for pulmonary function, but a significant O3 effect for forced vital capacity and expiratory volume at 1 s was observed. Altered exercise ventilatory pattern response was noted, but there was no significant O3 effect on exercise oxygen uptake, heart rate, VE, or alveolar ventilation. Subjective symptoms increased with O3 concentration. Statistically significant pulmonary function impairment observed at 0.20 ppm O3 suggests that endurance athletes may be more susceptible to the effects of a given O3 concentration than normal young adult males as a result of sustained high mean VE incurred during training and competition. Three subjects were unable to complete both the training and competitive simulations at 0.35 ppm O3. Performance decrements appeared to be the result of physiologically induced respiratory discomfort rather than decrements in pulmonary gas exchange and/or oxygen transport and delivery.
Effect of ketamine on control of breathing in cats
Authors: Jaspar N. , Mazzarelli M. , Tessier C. , Milic-Emili J.
Published: December 2017

We studied minute ventilation, breathing pattern, end-tidal CO2 partial pressure (PACO2), and tracheal occlusion pressure in cats anesthetized with ketamine (40 and 80 mg/kg) before and after CO2 inhalation. Before CO2 administration ventilation was reduced and PACO2 increased relative to unanesthetized cats at both ketamine doses. Breathing pattern was of the “apneustic” type, being characterized by 1) prolonged inspiratory duration and relatively short expiratory time and 2) markedly curvilinear (convex upward) inspiratory volume-time profile. The latter reflected a similar curvilinearity in the tracheal occlusion pressure waveform. During CO2 inhalation, the ventilatory response to CO2 was similar to that in unanesthetized cats in spite of a depressed tracheal occlusion pressure response. This discrepancy was due to the fact that in the presence of a convex upward inspiratory volume-time profile, the shortening of inspiratory duration with increasing CO2 results in a marked increase of mean inspiratory flow, and hence the ventilatory response to CO2 remains high.
Effects of prior dynamic leg exercise on static effort of the elbow flexors
Authors: Yates J. W. , Gladden L. B. , Cresanta M. K.
Published: December 2017

The isometric endurance of the elbow flexors was determined in a control condition and subsequent to a maximal effort exercise bout on a cycle ergometer in seven subjects. Maximum voluntary contraction (MVC), peak rate of tension development (+dP/dt), peak rate of tension relaxation (-dP/dt), one-half contraction time, and one-half relaxation time were also measured. Each subject was tested on four occasions: two control and two experimental sessions. During the control sessions each subject held 40% of MVC to exhaustion, whereas the experimental session included a 1-min maximal effort exercise bout on a cycle ergometer 6 min prior to the isometric endurance task. Arterialized blood samples were drawn and analyzed for lactate, pH, PCO2, and PO2. Plasma bicarbonate was calculated from the Henderson-Hasselbalch equation. Subsequent to the cycle ergometer bout, blood lactate concentration rose from 0.8 to 11 mM, pH decreased from 7.43 to 7.20, PCO2 decreased from 40 to 32 Torr, and plasma bicarbonate decreased from 26 to 12 mM. When compared with the control values, no significant changes were evident for any muscle contractile properties following the cycle ergometer bout. However, isometric endurance was significantly reduced from 115.0 +/- 7.2 to 86.3 +/- 7.3 s.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ethanol and naloxone on control of ventilation and load perception
Authors: Michiels T. M. , Light R. W. , Mahutte C. K.
Published: December 2017

The respiratory depressant effects of ethanol and their potential reversibility by naloxone were studied in 10 normal subjects. Ventilatory and mouth occlusion pressure (P0.1) responses to hypercapnia and hypoxia without and with an inspiratory resistive load (13 cmH2O X 1(-1) X S) were measured. The resistive load detected with 50% probability (delta R50) and the exponent (n) in Stevens' psychophysical law for magnitude estimation of resistive loads were studied using standard psychophysical techniques. Each of these studies was performed before ethanol ingestion, after ethanol ingestion (1.5 ml/kg, by mouth), and then again after naloxone (0.8 mg iv). Ethanol increased delta R50 (P less than 0.05) and decreased n (P less than 0.05). Naloxone caused no further change in these parameters. The load compensation (Lc), defined as the ratio of loaded to unloaded response slopes, was not significantly changed after ethanol and naloxone. No correlation was found between the Lc and delta R50 or n. The ventilatory and P0.1 responses to hypercapnia and hypoxia with and without inspiratory resistive loading decreased after ethanol (P less than 0.05, hypercapnia; NS, hypoxia). After naloxone the hypercapnic ventilatory responses increased (P less than 0.05). This suggests that the respiratory depressant effects of ethanol may be mediated via endorphins.
Fatigue from incompletely fused tetanic contractions in skeletal muscle in situ
Authors: MacIntosh B. R. , Stainsby W. N. , Gladden L. B.
Published: December 2017

The purpose of this study was to investigate the contractile response of skeletal muscle in situ when stimulation results in an unfused tetanic contraction. The left gastrocnemius-plantaris muscle group of anesthetized (pentobarbital sodium) dogs (n = 16) was connected to an isometric lever and stimulated indirectly for 30 min. During 10-Hz stimulation, total tension (the peak of each oscillation in tension) increased during the first 2 min of stimulation (staircase), then decreased during the remaining 28 min of stimulation. Since relaxation was incomplete at this rate of stimulation, the developed tension, the difference between peak tension and the lowest tension between successive contractions, did not follow the same pattern of staircase and fatigue as the peak tension did. Developed tension (delta T) decreased during the staircase response then increased from 2 to 10 min before finally decreasing again during the last 20 min, ending at 56 +/- 15 (mean +/- SE) % of the initial (first contraction) delta T. At 2 min of 10-Hz contractions, half-relaxation time (1/2 RT) was too long to measure (insufficient relaxation between contractions), but later, 1/2 RT decreased from greater than 65 ms to less than 40 ms. Increased 1/2 RT has been associated with reduced energy availability. If an increased 1/2 RT is an indication of insufficient energy, then it can be concluded that fatigue continued in spite of a recovery of energy supplies. This suggests a possible dissociation of fatigue and energy availability.
Removal of abdominal sources of caudal mediastinal node lymph in anesthetized sheep
Authors: Roos P. J. , Wiener-Kronish J. P. , Albertine K. H. , Staub N. C.
Published: December 2017

We investigated the conditions for and the quantity of abdominal contributions to caudal mediastinal node (CMN) efferent lymph in 15 anesthetized sheep with open thorax and lung lymph fistulas. Contractions of the diaphragm by phrenic nerve stimulation increased lymph flow by 29%. Adding large volumes (10 ml/kg) of 5% albumin solution to the peritoneal cavity increased lymph flow by 19 and 28% during diaphragm contraction. Tracer albumin specific activity in lymph indicated that about half the lymph flow increment came from the peritoneal liquid. Raising hepatic vein pressure 19 cmH2O increased CMN lymph flow 178%. Lymph protein concentration also increased markedly, from 0.72 to 0.91 of the plasma concentration. We devised a simple procedure to cauterize across the pleural surface of the diaphragm to destroy the aberrant lymphatics. This procedure markedly diminished both abdominal cavity and portal system contributions.
Effect of bradykinin on lung vascular permeability in sheep
Authors: Minnear F. L. , Kivlen C. M. , Malik A. B.
Published: December 2017

Bradykinin (BK, 0.03-3.11 micrograms X kg-1 X min-1) was infused intravenously for 4-5.5 h to assess its effects on pulmonary transvascular fluid and protein exchange in three groups of artificially ventilated sheep prepared with lung lymph fistulas. In group I, BK was infused alone for 5.5 h. In group II, BK and captopril (SQ 14,225), an inhibitor of angiotensin-converting enzyme (ACE), were infused together because the effects of BK may be attenuated by its rapid degradation in the lung by ACE. In group III, BK was infused in the presence of propranolol, a beta-adrenergic antagonist, to prevent any permeability-decreasing effects of beta-adrenergic activation. The dosages of BK used, which decreased systemic arterial blood pressure by 10-20 mmHg, did not alter either pulmonary transvascular fluid and protein exchange or pulmonary hemodynamics at any time during infusion of BK alone or in combination with captopril or propranolol. Raising pulmonary microvascular pressure (Pmv) by inflating a left atrial balloon during the last 2 h of infusion in all three groups slightly increased pulmonary lymph flow and markedly decreased the lymph-to-plasma protein concentration ratio. These results are comparable with those obtained after increasing Pmv in normal anesthetized sheep and indicate that BK did not alter the pulmonary vascular permeability to proteins.
Effect of tracheostomy on lung development in fetal lambs
Authors: Fewell J. E. , Hislop A. A. , Kitterman J. A. , Johnson P.
Published: December 2017

The effects of fetal tracheostomy on lung development in lambs have been investigated. Seven ewes, all with twin fetuses, were given a general anesthetic. One fetus in each set of twins was tracheostomized and the other fetus was sham operated (117-122 days gestation). The fetuses were delivered by cesarean section between 137 and 140 days gestation. Fetal tracheostomy decreased lung weight and volume, altered DNA concentration and the structural development of the acinus, and decreased lung distensibility. However, tissue and airway saturated phosphatidylcholine and lung stability during deflation were not significantly affected by fetal tracheostomy. It seems that tracheostomy in fetal lambs alters lung growth but does not affect the formation or release of surfactant. These data support the hypothesis that lung volume is actively maintained and lung growth promoted by the secretion of lung fluid against the resistance of the upper airway in fetal lambs.
Polycythemia and the acute hypoxic response in awake rats following chronic hypoxia
Authors: Fried R. , Meyrick B. , Rabinovitch M. , Reid L.
Published: December 2017

The acute hypoxic pressor response was studied in 22 chronically catheterized awake rats, 13 in whom the pulmonary arterial circulation had been remodeled by 10 days of exposure to hypobaric hypoxia. Five of these had their hematocrit lowered to normocytic levels after the chronic hypoxic exposure. Nine were controls. After 24 h in room air the pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (Rp) of hypoxic-polycythemic rats was at least twice the control value; in the hypoxic-normocytic rats Ppa and Rp were less than that of hypoxic-polycythemic animals and greater than that of controls. Cardiac index, heart rate, and O2 saturation were similar in all groups. In 10% O2 a rise in Ppa and Rp occurred in all groups; in absolute terms the rise was greater in hypoxic rats than in controls and greater in polycythemic than in normocytic animals. In the intact animal the acute hypoxic pressor response can still be elicited in a pulmonary vascular bed structurally altered by chronic hypoxia. When calculated as a percent increase over base line, its intensity was greater than in room air controls and for Ppa was independent of hematocrit.
"Anaerobic threshold": problems of determination and validation
Authors: Yeh M. P. , Gardner R. M. , Adams T. D. , Yanowitz F. G. , Crapo R. O.
Published: December 2017

Despite the popularity of the concept of “anaerobic threshold” (AT), the noninvasive detection criteria remain subjective, and invasive validations of AT have been based on lactate data of arterial, mixed venous, venous, and capillary blood samples without any concern for the possible lactate differences from these sources. Eight normal subjects underwent two exercise tests on a bicycle ergometer. The protocol consisted of 3 min of rest, 3 min of 0 work load, and a 20 W/min ramp (1 W/3 s) until exhaustion. Simultaneous arterial and venous blood samples were drawn during the second test. Noninvasive gas response data were measured using a computerized breath-by-breath stress test system. Threshold phenomenon of the lactate accumulation was not found. The arterial lactate levels increased continuously after the start of the exercise ramp. The rise in venous lactate lagged behind the rise of the arterial lactate by about 1.5 min, and therefore venous lactate was not considered suitable for AT detection. Four independent exercise physiologists determined AT from the gas response data. The reviewer variability (avg range 16%) of AT for a given subject was representative of AT values reported for untrained and trained individuals (40-70% maximum O2 consumption). We concluded that 1) AT is not detectable using invasive methods (arterial and venous lactates); and 2) the noninvasive gas response determination has such a large range of reviewer variability that it is unsuitable for clinical use.
Behavior of magnetic particles in hamster lungs: estimates of clearance and cytoplasmic motility
Authors: Gehr P. , Brain J. D. , Nemoto I. , Bloom S. B.
Published: December 2017

Ferrimagnetic particles suspended in saline were instilled intratracheally into the lungs of Syrian golden hamsters. The particles were magnetized and aligned by applying an external magnetic field. Upon removal of the external field, the particles produced a remanent magnetic field from the lungs which decayed due to random misalignment of the particles (relaxation). Magnetization and relaxation measurements were performed immediately after instillation, then repeatedly during the first 24 h, and finally at intervals of several days up to 30 days after the instillation. The size of the initial remanent magnetic field immediately following each external magnetization is a measure of the amount of iron oxide in the lungs. It decreased with time, reflecting particle clearance. The rate of relaxation increased steeply during the first 12 h after the instillation and decreased slowly between the 5th and 30th day. Changes in the location of particles from extracellular to intracellular sites and movements from ectoplasmic to endoplasmic sites within cells may be responsible for the observed changes in relaxation rates with time.
Effect of a 42.2-km footrace and subsequent rest or exercise on muscle glycogen and enzymes
Authors: Sherman W. M. , Costill D. L. , Fink W. J. , Hagerman F. C. , Armstrong L. E. , Murray T. F.
Published: December 2017

The purpose of this study was to determine the effect of running a marathon and subsequent rest or exercise during a 7-day recovery period on muscle glycogen, glycogen synthase, hexokinase, and the activity of hexose monophosphate pathway enzymes. Ten well-trained runners were randomly assigned to either a postmarathon rest or exercise group. The rest group (n = 5) performed no physical activity, whereas the exercise group ran at their highest tolerable volitional intensity for 20-45 min during the recovery period. Muscle biopsies were obtained from the gastrocnemius before and after the marathon and 1, 3, 5, and 7 days after the marathon. Muscle glycogen was supercompensated before the marathon (196 mmol glucosyl units kg wet tissue wt-1, mmol X kg-1) and was reduced to 25 mmol X kg-1 after the marathon. Seven days later it was 141 and 109 mmol X kg-1 in the rest and exercise groups, respectively. Measurement of glycogen synthase activity ratio indicated an active enzyme only immediately postmarathon, whereas measurement of glycogen synthase fractional velocity and relative velocity indicated an active enzyme immediately postmarathon and 1 day postmarathon. Hexokinase activity was significantly elevated immediately after the marathon and remained elevated through 5 days postmarathon. The activities of the hexose monophosphate pathway enzymes declined steadily during the experimental period and were significantly reduced 5 and 7 days postmarathon. Low-intensity exercise during the recovery week did not significantly differentiate the exercise group from the rest group.
Behavioral and autonomic thermoregulation in mice exposed to microwave radiation
Authors: Gordon C. J.
Published: December 2017

Preferred ambient temperature (Ta) and breathing rate were measured in free-moving mice exposed to 2,450-MHz microwaves. A waveguide-exposure system was imposed with a longitudinal temperature gradient that permitted mice to select their preferred Ta. Breathing rate was determined by analyzing the rhythmic shifts in microwave energy not absorbed by the animal. Without microwave exposure mice selected an average Ta of 31 degrees C. This preferred Ta did not change until the specific absorption rate (SAR) at 2,450 MHz exceeded approximately 7.0 W X kg-1. Mice maintained their breathing rate near baseline levels by selecting a cooler Ta during microwave exposure. In contrast, mice maintained at 31 degrees C underwent a sharp increase in breathing rate when SAR exceeded approximately 7.0 W X kg-1. Mice exposed to microwaves in a waveguide with a temperature gradient increased breathing rate 0.6 breaths/min per unit increase in SAR, whereas without the temperature gradient breathing rate increased by 9.6 breaths/min per unit increase in SAR. Data from this study support previous studies that have shown behavioral thermoregulation is more effective (or efficient) in minimizing a thermal load than autonomic thermoregulation.
Effect of lung inflation on alveolar-airway barrier protein permeability in dog lung
Authors: Conhaim R. L. , Gropper M. A. , Staub N. C.
Published: December 2017

To determine the leakiness to protein of the barrier that separates the air space and interstitial compartment of the lung, we measured perivascular interstitial fluid cuff protein concentration and volume in 10 isolated and 9 intact closed-chest dog lung lobes, which we degassed and inflated to 25, 50, 75, or 100% of capacity with 5% bovine serum albumin labeled with Evans blue dye. After 1 h we froze the lobes in liquid N2 and made color transparencies of 20 randomly selected frozen samples of each lobe. We measured Evans blue dye-albumin concentrations from absorption by cuff images of a 50-micron-diam red (lambda = 620 nm) microspot. We measured absolute cuff volume (ml/g dry lung) by point counting on the transparencies. Using specific Evans blue-albumin fluorescence we determined that the dye was protein bound in airways and cuffs. Cuff protein concentration averaged 37% of instillate concentration and did not vary with inflation volume or between isolated and intact lobes. Cuff volume was 3.4 ml/g dry lung at total lung capacity in both isolated and intact lobes. We conclude that at some point the barrier is permeable to albumin as well as liquid at all lung volumes in dogs and that the protein sieving properties of the barrier do not change with lung expansion over the range examined. The liquid storage capacity of the cuffs can increase as much as 20-fold between low and high lung volumes.
Superoxide dismutase with heparin prevents increased lung vascular permeability during air emboli in sheep
Authors: Flick M. R. , Hoeffel J. M. , Staub N. C.
Published: December 2017

We studied the effects of bovine superoxide dismutase on the increased lung microvascular permeability to fluid and protein during air emboli in unanesthetized sheep. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and lymph and plasma protein concentrations. In air emboli experiments we continuously infused the same dose of air bubbles 1 mm in diameter into the right atrium of each sheep to increase pulmonary vascular resistance to 2-4 times base-line values. We did experiments in pairs so that each sheep served as its own control. We found an increase in protein-rich lymph flow from the lung during embolization in untreated sheep, indicating an increase in microvascular permeability to both fluid and protein. When we pretreated the sheep with heparin (300 U/kg) and infused them with intravenous bovine superoxide dismutase (1 mg X kg-1 X h-1 beginning before the air infusion), we found that vascular pressures and pulmonary vascular resistance were not different from untreated sheep but that the expected increases in transvascular fluid and protein flow during emboli were significantly decreased (P less than 0.0005). Heparin alone did not significantly attenuate the increased microvascular permeability but we found that it greatly enhanced the effectiveness of superoxide dismutase in preserving microvascular functional integrity during air emboli. We conclude that superoxide anion, probably produced and released by leukocytes, is a central factor in the microvascular injury that results in increased permeability in the lungs of sheep during air microembolization.
Interaction of excitatory and inhibitory respiratory afterdischarge mechanisms in piglets
Authors: Lawson E. E. , Long W. A.
Published: December 2017

Afferent inputs to the central neuronal networks responsible for respiratory control can have effects on respiratory output that persist even after cessation of the original stimulus. In adults, carotid sinus nerve (CSN) stimulation activates a central excitatory mechanism which causes prolonged elevation of respiratory output. In newborns, superior laryngeal nerve (SLN) stimulation activates a central inhibitory mechanism which causes prolonged inhibition of respiratory output. The present study was designed to confirm that CSN stimulation in newborns also activates a long-acting central excitatory mechanism and to determine in what way the long-acting excitatory and inhibitory mechanisms interact. Anesthetized, paralyzed, and vagotomized piglets (2-30 days) were studied. Integrated phrenic nerve activity was determined before, during, and after stimulus trials consisting of CSN and SLN stimulation alone or following trials of sequential or simultaneous CSN and SLN stimulation. Respiratory output following CSN stimulation remained elevated and only gradually declined to the base-line value. Respiratory output following SLN stimulation remained depressed and only gradually recovered to the base-line value. One minute after cessation of the sequential trials, the respiratory output was intermediate between that of CSN or SLN stimulation alone at equivalent poststimulus times. We conclude that the central neural mechanisms which mediate the persistent poststimulus effects of CSN and SLN stimulation are independent but that they interact for a prolonged period following simultaneous or sequential activation. In infants, this interaction may effect respiratory stability during episodes of central or obstructive apnea and hypoxia.
Dynamic BTPS correction factors for spirometric data
Authors: Hankinson J. L. , Viola J. O.
Published: December 2017

Because it is often difficult to completely control ambient temperature, a study was conducted to investigate dynamic body temperature pressure saturated (BTPS) correction factors for spirometric data. A forced expiratory simulator system was heated to 37 degrees C and loaded with air saturated with water vapor. This air was then forced from the simulator into a dry rolling-seal spirometer maintained at various ambient temperatures from 3 to 32 degrees C. Errors in forced expiratory volume in 1 s (FEV1) and peak flow from assuming a constant BTPS correction ranged from 7.7 and 14.1% at 3 degrees C to 2.1 and 4.6% at 23 degrees C. Differences between errors observed when saturated and dry air were forced into the spirometer indicate that water vapor condensation introduces an added heat load to the spirometer, adding approximately one percent to the error in FEV1 at lower temperatures. By use of a model to estimate the dynamic BTPS correction factor, errors in FEV1 at all temperatures between 3 and 32 degrees C were reduced to less than 1.5%.
Chronic extracellular recording of fetal medullary neuronal activity
Authors: Ioffe S. , Jansen A. H. , Chernick V.
Published: December 2017

A technique for chronic extracellular recording of neuronal activity in the medullary region of fetal sheep during different sleep states is described. Of 51 recorded neurones, 54% were associated with respiration, blood pressure changes, or muscle electromyograms, and 46% were nonspecific. During apnea (nonrapid-eye-movement sleep) both inspiratory and expiratory neurons had random intermittent activity. Thus apnea is not associated with tonic expiratory neuronal activity.
Effect of high-frequency oscillation on lung lymph flow
Authors: Jefferies A. L. , Hamilton P. , O'Brodovich H. M.
Published: December 2017

We investigated the effect of high-frequency oscillation (HFO) on lung lymphatic function under normal conditions and when lung lymph flow was increased by air microembolization. In six experiments, sheep and goats with chronic lung lymph fistulas and vascular catheters were anesthetized, paralyzed, intubated, and ventilated according to the following protocol: 1) intermittent positive-pressure ventilation (IPPV) for 1 h, 2) HFO with a frequency of 15 Hz and an estimated tidal volume of 1-2 ml/kg for 1-2 h, and 3) IPPV for 0.5 h. Ventilator settings were adjusted to maintain arterial Po2 above 100 Torr and a normal arterial Pco2. Vascular, esophageal, and mean airway pressures were monitored continuously. Lymph flow and cardiac output were recorded every 15 min. With this protocol, there were no changes in pulmonary vascular or esophageal pressures, and lymph flow remained stable throughout the experiment. In an additional five experiments, air microemboli were infused for approximately 30 min during HFO. Left atrial pressure was unchanged and lymph flow tripled. This response was qualitatively and quantitatively similar to that previously reported for unanesthetized spontaneously breathing sheep. We conclude that HFO does not impair lymphatic function under resting conditions and that lymphatics retain their ability to increase water and protein clearance during HFO.
Effect of threshold loads on voluntary control of slow and rapid inspiratory movements
Authors: Folinsbee L. J. , Gliner J. A. , Horvath S. M.
Published: December 2017

The purpose of this study was to examine the hypothesis that voluntarily produced inspiratory movements are preplanned. Subjects performed both rapid (0.5 s) and slow (2.0 s) voluntary inspirations to a target volume of 50% of their inspiratory capacity under two conditions: 1) normally unloaded with random loading; and 2) normally loaded with random unloading. The load was a 10 cmH2O threshold load. When the load was unexpectedly applied, the subjects undershot the target volume by 397 ml (fast) and 284 ml (slow). When the load was unexpectedly removed, the subjects overshot the target volume by 303 ml (fast) and 224 ml (slow). The duration of inspiration did not change significantly. These observations are consistent with an “impulse-timing” model of preplanned voluntary movement, which incorporates reflex modification of the movement to compensate for loads which may be added or removed.
Food deprivation and surfactant in adult rats
Authors: D'Amours R. , Clerch L. , Massaro D.
Published: December 2017

We sought to determine if fasting (80% reduction of food intake for 72 h) diminishes airway or tissue disaturated phosphatidylcholine (DSPC) relative to alveolar surface area, or alters the lung response to overventilation. The lungs of fasted rats were lighter, but the size and recoil of saline-filled lungs, and the alveolar surface area of lungs fixed in glutaraldehyde, were the same in fed and fasted rats. In their airways fed rats had 0.32 +/- 0.01 microgram DSPC/cm2 of alveolar surface; fasted rats had 0.28 +/- 0.02 microgram DSPC/cm2 (P less than 0.05) (surface area determined at 20 cmH2O transpulmonary pressure). Fasted rats had 13% less tissue DSPC/cm2 alveolar surface than fed rats (P less than 0.01). After 1 h of mechanically produced overventilation the unequal amounts of airway, but not tissue, DSPC were eliminated and pulmonary compliance was similar in both groups. We conclude food reduction decreases the quantity of airway and tissue DSPC/cm2 of alveolar surface but does not increase lung recoil of spontaneously breathing rats (Gail, Massaro, and Massaro, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 88-92, 1977) or overventilated rats.
Effects of small changes in PaO2 on the ventilatory response to CO2 infusion
Authors: Bennett F. M. , Tallman R. D. , Grodins F. S.
Published: December 2017

The steady-state ventilatory responses to CO2 inhalation and two levels of intravenous CO2 infusion were examined in chronic awake dogs. Responses were obtained for four treatments: 1) air breathing, in which arterial O2 tension (PaO2) increased during infusion; 2) normoxia, PaO2 maintained at control levels; 3) hypoxia, PaO2 = 70 Torr; and 4) hyperoxia, PaO2 = 160 Torr. In three dogs, the ventilatory responses were obtained for treatments 1, 2, and 4 and in an additional three dogs for treatments 2, 3, and 4. Analysis of the data by directional statistics indicates that the response to infusion was hypercapnic for all treatments, and the slope of the response (change in minute ventilation divided by change in arterial CO2 tension) was identical to that of CO2 inhalation. Also, the slopes of the responses for the low infusion rate, CO2 output (VCO2) = 50%, and the high infusion rate, VCO2 = 270%, were identical, which suggests that the CO2 response is not significantly curvilinear near the eucapnic region. Finally, changing PaO2 between 70 and 160 Torr had no significant effect on the response slopes. Thus the ventilatory response to CO2 infusion in the awake dog is a hypercapnic hyperpnea that is not due to ventilatory inhibition arising from an increase in PaO2.
Effects of aging on sensation of respiratory force and displacement
Authors: Tack M. , Altose M. D. , Cherniack N. S.
Published: December 2017

The psychophysical technique of magnitude production was used to evaluate the sensation of inspiratory force and inspired volume in young and older subjects. Inspiratory force was generated during a static inspiratory maneuver against a closed airway. The exponent of the power function relationship between airway pressure and sensation intensity during force scaling was not significantly different between young and older subjects. In contrast, the exponents for the magnitude production of inspired volume were significantly greater in the older compared with the young group. We also assessed the effects of age on the relative importance of force and displacement signals on the sensation of inspired volume. Subjects attempted to reproduce a control tidal volume while breathing against a series of inspiratory resistive and elastic loads. In both groups error in tidal volume reproduction increased progressively as the severity of the load increased. During moderate and severe loading the error in the older subjects was significantly greater than in the young group. Correspondingly, the peak inspiratory airway pressures at tidal volume reproduction against these loads were significantly smaller in the older compared with the young subjects. The results suggest that in older subjects cues related to respiratory muscle force are more important than volume in the sensation of lung volume changes. In young subjects the sensation of lung volume changes is based to a greater degree on signals of volume or displacement.
Changes in arteriole in acute and chronic hypoxic pulmonary hypertension and recovery in rat
Authors: Sobin S. S. , Tremer H. M. , Hardy J. D. , Chiodi H. P.
Published: December 2017

After 1 h of exposure to 0.5 atm of pressure, the electron microscopy of intra-acinar arterioles of the young female adult rat showed edema and subendothelial blebs. Pulmonary hypertension developed rapidly with an increase in hemoglobin, hematocrit, and right ventricular weight. By 24 h, there was a threefold increase in the number of fibroblasts within the arteriolar wall, followed during the next 2 days by transformation of the fibroblast through a transitional cell form to a smooth muscle cell. By 1 wk, the neomuscularization was essentially complete. There was further minor thickening and increase in density of the wall over the next 9 mo. On return to 1 atm after prolonged hypoxia, within 4 wk, the smooth muscle of neomuscularized arterioles dedifferentiated but did not disappear. There was a concurrent rapid fall in the pulmonary arterial pressure, hemoglobin, hematocrit, and right ventricular weight. Veins, capillaries, and arteries remained normal. Parallel studies in the male rat during 14 days of hypoxia demonstrated the same phenomena except slightly accelerated over the female. The rapid sequential changes in the arteriole, beginning with subendothelial blebs and wall edema, followed by fibroblast recruitment and transformation into smooth muscle through a transitional cell form, suggest a cascade. The anatomic and physiological responses to hypoxia are not sex related.
Prevention of thiourea-induced pulmonary edema by hydroxyl-radical scavengers
Authors: Fox R. B. , Harada R. N. , Tate R. M. , Repine J. E.
Published: December 2017

Thiourea (TU), a very effective hydroxyl radical (.OH) scavenger, has little value as a probe of .OH in vivo because it causes fatal pulmonary edema. To test the hypothesis that TU-induced lung injury results from .OH-mediated oxidation of TU to toxic cyanamide, we pretreated rats with .OH scavengers, dimethylsulfoxide (DMSO), ethanol, and mannitol, prior to treatment with TU (3 mg/kg), preventing 91, 63, and 53%, respectively, of increases in lung weight to body weight ratios and 93, 67, and 46% of increases in lung lavage albumin concentrations. Furthermore, treatment of rats with cyanamide (CYN) (100 mg/kg) also caused increases in lung weight to body weight ratios (CYN: 7.39 +/- 0.57 X 10(-3) vs. controls: 5.46 +/- 0.26). N,N′-dimethylation of TU (DMTU) prevented TU toxicity, because treatment with DMTU did not significantly increase lung weight to body weight ratios (DMTU: 5.12 +/- 0.16 X 10(-3) vs. controls: 5.46 +/- 0.26) or lung lavage albumin (DMTU: 14 +/- 1 mg/100 ml vs. controls: 11 +/- 1). DMTU remained a very effective in vivo .OH scavenger, increasing survival of lethally irradiated mice treated with 600 mg/kg DMTU to 79% compared with 8% in untreated controls.
Effects of hypoproteinemia and increased vascular pressure on lung fluid balance in sheep
Authors: Kramer G. C. , Harms B. A. , Bodai B. I. , Renkin E. M. , Demling R. H.
Published: December 2017

We compared the effects of a sustained decrease in plasma oncotic pressure on lung fluid balance with those of an increase in vascular pressure in six unanesthetized sheep. Initial plasma protein concentration of 58.0 +/- 2.2 (SE) mg/ml was quickly reduced to 34.0 +/- 1.4 mg/ml via plasmapheresis and held at this value for 24 h. Red cells were returned with lactated Ringer solution infused at a rate adjusted to maintain central venous pressure; cardiac output and pulmonary vascular pressures also remained at base line. Steady-state lymph flows increased from a base-line value of 8.8 +/- 3.2 to 20.1 +/- 5.6 ml/h, while the lymph-to-plasma protein concentration ratio ( [L/P] ) decreased from 0.65 +/- 0.03 to 0.44 +/- 0.04. Decreased lymph protein resulted in reestablishment of base-line plasma-to-lymph oncotic gradient. The increased lymph flow was not the result of increased filtration forces, since all vascular pressures and the oncotic gradient were unchanged; nor was it due entirely to increased surface area since [L/P] was decreased. The decrease in plasma oncotic pressure, delta pi P, was twice as effective at increasing lymph flow (1.66 ml X h-1 X mmHg-1, delta pi P) as an equivalent increase in microvascular pressure, delta PC, at normal plasma protein concentration (0.82 ml X h-1 X mmHg-1, delta PC). Elevation of microvascular pressure during hypoproteinemia had a greater effect on lymph flow (1.44 ml X h-1 X mmHg-1, delta PC) than at normal plasma protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Method for cisterna magna perfusion of synthetic cerebrospinal fluid in the awake goat
Authors: Jameson L. C. , Smith C. A. , Dempsey J. A.
Published: December 2017

We developed a method to produce stable alterations in the ionic composition of the medullary chemoreceptor environment. A double-lumen catheter system (Hustead epidural needle and epidural catheter) was placed through a plastic cisternal guide tube into the cisterna magna of awake goats. A push-pull perfusion system using a modified infusion pump delivered matched cerebrospinal fluid (CSF) perfusate inflow and outflow of 3.1 ml/min. Ventilation changed within 15 min of the initiation of perfusion and reached steady state within 45-65 min. Steady-state ventilatory responses could be maintained for up to 240 min and were readily reversed in response to a change in [HCO-3]. Perfusions with normal mock CSF ( [HCO-3] = 23 meq/l) caused no change from nonperfused values. Over the range of CSF perfusate [HCO-3] used (13.5-34.4 meq/l), the gain of the steady-state ventilatory response averaged 0.6 Torr X meq-1 X l. [3H]inulin and [HCO-3] were equal in inflow and outflow by 20-30 min of perfusion indicating complete mixing of bulk CSF in the cistern. Anatomic study after methylene blue dye perfusion showed dye distribution to subarachnoid spaces of midbrain, cervical cord, cerebellum, medulla, and most of the cortex but not to any ventricles. This perfusion technique produces prolonged, stable, reproducible, and repeatable changes in the medullary chemoreceptor ionic environment of awake goats, is relatively atraumatic, and permits high flow through the cisternal subarachnoid space.
Maximum shortening velocity of smooth muscle: zero load-clamp vs. afterloaded method
Authors: Mitchell R. W. , Stephens N. L.
Published: December 2017

Previous reports from this laboratory of force-velocity relationships of canine tracheal smooth muscle (TSM) have presented maximum shortening velocities (Vmax) mathematically derived from the linearized transformation of the Hill equation (A. V. Hill, Proc. Roy. Soc. London, Ser. B., 126:136-195, 1938). Recent technical advances enable us to measure Vmax directly using an electromagnetic lever system that can instantaneously clamp to a zero load, thus we compared values of Vmax derived mathematically and those directly measured on the same TSM strips. Derived Vmax values from afterloaded isotonic shortening curves for loads greater than preload were 0.328 +/- 0.021 optimal length (lO)/s and were not significantly different from zero load-clamp measurements of 0.301 +/- 0.022 lO/s from the same (n = 15) muscles. These data indicate that Vmax values mathematically derived for TSM from conventional isotonic afterloaded force-velocity curves are valid estimates of zero load velocity, because they were not significantly different from values obtained by direct measurement using the zero load-clamp technique.
Magnetic resonance behavior of normal and diseased lungs: spherical shell model simulations
Authors: Durney Carl H. , Cutillo Antonio G. , Ailion David C.
Published: December 2017

The alveolar air-tissue interface affects the lung NMR signal, because it results in a susceptibility-induced magnetic field inhomogeneity. The air-tissue interface effect can be detected and quantified by measuring the difference signal (Δ) from a pair of NMR images obtained using temporally symmetric and asymmetric spin-echo sequences. The present study describes a multicompartment alveolar model (consisting of a collection of noninteracting spherical water shells) that simulates the behavior of Δ as a function of the level of lung inflation and can be used to predict the NMR response to various types of lung injury. The model was used to predict Δ as a function of the inflation level (with the assumption of sequential alveolar recruitment, partly parallel to distension) and to simulate pulmonary edema by deriving equations that describe Δ for a collection of spherical shells representing combinations of collapsed, flooded, and inflated alveoli. Our theoretical data were compared with those provided by other models and with experimental data obtained from the literature. Our results suggest that NMR Δ measurements can be used to study the mechanisms underlying the lung pressure-volume behavior, to characterize lung injury, and to assess the contributions of alveolar recruitment and distension to the lung volume changes in response to the application of positive airway pressure (e.g., positive end-expiratory pressure).
Responses of the anterolateral abdominal muscles during cough and expiratory threshold loading in the cat
Authors: Bolser Donald C. , Reier Paul J. , Davenport Paul W.
Published: December 2017

The present study was conducted to determine the pattern of activation of the anterolateral abdominal muscles during the cough reflex. Electromyograms (EMGs) of the rectus abdominis, external oblique, internal oblique, transversus abdominis, and parasternal muscles were recorded along with gastric pressure in anesthetized cats. Cough was produced by mechanical stimulation of the lumen of the intrathoracic trachea or larynx. The pattern of EMG activation of these muscles during cough was compared with that during graded expiratory threshold loading (ETL; 1–30 cmH2O). ETL elicited differential recruitment of abdominal muscle EMG activity (transversus abdominis > internal oblique > rectus abdominis ≅ external oblique). In contrast, both laryngeal and tracheobronchial cough resulted in simultaneous activation of all four anterolateral abdominal muscles with peak EMG amplitudes 3- to 10-fold greater than those observed during the largest ETL. Gastric pressures during laryngeal and tracheobronchial cough were at least eightfold greater than those produced by the largest ETL. These results suggest that, unlike their behavior during expiratory loading, the anterolateral abdominal muscles act as a unit during cough.