bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic effects of positive end-expiratory pressure applied as a ramp
Authors: Schreuder J. J. , Jansen J. R. , Bogaard J. M. , Versprille A.
Published: December 2017

Hypotheses on the decrease in cardiac output due to positive end-expiratory pressure (PEEP) were tested during positive-pressure ventilation by application of PEEP from 0 to 15 cmH2O as a ramp input function, i.e., a continuous rise. Yorkshire pigs (n = 47, 5–7 wk old) were used under steady-state anesthesia (pentobarbital) and muscle relaxation. Cardiac output decreased nonlinearly in three distinct phases, I up to PEEP 3 cmH2O, II from 3 to 10 cmH2O, and III above 10 cmH2O, with the sharpest decline occurring in phase II. This three-phase cardiac output decrease was more pronounced when the individual responses were normalized to the inflection points between the phases. Heart rate did not change when related to PEEP, but when normalized to the inflection points a significant increase was observed in the phase I and III, whereas in phase II a decrease was evident. Based on a diversity of hemodynamic responses myocardial depression and right ventricular afterload were rejected as major causal mechanisms for the decrease of cardiac output. We hypothesized that the nonlinear response of cardiac output on PEEP is due to a combination of three types of mechanisms. First, the rise of central venous pressure with PEEP decreases cardiac output linearly. Second, the concomitant fall of arterial pressure elicits compensatory mechanisms, which flatten the slope of this venous return curve. Finally, above 3 cmH2O PEEP a lung stretch reflex is elicited, which performs an inhibitory effect on the circulation, causing the steeper fall in cardiac output as well as the decrease in heart rate in phase II.
Determination of human muscle pH in needle-biopsy specimens
Authors: Costill D. L. , Sharp R. L. , Fink W. J. , Katz A.
Published: December 2017

The homogenate technique for the determination of muscle pH (pHm) has been studied to assess the influence of delayed freezing and the composition and volume of the homogenizing medium on human muscle pH at rest and after exhaustive exercise. It was concluded that resting muscle samples must be frozen within 2 s to prevent falsely high pHm values. Muscle specimens used for lactate determinations (HLam), on the other hand, can be delayed in freezing for up to 30 s without altering the HLam content. A 30- to 40-s delay in biopsying the muscle after the cessation of exhaustive exercise does not appear to alter pHm or HLam values. Although the homogenate method does not provide information relative to the status of selected muscle fibers, it does offer a reliable sensitive measure of mean changes in the acidification of muscle with intense exercise.
Ventilatory phase duration in the chicken: role of mechanical and CO2 feedback
Authors: Ballam G. O. , Clanton T. L. , Kunz A. L.
Published: December 2017

Awake upright White Leghorn roosters (Gallus domesticus) were unidirectionally ventilated. Electromyographic activity from inspiratory and expiratory muscles was recorded to demarcate inspiration and expiration. During inspiration, the rate of inflation of the air sac system was varied while the CO2 concentration of the gas passing through the lungs was maintained constant. Inspiratory duration was inversely related to the rate of inflation, producing an inspiratory volume-time threshold (VT) curve with a negative slope. When the CO2 concentration was increased in the lungs, the inspiratory VT curve shifted to the right with a concurrent increase in slope. If the rate of deflation was varied during expiration, it was found that expiratory duration was inversely related to the rate of deflation, producing an expiratory VT curve with a positive slope. Increasing the CO2 concentration shifted the curve to the left with an increased slope. These results indicate that inspiratory and expiratory phase durations are a function of both mechanical and chemical feedback.
Lengthening of inspiration by intrapulmonary chemoreceptor discharge in ducks
Authors: Berger P. J. , Tallman R. D.
Published: December 2017

The influence of avian intrapulmonary chemoreceptors (IPC) on inspiratory duration (TI) was tested by experimentally reducing their level of discharge for a single inspiration. The seven major air sacs of decerebrate or anesthetized ducks were cannulated with wide-bore tubing and then connected to a single clamped outlet. In self-ventilating animals, opening the sac line for a single inspiration caused the inspiratory discharge of 17 IPC to disappear and that of a further 7 to fall substantially; no IPC showed a rise in discharge, nor did the 6 presumed respiratory stretch receptors from which recordings were made. The reduction of IPC discharge was accompanied by a fall in TI rather than the rise required if IPC were to resemble mammalian pulmonary stretch receptors in their action on TI. We propose that in eupnea inspiratory IPC discharge prolongs inspiration.
Control of ventilation in running birds: effects of hypoxia, hyperoxia, and CO2
Authors: Brackenbury J. H. , Gleeson M. , Avery P.
Published: December 2017

Minute volume (V), tidal volume (VT), respiratory frequency (f), venous lactate, and clavicular air sac gas composition were measured in domestic fowl at rest and during exercise, breathing hypoxic, hyperoxic, or hypercapnic gas. Hyperoxia produced no significant change in ventilation, CO2 inhalation produced increases in V and VT, but the changes in f appeared to be related to the stage of exercise at which CO2 was administered. The sensitivity of the hypercapnic response was similar in resting and exercising birds. Compared with the effects of CO2, hypoxia elicited only a weak ventilatory response in rest and exercise conditions despite severe tissue anaerobiosis.
Pulmonary blood flow distribution in panting ostriches
Authors: Jones J. H.
Published: December 2017

Ostriches (Struthio camelus) are the only birds known that can increase post-dead space ventilation during severe heat stress without experiencing hypocapnia and respiratory alkalosis. To determine whether this phenomenon occurs due to redistribution of pulmonary blood flow during panting, thus creating an extreme ventilation-perfusion (V/Q) imbalance, the distributions of pulmonary blood flow in ostriches at rest (15 degrees C) and in severe panting (45 degrees C) were determined using radioactively labeled microspheres. Blood flow distribution at rest was greatest in the neopulmo [18% greater than mean pulmonary blood flow (MPBF)] and the cranial (23% greater than MPBF) and distal (12% greater than MPBF) regions of the paleopulmo. During panting blood flow was not shunted around the lung, and flow to the neopulmo decreased to MPBF, became more homogeneous along the craniocaudal axis, and remained nonhomogeneous along the mediolateral axis. The results suggest that the observed decrease in gas exchange during panting is probably due primarily to shunting of the increased ventilation around the parabronchial exchange region rather than to alterations in the patterns of V/Q within the lung.
Deposition and clearance of inhaled aerosol in the respiratory tract of chickens
Authors: Mensah G. A. , Brain J. D.
Published: December 2017

Sixteen unanesthetized adult White Leghorn chickens (Gallus domesticus) were exposed to an aerosol of 99mTc-labeled submicrometric particles and killed 0, 1, 12, or 36 h later. The amount and distribution of radioactive particles retained in the lungs and skeletal system were measured to describe regional deposition and clearance. Particles were present in the lungs, air sacs, and skeletal system immediately after exposure. Reduction in activity with time suggested clearance of aerosol from the lungs and pneumatized bones. Aerosol particles were not distributed uniformly within the lungs; there was greater retention in the caudal regions. No dorsoventral gradients were observed. Of the initial lung deposition, 54 +/- 13.9% (SD) remained 1 h postexposure and 35.6 +/- 20.9% remained 36 h later. These data suggest an early fast phase of lung clearance followed by a slower phase. Detailed morphological studies are needed to understand the underlying clearance mechanisms and the bases for the differences in regional deposition.
Changes in eggshell conductance after transfer of hens from an altitude of 3,800 to 1,200 m
Authors: Rahn H. , Ledoux T. , Paganelli C. V. , Smith A. H.
Published: December 2017

Hens acclimated to an altitude of 3,800 m (PB 480 Torr) were transferred to 1,200 m (PB 657 Torr). Eggs were collected before departure and daily after the transfer so that changes in eggshell conductance could be studied. Over the next 2 mo eggshell conductance increased 30%, presumably to compensate for the 37% reduction (from 657 to 480 Torr) in gas diffusivity at the lower altitude. Measurements of shell thickness and number of pores in the shell allow one to calculate that most of the change in total pore area occurred by an increase in cross-sectional area of individual pores.
Effect of change in P50 on exercise tolerance at high altitude: a theoretical study
Authors: Bencowitz H. Z. , Wagner P. D. , West J. B.
Published: December 2017

Acclimatization to altitude often results in a rightward shift of the O2 dissociation curve (ODC). However, a left-shifted ODC is reported to increase exercise tolerance in humans at medium altitude and increase survival in rats breathing hypoxic gas mixtures. We examined this paradox using a computer model of pulmonary gas exchange. A Bohr integration procedure allowed for alveolar-capillary diffusion. When diffusion equilibration was complete, mixed venous (PVO2) and arterial PO2 fell as O2 consumption (VO2) was increased, but PVO2 approached a plateau. Under these conditions a right-shifted ODC is advantageous (higher PVO2) at all but very high altitudes. However, diffusion limitation of O2 transfer may occur at any altitude if VO2 is increased sufficiently. If this occurs, a left-shifted ODC results in higher calculated VO2max (compared with the standard ODC). Further, diffusion limitation always occurs at a lower VO2 with a right-shifted ODC than with a left-shifted ODC. We conclude that whether a leftward or rightward shift in the ODC is advantageous to gas exchange at altitude depends on the presence or absence of diffusion limitation.
Central and peripheral chemoreceptor inputs to phrenic and hypoglossal motoneurons
Authors: Bruce E. N. , Mitra J. , Cherniack N. S.
Published: December 2017

We tested the hypothesis that phrenic and hypoglossal responses to progressive hypercapnia differ qualitatively because the CO2-related drive inputs to their respective motoneuron pools are different. The relative contributions of carotid sinus and central chemoreceptor inputs to hypoglossal and phrenic responses during hyperoxic hypercapnia were determined by comparing the two nerve activities during rebreathing runs done either before and after bilateral carotid sinus nerve (CSN) section, or without and with cooling of the intermediate, I(s), area on the ventral surface of the medulla. The studies were performed on chloralose-anesthetized, vagotomized, paralyzed cats. Cooling of the I(s) area impaired phrenic responsiveness to hypercapnia more than hypoglossal responsiveness, whereas CSN section had the opposite effect. Thus phrenic nerve response was more dependent on central chemoreceptor input than was the hypoglossal response, but hypoglossal response was more dependent on carotid sinus chemoreceptor input. We conclude that the phrenic and hypoglossal motoneuron pools each receive a different functional input from both the medullary and the carotid sinus chemoreceptors.
Effect of atelectasis and embolization on extravascular thermal volume of the lung
Authors: Beckett R. C. , Gray B. A.
Published: December 2017

The extravascular volume of distribution for heat in the lung has been advocated for the measurement of lung water. The purpose of these experiments was to investigate how extremes of ventilation-perfusion mismatch influence this measurement. Twenty-six dogs were studied with right and left atrium-to-aorta thermal and dye-dilution curves before and 60 min after total right main-stem bronchial obstruction or microembolization of the pulmonary circulation with 0.275-mm glass beads. Whereas atelectasis had no influence on our measurements, embolization with 0.32 g/kg of beads decreased the detected pulmonary blood volume from 10.63 to 8.55 ml/kg and increased the extravascular thermal volume (ETV) from 9.89 to 10.99 ml/kg. Embolization with 0.65 g/kg decreased the detected ETV from 9.29 to 8.38 ml/kg, while the extravascular wet-to-dry weight ratio was increased, and the regression of postmortem extravascular mass on ETV differed from control. We conclude that microembolization but not atelectasis causes errors in the measurement of lung fluid when the thermodye technique is used. The errors are variable and depend on the degree of embolization.
Oxygen consumption measured with microcomputer-assisted Warburg manometry
Authors: Johnson T. A. , Mercer R. R. , Taylor P. C. , Graham J. A. , O'Neil J. J.
Published: December 2017

We have developed and tested an automated system that measures in vitro oxygen consumption by Warburg manometry in as many as 16 units that are under the simultaneous control of a microcomputer which requires attention at the beginning of the study only. The all-glass Submarine Volumometers used are readily adapted to automation using a microcomputer that interacts with an infrared photodetector sensitive to manometric changes in the reaction vessel and a stepper motor that can advance the calibrated micrometer in response to these changes. The microcomputer interacts with the user at the start of the study during data entry and subsequently determines volume changes related to oxygen consumption, calculates respiration rates, and prints or graphs the results without further user interaction. We compared this automated system with manual methods by measuring the oxygen consumption of lung tissue slices and by determining the ability of the system to match known volumes entered manually. We found that the results obtained using the automated system were not significantly different from known manual methods (P less than 0.05).
Nonlinear fluid systems identified by random noise input
Authors: Delavault E. , Saumon G. , Georges R.
Published: December 2017

The usual impedance measurement by Fourier analysis leads to undetectable errors when applied to nonlinear fluid systems where a nonlinear pressure drop p = K X V2 adds to the linear pressure-flow relationship, but processing series of impedance data with various input levels allows the measurement of such systems. This new method has been tested on simulations, nonlinear resistances, and intubation tubings. It gives accurate estimates of the nonlinear coefficient K together with the true linear impedance of the measured system. This way, the usual respiratory impedance measurement may be applied to intubated patients, as the respiratory impedance of the subject can be separated from the nonlinear behavior of the endotracheal tube or cannula.
Blood osmolality in vitro: dependence on PCO2, lactic acid concentration, and O2 saturation
Authors: Boning D. , Maassen N.
Published: December 2017

Changes of osmolality (Osm) were measured by freezing-point determination in true plasma of 10 healthy subjects. This was done after equilibration with CO2 (0.5–10.0%), after the addition of lactic acid (10 and 20 mmol/l), and after deoxygenation. The graph for the dependence of Osm on CO2 partial pressure (PCO2) in oxygenated blood resembles the classical CO2 absorption curve. The increase of Osm with PCO2 (approximately 0.2 mosmol . kg H2O-1 . Torr-1) is almost as great as the increase in dissolved CO2 plus bicarbonate (HCO-3). Addition of lactic acid shifts the curve upward by only 0.6 mosmol/mmol because of displacement of HCO-3. Deoxygenation has no significant effect at constant PCO2 despite an increase in [HCO-3]. This is probably due to the binding of 2,3-diphosphoglycerate to hemoglobin. It can be seen in the Osm-pH diagram that differences between CO2 and lactic acid titration largely disappear. For each lactic acid concentration there is a linear dependence corresponding to the linear [HCO-3]-pH relation in plasma. At constant pH, Osm increases after deoxygenation. The observed in vitro relation might explain part of the osmolality increase during physical exercise.
Blood osmolality during in vivo changes of CO2 pressure
Authors: Boning D. , Vaas U. , Braumann K. M.
Published: December 2017

In 16 experiments male subjects, age 22.4 +/- 0.5 (SE) yr, inspired CO2 for 15 min (8% end-tidal CO2) or hyperventilated for 30 min (2.5% end-tidal CO2). Osmolality (Osm) and acid-base status of arterialized venous blood were determined at short intervals until 30 min after hypo- and hypercapnia, respectively. During hypocapnia [CO2 partial pressure (PCO2) -2.31 +/- 0.32 kPa (-17.4 Torr), pH + 0.19 units], Osm decreased by 3.9 +/- 0.3 mosmol/kg H2O; during hypercapnia [PCO2 + 2.10 +/- 0.28 kPa (+15.8 Torr), pH -0.12 units], Osm increased by 5.8 +/- 0.7 mosmol/kg H2O. Presentation of the data in Osm-PCO2 or Osm-pH diagrams yields hysteresis loops probably caused by exchange between blood and tissues. The dependence of Osm on PCO2 must result mainly from CO2 buffering and therefore from the formation of bicarbonate. In spite of the different buffer capacities in various body compartments, water exchange allows rapid restoration of osmotic equilibrium throughout the organism. Thus delta Osm/delta pH during a PCO2 jump largely depends on the mean buffer capacity of the whole body. The high estimated buffer value during hypercapnia (38 mmol/kg H2O) compared with hypocapnia (19 mmol/kg H2O) seems to result from very strong muscle buffering during moderate acidosis.
Lactate accumulation relative to the anaerobic and respiratory compensation thresholds
Authors: Simon J. , Young J. L. , Gutin B. , Blood D. K. , Case R. B.
Published: December 2017

Anaerobic thresholds of five male subjects were determined invasively (ATi), from a marked increase in plasma lactate above resting levels (delta La), and noninvasively (ATn), from a nonlinear increase in minute ventilation (VE) during incremental work (IW) leg cycling tests; work rate was increased 30 W every 2 min. Each subject also performed four constant-load work (CLW) tasks just above and just below their ATn and respiratory compensation threshold (RCT), i.e., the point expressed as O2 consumption (VO2) or work rate, at which VE increases disproportionally to CO2 output during IW. In four of the five subjects the ATn preceded the ATi during IW. Yet the ATn delineated the CLW in which marked lactate accumulation did or did not occur. During CLW just above the ATn in these same four subjects, VE/VO2 and fractional expired O2 (FEO2) peaked well before delta La plateaued. These findings suggest that exercise hyperventilation is not necessarily proportional to increases in plasma lactate.
Potentiation of oxygen toxicity in rats by dietary protein or amino acid deficiency
Authors: Deneke S. M. , Gershoff S. N. , Fanburg B. L.
Published: December 2017

Rats fed 3% casein diets for 6 days showed an increased susceptibility to greater than 98% oxygen [mean survival time 46.9 +/- 4.1 (SD) h] compared with animals fed 25% casein diets (mean survival time 60 +/- 5 h). The 3% casein diet did not reduce the responses to hyperoxia of lung glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase (NAD(P)H), which maintain tissue levels of reduced glutathione or lung superoxide dismutase levels. While supplementation of the 3% casein diet with the sulfur-containing amino acids (cysteine, cystine, or methionine) prevented the increased oxygen toxicity, supplementation with leucine, a nonsulfur-containing amino acid, had no effect on potentiation of toxicity. Animals fed the unsupplemented 3% casein diet failed to show an elevation of lung glutathione in response to hyperoxia. When the 3% casein diet was supplemented with cysteine, total lung glutathione levels increased normally during oxygen exposure. Supplementation of the 25% protein diet with cysteine did not further protect these animals. We conclude that potentiation of oxygen toxicity by dietary protein deficiency in the rat is due to the low sulfur-containing amino acid content of the diet; the mechanism of increased toxicity by hyperoxia is probably related to an inability to increase glutathione levels due to a shortage of the cysteine component of the glutathione tripeptide.
Elastic properties of the lung in acute induced asthma
Authors: Rodenstein D. , Stanescu D. C.
Published: December 2017

In acute induced asthma, plethysmographic total lung capacity (TLCm) was reported to increase and lung elastic recoil [Pst(L)] to decrease. The increase in TLC is spurious (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 939–954, 1982), so that the rapid loss in Pst(L) could be due to errors in lung volume. We studied seven asthmatic patients before and during an induced bronchospasm. TLC was derived simultaneously from mouth and esophageal pressure vs. plethysmographic volume plots (TLCm and TLCes, respectively). Before bronchospasm, TLCm and TLCes were similar. During bronchospasm average TLCm increased, from 7.30 +/- 1.34 (SD) to 8.12 +/- 1.49 liters (P less than 0.001), whereas TLCes did not (P greater than 0.60). Static pressure-volume curves, derived from TLCes (P-Ves), were superimposed on prechallenge curves or only slightly shifted to the left, whereas those derived from TLCm (P-Vm) showed a clear-cut parallel shift to the left. At 70% of control TLC there was no significant change in Pst(L) measured from P-Ves curves (7.3 +/- 3.1 cmH2O before bronchospasm; 6.7 +/- 2.3 cmH2O during bronchospasm, P greater than 0.10), whereas Pst(L) measured from P-Vm curves decreased from 7.3 +/- 3.1 to 5.1 +/- 2.4 cmH2O (P less than 0.01). No significant change in Pst(L) at TLC was observed during bronchospasm. We conclude that in our patients acute decrease in Pst(L) during induced asthma was artifactual, secondary to lung volume overestimation by body plethysmography.
Effects of hypercapnia, hypoxia, and rebreathing on heart rate response during apnea
Authors: Lin Y. C. , Shida K. K. , Hong S. K.
Published: December 2017

Five series of breath-hold (BH) experiments were conducted on eight male subjects with the purpose of partitioning the effects of apnea per se, hypercapnia, and hypoxia on the development and maintenance of BH bradycardia. All BH were 90 s in duration and were achieved by face immersion at room temperature. Of the five series of BH, one was a continuous BH and the remaining included rebreathing at 15-s intervals while the face remained immersed. Comparison of heart rate (HR) responses between the continuous BH with air and that interrupted every 15 s by rebreathing without improving the alveolar gas composition yields the attenuating effect of respiratory activity. The hypercapnic effect was calculated from the difference in HR responses between two series of BH with O2, in which hypoxia was not present and rebreathing was common to both; in one rebreathing was through a CO2 scrubber thus creating different alveolar CO2 levels in the two series. The effect of hypoxia was deduced by finding the difference between the total bradycardial response (continuous BH) and the summed effects of hypercapnia and apnea per se. By this procedure, it was found that apnea and hypoxia reduced the HR by 19 and 18%, respectively, from the pre-BH value, and hypercapnia increased HR by 6% from the pre-BH level, thus accounting for the total 31% reduction in HR in a continuous BH.
Blood lactate threshold in some well-trained ischemic heart disease patients
Authors: Coyle E. F. , Martin W. H. , Ehsani A. A. , Hagberg J. M. , Bloomfield S. A. , Sinacore D. R. , Holloszy J. O.
Published: December 2017

Six patients with ischemic heart disease who had exercised intensely for longer than 1 yr appeared to have a disproportionately high capacity for endurance exercise relative to VO2 max. They were compared with healthy runners of the same age (mean 55 yr) with similar training programs (6–12 km/day, 5 day/wk). The trained patients had a significantly (P less than 0.05) lower maximal cardiac output (-17%) and VO2 max (-18%, 37 vs. 45 ml . kg-1 . min-1). Despite their lower VO2 max, the trained patients were able to run 8 km at the same speed as the normal runners (approximately 189 m/min). The trained patients' ability to keep pace with the normal subjects was apparently due to a very high lactate threshold (LT) relative to VO2 max. The patients' LT (lactate 1 mM above base line) occurred at a treadmill running speed of 176 m/min, which elicited 100% of their VO2 max, compared with a LT at 178 m/min and 84% of VO2 max in the normal subjects (P less than 0.01). Our results show that some individuals with VO2 max limited by impaired cardiac function can undergo adaptations to training that enable them to maintain close to a metabolic steady state during exercise that elicits VO2 max.
Axial distortion of airways in the lung
Authors: Kallok M. J. , Lai-Fook S. J. , Hajji M. A. , Wilson T. A.
Published: December 2017

Axial loads were applied around the circumference of an airway lumen by pulling on a cup-shaped anchor that embedded itself in the airway wall. Axial displacements were measured as a function of distance from the load, and the data were compared to the results of mathematical analyses of continuum mechanics models. In the modeling it was assumed that the elastic tube representing the airway is bonded to the surrounding elastic continuum representing the parenchyma and that axial forces are transmitted between the tube and the continuum by shear stresses at the interface. The agreement between the measured and computed axial displacements supports the hypothesis that the shear stresses are the dominant coupling mechanism. The following quantitative relations between force and displacement were obtained. The axial displacement produced by the load L was approximately 0.05 L/pi alpha mu, where alpha is the airway radius and mu is the shear modulus of the parenchyma. The displacement decayed to approximately one-half this maximal value at two diameters from the load.
Endotoxin protects against hyperoxic alterations in lung endothelial cell metabolism
Authors: Block E. R.
Published: December 2017

By evaluating the ability of endotoxin to prevent hyperoxic depressions in lung amine uptake, this study assessed whether bacterial endotoxin protects against hyperoxic injury to the pulmonary endothelium. Rats were given 500 or 1,500 micrograms/kg body wt of endotoxin or saline (controls) 30 min before a 24-h or 7-day exposure to air or 100% O2 at 1 ATA. Immediately after exposure, lungs were isolated, ventilated, and perfused via the pulmonary artery and the uptake of two amines, [14C] serotonin and [3H]norepinephrine, was measured. Amine uptake by the lungs of control rats exposed to 100% O2 for 24 h was significantly depressed, whereas amine uptake by the lungs of endotoxin-treated rats exposed to 100% O2 for 24 h was comparable to that in air-exposed controls. Endotoxin also prevented hyperoxic depression of lung amine uptake and prolonged survival in rats exposed to 100% O2 for 7 days. Pretreatment of rats with endotoxin protects against hyperoxic injury to the pulmonary endothelium, which may account for the reduced mortality in endotoxin-treated animals.
Effects of water immersion on plasma catecholamines in normal humans
Authors: Epstein M. , Johnson G. , DeNunzio A. G.
Published: December 2017

Recent evidence indicates that stimulation of cardiopulmonary receptors in experimental animals results in a diminution of autonomic nervous system activity. Water immersion to the neck (NI) results in a preferential central hypervolemia (CV); thus it might be anticipated that NI would alter plasma catecholamine levels. Because two earlier studies have yielded divergent findings, we designed the present study utilizing more updated methodology to determine whether NI alters plasma catecholamines in normal humans. Eight normal subjects were studied on two occasions; during a seated control study (C) and during 4 h of NI. Norepinephrine (NE) and epinephrine (E) levels, determined by radioenzymatic assay, were measured hourly. Despite the induction of a marked natriuresis and diuresis indicating significant CV, NI failed to alter plasma NE or E levels compared with those of either C or the corresponding prestudy 1.5 h. Furthermore, the diuresis and natriuresis varied independently of NE. The current findings suggest that the response of the sympathetic nervous system to acute volume alteration may differ from the reported response to chronic volume expansion.
Response of ventral respiratory group inspiratory neurons to mechanical loading
Authors: Seaman R. G. , Zechman F. W. , Frazier D. T.
Published: December 2017

The bursting patterns of 32 ventral respiratory group (VRG) medullary inspiratory neurons were studied in response to selected mechanical loads in 68 allobarbital-urethan-anesthetized cats. Mechanical loads consisted of three levels of resistive loads, one elastic load, and tracheal occlusion (TO). The application of each load was manipulated to oppose either inspiration or expiration. Loads were applied for only one inspiration or expiration to prevent changes in chemical drive. All loaded breath unit responses were analyzed and compared with control values for inspiratory time (TI), expiratory time (TE), spikes per burst (SPB), and average firing rate (FR). Inspiratory mechanical loads resulted in statistically significant increases in TI and SPB but only small nonsignificant increases in FR and TE. Expiratory resistive loading produced its predominant effect on TE. The higher expiratory mechanical loads also caused significant increases in the subsequent unloaded TI and SPB. In contrast to expiratory loading, large inspiratory loads did not significantly affect the next unloaded TE. Bilateral cervical vagotomy eliminated the observed neural responses to loading for both inspiratory and expiratory loads. All of the 71 neurons tested with lung inflations and TO at end inspiration showed inhibition (Ra type) rather than facilitation (R beta).
Pulmonary vascular tone is a determinant of basal lung perfusion in normal seated subjects
Authors: Nemery B. , Wijns W. , Piret L. , Cauwe F. , Brasseur L. , Frans A.
Published: December 2017

In the human upright lung the downward increase in lung perfusion reverses in the lower third, thus giving rise to a zone of reduced basal perfusion (zone 4). The flow in zone 4 is regulated by the extra-alveolar vessels, the diameter of which is determined by lung volume, perivascular interstitial pressure, and vasomotor tone. To estimate the role of pulmonary vascular tone in the formation of zone 4, we infused nitroprusside (NTP), a potent pulmonary vasodilator, in six normal seated subjects. We measured their regional perfusion distribution using 133Xe in control conditions and at two dose levels of NTP (20.8 and 52.1 micrograms/min). Regional perfusion distribution was measured similarly and according to the same protocol in six subjects receiving only a placebo solution. In four of the six subjects receiving NTP, right-heart catheterization allowed simultaneous estimations of cardiac output and pulmonary arterial pressure to be made. NTP slightly decreased the perfusion of the nondependent parts of the lungs and markedly increased the perfusion of the lung bases, thus reducing the extent of zone 4. No changes were observed in the placebo experiments. Cardiac output and indices of ventilation and gas exchange did not change significantly. Peripheral and pulmonary arterial pressure fell slightly but significantly during NTP infusion. We attribute the observed changes in basal perfusion to the vasodilatory effects of NTP on the extra-alveolar vessels. Our findings thus support the hypothesis that in normal subjects zone 4 is partly created by the pulmonary vascular tone.
Ionic mechanisms of cerebrospinal fluid acid-base regulation
Authors: Nattie E. E.
Published: December 2017

This review emphasizes the importance of strong ions in the regulation of cerebrospinal fluid (CSF) acid-base balance. In a solution like CSF that is devoid of nonbicarbonate buffers. [H+] and [HCO-3] are dependent variables, the independent variables being the CO2 partial pressure (PCO2) and the strong ion difference. Any measureable changes in CSF [HCO-3] and any change in [H+] that occur independent of changes in PCO2 must be accompanied by, if not caused by, changes in strong ions. The role of H+ and HCO-3 vs. strong ions in the ionic mechanisms of CSF acid-base regulation is unknown. For example, these mechanisms could depend only on changes in strong ions that accompany acid-base disorders, or they could be triggered by changes in [H+] or PCO2. These ideas are presented within the context of current concepts concerning the relationship of CSF to brain interstitial fluid (ISF) and the importance of choroid plexus and blood-brain barrier mechanisms in determining CSF and ISF ionic composition. Studies concerning CSF strong ions in normal and abnormal acid-base states are reviewed.
Dynamic measurements of CO diffusing capacity using discrete samples of alveolar gas
Authors: Graham B. L. , Mink J. T. , Cotton D. J.
Published: December 2017

It has been shown that measurements of the diffusing capacity of the lung for CO made during a slow exhalation [DLCO(exhaled)] yield information about the distribution of the diffusing capacity in the lung that is not available from the commonly measured single-breath diffusing capacity [DLCO(SB)]. Current techniques of measuring DLCO(exhaled) require the use of a rapid-responding (less than 240 ms, 10–90%) CO meter to measure the CO concentration in the exhaled gas continuously during exhalation. DLCO(exhaled) is then calculated using two sample points in the CO signal. Because DLCO(exhaled) calculations are highly affected by small amounts of noise in the CO signal, filtering techniques have been used to reduce noise. However, these techniques reduce the response time of the system and may introduce other errors into the signal. We have developed an alternate technique in which DLCO(exhaled) can be calculated using the concentration of CO in large discrete samples of the exhaled gas, thus eliminating the requirement of a rapid response time in the CO analyzer. We show theoretically that this method is as accurate as other DLCO(exhaled) methods but is less affected by noise. These findings are verified in comparisons of the discrete-sample method of calculating DLCO(exhaled) to point-sample methods in normal subjects, patients with emphysema, and patients with asthma.
Inhibition of pulmonary macrophage function by airway mucus
Authors: Woodside K. H. , Denas S. M. , Smith K. L. , Kim C. S. , Wanner A.
Published: December 2017

As a model for the interaction between macrophages and mucus in the tracheobronchial tree, we incubated sheep alveolar macrophages in vitro with and without airway mucus from the same animal and tested their phagocytic function and rates of general protein synthesis. Airway mucus was obtained by tracheal suction after previous subcutaneous injection of the sheep with pilocarpine (0.5 mg/kg) and subsequently diluted. Pulmonary macrophages were obtained by saline lavage through a balloon-tipped fiber-optic bronchoscope. In incubated attached macrophages, phenylalanine incorporation into protein was inhibited 51% by mucus (P less than 0.001). Phagocytosis of 1.09-microns latex particles was inhibited 75% by mucus at nonsaturating levels of particles (P less than 0.001) and by 47% at saturating levels of particles (P less than 0.001). Inhibitory activity for protein synthesis and phagocytosis was retained in the 104,000 g supernatant fraction of whole mucus (sol), while the gel fraction inhibited phagocytosis only. This difference did not appear to be related to physical factors. We conclude that diluted airway mucus interferes with pulmonary macrophage function as assessed by rates of general protein synthesis and phagocytosis.
Effects of the Clara cell toxin, 4-ipomeanol, on pulmonary function in rats
Authors: Sabo J. P. , Kimmel E. C. , Diamond L.
Published: December 2017

The naturally occurring compound, 4-ipomeanol (IPO, 1-[3-furyl]-4-hydroxy-1-pentanone), selectively damages the nonciliated epithelial (Clara) cells of the terminal bronchioles. Because information is not available concerning functional changes in IPO-treated lungs, an investigation was undertaken to evaluate the in vivo pulmonary ventilatory, mechanical, and gas exchange functions of female Long-Evans rats 24 h after treatment with a single intraperitoneal dose of 1 or 5 mg IPO/kg body wt. A preliminary toxicity study established the 24-h LD50 for intraperitoneally administered IPO at 19 +/- 3 (SD) mg/kg. Significant increases in lung fluid occurred in animals treated with 15 mg IPO/kg, and histological evidence of pulmonary edema was observed in animals treated with 10 mg IPO/kg. Treatment of rats with 5 mg IPO/kg caused a significant decrease in tidal volume and a significant increase in respiratory rate and functional residual capacity-to-total lung capacity ratio (%). In rats treated with 1 mg IPO/kg, pulmonary functions were minimally affected. The functional changes observed in IPO-treated animals can be attributed to swelling and possible dysfunction of Clara cells, with subsequent alveolar interstitial edema and stimulation of juxtapulmonary capillary receptors, or to a direct effect of the toxin on respiratory control mechanisms.
Effects of androgenic-anabolic steroids on neuromuscular power and body composition
Authors: Crist D. M. , Stackpole P. J. , Peake G. T.
Published: December 2017

The effects of androgenic-anabolic steroids on neuromuscular power and body composition were studied in nine volunteers experienced with progressive-resistance weight training. By use of double-blind procedures, testosterone cypionate, nandrolone decanoate, and sesame oil (placebo) were administered in a repeated-measures design that counterbalanced treatment order. Duration of each treatment condition was 3 wk. Supplemental protein was provided, and dietary records were maintained throughout the study. Subjects were trained with progressive-resistance weight-training exercises. Isokinetic dynamometer testing revealed that peak torque output was not significantly changed between treatments in 7 out of 10 isolated-joint actions. The hydrostatic weighing results revealed insignificant differences in lean body mass and percent body fat. Significant changes in some treatment means of three peak torque output tests were insufficient to identify any consistent treatment alterations. Since protein and caloric intake was sufficient to elicit anabolic effects from the steroid treatments and weight-training program, the lack of significant results could not be attributed to dietary considerations. Subjects reported subjective feelings of increased strength after administration of anabolic agents, which may partially account for their widespread use. In conclusion, anabolic steroids did not substantially change body composition or the objective power measurements used in this study.
Production of pharmacologic monodisperse aerosols
Authors: Smaldone G. C. , Itoh H. , Swift D. L. , Kaplan J. , Florek R. , Wells W. , Wagner H. N.
Published: December 2017

Monodisperse aerosols containing a range of chemical material, including pharmacologically active substances, were produced by using a modified Sinclair-LaMer condensation generator. Instead of the usual hot-wire technique, an ultrasonic nebulizer was used to suspend nuclei in the gas phase as an aqueous polydisperse aerosol. This technique allowed the generation of monodisperse oil (sebacate) aerosols containing nuclei of sodium chloride, histamine, methacholine, antigen, iron oxide, methylene blue, uranine, radioactive technetium pertechnetate, and technetium-labeled human serum albumin. Quantitative agonist activity was demonstrated for each active nucleus. Particle sizes ranged from 0.65 to 3 microns, with a geometric standard deviation of 1.1–1.2. This system can produce a stable, monodisperse, biologically active radiolabeled aerosol for a period of several hours.
Tissue ammonia and amino acids in rats at various oxygen pressures
Authors: Singh A. K. , Banister E. W.
Published: December 2017

The amino acid and ammonia profiles in various tissues of the rat exposed to different pressures of pure oxygen have been studied. Well-defined changes in behavioral activity accompanied a profile of increasing pressure, culminating in convulsive activity in each group of exposed animals. After an initial depression of ammonia, in all tissues studied at 0.68 atm oxygen ammonia increased significantly at higher oxygen pressures. A rise in tissue ammonia took place in the absence of undue muscular activity on the part of the exposed animals. A significant increase in ammonia occurred first in brain and liver at 3.40 atm. Ammonia concentration was high in all tissues after convulsions occurred at 4.08 atm. Between 0.68 and 2.72 atm oxygen, tissue ammonia concentration was generally low and brain glutamate and gamma-aminobutyric acid were high. At pressures higher than 2.72 atm oxygen, tissue glutamate declined and glutamine increased. Alanine became significantly elevated in serum and muscle at high oxygen pressure, and aspartate was depressed in heart, liver, and muscle. These pressure-course experiments on ammonia accumulation in tissue confirm previous serial time course observations that ammonia accumulates in the brain and several tissues of the rat even in the absence of undue muscular activity during high-pressure oxygen exposure and is a significant factor in inducing convulsions.
Phrenic activity and intercostal muscle emg during inspiratory loading in newborn kittens
Authors: Trippenbach T. , Kelly G.
Published: December 2017

The effects of airway occlusions at functional residual capacity (FRC) on both “integrated” phrenic activity (Phr) and intercostal muscle electromyogram (intEMG) were studied in intact and vagotomized spontaneously breathing kittens during the 1st wk of life. Animals were anesthetized im with a mixture of ketamine (30 mg/kg) and acepromazine (1.1 mg/kg). In the intact kittens, inspiratory loading led to a significant increase in peak amplitudes of both Phr and intEMG and prolongation of inspiratory (TI) and expiratory (TE) times. Mean values of rate of rise of Phr and intEMG measured at 200 ms (intEMG200) from the onset of inspiration were unaffected. The results indicated that in newborns the vagal component of the load compensation is of great importance. Following vagotomy, airway occlusion produced a significant increase in mean values of TI and intEMG only. These small but significant changes suggest that most of the load compensation reflex is dependent on prolongation of TI. Increased intEMG200 during loading in the vagotomized kittens, observed during several trials, implies that the intercostal fusion-alpha interaction may operate in newborns.
Breathing He-O2 shifts the lung pressure-volume curve of the dog
Authors: Berend N. , Christopher K. L. , Voelkel N. F.
Published: December 2017

To determine whether breathing a mixture of 80% He-20% O2 affects the lung pressure-volume (PV) curve, eight anesthetized paralyzed dogs were studied in a volume-displacement plethysmograph. Static PV curves on air were compared with PV curves obtained after equilibration with He-O2. The He-O2 PV curves were significantly shifted upward by an average of 5% total lung capacity. There was no change in compliance, indicating that the shift was due to lung expansion rather than a change in elasticity. Pretreatment of the dogs with cyclooxygenase inhibitors abolished the PV shift with He-O2. Four dogs had PV curves recorded on air and a mixture of O2, SF6, and Ne, a gas mixture with the same density as air but with 45% greater viscosity. The PV curve shift was even greater than observed with He-O2 and could again be virtually abolished with a cyclooxygenase inhibitor. These results suggest that breathing a high-viscosity gas mixture results in alveolar duct dilatation due to the release of a prostaglandin bronchodilator. This may need to be taken into account in the analysis of flow augmentation with He-O2.
A new method for measurement of respiratory resistance
Authors: Shaw C. F. , Chiang S. T. , Hsieh Y. C. , Milic-Emili J. , Lenfant C.
Published: December 2017

A new method for measuring the resistance of the total respiratory system is presented. The method uses a device comprising a solenoid valve, a multiperforated plate, and a pneumotachograph. The multiperforated plate serves as a constant resistor (Rk) that is used to partially occlude the airway opening, thus rapidly and briefly reducing airflow during natural expiration. If it is assumed that the driving pressure remains constant during the very short period the airway is partially occluded, the respiratory flow immediately preceding the addition of Rk (V) and the flow reduction during partial occlusion (delta V) allow calculation of the resistance of the total respiratory system. The resistance of 14 normal subjects and 18 patients with chronic obstructive pulmonary disease (COPD) was measured with this new method as well as with the body plethysmographic method: 90% of the interrupter values fell within +/- 0.6 cmH2O . l-1.s of the plethysmographic values, and all fell within +/- 0.8 cmH2O . l-1.s.
Roles of stress and adaptation in the elicitation of face-immersion bradycardia
Authors: Natelson B. H. , Nary C. A. , Curtis G. A. , Creighton D.
Published: December 2017

Thirteen young healthy human volunteers immersed their faces in warm or cold water on one day while breathing through a snorkel and on another day while breath holding. The magnitude of the elicited bradycardia was most prominently due to water temperature, with apnea playing a less important role. Perceived stress could affect the magnitude of the response, but it was less important than the other variables. Thus statistically significant nonparametric correlations were found for the group but not for most individuals between a scoring technique that assessed perceived stress and heart rate. In contrast to animals, these data indicate that bradycardia may be reliably elicited in humans by face immersion in cold water and that stress is neither necessary nor sufficient to produce this phenomenon. Adaptation did not seem to play a role in the development of this physiological response.
Biochemical and physiological effects of compound 48/80 on canine trachea in vivo
Authors: Leff A. R. , Brown J. K. , Frey M. , Reed B. , Gold W. M.
Published: December 2017

We studied changes in tracheal histamine content and tracheal muscle tension after degranulation of tracheal mast cells by compound 48/80 in 32 anesthetized dogs. In four dogs compound 48/80 caused an increase in tracheal tension [13 +/- 5 (SD) g/cm], while femoral arterial blood pressure decreased only 14 +/- 11%. Tracheal tissue histamine decreased 17 +/- 6% in five dogs receiving intra-arterial compound 48/80 (5 X 10(-3) to 10(-1) mg/kg). Chlorpheniramine, an H1-antagonist, selectively inhibited tracheal contraction to compound 48/80 and histamine. Cimetidine, an H2-antagonist, did not alter the response to intra-arterial histamine. In 11 dogs, the doses of both intra-arterial histamine and acetylcholine required to produce a threshold increase in tracheal tension of 8 g/cm were compared. Threshold doses for acetylcholine varied 10-fold, compared with 100-fold variation for histamine among these dogs. There was a significant correlation between increased tracheal tension produced by compound 48/80 and histamine (r = 0.62). We conclude that compound 48/80 causes a variable increase in tracheal tension in vivo because of marked variability in the H1-receptor response of tracheal smooth muscle to histamine and because of variability in the release of mediator from respiratory mast cells by compound 48/80.