bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of hypoxic pulmonary vasoconstriction by pulsatile flow in dog lungs
Authors: Gregory T. J. , Newell J. C. , Hakim T. S. , Levitzky M. G. , Sedransk N.
Published: December 2017

We measured pulmonary arterial pressure in isolated lower lobes of dog lungs perfused in situ at several flows during ventilation with 95% O2–5% CO2 and with 3% O2–5% CO2. Pulsatile perfusion was provided by a piston pump, and steady perfusion was provided by a roller pump. The slope of the pressure-flow curve was 16.1 +/- 1.6 Torr X 1(-1) X min at all flows between 200 and 800 ml/min during 95–5 ventilation and increased to 19.4 +/- 3.7 in hypoxia. When flow was 600 ml/min, with 95–5 ventilation, mean arterial pressure was 16.2 +/- 1.2 Torr in steady flow and was unchanged at 15.0 +/- 1.0 Torr in pulsatile flow. At the same flow during hypoxic ventilation, mean arterial pressure increased to 27.9 +/- 2.4 Torr (P less than 0.01) when flow was steady but only to 19.3 +/- 1.6 Torr (P less than 0.01) when flow was made pulsatile. Thus hypoxia increased perfusion pressure by a nearly parallel shift of the pressure-flow curve to higher pressures, and this change was smaller in pulsatile than in steady flow.
Comparison of hemodynamic responses to static and dynamic exercise
Authors: Bezucha G. R. , Lenser M. C. , Hanson P. G. , Nagle F. J.
Published: December 2017

Eight healthy male adults (25–34 yr) were studied to compare hemodynamic responses to static exercise (30% MVC in leg extension), static-dynamic exercise (one-arm cranking, 66 and 79% VO2 max-arm), and dynamic exercise (two-leg cycling, 58 and 82% VOmax-legs). Leg extension (LE) strength was measured by a spring scale. Cranking and cycling were performed on a Quinton bicycle ergometer. VO2 was measured using an automated open-circuit system. Heart rate (HR) was monitored from a CM-5 ECG lead, and arterial pressure (Pa) was measured from an indwelling brachial artery catheter. Cardiac output (Q) was measured using a CO2-rebreathing procedure. Total peripheral resistance (TPR) was calculated using the mean arterial pressure (Pa) as the systemic pressure gradient. In 30% LE, a significant (P less than 0.05) Pa increase occurred (pressor response) mediated primarily by an increase in Q. One-arm cranking and two-leg cycling at similar relative VO2 demands resulted in nearly identical increases in Pa due to different contributions of Q and TPR. Q and the arteriovenous O2 difference varied as a function of VO2 regardless of the mode of exercise (static or dynamic). On the other hand, the HR response, which accounted for increased Q in the exercises containing a static component, and Pa varied with mode of exercise. Any generalized scheme of cardiovascular control during exercise must account for the potential influence of dynamic and static components of the exercise.
Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction
Authors: Nery L. E. , Wasserman K. , Andrews J. D. , Huntsman D. J. , Hansen J. E. , Whipp B. J.
Published: December 2017

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.
Fate of exogenous glucose during exercise of different intensities in humans
Authors: Pirnay F. , Crielaard J. M. , Pallikarakis N. , Lacroix M. , Mosora F. , Krzentowski G. , Luyckx A. S. , Lefebvre P. J.
Published: December 2017

The extent to which an oral load of glucose is absorbed from the gut and oxidized during prolonged exercise is a matter of controversy. Four healthy volunteers, 18–28 yr, were submitted on 4 different days to a 105-min treadmill exercise at 22, 39, 51, and 64% of their individual VO2max. After 15 min adaptation to exercise, they received orally 100 g naturally labeled [13C]glucose. Oxidation of the exogenous glucose was followed by 13CO2 measurements in the expired air; total carbohydrate and lipid oxidation were evaluated by indirect calorimetry. Between 22 and 51% VO2 max, total carbohydrate, lipid oxidation, and exogenous glucose oxidation were linearly correlated with the relative work load (r = 0.81; P less than 0.01). Between 51 and 64% VO2 max, exogenous glucose oxidation and lipid oxidation tended to level off, whereas endogenous carbohydrate oxidation was markedly enhanced. The lesser contribution of exogenous glucose during the most intense exercise might be due to a decrease in the oxidation in the muscles or to a lesser availability of this exogenous glucose.
A feedback system to control blood flow in dog lung lobes
Authors: Drake R. E. , Adcock D. K. , Scott R. L. , Gabel J. C.
Published: December 2017

We have developed an electromechanical feedback system to control blood flow to the lower left lung lobe of dogs. Blood flow is measured with an electromagnetic flowmeter. The feedback system compares the blood flow signal to an adjustable reference voltage and causes a motor to turn. The direction of motor rotation depends on the relative magnitude of the flow signal and the reference. The motor pushes the plunger of a syringe that is attached to a balloon in the right pulmonary artery. Inflation of the balloon causes increased blood flow to the lower left lobe. We have used the system to control lobe blood flow in three dogs.
Novel effects of PGF2 alpha on airway function in asthmatic subjects
Authors: Fish J. E. , Newball H. H. , Norman P. S. , Peterman V. I.
Published: December 2017

The effects of inhaled prostaglandin F2 alpha (PGF2 alpha) have been examined in eight subjects with asthma. Incremental PGF2 alpha aerosol concentrations, ranging from 1 to 5,000 micrograms/ml, were administered at 15-min intervals. Plethysmographic specific airway conductance (sGaw), forced expiratory volume at 1 s (FEV1), and maximum expiratory flow at 50% vital capacity breathing air (Vmax50% air) and 80% He-20% O2 (Vmax50% He-O2) were measured after each dose and compared with saline control values. We observed unexpected triphasic dose-response characteristics, i.e., an initial decline in physiological variables at low concentrations (1–100 micrograms/ml), followed by improvement at intermediate concentrations (100–1,000 micrograms/ml) and a subsequent steep decline at high concentrations (1,000–5,000 micrograms/ml). Improvement in FEV1 and Vmax50% air between 100 and 1,000 micrograms/ml was associated with sGaw increases above control levels in six subjects and a significant fall in density-dependent index (Vmax50% He-O2/Vmax50% air) when compared with values before challenge and at low concentrations. Inhaled atropine (5 mg) improved prechallenge lung function but had no effect on PGF2 alpha dose-response characteristics. Intermediate PGF2 alpha concentrations given as a single dose consistently induced greater FEV1 reductions than the same concentration during graded dose challenges. Our findings are consistent with the demonstration of in vivo airway tachyphylaxis and indicate that airway effects of PGF2 alpha are far more complex than previously reported. Moreover, these novel effects suggest that, in addition to its well-known bronchoconstrictor effects, PGF2 alpha directly or indirectly causes airway relaxation, predominantly in large airways.
Heteropore populations of bullfrog alveolar epithelium
Authors: Kim K. J. , Crandall E. D.
Published: December 2017

Diffusional fluxes of a large number of hydrophilic solutes and water across bullfrog (Rana catesbeiana) alveolar epithelium were measured in the Ussing-type flux chamber. Lungs were isolated from double-pithed animals and studied as flat sheets. Radioactive solutes and water were added to the upstream reservoir, and the rate of change of downstream reservoir radioactivity was monitored. A permeability coefficient was estimated for each substance from a linear relationship between radiotracer concentration in the downstream reservoir and time. These permeability data were used to analyze the equivalent water-filled pore characteristics of the alveolar epithelial barrier. The data reveal that the alveolar epithelium is best characterized by two distinct pore populations rather than by a single homogeneous pore population. The large-pore population consists of pores with a radius of about 5 nm and occupies 4% of the available pore area. The small-pore population consists of pores with a radius of about 0.5 nm and occupies 96% of the available pore area. The number of small pores to large pores is 2.68 X 10(3). After the alveolar surface was damaged by acid, a large-pore population with a radius of about 27 nm was seen, allowing nearly free diffusion of solutes. A major implication of the presence of two populations of pores in the alveolar epithelium is that hydrostatically driven bulk water flow occurs predominantly through the large pores, while osmotically driven bulk water flow takes place predominantly through the small pores. As a result, in general, hydrostatic and osmotic gradients may not be equally effective driving forces for water flow across this tissue.
Frequency dependence of plethysmographic volume in healthy and asthmatic subjects
Authors: Rodenstein D. O. , Stanescu D. C.
Published: December 2017

In airway obstruction, thoracic gas volume derived from mouth pressure vs. plethysmographic volume changes (TGVm) is overestimated, whereas TGVes, derived from esophageal pressure vs. plethysmographic volume changes, is not (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 939–954, 1982). The reason appears to be that mouth pressure swings are less than alveolar pressure swings. We measured TGVm and TGVes in six normal subjects and in nine asthmatic patients before and during bronchospasm, while panting at the same lung volume at 0.8 Hz (low), 2–2.5 Hz (medium), and 4.5–5 Hz (high). No difference was observed between TGVm and TGVes (P greater than 0.05) at any frequency (f) in normal subjects or asthmatics before bronchospasm. During bronchospasm, TGVm and TGVes were similar at low f. However, TGVm increased from 5.66 +/- 1.16 (SD) liters at low f to 6.50 +/- 1.71 liters at medium f (P less than 0.01), resulting in a TGVm 1.16 +/- 0.95 liters higher than TGVes (P less than 0.01). In three asthmatics during bronchospasm, mean TGVm-TGVes difference was 0.01 liter at low f, 0.26 liter at medium f, and 0.73 liter at high f. Surprisingly TGVes was in average 5% higher at low f than at medium or high f, both in normal subjects and asthmatics. A similar pattern was observed for TGVm, except in asthmatics during bronchospasm. We conclude that in airway obstruction overestimation of TGVm is frequency dependent and can be avoided by panting at low f. However, at this f TGV is 5% larger than at higher f, difference which is not related to airway obstruction.
Work-heat tolerance in endurance-trained rats
Authors: Fruth J. M. , Gisolfi C. V.
Published: December 2017

The purpose of this study was to determine if training in a cool (23 degrees C) environment would alter the potential for mortality or for tissue damage (as indicated by serum transaminase concentrations) during a work-heat tolerance test (WHTT) to exhaustion. Twenty-nine male Sprague-Dawley rats were trained (T) on a motorized treadmill for 6 wk, while 34 control animals of similar weight remained sedentary (S). Tissue damage among survivors 24 h following the WHTT and percent mortality were the same in both groups; however, T survivors 1) continued the test 44% longer (P less than 0.05), 2) performed significantly more work (P less than 0.05), and 3) sustained a 120% larger (P less than 0.05) thermal load [product of time and colonic temperature (Tc) above 40 degrees C] than S survivors. Mortality first occurred at a range in Tc of 40.6–41.0 degrees C in the S group compared with a range of 41.6–42.0 degrees C in the T group. Thus endurance T rats can run longer in the heat, sustain greater thermal loads, and are less susceptible to work-induced thermal fatality than S rats.
Sound speed in pulmonary parenchyma
Authors: Rice D. A.
Published: December 2017

The time it takes audible sound waves to travel across a lobe of excised horse lung was measured. Sound speed, which is the slope in the relationship between transit time and distance across the lobe, was estimated by linear regression analysis. Sound-speed estimates for air-filled lungs varied between 25 and 70 m/s, depending on lung volume. These speeds are less than 5% of sound speed in tissue and less than 20% of sound speed in air. Filling the lung with helium or sulfur hexafluoride, whose free-field sound speeds are 970 and 140 m/s, respectively, changed sound speed +/- 10% relative to air filling. Reducing the ambient pressure to 0.1 atm reduced sound speed to 30% of its 1-atm value. Increasing pressure to 7 atm increased sound speed by a factor of 2.6. These results suggest that 1) translobar sound travels through the bulk of the parenchyma and not along airways or blood vessels, and 2) the parenchyma acts as an elastic continuum to audible sound. The speed of sound is given by c = (B/rho)1/2, where B is composite volumetric stiffness of the medium and rho is average density. In the physiologic state B is affected by ambient pressure and percent gas phase. The average density includes both the tissue and gas phases of the parenchyma, so it is dependent on lung volume. These results may be helpful in the quantification of clinical observations of lung sounds.
Statistics of response slopes
Authors: Mardia K. V. , Bogle S. , Edwards R.
Published: December 2017

Daubenspeck and Ogden in a recent paper recommended the use of directional statistics in the analysis of response slopes, and their advice has been followed by other workers. Their method is not valid, since it does not follow directly from their model. An efficient estimator of the slope (i.e., an estimator with minimum variance) is well known and is given here with a confidence interval for the true slope. They were also concerned with the two-sample problem to compare the slopes from two different samples. The method for this is more complicated but is summarized here. The likelihood ratio test and point and interval estimates are given. We discuss Daubenspeck and Ogden's example and the reason why, despite its invalidity, their method gave good results using their own data. Their data are also used to illustrate the methods described in this paper, and examples are given to highlight the practical differences between the two methods. Step-by-step procedures are included in the appendixes to enable readers to use these methods.
Role of bacterial endotoxins of intestinal origin in rat heat stress mortality
Authors: DuBose D. A. , Basamania K. , Maglione L. , Rowlands J.
Published: December 2017

Using unanesthetized rats, the effect on heat stress mortality of endotoxin tolerance or zymosan treatment was determined. In addition, the incidence of invasion by gram-negative bacteria and their endotoxins was studied to evaluate the role of gut-derived bacterial endotoxins after heat stress. Endotoxin tolerance resulted in heat stress resistance. The estimated mean total thermal area, which induced an LD50 in endotoxin-tolerant rats (61.85 degrees C . min) was significantly greater (P less than 0.001) than that for non-tolerant rats (44.03 degrees C . min). Rats were significantly (P less than 0.005) more sensitive to endotoxin after zymosan treatment, but this treatment did not alter the heat stress mortality rate. The Limulus amoebocyte lysate test indicated that endotoxemia did not occur as a result of heat stress. Though a significantly increased incidence of high gram-negative bacterial count in the duodenum was noted, extraintestinal invasion was not found. It was concluded that resistance to heat stress may not be due to protection from gut-derived bacterial endotoxins, but resistance may possibly be associated with the ability of endotoxin tolerance to protect from shock syndromes. Thus bacterial endotoxins of intestinal origin did not appear to have a significant role in rat heat stress mortality.
Anesthesia alters the pattern of aerosol retention in hamsters
Authors: Sweeney T. D. , Brain J. D. , LeMott S.
Published: December 2017

General anesthesia was used to produce nonventilated areas of the lung, and aerosol inhalation was used to locate these areas, assuming that no aerosol deposits in a nonventilated region. Male Syrian golden hamsters were anesthetized with pentobarbital sodium (90 mg/kg), which reduced respiratory frequency, tidal volume, minute volume, and O2 consumption to 61, 41, 24, and 36%, respectively, of the corresponding awake levels. Awake and anesthetized hamsters were exposed to the aerosol for 30 min; then the lungs were excised, dried at total lung capacity, sliced into sections, and dissected into pieces. Autoradiographs were made of slices, and the activity and weight of pieces were determined. The evenness index (EI), a measure of the uniformity of retention, was calculated for each piece. With complete uniformity of retention, all EI's would be 1.0. In awake animals, only 0.2% (by wt) of the lungs had little or no retention (EI's less than 0.20). More particles deposited in the apex than in the base of the lungs. General anesthesia for extended periods of time with no deep breaths alters ventilation and therefore the distribution of aerosol retention. Many regions of the lungs in the anesthetized animals received few or no particles (11.6% of lungs had EI less than 0.20); however, no consistent pattern was observed in the location of these areas from animal to animal. The apex-to-base gradient for retention in these animals was also reversed. Radioactive aerosols can be used as probes to indicate the extent and distribution of nonventilated areas in the lungs.
Regulation of glycogenolysis in human muscle in response to epinephrine infusion
Authors: Chasiotis D. , Sahlin K. , Hultman E.
Published: December 2017

The regulation of glycogenolysis in human muscle during epinephrine infusion has been investigated. The content of cAMP in resting muscle was 2.7 +/- 0.7 (SD) mumol . kg dry muscle-1 and increased threefold during the first 5 min of infusion. Total glycogen phosphorylase and glycogen synthase activities were unchanged during the infusion. The proportion of phosphorylase in the a form in the basal state was estimated to be at least 22.5% and during infusion 80–90%. During infusion, synthase I activity decreased. The muscle glycogen content was 340 mmol . kg dry wt-1 and decreased during the first 2 min of infusion at a rate of 11.0 mmol glycosyl units . kg dry wt-1 . min-1. Prolonged infusion resulted in a much lower glycogenolytic rate, even though most of the phosphorylase was still in the a form. Accumulation of hexose monophosphates and lactate followed the changes in glycogen. It was concluded that despite the almost total transformation of phosphorylase to the a form, the in vivo activity was maintained at a low level. It is suggested that this may be due to a low concentration of inorganic phosphate at the active site of the enzyme.
Transvascular fluid flux measured from intravascular water concentration changes
Authors: Oppenheimer L. , Unruh H. W. , Skoog C. , Goldberg H. S.
Published: December 2017

We have measured transvascular water flux in eight canine left lower lobes perfused in a zone 3 of West with indocyanine green-stained plasma. Transvascular flux of water was induced by a step change in the inflow pressure. Assuming the indocyanine green-labeled protein did not significantly cross the capillary membrane in one pass, the rate of transvascular fluid flux could be calculated from the change in outflow-to-inflow concentration of water. The method was validated against gravimetric measurements of water exchange. By comparing our direct measurements of transvascular flux with the time course of lobar weight change, we conclude that following changes in inflow pressure, vascular volume changes occur rapidly and slow changes in lung mass can be accounted for exclusively by water exchange. Our method shows transvascular flux follows a biphasic course, suggesting both a membrane and an interstitial resistance to fluid transudation.
Effect of increased blood oxygen affinity on skeletal muscle surface oxygen pressure fields
Authors: Nylander E. , Lund N. , Wranne B.
Published: December 2017

A chronic left displacement of the blood O2 dissociation curve (ODC) was achieved in rats by administering cyanate over a period of 14 days. Control rats received NaCl. An acute left displacement of the ODC was achieved by exchange transfusion with bisulfite-treated erythrocytes. Control rats for this series received an exchange transfusion with fresh heparinized blood. In both series, skeletal muscle surface O2 pressure fields (expressed as PO2 histograms) were measured with the rats anesthetized, curarized, and artificially ventilated. The animals with chronically left-shifted ODC had normal PO2 histograms (for definition see DISCUSSION) when breathing air; during hypoxia (FIO2 0.12) four of the eight experimental and three of the seven control animals developed abnormal histograms, and all animals had normal histograms on return to air breathing. The majority, but not all, of the animals that were to receive exchange transfusions of left-shifted ODC blood had normal histograms before the transfusion, which caused some to become abnormal and others to become normal. Similar results were obtained in the control animals that received normal blood. The results do not provide evidence for an adverse effect of a left-shifted ODC on muscle tissue oxygenation.
Airway smooth muscle mechanics: reduced activation and relaxation
Authors: Kromer U. , Stephens N.
Published: December 2017

Reduced activation of skeletal muscle fibers at below-optimal lengths has been reported before. We studied tracheal smooth muscle (TSM) as a model of airway smooth muscle to see whether such a phenomenon existed in smooth muscle also; we found that active length-tension curves at normal and raised Ca2+ concentrations were significantly different. This indicated reduced activation of the TSM at below-optimal lengths. This reduction was in addition to that arising from the length-tension effect. We also studied the mechanics of relaxation in TSM and noted that in afterloaded isotonic tension records the time course of TSM relaxation appeared to closely follow that of the isometric contraction at all loads. In this it differed markedly from relaxation in skeletal muscle where the time courses of relaxation at different loads differed from each other and from that of the isometric muscle.
Lung vessel leak precedes right ventricular hypertrophy in monocrotaline-treated rats
Authors: Sugita T. , Hyers T. M. , Dauber I. M. , Wagner W. W. , McMurtry I. F. , Reeves J. T.
Published: December 2017

Monocrotaline induces microvascular leak and pulmonary hypertension in rats. We have hypothesized that the leak is related in some way to the pulmonary hypertension and precedes it. In rats given 40 mg monocrotaline/kg body wt subcutaneously, lung wet weight-to-dry weight ratios and lung albumin content began to increase within the first 3 days and became maximal at 1 wk. Alveolar lavage fluid showed little or no increase in protein. Right ventricular hypertrophy increased progressively from 2 through 3 wk. An increase in lung dry weight paralleled the right ventricular hypertrophy. The amount of blood retained in the lung did not account for the increased lung water, albumin, or weight. We considered that microvascular leak without leak into the alveolar space preceded pulmonary hypertension, right ventricular hypertrophy, and increased lung dry weight. In rats not given monocrotaline but exposed for 3 wk to hypobaric hypoxia, lung albumin, lung dry weight, and right ventricular weight increased. Increased lung dry weight probably reflects hyperplasia of lung cells. If so, an association of microvascular leak, lung cell hyperplasia, and right ventricular hypertrophy may occur in both monocrotaline- and hypoxia-induced pulmonary hypertension.
Responses of cat's internal intercostal motor units to hypercapnia and lung inflation
Authors: Arita H. , Bishop B.
Published: December 2017

Single motor unit potentials from the eighth internal intercostal (IIC) muscle were recorded along with tracheal pressure and end-tidal CO2 (PETCO2) in spontaneously breathing, Dial-urethane anesthetized cats during hypercapnia (3, 5, or 7% CO2) and during lung inflation (LI, 100 ml above functional residual capacity) before and after vagotomy. Hypercapnia depressed IIC activity in 5 of 7 cats; the higher the PETCO2, the lower was the firing rate and the fewer the number of spikes per breath. LI evoked an initial silent phase (ISP) in 6 of 10 cats followed by a prolonged IIC burst. Hypercapnia combined with LI abolished or diminished the ISP and shortened the prolonged burst with an increase in firing rate and a recruitment of new units. Vagotomy silenced IIC activity in 7 of 10 cats, but LI after vagotomy activated IIC activity in 10 of 10 cats, though neither an ISP nor prolonged activity occurred. Our data suggest that major factors in controlling IIC activity are reciprocal inhibition from bulbospinal inspiratory neurons, excitatory and inhibitory inputs mediated by vagal afferents, and a modulation of IIC activity via gamma-loop. Hypercapnia affects the former two factors.
Decay of inspiratory muscle pressure during expiration in anesthetized cats
Authors: Zin W. A. , Pengelly L. D. , Milic-Emili J.
Published: December 2017

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg) we studied the antagonistic pressure developed by the inspiratory muscles during expiration (PmusI). This was accomplished in two ways: 1) with our previously reported method (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 1266–1271, 1982) based on the measurement of changes in lung volume and airflow during spontaneous expiration, together with determination of the total passive respiratory system elastance and resistance; and 2) measurement of the time course of changes in tracheal/pressure after airway occlusion at end inspiration, up to the moment when the inspiratory muscles become completely relaxed. The agreement between the two methods is generally good, both in the amplitude of PmusI and in its time course. We also applied the first method to spontaneous expirations through added linear resistive loads. These did not alter the relative decay of PmusI. Thus in anesthetized cats the braking action of the inspiratory muscles does not decrease when expiratory resistive loads are added, i.e., when such braking is clearly not required.
Contact-angle hysteresis induced by pulmonary surfactants
Authors: Hills B. A.
Published: December 2017

Hydrophilic surfaces in the form of glass slides have been coated with monolayers of three of the major components of pulmonary surfactant, and the wettabilities of the resulting surfaces have been studied by applying a single drop of saline. As fluid was added and removed over successive cycles, there was much hysteresis between the contact angle measured by a goniometer and the location of the triple point. All three surfactants, especially dipalmitoyl lecithin, were found to impart antiwetting properties, with maximum (advancing) contact angles sometimes exceeding 90 degrees and minimum (receding) contact angles seldom less than 28 degrees. In all cases (216 cycles on 36 films) fluid receded to expose the dry subphase. The hysteresis loops agree well with a similar loop calculated from published data for a cat lung in which the pressure-volume cycle has been established for both liquid and air inflation. Contact-angle hysteresis is offered as a possible alternative to surface tension as the surface parameter primarily responsible for the interfacial contribution to compliance hysteresis in the excised lung.
High-frequency oscillations via the pleural surface: an alternative mode of ventilation?
Authors: Ward H. E. , Power J. H. , Nicholas T. E.
Published: December 2017

We applied high-frequency oscillatory ventilation (HFOV) of low amplitude to the pleural surface of the isolated rat lung (IPL) perfused at 10 ml X min-1 with Krebs bicarbonate containing 4.5% albumin (hematocrit 34%). Lung volume was held constant by a continuous positive airways pressure (CPAP) of 5 cmH2O. Varying CPAP from 2 to 15 cmH2O did not affect O2 uptake. Tidal volume (VT) was estimated with an impedance pneumograph, and it bore a direct linear relationship to the amplitude of both the loudspeaker input signal and the pressure change in the chamber up to 30 Hz; VT was inversely proportional to the frequency (f). However, at a constant loudspeaker input of 10 V, minute expired ventilation (VE) remained constant (mean 104 ml X min-1) as f increased from 5 to 30 Hz. Hemoglobin saturation increased by more than 80% during HFOV of 5–30 Hz and amplitude of 10 V, the maximum O2 uptake being 14.6 ml O2 per 100 ml perfusate. Whereas dead space was approximately 335 microliters, a VT of less than 40 microliters could effect normal O2 uptake, suggesting that bulk flow is playing only a minor role in gas exchange. HFOV for 60 min (CPAP 5 cmH2O) did not affect the amount of alveolar surfactant compared with conventional ventilation at the same mean airway pressure. We conclude that normal O2 uptake can be maintained by applying HFOV to the pleural surface of the IPL held at constant volume.
Role of chemical afferents in the maintenance of rhythmic respiratory movements
Authors: See W. R. , Schlaefke M. E. , Loeschcke H. H.
Published: December 2017

In seven anesthetized cats central chemosensitivity was eliminated (cold block) and peripheral chemoreceptors were either stimulated or eliminated (sectioned) to test whether nonchemical vagal afferents can maintain rhythmic ventilation and to determine the relative contribution of the carotid and aortic chemoreceptors to ventilatory drive without central chemosensitivity. Elimination of all chemical afferents invariably induced apnea, whereas ventilation was reduced from 533 to 159 ml X min-1 during cold block of central chemosensitivity and to 478 ml X min-1 after sectioning both sinus nerves. Cold block with only the aortic chemoreceptors and vagal afferents intact produced apnea in four of six cases tested. Stimulation of peripheral chemoreceptors during cold block remained effective and interrupted apnea in three of the four cats with only aortic chemoreceptors intact. We conclude that the nonchemical vagal respiratory afferents alone are unable to maintain rhythmic ventilation. Respiratory rhythm generation is, under the conditions of our experiments, critically dependent on sufficient afferent input from chemical afferents. Of these, central chemosensitivity plays the major role, followed by carotid body and, least importantly, by aortic afferents.
Diaphragmatic contractility enhanced by aminophylline: role of extracellular calcium
Authors: Aubier M. , Murciano D. , Viires N. , Lecocguic Y. , Pariente R.
Published: December 2017

We have studied the effects of aminophylline on diaphragmatic contractility in 12 anesthetized dogs. The phrenic nerves were stimulated supramaximally (20 Hz, 0.1 ms) with electrodes placed around the fifth roots, and the transdiaphragmatic pressure (Pdi) generated at functional residual capacity (FRC) was measured with balloon catheters. Constancy of FRC was monitored by measuring the end-expiratory transpulmonary pressure, the dogs being occluded at FRC before the stimulations. The electrical activity of the diaphragm (Edi) during the stimulations was recorded with electrodes inserted in both hemidiaphragms. Phrenic stimulations during an infusion of aminophylline (10 mg/kg in 5 min) increased Pdi by 25 +/- 8% of control values, whereas the Edi remained unchanged. This potentiating effect of aminophylline was abolished when an identical dose was injected during a continuous infusion of a calcium blocker (verapamil, 0.1 mg X kg-1 X min-1). Infusion of another methylxanthine compound, caffeine (10 mg/kg), also increased Pdi for an identical electrical phrenic nerve stimulation by 21 +/- 6% compared with control values. However, the potentiating effect of caffeine was not abolished by verapamil. We conclude that aminophylline in vivo increases diaphragmatic contractility and that extracellular calcium is necessary for this action, a mechanism not shared by another methylxanthine compound, caffeine.
Effect of glycogen depletion on the ventilatory response to exercise
Authors: Heigenhauser G. J. , Sutton J. R. , Jones N. L.
Published: December 2017

Five male subjects performed two graded exercise studies, one during control conditions and the other after reduction of muscle glycogen content by repeated maximum exercise and a high fat-protein diet. Reduction in preexercise muscle glycogen from 59.1 to 17.1 mumol X g-1 (n = 3) was associated with a 14% reduction in maximum power output but no change in maximum O2 intake; at any given power output O2 intake, heart rate, and ventilation (VE) were significantly higher, CO2 output (VCO2) was similar, and the respiratory exchange ratio was lower during glycogen depletion compared with control. The higher VE during glycogen depletion was associated with a higher VE/VCO2 ratio, lower end-tidal and mixed venous CO2 partial pressures, and higher blood pH than in the control studies. Changes in exercise VE accompanying glycogen depletion were not explained by changes in CO2 flux to the lungs suggesting that other factors served to modulate VE in these experimental conditions.
Plasma volume shifts during progressive arm and leg exercise
Authors: Miles D. S. , Sawka M. N. , Glaser R. M. , Petrofsky J. S.
Published: December 2017

Upper and lower body exercise was performed to assess the influence muscle mass has on plasma volume (PV) shifts. Nine male subjects (mean = 28 yr) completed a progressive intensity, discontinuous test with an arm crank (AC) and cycle (CY) ergometer. Power output (PO) levels for the AC were 25, 74, 98, and 133 W. PO levels for the CY were 49, 98, 147, and 263 W. At a given submaximal oxygen uptake (VO2), PV efflux was significantly greater for AC compared with CY exercise. When PV efflux was related to the relative intensity of the exercise (ergometer specific % peak VO2), responses were nearly identical. Maximal PV efflux was 18% for both AC and CY exercise. Mean arterial pressure (MAP) was significantly greater for AC compared with CY exercise for a given VO2. MAP plotted against the relative intensity of exercise, however, was similar for both AC and CY exercise. These results suggest that the amount of plasma efflux during exercise is related to the MAP, which is directly related to the relative intensity of the exercise.
Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities
Authors: Man G. C. , Man S. F. , Kappagoda C. T.
Published: December 2017

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8–10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.
Simulation of continuous blood O2 equilibrium curve over physiological pH, DPG, and Pco2 range
Authors: Winslow R. M. , Samaja M. , Winslow N. J. , Rossi-Bernardi L. , Shrager R. I.
Published: December 2017

We analyzed 56 O2 equilibrium curves of fresh human blood, each from 0 to 150 Torr Po2. The data were collected over ranges of values for the 2,3-diphosphoglyceric acid-to-hemoglobin concentration ratio [DPG]/[Hb] of 0.2–2.7, for pH of 7.0–7.8, and for Pco2 of 7–70 Torr. Each curve was characterized according to the Adair scheme for the stepwise oxygenation of Hb, and the resulting constants (a1, a2, a3, a4) were analyzed to allow the simulation of the entire O2 equilibrium curve under any conditions of [DPG]/[Hb], pH, and Pco2 in the specified range. This analysis provides a powerful tool to study the affinity of Hb for O2 within the red blood cell and to predict the shape of the O2 equilibrium curve in various physiological and pathological states. Other attempts to predict blood O2 affinity have considered only P50 (the Po2 at one-half saturation with O2) or have provided too little data for continuous simulations.
Development of histochemical and functional properties of baboon respiratory muscles
Authors: Maxwell L. C. , McCarter R. J. , Kuehl T. J. , Robotham J. L.
Published: December 2017

We assessed morphological, histochemical, and physiological characteristics of respiratory muscles of a non-human primate, Papio cynocephalus, from midgestation through adult life. Samples were taken of diaphragm muscles for histochemical analysis, electron microscopy, and assessment of contractile properties and fatigability. Histochemical analyses were also performed on samples of intercostal muscles. Initially, developing fibers are type IIc but differentiate into types I and IIa fibers by term. We observed no IIb fibers in respiratory muscles of premature baboons. Beginning late in gestation, muscle fibers grew rapidly. After term, IIb fibers were found, and fiber size ranked by increasing mean fiber area became types I, IIa, and IIb. After term, we rarely observed type IIc fibers. In electron micrographs we observed large numbers of interfibrillar mitochondria in all muscle fibers of premature baboons but not in all IIb fibers of adults. Histochemical observations were supported by contractile properties. Muscles of premature baboons had significantly longer contraction and relaxation times than adult muscles. Muscles from premature baboons were more resistant to fatigue than those of adult baboons. We conclude that the fibers of respiratory muscles are high in oxidative capacity and are resistant to fatigue during gestation. Fatigue of the respiratory muscle fibers secondary to low oxidative capacity is not a likely cause of respiratory distress in premature baboons.
Muscle fiber composition and blood ammonia levels after intense exercise in humans
Authors: Dudley G. A. , Staron R. S. , Murray T. F. , Hagerman F. C. , Luginbuhl A.
Published: December 2017

The relationship between fiber type composition and the increase in blood ammonia was examined following a maximal O2 consumption (VO2max) test. Muscle biopsies were taken from the middle portion of the vastus lateralis for determination of fiber type percentages. Two subject groups were selected on the basis of a high (HST) or low (LST) percentage of slow-twitch fibers and compared for blood ammonia and lactate levels after exercise at work loads of approximately 85 and 110% of VO2max. An inverse relationship was found between the percentage of slow-twitch fibers and the increase in blood ammonia. Blood ammonia increased after exercise at both 85 and 110% of VO2max. However, the increase was twofold greater for the LST group following the 110% work effort. The increases in blood ammonia and lactate were positively correlated for both groups following exercise. The results suggest that the proportion of slow-twitch fibers plays an important role in determining the magnitude of the increase in blood ammonia after intense exercise.
Control of respiratory pattern in conscious dog: effects of heat and CO2
Authors: Iscoe S. , Young R. B. , Jennings D. B.
Published: December 2017

We measured tidal volume (VT) and inspiratory (TI) and expiratory (TE) durations in five conscious tracheostomized dogs breathing air or 5% CO2 in air either at normal (20 degrees C) or elevated (30 degrees C) ambient temperatures. Respiratory frequency ranged between 16 and 333/min due to changes in both TI and TE. During panting TI exceeded TE. During air inhalation instantaneous ventilation (V) spontaneously ranged from 100 to 1,600 ml . kg-1 . min-1. Hypercapnia, heat stress, or both, increased this range of V by increasing maximum V, primarily due to increases in mean inspiratory flow. Under these conditions, changes in TI accounted for more of the spontaneous changes in breath duration. During inhalation of air and 5% CO2, a positive correlation between VT and TI was obtained for TI between 0.13 and 1.05 s; above 1.05 s VT decreased. Heat stress increased VT at a given TI. We suggest that either the decay rate or position of the inspiratory off-switch threshold curve (Clark and von Euler, J. Physiol. London 222: 267, 1972) varies in conscious dogs. Shifts in either the reset (onset) value or decay rate of the curve yield a positive correlation between VT and TI. This modification to the Clark-von Euler model implies that the primary effect of anesthesia on respiratory control is fixation of the inspiratory off-switch threshold curve.
Adaptation of vascular pressure-flow-volume hysteresis in isolated rabbit lungs
Authors: Beck K. C. , Hildebrandt J.
Published: December 2017

Hysteresis within two pairs of variables describing the state of the lung vascular system [pulmonary arterial pressure (Ppa) and flow (Q) and Ppa and change in vascular volume (delta Vvasc)] was investigated in isolated plasma-perfused rabbit lungs. Q was increased and decreased stepwise, in series of five cycles each, while pulmonary venous pressure (Ppv) and lung volume were held constant. Changes in Vvasc were estimated from changes in fluid volume of the venous reservoir. The relationships within pairs of variables over each complete cycle were described by loops whose areas and widths were used to quantify the hysteresis. In successive cycles, these parameters decreased toward constant values (limit cycles), most of the change occurring by the second cycle. Areas of Ppa-delta Vvasc loops correlated closely with areas of Ppa-Q loops over all five cycles of a series. For Ppa-Q loops, the ratio of average pressure-width to total pressure excursion decreased from 0.15 initially to around 0.05 in the fifth cycle. It was concluded that the relationships between Ppa and Q and Ppa and delta Vvasc are markedly sensitive to vascular pressure or flow history.
Distribution of histamine receptors in isolated canine airways
Authors: Bradley S. L. , Russell J. A.
Published: December 2017

The distribution of histamine receptors was examined in isolated trachealis smooth muscle strips and helical strips of large (5 mm) and small (1.5 mm) intrapulmonary airways. All airways contracted in response to histamine, but the sensitivity to this agent was significantly greater in intrapulmonary airways than in trachealis strips. A dose-dependent tachyphylaxis to histamine occurred when airways were exposed repeatedly to 10(-4) M histamine but not to 5 X 10(-6) M histamine. The H1-agonist, 2-methylhistamine, also caused airway contractions, although they were less forceful than those caused by histamine. Both histamine- and 2-methylhistamine-induced contractions were blocked by the H1-antagonist, pyrilamine. The H2-agonists, 4-methylhistamine and dimaprit, as well as histamine in the presence of pyrilamine failed to relax both acetylcholine- and 5-hydroxytryptamine-induced contractions. Moreover, the H2-antagonist, metiamide, had no effect on histamine-induced contractions. We conclude that histamine H1-receptors are present in both extrapulmonary and intrapulmonary airways of the dog and cause contraction when stimulated. In contrast, histamine H2-receptor activity could not be demonstrated in the airways of this species.
Effects of 0.1 ppm nitrogen dioxide on airways of normal and asthmatic subjects
Authors: Hazucha M. J. , Ginsberg J. F. , McDonnell W. F. , Haak E. D. , Pimmel R. L. , Salaam S. A. , House D. E. , Bromberg P. A.
Published: December 2017

It has been reported (J. Clin. Invest. 57: 301–307, 1976) that inhalation of nitrogen dioxide (NO2) will enhance the bronchial reactivity of asthmatics. This study was designed to evaluate the respiratory effect of a 1-h exposure of normal subjects and of atopic asthmatics to 0.1 parts per million (ppm) NO2. Fifteen normal and 15 asthmatic subjects were exposed to air and to NO2 in a randomized double-blind crossover design. Exposure to either atmosphere was bracketed by bronchial inhalation challenge using aerosolized metacholine chloride solutions. Plethysmographic measurements of specific airway resistance (sRaw) and the forced random noise impedance spectrum (5–30 Hz) were obtained immediately after each methacholine dose. Following acute exposure to NO2, there was a slight but not significant increase in mean base-line sRaw in both normals and asthmatics. The overall base-line resistive properties of the respiratory system determined by forced random noise excitation were not significantly affected by NO2 inhalation either. Finally, there was no change in bronchial response to methacholine challenge in either group. These findings indicate that 0.1 ppm NO2 exposure for 1 h without exercise had no demonstrable airways effects in either young atopic asthmatics with mild disease or young normal subjects.