bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary vascular tone improves VA/Q matching in obliterative pulmonary hypertension
Authors: Dantzker D. R. , Bower J. S.
Published: December 2017

We have studied the influence of pulmonary vascular tone on ventilation-perfusion relationships in subjects with chronic obliterative pulmonary vascular disease. We administered oxygen, isoproterenol, or nitroprusside on 15 occasions in 7 subjects and observed a fall in pulmonary vascular resistance of greater than 15% in 8 of these 15 trials. When pulmonary vascular resistance was reduced, there was an increase in the perfusion of lung units with low ventilation-perfusion ratios (VA/Q) and/or shunt as determined by the multiple inert gas technique. The pattern of increased VA/Q inequality was independent of the specific agent used. In only one instance in which pulmonary vascular resistance was not reduced did drug administration lead to a worsening of VA/Q relationships. The detrimental effect of the increased perfusion of low VA/Q units on arterial oxygenation was frequently attenuated by an increased mixed venous oxygen content due to an increase in total cardiac output. We conclude that pulmonary vascular tone contributes to the maintenance of VA/Q matching in subjects with obstruction of the pulmonary vascular bed.
Specific conductance using forced airflow oscillation in mechanically ventilated human subjects
Authors: Jordan C. , Lehane J. R. , Jones J. G. , Altman D. G. , Royston J. P.
Published: December 2017

A method is described to measure specific airway conductance in mechanically ventilated patients. Airflow resistance (R) was measured continuously using the forced airflow oscillation method and plotted against volume during slow deflation of the lungs. The previously reported hyperbolic configuration of the resistance-volume curve was confirmed, but a nonlinear conductance-volume relationship was found that could be explained by a constant resistance (A) in series with the volume-dependent resistance of the lower airways. A computer-aided analysis of the resistance-volume curve determined the parameters of the hyperbola that best fitted the data and from this the volume-dependent conductance, Glaw = 1/(R - A), was calculated. This method consistently provided a very good fit to the data and resulted in a linear lower airway conductance-volume relationship in anesthetized and in awake subjects. The slope of this linear relationship (Glaw) was therefore independent of volume, and specific lower airway conductance was used as an index of bronchomotor tone. In awake subjects given bronchoconstrictor and bronchodilator aerosols, good correlation was shown between changes in specific conductance measured by this technique and by the standard plethysmographic method.
Effects of hypercapnia and hypoxia on phrenic nerve activity and respiratory timing
Authors: Ledlie J. F. , Kelsen S. G. , Cherniack N. S. , Fishman A. P.
Published: December 2017

In the spontaneously breathing animal, respiratory responses to chemical stimuli are influenced by phasic proprioceptive inputs from the thorax. We have compared the effects of hypercapnia and hypoxia on the level and timing of phrenic nerve activity while these phasic afferent signals were absent. Progressive hyperoxic hypercapnia and isocapnic hypoxia were produced in anesthetized paralyzed dogs by allowing 3–5 min of apnea to follow mechanical ventilation with 100% O2 or 35% O2 in N2, respectively; during hypoxia, isocapnia was maintained by intravenous infusion of tris(hydroxymethyl)aminomethane buffer. The peak height (P) of nerve bursts, inspiratory time (TI), and expiratory time (TE) were measured from the phrenic neurogram. With the vagi intact or severed, hypoxia decreased TI, whereas hypercapnia did not; both stimuli decreased TE. At the same minute phrenic activity (P x frequency), P, TI, and TE were all less during hypoxia than during hypercapnia. The decreases in TI and TE with hypoxia were significantly less after carotid sinus denervation. The results indicate that the patterns of phrenic nerve activity in response to hypoxia and hypercapnia are different: hypoxia has a greater effect on respiratory timing, whereas hypercapnia has a greater effect on peak phrenic nerve activity. The effect of hypoxia on respiratory timing is largely mediated by the peripheral chemoreceptors.
One-step N2-dilution technique for calibrating open-circuit VO2 measuring systems
Authors: Fedak M. A. , Rome L. , Seeherman H. J.
Published: December 2017

A simple one-step procedure that eliminates the need to calibrate the O2 analyzer or measure the flow past the animal is described for calibrating an open-flow respirometry system. The technique is particularly useful for situations of high ambient humidity and for large or active animals where a mask is employed to capture expired gases. A measured N2 flow is used to calibrate the system. The equations describing the technique are given, and the accuracy of the method is discussed in detail. The errors associated with the technique are compared with those of more conventional procedures and are usually smaller.
Alveolar pressure-airflow characteristics in humans breathing air, He-O2, and SF6-O2
Authors: Slutsky A. S. , Drazen J. M. , O'Cain C. F. , Ingram R. H.
Published: December 2017

In a system of rigid tubes under steady flow conditions, the coefficient of friction [CF = 2 delta P/(rho V2/A2)] (where delta P is pressure drop, rho is density, V is flow, and A is cross-sectional area) should be a unique function of Reynolds' number (Re). Recently it has been shown that at any given Re, the value of CF using transpulmonary pressure (PL) was lower when breathing He-O2 compared with air (Lisboa et al., J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 48: 878–885, 1980). One explanation for this discontinuity is that PL includes the pressure drop due to tissue viscance, which is independent of V, and thus would lead to an overestimate of CF on air compared with He-O2 at any Re. We tested this hypothesis by measuring V related to alveolar pressure, rather than PL, in normal subjects breathing air, He-O2, and SF6-O2. In each subject, for a given Re, CF was greatest breathing SF6-O2 and lowest breathing He-O2, similar to results using PL. Thus tissue viscance is not the sole cause of the discontinuous plot of CF vs. Re, and this phenomenon must be due to other factors, such as changing geometry or nonsteady behavior.
Calculator/computer-assisted calibration and use of the IL-182 CO-Oximeter
Authors: Linberg S. E. , Deno N. S. , Britten J. S.
Published: December 2017

Of the many techniques and methods available for measuring carbon monoxide in blood, one of the easiest involves the use of the IL-182 CO-Oximeter, a specialized triple-wavelength spectrophotometer. Although easy to use, the calibration procedure can be lengthy and impractical if performed routinely to ensure accuracy. A method is described for an equivalent calibration by using a programmable calculator or minicomputer. The new method allows rapid and easy calibration as well as the analysis of unknown blood samples. Three anticoagulated blood samples, each containing as little as 2 ml, are required to calibrate. One sample is chemically reduced, one is tonometered in pure oxygen, and the third is tonometered in pure carbon monoxide. The optical densities of these three known calibration samples, determined at each of the three specific wavelengths used by the IL-182, allow one to derive the constants used in the equations needed to solve for an unknown sample.
Effect of beta-adrenergic blockade on respiratory and metabolic responses to exercise
Authors: Twentyman O. P. , Disley A. , Gribbin H. R. , Alberti K. G. , Tattersfield A. E.
Published: December 2017

The responses to oral propranolol (80 mg) and placebo were compared in normal subjects during three studies on a cycle ergometer (progressive exercise and two 5-min constant work rate studies at 50 and 70% maximum). Heart rate (HR), ventilation (VE), CO2 output (VCO2) and O2 uptake (VO2) were measured in each study and metabolites in venous blood in the 70% study. Propranolol reduced HR in all studies and endurance time during progressive exercise. During constant-work-rate exercise the changes with propranolol depended on time and work rate. At 50% max, VO2, VCO2, and VE were reduced in early exercise but were similar by min 5. At 70% max, VO2 and VCO2 were again lower initially with propranolol but then rose more rapidly. By min 5 VE was greater with propranolol, coinciding with a rapidly rising venous lactate. We interpret the initial reduction in VO2 and VCO2 to reduced cardiac output and muscle perfusion with propranolol. The resulting increase in anaerobic metabolism during heavy exercise would explain the increased VE at min 5. The metabolic data are compatible with glycogen being the predominant muscle fuel.
Body fluid and hematologic changes in the toad exposed to 48 h of simulated high altitude
Authors: Biswas H. M. , Patra P. B. , Boral M. C.
Published: December 2017

Body fluid and hematologic changes were found in three groups of adult male toads that had been exposed to 48 h of continuous simulated altitudes of 12,000, 18,000, and 24,000 ft, respectively. Erythrocyte counts and hematocrit ratios were increased significantly in all the high-altitude-exposed animals compared with the control group of animals kept at sea level, whereas the hemoglobin concentrations were significantly increased only in the 18,000- and 24,000-ft-exposed animals. Exposure to high altitude generally caused a reduction of plasma volume, blood volume, extracellular fluid volume, and total body water. These reductions were markedly lower in the animals exposed to 24,000 ft. These simulated high-altitude effects on body fluids and hematology in the toad (Bufo melanostictus) were compared with those of the rat, birds, and humans acutely acutely exposed at various high altitudes and were found to be qualitatively similar.
Extrapericardial and esophageal pressures with positive end-expiratory pressure in dogs
Authors: Craven K. D. , Wood L. D.
Published: December 2017

Using flat balloon techniques to minimize distortion and artifacts, we studied the effect of positive end-expiratory pressure (PEEP) on local surface pressures between the lung and pericardium overlying the right (R) and left (L) ventricles of ventilated closed-chest anesthetized dogs in right lateral decubitus position. To test the hypothesis that local extrapericardial [Pep(L) and Pep(R)] and average pleural pressures change equally with PEEP, we also measured esophageal pressure (Pes). When 10-cmH2O PEEP was applied, mean increases in Pes, Pep(L), and Pep(R) were 6.2, 5.6, and 5.3 cmH2O, respectively. When PEEP was raised to 20 cmH2O, further average increases in Pes, Pep(L), and Pep(R) were 5.8, 5.0, and 5.4 cmH2O. At each level of PEEP, volume infusion was used to increase stroke volume. Volume infusion at 20-cmH2O PEEP was associated with small 1.0- and 1.5-cmH2O increases in Pep but no change in Pes. Analysis of confidence limits showed that application of up to 20-cmH2O PEEP, with or without volume infusion to restore stroke volume, is associated with nearly equal changes in esophageal and local extrapericardial pressures.
Effects of lung inflation on airway and tissue responses to aerosol histamine
Authors: Loring S. H. , Ingram R. H. , Drazen J. M.
Published: December 2017

The pulmonary effects of aerosol histamine exposure include an increase in pulmonary resistance (RL) and a decrease in dynamic compliance (Cdyn). These changes are substantially reversed by inflation of the lungs to 30 cmH2O transpulmonary pressure (TLC). Although histamine has been shown to change both the airway and tissue components of RL and Cdyn, it is not known whether lung inflation reverses the changes in airways, in tissue, or in both. We studied six anesthetized, paralyzed, open-chest dogs. We sequentially measured RL and Cdyn during oscillations in lung volume at 0.6 Hz with the airway open and during compression-decompression of the lungs without tracheal airflow. In the control state after saline aerosol, inflation to TLC resulted in a slight increase in compliance and a decrease in the tissue component of RL. Aerosol histamine exposure caused an increase in resistance and a decrease in compliance due to both airway and tissue changes. Inflation of the lungs to TLC largely reversed the changes due to airway constriction without consistently affecting the changes due to tissue. We conclude that after histamine exposure smooth muscle responsible for airway narrowing is stretched by lung inflation but that contractile elements responsible for alterations in air-space distensibility and hysteresis of dynamic lung recoil are either not stretched by lung inflation or are stretched and shorten again rapidly.
Factors determining temporal pattern of isobaric supersaturation
Authors: Young C. , D'Aoust B. G.
Published: December 2017

It is possible to produce a transient supersaturation or undersaturation in tissues and blood by sequentially breathing gases with different equilibration rates. If the ambient gas pressure is sufficiently high, the induced supersaturation can produce vascular bubbles. By means of the classical perfusion-dependent model of inert gas elimination, which assumes that the effects of diffusion are minimal, the magnitude of the total inert gas pressure can be predicted. If, however, the effects of diffusion cannot be ignored, the supersaturation could be substantially larger. This paper estimates the effects of diffusion in a Krogh cylinder on the supersaturation produced by suddenly changing the inert gas partial pressure in the blood. The results of these estimates indicate that diffusion plays a role in this transient supersaturation only in long Krogh cylinders with high blood flows. The effects of diffusion are further reduced by the finite time necessary to switch the inert gases in arterial blood. The conclusions are supported by experiments that measure vascular bubble production after a switch of the inert portion of the inspired gas. These experiments further show that the formation of vascular bubbles after such a switch cannot be entirely explained by the different diffusion constants of the gases used.
Nonlinear increases in diffusing capacity during exercise by seated and supine subjects
Authors: Stokes D. L. , MacIntyre N. R. , Nadel J. A.
Published: December 2017

To study the effects of exercise on pulmonary diffusing capacity, we measured the lungs' diffusing capacity for carbon monoxide (DLCO) during exhalation from 30 to 45% exhaled vital capacity in eight healthy subjects at rest and during exercise while both sitting and supine. We found that DLCO at these lung volumes in resting subjects was 26.3 +/- 3.2% (mean +/- SE) higher in the supine than in the sitting position (P less than 0.001). We also found that, in both positions, DLCO at these lung volumes increased significantly (P less than 0.001) with increasing exercise and approached similar values at maximal exercise. The pattern of increase in DLCO with an increase in oxygen consumption in both positions was curvilinear in that the rate of increase in DLCO during mild exercise was greater than the rate of increase in DLCO during heavy exercise (P = 0.02). Furthermore, in the supine position during exercise, it appeared that DLCO reached a physiological maximum.
Plasma and platelets potentiate a hypoxic vascular response of the isolated lung
Authors: Kivity S. , Souhrada J. F.
Published: December 2017

To determine whether plasma and /or platelets play a role in the hypoxic response of pulmonary circulation, we perfused isolated rat lungs with different concentrations of plasma and varying numbers of platelets. As the lungs were perfused with a constant flow (8–13 ml/min), a change in the mean pulmonary artery perfusion pressure (PApP) during acute alveolar hypoxia was a measure of increased tone of the pulmonary circulation. It was found that the presence of plasma in the perfusate (both 20% and 100%) significantly (P less than 0.05) potentiated the PApP response during repeated acute alveolar hypoxia, compared with the response to artificial perfusate without plasma. An isolated rat lung perfused with 6.5% dextran or 3% albumin (both in a physiological salt solution) showed only minimal pressure response during acute alveolar hypoxia. In the second part of the experiment, isolated lungs were perfused with a fresh 100% plasma containing different numbers of platelets. A dose-response-like relationship was observed between the number of platelets in the perfusate and the response of the pulmonary vasculature to acute hypoxia. The highest hypoxic response of the pulmonary vessels, as indicated by the increase in PApP, was shown when the perfusate contained a nearly normal in vivo number of platelets. It can be concluded that both plasma and platelets are important factors that can significantly alter the hypoxic response of the pulmonary vasculature in isolated rat lungs.
Alveolar function following surfactant deactivation
Authors: Nieman G. F. , Bredenberg C. E. , Clark W. R. , West N. R.
Published: December 2017

In vivo cinemicroscopic studies of subpleural alveoli were conducted in dogs for 4 h after pulmonary lavage with 5% Tween 20 and after lavage with normal saline. Saline-lavaged alveoli showed little change in alveolar size during tidal ventilation, whereas Tween lavage resulted both in alveolar recruitment and marked variation in alveolar size from end expiration to peak inspiration, with total collapse frequently occurring by end expiration. Following Tween, alveolar stability decreased, but alveolar capillary perfusion increased. Marked recovery of stability by 4 h was noted in most alveoli. Wilhelmy balance studies on lung extracts showed a decrease in surfactant function 30 min after Tween and a partial recovery of surfactant activity after 4 h. This study provides in vivo evidence that normal surfactant function is critical to alveolar stability and that alveolar stability is markedly restored 4 h after acute deactivation or displacement by Tween. Surfactant deactivation and loss of alveolar stability are associated with increased alveolar capillary perfusion creating significant ventilation-perfusion ratio abnormalities.
A model for the relation between respiratory neural and mechanical outputs. I. Theory
Authors: Younes M. , Riddle W.
Published: December 2017

A model for the conversion of respiratory neural output to mechanical output, and vice versa, is described. Neural output was expressed in terms of isometric pressure generated at passive functional residual capacity. The mechanical response time constant of respiratory muscle was assumed to be 0.06 s. The effect of volume and configuration on pressure output was modeled after the data of Grassino et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 829–839, 1978). Equations were developed to examine the effect of different configurational pathways during inspiration. We utilized Hill's hyperbolic force-velocity relation to model the effect of flow on pressure output. The pressure asymptote of the hyperbola was considered to be similar to that in other skeletal muscles (0.25 isometric pressure). The flow asymptote was derived from data obtained during maximal voluntary inspiration. A major feature of the model is the dependence of volume, configuration, and flow-related pressure losses on level of inspiratory activity. The practical effect of potential errors and the overall accuracy of the model are presented in the two succeeding communications.
A model for the relation between respiratory neural and mechanical outputs. II. Methods
Authors: Riddle W. , Younes M.
Published: December 2017

In the preceding communication we developed a model for the conversion of neural output to mechanical output. We were left with two qualitative uncertainties, namely, the relation between neural output and isometric pressure, and the behavior of inspiratory muscles during expiratory flow; and two quantitative uncertainties concerning the effect of configurational pathway on pressure output, and the slope of the pressure-flow relation. For each of the above uncertainties we made certain assumptions based on indirect evidence but defined reasonable error limits. In the present communication we describe the method of implementing the model and evaluate the significance, in terms of spirometric output, of possible errors in the assumptions. Volume and flow profiles were generated from different neural output profiles. Analysis was repeated when the different assumptions were systematically altered within the limits set by the previous theoretical analysis. We conclude that the pattern of inspiratory muscle activation during spontaneous breathing and the existence of several mechanical interactions within the respiratory system combine to render spirometric output fairly insensitive to most potential errors in our assumptions.
Hypoxic vasoconstriction and fluid filtration in pig lungs
Authors: Mitzner W. , Sylvester J. T.
Published: December 2017

We have studied the effect of hypoxia [inspired partial pressure of O2 (Po2) 50 mmHg] on the relationships among pulmonary blood flow, pulmonary arterial pressure, and fluid filtration rates in isolated blood-perfused pig lungs. Our results indicate that hypoxia constricted the vasculature in a manner that caused a parallel shift of the pressure-flow curve to higher pressures. During normoxia, filtration rate was zero at flows less than 1.5 1/min but increased with increases in blood flow above this level. In both cases the shape of this relationship was similar, but during hypoxia it was shifted to higher filtration rates. These findings can be interpreted using a parallel-channel Starling resistor model of the lung with a distribution of critical pressures. All the effects of hypoxia found in this study could be explained simply by an increase in critical pressure. According to the model, this increase in critical pressure during hypoxia caused a greater filtration rate because of an increase in the mean intravascular filtration pressure and an increase in the mean filtration coefficient.
Arm and leg intravascular temperatures of men during submaximal exercise
Authors: Aulick L. H. , Robinson S. , Tzankoff S. P.
Published: December 2017

Rectal (Tre) and blood temperatures in the femoral artery (Tfa), femoral vein (Tfv), axillary artery (Taa), and axillary vein (Tav) were determined in three men over a range of steady-state treadmill exercise (173–401 W/m2) in a 24 degree C db, 15 degree C wb environment. When the men were standing quietly before the walks Tre greater than Tfa greater than Taa greater than Tfv greater than Tav, indicating that under these resting conditions both the arms and the legs served as avenues for arterial heat dissipation. By the end of all 1-h walks, Tre, Tfa, Tasa, and Tfv had increased in a linear fashion with work load, Tav had dropped, and Tre greater than Tfv greater than or equal to Tfa greater than or equal to Taa greater than Tav. The maintenance or expansion of axillary arteriovenous temperature differences during exercise indicated that the less active arms continued to serve as routes for arterial heat loss. The lack of femoral arteriovenous temperature differences demonstrated that under these steady-state exercise conditions there was little or no net vascular heat transfer between the active legs and the central circulation. Rectal-femoral intravascular temperature differences at rest and over the full range of submaximal work employed favor heat transfer from the rectum to the circulation. Consequently the rise in Tre during leg work was considered the result of a reduction in local heat dissipation and some possible heat gained from nearby intrapelvic muscles.
Effect of exhaustive exercise on myocardial performance
Authors: Grimditch G. K. , Barnard R. J. , Duncan H. W.
Published: December 2017

Several investigators have reported ultrastructural changes in hearts of animals exercised to exhaustion. The present study was designed to determine whether functional changes occur in the intact heart at exhaustion. Adult mongrel dogs (n = 8) were chronically instrumented to measure cardiac output, coronary blood flow, aortic blood pressure, left ventricular pressure, +dP/dtmax, and -dP/dtmax. After recovery, the dogs were run to exhaustion at a constant work load, eliciting approximately 70% of maximum heart rate. The exhaustive bouts were terminated when the animals either refused or were unable to continue running, at which time their rectal temperatures approaches 42.2 degree C. The mean exhaustion time was 76.7 +/- 11.8 min. All parameters increased from rest to steady state with the exception of stroke volume (23.2 +/- 4.9 vs. 20.5 +/- 1.6 ml), which remained constant. In the transition from steady state to exhaustion, only +dP/dtmax (6,652 +/- 291 vs. 7,689 +/- 479 Torr/s) and -dP/dtmax (4,110 +/- 227 vs. 4,890 +/- 215 Torr/s) increased significantly; all other values exhibited no significant change. Similarly, when maximum cardiovascular parameters were measured before and after exhaustion, no significant changes were found. These data show that cardiac contractile function is not depressed in dogs as a result of exhaustive exercise.
Ventilatory responses to cardiac output changes in patients with pacemakers
Authors: Jones P. W. , French W. , Weissman M. L. , Wasserman K.
Published: December 2017

Cardiac output changes were induced by step changes of heart rate (HR) in six patients with cardiac pacemakers during monitoring of ventilation and gas exchange, breath-by-breath. Mean low HR was 48 beats/min; mean high HR was 82 beats/min. The change of oxygen uptake immediately after the HR change was used as an index of altered cardiac output. After HR increase, oxygen uptake (V02) rose by 34 +/- 20% (SD), and after HR decrease, Vo2 fell by 24 +/- 11%. There was no change in arterial blood pressure. After HR increase, ventilation increased, after a mean delay of 19 +/- 4 s; after HR reduction, ventilation fell, after a mean delay of 29 +/- 7 s. In the period between HR increase and the resulting increase in ventilation, end-tidal PCO2 (PETCO2) rose by 2.6 +/- 2.0 Torr, and in the period between HR decreases and the fall in ventilation, PETCO2 dropped by 2.9 +/- 2.2 Torr. The response time and end-tidal gas tension changes implicate the chemoreceptors in the reflex correction of blood gas disturbances that may result from imbalances between cardiac output and ventilation.
Effects of rib cage or abdominal restriction on lung mechanics
Authors: Scheidt M. , Hyatt R. E. , Rehder K.
Published: December 2017

The effects on lung mechanics of equal (37%) reduction in total lung capacity (TLC) by rib cage or abdominal restriction were studied in 10 healthy males. Lung recoil pressure (Pst) was simultaneously measured from three sites in the esophagus. This also provided an estimate of the vertical pleural pressure gradient (PPG). Deformation of the right hemithorax was quantified by roentgenograms in three subjects. At the same lung volume, abdominal restriction decreased lung height and increased anteroposterior diameter compared with the control case, whereas rib cage restriction had opposite effects. Maximum expiratory flow increased equally with both types of restriction, and average Pst increased equally with both types of restriction. There was a significant correlation between degree of TLC reduction and increase in Pst that was similar for both types of restriction. This study indicates that changes in lung mechanics depend primarily on the amount of volume reduction and not on the type of deformation producing the volume decrease.
Body temperature, oviposition, and food intake in the hen during continuous light
Authors: Kadono H. , Besch E. L. , Usami E.
Published: December 2017

Deep-body temperature of the laying hen was measured with an implantable radio transmitter. Food and water intake and oviposition time were recorded, remotely, based on electric signals from microswitches attached to the individual cages. Body temperature and feeding activity of the laying hen under continuous light displayed a circadian rhythm. The length of the body-temperature cycle was 25.2 h, and the feeding cycle was 25.3 h. These values appear to be associated with the animal's laying cycle which was 25.3 h. The laying cycle of the hen can play an important role in the maintenance of circadian rhythms of body temperature and feeding activity. Both the marked temperature rise found at the time of oviposition and the prelaying (or nesting) behavior may be controlled by a preovulatory surge of luteinizing hormone (LH) and progesterone.
Respiratory responses in reversible diaphragm paralysis
Authors: Nochomovitz M. L. , Goldman M. , Mitra J. , Cherniack N. S.
Published: December 2017

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.
Maximum leg force and power output during short-term dynamic exercise
Authors: Sargeant A. J. , Hoinville E. , Young A.
Published: December 2017

Force exerted and power generated were measured during short-term exercise performed on a bicycle ergometer that had been modified by the addition of an electric motor driving the cranks at a chosen constant velocity. Five subjects made a series of 20-s maximum efforts at different crank velocities (range 23--171 rev/min). The forces exerted were continuously monitored with strain gauges bonded to the cranks. Peak force was exerted at approximately 90 degrees past top dead center in each revolution. During the 20-s effort peak force declined from the maximum level (PFmax) attained near the start of exercise, the rate of decline being velocity dependent. PFmax was found to be inversely and linearly related to crank velocity and when standardized for upper leg muscle (plus bone) volume (ULV) was given by PFmax (kgf/l ULV) = 27.51--0.125 crank velocity (rev/min). Integration of the force records with pedal velocity enabled power output to be calculated. Maximum power output was a parabolic function of crank velocity, the apex of the relationship indicating that the velocity for greatest power output was 110 rev/min. At this velocity our subjects achieved a maximum mean power output, averaged over a complete revolution, of 840 +/- 153 W (85 +/- 5 W/l ULV). This was compared with the calculated value for maximum mechanical power output from aerobic sources, which was 272 +/- 49 W (30 +/- 1 W/l ULV).
Tritiated water for estimating total body water and water turnover rate in birds
Authors: Degen A. A. , Pinshow B. , Alkon P. U. , Arnon H.
Published: December 2017

The use of tritiated water (TOH) to estimate total body water (TBW) and total water turnover rate was validated in chukar partridges (Alectoris chukar) and sand partridges (Ammoperdix heyi). For six chukar partridges weighing between 315 to 475 g, TOH equilibration with body fluids was less than 45 min after intramuscular or intravenous injections. Mean TOH space in eight chukar partridges was 99.8% of the mean TBW measured by desiccation with individuals ranging between 97.9 and 103.2%. TOH space best approximated TBW when TBW was calculated by using the mean body mass for a bird weighed at TOH injection and at TOH equilibration. Total water intake as estimated by TOH ranged between 90.7 and 113.3% of measured water intake in three sand and three chukar partridges, birds ranging in mass from 145 to 446 g. We conclude that the TOH method provides accurate estimations of TBW and water turnover rates in birds. For birds of up to 500-g body mass, we recommend 45 min for TOH equilibration with body fluids, and intramuscular injections of 0.05 muCi TOH/g body mass for TBW estimations and 0.1 muCi TOH/g body mass for water turnover estimations.
Acute pulmonary hemodynamic effects of intravenous copper sulfate: role of alpha-adrenergic system
Authors: Ahmed T. , Januszkiewicz A. , Eyre P. , Robinson M. J. , Sackner M. A.
Published: December 2017

We investigated the acute pulmonary hemodynamic effects of intravenous copper sulfate (CuSO4) infusion and its mechanism of action in six groups of conscious sheep (total 40). After 300 mg CuSO4 alone, mean pulmonary artery pressure (Ppa) increased from 10.3 to 22.5 Torr and pulmonary artery wedge pressure (Ppaw) from 3.5 to 7.6 Torr, whereas systemic arterial pressure (Psa) increased from 95 to 102 Torr. Cardiac output (Qp) decreased from 4.7 to 3.3 l/min. Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) increased to 320 and 160% of base line, respectively. The hemodynamic changes correlated well with serum copper, which increased from a base-line value of 0.12 to 3.5 mg/dl after the CuSO4. Serum dopamine beta-hydroxylase increased from 3.2 U/l before CuSO4 injection to 5.7 after its administration, signifying activation of adrenergic nervous system. H1-histamine receptor blockade with chlorpheniramine failed to prevent the effects of CuSO4. Pretreatment with methysergide, a serotonin antagonist, partially attenuated the effects of CuSO4. Phenoxybenzamine, an alpha-adrenergic receptor blocker, and 6-hydroxydopamine, a catecholamine depleting agent, completely blocked the effects of CuSO4. beta-Adrenergic receptor blockade with propranolol enhanced the effects of CuSO4. We conclude, that, in conscious sheep, acute infusion of CuSO4 caused a marked reversible increase in PVR with a slight transient increase in SVR, and this pulmonary hypertension was produced by stimulation of the alpha-adrenergic nervous system.
Pulmonary injury in rats following continuous exposure to 60% O2 for 7 days
Authors: Hayatdavoudi G. , O'Neil J. J. , Barry B. E. , Freeman B. A. , Crapo J. D.
Published: December 2017

Morphological, biochemical, and physiological studies were done on rats exposed to 60% O2 for 7 days. This exposure did not induce O2 tolerance but instead caused a significant decrease in survival time of animals subsequently exposed to pure O2. The activity of lung superoxide dismutases and glucose-6-phosphate dehydrogenase were unchanged after exposure to 60% O2. A decrease in lung compliance was suggested by changes in the total lung capacity and in the pressure-volume curves of excised lungs. Ventilation of these animals with large tidal excursion resulted in pulmonary edema. Morphometric analyses revealed a significant decrease in alveolar air volume and an increase in the number of alveolar macrophages. The most significant lesions involved the pulmonary vascular bed. The volume and thickness of the capillary endothelium was decreased. There were focal areas of pericapillary fluid accumulations, and a number of the smaller vessels had perivascular edema. These findings suggest that significant pulmonary injury occurs in rats exposed to 60% O2 and that the primary site of injury is the pulmonary capillary endothelium.
Gas exchange in nonperfused dog lungs
Authors: Shepard J. W. , Minh V. D. , Dolan G. F.
Published: December 2017

Gas exchange was studied under conditions of zero perfusion both in situ and in vitro. Six dogs, anesthetized with pentobarbital sodium, underwent surgical interruption of both pulmonary and bronchial circulations to the left lung. Despite the absence of perfusion, O2 uptake for the left lung ranged from 0.76 to 0.98 ml/min, whereas CO2 elimination greatly exceeded O2 uptake ranging from 1.68 to 4.34 ml/min. In addition, CO2 output was observed to vary directly with the level of minute ventilation (VE) and inversely with end-tidal CO2 concentration. To investigate the mechanisms responsible for these findings we studied 20 excised, ventilated, but nonperfused dog lungs to evaluate the relative roles of tissue metabolism and transpleural diffusion to gas exchange. The results obtained with these excised lungs under conditions of varying VE and extrapleural gas concentrations indicate that the high respiratory exchange ratios observed in situ can be explained by the greater rate with which CO2 diffuses through the pleura, and that reduced ventilation decreases total gas transfer by decreasing the transpleural partial pressure driving gradient. Our data further document that the concentration of CO2 in alveolar gas may differ significantly from that present in inspired gas under conditions of ventilation-perfusion ratio equal to infinity, and that tissue metabolism as well as transpleural diffusion contribute to gas exchange in nonperfused lung.
Liver metabolites in resting and exercising rats at 1 and 4 bar
Authors: Hanson R. D. , Gray R. M. , Alberti K. G.
Published: December 2017

Groups of six rats were put into a compression chamber and exposed to an air pressure of 4 bar or remained at 1 bar. Half of each group was forced to swim in a tank of warm water; the other half remained at rest. A total of 28 rats was used. After 30 min the rats were killed, and part of the liver was rapidly (less than 10 s) removed and pressed between metal plates that had been cooled in liquid nitrogen. Analyses of the metabolites indicated a significant reduction gluconeogenesis in the animals exercising under pressure, probably due to a diminished return of substrates from the muscles. There also appeared to be the possibility of enzymatic control between fructose 6-phosphate and the triose phosphates.
Steady expiratory flow in dog lungs: an isovolume preparation
Authors: Sneddon S. L. , Brain J. D.
Published: December 2017

By supplying air and other gases through discs glued to the pleural surface, we studied steady expiratory flow at constant volume. Dog lungs were studied at constant PA - Ppl (alveolar minus pleural pressure) of 7 to 10 cmH2O, as increasing flow was achieved by increasing driving pressure [Ppl - Pao (airway opening pressure)]. Flow became limited (independent of further increases in Ppl - Pao) at between 3.5 and 5.5 l/s. Isovolume-pressure-flow (IVPF) curves constructed from forced expirations at graded efforts yielded similar maximal flows. When the airways were made rigid by drying, flow limitation was abolished. When various gases were passed through the dried lung Moody plots of normalized pressure drop (CD) vs. Reynolds number (Re) showed that all of the data could be plotted on a single curve. Although variable among animals, all Moody plots showed a laminar flow region at Re below 100 and an inertial region at Re above 10,000, with a distinct transition.
Steady and unsteady pressure-flow relationships in central airways
Authors: Isabey D. , Chang H. K.
Published: December 2017

We measured pressure-flow relationships in a noncompliant five-generation cast of human central airways using air, HeO2, and SF6O2 at 0, 0.25, 0.50, 1.0, and 2.0 Hz with tidal volumes of 0.25, 0.5, and 1.0 liter. When dimensionless pressure drops for steady inspiratory and expiratory flows of the various gas mixture were plotted against Reynolds' number on a log-log scale (Moody diagram), they formed two curves as fluid mechanical theory predicts. At frequencies higher than 0.25 Hz, data obtained from 1) the same gas and same stroke volume, 2) the same frequency and same stroke volume but different gases, and 3) the same gas at the same frequency but with different stroke volumes, all deviated from the steady flow curves in the Moody diagram, always tending to increase the dimensionless pressure drop. The increase was largest when instantaneous flow was near zero and was minimal at the peak flow in a given inspiration or expiration. These data led to the identification of a dimensionless parameter (epsilon) that reflects the relative importance of local acceleration (unsteadiness) to convective acceleration at any given instant during a flow cycle. A dimensional analysis then reveals that the pressure-flow relationship in a given airway system is uniquely and completely determined by a combination of three dimensionless parameters: Reynolds number (Re), Womersley number (alpha), and the new parameter (epsilon). With this set of parameters we can explain all reported apparent paradoxes as well as the present findings.
Rapid brain cooling in the free-running hamster Mesocricetus auratus
Authors: Gordon C. J. , Rezvani A. H. , Fruin M. E. , Trautwein S. , Heath J. E.
Published: December 2017

A thermocouple reentrant tube was stereotaxically implanted in the rostral brain stem of the golden hamster, Mesocricetus auratus. Brain temperature was continuously recorded while the hamster was permitted volitional running on an activity wheel. There was an immediate decrease in brain temperature at the start of running activity, reaching a mean of 0.49 degrees C below the prerunning level. Spontaneous or forced cessation of running activity was associated with a rapid recovery of brain temperature. The time course of brain cooling during exercise greatly differed from the exponential decay of brain temperature in hyperthermic and dead animals. Air flow through the nose may contribute to the maintenance of a low brain temperature because nasal blockade promotes an increase in brain temperature. Below an ambient temperature of 33 degrees C, the resting hamster maintains its brain temperature below deep-body (abdominal) temperature. Vinyl acetate casts of the arterial and venous systems revealed several potential sites for heat exchange that might account for brain cooling under resting and exercising conditions.
Blind oral tracheal intubation of rats
Authors: Stark R. A. , Nahrwold M. L. , Cohen P. J.
Published: December 2017

Tracheal intubation is often necessary for experiments involving anesthetized rats. Previously described methods for endotracheal intubation have required either a tracheostomy or intubation under direct vision. These techniques require considerable time and skill. Therefore we dissected rats to evaluate the anatomy of the airway. Using these data, we originated a technique for blind oral tracheal intubation using a modified 16-gauge intravenous catheter. The technique has a reasonable success rate and can be performed much more rapidly than conventional methods.
Influence of hematocrit and temperature on solubility of acetylene and dimethyl ether
Authors: Jibelian G. , Mitchell R. R. , Overland E. S.
Published: December 2017

Estimation of pulmonary capillary blood flow (Qc) and tissue volume (Vt) by rebreathing acetylene (Ac) and dimethyl ether (DME) is dependent on the blood-gas partition coefficient (lambda) of these gases. We investigated the effects of hematocrit (Hct) and temperature on lambda. Human and canine blood was equilibrated at different Hct for 40 min at 37.5 degrees C with 1% Ac and 1% DME in air. Gas concentration in the headspace was measured by gas chromatography. lambda Ac increased with increasing Hct, suggesting a slight lipid affinity, whereas lambda DME decreased with increasing Hct, displaying the known blood-water content dependence. The influence of temperature on lambda in the range of 32--47 degrees C was investigated also. lambda Ac and lambda DME decreased as the temperature was raised, in accordance with the Gibbs-Helm-holtz equation. Empirical equations were derived to relate lambda to to Hct and temperature.
Measurement of pulmonary tissue volume and blood flow in persons with normal and edematous lungs
Authors: Overland E. S. , Gupta R. N. , Huchon G. J. , Murray J. F.
Published: December 2017

We measured pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) by a rebreathing method using two soluble gases, acetylene (C2H2) and dimethyl ether (DME), in 32 normal subjects and 14 patients who had had pulmonary edema. In 18 of the normal subjects, studies were performed at three or more different rebreathing volumes (VA). To normalize for differences in body size, results were expressed as the ratio of Vt or VA to predicted total lung capacity (TLC). We found that 1) changes in VA/TLC had a significant effect on Vt/TLC and Qc measured with both gases, 2) the range of normal values for Vt was best defined by expressing the relationship between Vt/TLC and VA/TLC, 3) using this approach, many patients with clinically mild or inapparent pulmonary edema had abnormal values of Vt, and 4) when comparing mean values of C2H2 and DME in 82 simultaneous measurements at constant VA/TLC, Vt was significantly higher in 87% (71/82) and Qc in 63% (52/82) of the paired tests.
Effects of vasopressin administration on diuresis of water immersion in normal humans
Authors: Epstein M. , DeNunzio A. G. , Loutzenhiser R. D.
Published: December 2017

Although previous studies have demonstrated that water immersion to the neck (NI) results in a significant diuresis, the mechanisms are incompletely delineated. Because recent studies in our laboratory have demonstrated that NI is associated with a suppression of antidiuretic hormone (ADH), it is possible that such a suppression mediates the encountered diuresis. The present study was undertaken to assess more directly the relative role of ADH suppression by determining the effects of vasopressin administration. Six hydrated normal subjects were studied on two occasions while undergoing 6 h of NI. During the second NI study, aqueous vasopressin (20 mU/h) was infused for the initial 4 h of study (NI + vasopressin). NI resulted in a significant increase in urinary flow rate beginning during hour 1 and persisting throughout NI. In contrast, during NI + vasopressin, the anticipated diuresis was abolished throughout the 4 h of vasopressin administration. Cessation of vasopressin administration during the final 2 h of NI + vasopressin resulted in a marked and prompt diuresis. The present observations are consistent with the formulation that ADH suppression participates importantly in mediating the diuresis of NI in hydrated normal subjects.