bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilatory and arousal patterns during sleep in normal young and elderly subjects
Authors: Shore E. T. , Millman R. P. , Silage D. A. , Chung D. C. , Pack A. I.
Published: December 2017

Since elderly subjects have lower chemosensitivity, we postulated that ventilation might be more state dependent in the elderly. To address this we investigated the changes in ventilation, measured by respiratory inductive plethysmography, with sleep in 12 healthy young (19–29 yr) and 13 elderly (greater than 65 yr) subjects. Ventilation was measured in representative periods in each sleep state. These data showed that there is no difference between the elderly and the young either in mean ventilation or in the variability of ventilation awake or in the different states of sleep. In both groups ventilation was variable in stage 1–2 sleep and least variable in stage 3–4 sleep. The variability in stage 1–2 sleep was due to periodic breathing (cycle time approximately 45 s) in both age groups. Although within a sleep state no differences were observed, over the night of study the elderly behaved differently from the young. Apneas occurred more frequently in the elderly, and 5 of 13 elderly met the criteria for sleep apnea syndrome compared with 1 of 12 young subjects. Apneas tended to occur predominantly in stage 1–2 sleep and seem to be an exaggeration of the periodicity that is typical of this state. Four of the elderly with apnea remained in this stage of sleep throughout the night of study. The apneic episodes usually terminated with an electroencephalogram arousal that occurred prior to or simultaneously with the onset of ventilation.
Vascular and interstitial mechanics in canine pulmonary emphysema
Authors: Mink S. N. , Unruh H. W. , Oppenheimer L.
Published: December 2017

We examined the changes in vascular and interstitial mechanics in pulmonary emphysema (PE) using a canine lobar model. PE was produced in the left lower lobe (LLL) of five dogs (group E) by six weekly intrabronchial instillations of the enzyme papain. In five control dogs (group C), a normal saline solution was used. In our in vivo preparation, vascular flow (Q) to the LLL was measured. Inflow (Ppa) and outlow (Pv) pressures to the LLL could be varied independently. The relationship of Ppa to Q was examined in zones 2 and 3 of West. The slope of the Ppa-Q relationship was used to determine vascular conductance, whereas the extrapolation to zero flow in zone 2 conditions represented the mean pressure required for vascular recruitment (Pi). Lobar weight gain was measured continuously. Following step increases in Ppa, the rapid increase in wet weight measured when Q to the LLL was zero was used to obtain vascular compliance (C). Subsequent slow increases in wet weight were used to determine the rate of fluid exchange with the interstitium (Qf). The slope of the Qf-Ppa relationship represented fluid conductance (Kf). The extrapolation to zero Qf gave the minimal pressure required for continuous edema formation (Pm). Compared with group C, vascular conductance (G) decreased and Pi increased in group E, whereas fluid conductance (Kf) and Pm increased. The decrease in G most likely resulted from the loss of vascular cross-sectional area in emphysematous lungs, whereas the increase in Pi was possibly due to mechanical changes in the lung interstitium which increased vessel closure. We propose that the increase in Kf in group E reflected an increase in interstitial conductance, such that due to structural changes in the interstitium in emphysematous lungs, tissue resistance to fluid flux decreased.
Respiratory responses to ventilatory loading following low cervical spinal cord injury
Authors: Kelling J. S. , DiMarco A. F. , Gottfried S. B. , Altose M. D.
Published: December 2017

This study compared the respiratory responses to ventilatory loading in 8 normal subjects and 11 quadriplegic patients with low cervical spinal cord transection. Progressive hypercapnia was produced by rebreathing. Rebreathing trials were carried out with no added load and with inspiratory resistive loads of 5 and 16 cmH2O. l-1 X s. Measurements were made of ventilation and of diaphragmatic electromyographic activity. Base-line hypercapnic ventilatory responses were significantly lower than normal in the quadriplegic patients, but the effects of resistive loading on the ventilatory responses were comparable in the two groups. The change in peak moving-average diaphragmatic electrical activity (DI peak) for a given change in CO2 partial pressure (PCO2) and DI peak at PCO2 55 Torr increased significantly with resistive loading both in the normal subjects and the quadriplegic patients. In the normal subjects, but not in the quadriplegic patients, inspiratory duration increased progressively with increasing resistance. The increase in DI peak during ventilatory loading in the normal subjects was a consequence of inspiratory prolongation. In contrast, in the quadriplegic patients during breathing against the larger resistive load, there was a significant increase in the average rate of rise (DI peak divided by the time from onset to peak) of diaphragmatic activity. The change in DI rate of rise for a given change in PCO2 increased to 137 +/- 13% (SE), and the DI rate of rise at PCO2 55 Torr increased to 128 +/- 8% (SE) of control values. These results indicate that compensatory increases in diaphragmatic activation during ventilatory loading occur in quadriplegic patients in whom afferent feedback from rib cage receptors is disrupted.
Changes in lung volume and deflation stability in hyaline membrane disease
Authors: Jackson J. C. , Standaert T. A. , Truog W. E. , Murphy J. H. , Palmer S. , Chi E. Y. , Woodrum D. E. , Watchko J. F. , Hodson W. A.
Published: December 2017

Total lung capacity (TLC), inspiratory capacity, functional residual capacity, and deflation stability of prematurely delivered Macaca nemestrina primates were measured serially during development of, and recovery from, hyaline membrane disease (HMD) to relate changes in lung volumes to changes in deflation stability. Gestational age-matched primates that did not develop HMD served as controls. TLC, measured by N2 washout, fell at 2–12 h of age (P less than 0.0001) in animals with HMD and remained lower than controls for at least 48 h (P less than 0.005). However, deflation stability, defined as the fraction of TLC remaining upon deflation to 10 cm H2O, improved from 2 to 12 h of age (P less than 0.001). Postmortem studies confirm the measurements of TLC and deflation stability and provide evidence that interstitial thickening and obstruction of air spaces with debris may be partially responsible for the observed changes in TLC in primates that develop HMD. It has been assumed that TLC is reduced in HMD because of atelectasis from elevated alveolar surface tension, but the sequential measurements in these animals suggest that other mechanisms also contribute.
Increased in vitro airway responsiveness in sheep following repeated exposure to antigen in vivo
Authors: Wagner E. M. , Kleeberger S. R. , Spannhake E. W. , Adams G. K.
Published: December 2017

We have studied the effect of repeated in vivo antigen exposure on in vitro airway responsiveness in sensitized sheep. Fourteen sheep underwent five biweekly exposures to aerosolized Ascaris suum antigen or saline. Following this exposure regimen, the animals were killed and tracheal smooth muscle and lung parenchymal strips were prepared for in vitro studies of isometric contraction in response to histamine, methacholine, prostaglandin F2 alpha, and a thromboxane A2 analogue. No alteration in tracheal smooth muscle responsiveness was observed between saline- and antigen-exposed tissue. In contrast, by use of lung parenchymal strips as an index of peripheral airway responsiveness, significant increases in responsiveness to histamine and a thromboxane A2 analogue (10(-6) and 10(-5) M) were observed in antigen-exposed tissue compared with saline controls. These results demonstrate that repeated antigen exposure in vivo selectively increase the responsiveness of peripheral lung smooth muscle to certain chemical mediators of anaphylaxis.
Significance of thromboxane generation in ozone-induced airway hyperresponsiveness in dogs
Authors: Aizawa H. , Chung K. F. , Leikauf G. D. , Ueki I. , Bethel R. A. , O'Byrne P. M. , Hirose T. , Nadel J. A.
Published: December 2017

To determine whether thromboxane A2 may be involved in ozone (O3)-induced airway hyperresponsiveness, we studied the effect of a thromboxane synthase inhibitor (OKY-046, 100 micrograms X kg-1 X min-1 iv) in five dogs exposed to O3. Airway responsiveness was assessed by determining the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance by 5 cmH2O X l-1 X s. O3 (3 ppm) increased airway responsiveness as demonstrated by a decrease in acetylcholine provocative concentration from 2.42 (geometric SEM = 1.64) to 0.14 mg/ml (geometric SEM = 1.30). OKY-046 significantly inhibited this effect without altering pre-O3 responsiveness or the O3-induced increase in neutrophils and airway epithelial cells in bronchoalveolar lavage fluid. To further examine the role of thromboxane A2, we studied the effect of a thromboxane A2 mimetic, U-46619, on airway responsiveness in five additional dogs. U-46619 in subthreshold doses (i.e., insufficient to increase base-line pulmonary resistance) caused a fourfold increase in airway responsiveness to acetylcholine. Subthreshold doses of histamine had no effect. These results suggest that thromboxane A2 may be an important mediator of O3-induced airway hyperresponsiveness.
Movement of ions and small solutes across endothelium and epithelium of perfused rabbit lungs
Authors: Effros R. M. , Mason G. R. , Silverman P. , Reid E. , Hukkanen J.
Published: December 2017

In situ and isolated fluid-filled rabbit lungs were used to study the transport of indicators between the air space and vascular compartments. These indicators were placed in either the perfusate or air spaces and samples were collected from the perfusate at intervals during a 1-h perfusion period. At the end of the hour, fluid was pumped out of the air space compartment into serial tubes and indicator concentrations were determined in both the air space and perfusion fluids. One hour after introducing the indicators into the air space, the relative decreases in solute concentration were (arranged from the greatest to the least decline): [14C]urea greater than 36Cl- = 125I- greater than 22Na+ greater than [3H]mannitol. The relative rates at which the indicators appeared in the perfusate were similar. When the indicators were placed in the perfusate, a similar relationship was observed in the increase in air space concentrations, but the loss of 22Na+ from the perfusate was similar to those of 36Cl- and 125I-. Losses of all indicators from the perfusate were two or more times those from the air spaces, and although the loss of [3H]mannitol from the perfusate was similar to that of 22Na+ for about 30 min, subsequent loss was much slower. Very little 125I-albumin traversed the tissue barrier, and the small changes in the concentrations of 125I-albumin in the air spaces suggested that little fluid movement had occurred. These studies suggest that the epithelium is less permeable to solutes than the endothelium and permits passage of anions at a faster rate than 22Na+.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of carbonic anhydrase by plasma of dogs and rabbits
Authors: Hill E. P.
Published: December 2017

Carbonic anhydrase (CA) activity was measured by the Bowes-Davis technique in diluted hemolysates of dog erythrocytes, rabbit erythrocytes, and dog lung tissue homogenates. Plasma (from the same animal) inhibited the CA activity in each case. For 1:16,700 dilution of dog erythrocytes, the CA catalyzed the CO2 hydration reaction by 5.3 +/- 0.4-fold above the uncatalyzed rate, and half that activity was inhibited by plasma concentrations of 0.44 +/- 0.05%. Similar rabbit CA concentrations were inhibited by plasma concentrations of 1.02 +/- 0.24%. CA from dog lung tissue homogenate is only partially inhibited by plasma even at high plasma concentrations, suggesting different isozymes, at least one of which is not inhibited by plasma. The results suggest that extrapolating from artificially perfused lungs or histological observations to in vivo conditions may not be valid, and the possibility of inhibition by plasma in at least some species should be considered.
Functional adaptation of diaphragm to chronic hyperinflation in emphysematous hamsters
Authors: Oliven A. , Supinski G. S. , Kelsen S. G.
Published: December 2017

Costal strips of diaphragmatic muscle obtained from animals with elastase-induced emphysema generate maximum tension at significantly shorter muscle fiber lengths than muscle strips from control animals. The present study examined the consequences of alterations in the length-tension relationship assessed in vitro on the pressure generated by the diaphragm in vivo. Transdiaphragmatic pressure (Pdi) and functional residual capacity (FRC) were measured in 22 emphysematous and 22 control hamsters 4–5 mo after intratracheal injection of pancreatic elastase or saline, respectively. In 12 emphysematous and 12 control hamsters Pdi was also measured during spontaneous contractions against an occluded airway. To allow greater control over muscle excitation, Pdi was measured during bilateral tetanic (50 Hz) electrical stimulation of the phrenic nerves in 10 emphysematous and 10 control hamsters. Mean FRC in the emphysematous hamsters was 183% of the value in control hamsters (P less than 0.01). During spontaneous inspiratory efforts against a closed airway the highest Pdi generated at FRC tended to be greater in control than emphysematous hamsters. When control hamsters were inflated to a lung volume approximating the FRC of emphysematous animals, however, peak Pdi was significantly greater in emphysematous animals (70 +/- 6 and 41 +/- 8 cmH2O; P less than 0.05). With electrophrenic stimulation, the Pdi-lung volume curve was shifted toward higher lung volumes in emphysematous hamsters. Pdi at all absolute lung volumes at and above the FRC of emphysematous hamsters was significantly greater in emphysematous compared with control animals. Moreover, Pdi continued to be generated by emphysematous hamsters at levels of lung volume where Pdi of control subjects was zero.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of impedance cardiography in the canine pup
Authors: Miles D. S. , Gotshall R. W. , Sexson W. R.
Published: December 2017

This study evaluated the use of the noninvasive technique of impedance cardiography to assess central hemodynamics in an animal model similar in size to the neonate. Seven canine pups 5–6 wk of age, with an average weight of 2.2 kg, were studied. To alter cardiac output (Q), the pups were given 12 and 8% O2 to breathe, which produced an arterial PO2 of 30 and 21 Torr, respectively. Q was obtained simultaneously by impedance and thermal dilution under both normoxic and hypoxic conditions. The average Q measured by impedance and thermal dilution were within 10% agreement and moderately correlated (r = 0.76). Impedance Q and stroke volume (SV) averaged 201 ml X min-1 X kg-1 and 2.8 ml, respectively. Thermal dilution Q and SV averaged 212 ml X min-1 X kg-1 and 2.9 ml, respectively. Individual responses to the hyoxemia were variable, but the impedance technique appeared to measure these individual responses as well as the thermal-dilution technique. These findings demonstrate that impedance cardiography may be suitable to assess either the absolute or relative changes in central hemodynamics. The use of this technique in critical care neonatal and pediatric medicine seems justified.
Pressure-flow effects on endurance of inspiratory muscles
Authors: McCool F. D. , McCann D. R. , Leith D. E. , Hoppin F. G.
Published: December 2017

We examined the effects of varying inspiratory pressures and flows on inspiratory muscle endurance. Four normal subjects performed voluntary forced breathing with various assigned inspiratory tasks. Duty cycle, tidal volume, and mean lung volume were the same in all tasks. Mean esophageal pressure, analogous to a pressure-time integral (PTes), was varied over a wide range. In each task the subject maintained an assigned PTes while breathing on one of a range of inspiratory resistors, and this gave a range of inspiratory flows at any given PTes. Inspiratory muscle endurance for each task was assessed by the length of time the task could be maintained (Tlim). For a given resistor, Tlim increased as PTes decreased. At a given PTes, Tlim increased as the external resistance increased and therefore as mean inspiratory flow rate (VI) decreased. Furthermore, for a given Tlim, PTes and VI were linearly related with a negative slope. We conclude that inspiratory flow, probably because of its relationship to the velocity of muscle shortening, is an independent variable importantly influencing endurance of the inspiratory muscles.
Quantitative measurement of regional pulmonary blood flow with positron emission tomography
Authors: Mintun M. A. , Ter-Pogossian M. M. , Green M. A. , Lich L. L. , Schuster D. P.
Published: December 2017

We have measured regional pulmonary blood flow (PBF) in normal dogs with positron emission tomography (PET) and 15O-labeled water (H2(15)O). The method is nondestructive, quantitative, and repeatable. To measure PBF, PET is used to measure both the initial and equilibrium distribution of lung activity after H2(15)O infusion. The data are then interpreted with a one-compartment mathematical model. Measurements of PBF in dogs with H2(15)O (PBF-water) were compared with PBF measured with 68Ga microspheres (PBF-MS), and a close correlation was observed: PBF-water = 0.82 PBF-MS + 25.4 (R = 0.97, n = 52). In another set of animals an important assumption of the method, namely that the tracer is fully extracted during a single pass through the lung, was demonstrated using a single-probe residue-detection technique. Computer simulations were performed to illustrate the sensitivity of the method to errors in the measured variables of tracer activity or tissue-blood partition coefficient. Results showed only small error magnification for the range of values observed in these studies.
Physiological dead space and effective parabronchial ventilation in ducks
Authors: Hastings R. H. , Powell F. L.
Published: December 2017

Gas exchange in avian lungs is described by a cross-current model that has several differences from the alevolar model of mammalian gas exchange [e.g., end-expired PCO2 greater than arterial PCO2 (PaCO2)]. Consequently the methods available for estimating effective ventilation and physiological dead space (VDphys) in alveolar lungs are not suitable for an analysis of gas exchange in birds. We tested a method for measuring VDphys in birds that is functionally equivalent to the conventional alveolar VDphys. A cross-current O2-CO2 diagram was used to define the ideal expired point (PEi) and VDphys was calculated as from the equation, VDphys = [(PEiCO2--PECO2)/PEiCO2]. VT, where VT is tidal volume. In seven Pekin ducks VDphys was 13.8 ml greater than anatomic dead space and measured changes in the instrument dead space volume. VDphys also reflected changes in ventilation-perfusion inequality induced by temporary unilateral pulmonary arterial occlusion. Bohr dead space, calculated by substituting end-expired PCO2 for PEiCO2, was insensitive to such inhomogeneity. Enghoff dead space, calculated by substituting PaCO2 for PEiCO2, is theoretically incorrect for cross-current gas exchange and was often less than anatomic dead space. We conclude that VDphys is a useful index of avian gas exchange and propose a standard definition for effective parabronchial ventilation (VP) analogous to alveolar ventilation (i.e., VP = VE--VDphys, where VE is total ventilation).
Effects of detraining on cardiovascular responses to exercise: role of blood volume
Authors: Coyle E. F. , Hemmert M. K. , Coggan A. R.
Published: December 2017

In this study we determined whether the decline in exercise stroke volume (SV) observed when endurance-trained men stop training for a few weeks is associated with a reduced blood volume. Additionally, we determined the extent to which cardiovascular function could be restored in detrained individuals by expanding blood volume to a similar level as when trained. Maximal O2 uptake (VO2max) was determined, and cardiac output (CO2 rebreathing) was measured during upright cycling at 50–60% VO2max in eight endurance-trained men before and after 2–4 wk of inactivity. Detraining produced a 9% decline in blood volume (5,177 to 4,692 ml; P less than 0.01) during upright exercise, due primarily to a 12% lowering (P less than 0.01) of plasma volume (PV; Evans blue dye technique). SV was reduced by 12% (P less than 0.05) and VO2max declined 6% (P less than 0.01), whereas heart rate (HR) and total peripheral resistance (TPR) during submaximal exercise were increased 11% (P less than 0.01) and 8% (P less than 0.05), respectively. When blood volume was expanded to a similar absolute level in the trained and detrained state (approximately 5,500 +/- 200 ml) by infusing a 6% dextran solution in saline, the effects of detraining on cardiovascular response were reversed. SV and VO2max were increased (P less than 0.05) by PV expansion in the detrained state to within 2–4% of trained values. Additionally, HR and TPR during submaximal exercise were lowered to near trained values. These findings indicate that the decline in cardiovascular function following a few weeks of detraining is largely due to a reduction in blood volume, which appears to limit ventricular filling during upright exercise.
Responses of ganglioglomerular nerve activity to respiratory stimuli in the cat
Authors: Lahiri S. , Matsumoto S. , Mokashi A.
Published: December 2017

We studied the responses of the ganglioglomerular nerve (GGN) efferents to brief periods of hypoxia and hypercapnia and to several levels of steady-state arterial PO2 and PCO2 and to intravascular injection of cyanide in thirteen anesthetized cats. The cats breathed spontaneously. A branch of the GGN which was cut close to the carotid body was divided into several filaments, and the activity of each filament was tested until clean and identifiable action potentials were obtained. The GGN efferent activity, breath-by-breath inspiratory volume, tracheal PO2 and PCO2 and arterial blood pressure were recorded simultaneously. We found that the GGN contained spontaneously active fibers which showed a range of responses to the respiratory stimuli. Fifty-eight percent of the filaments with dominant cardiovascular rhythm showed the least response to blood gas stimuli. Forty-two percent showed clear responses to hypoxia and hypercapnia. These responses developed slowly with the onset of the stimulus but decreased promptly with the withdrawal of the stimulus. These GGN efferents were also promptly stimulated by sodium cyanide. The steady-state response curve to hypoxia was hyperbolic and to hypercapnia it was linear. Some of these fibers showed stronger respiratory rhythms than others. The responses of these GGN efferents were associated with the respiratory responses to hypoxia and hypercapnia. For the same respiratory drive, however, the steady-state hypoxic stimulus elicited a greater GGN response than did hypercapnia.
Ear oximetry during combined hypoxia and exercise
Authors: Smyth R. J. , D'Urzo A. D. , Slutsky A. S. , Galko B. M. , Rebuck A. S.
Published: December 2017

Ear oximetry is widely used to detect arterial O2 desaturation during exercise in patients with cardiopulmonary disease. Although oximeters have been evaluated for accuracy, response time, and the influence of skin pigmentation, tests of their reliability have not been reported during strenuous exercise. Accordingly, we compared arterial O2 saturation (Sao2) measurements obtained by Hewlett-Packard (HP, model 47201A) and Biox II oximeters with those determined directly from arterial blood in six healthy volunteers during progressive exercise while rebreathing hypoxic gas mixtures. The relationship between the HP oximeter value and blood Sao2 was described by the equation: HP = 0.93 (Sao2) + 5.37 and for the Biox II: Biox = 0.55 (Sao2) + 38.97. With these equations, at a blood Sao2 value of 90%, the underestimation by both oximeters was less than 2%. At a blood value of 70%, the HP oximeter overestimated blood Sao2 by 0.7%, whereas the Biox II showed an overestimation of 10.7%. Below blood Sao2 of 83%, the Biox II tended to overestimate blood Sao2 by an amount greater than the error of the instrument, whereas the HP estimations were within the error of the instrument over all levels of blood Sao2 studied. We conclude that the HP oximeter provides valid estimates of Sao2 during exercise but that the Biox II oximeter, although reflecting qualitative changes in oxygenation that occur during exercise, does not provide accurate records of the degree of desaturation.
Critique on application of diaphragmatic time-tension index to spontaneously breathing humans
Authors: Barnard P. A. , Levine S.
Published: December 2017

Bellemare and Grassino (J. Appl. Physiol. 53: 1196–1206, 1982) have reported that the diphragmatic time-tension index (TTdi) (i.e., the product of mean transdiaphragmatic pressure/maximum transdiaphragmatic pressure and the inspiratory duty cycle) can be used as a predictor of diaphragmatic fatigue in humans. However, the publications of these authors do not directly address the question of whether inspiratory flow or transdiaphragmatic pressure should be used to calculate the inspiratory duty cycle. To gather data on this point, we computed TTdi by both methods in spontaneously breathing normal adult males (AMN) and age-matched males with chronic obstructive pulmonary disease (COPD) at rest and during treadmill exercise. During rest and exercise in both AMN and COPD, the fraction of the breathing cycle over which diaphragmatic tension was maintained (Tdi/TT) exceeded the fraction of the breathing cycle over which inspiratory airflow was maintained (TI/TT). Therefore, TTdi calculations using Tdi/TT were greater (P less than 0.05) than TTdi computations using TI/TT. However, this difference in TTdi values was relatively small (approximately 15%).
Description and validation of an ECG removal procedure for EMGdi power spectrum analysis
Authors: Levine S. , Gillen J. , Weiser P. , Gillen M. , Kwatny E.
Published: December 2017

We describe a cross-correlation procedure for removing contaminating electrocardiogram (ECG) complexes from the diaphragmatic electromyogram (EMGdi). First, the operator selects ECG templates from the EMGdi signal during expiratory intervals. Second, these templates are used to locate ECG complexes occurring during inspiratory EMGdi activity. Third, at the point of maximum correlation between the template and these ECG complexes, the template is adjusted in size and offset to “match” the ECG complex, and adjustments are determined by the linear regression coefficients. Finally, the modified template is subtracted from the EMGdi signal. To evaluate our method, we compared the power spectral density (PSD) obtained from processing EMGdi signals by our method with those obtained from the EMGdi signal in which ECG complexes had been removed by gating. Our results indicate that PSD obtained by these two different methods shows no statistically significant differences with respect to the following features: centroid frequency, median frequency, total power, standard deviation, skewness, and kurtosis.
Method of high-precision microsample blood and plasma mass densitometry
Authors: Hinghofer-Szalkay H.
Published: December 2017

The reliability of the mechanical oscillator technique (MOT) for blood and plasma mass density measurements on small samples is quantified in this paper. Sources of measurement errors that can reduce both the accuracy and precision of density determinations include storage of plasma samples, inhomogeneity of blood samples, and density reading before adequate temperature equilibration. Measurements on fractions from identical samples and repeated samplings from test subjects under steady-state conditions revealed a 10(-2) g/l reproducibility of density readings. The mean plasma density (PD) readings did not change significantly after up to 1-wk storage at +4 degrees C or up to 2 mo storage at -20 degrees C. The variability of the PD findings increased with storage time and were generally higher with storage at -20 degrees C, compared with +4 degrees C. Densitometers of different sizes were used to evaluate rheological influences on blood density (BD) readings. Linear correlations between PD and plasma protein concentration, between BD and blood hemoglobin concentration, and between erythrocyte density and mean corpuscular hemoglobin concentration were significant (P less than 0.001). Rapid density measurements with up to 10(-2) g/l reliability on small (less than 0.1 ml) volumes of biological fluids and continuous blood densitometry can be performed with use of the MOT.
Velocity profiles in central airways with endotracheal intubation: a model study
Authors: Menon A. S. , Weber M. E. , Chang H. K.
Published: December 2017

Steady inspiratory velocity profiles were measured at two flow rates in a 3:1 scale model of the human central airways in the presence of five modes of endotracheal intubation. The presence of an orifice or a short endotracheal tube had no significant effect on the velocity profiles distal to the carina. Long endotracheal tubes change the profiles in both main bronchi. A significant peak occurred in the frontal plane near the walls, and the maximum velocity in the airway was almost identical to the endotracheal tube center-line velocity. The flow impinging on the medial wall of the main bronchus was redirected up around the anterior and posterior walls yielding bipeak velocity profiles in the sagittal plane. A tube placed eccentrically in the trachea over the right main bronchus did not alter the velocity profiles in the left main bronchus, suggesting a redirection of flow over the carina into the left lung. An endobronchial tube at the mouth of the right main bronchus did change the shape of the velocity profiles in the left main bronchus. In the left upper lobar bronchus the presence of trachea intubation had no effect on the velocity profiles. However, in the right upper lobar bronchus, the long endotracheal tube flattened the velocity profiles from the strongly skewed ones seen in the absence of the endotracheal inserts. These results not only are relevant to distribution of ventilation and aerosol particle deposition, but also have strong implications in intrapulmonary gas mixing, especially when high-frequency low tidal-volume ventilation is involved.
Effect of cardiogenic oscillations on gas mixing during tracheal insufflation of oxygen
Authors: Burwen D. R. , Watson J. , Brown R. , Josa M. , Slutsky A. S.
Published: December 2017

In a previous study using tracheal insufflation of O2 (TRIO) at a rate of 2 l/min, we showed that anesthetized paralyzed dogs could be adequately oxygenated for up to 5 h, albeit with hypercapnia (mean arterial PCO2 approximately 160 Torr). To examine the contribution of cardiogenic oscillations in producing this gas exchange, we studied seven anesthetized paralyzed dogs weighing between 19.6 and 25.5 kg and quantified gas transport by analyzing continuous N2-washout curves in vivo and postmortem. We found that cardiogenic oscillations increase gas mixing roughly fourfold and that this value was independent of insufflation flow rate (0.2–10.0 l/min). Our results lend indirect evidence that, with regard to gas exchange, there are two mechanistically different zones in the lung during TRIO. One zone, located in the more peripheral areas of the lung, is dominated by the effects of cardiac oscillations and molecular diffusion and accounts for the increase in gas mixing found in the alive vs. dead dog. A second zone, close to the insufflated jet of O2, uses convective streaming to produce greater gas mixing at higher flows.
Cutaneous vascular responses to heat simulated at a high altitude of 5,600 m
Authors: Sagawa S. , Shiraki K. , Konda N.
Published: December 2017

Six healthy young men were studied in a high-altitude chamber during a 60-min heat exposure at a simulated altitude of 5,600 m or 0.5 atmosphere absolute (ATA). The heat load was provided by increasing the chamber temperature to 38 degrees C at the rate of 1 degree C/min after a 60-min equilibrium period at thermoneutrality (28 degrees C). Our question was whether or not hypoxia causes differential changes in regional cutaneous circulation during heat exposure. Skin blood flow in the forearm (FBF) and the finger (FiBF), temperatures of the esophagus (Tes) and of the skin, and cardiac output (CO) were measured during the heat exposure at 0.5 ATA and at the sea level (1 ATA). During the equilibrium period, hypoxia increased the mean skin temperature and mean heat transfer coefficient, as well as FBF and forearm vascular conductance. The increased blood flow in the cutaneous circulation during the hypoxic exposure may reflect cutaneous vasodilation and vasoconstriction in other regions of the body, since there was no alteration in CO and total peripheral resistance. During heat exposure, Tes rose faster at high altitude than at sea level. However, at the end of the 60-min heat exposure, all thermal as well as circulatory parameters showed no difference between the two altitudes, except for the FiBF. An attenuated vasodilation in the fingers during heat exposure at high altitude suggests differential vascular controls and possible impairment of thermoregulation when additional stress, such as heat, is imposed. The data suggest that cutaneous blood flow during heat exposure is not uniform throughout the entire skin in a hypoxic environment.
Transvascular clearance and distribution of charged macromolecules in ANTU lung injury
Authors: Parker J. C.
Published: December 2017

Tissue uptake, extravascular distribution volumes, and plasma-lymph equilibration of two isozymes of lactate dehydrogenase (LDH) were labeled with radioiodine and studied in dogs with either normal or injured lungs. Cationic LDH 5 [isoelectric point (pI) = 7.9] was initially cleared from plasma by lung tissue at a rate 1.61 times higher (9.3 vs. 5.8 X 10(-3) ml X min-1 X g-1 extravascular wet wt) than anionic LDH 1 (pI = 5.0). LDH 5 also had a significantly higher extravascular distribution volume but equilibrated more slowly between plasma and pulmonary lymph (t1/2 = 120 min) than LDH 1 (t1/2 = 78 min) in normal lungs. Respective lymph-to-plasma ratios were 0.53 and 0.43 for LDH 1 and LDH 5 after 4 h of infusion. Infusion of the isozymes 2 h after injection of alpha-naphthylthiourea (ANTU) resulted in larger initial tissue plasma clearances for both isozymes compared with control, but greater relative tissue plasma clearances and extravascular distribution volumes for LDH 5 compared with LDH 1. Plasma-lymph equilibration half times of LDH 5 and LDH 1 were reduced after ANTU to 50 min and 41 min, respectively, whereas the respective alveolar fluid-to-plasma ratios of the two isozymes at termination of the ANTU experiments were 0.56 and 0.84. These data suggest that the fixed anionic charges on endothelial cell surfaces, intercellular junctions, basement membranes, and interstitial structures act much like a cation exchange gel to rapidly take up cationic proteins and retard the plasma-lymph equilibration of these proteins relative to anionic proteins of the same size.(ABSTRACT TRUNCATED AT 250 WORDS)
Maternal hypoxic ventilatory response, ventilation, and infant birth weight at 4,300 m
Authors: Moore L. G. , Brodeur P. , Chumbe O. , D'Brot J. , Hofmeister S. , Monge C.
Published: December 2017

To test the hypothesis that increased hypoxic ventilatory responsiveness (HVR) raised maternal ventilation and arterial oxygenation during high-altitude pregnancy and related to the birth weight of the offspring, we studied 21 residents of Cerro de Pasco, Peru (4,300 m), while eight of them were 36 +/- 0 wk pregnant and 15 of them 13 +/- 0 wk postpartum. HVR was low in the nonpregnant women (mean +/- SE shape parameter A = 23 +/- 8) but increased nearly fourfold with pregnancy (A = 87 +/- 17). The increase in HVR appeared to account for the 25% rise in resting ventilation with pregnancy (delta VE observed = 2.4 +/- 0.7 l/min BTPS vs. delta VE predicted from delta HVR = 2.6 +/- 1.7 l/min BTPS, P = NS). Hyperoxia decreased ventilation in the pregnant women (P less than 0.01) to levels similar to those measured when nonpregnant. The increased ventilation of pregnancy raised arterial O2 saturation (SaO2) from 83 +/- 1 to 87 +/- 0%, and SaO2 was correlated positively with HVR in the pregnant women. The rise in SaO2 compensated for a 0.9 g/100 ml decrease in hemoglobin concentration to preserve arterial O2 content at levels present when nonpregnant. Cardiac output in the 36th wk of pregnancy did not differ significantly from values measured postpartum. The increase in HVR correlated positively with infant birth weight. An increase in HVR may be an important contributor to increased maternal ventilation with pregnancy and infant birth weight at high altitude.
Effects of beta-blockade on exercise capacity of trained and untrained men: a hemodynamic comparison
Authors: Joyner M. J. , Freund B. J. , Jilka S. M. , Hetrick G. A. , Martinez E. , Ewy G. A. , Wilmore J. H.
Published: December 2017

To study the effects of cardiovascular fitness on hemodynamic responses to exercise during beta-adrenergic blockade (BAB), submaximal [60% of maximum O2 uptake (VO2max)] and maximal treadmill exercise data were collected in 11 trained (T, VO2max 63.3 ml X kg-1 X min-1, 26.8 yr) and 11 untrained (UT, VO2max 44.5 ml X kg-1 X min-1, 25.0 yr) male subjects. Subjects completed two maximal control tests followed by a randomized, double-blind series of maximal tests after 1-wk treatments with placebo (PLAC), propranolol (PROP, 160 mg/day, beta 1- and beta 2-blockade), and atenolol (ATEN, 100 mg/day, beta 1-blockade). Treatments were separated by 1-wk washout periods. At 60% of control VO2max T and UT subjects experienced no reductions in O2 uptake (VO2) with either drug. Submaximal heart rate (HR, beats/min) was 134.8 PLAC, 107.0 PROP, 107.9 ATEN (P less than 0.05 both drugs vs. PLAC) in T subjects and 141.1 PLAC, 106.1 PROP, and 105.0 ATEN (P less than 0.05 both drugs vs. PLAC) in UT subjects. Cardiac output (1/min) for T was 17.3 PLAC, 16.9 PROP, 16.5 ATEN (P less than 0.05 ATEN vs. PLAC in T only) and for UT it was 12.2 (PLAC), 11.7 (PROP), 11.5 (ATEN) (P less than 0.05 both drugs vs. PLAC in UT). Stroke volume increased from 129.8 ml (PLAC) to 158.6 (PROP) and 156.2 (ATEN) in T (P less than 0.05 both drugs vs. PLAC) and from 86.8 (PLAC) to 110.0 (PROP) and 109.8 (ATEN) (P less than 0.05 both drugs vs. PLAC) in UT. The increases in stroke volume (SV) were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of pressure on uptake and release of calcium by brain synaptosomes
Authors: Gilman S. C. , Kumaroo K. K. , Hallenbeck J. M.
Published: December 2017

Uptake of radioactive calcium from guinea pig brain fractions enriched in synaptosomes could be significantly and reproducibly decreased by exposure to high pressure. Calcium efflux from preloaded synaptosomes was unaffected by pressure exposure. It was hypothesized that the development of pressure-induced encephalopathy may be related to an effect of pressure on the central nervous system calcium transport system.
Upper airway stability and apnea during nasal occlusion in newborn infants
Authors: Cohen G. , Henderson-Smart D. J.
Published: December 2017

Brief end-expiratory airway occlusions were performed in 22 preterm babies, 17 with and 5 without clinical apnea, and 4 full-term babies, 1 with Pierre-Robin syndrome. Airway stability was evaluated by comparing pressures measured simultaneously in the chest and nasal passages during occluded inspiratory efforts. The airway remained patent throughout all 301 trials in 20 babies during rapid-eye-movement (REM) and quiet sleep. Airway closure occurred during 31/102 trials in 6 babies (5 preterm and 1 term with Pierre-Robin syndrome), more commonly in quiet than in REM sleep. Overall and within individuals, mean closing pressures were significantly lower than the mean maximum falls in airway pressure recorded during occlusions without closure. Mixed-obstructive and obstructive apnea was significantly more frequent in babies with airway closure than in those without (5.3 +/- 4.0 vs. 0.4 +/- 0.8 episodes/h). Pauses in breathing greater than or equal to 3 s occurred during 28% of occlusions in preterm infants and 2% of occlusions in full-term babies. There was no significant difference between the mean frequency of pauses during occlusion and during the preceding control period or in the incidence of pauses in occlusions with vs. those without closure. It is concluded that the airway of most preterm and full-term babies is remarkably stable under load. Intermittent closure occurs in certain infants and may be related to airway muscle dysfunction.
Muscle lipoprotein lipase activity in voluntarily exercising rats
Authors: Bagby G. J. , Johnson J. L. , Bennett B. W. , Shepherd R. E.
Published: December 2017

Voluntary exercise of rats in freely rotating work wheels has been extensively used, but muscle adaptations that result from such exercise training are poorly documented. The purpose of this study was to determine whether the exercise performed by voluntarily active rats would increase succinate dehydrogenase or lipoprotein lipase activities in the soleus muscle (SM) or the red portion of the vastus lateralis muscle (RV). In SM the activities of these two enzymes were not increased after 7 or 16 wk of voluntary exercise. Succinate dehydrogenase activity in RV was moderately increased after 7 and 16 wk of voluntary activity (P less than 0.05). Substantial increases occurred in RV lipoprotein lipase activity (P less than 0.01). The increase in RV lipoprotein lipase activity was positively related to distance run by the rats. The results indicate that only small muscle-dependent increases in mitochondrial enzymes occur in rats allowed to exercise voluntarily in rodent work wheels. Voluntary exercise training induced a selective increase in lipoprotein lipase activity in a muscle containing a high percentage of fast-twitch red fibers, a response absent in a muscle containing a predominance of slow-twitch red fibers. It is unlikely that this differential response can be explained by exercise-induced changes in plasma hormone concentrations involved in the regulation of lipoprotein lipase.
Exercise conditioning increases rat myocardial calcium uptake
Authors: Levine S. N. , Kinasewitz G. T.
Published: December 2017

To investigate potential mechanisms underlying the enhanced myocardial performance consequent to exercise training, the adrenergic receptors of myocardial tissue and Ca2+ uptake into sarcoplasmic reticulum-enriched fractions from exercise conditioned animals were compared with that of sedentary controls. Female Wistar rats were exercised by swimming 30 min (5 days/wk) for 12 wk. Exercise conditioning was effective in producing myocardial hypertrophy, as reflected by an increase in heart weight (1.179 +/- 0.022 vs. 1.031 +/- 0.020 g, P less than 0.001) and heart weight-to-body weight ratio (3.29 +/- 0.06 vs. 2.77 +/- 0.05 X 10(-3), P less than 0.001) but no difference in body weight. Despite the myocardial hypertrophy, neither the affinity nor the density of the alpha 1-adrenergic receptors or the beta-adrenergic receptors determined by Scatchard analysis of the ligands [3H]prazosin and [3H]dihydroalprenolol were significantly different between the two groups. The basal Ca2+ uptake into the sarcoplasmic reticulum was also similar (9.90 +/- 0.97 vs. 9.04 +/- 0.75 nmol/mg protein/min), but the addition of calmodulin produced a significantly greater increment in Ca2+ uptake into sarcoplasmic reticulum from the exercised-conditioned animals (1.90 +/- 0.23 vs. 1.21 +/- 0.19 nmol/mg protein/min, P less than 0.03). The adenosine triphosphatase (ATPase) activities of the sarcoplasmic reticulum-enriched fractions of the two groups were similar. We conclude that exercise conditioning produces an enhancement of calmodulin-mediated calcium uptake that is independent of any effect on Ca2+-ATPase.
Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity
Authors: Coon R. L. , Zuperku E. J. , Kampine J. P.
Published: December 2017

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.
Lung beta-adrenoreceptor blockade affects perinatal surfactant release but not lung water
Authors: McDonald J. V. , Gonzales L. W. , Ballard P. L. , Pitha J. , Roberts J. M.
Published: December 2017

We induced beta-adrenergic receptor blockade at 28 days gestation in the fetal rabbit with an irreversible beta-antagonist, bromace-tylalprenolomenthane (BrAlp). There was a marked decrease in concentration of available receptors in lung with increasing doses of BrAlp. BrAlp treatment decreased isoproterenol, but not prostaglandin, stimulated adenosine 3′,5′-cyclic monophosphate (cAMP) generation in lung minces, and had no effect on activation of adenylate cyclase through non-beta-receptor-mediated components of the cyclase system in particulate preparations. Phospholipid recovery via lung lavage was significantly less from treated fetuses than from controls in groups delivered by cesarean section at 30 days (-31%) or vaginally at 31 days (-34%) and not allowed to air breathe. However, if fetuses from either group were allowed to air breathe, the difference was abolished. BrAlp treatment did not affect the phospholipid composition in lavage fluid, the rate of phosphatidylcholine synthesis, or tissue content of total or saturated phosphatidylcholine. Beta-adrenergic receptor blockade did not produce a significant change in lung water content either at or after birth regardless of the route of delivery. These data indicate that endogenous catecholamines play a role in surfactant secretion in both the fetal and newborn rabbit. We found no effects of BrAlp treatment on lung water, suggesting perhaps a less important role of endogenous catecholamines or that fewer receptors are required for this response than remained after treatment.