bluuebunny/crossref_metadata_2025 huggingface dataset:
Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep
Authors: Murai D. T. , Lee C. C. , Wallen L. D. , Kitterman J. A.
Published: December 2017

The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0–5 and 6–13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements.
Relation of blood-free to blood-inclusive postmortem lung water measurements in sheep
Authors: Collins J. C. , Newman J. H. , Wickersham N. E. , Vaughn W. K. , Snapper J. R. , Harris T. R. , Brigham K. L.
Published: December 2017

Our purpose was to see if the postmortem weight ratio of extravascular lung water to blood-free dry lung (blood-free ratio) was related to similar ratios in blood-inclusive lung and in blood. We developed linear regressions of blood-free ratio on ratios for blood-inclusive lung and blood together and for blood-inclusive lung alone for 73 sheep studied under 11 different protocols and for two subgroups of sheep, one with plasma space expansion and the other without expansion. The relation of ratios of blood-free to blood-inclusive lungs was different between the two subgroups. Although all regressions were highly correlated, the fits of the blood-free ratio on ratios for blood-inclusive lung and blood together were better than for blood-inclusive lung alone. The mean error of prediction of extravascular lung water for all sheep was significantly less for the regression of blood-free ratio on ratios for blood and blood-inclusive lung together (11 g) than for blood-inclusive lung alone (18 g). This study shows that weights of lung homogenate and blood samples before and after simple oven drying can be used to provide accurate inexpensive estimates of postmortem extravascular lung water.
Pleural space thickness in situ by light microscopy in five mammalian species
Authors: Lai-Fook S. J. , Kaplowitz M. R.
Published: December 2017

The thickness of the pleural space was measured by a focusing method using a light microscope (X157, 2.5-micron depth of focus). In anesthetized animals, thin transparent parietal pleural windows were made by dissection of intercostal muscle. Multiple postmortem measurements were made of the combined thickness of the pleural space and the window by focusing in sequence on the lung surface and on 1- to 2-micron tantulum particles sprayed on the window. The window thickness was measured after creating a pneumothorax and retracting the lungs. In supine rabbits the pleural space measured at various heights on the costal surface was of uniform thickness (16 micron) except for a thicker region (62 micron) located within 3 mm of the most dependent part of the lung. The thicker region reverted to the uniform thickness after it was placed in a nondependent position by inverting the animal from the supine to prone position, indicating fluid drainage by gravity. In the prone position near midchest, pleural space thickness (t) averaged 6.9 micron in the mouse, 10.2 in the rat, 17.2 in the rabbit, 18.3 in the cat, and 23.6 in the dog. Animals of larger body mass (M, kg) had a wider pleural space: t = 13.1 X M0.20. There was no contact between the two pleurae, indicating that fluid lubrication facilitates sliding between the lung and chest wall. Based on the t vs. M relationship and estimates of the viscous flow of pleural liquid, pleural fluid exchange rate would be proportional to body mass and the work of sliding as a fraction of the work of breathing would be smaller in larger animals.
Photographic measurement of pleural surface motion during lung oscillation
Authors: Lehr J. L. , Butler J. P. , Westerman P. A. , Zatz S. L. , Drazen J. M.
Published: December 2017

The regional pleural surface expansion of an excised dog lung was measured during high-frequency ventilation (HFV) using synchronized stroboscopic photography to stop lung motion at 20 evenly spaced intervals over a respiratory cycle during ventilation at 1 Hz with a volume of 100 ml, 15 Hz with 100 ml, or 30 Hz with 50 ml. The lungs were also photographed during quasi-static deflation. The pleural surface was marked with ink dots to form 84 approximately square figures. The side lengths and areas of each of the 84 “squares” were measured for each frame of each photo sequence. At 1 Hz and during the quasi-static deflation the lung ventilated nearly synchronously, although minor nonuniformities were noted on both small and large length scales. At 15 and 30 Hz, the lung expanded asynchronously and nonuniformly, with a 78% increase in surface expansion per 100 ml of tracheal tidal volume, as frequency was increased from 1 to 30 Hz. These nonuniformities in expansion suggest marked interregional airflow and elastic wave propagation in the parenchyma during HFV.
Interrupter technique for measurement of respiratory mechanics in anesthetized humans
Authors: Gottfried S. B. , Higgs B. D. , Rossi A. , Carli F. , Mengeot P. M. , Calverly P. M. , Zocchi L. , Milic-Emili J.
Published: December 2017

Flow (V), volume (V), and tracheal pressure (Ptr) were measured throughout a series of brief (100 ms) interruptions of expiratory V in six patients during anesthesia (halothane-N2O) and anesthesia-paralysis (succinylcholine). For the latter part of spontaneous expiration and throughout passive deflation during muscle paralysis, a plateau in postinterruption Ptr was observed, indicating respiratory muscle relaxation. Under these conditions, passive elastance of the total respiratory system (Ers) was determined as the plateau in postinterruption Ptr divided by the corresponding V. The pressure-flow relationship of the total system was determined by plotting the plateau in Ptr during interruption against the immediately preceding V. Ers averaged 23.5 +/- 1.9 (SD) cmH2O X l-1 during anesthesia and 25.5 +/- 5.4 cmH2O X l-1 during anesthesia-paralysis. Corresponding values of total respiratory system resistance were 2.0 +/- 0.8 and 1.9 +/- 0.6 cmH2O X l-1 X s, respectively. Respiratory mechanics determined during anesthesia paralysis using the single-breath method (W.A. Zin, L. D. Pengelly, and J. Milic-Emili, J. Appl. Physiol. 52: 1266–1271, 1982) were also similar. Early in spontaneous expiration, however, Ptr increased progressively during the period of interruption, reflecting the presence of gradually decreasing antagonistic (postinspiratory) pressure of the inspiratory muscles. In conclusion, the interrupter technique allows for simultaneous determination of the passive elastic as well as flow-resistive properties of the total respiratory system. The presence of a plateau in postinterruption Ptr may be employed as a useful and simple criterion to confirm the presence of respiratory muscle relaxation.
Accurate measurement of N2 volumes during N2 washout requires dynamic adjustment of delay time
Authors: Brunner J. X. , Wolff G. , Cumming G. , Langenstein H.
Published: December 2017

Measurement of respiratory gas composition by a mass spectrometer lags behind the measurement of gas flow. To obtain specific gas volumes (e.g., the N2 volume) by multiplication and integration of concentration and flow, one has to synchronize flow and concentration signals using the delay time (TD) of the gas analyzer. During the N2 washout, however, gas composition changes and causes alterations of TD. This leads to errors of up to 17 and 70% in the measurement of pulmonary volume and series dead space, respectively, in an ideally mixing physical model of the lung. On the basis of Poiseuille's law and exact measurements of the characteristics of the capillary it is possible to adjust the synchronization, which improves the absolute accuracy considerably.
Delayed onset muscle soreness following repeated bouts of downhill running
Authors: Byrnes W. C. , Clarkson P. M. , White J. S. , Hsieh S. S. , Frykman P. N. , Maughan R. J.
Published: December 2017

Perceived muscle soreness ratings, serum creatine kinase (CK) activity, and myoglobin levels were assessed in three groups of subjects following two 30-min exercise bouts of downhill running (-10 degrees slope). The two bouts were separated by 3, 6, and 9 wk for groups 1, 2, and 3, respectively. Criterion measures were obtained pre- and 6, 18, and 42 h postexercise. On bout 1 the three groups reported maximal soreness at 42 h postexercise. Also, relative increases in CK for groups 1, 2, and 3 were 340, 272, and 286%, respectively. Corresponding values for myoglobin were 432, 749, and 407%. When the same exercise was repeated, significantly less soreness was reported and smaller increases in CK and myoglobin were found for groups 1 and 2. For example, the percent CK increases on bout 2 for groups 1 and 2 were 63 and 62, respectively. Group 3 demonstrated no significant difference in soreness ratings, CK activities, or myoglobin levels between bouts 1 and 2. It was concluded that performance of a single exercise bout had a prophylactic effect on the generation of muscle soreness and serum protein responses that lasts up to 6 wk.
Airway protective and abdominal expulsive mechanisms in infantile regurgitation
Authors: Menon A. P. , Schefft G. L. , Thach B. T.
Published: December 2017

To define the expulsive and airway protective mechanisms involved in infantile regurgitation, we studied 15 infants (9 premature and 6 mature infants) with histories of frequent postfeeding regurgitation. In 13 infants we recorded pharyngeal pressure, pH, nasal and oral airflow, and abdominal respiratory movements. In two additional infants we recorded gastric pressure. In eight infants observations were made without intrapharyngeal recording devices. Distinctive abdominal regurgitation movements (RMs) immediately preceded 84% of regurgitation episodes. These RMs were characterized by one or more large brief increases in abdominal girth. In the two infants with gastric pressure recordings, large increases in gastric pressure, with duration and frequency characteristics similar to the RMs, immediately preceded regurgitation episodes. Thus, in contrast to the generally accepted concept that flow of gastric contents out of the stomach is passive during infantile regurgitation, we documented an active expulsive mechanism similar to that of vomiting in the adult. In all regurgitation episodes, upper airway closure occurred at the onset of the regurgitation movement. One or more swallows occurred immediately following RMs and prior to airway reopening in 97% of regurgitation episodes. Brief respiratory pauses occurred during regurgitation in all premature infants and occasionally in mature infants. Nasal regurgitation, coughing, and sneezing occasionally accompanied regurgitation episodes. Thus upper airway closure and swallowing prior to airway reopening were the most frequently observed airway protective mechanisms during regurgitation. Brief respiratory pauses, sneezing, and coughing may be secondary airway protective mechanisms. Nasal regurgitation likely represents immaturity of airway protective mechanisms.
Postnatal maturation of respiration in intact and carotid body-chemodenervated lambs
Authors: Bureau M. A. , Lamarche J. , Foulon P. , Dalle D.
Published: December 2017

The contribution of the carotid body chemoreceptor to postnatal maturation of breathing was evaluated in lambs from 7 to 70 days of age. The study was conducted by comparing the eupneic ventilation and resting pneumograms in intact conscious lambs with those of lambs that were carotid body chemodenervated (CBD) at birth. In comparison to the 1-wk-old intact lambs, the CBD lambs had significant decreases in minute ventilation (VE, 313 vs. 517 ml/kg), tidal volume (VT, 7.2 vs. 10.5 ml/kg), respiratory rate (f, 44 vs. 51 breaths/min), and occlusion pressure (P0.1, 2.8 vs. 7.2 cmH2O). Arterial PO2's were 59 vs. 75 Torr (P less than 0.05) and arterial PCO2's 47 vs. 36 Torr (P less than 0.05), respectively, in CBD and intact lambs. In intact lambs from 7 to 70 days, resting VE decreased progressively from 517 to 274 ml/kg (P less than 0.01) due to a fall in VT, mean inspiratory flow (VT/TI), and f, whereas the ratio of inspiratory time to total breath duration remained constant. P0.1 decreased from 7.2 to 3.9 cmH2O from 7 to 42 days. In contrast the CBD lambs experienced only minimal changes in VE, VT, VT/TI, and f during the same period. VE only decreased from 313 to 218 and P0.1 from 2.8 to 2.4 cmH2O. In contrast to that of intact lambs the resting pneumogram of CBD lambs remained relatively fixed from 7 to 70 days. Three CBD lambs died unexpectedly, without apparent cause, in the 4th and 5th wk of life.
Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males
Authors: Fleg J. L. , Tzankoff S. P. , Lakatta E. G.
Published: December 2017

Although plasma norepinephrine (NE) increases with age in response to a variety of submaximal adrenergic stimuli, the effect of age on plasma catecholamine levels during maximal aerobic effort and during submaximal work at a fixed percent of peak O2 consumption (VO2) is unknown. We therefore measured NE, epinephrine (E), and VO2 at rest and during graded maximal treadmill exercise in 24 healthy male volunteers (ages 22–77 yr) from the Baltimore Longitudinal Study of Aging who were rigorously screened to exclude the presence of cardiovascular disease. At rest neither heart rate (HR) nor VO2 were age related. Resting NE (pg/ml) was not age related, but resting E (pg/ml) was higher in male subjects 68–77 yr old (group III) than in those aged 22–37 (group I) or 44–55 yr (group II), P less than 0.01. Maximal HR (beats/min) showed a strong inverse relationship to age (203.5 - 0.65 age, r = -0.80, P less than 0.001). Peak VO2 in milliliters per kilogram total body weight per minute decreased with age (47.7 - 0.23 age, r = -0.71, P less than 0.001). At maximal effort both NE (P less than 0.01) and E (P less than 0.05) were higher in group III than in either of the younger groups. At submaximal work levels NE and E also increased with age, and when normalized for relative effort at loads between 45 and 80% of peak VO2 both NE and E were higher in the group III male subjects, although statistical significance was reached for NE (P less than 0.01) but not for E (P = 0.09).
Effect of exercise on epinephrine turnover in trained and untrained male subjects
Authors: Kjaer M. , Christensen N. J. , Sonne B. , Richter E. A. , Galbo H.
Published: December 2017

The kinetics underlying plasma epinephrine concentrations were studied. Six athletes (T) and six sedentary males (C) were given intravenous infusions of 3H-labeled epinephrine, after which arterial blood was drawn. They rested sitting and bicycled continuously to exhaustion (60 min at 125 W, 60 min at 160 W, 40 min at 200 W, and 240 W to the end). Work time was 154 +/- 13 (SE) (T) and 75 +/- 6 (C) min. At rest, epinephrine clearance was identical [28.4 +/- 1.3 (T) vs. 29.2 +/- 1.8 (C) ml . kg-1 . min-1], but plasma concentration [1.42 +/- 0.27 (T) vs. 0.71 +/- 0.16 (C) nmol . l-1] and, accordingly, secretion [2.9 +/- 0.7 vs. 1.5 +/- 0.4 nmol . min-1] were higher (P less than 0.05) in T than C subjects. Epinephrine clearance was closely related to relative work load, decreasing from 15% above the basal level at 30% of maximal O2 uptake (VO2 max) to 22% below at 76% of VO2 max. Epinephrine concentrations increased much more with work intensity than could be accounted for by changes in clearance and were, at exhaustion, higher (P less than 0.05) in T (7.2 +/- 1.6) than in C (2.5 +/- 0.7 nmol . l-1) subjects despite similar glucose, heart rate, and hematocrit values. At a given load, epinephrine clearance rapidly became constant, whereas concentration increased continuously. Forearm extraction of epinephrine invalidated use of blood from a cubital vein or a hand vein arterialized by hot water in turnover measurements. During exercise, changes in epinephrine concentrations reflect changes in secretion rather than in clearance. Training may increase adrenal medullary secretory capacity.
Central adaptation to inspiratory-inhibiting expiratory-prolonging vagal input
Authors: Younes M. , Polacheck J.
Published: December 2017

We reported earlier on the changes in excitability of central respiratory switching mechanisms in the course of a brief inspiratory-inhibiting vagal stimulus (J. Appl. Physiol. 50: 1183–1192, 1981). To further define the dynamics of central processing of such input we studied the changes in the excitability of timing mechanisms in the immediate (less than 1.0 s) and late (1–20 s) periods after stimulus removal. We also examined the changes in respiratory timing in the course of protracted (greater than 20 s) stimulation. Studies were done using pentobarbital-anesthetized cats. For studies involving long-term stimulation or late off responses, cats were paralyzed, vagotomized, carotid denervated, and artificially ventilated. We found that the inspiratory inhibitory influence of a brief stimulus continues, in a declining fashion, for 0.3–10 s after removal of the stimulus. This was followed by a paradoxical response, inspirations were prolonged and expirations were shortened, which was maximal 1–2 s after stimulus removal and which declined gradually over a period of 6–16 s. There was progressive decline in inspiratory-shortening expiratory-prolonging influence in the course of sustained stimuli. These results indicate substantial adaptation in the course of even brief stimuli and provide an explanation for inspiratory-expiratory duration and expiratory-inspiratory duration linkages.
Effect of high-frequency ventilation on gas exchange and pulmonary vascular resistance in lambs
Authors: Truog W. E. , Standaert T. A.
Published: December 2017

We studied the effects of conventional mechanical ventilation (CMV) (15 ml/kg tidal volume delivered at 18–25 breaths/min) and high-frequency oscillatory ventilation (HFOV) (less than or equal to 2 ml/kg delivered at 10 Hz) on pulmonary hemodynamics and gas exchange during ambient air breathing and hypoxic gas breathing in 10 4-day-old lambs. After instrumentation and randomization to either HFOV or CMV the animals breathed first ambient air and then hypoxic gas (inspired O2 fraction = 0.13) for 20 min. The mode of ventilation was then changed, and the normoxic and hypoxic gas challenges were repeated. The multiple inert gas elimination technique was utilized to assess gas exchange. There was a significant increase with HFOV in mean pulmonary arterial pressure (Ppa) (20.1 +/- 4.2 vs. 22 +/- 3.8 Torr, CMV vs. HFOV, P less than 0.05) during ambient air breathing. During hypoxic gas breathing Ppa was also greater with HFOV than with CMV (29.5 +/- 5.7 vs. 34 +/- 3.1 Torr, CMV vs. HFOV, P less than 0.05). HFOV reduced pulmonary blood flow (Qp) during ambient air breathing (0.33 +/- 0.11 vs. 0.28 +/- 0.09 l . kg-1 . min-1, CMV vs. HFOV, P less than 0.05) and during hypoxic gas breathing (0.38 +/- 0.11 vs. 0.29 +/- 0.09 l . kg-1 . min-1, P less than 0.05). There was no significant difference in calculated venous admixture for sulfur hexafluoride or in the index of low ventilation-perfusion lung regions with HFOV compared with CMV.
Regional differences in erythrocyte transit in normal lungs
Authors: Hogg J. C. , Martin B. A. , Lee S. , McLean T.
Published: December 2017

We measured regional blood volume and flow in the lungs of nine mongrel dogs. The time taken for the erythrocytes to transit through individual lung regions was calculated from the relationship t = V/Q, where V is blood volume and Q is flow. The data show that the total pulmonary blood volume was 82 +/- 6 ml and that the average time spent in the pulmonary vascular bed was 2.86 +/- 0.31 s. The frequency distribution of the transit times ranged from 0.41 to 6 s in the experiment with the shortest mean transit (1.62 s) and from 0.9 to greater than 20 s in the experiment with the longest mean transit time (4.6 s). The regional data show that the longer transit times were in the upper lung and that expansion of the blood volume as flow increased down the lung prevented an excessive shortening of the transit time. We conclude that increasing regional blood flow is associated with an expansion of regional blood volumes so that the transit times remain relatively constant.
Antagonism by theophylline of respiratory inhibition induced by adenosine
Authors: Eldridge F. L. , Millhorn D. E. , Kiley J. P.
Published: December 2017

The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites.
Relationship for gas transport during high-frequency ventilation in dogs
Authors: Venegas J. G. , Custer J. , Kamm R. D. , Hales C. A.
Published: December 2017

Alveolar ventilation during high-frequency ventilation (HFV) was estimated from the washout of the positron-emitting isotope (nitrogen-13-labeled N2) from the lungs of anesthetized paralyzed supine dogs by use of a positron camera. HFV was delivered at a mean lung volume (VL) equal to the resting functional residual capacity with a ventilator that generated tidal volumes (VT) between 30 and 120 ml, independent of the animal's lung impedance, at frequencies (f) from 2 to 25 Hz, with constant inspiratory and expiratory flows and an inspiration-to-expiration time ratio of unity. Specific ventilation (SPV), which is equivalent to ventilation per unit of compartment volume, was found to follow closely the relation: SPV = 1.9(VT/VL)2.1 X f. From this relation and from arterial PCO2 measurements we found an expression for the normocapnic settings of VT and f, given VL and body weight (W). We found that the VL was an important normalizing parameter in the sense that VT/VL yielded a better correlation (r = 0.91) with SPV/f than VT/W (r = 0.62) or VT alone (r = 0.8).
Chemosensitivity of crayfish slowly adapting stretch receptors to nicotine
Authors: Taylor R. F. , Frazier D. T.
Published: December 2017

It has recently been demonstrated that slowly adapting stretch receptors (SASRs) in the airways of the dog respond directly to nicotine (Federation Proc. 43: 318, 1984). The purpose of the present experiment was to investigate this chemical effect on an isolated stretch receptor. The crayfish muscle receptor organ was chosen, since crayfish muscle is reported to be insensitive to nicotine or acetylcholine and therefore permits the testing of any direct chemical effect of nicotine on the muscle stretch receptors. The tail was removed and pinned out in a tissue bath, and a stretch receptor organ was surgically isolated. Single-unit SASR extracellular nerve recordings were made while simultaneously measuring tension in the tail. Drugs were prepared in Van Harreveld's solution and administered into the bath kept at 18 degrees C. When resting muscle tension was essentially reduced to zero by cutting both ends of the receptor organ muscle, nicotine (0.07 microM) added to the bath increased receptor activity fourfold. This response was abolished by treatment with hexamethonium (690 microM). In a second group of animals in which the muscle was left intact, nicotine was shown to significantly increase receptor sensitivity to step changes in muscle tension. Once again hexamethonium blocked the response to nicotine. These results demonstrate that the sensitivity of mechanoreceptor can be altered by chemical interaction with nicotinic receptors, which dramatically alter sensory receptor activity.
Forced oscillation technique: comparison of two devices
Authors: Franken H. , Cauberghs M. , Ringelhann A. , Clement J. , Van de Woestijne K. P.
Published: December 2017

The respiratory impedances in healthy subjects and patients with advanced obstructive lung disease were measured between 2 and 32 Hz, using two forced oscillation techniques: the setup used previously by Grimby et al. (J. Clin. Invest. 47: 1455–1465, 1968) and a modified device in which the pneumotachograph is replaced by a 2-m-long tube and the ratio of pressures at both ends of the tube is determined. The advantages of the latter device are that 1) its impedance and frequency characteristics can be predicted by classical physics, 2) the only requirement for correct measurements are a match of the pressure transducers, and 3) high-pass filters are not needed to suppress the influence of breathing. On the other hand, the device is more sensitive to the turbulences induced by the subject's own breathing. This drawback can be avoided by interposing a piece of tubing between the mouth and proximal pressure recording site.
Rib cage and diaphragm-abdomen compliance in humans: effects of age and posture
Authors: Estenne M. , Yernault J. C. , De Troyer A.
Published: December 2017

The influence of age and posture on compliance of the rib cage (Crc) and diaphragm-abdomen (Cab) compartments of the chest wall was studied in 61 healthy adults (33 men, 28 women) aged 24–75 yr. Chest wall compliance (Cw) was measured by the weighted spirometer technique; Crc and Cab were derived from the slope of the relaxation line of the thoracoabdominal system obtained with two pairs of linearized magnetometers. While Cw was being measured, we monitored electrical activity of the abdominal external oblique muscle with a concentric needle electrode and thoracoabdominal configuration. In 52 subjects, the electromyogram did not show any abdominal muscle activity and the end-expiratory level never departed from the relaxed thoracoabdominal configuration, thus suggesting adequate respiratory muscle relaxation. Aging was associated with significant decreases in Crc and Cab. In the upright posture Crc decreased from 0.164 +/- 0.041 (mean +/- SD) l/cmH2O in the younger subjects (24–39 yr) to 0.114 +/- 0.027 l/cmH2O in the older subjects (55–75 yr). Cab concomitantly fell from 0.032 +/- 0.012 l/cmH2O to 0.020 +/- 0.007 l/cmH2O. These reductions were statistically significant (P less than 0.05–0.01) and were also present in the supine posture. Shifting from the seated to the supine posture did not cause any significant change in Cw but was invariably associated with a decrease in Crc and an increase in Cab.
Effects of static and fluctuating airway pressure on intact pulmonary circulation
Authors: Fuhrman B. P. , Smith-Wright D. L. , Kulik T. J. , Lock J. E.
Published: December 2017

The direct effects on the pulmonary circulation of static and fluctuation airway pressure were compared in intact close-chest infant lambs with reactive pulmonary vasculature under alpha-chloralose anesthesia. A preparation developed to permit independent ventilation of right and left lungs and independent measurement of right and left lung blood flow was employed to separate direct from indirect effects of unilateral airway pressure changes on pulmonary vascular resistance (PVR). Both static and fluctuating unilateral airway pressure interventions directly elevated ipsilateral PVR. For purposes of comparison mean alveolar pressure (PA) was estimated for both static and fluctuating trials. Fluctuating interventions increased PVR more than did static trials at comparable levels of PA. Substantially less PA was needed to double ipsilateral PVR by fluctuating than by static interventions (16 vs. 26 mmHg, respectively). These data indicate that, in the intact animal with reactive pulmonary vasculature, both PA and the waveform of airway pressure applied can influence PVR.
Plasma expansion effect on cardiac capillary and adrenergic exchange in intact dogs
Authors: Cousineau D. , Rose C. P. , Goresky C. A.
Published: December 2017

The effect of plasma volume expansion on transcapillary exchange and norepinephrine release in the heart was examined in pentobarbital sodium-anesthetized dogs by use of the multiple indicator-dilution technique. Animals were studied under basal conditions and following infusion of the plasma expander, dextran. Catheters were placed in coronary artery and coronary sinus in a closed-chest preparation. Labeled albumin, sucrose, and norepinephrine were injected into the coronary artery and outflow-dilution curves were secured. Analysis of these provided parameters reflecting coronary flow and permeability-surface product, and a norepinephrine tracer kinetic-bulk model provided simultaneous estimates of the rate of norepinephrine release into the myocardial interstitial space. The infusion of dextran resulted in a large increase in coronary flow without significant changes in myocardial norepinephrine release; at the same time the permeability-surface product values increased, amplifying the capacity of the higher flow to deliver substrates to sarcolemmal cells. The findings indicate that plasma volume expansion increases transcapillary exchange in the heart without activating the cardiac sympathetic system.
Juxtacardiac pressure in closed-chest dogs
Authors: Sasaki H. , Shirato K. , Nakamura M. , Takishima T.
Published: December 2017

We studied pressure (Ppc)-volume (Vpc) relationships of the pericardial sac by inserting air into it at constant end-diastolic heart volume in six dogs. The lungs were inflated by positive alveolar pressure while pleural pressure was monitored using the esophageal balloon technique. Ppc-Vpc relationships were measured at transpulmonary pressures (PL) of 30, 10, and 5 cmH2O in each of three states: closed chest, open chest with lung separation, and open chest with the pericardium dissected free of its mediastinal attachment. Ppc in the closed-chest condition was more positive than Ppc in the open chest with lung separation, with increase of Vpc and PL, which suggests that the lungs compress the pericardium. Ppc in the open-chest condition with lung separation was also more positive than Ppc in the pericardium after it was dissected free, which suggests that mediastinal attachment compresses the pericardium. It is suggested that lungs in the closed-chest condition as well as mediastinal attachment reduce the heart expansion by a similar magnitude.
Effects of inspiratory resistance loading on lung fluid balance in awake sheep
Authors: Loyd J. E. , Nolop K. B. , Parker R. E. , Roselli R. J. , Brigham K. L.
Published: December 2017

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.
Lung mechanics in papain-treated rabbits
Authors: McCormack G. S. , Moreno R. H. , Hogg J. C. , Pare P. D.
Published: December 2017

To further investigate the effects of airway cartilage softening on static and dynamic lung mechanics, 11 rabbits were treated with 100 mg/kg iv papain, whereas 9 control animals received no pretreatment. Lung mechanics were studied 24 h after papain injection. There was no significant difference in lung volumes, lung pressure-volume curves, or chest wall compliance. Papain-treated rabbits showed increased lung resistance: 91 +/- 63 vs. 39 +/- 22 cmH2O X l-1 X s (mean +/- SD; P less than 0.05), decreased maximal expiratory flows at all lung volumes, and preserved density dependence of maximal expiratory flows. We conclude that increased airway wall compliance is probably the mechanism that limited maximal expiratory flow in this animal model. In addition the increased lung resistance suggests that airway cartilage plays a role in the regulation of airway caliber during quiet tidal breathing.
A method for microinjection into subpleural alveoli of rat lung in situ
Authors: Patrick G. , Stirling C.
Published: December 2017

A new technique is described for the micropuncture of rat lung in the intact thorax. Under pentobarbital sodium anesthesia a glass micropipette is passed through a small area of the parietal pleura, which has been cleared of overlying intercostal muscle. The micropipette is passed into the lung parenchyma and withdrawn again without collapsing the lung. The current application of this technique is in the microinjection of fluid into subpleural alveoli, which is illustrated using a suspension of colloidal gold. The gold particles are immediately dispersed over the surface of many alveoli, a small proportion spreading laterally as far as 4–6 mm. There is no evidence of alveolar flooding.
Location and mechanisms of pulmonary vascular volume changes
Authors: Dawson C. A. , Rickaby D. A. , Linehan J. H.
Published: December 2017

We examined the influence of changing outflow pressure, P out, on the vascular and extravascular volumes (QV and QEV, respectively, as measured by indicator dilution) and on the outflow occlusion pressures in isolated dog lung lobes perfused with constant flow. Changing P out had a substantial effect on QV, but not on QEV, whether P out was less than or greater than alveolar pressure, PA. Since QEV did not change with QV, recruitment of previously unperfused vessels did not appear to contribute substantially to the increases in QV when P out was increased. The rapid jump in P out immediately following outflow occlusion was virtually independent of the difference between PA and P out suggesting that the alveolar vessels were an important volume storage site when P out was low relative to PA. We conclude that, over a certain range of pressures, alveolar vessel volume can be controlled by venous pressure even when the change in venous pressure has little effect on arterial pressure (zone 2). Further, we conclude that in zone 3 and within the transition from zone 2 to zone 3 increases in the intralobar blood volume occurring within the alveolar vessels may not require recruitment in the sense of opening of previously unperfused vessels.
Regulation of breathing movements in fetal sheep by prostaglandin E2
Authors: Wallen L. D. , Murai D. T. , Clyman R. I. , Lee C. H. , Mauray F. E. , Kitterman J. A.
Published: December 2017

In fetal sheep, plasma prostaglandin (PG) E2 concentrations are high, and fetal breathing movements (FBM) occur intermittently, primarily during low-voltage fast electrocortical activity (LVFA). There is evidence suggesting that prostaglandins, specifically PGE2, may regulate FBM. To define the physiological role of PGE2 in regulation of FBM, we infused meclofenamate (0.9 mg X kg-1 X h-1), a prostaglandin synthetase inhibitor, into six fetal sheep to suppress endogenous prostaglandin production. Afterward, PGE2 was added in mean doses of 9, 18, 36, and 90 ng X kg-1 X min-1. Meclofenamate decreased PGE2 concentrations and increased FBM, especially during high-voltage slow electrocortical activity (HVSA). Addition of PGE2 reversed the effects of meclofenamate, increasing PGE2 concentrations and decreasing FBM, especially during HVSA. The response to PGE2 was dose dependent; the overall incidence of FBM and incidences of FBM during HVSA and LVFA were inversely correlated with both the infused PGE2 dose and the mean PGE2 concentration. At higher doses of PGE2, FBM occurred intermittently and only during LVFA; thus PGE2 infusion restored the physiological pattern of FBM. These results indicate that PGE2 regulates FBM by inhibiting FBM during HVSA.
Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution
Authors: Rennard S. I. , Basset G. , Lecossier D. , O'Donnell K. M. , Pinkston P. , Martin P. G. , Crystal R. G.
Published: December 2017

Bronchoalveolar lavage is a powerful technique for sampling the epithelial lining fluid (ELF) of the lower respiratory tract but also results in a significant dilution of that fluid. To quantify the apparent volume of ELF obtained by bronchoalveolar lavage, urea was used as an endogenous marker of ELF dilution. Since urea diffuses readily through the body, plasma and in situ ELF urea concentrations are identical; thus ELF volume can be calculated using simple dilution principles. Using this approach, we determined that with a standard lavage procedure, the volume of ELF recovered from a normal human is 1.0 +/- 0.1 ml/100 ml of recovered lavage fluid. Time course experiments in which the saline used for lavage was permitted to remain in the lower respiratory tract for various “dwell times” suggested that diffusion of urea from sources other than recovered ELF can contribute to the total urea recovered resulting in an overestimate of the volume of ELF recovered. Thus, while reasonably accurate, the volume of ELF determined by urea must be considered an overestimate, or “apparent” volume. The ELF albumin concentration based on the apparent ELF volume was 3.7 +/- 0.3 mg/ml, a value that is in good agreement with direct measurements made by other techniques in experimental animals. The density of all inflammatory and immune effector cells on the epithelial surface of the lower respiratory tract, based on the apparent ELF volume, was 21,000 +/- 3,000 cells/microliter, a value that is twofold greater than that in blood.(ABSTRACT TRUNCATED AT 250 WORDS)
Muscle triglyceride utilization during exercise: effect of training
Authors: Hurley B. F. , Nemeth P. M. , Martin W. H. , Hagberg J. M. , Dalsky G. P. , Holloszy J. O.
Published: December 2017

The respiratory exchange ratio (RER) is lower during exercise of the same intensity in the trained compared with the untrained state, even though plasma free fatty acids (FFA) and glycerol levels are lower, suggesting reduced availability of plasma FFA. In this context, we evaluated the possibility that lipolysis of muscle triglycerides might be higher in the trained state. Nine adult male subjects performed a prolonged bout of exercise of the same absolute intensity before and after adapting to a strenuous 12-wk program of endurance exercise. The exercise test required 64% of maximum O2 uptake before training. Plasma FFA and glycerol concentrations and RER during the exercise test were lower in the trained than in the untrained state. The proportion of the caloric expenditure derived from fat, calculated from the RER, during the exercise test increased from 35% before training to 57% after training. Muscle glycogen utilization was 41% lower, whereas the decrease in quadriceps muscle triglyceride concentration was roughly twice as great (12.7 +/- 5.5 vs. 26.1 +/- 9.3 mmol/kg dry wt, P less than 0.001) in the trained state. These results suggest that the greater utilization of FFA in the trained state is fueled by increased lipolysis of muscle triglyceride.
Rat lung carbonic anhydrase: activity, localization, and isozymes
Authors: Henry R. P. , Dodgson S. J. , Forster R. E. , Storey B. T.
Published: December 2017

sCarbonic anhydrase activity in rat lungs perfused free of blood was localized by homogenization of the tissue followed by differential centrifugation. Four fractions were obtained from the homogenate, a cell debris pellet with a mitochondrial pellet and a microsomal pellet with a clear cytosol supernatant. The last named fraction contained 67% of the total enzyme activity; the cell debris contained 18%, and the mitochondrial and microsomal contained 8 and 7%, respectively. Of the 33% of enzyme activity associated with the pellet fraction, 25% could be experimentally defined as membrane associated by its solubilization with 0.3 M tris-(hydroxymethyl) aminoethane sulfate buffer. The remainder was defined as membrane bound. Purification of the soluble carbonic anhydrase from the lung yielded two isozymes with electrophoretic and inhibitor sensitivities apparently identical with the blood isozymes. Hemoglobin analysis showed that the lung isozymes could not have included more than 0.03% enzyme from blood contamination. The carbonic anhydrase activity present in the whole rat lung would give an average acceleration of the CO2 hydration reaction under physiological conditions over the uncatalyzed rate of 122, sufficient to maintain equilibration between CO2 and plasma HCO3- during blood transit of the lung. If the membrane-associated activity is mostly on the plasma membrane of the endothelial cells and available to the capillary blood, it would be sufficient to give this acceleration. We suggest that the possible source of this membrane-associated activity might be adsorption from the blood of carbonic anhydrase liberated by erythrocyte lysis.
Construction and evaluation of a coronary catheter for chronic implantation in dogs
Authors: Gwirtz P. A.
Published: December 2017

Construction of a Silastic catheter and the procedure for chronic implantation in a coronary artery in dogs is described. In addition, studies designed to evaluate whether chronic coronary artery catheterization altered coronary vascular reactivity and myocardial function are presented. The results of these studies indicate that chronic implantation of the catheter in a coronary artery of conscious dogs does not significantly interfere with the normal reactivity of the coronary vascular bed, does not compromise regional or global left ventricular function, and does not induce collateral vessel development. This technique will be useful in studies involving the neural and metabolic regulation of the coronary circulation in animals subjected to exercise and/or exercise training.
Determinants of intrapericardial pressure in dogs
Authors: Freeman G. L. , LeWinter M. M.
Published: December 2017

This study investigates factors that influence the pressure measured in the intrapericardial (IP) space. Seven dogs were studied after they were anesthetized with pentobarbital sodium. With the chest closed, intravascular volume expansion by dextran infusion from a mean left atrial (LA) transmural pressure of 8.4 +/- 1.2 (SD) to 15.5 +/- 1.6 Torr caused an increase in mean IP of from 2.6 +/- 1.2 to 3.9 +/- 1.7 Torr (P less than 0.01). This reflected a predominant increase in the influence of the cardiac fossa (CF), which accounted for 56% of the IP pressure after volume expansion. In the open-chest state an increase in mean LA transmural pressure from 9.5 +/- 2.5 to 16.4 +/- 0.6 Torr caused IP pressure to increase from 1.1 +/- 0.9 to 3.0 +/- 1.6 (P less than 0.005), representing the influence of the elastic pericardium alone. The use of positive end-expiratory pressure (PEEP) significantly increased the influence of the CF. Of note, the relation of LA to right atrial (RA) pressure was significantly different with and without the influence of the CF; the RA-to-LA ratio was higher with the chest open under each set of volume conditions with and without PEEP. In four dogs, acute transection of the pericardiodiaphragmatic ligaments led to a small (1–2 Torr) but distinct drop in IP pressure. Thus, IP pressure is affected by the intracardiac volume, the elastic pericardium, the CF, and the pericardiodiaphragmatic attachments, all of which must be considered in an analysis of diastolic properties of the heart in situ.
Aortic baroreceptor deafferentation in the baboon
Authors: Bishop V. S. , Haywood J. R. , Shade R. E. , Siegel M. , Hamm C.
Published: December 2017

Previous animal studies have indicated that removal of the aortic baroreceptors causes a moderate increase in arterial pressure that is not fully buffered by receptors in the carotid sinus. However, the role of these separate baroreceptors in the conscious nonhuman primate has not been examined. To address this question, adult male baboons were chronically maintained on a tether system that permitted them to move freely about their cage. With this system, arterial pressure and heart rate could be monitored continuously over 24-h periods with periodic drug administration to test cardiovascular function. Control values of arterial pressure and heart rate were 85.6 +/- 4.0 mmHg and 77.5 +/- 2.9 beats/min, respectively. Following removal of the aortic baroreceptors, arterial pressure rose to 104.6 +/- 5.5 mmHg and heart rate increased to 117.9 +/- 3.1 beats/min. The variability of these parameters did not change following denervation. There was, however, a suppression of the arterial pressure-heart period relationship and an augmentation in the depressor response to ganglionic blockade with hexamethonium. These data indicate that removal of the aortic baroreceptors causes a reduction in the sensitivity of the heart rate baroreflex and subsequent increase in arterial pressure that is a result of an increased sympathetic nervous system function.