bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of pulmonary angiotensin-converting enzyme activity in conscious developing lambs
Authors: Pitt B. R. , Lister G.
Published: December 2017

Apparent enzyme kinetics were determined for pulmonary angiotensin-converting enzyme (ACE) as a function of postnatal development and alveolar hypoxia in intact conscious lambs (9 newborn and 7 sheep, 8–23 wk). We injected into the right atrium a mixture of indocyanine green and 3H-labeled benzoyl-phenylalanyl-alanyl-proline (BPAP), a synthetic substrate for ACE, and sampled blood from the aorta at 1-s intervals. From this, we quantified the %BPAP metabolism during a single pass through the lungs by use of indicator-dilution techniques. By adding unlabeled BPAP to the injectate, combining outflow data from two to three measurements, and applying a nonlinear model of pulmonary metabolism (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51:405–414, 1981), we could determine 1) apparent maximum velocity (Vmax); 2) concentration at which velocity was one-half Vmax (Km); and 3) alpha, a measure of perfusion heterogeneity. All animals were studied during normoxia and while breathing 10% O2 for at least 15 min. Seven of the newborn lambs were studied 1 wk later. Km in the newborn was 15 +/- 3 microM and did not change significantly with age or hypoxia. Vmax increased markedly with development (newborn: 14 +/- 2 nmol X s-1 X g dry lung-1; sheep: 38 +/- 5 nmol X s-1 X g dry lung-1; P less than 0.01). Alveolar hypoxia significantly decreased Vmax in the newborn only (P less than 0.05); there was no significant change in Vmax in the same animal studied 1 wk later or in the older group.(ABSTRACT TRUNCATED AT 250 WORDS)
Ozone-induced changes in muscarinic bronchial reactivity by different testing methods
Authors: Roum J. H. , Murlas C.
Published: December 2017

We examined the effect of ozone (O3) on muscarinic bronchial reactivity in the guinea pig and compared reactivity determined by two different routes of agonist delivery. Reactivity before and from 4 h to 2 days after O3 exposure (3.0 ppm, 2 h) was determined by measuring specific airway resistance upon administration of intravenous acetylcholine and/or aerosolized methacholine challenge in 34 unanesthetized, spontaneously breathing animals. Before exposure, we observed more gradual and reproducible results to intravenous agonist. After exposure, hyperreactivity to parenteral agonist occurred consistently, but not to inhaled agonist. Hyperreactivity demonstrable by either route was similar in magnitude and time course within 14 h of exposure. Two days later, hyperreactivity to inhaled agonist had remitted; that to intravenous drug persisted. Our results indicate that variability in the occurrence and time course of O3-induced hyperreactivity to inhaled agonist may be a consequence of the technique employed. The consistent occurrence of hyperreactivity after O3 to parenteral agonist suggests mechanisms other than airway mucosal hyperpermeability are responsible for this hyperreactivity.
Pulmonary fibrin microembolism with Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor
Authors: Schaeffer R. C. , Chilton S. M. , Hadden T. J. , Carlson R. W.
Published: December 2017

We produced pulmonary fibrin microembolism using an infusion of a prothrombin activator (Echis carinatus venom, 30 min, 0.5 NIH thrombin equivalent units/kg) in open-chest mongrel dogs. To determine the nonclotting effects of this venom on edemagenesis we infused an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK, 57 nmol X kg-1 X min-1 for 120 min), alone (n = 5) or with venom (Echis + PPACK, n = 5). The control group (n = 5) was given 1 ml of 0.9% NaCl. A decline in left atrial pressure (means +/- SE, 5.3 +/- 0.4 to 4.0 +/- 0.5 mmHg, P less than 0.05) and cardiac index (149 +/- 10 to 82 +/- 13 ml X min-1 X kg-1, P less than 0.01) in association with a marked increase in pulmonary arterial pressure (14.5 +/- 0.6 to 26.6 +/- 2.5 mmHg, P less than 0.001) and pulmonary vascular resistance (64 +/- 5 to 304 +/- 42 mmHg X ml-1 X min-1 X kg-1, P less than 0.001) was observed after 20 min of venom infusion. During this interval, pulmonary artery wedge pressure increased (4 +/- 1 to 12 +/- 4 mmHg, P less than 0.01) in four of eight animals. Fibrinogen declined below measurable levels and fibrin microemboli were seen in many pulmonary arterioles. These changes were not observed in the Echis + PPACK, PPACK, or control groups. Leukopenia and thrombocytopenia were observed in the Echis and Echis + PPACK groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Central and local cholinergic components of histamine-induced bronchoconstriction in dogs
Authors: Shore S. A. , Bai T. R. , Wang C. G. , Martin J. G.
Published: December 2017

To determine the importance of central and local reflexes in the bronchoconstriction produced by inhaled aerosolized histamine, chloralose-urethan-anesthetized dogs were intubated with a double-lumen catheter, ventilated with a dual cylinder respirator, and instrumented for the measurements of pulmonary conductance (GL) and dynamic compliance (Cdyn) in each lung. In each dog, dose-response curves to inhaled aerosolized histamine were obtained in both lungs separately but synchronously. Four series of experiments were performed. In the first series (n = 10) the responses of the right and left lungs were compared and found to be approximately equal, indicating that one lung could be used as a control for the other. In the second and third series the dose-response curve of one lung that had either been treated with inhaled atropine sulfate (n = 6) (4 mg/ml) or vagotomized (n = 4) was compared with the contralateral control lung. At low concentrations of histamine, GL and Cdyn decreased more in the control lungs than in their atropine-treated or vagotomized counterparts, and approximately 40% of the bronchoconstriction induced was reflex in origin. At higher concentrations of histamine the responses of the control and atropine-treated or vagotomized lungs were not significantly different. In the fourth series of experiments (n = 6) histamine dose-response curves were obtained following combined bilateral vagotomy and unilateral delivery of inhaled aerosolized atropine. In these dogs GL, but not Cdyn, fell to a greater extent in the control than in the atropine-treated lung.
Influence of G-suit abdominal bladder inflation on gas exchange during +GZ stress
Authors: Modell H. I. , Beeman P. , Mendenhall J.
Published: December 2017

Available data relating duration of +GZ stress to blood gas exchange status is limited. Furthermore, studies focusing on pulmonary gas exchange during +GZ stress when abdominal restriction is imposed have yielded conflicting results. To examine the time course of blood gas changes occurring during exposure to +GZ stress in dogs and the influence of G-suit abdominal bladder inflation on this time course, seven spontaneously breathing pentobarbital-anesthetized adult mongrel dogs were exposed to 60 s of up to +5 GZ stress with and without G-suit abdominal bladder inflation. Arterial and mixed venous blood were sampled for blood gas analysis during the first and last 20 s of the exposure and at 3 min postexposure. Little change in blood gas status was seen at +3 GZ regardless of G-suit status. However, with G-suit inflation, arterial PO2 fell by a mean of 14.7 Torr during the first 20 s at +4 Gz (P less than 0.01, t test) and 20.6 Torr at +5 GZ (P less than 0.01). It continued to fall an additional 10 Torr during the next 40 s at both +4 and +5 GZ. Arterial PO2 was still 5–10 Torr below control values (P less than 0.05) 3 min postexposure. A second series of experiments paralleling the first focused on blood gas status during repeated exposure to acceleration. Blood gas status was assessed in five dogs during the late 20 s of two 60-s exposures separated by 3 min at 0 GZ. No significant differences between the initial and repeated exposures were detected. The data indicate that G-suit abdominal bladder inflation promotes increased venous admixture.
Thromboxane synthase inhibition and perinatal pulmonary response to arachidonic acid
Authors: Tod M. L. , Cassin S.
Published: December 2017

Arachidonic acid causes dose-dependent increases in pulmonary vascular resistance in perinatal lambs. The specific metabolites that produce this effect are not known; however, a role for thromboxanes (TX's), potent constrictors of vascular smooth muscle, has been proposed. The effects of a specific inhibitor of TX synthase, OKY-1581, were tested in newborn and ventilated fetal lambs using an in situ pump-perfused lower left lobe preparation. Pulmonary and systemic responses of newborns and ventilated fetuses to infusions of arachidonic acid were evaluated in the presence and absence of OKY-1581. Increases in pulmonary vascular resistance caused by arachidonic acid were diminished by TX synthase inhibition. The degree of systemic hypotension observed with arachidonic acid infusions was significantly greater in animals receiving OKY-1581 than in animals without the inhibitor. The effect of OKY-1581 on periods of hypoxia was also evaluated in newborn lambs. There were no significant differences in the hypoxic pressor response in lambs with and without TX synthase inhibition. These results suggest that OKY-1581 can reduce most of the pulmonary vasoconstriction produced by arachidonic acid in perinatal lambs.
Acute inhalation of cigarette smoke augments hypoxic chemosensitivity in humans
Authors: Yamamoto H. , Inaba S. , Nishiura Y. , Kishi F. , Kawakami Y.
Published: December 2017

Hypoxic and hypercapnic ventilatory responses were measured after two levels of acute inhalation of cigarette smoke, minimum-level nicotine smoke (smoke 1) and nicotine-containing smoke (smoke 2), in 10 normal men. Chemosensitivity to hypoxia and hypercapnia was assessed both in terms of slope factors for ventilation-alveolar PO2 curve (A) and ventilation-alveolar PCO2 line (S) and of absolute levels of minute ventilation (VE) at hypoxia or hypercapnia. Ventilatory response to hypoxia and absolute level of VE at hypoxia significantly increased from 23.5 +/- 22.6 (SD) to 38.6 +/- 31.3 l . min-1 . Torr and from 10.6 +/- 2.5 to 12.6 +/- 3.5 l . min-1, respectively, during inhalation of cigarette smoke 2 (P less than 0.05). Inhalation of cigarette smoke 2 tended to increase the ventilatory response to hypercapnia, and the absolute level of VE at hypercapnia rose from 1.42 +/- 0.75 to 1.65 +/- 0.58 l . min-1 . Torr-1 and from 23.7 +/- 4.9 to 25.5 +/- 5.9 l . min-1, respectively, but these changes did not attain significant levels. Cigarette smoke 2 inhalation induced an increase in heart rate from 64.7 +/- 5.7 to 66.4 +/- 6.3 beats . min-1 (P less than 0.05) during room air breathing, whereas resting ventilation and specific airway conductance did not change significantly. On the other hand, acute inhalation of cigarette smoke 1 changed none of these variables. These results indicate that hypoxic chemosensitivity is augmented after cigarette smoke and that nicotine is presumed to act on peripheral chemoreceptors.
Glycogen depletion during prolonged exercise: influence of glucose, fructose, or placebo
Authors: Koivisto V. A. , Harkonen M. , Karonen S. L. , Groop P. H. , Elovainio R. , Ferrannini E. , Sacca L. , Defronzo R. A.
Published: December 2017

We examined the influence of various carbohydrates of fuel homeostasis and glycogen utilization during prolonged exercise. Seventy-five grams of glucose, fructose, or placebo were given orally to eight healthy males 45 min before ergometer exercise performed for 2 h at 55% of maximal aerobic power (VO2max). After glucose ingestion, the rises in plasma glucose (P less than 0.01) and insulin (P less than 0.001) were 2.4- and 5.8-fold greater than when fructose was consumed. After 30 min of exercise following glucose ingestion, the plasma glucose concentration had declined to a nadir of 3.9 +/- 0.3 mmol/l, and plasma insulin had returned to basal levels. The fall in plasma glucose was closely related to the preexercise glucose (r = 0.98, P less than 0.001) and insulin (r = 0.66, P less than 0.05) levels. The rate of endogenous glucose production and utilization rose similarly by 2.8-fold during exercise in fructose group and were 10–15% higher than in placebo group (P less than 0.05). Serum free fatty acid levels were 1.5- to 2-fold higher (P less than 0.01) after placebo than carbohydrate ingestion. Muscle glycogen concentration in the quadriceps femoris fell in all three groups by 60–65% (P less than 0.001) during exercise. These data indicate that fructose ingestion, though causing smaller perturbations in plasma glucose, insulin, and gastrointestinal polypeptide (GIP) levels than glucose ingestion, was no more effective than glucose or placebo in sparing glycogen during a long-term exercise.
Inspiratory airway obstruction does not affect lung fluid balance in lambs
Authors: Hansen T. N. , Gest A. L. , Landers S.
Published: December 2017

The purpose of this study was to examine the effects of inspiratory airway obstruction on lung fluid balance in newborn lambs. We studied seven 2- to 4-wk-old lambs that were sedated with chloral hydrate and allowed to breathe 30–40% O2 spontaneously through an endotracheal tube. We measured lung lymph flow, lymph and plasma protein concentrations, pulmonary arterial and left atrial pressures, mean and phasic pleural pressures and airway pressures, and cardiac output during a 2-h base-line period and then during a 2- to 3-h period of inspiratory airway obstruction produced by partially occluding the inspiratory limb of a nonrebreathing valve attached to the endotracheal tube. During inspiratory airway obstruction, both pleural and airway pressures decreased 5 Torr, whereas pulmonary arterial and left atrial pressures each decreased 4 Torr. As a result, calculated filtration pressure remained unchanged. Inspiratory airway obstruction had no effect on steady-state lung lymph flow or the lymph protein concentration relative to that of plasma. We conclude that in the spontaneously breathing lamb, any decrease in interstitial pressure resulting from inspiratory airway obstruction is offset by a decrease in microvascular hydrostatic pressure so that net fluid filtration remains unchanged.
Comparison of cardiac output during exercise by single-breath and CO2-rebreathing methods
Authors: Inman M. D. , Hughson R. L. , Jones N. L.
Published: December 2017

Cardiac output (Q) was estimated in supine rest and in upright cycling at several work rates up to 200 W in five male and one female subjects. At least four repetitions of both the CO2-rebreathing plateau method (Collier, J. Appl. Physiol. 9:25–29, 1956) and the Kim et al. (J. Appl. Physiol. 21: 1338–1344, 1966) single-breath method were performed at each work rate, in a steady state of O2 consumption and heart rate. At supine rest and low work rates, estimates of Q were similar by the two methods. However, at higher work rates, the single-breath method significantly (P less than 0.05) underestimated the value obtained by CO2 rebreathing. The reason for the difference in estimates of Q by the two methods was traced to the determination of arterial partial pressure of CO2 (PaCO2) and mixed venous partial pressure of CO2 (PvCO2). The estimate of PaCO2 from the single-breath method was approximately 88.5% of the estimate from end-tidal PCO2 used with the rebreathing method (P less than 0.001). The oxygenated PvCO2 calculated from the single-breath Q averaged approximately 92.5% of the PvCO2 from CO2 rebreathing (P less than 0.0001). The difference in estimates of Q was not eliminated by using a logarithmic form of the CO2 dissociation curve with the single-breath method.
Failure of cholinergic blockade to prevent bronchodilatation following deep inspiration
Authors: Day A. , Zamel N.
Published: December 2017

The role of the cholinergic system in the phenomenon of bronchodilatation following a deep inspiration (BDFI) in humans has not been well established, although animal studies have suggested the cholinergic system to be of prime importance. We therefore induced cholinergic blockade with inhaled ipratropium bromide (Sch-1000) in five asymptomatic subjects and then assessed whether BDFI had been abolished. Since BDFI is only evident where there is normal or increased bronchomotor tone, prostaglandin F2 alpha (PGF2 alpha), a noncholinergic bronchoconstrictor, was used to re-establish bronchomotor tone in the presence of cholinergic blockade. At each stage the presence or absence of BDFI was assessed by comparing flows from a partial forced expiratory maneuver started at approximately 60% of vital capacity (Vmaxp) with flows from a forced expiratory maneuver started at lung capacity (Vmaxc). Flows were measured at the last 40% of vital capacity. The percent ratio of Vmaxp/Vmaxc was used as an indicator of BDFI. In the presence of cholinergic blockade and with reestablishment of bronchomotor tone with PGF2 alpha, BDFI could still be demonstrated (Vmaxp/Vmaxc percent ratio: control 110.3 +/- 10.6, after Sch-1000 129.4 +/- 10.3, after Sch-1000 and PGF2 alpha 59.4 +/- 6.9; P = 0.001). We conclude that there is not an essential role for the cholinergic system in the phenomenon of BDFI in healthy individuals.
Relationship between parasternal intercostal length and rib cage displacement in dogs
Authors: Decramer M. , Reid M. B. , De Troyer A.
Published: December 2017

The relationship between parasternal intercostal length and rib cage cross-sectional area was examined in nine supine dogs during passive inflation and during quiet breathing before and after phrenicotomy. Parasternal intercostal length (PSL) was measured with a sonomicrometry technique, and rib cage cross-sectional area (Arc) was measured with a Respitrace coil placed around the middle rib cage. During active inspiration as well as during passive inflation, PSL decreased as Arc increased. However, the relationship between PSL and Arc during active inspiration, whether in the intact or phrenicotomized animal, was almost invariably different from that during passive inflation, so that the same increase in Arc was associated with a greater decrease in PSL in the former than in the latter instance. This difference between passive inflation and active inspiration is probably due to the active contraction of the parasternals during inspiration and the consequent caudal displacement of the sternum. In upright humans, the sternum moves cephalad and not caudad during inspiration, so the relationship between PSL and Arc during active breathing might be similar to that during passive inflation.
Sleep apneic activity in older healthy subjects
Authors: Bixler E. O. , Kales A. , Cadieux R. J. , Vela-Bueno A. , Jacoby J. A. , Soldatos C. R.
Published: December 2017

The percentage of subjects with sleep apneic activity was significantly greater in a group of 60 healthy subjects who were 50 yr and older compared with a control group of 69 subjects who were younger than 50 yr. Sixteen of the older subjects (26.7%) and six of the younger subjects (8.7%) met the criteria for sleep apneic activity, i.e., 3–29 episodes per night. However, only one of the older subjects (1.7%) had enough sleep apneic activity (30 or more episodes in a night) to meet the definition of the condition of sleep apnea. In both age groups, sleep apneic activity (SAA) was slightly more prevalent in males than females. Older subjects with SAA were not significantly heavier than those without SAA but were so when compared with the younger subjects with SAA. In the 29 older subjects for whom hemoglobin O2 saturation (Sao2) was recorded, those with SAA had a significantly lower mean minimum Sao2 value (87%) than those without (92%).
Mechanical impedance as determinant of inspiratory neural drive during exercise in humans
Authors: Hussain S. N. , Pardy R. L. , Dempsey J. A.
Published: December 2017

Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This “load” is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise.
New method of respiratory gas analysis: light spectrometer
Authors: Fraser R. B. , Turney S. Z.
Published: December 2017

A multigas concentration analyzer particularly suited for respiratory gas analysis has been developed using a new principle based on the measurement of the intensity of light emitted by excited atoms or ions in a direct current glow discharge. This glow discharge spectral emission gas analyzer (GDSEA), or light spectrometer, simultaneously measures O2, N2, CO2, He, and N2O gas concentrations with a 0–90% response time of 100 ms and a sample rate of less than 20 ml/min in a short gas sample line configuration. Mole accuracy and resolution of the GDSEA using a short sample line were determined in the laboratory to be +/- 0.15 to +/- 0.7% and 0.02–0.05%, respectively. In the clinical setting a comparative evaluation was made with a mass spectrometer in a long sample line, computerized, multibed, respiratory monitoring system. Results indicate a close agreement between the two instruments with differences in mixed inspiratory or expiratory O2 and CO2 concentrations of less than 2% and of derived variables, such as O2 consumption, CO2 production, and respiratory exchange ratio, of less than 5%.
Changes in breathing when switching from nares to tracheostomy breathing in awake ponies
Authors: Forster H. V. , Pan L. G. , Bisgard G. E. , Flynn C. , Hoffer R. E.
Published: December 2017

We assessed the consequences of respiratory unloading associated with tracheostomy breathing (TBr). Three normal and three carotid body-denervated (CBD) ponies were prepared with chronic tracheostomies that at rest reduced physiological dead space (VD) from 483 +/- 60 to 255 +/- 30 ml and lung resistance from 1.5 +/- 0.14 to 0.5 +/- 0.07 cmH2O . l-1 . s. At rest and during steady-state mild-to-heavy exercise arterial PCO2 (PaCO2) was approximately 1 Torr higher during nares breathing (NBr) than during TBr. Pulmonary ventilation and tidal volume (VT) were greater and alveolar ventilation was less during NBr than TBr. Breathing frequency (f) did not differ between NBr and TBr at rest, but f during exercise was greater during TBr than during NBr. These responses did not differ between normal and CBD ponies. We also assessed the consequences of increasing external VD (300 ml) and resistance (R, 0.3 cmH2O . l-1 . s) by breathing through a tube. At rest and during mild exercise tube breathing caused PaCO2 to transiently increase 2–3 Torr, but 3–5 min later PaCO2 usually was within 1 Torr of control. Tube breathing did not cause f to change. When external R was increased 1 cmH2O . l-1 . s by breathing through a conventional air collection system, f did not change at rest, but during exercise f was lower than during unencumbered breathing. These responses did not differ between normal, CBD, and hilar nerve-denervated ponies, and they did not differ when external VD or R were added at either the nares or tracheostomy.
Important role of glucagon during exercise in diabetic dogs
Authors: Wasserman D. H. , Lickley H. L. , Vranic M.
Published: December 2017

To define the role of immunoreactive glucagon (IRG) during exercise in diabetes, 12 insulin-deprived alloxan-diabetic (A-D) dogs were run for 90 min (100 m/min, 12 degrees) with or without somatostatin (St 0.5 microgram . kg-1 . min-1). Compared with normal dogs, A-D dogs were characterized by similar hepatic glucose production (Ra), lower glucose metabolic clearance, and higher plasma glucose and free fatty acid levels during rest and exercise. In A-D dogs IRG was greater at rest and exhibited a threefold greater exercise increment than controls, whereas immunoreactive insulin (IRI) was reduced by 68% at rest but had similar values to controls during exercise. Basal norepinephrine, epinephrine, cortisol, and lactate levels were similar in normal and A-D dogs. However, exercise increments in norepinephrine, cortisol, and lactate were higher in A-D dogs. When St was infused during exercise in the A-D dogs, IRG was suppressed by 432 +/- 146 pg/ml below basal and far below the exercise response in A-D controls (delta = 645 +/- 153 pg/ml). IRI was reduced by 1.8 +/- 0.2 microU/ml with St. With IRG suppression the increase in Ra seen in exercising A-D controls (delta = 4.8 +/- 1.6 mg . kg-1 . min-1) was virtually abolished, and glycemia fell by 104 to 133 +/- 37 mg/dl. Owing to this decrease in glycemia, the increase in glucose disappearance was attenuated. Despite the large fall in glucose during IRG suppression, counterregulatory increases were not excessive compared with A-D controls. In fact, as glucose levels approached euglycemia, the increments in norepinephrine and cortisol were reduced to levels similar to those seen in normal exercising dogs. In conclusion, IRG suppression during exercise in A-D dogs almost completely obviated the increase in Ra, resulting in a large decrease in plasma glucose. Despite this large fall in glucose, there was no excess counterregulation, since glucose concentrations never reached the hypoglycemic range.
Can tritiated water-dilution space accurately predict total body water in chukar partridges?
Authors: Crum B. G. , Williams J. B. , Nagy K. A.
Published: December 2017

Total body water (TBW) volumes determined from the dilution space of injected tritiated water have consistently overestimated actual water volumes (determined by desiccation to constant mass) in reptiles and mammals, but results for birds are controversial. We investigated potential errors in both the dilution method and the desiccation method in an attempt to resolve this controversy. Tritiated water dilution yielded an accurate measurement of water mass in vitro. However, in vivo, this method yielded a 4.6% overestimate of the amount of water (3.1% of live body mass) in chukar partridges, apparently largely because of loss of tritium from body water to sites of dissociable hydrogens on body solids. An additional source of overestimation (approximately 2% of body mass) was loss of tritium to the solids in blood samples during distillation of blood to obtain pure water for tritium analysis. Measuring tritium activity in plasma samples avoided this problem but required measurement of, and correction for, the dry matter content in plasma. Desiccation to constant mass by lyophilization or oven-drying also overestimated the amount of water actually in the bodies of chukar partridges by 1.4% of body mass, because these values included water adsorbed onto the outside of feathers. When desiccating defeathered carcasses, oven-drying at 70 degrees C yielded TBW values identical to those obtained from lyophilization, but TBW was overestimated (0.5% of body mass) by drying at 100 degrees C due to loss of organic substances as well as water.
Effects of deep inhalation in asthma: relative airway and parenchymal hysteresis
Authors: Burns C. B. , Taylor W. R. , Ingram R. H.
Published: December 2017

Asthmatic subjects were screened for the effects or volume history on the degree of induced airway obstruction with methacholine by comparing isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume curves (P) begun near functional residual capacity (FRC) followed by maximal expiratory flow-volume (M) maneuvers begun from total lung capacity (TLC). The isovolumic Vmax values from M and P maneuvers defined two groups: one had a high M/P ratio (high group), indicating a large degree of reversal with deep inhalation, another had a low M/P ratio (low group), indicating minimal reversal. No differences were found between groups. A more complete study was later performed in which we measured specific airway conductance (sGaw) and anatomical dead space (VD) as indices of airway size and hysteresis before and after deep inhalation. The area of quasi-static transpulmonary pressure (Ptp) volume (V) curves from FRC to TLC and back to FRC was measured as an index of parenchymal hysteresis. At base line both groups showed a decrease in both sGaw and VD after a deep inhalation (DI). After constriction neither group changed VD after DI, whereas sGaw increased significantly in the high group after DI. This suggests that dilation of airways with DI occurred peripheral to those contributing to VD in the high group. The areas of the Ptp-V curves were equal at base line; yet the increase in areas with constriction in the low group was much greater.
On the maximum likelihood estimation of respiratory response slopes
Authors: Sherrill D. L. , Swanson G. D.
Published: December 2017

Several approaches have been suggested for estimating a respiratory response slope when both x and y variables are observed with error. Recently, a maximum likelihood estimate under the assumption of a bivariate normal distribution has been proposed. A method of moments solution yields a slope estimate of y/x as long as the underlying process mean is nonzero. This paper extends the maximum likelihood approach to the case where the process mean is zero. In this case, certain additional error assumptions must be made to yield a unique estimate. These concepts are applied to the problem of estimating an effective lung volume for steady-state breath-to-breath gas exchange data during exercise.
Implantable device for drug delivery and blood sampling in the rat
Authors: Chester J. F. , Weitzman S. A. , Malt R. A.
Published: December 2017

An implantable drug-delivery and venous sampling device is described that is constructed from a polyvinyl chloride catheter and a rubber intravenous catheter plug coated with Silastic. The implant was used for repeated venous sampling and for both administration of parenteral solutions and injections into the right colon of the rat for periods to 1 mo.
Formyl peptide-induced contraction of human airways in vitro
Authors: Armour C. L. , Black J. L. , Johnson P. R. , Vincenc K. S. , Berend N.
Published: December 2017

Formylmethionylleucylphenylalanine (FMLP) is a synthetic analogue of bacterial chemotactic factors. We studied the contraction of human airway tissue in vitro by FMLP. FMLP induced a concentration-dependent contraction of all bronchial spiral strips studied (n = 45). The maximum tension generated in response to FMLP was 86.6 +/- 7.0% (SE) of the maximum response to histamine. The contraction was not reduced by the histamine H1-receptor antagonist pyrilamine, the cyclooxygenase and lipoxygenase inhibitors indomethacin and BW755C, the muscarinic antagonist atropine, or capsaicin which depletes stores of substance P. The concentration-response curve was shifted to the right by the polypeptide antagonist N-t-BOC-phenylalanylleucylphenylalanylleucylphenylalanine and the leukotriene antagonist FPL 55712. When 2 successive FMLP concentration-response curves were performed the maximum response was significantly reduced from 114.8 +/- 9.1% of the histamine maximum to 39.3 +/- 6.1%. The contraction of human airways in vitro by an agent that is structurally and functionally similar to chemotactic peptides released from bacteria may have important implications in airway disease.
Dose effect of caffeine on control of breathing and respiratory response to CO2 in cats
Authors: Mazzarelli M. , Jaspar N. , Zin W. A. , Aranda J. V. , Milic-Emili J.
Published: December 2017

The dose effect of caffeine (10–70 mg/kg iv) on pulmonary ventilation (VE), mean inspiratory flow (VT/TI), and tracheal pressure generated 0.3 and 0.5 s (P0.3 and P0.5, respectively) after the onset of inspiration against airway occluded at end expiration was studied in cats anesthetized with pentobarbital sodium (35 mg/kg ip) breathing various gas mixtures. With air and 50% O2 (balance N2), increasing doses of caffeine caused a progressive increase in VE that was associated with a reduction in end-tidal PCO2. When the latter was maintained at control (precaffeine) level by inhalation of CO2, the increase in VE was, at all caffeine levels, about three times that under nonisocapnic conditions. Both under isocapnic and nonisocapnic conditions the greatest incremental changes of VE were observed after administration of the first 10-mg/kg aliquot of caffeine, i.e., the current acceptable clinical dose. In all instances, the changes in VE were proportionally the same as the corresponding changes in VT/TI, P0.3, and P0.5, suggesting that caffeine did not appreciably alter either the shape of the inspiratory driving pressure waveform or the impedance of the respiratory system but simply acted by increasing the amplitude of the neuromuscular inspiratory output. An additive interaction between caffeine and end-tidal PCO2 was observed in the VE, VT/TI, and P0.3 responses at levels of CO2 at or below the eucapnic range.
Role of vagal and spinal sensory pathways on eupneic diaphragmatic activity
Authors: Jammes Y. , Mathiot M. J. , Delpierre S. , Grimaud C.
Published: December 2017

The interactions between vagal and spinal afferents in the control of eupneic diaphragmatic activity were studied in two groups of cats anesthetized either with pentobarbital sodium (SPB) or with ethyl carbamate-alpha-chloralose (ECC), which enhanced spinal reflexes. Under both conditions of anesthesia two experimental protocols were performed: 1) bilateral cervical vagotomy followed by spinal section at C8 level or 2) spinal section followed by vagotomy. Changes in integrated diaphragmatic activity (Edi) were studied during eupneic ventilation and tracheal occlusion at end expiration. Vagotomy always significantly increased the amplitude of Edi during eupnea (SPB + 30%; ECC + 15%) and prolonged its duration (Tdi) (SPB + 110%; ECC + 75%) but did not modify the overall shape of the Edi vs. time relationship. Spinal section induced reverse changes in the amplitude of Edi, whether vagal afferents were present or suppressed and modified the shape of the Edi wave, but did not significantly modify Tdi. These results indicate that both vagal and spinal afferents may participate in the control of eupneic inspiration but exert different and interdependent influences on the recruitment and firing time of phrenic motoneurons. In addition, Tdi measured during tracheal occlusion (Todi) was markedly prolonged under ECC anesthesia. In this situation spinal section reduced Todi, which became close to the values obtained in intact or spinal cats under SPB anesthesia. Thus the response to tracheal occlusion at end expiration cannot be interpreted as resulting from the sole suppression of volume related vagal information.
Use of NMR for measurement of total body water and estimation of body fat
Authors: Lewis D. S. , Rollwitz W. L. , Bertrand H. A. , Masoro E. J.
Published: December 2017

A nuclear magnetic resonance (NMR) method is described for quantitatively measuring total body water (TBW) and for estimating the fat content of baboons. The hydrogen associated with water was measured as the amplitude of the free-induction decay voltage following a series of 90 degree radio frequency pulses at the Lamour frequency for hydrogen with a pulse length of 14 microseconds and a peak measuring time of 50 microseconds. TBW was calculated by multiplying the peak amplitude (volts) by the experimentally determined constant for a water standard (g water/V). This NMR method yielded TBW contents similar to those obtained in the same baboons by direct gravimetric procedures. In contrast, the widely used 3H2O-dilution method usually and variably overestimated body water. By providing an accurate measure of body water, this NMR procedure provides a rapid, noninvasive, reasonably accurate way of estimating body fat content.
Effects of preexercise snack feeding on endurance cycle exercise
Authors: Devlin J. T. , Calles-Escandon J. , Horton E. S.
Published: December 2017

We studied the effects of ingesting either a snack food (S) (260 kcal) or placebo (P) 30 min before intermittent cycle exercise at 70% maximal O2 consumption on endurance performance and muscle glycogen depletion in eight healthy human males. Immediately before exercise there were significantly greater increases in plasma glucose (PG) (S +28 +/- 9.7; P +0.1 +/- 0.8 mg/dl) and insulin (S +219 +/- 61.5; P -7 +/- 5.5 pmol/l) (P less than 0.05) following S feeding compared with P. These differences were no longer present by the end of the first exercise period. There were no differences in endurance times (S 52 +/- 6.4; P 48 +/- 5.6 min) or in the extent of muscle glycogen depletion following exercise (S 56 +/- 14.7; P 50 +/- 15.5 micrograms/mg protein) between the two groups. PG was maintained at base-line (prefeeding) concentrations following S, whereas there was a tendency for PG to steadily decrease after P. Total grams of carbohydrate oxidized during exercise did not differ between the two groups (S 120; P 118 g). These results demonstrate that the ingestion of a mixed-macronutrient snack 30 min before exercise does not impair endurance performance nor increase the extent of muscle glycogen depletion during high-intensity cycle exercise in untrained adult male subjects.
Effect of tracer infusion site on measurement of bicarbonate-carbon dioxide metabolism in dogs
Authors: Downey R. S. , Mellone A. , Matthews D. E.
Published: December 2017

Ten dogs were given a primed infusion of H13CO3- for 220 min while under general anesthesia. Isotopic steady state was reached within 60 min in exhaled CO2, femoral arterial blood HCO3-, and femoral venous blood HCO3-. Halfway through each infusion study, the site of tracer infusion was changed either from the central aorta to a peripheral vein, or vice versa. The mean HCO3(-)-CO2 flux measured from blood HCO3- enrichments was 15.7 +/- 2.1 (SD) mmol X kg-1 X h-1. The mean fraction of tracer recovered in exhaled CO2 was 79 +/- 7% (SD) of the infused dose. No significant difference in either HCO3- flux or recovery of tracer was found between the venous and arterial infusions of tracer. These results indicate that when venous administration of HCO3- tracer is compared with central arterial infusion, the initial loss of tracer into expired CO2 is an unimportant consideration in experiments measuring HCO3- kinetics.
Use of dantrolene plus multiple pulses to detect stress-susceptible porcine muscle
Authors: Quinlan J. G. , Iaizzo P. A. , Gronert G. A. , Taylor S. R.
Published: December 2017

Twitch characteristics of tibialis anterior muscles in situ were examined in stress-susceptible and normal swine. Three groups of pigs were studied: (1) purebred Pietrain stress-susceptible, (2) purebred Yorkshire normal, and (3) a crossbred (Pietrain-Yorkshire) litter containing both stress-susceptible and normal animals. Purebred and crossbred stress-susceptible pigs provided qualitatively similar results, as did purebred and crossbred normal pigs. Single stimuli produced greater than normal peak tensions and faster rates of tension development in stress-susceptible animals. Multiple stimuli (2–6 pulses at 5-ms intervals) increased peak tensions and rates of tension development, but did not augment differences between normal and stress-susceptible pigs. Intravenous administration of dantrolene reduced peak tensions and rates of tension development in all groups for single and multiple stimuli. However, the reduction was significantly less (P less than 0.01) for stress-susceptible pigs. Multiple stimuli (4–6 pulses) plus dantrolene amplified differences (P less than 0.01) in contractile properties between normal and stress-susceptible skeletal muscles, with stress-susceptible muscles obtaining larger peak tensions and faster rates of tension development. Normal and stress-susceptible pigs may, therefore, be distinguished by these procedures.
Solute conductance of blood-gas barrier in hamsters exposed to hyperoxia
Authors: Wangensteen D. , Piper R. , Johnson J. A. , Sinha A. A. , Niewoehner D.
Published: December 2017

Hamsters were exposed to greater than 95% O2 continuously for up to 5 days to determine longitudinal changes in the diffusive conductance of the alveolar epithelium and capillary endothelium as a result of hyperoxia. Permeability X surface area (PS, cm3/s X 10(-4)) was measured by isolated, perfused lung techniques. Alveolar epithelium PS for [14C]sucrose and 125I-bovine serum albumin (BSA) were determined at seven exposure times. Control PS (sucrose) and PS(BSA) averaged 1.00 and 0.022, respectively. Values were unchanged until 4.5 days, when significant increases in both, but especially PS(BSA), occurred. After 5 days, PS values were 4.69 and 0.691, respectively. Capillary endothelium PS for 125I-BSA and fluoresceinisothiocyanate dextran-150 (D-150) were measured at four exposure times. Control endothelium PS(BSA) and PS(D-150) averaged 0.232 and 0.048, respectively. These values were also unchanged after 4 days but increased to 0.440 and 0.131 after 5 days. Wet lung weight significantly increased after only 4 days. Hyperoxia thus increased both endothelium and epithelium PS, but epithelium changes were much greater. These functional changes do not occur for several days, occur simultaneously, and follow increases in lung wet weight.
Stimulation of fetal breathing activity by beta-adrenergic mechanisms
Authors: Jansen A. H. , Ioffe S. , Chernick V.
Published: December 2017

Experiments were done on chronically prepared fetal lambs, 125–135 days gestation, to test the effects of various catecholamines on fetal breathing (FB) as well as the influence of isoproterenol on the fetal respiratory response to hypoxemia. Bolus injections of epinephrine, norepinephrine, and isoproterenol (5–20 micrograms) were administered via the lingual artery or femoral or jugular vein during periods of FB activity or apnea. The effects of epinephrine and norepinephrine on FB were variable and not statistically significant. Isoproterenol produced a significant increase in FB, frequency of breathing, and mean inspiratory effort, when infused during rapid-eye-movement (REM) sleep but it failed to induce FB during non-rapid-eye-movement (NREM) sleep. The positive response during REM sleep was absent following pretreatment with 3–5 mg propranolol and after bilateral section of the sinus nerves. The effect of hypoxia on FB was tested before and during constant infusion of isoproterenol (1 microgram/min iv). A reduction of the fetal arterial PO2 by 3–10 Torr produced the characteristic depression of FB in either situation. These results indicate that the fetal carotid body chemoreceptors can reflexly stimulate FB under certain circumstances but that their effectiveness is limited by more powerful inhibitory mechanisms such as those operative during NREM sleep and hypoxemia.
Cardiogenic oscillation and phase III caused by pressure-volume heterogeneity: a model
Authors: Arieli R. , Wiener F. , Levitan E.
Published: December 2017

The effect of heterogeneity of pressure-volume (PV) behavior of lung units and the effect of the pulsations of the heart on expired N2 following a single breath of O2 were studied mathematically in a model of the lung. The lung was pictured as consisting of three compartments, one of high compliance (HC) and another of low compliance (LC), both affected by cardiac pulsations, and a third, nonoscillatory compartment (NC). Three sigmoid PV curves were assigned to the three compartments, for both acini and airway (generation 10–23), so that total compliance summed up to 200 ml/cmH2O. Bifurcation of NC was at generation 5/6 and that of HC and LC at any chosen generation. A steepness constant, K, was defined to characterize the sharply descending portion of the sigmoid PV curve. For a ratio of the steepness constant for the oscillatory compartments, KHC/KLC = 1, a sloping alveolar plateau was produced. The plateau was concave for KHC/KLC greater than 1 and slightly convex for KHC/KLC less than 1. Cardiogenic oscillations (CO) of the expired N2 were produced by alternate flows from either NC or HC and LC. CO diminished in fast expiration, and a phase shift between the heart pulsation and the CO was seen; both agree with experimental findings.
Analysis of bronchial mechanics and density dependence of maximal expiratory flow
Authors: Lambert R. K.
Published: December 2017

The computational model for expiratory flow in humans of Lambert and associates (J. Appl. Physiol. Respirat. Environ. Exercise Physiol. 52: 44–56, 1982) was used to investigate the effect of bronchial constrictions in three airway zones on the density dependence of maximal expiratory flow. It was found that constriction of the peripheral airways (less than 2 mm diam) reduced density dependence and increased the volume of isoflow. Constriction of the larger intraparenchymal airways resulted in increased density dependence at low lung volumes and essentially normal values at other volumes. The volume of isoflow was reduced. Extraparenchymal (but intrathoracic) airway constriction caused no change in the volume of isoflow but caused increased density dependence at the higher lung volumes. It was shown that in these model simulations the addition of extraparenchymal constriction to intraparenchymal constriction causes essentially no changes in density dependence. An increased volume of isoflow and significantly decreased density dependence at 50 and 25% vital capacity were produced by simulated constrictions only in the peripheral airways.
Inhibition of carbonic anhydrase by plasma of dogs and rabbits
Authors: Hill Esther P.
Published: December 2017

Page 191: Esther P. Hill. “Inhibition of carbonic anhydrase by plasma of dogs and rabbits.” Page 192: the eighth through the eleventh sentences of paragraph 2 should read: One milliliter of reaction solution (see below) was placed in a small reaction vessel and stirred with a magnetic stirrer. One-tenth milliliter of CO2-saturated saline was added....