bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of the caudal ventrolateral medulla decreases total lung resistance in dogs
Authors: Connelly J. C. , McCallister L. W. , Kaufman M. P.
Published: December 2017

Although the role played by the caudal ventrolateral medulla in the regulation of the cardiovascular system has been extensively investigated, little is known about the role played by this area in the regulation of airway caliber. Therefore, in alpha-chloralose-anesthetized dogs, we used both electrical and chemical means to stimulate the caudal ventrolateral medulla while we monitored changes in total lung resistance breath by breath. We found that electrical stimulation (25 microA) of 26 sites in this area significantly decreased total lung resistance from 7.1 +/- 0.4 to 5.7 +/- 0.3 cmH2O.1'1.s (P less than 0.001). The bronchodilation evoked by electrical stimulation was unaffected by beta-adrenergic blockade but was abolished by cholinergic blockade. In addition, chemical stimulation of seven sites in the caudal ventrolateral medulla with microinjections of DL-homocysteic acid (0.2 M; 66 nl), which stimulates cell bodies but not fibers of passage, also decreased total lung resistance from 8.3 +/- 1.1 to 6.5 +/- 0.8 cmH2O.l'1.s (P less than 0.01). In contrast, microinjections of DL-homocysteic acid into the nucleus ambiguus (n = 6) increased total lung resistance from 7.5 +/- 0.5 to 9.2 +/- 0.4 cmH2O.l'1.s (P less than 0.05). We conclude that the caudal ventrolateral medulla contains a pool of cell bodies whose excitation causes bronchodilation by withdrawing cholinergic input to airway smooth muscle.
Body composition in adolescents: estimation by total body electrical conductivity
Authors: Presta E. , Casullo A. M. , Costa R. , Slonim A. , Van Itallie T. B.
Published: December 2017

This comparative study, conducted on 28 boys and girls of widely varying fatness, was designed to validate a new whole-body composition method [total body electrical conductivity (TOBEC)], based on bioelectrical properties of the human body. A significant correlation [r = 0.911; standard error of the estimate (SEE) = 5.3 kg] was demonstrated between the transformed TOBEC scores (TOBEC0.5 X Ht) and lean body mass (LBM) determined by hydrodensitometry and corrected for individual variations in hydration (LBMd + W). TOBEC determinations also correlated well with 1) total body water determined by deuterium oxide dilution (r = 0.877; SEE = 4.5 liters), 2) total body potassium determined by means of a 4 pi whole-body counter (r = 0.860; SEE = 430.7 meq), 3) LBM derived from skinfold thicknesses (r = 0.850; SEE = 5.8 kg). The residuals of the regression between LBMd + W and TOBEC scores did not show any significant correlation with either the potassium or the water content of the LBM. The results indicate that TOBEC is a simple, rapid, reliable, and noninvasive technique for delineating changes in body composition that occur in children during growth.
Comparison of two synthetic progesterones on ventilation in normal males: CMA vs. MPA
Authors: Morikawa T. , Tanaka Y. , Maruyama R. , Nishibayashi Y. , Honda Y.
Published: December 2017

We administered chlormadinone acetate (CMA), medroxyprogesterone acetate (MPA), and placebo to 16 normal male subjects using a randomized double-blind crossover study. After CMA administration, minute alveolar ventilation increased by +1.04 +/- 0.22 (SE) 1/min (P less than 0.05) accompanied by decrements of arterial PCO2 (-4.0 +/- 1.0 Torr) (P less than 0.01) and [HCO3-] (-2.1 +/- 0.05 mM/l) (P less than 0.01). On the other hand, in the MPA runs the corresponding changes of the above parameters were +0.71 +/- 0.21 l/min (P less than 0.05), -2.9 +/- 0.6 Torr (P less than 0.01), and -1.3 +/- 0.3 mM/l (P less than 0.01), respectively. The slopes of hypoxic ventilatory and occlusion pressure response lines remained unchanged in hypocapnia after CMA or MPA ingestion, but they increased when entidal PCO2 was adjusted to the predrug level. The hypercapnic ventilatory and occlusion pressure response lines merely shifted to the left without changing their slopes with these agents. No significant differences in all the above parameters were found between CMA and MPA runs. We concluded that in the normal males the effect of CMA on ventilation was similar to that of MPA, despite the fact that the luteinizing activity of CMA was reported to be approximately 10 times higher than the latter.
Changes in end-expiratory lung volume during sleep in patients with occlusive apnea
Authors: Aronson R. M. , Alex C. G. , Onal E. , Lopata M.
Published: December 2017

Eight patients with occlusive sleep apnea were monitored during non-rapid-eye-movement (NREM) sleep to study the factors that contribute to negative inspiratory pressure generation and thus upper airway occlusion. End-expiratory lung volume assessed by respiratory inductive plethysmography [sum of end-expiratory levels (SUM EEL)] increased early and decreased late during the ventilatory phases (P less than 0.0001, one-way analysis of variance). Inspiratory change in esophageal pressure (Pes) and peak inspiratory diaphragmatic and genioglossal electromyograms (EMGdi and EMGge) decreased while the inspiratory pressure generated for a given diaphragmatic activity (Pes/EMGdi) increased during the preapneic phase (P less than 0.0001, for all). Multiple regression analysis with Pes/EMGdi as the dependent variable (R2 = 0.90) indicated that both the changes in SUM EEL and EMGge significantly contributed to the model (P less than 0.008 and 0.004, respectively). These results indicate that end-expiratory lung volume fluctuates during NREM sleep in patients with occlusive apnea and suggest that these changes along with the changes in upper airway muscle activity contribute to the generation of negative inspiratory pressure, leading to the passive collapse of the upper airways.
Resistance and reactance of the excised human larynx, trachea, and main bronchi
Authors: Jiang T. X. , Cauberghs M. , Van de Woestijne K. P.
Published: December 2017

We investigated the impedance of excised preparations of the human larynx before and after resection of the vocal cords and of the trachea whether or not in connection with the main bronchi for steady (75–700 ml.s-1) and oscillatory flows (4–64 Hz). To simulate the influence of respiratory flow on oscillatory resistance (Rosc), oscillatory and steady flow were superimposed. This resulted in a marked increase of Rosc, dependent on the value of steady flow, a change of the frequency dependence of Rosc, and a decrease of the reactance. The latter effects were particularly pronounced in the preparations of the larynx, especially with a narrow glottis opening. The influence of steady flow on oscillatory resistances is probably the expression of interactions of steady and oscillatory flow regimes in the larynx. Similar but less pronounced interactions are also met in the trachea. These effects lead to a systematic overestimation of upper airway resistance when measured during spontaneous breathing by means of a forced oscillation technique.
Acute changes in high-density lipoprotein cholesterol with exercise of different intensities
Authors: Hicks A. L. , MacDougall J. D. , Muckle T. J.
Published: December 2017

The purpose of this study was to investigate the acute effects of exercise on plasma high-density lipoprotein cholesterol (HDL-C) and to determine whether the magnitude of this response would be affected by the intensity of the exercise. Twelve men (19–41 yr) ran an equivalent distance (9–12 km) on a treadmill on two separate occasions. On one occasion the exercise was performed at a speed that elicited 60% of the subject's maximal O2 uptake (VO2max), and on the other occasion exercise was performed at a speed that elicited 90% of VO2max. Changes in total cholesterol, triglycerides (TG), HDL-C, HDL apoprotein A (HDL-A), HDL saturation, lactate (LA), and free fatty acids (FFA) were measured during the course of each run, and all values were corrected for changes in plasma volume as indicated by hematocrit. There were significant increases (P less than 0.01) in HDL-C, HDL-A, and HDL saturation with exercise at both intensities, but greater increases in HDL-C (25 vs. 14%) and HDL-A (18 vs. 8%) were observed with the higher intensity exercise. Plasma FFA and TG did not differ between conditions, but LA concentrations rose significantly during the high-intensity exercise. These results indicate that increases in HDL components can occur with a relatively moderate exercise session and that the magnitude of these increases are directly related to the exercise intensity.
Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate
Authors: Rouby J. J. , Houissa M. , Brichant J. F. , Baron J. F. , McMillan C. , Arthaud M. , Amzallag P. , Viars P.
Published: December 2017

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20–30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS)
Effectiveness of three field treatments for induced mild (33.0 degrees C) hypothermia
Authors: Giesbrecht G. G. , Bristow G. K. , Uin A. , Ready A. E. , Jones R. A.
Published: December 2017

Three field applicable treatments for hypothermia were compared. Subjects were cooled in stirred cold water (8.0 degrees C) to a core temperature (Tco) as low as 33 degrees C and rewarmed in a random order by each of three techniques: shivering, external heat, and treadmill exercise. Tco was monitored with an esophageal thermistor probe at the level of the heart. Treatment effectiveness was determined by calculating the amount of Tco afterdrop, length of afterdrop period, rate of Tco increase, and total recovery time. Rate of Tco increase for exercise (4.9 degrees C/h) was significantly higher (P less than 0.05) than shivering (3.5 degrees C/h) but not external heat (3.7 degrees C/h). Exercise afterdrop amount and afterdrop length values (0.95 degrees C and 24 min, respectively) were significantly higher (P less than 0.05) than both shivering (0.33 degrees C, 15 min) and external heat (0.32 degrees C, 14 min). Therefore, although rate of Tco increase during recovery for exercise was faster than for shivering or external heat, as it was preceded by a greater afterdrop length and amount, total recovery time did not differ among the three treatments.
Hypoxia enhances unilateral lung injury by increasing blood flow to the injured lung
Authors: Takeda K. , Knapp M. J. , Wolfe W. G. , Crapo J. D.
Published: December 2017

We hypothesized that in unilateral lung injury, bilateral hypoxic ventilation would induce vasoconstriction in the normal lung, redirect blood flow to the injured lung, and cause enhanced edema formation. Unilateral left lung injury was induced by intrabronchial instillation of 1.5 ml/kg of 0.1 N HCl. After HCl injury, blood flow to the injured left lung decreased progressively from 0.70 +/- 0.04 to 0.37 +/- 0.05 l/min and percent of flow to the injured left lung (QL/QT) decreased from 37.7 +/- 2.2 to 23.6 +/- 2.2% at 240 min. Exposure to hypoxia (12% O2) for three 10-min episodes did not affect QL/QT in normal animals, but after unilateral HCl injury, it caused blood flow to the injured left lung to increase significantly. A concomitant decrease in blood flow occurred to the noninjured right lung, resulting in a significant increase in QL/QT. The enhanced blood flow to the injured lung was associated with a significant increase in the wet-to-dry lung weight ratio in the dependent regions of the injured lung. These findings demonstrate that in unilateral HCl-induced lung injury, transient hypoxia can enhance blood flow to the areas of injury and increase lung edema formation.
A model for hypoxic constriction of the pulmonary circulation
Authors: Marshall B. E. , Marshall C.
Published: December 2017

The detailed anatomic and biodynamic data provided for the cat lung by Zhuang et al. (J. Appl. Physiol. 55: 1341-1348, 1983) allowed pressure-flow curves for the normal lung to be generated. This model has been modified to permit the stimulation of the pressure and flow distribution effects of hypoxic pulmonary vasoconstriction for a two-compartment lung and generalized to allow comparison with the experimental results from dogs (and probably other species). Hypoxic pulmonary vasoconstriction is simulated by reduction of the initial diameter of the smallest six orders of pulmonary arteries. Expressions are presented that relate the alveolar and mixed-venous O2 tensions to a graded constriction of these vessels. In addition, the diameter of the capillary sheet and the six small arteries is defined with a maximum diameter at a transmural pressure of 20 cmH2O. Pressure-flow curves are derived for any combination of alveolar and mixed-venous O2 tension, alveolar and pleural pressure, left atrial pressure, and hematocrit. The two-compartment model is solved by an iterative procedure to identify the distribution of the flow and the resulting pulmonary arterial pressure when the compartments differ by size, hypoxic constriction, or other imposed conditions. The results of the model are compared with those from a variety of experimental preparations. It is concluded that the model is useful for identifying the quantitative causes of changes in the response to hypoxic pulmonary vasoconstriction and for the exploration of the functional influence of mechanical properties of the vasculature.
Inspiratory muscle activity during unloaded and obstructed rebreathing in dogs
Authors: D'Angelo E. , Garzaniti N. , Bellemare F.
Published: December 2017

Moving-average electromyogram (EMG) of the diaphragm (DI), scalenes, and cranial and caudal parasternals was assessed in anesthetized, supine, and head-up dogs during rebreathing. The shape of EMG trajectory was similar for all muscles and conditions; activation of different muscles could be thus compared on the basis of changes in peak activity. In intact dogs changes in peak activity were greater for the scalenes and cranial parasternals than for the caudal parasternals and greater for the inspiratory thoracic muscles (ITM) than for the DI. Posture, vagotomy, and cordotomy at C7-T1 did not affect the rate of rise of DI activity. The relations between peak activity of ITM did not change because of posture, vagotomy, and phrenicotomy. Vagotomy selectively depressed the rate of rise of ITM activity, but relative changes in peak ITM activity for a given change in peak DI activity were independent of intact vagi. Differences in the pattern of activation between inspiratory muscles with rebreathing are largely independent of proprioceptive inputs and likely reflect properties of central control mechanisms. However, airway occlusion at end expiration caused a reflex fall of DI activity and reflex increase of ITM activity in intact and vagotomized dogs. Cordotomy at C7-T1 did not change DI response, whereas reduction of ITM activity occurred after phrenicotomy, indicating that both facilitatory and inhibitory segmental inputs are involved in ITM response to loading.
Intrapleural liquid flow down a gravity-dependent hydraulic pressure gradient
Authors: Miserocchi G. , Negrini D. , Pistolesi M. , Bellina C. R. , Gilardi M. C. , Bettinardi V. , Rossitto F.
Published: December 2017

We studied the vertical movement of 2 mg technetium-labeled albumin injected intrapleurally in 0.5 ml saline (15% of pleural liquid volume) in eight spontaneously breathing anesthetized dogs subject to a sudden change in posture (prone to supine or vice versa). The albumin movements were evaluated through a large field gamma camera placed laterally to the animal and detecting total (AT) and regional activities from two superimposed equal areas (At and Ab, top and bottom, respectively). The At/Ab ratio decreased from 2.1 to 1.3 in four animals up to 20 min from the change in posture and from 0.9 to 0.5 in four more animals studied from 50 to 90 min from turning maneuver. The rate of change in At and Ab was similar in the two groups of animals and unaffected by the acquisition posture. AT decreased by 7.7 and 3.5% for the two groups, respectively, reflecting albumin clearance from the pleural space. The opposite time course of regional activities and the independence of their rate of change of the At/Ab ratio and of the animal posture suggest a top-to-bottom albumin transfer occurring through a bulk flow of liquid estimated at 0.006 ml.kg-1.h-1. The data are consistent with a measured vertical pleural liquid pressure gradient that does not reflect a hydrostatic condition.
Gravitational independence of single-breath washout tests in recumbent dogs
Authors: Tomioka S. , Kubo S. , Guy H. J. , Prisk G. K.
Published: December 2017

To examine the mechanisms of lung filling and emptying, Ar-bolus and N2 single-breath washout tests were conducted in 10 anesthetized dogs (prone and supine) and in three of those dogs with body rotation. Transpulmonary pressure was measured simultaneously, allowing identification of the lung volume above residual volume at which there was an inflection point in the pressure-volume curve (VIP). Although phase IV for Ar was upward, phase IV for N2 was small and variable, especially in the prone position. No significant prone to supine differences in closing capacity for Ar were seen, indicating that airway closure was generated at the same lung volumes. The maximum deflections of phase IV for Ar and N2 from extrapolated phase III slopes were smaller in the prone position, suggesting more uniform tracer gas concentrations across the lungs. VIP was smaller than the closing volume for Ar, which is consistent with the effects of well-developed collateral ventilation in dogs. Body rotation tests in three dogs did not generally cause an inversion of phase III or IV. We conclude that in recumbent dogs regional distribution of ventilation is not primarily determined by the effect of gravity, but by lung, thorax, and mediastinum interactions and/or differences in regional mechanical properties of the lungs.
Subcellular changes in capillary endothelial cells during repair of hyperoxic lung injury
Authors: Mastin J. P. , Shelburne J. D. , Thet L. A.
Published: December 2017

We studied the changes in subcellular ultrastructure associated with the hypertrophy of capillary endothelial cells during repair of hyperoxic (100% O2) lung injury in rats. We used stereologic-morphometric measurements at different magnifications to determine the absolute volume of each subcellular compartment per average capillary endothelial cell. The increases in this value during the first 3 days of postexposure repair were 118% for cytoplasm, 786% for polyribosomes, 310% for rough endoplasmic reticulum, and 79% for mitochondria; the volume of pinocytotic vesicles did not change. By day 7 of repair, only the polyribosomes and rough endoplasmic reticulum were still increased; by day 14 all values were normal. We conclude that the capillary endothelial cell hypertrophy that develops during repair of hyperoxic lung injury is associated with large and heterogeneous increases in subcellular organelles and is not merely due to increases in the cytosol or to cellular edema. These increases seem to be an integral part of the repair process and may be important in the development of tolerance to subsequent oxygen exposure.
Reflex constriction of human limb resistance vessels to head-down neck flexion
Authors: Essandoh L. K. , Duprez D. A. , Shepherd J. T.
Published: December 2017

The effect of head-down neck flexion on forearm and calf blood flow was determined in 10 healthy male subjects. The subject lay prone, with the neck slightly extended and the chin resting on a soft-padded support at the edge of the table. The chin support was then removed, and the subject maximally flexed and lowered the neck. This was followed by return to the initial position. Neck flexion caused a rapid decrease in blood flow in both forearm and calf; at 30 s this averaged 39 and 35%, respectively. The flow in both forearm and calf gradually recovered as the neck flexion was sustained and approached the control values at the end of 10 min. The blood flow at the ankle was unchanged, indicating that the decrease occurred in the skeletal muscles. The arterial blood pressure and heart rate were unchanged; thus the decrease in flow was due to vasoconstriction. The fact that the decrease was evident as soon as the head was lowered indicated that it was nervously mediated. Neither contraction of the flexor muscles of the neck nor venous congestion of the head, in the absence of the head-down position, altered the blood flow. Although the mechanism of the decrease in flow has not been determined, the studies demonstrate that in response to certain stimuli, the resistance vessels in the skeletal muscles of the forearm and calf undergo a similar nervously mediated vasoconstriction.
Effects of almitrine on respiration in unanesthetized newborn rabbits
Authors: Weese-Mayer D. E. , Klemka L. M. , Brouillette R. T. , Hunt C. E.
Published: December 2017

We previously demonstrated that almitrine, a peripheral chemoreceptor stimulant, increased tidal volume (VT), expired minute ventilation (VE), and respiratory frequency (f) and decreased inspiratory (TI) and expiratory time (TE) in sleeping adult cats. We now hypothesized that almitrine would induce an increase in ventilation in a young animal model. Respiration was studied by the barometric method in 11 unanesthetized New Zealand White rabbit pups between 3 and 6 days of age. Recordings were made in 0.21 FIO2 at base line and after cumulative intraperitoneal infusions of almitrine (2.5, 5.0, and 7.5 mg/kg). The chamber pressure deflection (proportional to VT after appropriate calculation) was computer sampled at 200 Hz. At least 100 breaths for each dose in each animal were analyzed. We found that a 7.5-mg/kg intraperitoneal dose of almitrine increased f to 135 +/- 9% (SE) of base line and decreased TE and TI to 72 +/- 8% and 79 +/- 8% of base line, respectively. Changes in VE, VT/TI, and VT were not significant. Recognizing that apnea is associated with inadequate ventilation and a prolonged TE (failure of the "inspiratory on-switch"), these results, particularly the increase in f and decrease in TE, suggest that almitrine might be useful in treating apnea in preterm infants.
Numerical and experimental study of steady-state CO2 and inert gas washout
Authors: Scherer P. W. , Gobran S. , Aukburg S. J. , Baumgardner J. E. , Bartkowski R. , Neufeld G. R.
Published: December 2017

The predictions of a single-path trumpet-bell numerical model of steady-state CO2 and infused He and sulfur hexafluoride (SF6) washout were compared with experimental measurements on healthy human volunteers. The mathematical model used was a numerical solution of the classic airway convention-diffusion equation with the addition of a distributed source term at the alveolar end. In the human studies, a static sampling technique was used to measure the exhaled concentrations and phase III slopes of CO2, He, and SF6 during the intravenous infusion of saline saturated with a mixture of the two inert gases. We found good agreement between the experimentally determined normalized slopes (phase III slope divided by mixed expired concentration) and the numerically determined normalized slopes in the model with no free parameters other than the physiological ones of upper airway dead space, tidal volume, breathing frequency, and breathing pattern (sinusoidal). We conclude 1) that the single-path (Weibel) trumpet-bell anatomic model used in conjunction with the airway convection-diffusion equation with a distributed source term is adequate to describe the steady-state lung washout of CO2 and infused He and SF6 in normal lungs and 2) that the interfacial area separating the tidal volume fron from the functional residual capacity gas, through which gas diffusion into the moving tidal volume occurs, exerts a major effect on the normalized slopes of phase III.
Spectral analysis of ventilation in elderly subjects awake and asleep
Authors: Pack A. I. , Silage D. A. , Millman R. P. , Knight H. , Shore E. T. , Chung D. C.
Published: December 2017

We studied the periodicities of ventilation in elderly subjects using digital comb filtering. Two groups of subjects were studied, those with and without sleep apnea. Measurements were made in wakefulness, stage 1-2 sleep, and where possible in stage 3-4 sleep. For each of the digital filters we calculated the average power of the oscillatory output. To compare subject groups we first specifically determined the average power in the filter with the maximum output. The mean of this measurement was greater in elderly subjects with apnea compared with those without apnea, both during wakefulness and stage 1-2 sleep. In both groups of subjects the cycle time of the major ventilatory oscillations was on the order of 40-60 s. There was no difference in this cycle time between the two groups of subjects in wakefulness or stage 1-2 sleep. Thus, whereas similar oscillatory processes occur in subjects with and without apnea, it is the magnitude of the oscillation that differs between the two groups. These conclusions are supported by analysis of the output of individual filters of the digital comb filter. In both groups, stage 1-2 sleep produced significantly increased oscillations in ventilation. Both in wakefulness and stage 1-2 sleep, significantly greater periodicities occurred in the apneic compared with the nonapneic group. In the few subjects who had sufficient data in stage 3-4 sleep for spectral analysis, ventilatory oscillations were virtually absent in this state. Our data suggest that subjects who develop apnea during sleep have an increased propensity for periodic breathing even while awake.
Don't pool the wool over your eyes
Authors: Homer L. D.
Published: December 2017

You have just finished a series of experiments to discover if your two favorite variables (X1 and X2) are, as you have shrewdly suspected, linearly related to one another.
Rapid and transient excitation of respiration mediated by central chemoreceptor
Authors: Arita H. , Kogo N. , Ichikawa K.
Published: December 2017

We evaluated rapid and transient changes in phrenic nerve (PN) and internal intercostal (IIC) activities when 0.2-0.5 ml of saline saturated with 100% CO2 was injected into the vertebral artery during various respiratory phases in decerebrated spontaneously breathing cats. The injections evoked an initial transient inhibition of ongoing PN or IIC activity with a mean onset latency of 0.17 s, followed by excitation of subsequent respiratory activities with an onset latency ranging from 0.4 to 2.7 s; the average onset latency of expiratory excitation (1.49 s) was significantly longer than that of inspiratory facilitation (0.89 s). The initial inhibitory responses were analogous to reflex effects of injections of phenyl biguanide, indicating that the initial inhibition was due to activation of vascular nociceptors and the subsequent excitation was due to stimulation of the central chemoreceptors. In addition, CO2-saline injections during hypocapnic apnea developed a quick reappearance of respiratory rhythm, and the first facilitatory effect appeared in tonic IIC activity, which became more active before rhythm started. In summary, the present study, by use of a technique of vertebral arterial injections of 100% CO2-saline, revealed dynamic properties of respiratory control system mediated by central chemoreceptors and vascular nociceptors.
Anaerobic metabolism during pubertal development at high altitude
Authors: Fellmann N. , Bedu M. , Spielvogel H. , Falgairette G. , Van Praagh E. , Jarrige J. F. , Coudert J.
Published: December 2017

In a previous study we showed that there were no differences in anaerobic metabolism between groups of 11-yr-old children living at high (3,700 m) and low (330 m) altitudes. The aim of this study is to investigate changes in this metabolism during pubertal development. We compare blood lactate concentration ([L]) after maximal bicycle exercise in 20 boys acclimatized to high altitude (HA, 12 yr old) and at low altitude in 14 boys (LA1, 12 yr old) and in 13 boys (LA2, 14 yr old). The subjects had the same level of physical fitness and the same nutritional and socioeconomic status. Pubertal development was identified by salivary testosterone concentration ([T]). Results (means ± SE) showed 1) at the age of 12 years, [L] and [T] in HA were significantly higher than in LA1 ([L] was 9.2 ± 0.5 vs. 6.8 ± 0.5 mmol/l, [T] was 233 ± 66 vs. 132 ± 30 pmol/l), 2) [L] and [T] in HA were statistically the same as in LA2, and 3) a linear relationship between [L] and [T] was significant (P less than 0.05) in all HA and LA subjects. This suggests that the higher [L] in 12-yr-old boys living at HA could result in an enhanced anaerobic metabolism linked to an earlier gonadal maturation evaluated by testosterone level.
Ventilatory responses to lung inflation and arterial CO2 in halothane-anesthetized dogs
Authors: Mitchell G. S. , Selby B. D.
Published: December 2017

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration (TE) in chloralose-urethan-anesthetized dogs. Surgical removal of the carotid bodies abolishes this interaction. Since halothane anesthesia in hyperoxia greatly impairs peripheral chemoreflexes, experiments were conducted to determine whether hypercapnia would attenuate the effects of Paw on f and TE in halothane-anesthetized dogs (approximately 1.5 minimum alveolar concentration). Integrated activity of the phrenic nerve was monitored as a function of Paw (2-12 cmH2O) in a vascularly isolated left lung at varied levels of arterial PCO2 (PaCO2; 38-80 Torr) controlled by inspired gas concentrations ventilating the denervated but perfused right lung. Halothane was administered only to the right lung. The results were as follows: 1) integrated phrenic amplitude increased with PaCO2 but was unaffected by Paw; 2) f decreased as Paw increased but was not affected by PaCO2; 3) the inspiratory duration (TI) increased as PaCO2 increased but was unaffected by Paw; 4) TE increased as Paw increased but was unaffected by PaCO2; and 5) there was no phrenic response to intravenous sodium cyanide (50-100 micrograms/kg). Thus, unlike chloralose-urethan-anesthetized dogs, hypercapnia does not attenuate the effect of lung inflation on f or TE in halothane-anesthetized dogs. Furthermore, hypercapnia increases TI during halothane anesthesia, an effect found after carotid denervation but not found in intact chloralose-urethan-anesthetized dogs. It is suggested that these differences between chloralose-urethan- and halothane-anesthetized dogs may be due to functional carotid chemoreceptor denervation by halothane.
Transient analysis of cardiopulmonary interactions. I. Diastolic events
Authors: Peters J. , Kindred M. K. , Robotham J. L.
Published: December 2017

The etiology of the fall in left ventricular stroke volume (LVSV) with negative intrathoracic pressure (NITP) during inspiration has been ascribed to a reduction in LV preload. This study evaluated the effects of NITP with and without airway obstruction confined to early (ED), mid- (MD), or late diastole (LD) on the subsequent LVSV, anteroposterior (AP), and right-to-left (RL) aortic diameters (DAO) (series I, n = 6) as well as on phasic arterial blood flow out of the thorax (series II, n = 6) in anesthetized dogs. Transient NITP was obtained by electrocardiogram-triggered phrenic nerve stimulation. In series I, NITP applied for 60% of diastole with the airway obstructed caused decreases of LVSV during ED [-7.7 +/- 3.2% (SE) NS], MD (-11.7 +/- 3.9%, P less than 0.05), and LD (-14.6 +/- 1.5%, P less than 0.01) associated with significant increases of left ventricular end-diastolic pressures relative to both atmospheric and esophageal pressures during MD and LD. NITP increased DAO(AP) and DAO(RL), resulting in increases in diastolic aortic cross-sectional area by an average of 6.1-8.3% (P less than 0.01). Similar changes were seen with the airway unobstructed during NITP. In series II, NITP caused diminished diastolic antegrade carotid artery and/or descending aortic flow run off in all dogs. Transient retrograde arterial flows with NITP were observed in more than half of the animals consistent with increases in aortic diameters. We conclude that a decrease of intrathoracic pressure confined to diastole can 1) diminish the ensuing LVSV, presumptively reducing preload by ventricular interdependence; 2) distend the intrathoracic aorta; 3) diminish antegrade flow out of the thorax independent of effects on cardiac performance; and 4) cause transient retrograde carotid and aortic blood flow. The intrathoracic aorta and, presumably, the arterial intrathoracic vascular compartment can be viewed as an elastic container driven by changes in intrathoracic pressure.
Properties of steady maximal expiratory flow within excised canine central airways
Authors: Solway J.
Published: December 2017

Using our transistor model of the lung during forced expiration (J. Appl. Physiol. 62: 2013-2025, 1987), we recently predicted that 1) axially arranged choke points can exist simultaneously during forced expiration with sufficient effort, and 2) overall maximal expiratory flow may be relatively insensitive to nonuniform airways obstruction because of flow interdependence between parallel upstream branches. We tested these hypotheses in excised central airways obtained from five canine lungs. Steady expiratory flow was induced by supplying constant upstream pressure (Pupstream = 0-16 cmH2O) to the bronchi of both lungs while lowering pressure at the tracheal airway opening (16 to -140 cmH2O). Intra-airway pressure profiles obtained during steady maximal expiratory flow disclosed a single choke point in the midtrachea when Pupstream was high (2-16 cmH2O). However, when Pupstream was low (0 cmH2O), two choke sites were evident: the tracheal site persisted, but another upstream choke point (main carina or both main bronchi) was added. Flow interdependence was studied by comparing maximal expiratory flow through each lung before and after introduction of a unilateral external resistance upstream of the bronchi of one lung. When this unilateral resistance was added, ipsilateral flow always fell, but changes in flow through the contralateral lung depended on the site of the most upstream choke. When a single choke existed in the trachea, addition of the external resistance increased contralateral flow by 38 +/- 28% (SD, P less than 0.003). In contrast, when the most upstream choke existed at the main carina or in the bronchi, addition of the external resistance had no effect on contralateral maximal expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep
Authors: Ahmed T. , D'Brot J. , Wasserman M. , Muccitelli R. , Robinson M. , Tucker S. , Marchette B.
Published: December 2017

Leukotrienes have been suggested to play a role in the endotoxin-induced changes of the pulmonary hemodynamics and airway mechanics. Since Ca2+ is necessary for contraction of airway and vascular smooth muscle as well as for activation of phospholipase A2 and 5-lipoxygenase enzymes, we wondered whether the calcium antagonist verapamil would modify the endotoxin-mediated pulmonary effects as well as the generation of circulating eicosanoids. In twelve conscious sheep, measurements of pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), lung resistance (RL), arterial PO2 (PaO2), leukocyte (WBC) count, arterial thromboxane B2 (TxB2), prostaglandin (PG) F2 alpha, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentrations were obtained before and at predetermined intervals after a 10-min infusion of Escherichia coli endotoxin (0.3 microgram/kg). On separate occasions, the sheep received a bolus injection of verapamil (150 micrograms/kg) before endotoxin, followed by a continuous infusion of verapamil [10 micrograms.kg-1.min-1 (n = 5) or 20 micrograms.kg-1.min-1 (n = 7)] for up to 4 h post-endotoxin. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 326 and 276% of base line during phase I (0-1 h) and lesser increases to 177 and 157% of base line during phase II (1.5-4 h), respectively (P less than 0.05). SVR also showed biphasic increases of 44 and 42% during phase I and II, respectively. Mean PaO2 decreased by 16 Torr and WBC count decreased from 6.4 +/- 1.5 to 3.3 +/- 1.1 thousand/mm3, associated with marked increases in plasma TxB2, PGF2 alpha, and 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
Thromboxane effects on canine trachealis neuromuscular function
Authors: Serio R. , Daniel E. E.
Published: December 2017

The objective of this study is to determine which inflammatory mediators had direct effects on canine trachealis muscle neuromuscular control to identify candidate mediators of the hyperresponsiveness observed in vitro after O3 exposure. Studies were carried out in the sucrose gap at 29 degrees C and in the muscle bath at 37 degrees C. Leukotriene (LT) B4, LTD4, and prostaglandin (PG) D2 had neither direct nor significant effects on the excitatory junction potentials (EJP's), the secondary membrane potential oscillations, or the associated contractions that followed field stimulation of cholinergic nerves. U 46619, a stable analogue of thromboxane (Tx) A2, enhanced (10(-10)-10(-7) M) the duration and the amplitude of secondary oscillations and associated contractions without affecting the EJP's. In the muscle bath, U 46619 enhanced field-stimulated contractions; this was antagonized competitively by SQ 29548. In both the sucrose gap and the muscle bath, higher concentrations (10(-9) M and higher) caused direct effects, small depolarizations, and contractions. These effects of U 46619 were unaffected by indomethacin or guanethidine but were abolished by SQ 29548, an antagonist selective at TxA2-PGH2 receptors. U 46619 at 10(-9) M did not affect electrical or mechanical responses to acetylcholine and at 10(-9) M did not increase the sensitivity to acetylcholine. Platelet-activating factor (PAF) was inactive in all muscle-bath and most sucrose-gap experiments. In 7 of 20 of the latter, it caused effects qualitatively like those of U 46619, but whether it acted through release of TxA2 could not be tested because of the rapid tachyphylaxis to PAF. We conclude that TxA2 may mediate the hyperresponsiveness found in vitro after O3 treatment.
Tone-dependent responses to acetylcholine in the feline pulmonary vascular bed
Authors: Hyman A. L. , Kadowitz P. J.
Published: December 2017

The effects of an increase in base-line tone on pulmonary vascular responses to acetylcholine were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, intralobar injections of acetylcholine under low-tone base-line conditions increased lobar arterial pressure in a dose-related manner. When tone was increased moderately by alveolar hypoxia, acetylcholine elicited dose-dependent decreases in lobar arterial pressure, and at the highest dose studied, acetylcholine produced a biphasic response. When tone was raised to a high steady level with the prostaglandin analogue, U46619, acetylcholine elicited marked dose-related decreases in lobar arterial pressure. Atropine blocked both vasoconstrictor responses at low tone and vasodilator responses at high tone, whereas meclofenamate and BW 755C had no effect on responses to acetylcholine at low or high tone. The vasoconstrictor response at low tone was blocked by pirenzepine (20 and 50 micrograms/kg iv) but not gallamine (10 mg/kg iv). The vasodilator response at high tone was not blocked by pirenzepine (50 micrograms/kg iv) or gallamine or pancuronium (10 mg/kg iv). The present data support the concept that pulmonary vascular responses to acetylcholine are tone dependent and suggest that the vasoconstrictor response under low-tone conditions is mediated by a high-affinity muscarinic (M1)-type receptor. These data also suggest that vasodilator responses under high-tone conditions are mediated by muscarinic receptors that are neither M1 nor M2 low-affinity muscarinic-type receptor and that responses to acetylcholine are not dependent on the release of cyclooxygenase or lipoxygenase products.
Temporal and regional variability of collateral resistance response to histamine
Authors: Ludwig M. S. , Shore S. A. , Anderson K. , Drazen J. M.
Published: December 2017

Using the wedged bronchoscope technique, we measured the changes in collateral resistance (Rcoll) in dogs resulting from exposure to aerosols of increasing concentrations of histamine. Histamine dose-response curves were performed in each of two to three separate lobar segments of an individual mongrel dog's lungs. Five dogs were studied. The same segments were reexamined on later occasions (2–11 wk apart) to determine whether the responsiveness to histamine had altered with time. Measurements of base-line Rcoll for a given segment were reproducible (coefficient of variation 0.48). In contrast, we observed that the estimated dose of histamine required to increase Rcoll by 50% (ED150Rcoll) was extremely variable both among lung segments of an individual dog on a single experimental day (geometric mean variability of 40-fold) and for a given segment when reexamined on repeated occasions (geometric mean variability of 47-fold). The ED150Rcoll did not correlate with the base-line Rcoll. The degree of variability we observed suggests that peripheral contractile elements are under the influence of powerful local modulating factors that vary both regionally and temporally.
Protective effects of O2 radical scavengers and adenosine in PMA-induced lung injury
Authors: Allison R. C. , Hernandez E. M. , Prasad V. R. , Grisham M. B. , Taylor A. E.
Published: December 2017

We have previously shown that phorbol myristate acetate (PMA) produces acute lung injury in blood-perfused lungs but not in plasma-dextran-perfused lungs. This is compatible with the concept that its major mechanism of injury is the stimulation of O2 radicals by neutrophils, which in turn increase permeability by damaging the endothelial cells. In this study we measured vascular permeability and resistance before and 1 h after PMA in five groups of blood-perfused dog lungs: PMA alone in one group and pretreatment with catalase, superoxide dismutase, deferoxamine, and adenosine each in four other groups. By the use of two indexes of permeability, the filtration coefficient and the isogravimetric capillary pressure, we found that, compared with PMA alone, catalase, deferoxamine, and adenosine provided significant protection, whereas the results with superoxide dismutase were variable. These four drugs also significantly attenuated the marked increased resistance seen with PMA alone. Although the effects seen with the first three can be explained by their scavenging of O2 radicals, adenosine appears to provide protection through a separate mechanism.
IgE-challenged human lung mast cells excite vagal sensory neurons in vitro
Authors: Greene R. , Fowler J. , MacGlashan D. , Weinreich D.
Published: December 2017

Substances released from immunoglobin (Ig) E-stimulated mast cells are likely to be among the chemical mediators responsible for changes in the vagal component of airway reactivity. We have attempted to identify a direct role for mast cell mediators in the control of visceral afferent excitability by examining intracellular electrophysiological changes in vagal neurons after application of extracts prepared from purified and IgE-stimulated human lung mast cells (HLMC). HLMC's, applied by superfusion or by focal pressure ejection from micropipettes, reversibly enhanced the excitability of a subpopulation of rabbit visceral sensory C-fiber neurons by 1) abolishing the slow Ca2+-dependent post-spike after hyperpolarization that uniquely resides in these neurons and controls their spike frequency, 2) depolarizing the cell membrane potential, and 3) increasing membrane input resistance. Control HLMC prepared by subjecting purified human lung mast cells to normal goat serum had no measurable affects on neuronal excitability. The immunologically released constituents responsible for these excitability changes are likely to be lipid mediators, because essentially all biological activity is extractable into an organic phase after methanol-chloroform solvent extraction of the HLMC preparations. These results provide the first unambiguous evidence that products released from immunologically challenged HLMC's directly affect visceral afferent nerve cell function.
Modulation of cholinergic neurotransmission by vasoactive intestinal peptide in ferret trachea
Authors: Sekizawa K. , Tamaoki J. , Graf P. D. , Nadel J. A.
Published: December 2017

We studied the effect of vasoactive intestinal peptide (VIP) on the contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. VIP did not change resting tension up to 2 X 10(-7) M, but it showed a biphasic effect on the responses to EFS. In concentrations up to 10(-9) M, VIP potentiated the response; at higher concentrations VIP reduced responses. Thus, at a concentration of 10(-9) M, VIP decreased the mean (+/- SE) log EFS frequency, producing 50% of maximum contraction significantly from a control value of 0.476 +/- 0.062 to 0.214 +/- 0.057 Hz (P less than 0.01); at a concentration of 2 X 10(-7) M VIP increased the half-maximal frequency from a control value of 0.513 +/- 0.086 to 0.752 +/- 0.053 Hz (P less than 0.05). The potentiating effect of VIP (10(-9) M) was not inhibited by hexamethonium, indomethacin, pyrilamine, methysergide, or [D-Pro2,D-Trp7,9] substance P. The inhibitory effect of VIP (2 X 10(-7) M) was also not inhibited by hexamethonium, indomethacin, or naloxone. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by VIP at concentrations of 10(-9) and 2 X 10(-7) M. These results suggest that VIP modulates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific VIP receptor.