Changes in control of ventilation, awake and asleep, in the elderly.
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Aged↗
Biomedical subjects
A I Pack
Publications and source records attributed to A I Pack.
Responses of pulmonary stretch receptors during ramp inflations of the lung.
Studies were conducted in anesthetized paralyzed dogs to determine how the dynamic and proportional sensitivity of pulmonary stretch receptors change during lung inflation. The firing of each receptor was examined at multiple levels of static transpulmonary pressure and during multiple identical inflations at each of several rates. The averaged response of the receptor was computed and receptor activity related to transpulmonary pressure. On the basis of a quantitative criterion, employed to distinguish type I from type II receptors, the receptors could not be divided into distinct subpopulations. Thus all receptors were treated as coming from a single population. For all receptors we observed that their proportional sensitivity (increases in firing produced by increases in lung expansion at a constant rate of inflation) declined as the lung was inflated. In contrast, the dynamic sensitivity (increases in firing produced by increased rates of inflation at constant transpulmonary pressure) increased or remained relatively constant with increasing lung expansion. Thus, as inflation volume increases, the pulmonary stretch receptor acts increasingly as a rate receptor. The rate of inflation may have a more important role in control of the inspiratory duration than previously realized.
Adaptation, Physiological↗
Control of activity of the diaphragm in rapid-eye-movement sleep.
Respiration in rapid-eye-movement sleep (REMS) is known to be highly variable. The purpose of this study was to investigate the source of this variability and to determine which ordering principles remained operative in REM sleep. In unrestrained, naturally sleeping cats we recorded the electroencephalogram, electrooculogram, neck electromyogram, and diaphragmatic electromyogram (EMG) and computed its moving average (MAdi). As a reference, we first examined MAdi during "tonic" REMS, since breathing is fairly regular in this state. "Control" ranges for peak amplitude (PEMG), inspiratory time (TI), duration of postinspiratory inspiratory activity, expiratory time, and the calculated inspiratory slope (PEMG/TI) were determined by overlaying individual breath traces of the time course of MAdi during tonic REMS to form a composite tracing. Next, the time course of the EMG during individual breaths in slow-wave sleep (SWS) and a complete period of consecutive breaths in REMS (both tonic and phasic) were compared with this tonic REMS composite. The number of eye movements per breath was tabulated as an index of phasic activity. The inspiratory slopes during SWS and tonic REMS were similar. However, during phasic REMS, many breaths displayed either increases (excitation) or decreases (inhibition) in slope compared with the "typical" breaths seen in tonic REMS. The occurrence of these altered slopes increased with the frequency of phasic events. TI was inversely related to the slope of the EMG, which tended to minimize changes in PEMG.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The effect of antigen-induced bronchoconstriction on phrenic nerve activity.
The effects of acute bronchoconstriction, produced by inhalation of Ascaris suum antigen, on both the amplitude and timing of phrenic nerve activity were studied in anesthetized dogs. Blood gas tensions and inspiratory air flow were maintained constant. Bronchoconstriction resulted in a significant increase in the magnitude and rate of rise of the phrenic neurogram during both normal respiratory cycles and cycles when lung inflation was prevented. The increase in the slope of the phrenic neurogram that results from lung inflation was further increased during bronchoconstriction. In addition, in half the animals, there was a significant increase in the tonic phrenic activity measured during expiration. All of these changes were abolished by bilateral cervical vagotomy. Antigen administration did not affect the timing of the different phases of the cycle equally; inspiratory duration was reduced by 51.8% and expiratory duration by 67.6%. Postinspiratory activity of the phrenic (PIIA) was reduced by only 34.7%; thus, during bronchoconstriction PIIA occupied a proportionally greater fraction of the expiratory phase. Vagotomy abolished the changes in respiratory timing and eliminated all PIIA.
Animals↗
Role of the diaphragm in the genesis of lower esophageal sphincter pressure in the cat.
To determine the role of the diaphragm in the genesis of the high-pressure zone at the lower esophageal sphincter (LES) we studied the effect of diaphragmatic contraction on lower esophageal sphincter pressure in 10 anesthetized adult cats. Despite anchoring the pressure recording assembly within the LES to prevent axial movement of the sphincter during respiration relative to the pressure recording ports, there was an average oscillation in LES pressure of 17.4 +/- 5.5 mmHg, the frequency of which was the same as the respiratory rate. Peak LES pressure occurred at end-inspiration corresponding with peak diaphragmatic electromyogram. During periods of central apnea induced by manual hyperventilation there was absence of both diaphragmatic electromyogram and the oscillations in LES pressure. Lower esophageal sphincter pressure during apnea was equal to end-expiratory pressure during spontaneous respiration. Following complete neuromuscular blockade with pancuronium, artificial respiration with increasing tidal volumes resulted in increasing oscillations in pressure. However, the magnitude of the pressure oscillation even at tidal volumes four times normal was always significantly below that observed during spontaneous eupnic respiration. Furthermore, progressive augmentation of diaphragmatic electromyogram activity by breathing 5% CO2 in air revealed a linear correlation between the magnitude of the respiratory-induced pressure oscillations of the LES and peak integrated diaphragmatic electromyogram in individual animals. It is concluded, therefore, that (a) intrinsic LES tone is best approximated by end-expiratory pressure during spontaneous respiration, (b) the respiratory-induced oscillations in LES pressure are primarily the result of active diaphragmatic contraction, and (c) the level of diaphragmatic electrical activity directly influences the magnitude of the pressure oscillation.
Analysis of Variance↗
Simultaneous reflex inhibition of lower esophageal sphincter and crural diaphragm in cats.
We have previously suggested that both the lower esophageal sphincter and diaphragm contribute to the high-pressure zone (HPZ) at the gastroesophageal junction. The purpose of this study in anesthetized cats was to compare changes in diaphragmatic electrical activity with changes in the intraluminal pressure profile in the HPZ following either balloon distension of the esophagus or swallowing evoked by pharyngeal stimulation. Intraluminal pressure was continuously recorded by a perfused manometric assembly anchored to the gastric fundus through an abdominal surgical approach. Integrated EMG was simultaneously measured in the costal and crural parts of the diaphragm. Our results indicate that simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm follows both swallowing and balloon distension of the esophagus; during swallowing both inhibitory reflexes depend on the initiation of esophageal peristalsis; crural relaxation abolishes respiratory-induced pressure oscillations in the HPZ during LES relaxation; ventilation is maintained during relaxation of the HPZ in part by continued contraction of the costal diaphragm; and different neural pathways control LES relaxation and crural relaxation. The data support the view that the crural diaphragm augments the intrinsic smooth muscle sphincter mechanism at the gastroesophageal junction and that crural relaxation may be an important factor in mouth-to-gastric transit.
Animals↗
Adaptation to reflex effects of prolonged lung inflation.
Adaptation to the reflex effects of sustained changes in lung volume on inspiratory duration (TI), expiratory duration (TE), and the phrenic neurogram was examined. Test inflations in gallamine-paralyzed dogs anesthetized with pentobarbital sodium were made during a 6-min trial while the animal was not ventilated: 2 min at functional residual capacity (FRC), 2 min at elevated airway pressure, and 2 min back at FRC. The dogs were hyperoxygenated and arterial PCO2 was kept constant by an infusion of tris (hydroxymethyl) aminomethane. The maintained inflations produced minimal changes in TI. On return to FRC, TI was prolonged in proportion to the magnitude of the prior inflation. In contrast, inflation produced marked prolongation of TE, which then adapted back toward preinflation values. On return to FRC, TE shortened initially to values below control. This shortening increased with greater prior lung inflations. The times to reestablish steady-state values upon return to FRC differed for TI (14.8 +/- 4.6 s) and TE (33.8 +/- 12.7 s). The magnitude of the phrenic neurogram at a fixed time from onset of inspiration and its slope were unchanged with inflation. These results indicate that respiratory phase durations are influenced not only by pulmonary afferent input within each respiratory cycle but also by prior vagal afferent activity that engages central processes with long, although different, time constants. Afferent input to the slow central process controlling TI is not gated to only one phase of the respiratory cycle.
Adaptation, Physiological↗
Ventilatory and arousal patterns during sleep in normal young and elderly subjects.
Since elderly subjects have lower chemosensitivity, we postulated that ventilation might be more state dependent in the elderly. To address this we investigated the changes in ventilation, measured by respiratory inductive plethysmography, with sleep in 12 healthy young (19-29 yr) and 13 elderly (greater than 65 yr) subjects. Ventilation was measured in representative periods in each sleep state. These data showed that there is no difference between the elderly and the young either in mean ventilation or in the variability of ventilation awake or in the different states of sleep. In both groups ventilation was variable in stage 1-2 sleep and least variable in stage 3-4 sleep. The variability in stage 1-2 sleep was due to periodic breathing (cycle time approximately 45 s) in both age groups. Although within a sleep state no differences were observed, over the night of study the elderly behaved differently from the young. Apneas occurred more frequently in the elderly, and 5 of 13 elderly met the criteria for sleep apnea syndrome compared with 1 of 12 young subjects. Apneas tended to occur predominantly in stage 1-2 sleep and seem to be an exaggeration of the periodicity that is typical of this state. Four of the elderly with apnea remained in this stage of sleep throughout the night of study. The apneic episodes usually terminated with an electroencephalogram arousal that occurred prior to or simultaneously with the onset of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Mechanisms for the association of gastroesophageal reflux and bronchospasm.
The mechanism for the association between gastroesophageal reflux and bronchospasm is probably multifactorial. Our data support the view that microaspiration into the trachea may be an important mechanism for bronchospasm induced by gastroesophageal reflux and needs to be distinguished from simple reflux into the esophagus. Intraesophageal acidification alone quantitatively produces a much smaller airway response than does intratracheal acidification. A challenge test should be developed to correlate airway response following intraesophageal acidification to airway hyperactivity. We believe that the relationship of the diaphragm to the antireflux barrier deserves further study.
Animals↗
Effect of aging on ventilatory response to exercise and CO2.
Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.
Adult↗
Comparison of airway responses following tracheal or esophageal acidification in the cat.
To determine a possible mechanism for the association between gastroesophageal reflux and obstructive pulmonary disease, we quantitatively compared the short latent airway response after acid infusion into the trachea or esophagus in 13 anesthetized adult cats. Total lung resistance was calculated from synchronous measurements of air flow and intrapleural pressure differences from those at end expiratory level. Tracheal infusion of as little as 0.05 ml of 0.2 N HCl evoked an average 4.65-fold increase in total lung resistance from baseline in all animals tested (p less than 0.005). Intratracheal saline had no effect. The response to intratracheal acid infusion was rapidly adapting, pH dependent, and vagally mediated. Infusion of a much larger volume of 10 ml of 0.2 N HCl into the esophagus produced an average 1.47-fold increase in total lung resistance from baseline (p less than 0.05). No change was seen with intraesophageal saline. In contrast to intratracheal acid infusion, a clearly significant increase in resistance was seen in only 8 of 13 animals tested after intraesophageal acidification. When it occurred, the response was sustained for at least 60 s after acid infusion. The magnitude of the response was not augmented by the presence of severe esophagitis. These studies strengthen the concept that reflex pathways in the trachea and esophagus may explain a causal relationship between gastroesophageal reflux and obstructive pulmonary diseases. The results support the view that microaspiration into the trachea is a much more likely mechanism for bronchospasm associated with gastroesophageal reflux than simple acid reflux into the esophagus.
Airway Resistance↗
Pulmonary mechanoreceptors in the dipnoi lungfish Protopterus and Lepidosiren.
Pulmonary mechanoreceptors in the dipnoi lungfish Protopterus aethiopicus and Lepidosiren paradoxa were identified and characterized both in vivo and in vitro. Both slowly adapting receptors (SAR) and rapidly adapting receptors (RAR) were found, with the majority of receptors being of the slowly adapting type. The SAR discharged during inflation once their threshold volume was exceeded, and this activity persisted during prolonged lung inflation. For most of the SAR, interaction between the rate of inflation and lung volume was involved in setting the firing rate of the receptor. Increase in intrapulmonary carbon dioxide partial pressure decreased the activity of the SAR during sustained inflation at a constant intrapulmonary pressure. The RAR also discharged during inflation once the threshold volume was exceeded. However, in contrast to the SAR, the RAR became silent within 1.5 - 15 s after the end of inflation. The activity of these receptors during inflation was influenced predominantly by the rate and influenced little by the volume of inflation. According to these observations, the behavior of lungfish pulmonary mechanoreceptors closely resembles that of pulmonary mechanoreceptors in amphibians but differs from that of mechanoreceptors in the swim bladder of teleosts.
Acclimatization↗
Response of pulmonary rapidly adapting receptors during lung inflation.
Studies were conducted to establish the factors that determine the response of canine pulmonary rapidly adapting receptors (RAR) during lung inflation. Inflations of the lung were performed at several constant rates during which the activity of individual RAR was counted. At each rate of inflation tested multiple identical tests were performed. The volume of each test inflation was controlled. Data obtained in all tests at each flow rate were averaged to give the mean response of the receptor at that rate of inflation. These studies indicate the major response characteristics of RAR during lung inflation in conditions of relatively constant lung mechanics. First, at a constant rate of inflation, the activity of RAR augments increasingly as the lung is expanded. Second, their activity is influenced markedly by the rate of inflation. However, this sensitivity is nonlinear. Specifically, at low rates of inflation increases in flow rate produce more marked augmentation of RAR firing than do identical increases in flow at higher rates of inflation. The major difference between receptors is in their threshold; however, this too is a function of flow rate. With increasing flow rate the threshold, whether measured as the inflation volume or transpulmonary pressure at which receptors begin to fire, declines. The response of receptors, however, with thresholds over the entire range show the major features discussed above. The present results provide quantitative information which are necessary to begin to eludicate the transduction properties of this receptor type.
Animals↗
Effects of hypercapnia and hypoxia on abdominal expiratory nerve activity.
We examined the effects of progressive hypercapnia and hypoxia on the efferent neural activity in a whole abdominal expiratory nerve (medial branch of the cranial iliohypogastric nerve (L1) in anesthetized, paralyzed dogs. To eliminate effects of phasic lung and chest-wall movements on expiratory activity, studies were performed in the absence of breathing movements. Progressive hyperoxic hypercapnia and isocapnic hypoxia were produced in the paralyzed animals by allowing 3-5 min of apnea to follow mechanical ventilation with 100% O2 or 35% O2 in N2, respectively; during hypoxia, isocapnia was maintained by intravenous infusion of tris(hydroxymethyl)aminomethane buffer at a predetermined rate. To quantify abdominal expiratory activity, mean abdominal nerve activity in a nerve burst was computed by integrating the abdominal neurogram and dividing by the duration of the nerve burst. Hypercapnia and hypoxia both increased mean abdominal nerve activity and decreased expiratory duration. In contrast to the ramplike phrenic neurogram, the abdominal neurogram consisted of three phases: an initial rising phase, a plateau phase in which abdominal nerve activity was approximately constant, and a terminal declining phase in which the activity returned to the base-line level. The height of this plateau phase and the rates of rise and decline of abdominal nerve activity all increased with increasing hypercapnia and hypoxia. We conclude that, with proprioceptive inputs constant, both hypercapnia and hypoxia are excitatory to abdominal expiratory neural activity.
Abdomen↗
Central sleep apnea in hypothyroidism.
This is a report of a 45-yr-old male patient who developed central sleep apnea syndrome because of hypothyroidism. In response to L-thyroxine therapy, the patient became euthyroid, and the apneic phenomenon disappeared. Previous reports have suggested that hypothyroidism can produce obstructive sleep apnea from either narrowing of the upper airway secondary to deposition of mucopolysaccharides and protein extravasation into the tissues or from abnormalities in ventilatory control. The present patient did demonstrate evidence of profound dysfunction of his respiratory control center: before therapy, the patient manifested blunted ventilatory and occlusion pressure responses to hypoxia and normal responsiveness to hypercapnia; after therapy, hypoxic responsiveness was restored and the ventilatory response to hypercapnia doubled. Hypothyroidism should be included in the differential diagnosis of central sleep apnea.
Diagnosis, Differential↗
Action of positive feedback related to lung inflation in the control of ventilation.
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Animals↗
Effect of gaseous interaction between lung units on the expired concentration of nitrogen.
There is debate over the mechanisms that produce the alveolar slope, with theories relating to both series and parallel inhomogeneity being proposed. We use a mathematical model of pulmonary gas transport, which incorporates both series and parallel effects, to investigate the relevance of each in the production of this alveolar slope. Interaction between lung units is specifically studied by simulating mixing at both proximal- and distal-branch points in the bronchial tree. During expiration mixing of the gas from inhomogeneous parallel lung units leads to concentration gradients within each unit. The resultant effect on the concentration of the expirate depends on the position in the bronchial tree at which this mixing takes place; proximal interaction alters the initial phase of the expired concentration profile, whereas distal interaction changes the magnitude of the alveolar slope. The net effect of distal interaction is to produce a greater alveolar slope for gases with low molecular diffusivity. These effects are present even in the absence of asynchronous emptying of lung units but may be enhanced by it. These results help to clarify controversies about the mechanisms underlying production of the alveolar slope.
Humans↗
Effect of aerosolized histamine on occlusion pressure and ventilation in humans.
To define further the mechanism by which inspiratory neural activity is increased in asthma, we studied the effect of aerosolized histamine on occlusion pressure (P100) and ventilation in conscious humans while end-tidal CO2 partial pressure was maintained at a constant, slightly hypercapnic level. The dose of histamine we employed varied from subject to subject but was such that it produced a 70% reduction in specific airway conductance in each subject. In 9 of the 13 subjects tested, inhaled histamine significantly increased P100. This increase was not due to changes in functional residual capacity, which was not affected by aerosolized histamine. Inhalation of isoproterenol abolished the effects of histamine on specific airway conductance and P100. Anesthesia of the airways by lidocaine eliminated the effect of histamine on P100 but did not alter the magnitude of the change in specific airway conductance produced by histamine. We conclude that the increase in occlusion pressure seen after the inhalation of histamine in humans depends on both contraction of bronchial smooth muscle and stimulation of airway receptors.
Adult↗