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A I Pack

Publications and source records attributed to A I Pack.

At least 19 recordsLinked to original sources
PubMed1992

Evocation of postural atonia and respiratory depression by pontine carbachol in the decerebrate rat.

To study mechanisms underlying the postural muscle atonia and respiratory depression associated with rapid eye movement (REM) sleep, the cholinergic agonist, carbachol, was microinjected into the pontine reticular formation in decerebrate, spontaneously breathing rats. Carbachol injection led to a simultaneous depression of neck and tonic intercostal EMG activity (lasting 14.5 min +/- 7.6 (S.D.)) and a reduction of the respiratory rate. Phasic inspiratory intercostal activity was not consistently depressed. After a spontaneous recovery from the atonia and respiratory depression, subsequent carbachol injections at the same site produced similar responses. Thus, the decerebrate rat may provide a useful model for studies of the inhibitory neural mechanisms activated by the increased acetylcholine levels in the pons that occur in REM sleep. Pontine carbachol effects in rats differ from those described in cats in a manner analogous to differences in the patterns of natural REM sleep in these two species.

Acetylcholine↗
PubMed1992

Behavior of VRG neurons during the atonia of REM sleep induced by pontine carbachol in decerebrate cats.

The microinjection of carbachol into the pons of acute decerebrate cats elicits a REM sleep-like atonia and a profound suppression of respiratory motoneuronal activity (J. Appl. Physiol., 69 (1990) 2280-2289). To assess whether this suppression is mediated by medullary neurons that provide respiratory drive to motoneurons of the respiratory pump muscles (diaphragm and intercostals), we studied the effect of pontine carbachol on the activity of neurons of the ventral respiratory group (VRG) in decerebrate, vagotomized, paralyzed and artificially ventilated cats. VRG neurons were recorded extracellularly along with the activity of phrenic and intercostal (external and internal) nerves. Both inspiratory (I) and expiratory (E) VRG neurons had incrementing, ramp-like bursts of activity during their firing periods and were not vagal motoneurons. Carbachol produced a depression of the peak firing rate in most (42/57) neurons studied. However, five cells showed no change and ten had an increase in activity in spite of consistent depression at the motoneuronal level. For the total population of cells (34 I and 23 E), the peak firing was reduced to 88.5% +/- 16.3 (S.D.) of control. The simultaneously recorded phrenic activity was reduced to 77.9% +/- 11.5, while inspiratory intercostal activity fell to 63.4% +/- 21.6 and expiratory to 23.2% +/- 21.2 of control. The carbachol-induced changes in peak firing of both I and E cells were quantitatively similar, and positively correlated to changes in peak phrenic activity. Analysis of this correlation suggested that phrenic and intercostal activities will be depressed to some degree by carbachol even when the average VRG cell activity remains unchanged. In addition, our data show that VRG cells may receive a combination of inhibitory and excitatory inputs during the carbachol-induced depression of respiratory motoneurons. Thus, although some disfacilitation from VRG cells may occur, there must be additional inhibitory or disfacilitatory pathways that mediate the decrease in activity of both phrenic and intercostal motoneurons that accompanies the REM sleep-like atonia.

Animals↗
PubMed1992

Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat.

In decerebrate, paralyzed, vagotomized and artificially ventilated cats, serotonin (5-HT) and its analogues, microinjected into the hypoglossal (XII) motor nucleus, altered the activity of the genioglossal branch of XII nerve. 5-HT, carboxamidotryptamine maleate (5-CT) and DOI (1-5 mM) increased the activity by over 200%. Methysergide reversed this increase. Methysergide, mianserin, or ketanserin (100-250 nl, 1 mM) reduced the spontaneous hypoglossal activity by 20-50%. Buspirone, 8-OH-DPAT and (-)-propranolol were without effect. Thus, 5-HT provides a substantial tonic excitatory drive to XII motoneurons. The 5-HT receptors involved are likely to be type 1C or 2, but uncertainty regarding the affinity profiles of the drugs used in in vivo conditions in the cat precludes a definite identification.

Animals↗
PubMed1992

Role of lung inflation in control of air breath duration in African lungfish (Protopterus annectens).

Studies were conducted in the African lungfish (Protopterus annectens) to investigate the role of lung inflation on control of the duration of the lung breath. The studies were done in decerebrate spinalectomized animals. Two types of tests were performed: 1) a no-inflation test (airway occluded) in which the lungs were not inflated during an air breath, and 2) an inflation test in which the lungs were inflated at the onset of the lung breath to different levels of intrapulmonary pressure (2.5, 5.0, 7.5, and 10.0 cmH2O). Lung inflation shortened the duration of the lung breath. The relationship between intrapulmonary pressure and breath duration was curvilinear and similar to the relationship between tidal volume and inspiratory duration in mammals. Likewise, the relationship could be described by a hyperbola with a linear relationship between intrapulmonary pressure and the inverse of breath duration. This relationship was essentially not affected by changing the composition of the gas used to inflate the lungs: air, oxygen, or nitrogen. Vagotomy, however, largely abolished the effect of lung inflation on breath duration. Because there is such similarity between these results and effect of lung inflation on control of inspiratory time in mammals, it is postulated that neural circuits for control of respiratory timing were already developed and similar in the lungfish. Because the muscles used in the lungfish to ventilate the lung are totally different (buccal force pump) from those in mammals, the neural circuits for timing control and those for shaping the pattern of motor output appear to be separate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A network model of respiratory rhythmogenesis.

A mathematical model of the three-phase respiratory network proposed by Richter et al. (News Physiol. Sci. 1: 109-112, 1986) is developed and its properties are examined. The model reproduces the experimentally determined trajectories of membrane potential for the five physiologically distinct types of neurons included. Stepwise parameter changes can produce a respiratory rhythm with only two separate electrophysiological phases, result in apnea, or produce more complex patterns of firing. The phase-resetting behavior of the model was obtained with perturbing stimuli and is comparable to experimentally determined phase-resetting data. There is reasonable agreement between model predictions and experimental results. In the model, the properties of the phase singularity make termination of the respiratory rhythm by an appropriately timed perturbation virtually impossible, which is in agreement with experimental observations. The rhythm can be stopped by alterations that simulate the effect of input from the superior laryngeal nerve; the rhythm is locked in the postinspiratory phase. We conclude that our results are consistent with the concept of a network oscillator as the source of the respiratory rhythm.

Animals↗
PubMed1992

Effects of selective sleep deprivation on ventilation during recovery sleep in normal humans.

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.

Adult↗
PubMed1992

Correlation between oscillations in ventilation and frequency content of the electroencephalogram.

Periodicities of ventilation are common in elderly subjects during stage 1/2 sleep. The mechanism producing these periodicities is unknown. We hypothesized that the oscillations in ventilation might be related to oscillations in sleep state. To address this hypothesis, we examined, using cross correlation, the relationship between the oscillations in ventilation and parameters (alpha power, mean frequency) derived from spectral analysis of the electroencephalogram. In wakefulness, although ventilation and mean frequency, and ventilation and alpha power, were related, there were no consistent patterns to these relationships. Both positive and negative correlations were found. Clearer relationships were found in stage 1/2 sleep. Correlation between mean frequency and ventilation was the most consistent. All correlations were positive; i.e., ventilation fell as mean frequency fell. The maximum correlation occurred at zero lag between the time series. Thus these oscillations are synchronous within the time resolution of our methodology. These data are compatible with the hypothesis that the initiation of apnea in stage 1/2 sleep is related to a reduction in the state-dependent input to the ventilatory control system.

Aged↗
PubMed1992

Effect of hypothyroidism on myosin heavy chain expression in rat pharyngeal dilator muscles.

Although the association between hypothyroidism and obstructive sleep apnea is well established, the effect of thyroid hormone deficiency on contractile proteins in pharyngeal dilator muscles responsible for maintaining upper airway patency is unknown. In the present study, the effects of hypothyroidism on myosin heavy chain (MHC) expression were examined in the sternohyoid, geniohyoid, and genioglossus muscles of adult rats (n = 20). The relative proportions of MHC isoforms present were determined using MHC-specific monoclonal antibodies and oligonucleotide probes. All control muscles showed a paucity of type I MHC fibers, with greater than 90% of fibers containing fast-twitch type II MHCs. In the genioglossus muscle, a population of non-IIa non-IIb fast-twitch type II fibers (putatively identified as type IIx MHC fibers) were detected. Hypothyroidism induced significant changes in MHC expression in all muscles studied. In the sternohyoid, type I fibers increased from 6.2 to 16.9%, whereas type IIa fibers increased from 25.9 to 30.7%. Type I fibers in the geniohyoid increased from 1.2 to 12.8%, whereas type IIa fibers increased from 34.1 to 42.7%. The genioglossus showed the smallest relative increase in type I expression but the greatest induction of type IIa MHC. None of the muscles examined demonstrated reinduction of embryonic or neonatal MHC in response to thyroid hormone deficiency. In summary, hypothyroidism alters the MHC profile of pharyngeal dilators in a muscle-specific manner. These changes may play a role in the pathogenesis of obstructive apnea in hypothyroid patients.

Animals↗
PubMed1991

Sleep-induced periodic breathing and apnea: a theoretical study.

To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations.

Airway Obstruction↗
PubMed1991

Ventilation during early and late rapid-eye-movement sleep in normal humans.

Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters.

Adult↗
PubMed1990

Reduction of thyrotropin-releasing hormone concentrations in central nervous system of African lungfish during estivation.

Thyrotropin-releasing hormone (TRH) has been implicated as an important modulator of arousal state in mammals. Changes in the content of TRH in several brain regions accompany hibernation in the ground squirrel. In the present study, the involvement of TRH in the regulation of arousal was further investigated in the African lungfish, Protopterus annectens, which contain high concentrations of TRH throughout its central nervous system and enter a hibernation-like state, estivation. Lungfish were divided into three groups. Group 1 was fed normally, group 2 was starved while aquatic, and group 3 was allowed to enter into a state of estivation. After 3 months, the lungfish were sacrificed and the concentrations of TRH, norepinephrine, dopamine, and serotonin were determined in the telencephalon, diencephalon, medulla, and spinal cord. In estivation, there was a significant decline in the concentration of TRH in the diencephalon, with no alteration in other regions. Starvation had no effect on regional TRH concentrations. The concentration of norepinephrine, dopamine, and serotonin did not change in estivation; however, a significant elevation of norepinephrine in the diencephalon and dopamine in the telencephalon was observed in starvation. Starvation and estivation were associated with significant declines in the protein content of the diencephalon and medulla. The estivation-linked decline in TRH in the diencephalon of the lungfish is similar to the decrease in TRH content in the hypothalamus in hibernating ground squirrels. These findings lend further support to the importance of TRH in the regulation of arousal state.

Adaptation, Physiological↗
PubMed1990

Control of interbreath interval in the African lungfish.

We have performed studies to examine the effect of variations in intrapulmonary pressure on the interval between lung breaths in the African lungfish. Studies were performed in two different preparations. In the first we produced changes in lung pressure using a controlled-infusion pump. Increases in intrapulmonary pressure prolonged the interval between lung breaths. At a pressure of 2.5 cmH2O the average interval was 2.6 +/- 1.8 min (mean +/- SD); at 5.0 cmH2O, 8.1 +/- 3.5 min; and at 7.5 cmH2O, 16.2 +/- 3.8 min. Inflations of the lung early in the interbreath interval had less of an effect on its duration than inflations later in the interval. In the second preparation we used a system in which gas flowed continuously through both lungs. Intrapulmonary pressure was varied by changing outlet pressure and O2 concentration by changing the composition of the gas mixture. This allowed separate control of both O2 concentration and intrapulmonary pressure. At a fixed O2 concentration intrapulmonary pressure increased the duration of the interval between lung breaths. At a fixed pressure, reductions in O2 concentration shortened the interval. There was no significant interactive effect of O2 and pressure. Lung inflation did not alter the frequency of gill ventilation. These results imply that a reflex highly similar to the Hering-Breuer expiratory-promoting reflex was already present in the African lungfish.

Animals↗
PubMed1990

Startle-evoked changes in diaphragmatic activity during wakefulness and sleep.

Tonic inhibition of some respiratory muscles occurs as part of the generalized muscle atonia of rapid-eye-movement sleep (REMS). A second type of inhibition of the diaphragm during REMS, fractionations, consists of brief pauses in the diaphragmatic electromyogram (DIA EMG) in association with phasic events. Because motor inhibition can occur as part of the startle response, and the brain is highly activated during REMS, we hypothesized that the neural basis of the fractionations might be activation of a startle network. To test this hypothesis, tone bursts (100 dB, 20-ms duration at 15-s intervals) were applied to cats at a fixed inspiratory level in the DIA moving average during REMS, non-rapid-eye-movement sleep (NREMS), and wakefulness. Parallel sham studies (no tone applied) were obtained for each state. The response of the DIA EMG was averaged over 100 ms by using the tone pulse as a trigger, and the following parameters of the DIA EMG were measured: latency to peak and/or nadir, increment or decrement in activity, and duration of peak and/or nadir. After a tone, all five animals studied displayed a profound suppression of DIA activity during REMS (latency to nadir 42.4 +/- 10.0 ms, duration of suppression 35.9 +/- 17.6 ms). Similarly, DIA activity was suppressed in all cats during NREMS (latency to nadir 40.9 +/- 13.3 ms, duration 23.9 +/- 13.4 ms). An excitatory response was observed in only two cats during NREMS and wakefulness. The similarity of startle-induced DIA EMG pauses to spontaneous fractionations of DIA activity during REMS suggests that the latter result from activation of a central startle system.

Acoustic Stimulation↗
PubMed1990

Effect of dorsolateral pontine lesions on diaphragmatic activity during REMS.

Muscle atonia is a feature of normal rapid-eye-movement sleep (REMS). The suppression of accessory respiratory muscle activity has been investigated and a role for sleep-disordered breathing hypothesized, but the suppression of diaphragmatic activity has rarely been considered. We hypothesized that the activity of the diaphragm was suppressed by an area of the dorsolateral pons during REMS. Lesions in this region have previously been shown to abolish the atonia of REMS. The diaphragmatic electromyogram (EMG) activity was analyzed in five naturally sleeping cats before and after pontine lesions leading to REMS without atonia. Although respiratory timing parameters were not altered by the lesion, the inspiratory rate of rise was significantly increased in all cats, and the brief pauses (40-100 ms) in the diaphragmatic EMG normally seen in REMS were virtually abolished. We conclude that the dorsolateral pons has a role in suppressing diaphragmatic activation during REMS. This suppression affects the average rate of rise of diaphragmatic activity and also leads to brief intermittent complete cessation of ongoing muscle activity. These decrements in diaphragm activity could jeopardize ventilation during REMS.

Animals↗
PubMed1990

Cholinergic stimulation of the pons depresses respiration in decerebrate cats.

The injection of carbachol into the pontine tegmentum of decerebrate cats evokes a postural motor atonia that has many of the characteristics of the atonia of natural rapid-eye-movement (REM) sleep (Morales et al. J. Neurophysiol. 57: 1118-1129, 1987). We have used the carbachol-injected decerebrate cat to study the changes in respiratory neuronal activity that accompany the atonia. The activities of representative respiratory motor nerves--phrenic, intercostal, and hypoglossal--and that of a motor branch of C4 were recorded in decerebrate, vagotomized, paralyzed, and artificially ventilated cats. After the microinjection of carbachol, there was a profound suppression of activity in all the nerves and a decrease in respiratory rate. This was a consistent stereotyped response in which the magnitude of the suppression of respiratory-related activity was phrenic (to approximately 65% of control) less than inspiratory intercostal (approximately 50%) less than hypoglossal (approximately 10%) less than expiratory intercostal (approximately 5%). The decrease in respiratory rate (to approximately 70% of control) was caused by a prolongation of both inspiratory and expiratory durations. Complete reversal of the carbachol effect was elicited by the microinjection of atropine into the same site as the carbachol injection. This allowed us to produce a second episode of atonia by the injection of carbachol into the contralateral pons. Thus we have demonstrated the existence of neural pathways originating in the cholinoceptive cells of the pons that have the potential to powerfully and differentially depress various respiratory motoneuronal pools and to reduce the respiratory rate. These pathways are likely to be activated along with the atonia of REM sleep.

Animals↗