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Biomedical subjects

A I Pack

Publications and source records attributed to A I Pack.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1989

Response of stretch receptors to static inflations and deflations in an isolated tracheal segment.

It has been proposed on the basis of differing responses to static lung inflations that there are two types of pulmonary stretch receptor which are organized in series or in parallel with airway smooth muscle. However, in prior studies, in which we examined the responses of a few receptors in a number of animals, we were unable to confirm this finding. In the present study we sought to definitively address this question by examining the response of a reasonable sample of receptors (greater than or equal to 5) from a single airway with a controlled mechanical environment. We examined the firing patterns of slowly adapting receptors in a tracheal segment, isolated in vivo, during inflations and deflations to different static levels of pressure between -20 and +30 cm H2O. The relationship between afferent firing and intra-tracheal pressure under static conditions was determined. We did not observe any evidence to support the existence of two distinct subtypes of receptors. During these studies we also looked for abrupt changes in the variability of afferent firing during the period of adaptation after the end of an inflation or deflation. Such changes have been described for other receptors with branched endings capable of generating spike potentials. These changes occur when the region generating the spike train seen in the parent fiber switches from one branch to another (pace-maker switching) and reflect the difference in the intrinsic variability of each branch. In the majority of fibers studied we saw no evidence of such switching and thus of the presence of multiple encoders in the receptor structure.

Air Pressure↗
PubMed1988

Characterization of thyrotropin-releasing hormone in the central nervous system of African lungfish.

Central administration of thyrotropin-releasing hormone (TRH) produces potent effects on various physiological parameters, such as arousal, respiration, and cardiovascular function, in several species. As part of an investigation into the evolution of this tripeptide as a central modulator of these parameters, we examined its distribution in the central nervous system of the African lungfish (Protopterus). Lungfish brains were dissected into three regions: telencephalon, diencephalon, and medulla. Each region was assayed for TRH by radioimmunoassay and for norepinephrine, dopamine, and serotonin by HPLC/electrochemical methods. TRH immunoreactivity (IR-TRH) was present in all regions of lungfish brain examined. The telencephalon contained the highest concentrations of TRH, the diencephalon also contained a high concentration of TRH, and the medulla contained a markedly lower concentration. Similar concentration gradients (telencephalon greater than diencephalon greater than medulla) were observed for norepinephrine, dopamine, and serotonin. The identity of IR-TRH as authentic TRH was confirmed by elution profiles on HPLC. The results of this investigation demonstrated that TRH and the monoamine neurotransmitters are present in high concentrations in various regions of lungfish brain. The lungfish may represent a promising model for further studies of the interactions of TRH with these neurotransmitter systems.

Animals↗
PubMed1988

Spectral analysis of ventilation in elderly subjects awake and asleep.

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.

Aged↗
PubMed1988

Changes in compartmental ventilation in association with eye movements during REM sleep.

The effect of phasic eye movement activity on ventilation during rapid-eye-movement (REM) sleep was studied in seven healthy young adults by use of the respiratory inductive plethysmograph. Mean ventilation (VE) and ventilatory components during REM sleep were not significantly different from that seen in either stages 1-2 or 3-4 sleep. The percent of rib cage contribution to ventilation in REM sleep, 29.3 +/- 5.1%, was reduced compared with 54.4 +/- 5.8% in stage 1-2 and 52.2 +/- 4.3% in stage 3-4 sleep (P less than 0.005). When one separated breaths by the degree of associated phasic eye movement activity, it became apparent that breathing during REM sleep is very heterogeneous. Increasing eye movement activity was associated with inhibition of ventilation with a reduction in VE from 5.1 +/- 0.3 to 3.8 +/- 0.3 l/min. Tidal volume and frequency both fell, whereas inspiratory duration was unchanged. Compartmental ventilation was also affected, with the fall in the rib cage contribution from 37.8 +/- 6.4 to 15.3 +/- 5.6%. Chest wall and abdominal movement became more asynchronous as phasic-eye-movement activity increased and frank paradoxical breathing was seen.

Adult↗
PubMed1987

Pulmonary stretch receptor relay neurones of the cat: location and contralateral medullary projections.

1. The activity of pump (p.) cells, second-order neurones in the pulmonary stretch receptor pathway, was recorded extracellularly in the nucleus of the tractus solitarius (n.t.s.) of the decerebrate cat. Their firing was proportional to changes in lung volume but unrelated to the centrally determined respiratory rhythm. A systematic search of the n.t.s. for the location of p. cells was made and an assessment of their efferent projection to the contralateral n.t.s. was determined electrophysiologically by the antidromic mapping technique. 2. P. cells were located around, and in close proximity to, the solitary tract. The two sites of greatest density were ventromedial and dorsolateral to the tract, with lower concentrations found laterally and ventrolaterally. 3. For twelve of the thirty p. cells tested, evidence of a projection to the contralateral n.t.s. was obtained; in seven of these cells, axonal arborizations within the projection area were identified. Almost all the cells that sent axons to the contralateral n.t.s. were located dorsolateral to the tract; there was no evidence that cells in the ventromedial region had contralateral projections. 4. No evidence that R beta neurones project to the contralateral commissural and ventrolateral subnuclei was found. 5. No p. cells projected to the contralateral ventrolateral n.t.s. The site of projection and branching was consistently localized just caudal to the obex and medial to the solitary tract, in the caudal medial, and commissural subnuclei of the n.t.s. This same region has been shown to receive a dense, direct projection from pulmonary rapidly adapting receptors.

Animals↗
PubMed1987

Role of medullary inspiratory neurones in the control of the diaphragm during oesophageal stimulation in cats.

1. The effect of oesophageal distension and swallowing on the activity of medullary respiratory neurones was recorded in decerebrate, spontaneously breathing cats. The distension, produced by inflating a balloon in the thoracic portion of the oesophagus, was of sufficient magnitude to induce inhibition of the peri-oesophageal part of the crural diaphragm, with little effect on the respiratory function of the diaphragm as measured by the activity in the C5 branch of the phrenic nerve. 2. 424 neurones were tested. They were located bilaterally, in the region of the nucleus tractus solitarius (dorsal respiratory group) or the ambiguous complex (ventral respiratory group). No cell exhibited a change in activity during periods of strong inhibition of crural electrical activity induced by distension or swallowing. The activity of all cells paralleled that of the C5 phrenic neurogram, which was unaffected by the tests. 3. We conclude that the reflex inhibition of the crural diaphragm during oesophageal distension does not result from an inhibition of medullary premotor inspiratory neurones of the dorsal and ventral groups. Additional central pathways must exist that inhibit motoneurones to the crural diaphragm during gastrointestinal reflexes.

Action Potentials↗
PubMed1987

Responses of feline gastroesophageal junction to changes in abdominal pressure.

The responses of the lower esophageal sphincter (LES), stomach, and diaphragm and their contribution to changes in the high-pressure zone (HPZ) at the gastroesophageal junction were determined during extrinsic abdominal compression or intragastric balloon distension in anesthetized cats. Abdominal compression consistently induced an increase in intraluminal end-expiratory LES and gastric pressure (P less than 0.01). Changes in LES pressure significantly exceeded the changes in gastric pressure (P less than 0.01). In contrast, the LES response during gastric distension was variable in the group of animals despite a consistent volume-dependent increase in gastric pressure. Mean LES pressure for the group was unchanged, although 33% of individual animals exhibited a decrease in LES pressure during gastric distension. Both abdominal stimuli induced sustained inhibition of crural (P less than 0.01), but not costal, diaphragmatic electromyographic activity. Vagotomy affected the LES but not the gastric or diaphragmatic responses to both stimuli. In the group of animals, the combined effect of the changes in the three measured variables on the HPZ resulted in maintenance of the antireflux barrier during abdominal compression but a significant decrease in the barrier during gastric distension.

Abdomen↗
PubMed1987

The English bulldog: a natural model of sleep-disordered breathing.

To establish a natural model of sleep-disordered breathing, we investigated respiration during wakefulness and sleep in the English bulldog. This breed is characterized by an abnormal upper airway anatomy, with enlargement of the soft palate and narrowing of the oropharynx. During sleep, the animals had disordered respiration and episodes of O2 desaturation. These were worst in rapid-eye-movement (REM) sleep, with most bulldogs having O2 saturations of less than 90% for prolonged durations. In contrast, control dogs never desaturated. In REM sleep, the bulldogs had episodes of both central and obstructive apnea, the latter being associated with paradoxical movements of the rib cage and abdomen. During wakefulness, the bulldogs were hypersomnolent as evidenced by a shortened sleep latency (mean of 12 min compared with greater than 150 min for controls). This animal model should facilitate studies of the natural history of the sleep apnea syndrome and its complications.

Animals↗
PubMed1987

Clinical significance of sleep apnea in the elderly.

The generally accepted polysomnographic criteria for diagnosis of sleep apnea is exceeded by elderly subjects with such frequency that the validity of its application to this age group has been questioned. We studied a group of elderly volunteers with nocturnal polysomnography and partitioned them into 2 groups based upon an apnea index of greater than or less than 5 per hour. The results of a protocol evaluating the presence of potential complications of sleep apnea including cardiac arrhythmias, systemic hypertension, cor pulmonale, daytime sleepiness, and cognitive impairment were compared for the 2 groups. No excess incidence of cardiovascular complications was found. Although an increase in daytime sleep tendency was shown for the group with more frequent apneas, no appreciable deficits in cognitive performance were demonstrated. Although apnea during sleep in the elderly may be associated with an increase in daytime sleepiness, it may not necessarily result in other physiologic or neuropsychologic consequences. Therapeutic intervention for these abnormalities should be carefully considered prior to the institution of treatment in light of these observations.

Aged↗
PubMed1987

Detecting errors in blood-gas measurement by analysis with two instruments.

We performed a two-stage prospective evaluation of the error detection capabilities of duplicate analysis of blood-gas specimens. In the first stage we analyzed 1601 specimens with a Corning Model 175 blood-gas analyzer as the test instrument and a Corning Model 178 analyzer as the reference instrument, and in the second stage we analyzed 1544 specimens with two Model 178 analyzers. In each stage the designated reference instrument underwent troubleshooting whenever an analytical error was detected; the test instrument underwent troubleshooting only when error conditions were indicated by means other than duplicate analysis. An error was considered to have occurred if the difference between the duplicate analyses exceeded 0.02 (for pH), 0.53 kPa, i.e., 4 mmHg (pCO2), or 7% (pO2). The number of specimens for which errors were detected was 97 (6.1%) in the first stage, 23 (1.5%) in the second. For each analyte more errors were detected with the Model 175 analyzer (of older design) than with the newer Model 178 analyzer. Furthermore, in certain periods associated with the use of particular electrodes there were very high error rates for individual analytes: 8% for pCO2, 18% for pO2. We conclude that duplicate analysis should be considered as a possible required standard for error detection.

Blood Gas Analysis↗
PubMed1986

Effects of lung inflation on the excitability of dorsal respiratory group neurons.

The effect of lung inflation on the excitability of inspiratory neurons of the dorsal respiratory group was studied in decerebrate, paralyzed, artificially ventilated cats. Variations in the antidromic latency (AL) were used as a measure of the changes in excitability. The antidromic responses of single cells were recorded extracellularly during electrical stimulation (20 Hz) of their spinal axons. Single-breath test inflations were delivered at the onset of inspiration (I) or expiration (E), and then maintained for the duration of that respiratory phase. In the absence of inflation during E, most of the inspiratory cells underwent progressive lengthening of the AL, indicating inhibition or disfacilitation. This effect was stronger in I beta than in I alpha cells but there was considerable overlap. In every cell (21 I alpha, 17 I beta), inflation during E caused a prompt AL shortening (excitation or disinhibition) that was evident in single tests. On average, I beta neurons were more strongly excited by the test inflation during E, but again there was considerable overlap. The excitation was maintained for the duration of the inflation, indicating that pulmonary stretch receptor afferents (PSR) were involved. The response to slow inflations (that preferentially excite PSR) was a progressive shortening of the AL that mirrored the increase in lung volume. The results emphasize the qualitative similarity in the responses of I alpha and I beta neurons to lung inflation and in their excitability changes during normal respiratory cycles.

Adaptation, Physiological↗