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Biomedical subjects

A I Pack

Publications and source records attributed to A I Pack.

At least 55 records · Page 3Linked to original sources
PubMed1996

Quantitative magnetic resonance imaging of upper airways musculature in an animal model of sleep apnea.

Electromyographic studies of patients with sleep apnea and of the English bulldog, an animal model of sleep apnea, indicate that there is increase activity of the airways dilator muscles. The muscles, when biopsied, show both adaptation and muscle injury. In this study we have utilized quantitative magnetic resonance imaging to characterize changes in the upper airway musculature of the bulldog in vivo. The imaging procedure utilized provided a quantitative measurement of the T2 relaxation times of airway muscle (geniohyoid, sternohyoid, sternothyroid, thyropharyngeus, and hyopharyngeus) and nonairway muscles spatially localized to submillimeter-resolution levels. Quantitative differences between the medians and distributions of T2 relaxation times of airway vs. nonairway muscles were demonstrated. These differences were related to the degree of sleep-disordered breathing. The changes observed are compatible with the hypothesis that there is both increased edema and fibrosis in upper airway muscle in sleep apnea.

Animals↗
PubMed1996

The effects of serotonin antagonists in an animal model of sleep-disordered breathing.

Recent studies have shown excitatory effects of serotonin on upper airway motoneurons. This excitatory effect is normally present and arises from cells in the caudal raphe nuclei. The firing of these serotonergic neurons is reduced during sleep. To determine the importance of serotonin in the maintenance of patient airways and normal respiration in waking in obstructive sleep apnea, we studied the effects of two serotonin antagonists on upper airway dilator muscle activity, diaphragm activity, Sao2, and upper airway cross-sectional area in an animal model of sleep-disordered breathing, the English bulldog. Systemic administration of both antagonists resulted in significant reductions in the peak amplitudes of upper airway muscle respiratory bursts (range, 39 to 62% suppression; p < 0.05). Lesser reductions in diaphragm activity were noted (range, 10 to 33% suppression; p < 0.05). Oxyhemoglobin saturations also fell (p < 0.05), coinciding with suppressions in upper airway muscle activity. With reductions in dilator muscle activity, upper airway cross-sectional areas, as measured with cine CT, showed significant inspiratory collapse. These results support the hypothesis that serotonin is important in the maintenance of patent upper airways in obstructive sleep apnea.

Animals↗
PubMed1996

Upper airway and soft tissue structural changes induced by CPAP in normal subjects.

Nasal continuous positive airway pressure (CPAP) is the treatment of choice for adults with obstructive sleep apnea. CPAP is known to increase upper airway size; however, the direct effects of CPAP on soft tissue structures surrounding the upper airway are less well understood. Magnetic resonance imaging was used to study the effect of incremental levels (0, 5, 10, and 15 cm H2O) of CPAP on the upper airway and surrounding soft tissue structures in 10 normal subjects. Progressive increases in CPAP resulted in the following major findings: (1) airway volume and airway area (measured at several different locations [midregion, minimal, maximal]) within the retropalatal and retroglossal regions increased; (2) lateral airway dimensional changes were greater than anterior-posterior changes; (3) lateral upper airway soft tissue structural changes were significantly greater than anterior-posterior changes; (4) lateral pharyngeal wall thickness decreased and the distance between the lateral parapharyngeal fat pads increased. An inverse relationship was demonstrated between CPAP level and pharyngeal wall thickness; (5) minimal changes were noted in the soft palate and tongue. These data suggest that the lateral pharyngeal walls are more "compliant" than the soft palate and tongue. This investigation provides further evidence that the lateral pharyngeal walls play an important role in mediating upper airway caliber.

Adult↗
PubMed1996

Interaction of serotonergic excitatory drive to hypoglossal motoneurons with carbachol-induced, REM sleep-like atonia.

The facilitatory effect of serotonin (5HT) on hypoglossal (XII) motoneurons is likely to be reduced during rapid eye movement (REM) sleep, when the activity of the brainstem serotonergic system reaches its nadir. Therefore, we assessed the hypothesis that application of exogenous 5HT will attenuate the REM sleep-like suppression of XII motoneurons produced in decerebrate cats by pontine microinjections of a cholinergic agonist, carbachol. Microinjections of 5HT or 5-carboxamidotryptamine into the XII nucleus increased XII nerve activity to 182 +/- 53% (standard deviation; SD) of control. Subsequent pontine microinjections of carbachol reduced XII nerve activity by 55 +/- 21% of the pre-5HT level (n = 12). Microinjections of methysergide (a 5HT antagonist) into the XII nucleus reduced XII nerve activity to 54 +/- 17% of the pre-methysergide control (n = 6). Pontine carbachol injections after methysergide further reduced XII nerve activity by 49 +/- 20% of the pre-methysergide level. Treatments with both agonists and the antagonist attenuated the carbachol-induced decrease when compared to two previous studies using the same model: 1) In experiments with no injections of serotonergic agents, pontine carbachol injections decreased XII nerve activity by 90 +/- 6% of control. 2) After enhancement of XII nerve activity by inhibitory amino acid antagonists (to 135 +/- 60%), the subsequent carbachol-induced decrease was even larger, 112 +/- 62% of control. We propose that serotonergic excitation can significantly attenuate the REM sleep-like suppression of XII nerve activity, and that this is achieved, in part, by substituting for the decreased endogenous 5HT in the XII nucleus. The study also demonstrates that other, non-serotonergic, mechanisms also contribute to the carbachol-induced suppression.

Animals↗
PubMed1995

Characteristics of crashes attributed to the driver having fallen asleep.

While it has been known for some time that crashes can result from the driver falling asleep at the wheel, this issue has received less attention in traffic safety programs than the role of alcohol or speed of the vehicle. The present study was done to investigate the characteristics of crashes attributed to the driver being asleep. The study utilized the database at the Highway Safety Research Center at the University of North Carolina that is based on the uniform crash reporting system in that state. Over the years 1990-1992, inclusive, there were 4333 crashes in which the driver was judged to be asleep but not intoxicated. The crashes were primarily of the drive-off-the-road type (78% of the total) and took place at higher speeds (62% in excess of 50 mph). The fatality rate was of similar magnitude to that in alcohol-related crashes with fatalities in 1.4% of such crashes (alcohol crashes had fatalities in 2.1%). The crashes occurred primarily at two times of day--during the nighttime period of increased sleepiness (midnight to 7.00 a.m.) and during the mid-afternoon "siesta" time of increased sleepiness (3.00 p.m.). These crashes occurred predominately in young people. Fifty-five percent of these were in individuals 25 years of age or younger, with a peak age of occurrence at age 20 years. Sleepiness may play a role in crashes other than those attributed by the police to the driver being asleep. Determining the magnitude of this role is a challenge to the traffic safety community.

Accidents, Traffic↗
PubMed1995

A survey screen for prediction of apnea.

Questionnaire data from patients presenting at three sleep disorders centers were used to develop and assess a screening tool for sleep apnea based on the reporting of the frequency of various symptoms of sleep apnea and other sleep disorders plus age, body mass index (BMI) and gender. Patients were not specifically referred for suspicion of sleep apnea. Separate factor analyses of survey responses from 658, 193 and 77 respondents from the first, second and third sites, respectively, each yielded four orthogonal factors, one of which accounted for all the questions concerned with the frequency of disordered breathing during sleep. The survey was shown to be reliable in a subset of patients from one of the sites (test-retest correlation = 0.92). Survey data were then compared to a clinical measure of sleep apnea (respiratory disturbance index) obtained from polysomnography. A multivariable apnea risk index including survey responses, age, gender and BMI was estimated using multiple logistic regression in a total sample of 427 respondents from two of the sites. Predictive ability was assessed using receiver operating characteristic (ROC) curves. The area under the ROC curve was 0.79 (p < 0.0001). For BMI alone, it was 0.73, and for an index measuring the self-report of the frequency of apnea symptoms, it was 0.70. The multivariable apnea risk index has potential utility in clinical settings.

Adult↗
PubMed1995

Review of regulations and guidelines for commercial and noncommercial drivers with sleep apnea and narcolepsy.

Studies show that persons with sleep disorders, such as sleep apnea and narcolepsy, have an increased incidence of automobile accidents. The goal of this study was to review any regulations or guidelines dealing with fitness to drive of persons with sleep disorders in all the 50 states and countries around the world. Several authorities in the United States and abroad in fact have produced guidelines or regulations stating that certain of these persons are not fit to drive. As of March 1994, only four states in the United States (Maryland, North Carolina, Oregon and Utah) had guidelines for narcolepsy, while two had guidelines for both narcolepsy and sleep apnea (California and Texas). In Maine, guidelines had been proposed for sleep apnea. In contrast, almost all Canadian provinces have guidelines for both sleep apnea and narcolepsy, as does the United Kingdom. There are, however, considerable variations in the nature of the regulations used in different states, Canadian provinces and countries. These variations are not based on scientific data. Currently the impact of these regulations on crash rates or on the practice of sleep medicine has not been assessed.

Accidents, Traffic↗
PubMed1995

Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls.

The geometry and caliber of the upper airway in apneic patients differs from those in normal subjects. The apneic airway is smaller and is narrowed laterally. Examination of the soft tissue structures surrounding the upper airway can lead to an understanding of these apneic airway dimensional changes. Magnetic resonance imaging was utilized to study the upper airway and surrounding soft tissue structures in 21 normal subjects, 21 snorer/mild apneic subjects, and 26 patients with obstructive sleep apnea. The major findings of this investigation in the 68 subjects were as follows: (1) minimum airway area was significantly smaller in apneic compared with normal subjects and occurred in the retropalatal region; (2) airway narrowing in apneic patients was predominantly in the lateral dimension; there was no significant difference in the anterior-posterior (AP) airway dimension between subject groups; and (3) distance between the rami of the mandible was equal between subject groups, and thus the narrowing of the lateral dimension was not explained by differences in bony structure; (4) lateral airway narrowing was explained predominantly by larger pharyngeal walls in apneic patients (the parapharyngeal fat pads were not closer together as one would expect if the airway walls were compressed by fat); and (5) fat pad size at the level of the minimum airway was not greater in apneic than normal subjects. At the minimum airway area, thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeal fat pads was the predominant anatomic factor causing airway narrowing in apneic subjects.

Adult↗
PubMed1994

Changes in serotonin level in the hypoglossal nucleus region during carbachol-induced atonia.

The excitability of hypoglossal (XII) motoneurons innervating genioglossal muscles is markedly suppressed during the rapid-eye-movement (REM) stage of sleep. This may contribute to airway obstructions in sleep apnea patients. Based on our earlier studies in decerebrate cats using injections of carbachol into the pons to induce a REM sleep-like atonia and microinjections of serotonin (5HT) into the XII motor nucleus, we hypothesized that a sleep-related withdrawal of the serotonergic excitatory input to XII motoneurons may play a major role in these processes. To test one aspect of this hypothesis, we inserted microdialysis probes into the XII nucleus region of decerebrate, paralyzed, vagotomized and artificially ventilated cats. The probes were perfused without or with the addition of a 5HT reuptake blocker, clomipramine. The levels of 5HT and its metabolite, 5-hydroxyindoleacetic acid (5HIAA), were determined using HPLC and electrochemical detection in dialysate samples collected over successive 20 min periods under four successive experimental conditions: control (at least 2 h after probe insertion); during the postural atonia and respiratory depression produced by pontine microinjection of carbachol; recovery from the effects of carbachol produced by pontine microinjection of atropine; and, to verify that the presence of 5HT in the dialysate was related to the activity of serotonergic cells of the brainstem, following administration of 8-OH-DPAT, a 5HT 1A receptor agonist known to suppress activity in the serotonergic cells of the raphe system. After correcting for recovery rates of individual probes, the mean control 5HT level in the extracellular space of the XII nucleus region was 7.9 +/- 4.4 nM (S.D.) in eight experiments without reuptake blockers. During the carbachol-induced depression, it was reduced to 70 +/- 20% of the pre-carbachol level. It increased to the original control level 98 +/- 27% after pontine injection of atropine. 8-OH-DPAT reduced the 5HT level to 43 +/- 14% of the post-atropine level. Changes in the 5HIAA level were not as consistent as for 5HT and did not reach statistical significance under any of the experimental conditions. Thus, a functionally significant amount of 5HT is present in the extracellular space within the XII nucleus region, and its decrement during carbachol-induced, REM sleep-like atonia is likely to reflect that occurring during natural REM sleep; this may contribute to the decreased tone of upper airway muscles and airway patency.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Pharyngeal myopathy of loaded upper airway in dogs with sleep apnea.

Recent work indicates that upper airway dilator muscles of individuals with obstructive sleep apnea syndrome (OSAS) demonstrate an increased level of activity during wakefulness compared with normal subjects. In addition, massive bursts of pharyngeal dilator activity are associated with the termination of upper airway occlusive events during sleep. This complex pattern of altered pharyngeal dilator activation is also observed in the English bulldog, an animal model of OSAS. In the present study, it was hypothesized that such alterations in activity level might lead to changes in the structure of pharyngeal muscles in the bulldog. Full-thickness biopsies were obtained from two pharyngeal dilator muscles, the sternohyoid (SH) and geniohyoid, as well as a limb muscle, the anterior tibialis, in bulldogs (n = 5) and control dogs (n = 7). Immunohistochemical analysis of myosin heavy chain expression revealed an increased contribution of fast type II myosin heavy-chain fibers to SH in bulldogs. The bulldog SH also demonstrated increased connective tissue content compared with control dogs, consistent with the presence of fibrosis. Both pharyngeal dilators in the bulldog exhibited an elevated proportion of morphologically abnormal fibers indicative of ongoing or prior injury. No differences in any of the above parameters were seen between bulldogs and control dogs in the anterior tibialis limb muscle. We conclude that the chronic load and altered pattern of usage imposed on the upper airway dilators in OSAS lead to myopathic changes that may ultimately impair the ability of these muscles to maintain pharyngeal patency.

Airway Obstruction↗