Search PubMed⌕ Search

Biomedical subjects

A I Pack

Publications and source records attributed to A I Pack.

At least 37 records · Page 2Linked to original sources
PubMed1998

MRI study of regional variations of pharyngeal wall compliance in cats.

Upper airway compliance indicates the potential of the airway to collapse and is relevant to the pathogenesis of obstructive sleep apnea. We hypothesized that compliance would vary over the rostral-to-caudal extent of the pharyngeal airway. In a paralyzed isolated upper airway preparation in cats, we controlled static upper airway pressure during magnetic resonance imaging (MRI, 0.391-mm resolution). We measured cross-sectional area and anteroposterior and lateral dimensions from three-dimensional reconstructed MRIs in axial slices orthogonal to the airway centerline. High-retropalatal (HRP), midretropalatal (MRP), and hypopharyngeal (HYP) regions were defined. Regional compliance was significantly increased from rostral to caudal regions as follows: HRP < MRP < HYP (P < 0.0001), and compliance differences among regions were directly related to collapsibility. Thus our findings in the isolated upper airway of the cat support the hypothesis that regional differences in pharyngeal compliance exist and suggest that baseline regional variations in compliance and collapsibility may be an important factor in the pathogenesis and treatment of obstructive sleep apnea.

Air Pressure↗
PubMed1998

Central administration of a 5-HT2 receptor agonist and antagonist: lack of effect on rapid eye movement sleep and pgo waves.

Serotonin (5-HT) has a role in regulating behavioral state and controlling the production of ponto-geniculo-occipital (PGO) waves, though the exact mechanism of action is not known. The most prevailing explanation is that 5-HT exerts its influence on behavioral state and PGO waves by inhibiting and disinhibiting cholinergic cells in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT), which have been implicated in their generation. Recent work in rats has demonstrated 5-HT2 receptors on most cholinergic cells in PPT/LDT. We microinfused the relatively specific 5-HT2 agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), the relatively specific 5-HT2 antagonist, ketanserin, and the nonspecific 5-HT antagonist, methysergide, locally into the peribrachial region of PPT in cats and monitored behavioral state and PGO waves. Neither drug significantly affected behavioral state or PGO wave activity. These results suggest that 5-HT2 receptors associated with cholinergic cells are minimally involved in the control of behavioral state and, together with the recent findings of others, suggest that 5-HT may not modulate PGO wave generation via direct action on cholinergic neurons in PPT/LDT, a departure from the long-held but minimally-tested view.

Analysis of Variance↗
PubMed1998

Microinjections into the pedunculopontine tegmentum: effects of the GABAA antagonist, bicuculline, on sleep, PGO waves and behavior.

Neurons in the peribrachial region (PB) at the pontine border are implicated in the generation of ponto-geniculo-occipital (PGO) waves, which appear spontaneously during rapid eye movement sleep (REM) and in association with alerting behaviors during waking, as well as in the regulation of REM itself. It has been hypothesized that PGO-related bursting in a subpopulation of these neurons results from low threshold spikes triggered by phasic hyperpolarizations or by excitatory inputs reaching a steadily hyperpolarized neuron. The hyperpolarization necessary for triggering the low threshold spikes may come from local GABA neurons or from GABAergic input into PB. To test the hypothesis that antagonizing GABA would alter PGO wave generation and/or behavioral state, we microinfused, in cats, the GABAA antagonist, bicuculline, locally into PB and monitored behavior, behavioral state and PGO waves recorded in the lateral geniculate bodies. Bicuculline produced no significant alteration in PGO wave activity. In 3 cats, bicuculline produced behaviors ranging from spontaneous orienting and startle (4 cats) to flight behaviors (2 cats) and aggressiveness (2 cats), an effect probably due to diffusion into the central gray region. Thus, the results do not support a GABAA-ergic role in PB in the generation of PGO waves.

Animals↗
PubMed1997

Activation of a distinct arousal state immediately after spontaneous awakening from sleep.

In contrast to the many neural studies into the mechanisms of sleep onset and maintenance, few studies have focused specifically on awakening from sleep. However, the abrupt electrographic changes and large brief cardio-respiratory activation at awakening suggest that a distinct, transiently aroused, awake state may exist compared to later wakefulness. To test this hypothesis we utilized the acoustic startle reflex, a standard un-conditioned reflex elicited by a sudden loud noise. This reflex is modulated under specific conditions, one being a diminution of startle when a quieter pre-stimulus is presented immediately before the loud stimulus. This pre-pulse inhibition (PPI) is used as a measure of sensorimotor gating, with smaller PPI indicating less filtering of sensory inputs and increased responsiveness to external stimuli. Eight rats with electrodes for recording sleep-wake state were studied. An accelerometer measured startle responses. The startle reflex was elicited by 115 dB, 40 ms tones. PPI was produced by 74 dB, 20 ms tones preceding the 115 dB tone by 100 ms. Responses within 100 ms were measured. Stimuli were applied either 3-10 s after spontaneous awakenings, or in established wakefulness (> 30 s). Responses to the startle stimuli alone were similar in the different awake states (P = 0.821). However, PPI was smaller at awakening from non-REM sleep compared to established wakefulness (45.4 +/- 7.5% vs. 74.3 +/- 6.1%, P = 0.0002). PPI after awakening from REM sleep (52.8 +/- 17.9%) was not significantly different than established wakefulness (P = 0.297). Reduced PPI of the startle reflex at awakening from non-REM sleep supports the hypothesis that wakefulness immediately after spontaneous sleep episodes is neurophysiologically distinct from later wakefulness and associated with reduced gating of motor responses to sensory inputs. Spontaneous activation of this distinct, transiently aroused, state upon awakening may serve a protective function, preparing an animal to respond immediately to potentially threatening stimuli.

Acoustic Stimulation↗
PubMed1997

Serotonin at the laterodorsal tegmental nucleus suppresses rapid-eye-movement sleep in freely behaving rats.

Serotonin [5-hydroxytryptamine (5-HT)] is believed to play an important inhibitory role in the regulation of rapid-eye-movement (REM) sleep. 5-HT may exert this effect on neurons of the laterodorsal tegmental (LDT) nuclei that are implicated as important in the generation of REM sleep and phasic REM events such as ponto-geniculo-occipital (PGO) waves and respiratory variability. In rat brainstem in vitro, 5-HT hyperpolarizes and inhibits the bursting properties of LDT neurons assumed to be involved in generating REM sleep and PGO waves. This study tests the hypothesis that in vivo 5-HT at the LDT nuclei suppresses REM sleep and phasic REM events. Ten rats were implanted with bilateral cannulae aimed at the LDT and with electrodes for recording the electroencephalogram, neck electromyogram, PGO waves, and diaphragm electromyogram. During REM sleep, 5-HT (100 nl; 1-1.5 mM), saline, or sham microinjections were performed; repeated microinjections were separated by approximately 1 hr. After the first microinjection, REM sleep as a percent of the total sleep time was reduced with 5-HT (mean percent REM, 19.9 +/- 2.5% for 5-HT vs 26.8 +/- 2.4% for saline; p = 0.02). REM duration was reduced by 37% with 5-HT (p = 0.01), but REM episode frequency was changed less consistently (p = 0.21), suggesting that 5-HT mainly disrupted REM sleep maintenance. Per unit time of REM sleep, 5-HT had no effect on the amount or variability of REM PGO activity (p > 0.740) or on the mean or coefficient of variation of REM respiratory rate (p > 0.11). With subsequent microinjections, the effects of 5-HT on REM sleep were similar. A dose-dependent REM sleep suppression with 5-HT was observed in five rats tested. These data suggest that in vivo 5-HT at the LDT nuclei suppresses REM sleep expression. Although 5-HT did not disproportionately reduce the occurrence of phasic events within REM, total REM phasic activity was reduced because of less REM sleep after 5-HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Differential sensitivity of laryngeal and pharyngeal motoneurons to iontophoretic application of serotonin.

Serotonergic neurons decrease their activity during sleep, especially rapid eye movement sleep, thereby reducing their facilitatory effect on upper airway motoneurons. The magnitude of teh sleep-related loss of tone varies among upper airway muscles (e.g., pharyngeal dilator motoneurons are more suppressed than laryngeal motoneurons). We hypothesized that these differences may be related to the sensitivity of different groups of upper airway motoneurons to serotonin. Experiments were done on decerebrate, vagotomized, paralysed and artificially-ventilated cats. Hypoglossal and laryngeal motoneurons were recorded extracellularly using five-barrel pipettes filled with: serotonin, glutamate and methysergide (serotonergic antagonist) for iontophoresis, and NaCl for recording and current balancing. All but two of the 65 hypoglossal motoneurons (45 inspiratory, 10 expiratory, 10 tonic) and 27 out of 32 laryngeal motoneurons (14 inspiratory, 18 expiratory) were excited by serotonin, and the excitation was abolished by methysergide. To compare the magnitude of the excitatory effect among distinct motoneuronal groups, we applied small ejection currents in a standardized manner (+15 nA for 3 min; 10 mM serotonin in 150 NaCl) onto spontaneously active motoneurons (13 inspiratory hypoglossal, 11 inspiratory laryngeal and 11 expiratory laryngeal). Serotonin increased the number of spikes per respiratory burst of inspiratory hypoglossal motoneurons from 19 +/- 4.0 (S.E.M.) to 35 +/- 4.8, of inspiratory laryngeal motoneurons from 44 +/- 8.3 to 55 +/- 8.8, and of expiratory laryngeal motoneurons from 23 +/- 4.8 to 33 +/- 6.2. The relative increases in activity (to 220% +/- 24, 147% +/- 23 and 148% +/- 9 of control, respectively) were significantly higher in hypoglossal than in laryngeal motoneurons. In addition, the excitatory effect developed significantly faster in hypoglossal than in laryngeal motoneurons. Methysergide reduced the spontaneous activity of about half the hypoglossal and laryngeal motoneurons to 66% +/- 5 of control. Thus, the sensitivity to the excitatory effects of serotonin varies among different pools of upper airway motoneurons. These differences correlate with the pattern of airway muscle hypotonia seen during sleep.

Action Potentials↗
PubMed1997

Night-to-night variability in CPAP use over the first three months of treatment.

The purpose of this study was to examine the relationship between night-to-night variability and nightly duration of continuous positive airway pressure (CPAP) therapy over the first 9 weeks of treatment and to determine when patients begin to establish a nonadherent pattern of use. Data were analyzed from a study of daily CPAP use covertly monitored in 32 diagnosed patients with obstructive sleep apnea (OSA) using a microprocessor monitor encased in a CPAP machine. Patterns of CPAP use were bimodal, based on the frequency of nightly use. Approximately half the subjects were consistent users of CPAP, applying it > 90% of the nights for an average of 6.22 +/- 1.21 hours per night, while the other half comprised intermittent users who had a wide range of daily use averaging 3.45 +/- 1.94 hours per night on the nights CPAP was used. The percent of days skipped was significantly correlated with decreased nightly duration (rho = -0.73, p < 0.0001). Analysis of the night-to-night pattern of use revealed that the two groups differed significantly in the nightly duration of CPAP use by the fourth day of treatment (p = 0.001). Exploration of factors that potentially differentiate the two groups revealed no reliable predictors. However, intermittent users continued to report significantly greater OSA symptoms (snoring, snorting, and apnea) posttreatment, suggesting that they continued to experience sleep disordered breathing.

Adult↗
PubMed1997

Population and occupational screening for obstructive sleep apnea: are we there yet?

Several features of obstructive sleep apnea (OSA) suggest that it may be an appropriate disease for screening programs for general populations and more specific high-risk groups. Preliminary data suggest that OSA represents an important health problem in terms of high prevalence, increased levels of morbidity and mortality, and increased public safety risk. Furthermore, the chronicity of the disease and the relatively low levels of recognition of the disorder in the medical community suggest a potential for lead-time gains for screening programs. Specific groups that might be considered for screening programs include commercial vehicle operators, hazardous duty personnel, and certain groups of medical patients. The purpose of this clinical commentary is to consider the issues of population and specific group screening for OSA by reviewing the general principles of screening for chronic disease and then applying these principles specifically in the case of OSA. More extensive outcomes data relating levels of severity of the disorder to its potential adverse outcomes are needed and will assist in tailoring appropriate screening programs and determining the cost-effectiveness of screening various populations.

Chronic Disease↗
PubMed1997

Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night.

To determine whether a cumulative sleep debt (in a range commonly experienced) would result in cumulative changes in measures of waking neurobehavioral alertness, 16 healthy young adults had their sleep restricted 33% below habitual sleep duration, to an average 4.98 hours per night [standard deviation (SD) = 0.57] for seven consecutive nights. Subjects slept in the laboratory, and sleep and waking were monitored by staff and actigraphy. Three times each day (1000, 1600, and 2200 hours) subjects were assessed for subjective sleepiness (SSS) and mood (POMS) and were evaluated on a brief performance battery that included psychomotor vigilance (PVT), probed memory (PRM), and serial-addition testing, Once each day they completed a series of visual analog scales (VAS) and reported sleepiness and somatic and cognitive/emotional problems. Sleep restriction resulted in statistically robust cumulative effects on waking functions. SSS ratings, subscale scores for fatigue, confusion, tension, and total mood disturbance from the POMS and VAS ratings of mental exhaustion and stress were evaluated across days of restricted sleep (p = 0.009 to p = 0.0001). PVT performance parameters, including the frequency and duration of lapses, were also significantly increased by restriction (p = 0.018 to p = 0.0001). Significant time-of-day effects were evident in SSS and PVT data, but time-of-day did not interact with the effects of sleep restriction across days. The temporal profiles of cumulative changes in neurobehavioral measures of alertness as a function of sleep restriction were generally consistent. Subjective changes tended to precede performance changes by 1 day, but overall changes in both classes of measure were greatest during the first 2 days (P1, P2) and last 2 days (P6, P7) of sleep restriction. Data from subsets of subjects also showed: 1) that significant decreases in the MSLT occurred during sleep restriction, 2) that the elevated sleepiness and performance deficits continued beyond day 7 of restriction, and 3) that recovery from these deficits appeared to require two full nights of sleep. The cumulative increase in performance lapses across days of sleep restriction correlated closely with MSLT results (r = -0.95) from an earlier comparable experiment by Carskadon and Dement (1). These findings suggest that cumulative nocturnal sleep debt had a dynamic and escalating analog in cumulative daytime sleepiness and that asymptotic or steady-state sleepiness was not achieved in response to sleep restriction.

Adult↗
PubMed1997

An instrument to measure functional status outcomes for disorders of excessive sleepiness.

This article reports the development of the functional outcomes of sleep questionnaire (FOSQ). This is the first self-report measure designed to assess the impact of disorders of excessive sleepiness (DOES) on multiple activities of everyday living. Three samples were used in the development and psychometric analyses of the FOSQ: Sample 1 (n = 153) consisted of individuals seeking medical attention for a sleep problem and persons of similar age and gender having no sleep disorder; samples 2 (n = 24) and 3 (n = 51) were composed of patients from two medical centers diagnosed with obstructive sleep apnea (OSA). Factor analysis of the FOSQ yielded five factors: activity level, vigilance, intimacy and sexual relationships, general productivity, and social outcome. Internal reliability was excellent for both the subscales (alpha = 0.86 to alpha = 0.91) and the total scale (alpha = 0.95). Test-retest reliability of the FOSQ yielded coefficients ranging from r = 0.81 to r = 0.90 for the five subscales and r = 0.90 for the total measure. The FOSQ successfully discriminated between normal subjects and those seeking medical attention for a sleep problem (T157 = -5.88, p = 0.0001). This psychometric evaluation of the FOSQ demonstrated parameters acceptable for its application in research and in clinical practice to measure functional status outcomes for persons with DOES. Thus, the FOSQ can be used to determine how disorders of excessive sleepiness affect patients' abilities to conduct normal activities and the extent to which these abilities are improved by effective treatment of DOES.

Activities of Daily Living↗
PubMed1996

Respiratory activity in the facial nucleus in an in vitro brainstem of tadpole, Rana catesbeiana.

1. In studies of the central neural control of breathing, little advantage has been taken of comparative approaches. We have developed an in vitro brainstem preparation using larval Rana catesbeiana which generates two rhythmic neural activities characteristic of lung and gill ventilation. Based on the pattern of the facial (VII) nerve activity both lung and gill rhythm-related respiratory cycles were divided into three distinct phases. The purpose of this study was to characterize and classify membrane potential trajectories of respiratory motoneurons in the VII nucleus at intermediate stages (XII-XVII) of development. 2. Seventy-five respiratory-modulated neurons were recorded intracellularly within the facial motor nucleus region. Their resting membrane potential was between -40 and -80 mV. Sixty of them were identified as VII motoneurons and fifteen were non-antidromically activated. Membrane potentials of fifty-six of the seventy-five neurons were modulated with both lung (5-27 mV) and gill rhythms (3-15 mV) and the remaining nineteen neurons had only a modulation with lung rhythmicity (6-23 mV). No cells with gill modulation alone were observed. 3. All of the cells modulated with lung rhythmicity had only phase-bound depolarizing or hyperpolarizing membrane potential swings which could be categorized into four distinct patterns. In contrast, of the fifty-six cells modulated with gill rhythmicity, thirty-two were phasically depolarized during distinct phases of the gill cycle (four patterns were distinguished), whereas the remaining twenty-four were phase spanning with two distinct patterns. The magnitudes of lung and gill modulations were proportionally related to each other in the cells modulated with both rhythms. 4. In all sixteen neurons studied, a reduction or a reversal of phasic inhibitory inputs during a portion of the lung or gill respiratory cycle was observed following a negative current or chloride ion (Cl-) injection. The phasic membrane resistance modulation in relation to the gill rhythm was analysed in six neurons and a relative decrease in the somatic membrane resistance (0.7-8.1 M omega) was detected during the periods of hyperpolarization. 5. We propose that, at these intermediate stages of development: (a) both gill and lung respiratory oscillations in motoneurons are generated by respiratory premotor neurons having only a few distinct activity patterns; (b) these patterns delineate distinct portions of the centrally generated respiratory cycles; and (c) phasic synaptic inhibition, mediated by Cl-, contributes to shaping the membrane potential trajectories of respiratory motoneurons.

Animals↗
PubMed1996

Role of chloride-mediated inhibition in respiratory rhythmogenesis in an in vitro brainstem of tadpole, Rana catesbeiana.

1. The isolated brainstem of larval Rana catesbeiana maintained in vitro generates neural bursts that correspond to the lung and gill ventilatory activity generated in the intact specimen. To investigate the role of chloride channel-dependent inhibitory mechanisms mediated by GABA(A) and/or glycine receptors on fictive lung and gill ventilation, we superfused the isolated brainstems with agonists, antagonists (bicuculline and/or strychnine) or a chloride-free solution while recording multi-unit activity from the facial motor nucleus. 2. Superfusion with the agonists (GABA or glycine) produced differential effects on frequency, amplitude and duration of the neural bursts related to lung and gill ventilation. At a GABA or glycine concentration of 1.0 mM, fictive gill bursts were abolished while fictive lung bursts persisted, albeit with reduced amplitude and frequency. 3. At the lowest concentrations used (1.0-2.5 microM), the GABA(A) receptor antagonist bicuculline produced an increase in the frequency of lung bursts. At higher concentrations (5.0-2.0 microM) bicuculline produced non-specific excitatory effects. The glycine antagonist strychnine, at concentrations lower than 5.0 microM, caused a progressive decrease in the frequency and amplitude of the gill bursts and eventually abolished the rhythmic activity. At higher concentrations (7.5 microM), non-specific excitatory effects occurred. Superfusion with bicuculline (10 microM) and strychnine (5 microM) combined abolished the neural output for gill ventilation but increased the frequency, amplitude and duration of lung bursts. 4. Superfusion with Cl(-)-free solution also abolished the rhythmic neural bursts associated with gill ventilation, while it significantly increased the amplitude (228 +/- 51%; P < 0.05) (mean +/- S.E.M.) and duration of the lung bursts (3.5 +/- 0.1 to 35.3 +/- 3.7 s; P < 0.05) and improved the regularity of their occurrence. 5. We conclude that different neural systems generate rhythmic activity for lung and gill ventilation. Chloride-mediated inhibition may be essential for generation of neural bursts associated with gill ventilation. In contrast, the burst associated with lung ventilation can be generated in the absence of Cl(-)-mediated inhibition although the latter plays a role in shaping the normal lung burst.

Animals↗
PubMed1996

Behaviour of raphe cells projecting to the dorsomedial medulla during carbachol-induced atonia in the cat.

1. The activity of most brainstem serotonergic cells is suppressed during sleep, particularly the rapid eye movement (REM) phase. Thus, they may play a major role in state-dependent changes in CNS functioning. Our main goal was to search for medullary raphe cells having axonal branches in the region of the hypoglossal (XII) motor nucleus and assess their behaviour during the atonia produced by microinjections of a cholinergic agonist, carbachol, into the dorsal pontine tegmentum. In chronic animals, such microinjections evoke a desynchronized sleep-like state similar to natural REM sleep; in decerebrate animals, they produce eye movements and a motor suppression similar to the postural atonia of REM sleep. 2. In decerebrate, paralysed, vagotomized and artificially ventilated cats, we recorded extracellularly from medullary raphe cells antidromically activated from the XII nucleus region. Forty-five cells recorded in the raphe obscurus and pallidus nuclei were antidromically activated with latencies characteristic of non-myelinated fibres (4.4-42.0 ms). For thirty-three of the forty-five cells, we found one or more axonal branches within or just below the XII nucleus. The remaining twelve cells, in addition to the XII nucleus, had axonal ramifications in the medial nucleus of the solitary tract (NTS) and/or the dorsal motor nucleus of the vagus (DMV). 3. A subset of fourteen spontaneously active cells with identified axonal projections were held long enough to be recorded during the carbachol-induced atonia, and eight of these also during the subsequent recovery and a systemic administration of the serotonergic 1A receptor agonist (+/-)8-hydroxy-2-(di-N-propylamino)tetrealin hydrobromide (8-OH-DPAT). All but one were suppressed during the atonia in parallel to the suppression of XII, phrenic and postural nerve activities (firing rate, 1.3 +/- 0.7 Hz before and 0.1 +/- 0.2 Hz after carbachol (means +/- S.D.)). Following the recovery from the atonia, the firing rates of the eight cells increased to the pre-carbachol level (1.6 +/- 1.0 Hz). Subsequently, all were silenced by 8-OH-DPAT. 4. These cells fulfil most physiological criteria for serotonergic cells and have the potential to modulate, in a state-dependent manner, activities in the motor XII nucleus, visceral sensory NTS, and DMV. The decrements in serotonergic neuronal activity that occur during the carbachol-induced atonia suggest that a similar withdrawal of serotonergic input may occur during REM sleep and contribute to the characteristic reductions in upper airway motor tone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Modulation of IL-1 beta gene expression in the rat CNS during sleep deprivation.

We hypothesize that sleep homeostasis involves, at least in part, the immune system modulator interleukin-1 beta (IL-1 beta). Using the reverse transcription-polymerase chain reaction, IL-1 beta mRNA levels in the rat CNS were evaluated after a period of sleep deprivation. In addition, IL-1 beta gene expression was analyzed before the projected onset of activity and rest phase in free-running animals. No changes in IL-1 beta mRNA were observed in the circadian cycle, but 24 h of sleep deprivation resulted in a 2-fold increase in the level of IL-1 beta mRNA in the hypothalamus and in the brain stem compared with controls (p < 0.0002 and (p < 0.0001 respectively). The alteration in IL-1 beta mRNA levels following sleep deprivation supports the hypothesis that modulation of IL-1 beta gene expression is involved in the sleep homeostatic process.

Animals↗
PubMed1996

The scope and nature of the drowsy driving problem in New York State.

A telephone survey was conducted of a random sample of New York State licensed drivers to determine the prevalence and circumstances of drowsy driving. Based on the survey responses, 54.6% of the drivers had driven while drowsy within the past year; 22.6% had ever fallen asleep at the wheel without having a crash, 2.8% had ever crashed when they fell asleep, and 1.9% had crashed when driving while drowsy. Of the reported crashes due to driving while drowsy or falling asleep at the wheel, 82.5% involved the driver alone in the vehicle, 60.0% occurred between 11:00 p.m. and 7:00 a.m. 47.5% were drive-off-road crashes, and 40.0% occurred on a highway or expressway. Multiple regression analysis suggested that the following driver variables are predictive of an increased frequency of driving drowsy: demographic characteristics (younger drivers, more education, and men); sleep patterns (fewer hours of sleep at night and greater frequency of trouble staying awake during the day); work patterns (greater frequency of driving for job and working rotating shifts); and driving patterns (greater number of miles driven annually and fewer number of hours a person can drive before becoming drowsy).

Accidents, Traffic↗
PubMed1996

Does upper airway muscle injury trigger a vicious cycle in obstructive sleep apnea? A hypothesis.

Recent studies have indicated that the level of neural activation of upper airway dilator muscles is abnormally elevated in patients with obstructive sleep apnea (OSA). This is presumed to represent an adaptive mechanism that partially compensates for the anatomically small upper airway found in individuals with OSA. We have reviewed evidence that pharyngeal dilator muscles undergo secondary changes in structure as a direct consequence of their increased activity level in OSA. These alterations have the potential to be both beneficial and harmful with respect to the maintenance of upper airway patency. We propose a model outlining the possible role of activity-induced upper airway muscle remodeling and injury in the pathogenesis of OSA, and discuss potential implications for treatment of the disease.

Humans↗
PubMed1996

Modafinil decreases hypersomnolence in the English bulldog, a natural animal model of sleep-disordered breathing.

The English bulldog is a natural model of sleep-disordered breathing (SDB). This condition is marked by 1) hypersomnolence and 2) disordered breathing episodes that are most frequent and severe during rapid eye movement (REM) sleep. Modafinil has been found to increase arousal levels in animals and decrease excessive daytime sleepiness in humans. Therefore, in this study we focused mainly on the effects of the drug on total sleep time and sleep latency and secondarily assessed its effect on REM SDB. Five English bulldogs were implanted with subcutaneous electroencephalographic/electrooculographic (EEG/EOG) electrodes and instrumented with respiratory oscillation belts to measure abdominal and rib cage movements and an ear oximeter to measure saturation. The dogs were studied for approximately 8 hours each subsequent day on two consecutive days. On the first day, they received the vehicle dimethyl sulfoxide (DMSO) i.v. as a control. On the following day they received 10 mg/kg body weight of modafinil i.v. dissolved in the DMSO vehicle. Our findings indicate that modafinil significantly alleviates hypersomnolence (p < 0.05) in the bulldog, as evidenced by dramatically decreased mean total sleep time (from a control value of 50.5% to 8.3% with the drug) and increased mean sleep latency (from a control value of 71.0 minutes to a value of 346.6 minutes with the drug). We obtained limited data on the effect of modafinil on SDB because the drug either greatly diminished or entirely eradicated REM sleep in all five dogs.

Animals↗