Pathophysiological mechanisms in obstructive sleep apnea.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C E Sullivan.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We studied the effects of sleep fragmentation on arousal and ventilatory responses to hyperoxic hypercapnia, isocapnic hypoxia, and chemical stimulation of the larynx during sleep in 5 dogs. Sleep fragmentation was induced by repeatedly arousing the dogs with acoustic stimuli throughout 2 to 3 consecutive nights. Responses to respiratory stimuli were then studied during a subsequent daytime sleep. Arterial O2 saturation was measured with an ear oximeter, and sleep stage was determined by electroencephalographic and behavioral criteria. Hypercapnic and hypoxic ventilatory responses were unimpaired by sleep fragmentation. In contrast, alveolar PCO2 levels at arousal increased after sleep fragmentation, from a mean +/- SEM of 52.2 +/- 1.4 mm Hg to 55.6 +/- 1.5 mm Hg (p < 0.05) during slow-wave sleep, and from 57.9 +/- 1.5 mm Hg to 61.3 +/- 2.2 mm Hg (p < 0.05) during rapid-eye movement sleep. Similarly, arterial O2 saturation at arousal decreased after sleep fragmentation from 80.1 +/- 1.0% to 70.2 +/- 2.7% (p < 0.05) during slow-wave sleep, and from 66.3 +/- 3.6% to < 55% (p < 0.05) during rapid-eye-movement sleep. Arousal responses to laryngeal stimulation were also impaired after sleep fragmentation. We conclude that arousal responses to respiratory stimuli are decreased by sleep fragmentation.
Explore the source record for details and available documents.
We studied waking, ventilatory, and reflex tracheal smooth muscle (TSM) responses to tracheobronchial irritation or lung inflation in three sleeping dogs. The dogs breathed through a cuffed endotracheal tube, and airflow was measured with a pneumotachograph. TSM tone was monitored directly by measuring pressure in the water-filled cuff of the endotracheal tube. Mild degrees of tracheobronchia irritation, produced by squirting 0.1--1.0 ml of water into the lower trachea, or by having the dogs inhale one breath of acetic acid vapor (concentration 17 ppm), generally caused arousal from slow-wave sleep (SWS), but not from rapid-eye-movement (REM) sleep. During wakefulness the irritant stimuli caused coughing and TSM constriction; during SWS or REM sleep, these responses occurred only if the stimulus first produced arousal. In contrast, stimulation of pulmonary stretch receptors by lung inflation did not cause arousal, but readily produced apnea and TSM relaxation during SWS. The results indicate that cough and airway smooth muscle constriction in response to bronchopulmonary irritant stimuli do not occur in the absence of arousal, and that arousal responses to such stimuli are depressed in REM sleep.
Ventilatory responses to CO2 and to lung inflation were compared in four dogs during tonic and phasic segments of rapid-eye-movement (REM) sleep. Phasic REM sleep (P-REM) was identified by the presence of bursts of rapid eye movements, visible muscle twitchings, and frequent phasic discharges in the nuchal electromyogram. These features were absent during tonic REM sleep (T-REM). During P-REM the response of minute volume of ventilation (VI) to progressive hypercapnia (0.58 +/- 0.19 (l/min)/Torr, mean +/- SE) was significantly less than in slow-wave sleep (SWS) (1.40 +/- 0.14; P less than 0.05). In contrast, during T-REM the response (1.48 +/- 0.19) was similar to that in SWS. Similarly, during P-REM the duration of apnea (5.9 +/- 1.5 s) elicited by sustained inflation of the lungs with 1.0 liter of air, was significantly shorter than in SWS (25.8 +/- 0.8); in contrast, during T-REM the duration of apnea (17.8 +/- 3.6) was similar to that in SWS. The results indicate that previously described decreases in VI responses to CO2 and apneic responses to lung inflation during P-REM, compared to SWS, are related to the phasic phenomena of REM sleep, rather than to the REM sleep state per se.
We examined the influence of sleep state on airway smooth muscle tone in 4 unanesthetized dogs that were trained to sleep in the laboratory. The dogs had been prepared with a permanent side-hole tracheostomy and bilateral cervical vagal loops. During the studies, the dogs breathed through a cuffed endotracheal tube inserted through the tracheostomy. To monitor changes in tracheal smooth muscle tone, we measured the pressure in the water-filled cuff of the endotracheal tube. The technique was validated by examining changes in cuff pressure after administration to the dogs of a series of chemical agents and physiologic stimuli known to constrict or relax tracheobronchial smooth muscle. Sleep state of the dogs was determined by behavioral, electroencephalographic, and electromyographic criteria. During quiet wakefulness, tracheal smooth muscle tone was stable. With the onset and progression of sleep through the nonrapid-eye movement stages, airway smooth muscle tone relaxed (decrease in cuff pressure of 20 to 40 cm H2O), reaching a new steady level during slow-wave sleep. In contrast, during rapid-eye-movement sleep, tracheal smooth muscle tone fluctuated markedly and erratically, as reflected by changes in cuff pressure as large as 90 cm H2O. Partial blockade of the vagus nerves, by cooling the exteriorized cervical vagal loops, decreased or abolished the fluctuations in tracheal smooth muscle tone during rapid-eye-movement sleep at temperatures that did not abolish resting tone, demonstrating that the changes in tone during rapid-eye-movement sleep were related to variability in neural control of airway smooth muscle.
We examined waking and ventilatory responses to acute hypoxia in four dogs during natural sleep. Progressive hypoxia was induced by a rebreathing technique in which alveolar CO2 pressure (PACO2) was held at the eucapnic level. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and sleep stage was determined by electroencephalographic and behavioral criteria. Arousal from eucapnic hypoxia occurred at a SaO2 of 87.5 +/- 2.6% (mean +/- SE) during slow-wave sleep (SWS), and at a SaO2 of 70.5 +/- 3.4% during rapid-eye-movement (REM) sleep (P less than 0.005). The irregular pattern of breathing typical of REM sleep persisted during hypoxia. However linear regression analysis of breath-by-breath instantaneous minute volume of ventilation (VI) against SaO2 revealed regression coefficients in REM sleep that were similar to those found in SWS and wakefulness. This finding contrasts with earlier observations of a decreased response of VI to CO2 during REM sleep. The results indicate that although waking responses to hypoxia are delayed in REM sleep, ventilatory responses remain intact and therefore may be of importance in maintaining adequate ventilation during this stage of sleep.
We studied the effects on breathing rhythm of suppressing the major respiratory stimuli (wakefulness, vagal, peripheral and central chemoreceptors) in healthy, unanesthetized dogs. Respiratory frequency (f) was obtained with a pneumotachograph; the state of wakefulness (W) or sleep was determined by EEG and behavioral criteria. During quiet W, f averaged 17 breaths/min and minute volume of ventilation (VI), 8.4 l/min. In slow-wave sleep (SWS), f slowed to 14 breaths/min, and VI decreased to 6.8 l/min. Afferent vagal blockade during SWS slowed f to 4 breaths/min, due primarily to prolongation of expiratory duration (Te) to 13.3 s, and decreased VI to 4.8 l/min. One breath of 100% O2 prolonged Te further to 27.4 s. Central chemoreceptor sensitivity was then reduced by inducting a metabolic alkalosis that combined with SWS, vagal blockade, and hyperoxia prolonged Te to as long as 57 s and reduced f to as low as 1 breath/min. The results demonstrate that afferent respiratory stimuli are essential for sustaining adequate ventilation.
We studied waking and ventilatory responses to laryngeal stimulation during sleep in three dogs. The dogs breathed through an endotracheal tube inserted caudally into the trachea through a tracheostomy. Laryngeal stimulation was produced either by inflating a small balloon that was positioned in the rostral tracheal segment, or by squirting water onto the larynx through a catheter inserted through the tracheostomy. Airflow was measured with a pneumotachograph, and sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria. We found that the degree of laryngeal stimulation required to produce arousal and coughing was higher in rapid-eye-movement (REM) sleep than in slow-wave sleep (SWS). Stimuli that failed to cause arousal from SWS often produced a single expiratory effort, or brief apnea (1--2 s) and bradycardia. In contrast, during REM sleep subarousal stimuli often resulted in prolonged apnea (greater than 10 s) and marked bradycardia. We conclude that during REM sleep arousal responses to laryngeal stimulation are depressed, but ventilatory and cardiac responses are intact.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
13C nmr spectra of defatted aorta, obtained from chick embryos, ranging in age from 13 to 20 days, showed that linewidths were independent of the age of the embryo, this, in spite of the fact that crosslinking increases with age. As expected the dipolar decoupled spectrum of defatted aorta had a larger C-H signal intensity than the scalar decoupled spectrum, since collagen in the sample contributes signal intensity only in the former case. Significantly, the dipolar decoupled spectrum of autoclaved aorta also had a larger C-H signal intensity. This result indicates that ca. 30% of the carbons in the tissue, swollen by 0.15 M NaCl, has restricted motion at 37 degrees. Preliminary data indicate that tissue culture techniques can be used to enrich specific amino acids in chick aorta with 13C, thereby affording a means to study possible differences in molecular structure of the chemically distinct regions in elastin.
Reduced and methylated collagen from Ascaris lumbricoides cuticle was resolved into three major components by chromatography on phosphocellulose. The components have similar molecular weights of about 52,000 by sedimentation equilbrium and molecular sieve chromatography, but they have different amino acid compositions. Since they do not appear to be stoichiometrically related, they apparently represent chains from collagens of more than one type. All three chains contain about 27 residue % glycine, 36 residues of proline, and 17 residues of methylcysteine, suggesting that the collagens can be maximally about 80% triple helical and are extensively disulfide cross-linked in the native state. Two minor components from the cuticle are apparently derived from one of the major chains by cleavage in a single region to give two-third and one-third fragments.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Metronidazole is a 5-nitroimidazole that has selective activity against anaerobic microorganisms, including bacteria and protozoa. Intravenous metronidazole has recently been approved by the U.S. Food and Drug Administration for the treatment of serious anaerobic bacterial infections. It is usually bactericidal at low concentrations, and its spectrum of activity encompasses almost all anaerobic bacteria and some capnophilic organisms. Anaerobic bacteria known to be resistant to metronidazole include occasional anaerobic cocci, some nonsporulating gram-positive bacilli and propionibacterium. Metronidazole is the most active antimicrobial agent against Bacteroides fragilis, the most resistant of anaerobic bacteria. Kill-curve studies demonstrate that there is a 2 to 5 log decrease in the number of colony forming units of B. fragilis and Clostridium perfringens within one hour. The only well documented metronidazole-resistant strain is a B. fragilis isolated from the normal flora of a patient on long-term metronidazole therapy for Crohn's Disease. Metronidazole resistance in Trichomonas vaginalis has recently been described in a few strains that are able to survive at increased oxygen tensions. Metronidazole has been shown to be efficacious in certain protozoal infections including trichomonal vaginitis, extraintestinal amebiasis, and giardiasis. Clinical studies have shown metronidazole to be efficacious in the therapy of a variety of anaerobic infections, including non-traumatic brain abscesses, intraabdominal sepsis, pelvic suppuration and necrotizing soft tissue infections. There have been disappointing results in the therapy of anaerobic pleuropulmonary infections with a number of superinfections caused by aerobic bacteria. Since metronidazole lacks any activity against aerobic bacteria, it must be combined with other agents, usually aminoglycosides, in the treatment of mixed infections involving anaerobic and aerobic bacteria.