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A R Schwartz

Publications and source records attributed to A R Schwartz.

At least 19 recordsLinked to original sources
PubMed2006

A pilot study of quantitative assessment of mandible advancement using pressure-flow relationship during midazolam sedation.

It has been proposed that a titration of the mandibular positioner would be a promising method for predicting the outcome of nasal continuous positive airway pressure (CPAP) therapy. This study was carried out to test the hypothesis that mandible advancement could be evaluated by analysis of inspiratory flow limitation using a titration procedure. To explore its effect, we examined upper airway pressure-flow relationships using a titrated mandible positioner during midazolam sedation. Non-flow limited inspiration occurred when the mandible was advanced 7.1 +/- 1.2 mm from centric occlusion position. In the centric occlusion position (0 mm advancement), Pcrit was -1.9 +/- 2.9 cmH2O and Rua was 23.3 +/- 4.5 cmH2O L(-1) s(-1). In the eMAP position, Pcrit was -7.3 +/- 1.9 cmH2O and Rua was 27.8 +/- 3.3 cmH2O L(-1) s(-1). Essentially no CPAP was required to overcome flow limitation in eMAP position, whereas 3.7 +/- 2.2 cmH2O CPAP was required in centric occlusion position. We conclude that assessing inspiratory flow limitation using a titrated mandible positioner was effective for estimating individual-matched mandible positions.

Adult↗
PubMed2005

Effect of mandibular position on upper airway collapsibility and resistance.

It has been proposed that advancement of the mandible is a useful method for decreasing upper airway collapsibility. We carried out this study to test the hypothesis that mandibular advancement induces changes in upper airway patency during midazolam sedation. To explore its effect, we examined upper airway pressure-flow relationships in each of 4 conditions of mouth position in normal, healthy subjects (n = 9). In the neutral position, Pcrit (i.e., critical closing pressure, an index of upper airway collapsibility) was -4.2 cm H(2)O, and upstream resistance (Rua) was 21.2 cm H(2)O/L/sec. In the centric occlusal position, Pcrit was -7.1 cm H(2)O, and Rua was 16.6 cm H(2)O/L/sec. In the incisor position, Pcrit was significantly reduced to -10.7 cm H(2)O, and Rua was significantly reduced to 14.0 cm H(2)O/L/sec. Mandibular advancement significantly decreased Pcrit to -13.3 cm H(2)O, but did not significantly influence Rua (22.1 cm H(2)O/L/sec). We conclude that the mandibular incisors' position improved airway patency and decreased resistance during midazolam sedation.

Adult↗
PubMed2004

Elimination of central sleep apnoea by mitral valvuloplasty: the role of feedback delay in periodic breathing.

Central sleep apnoea is a form of periodic breathing which resembles Cheyne-Stokes respiration but occurs only during sleep. One mechanism in the pathogenesis is a delay in chemical feedback from the lungs to the medullary respiratory centre. We explored the relationship between circulatory feedback delay in a patient with central sleep apnoea and Cheyne-Stokes respiration before and after mitral valve repair. Preoperatively the patient had severe central sleep apnoea and an increased circulation time. Following mitral valvuloplasty the circulation time was decreased with resolution of central sleep apnoea. This case demonstrates the role of feedback delay in central sleep apnoea and suggests that similar haemodynamic mechanisms may lead to central sleep apnoea and Cheyne-Stokes respiration.

Cheyne-Stokes Respiration↗
PubMed2004

Mouth-opening increases upper-airway collapsibility without changing resistance during midazolam sedation.

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

Adult↗
PubMed2003

Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5.

We hypothesized that upper airway obstruction (UAO) leads to a compensatory increase in the duty cycle [ratio of inspiratory time to respiratory cycle length (Ti/Tt)], which is determined by genetic factors. We examined the compensatory Ti/Tt responses to 1). UAO and hypercapnia among normal individuals and 2). hypercapnia in different inbred strains, C3H/HeJ (C3) and C57BL/6J (B6), and their first- and second-generation (F2) offspring. 3). We then used the compensatory Ti/Tt response in the F2 to determine genetic linkage to the mouse genome. First, normal individuals exhibited a similar increase in the Ti/Tt during periods of hypercapnia (0.11 +/- 0.07) and UAO (0.09 +/- 0.06) compared with unobstructed breathing (P < 0.01). Second, the F2 offspring of C3 and B6 progenitors showed an average Ti/Tt response to 3% CO2 (0.42 +/- 0.005%) that was significantly (P < 0.01) greater than that of the two progenitors. Third, with a peak log of the odds ratio score of 4.4, Ti/Tt responses of F2 offspring are genetically linked to an interval between 58 and 64 centimorgans (cM) on mouse chromosome 5. One gene in the interval, Dagk4 at 57 cM, is polymorphic for C3 and B6 mice. Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological plausibility in mechanisms of upper airway patency and chemosensitivity, respectively. In summary, Ti/Tt may serve as an intermediate physiological phenotype for compensatory neuromuscular response mechanisms for maintaining ventilation in the face of UAO and hypoventilation and to help target specific candidate genes that may play a role in the expression of sleep-disordered breathing.

Adult↗
PubMed2002

Upper airway collapsibility: measurement techniques and therapeutic implications.

Several techniques are currently available that aim to characterize upper airway function/mechanics during wakefulness or sleep. Based on the concept of a Starling resistor, we propose a standardized protocol to measure the critical pressure (Pcrit) (an indicator of upper airway collapsibility) during sleep. The effect of therapeutic interventions such as weight loss, positional changes or uvulopalatopharyngoplasty on Pcrit is illustrated by data from the literature. We propose that measurement of Pcrit become implemented in the diagnostic work-up of selected patients with sleep-related breathing disorder to help making a correct therapeutic decision.

Airway Resistance↗
PubMed2001

Female gender exacerbates respiratory depression in leptin-deficient obesity.

Obese females are less predisposed to sleep-disordered breathing and have higher serum leptin levels than males of comparable body weight. Because leptin is a powerful respiratory stimulant, especially during sleep, we hypothesized that the elevated leptin level is necessary to maintain normal ventilatory control in obese females. We examined ventilatory control during sleep and wakefulness in male and female leptin-deficient obese C57BL/6J-Lep(ob) mice, wild-type C57BL/6J mice with dietary-induced obesity and high serum leptin levels, and normal weight wild-type C57BL/6J mice. Both male and female C57BL/6J-Lep(ob) mice had depressed hypercapnic ventilatory response (HCVR) in comparison with wild-type animals. In comparison with male C57BL/6J-Lep(ob) mice, female C57BL/6J-Lep(ob) mice had reduced HCVR and respiratory drive (a ratio of tidal volume to inspiratory time) both during non-rapid eye movement (NREM) sleep and wakefulness. In contrast, the HCVR did not differ between sexes in wild-type mice during NREM sleep and wakefulness, but was lower in females during REM sleep. Thus, leptin deficiency in female obesity is even more detrimental to hypercapnic ventilatory control during wakefulness and NREM sleep than in obese, leptin-deficient males.

Animals↗
PubMed2001

Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea.

BACKGROUND: Hypoglossal nerve stimulation has been demonstrated to relieve upper airway obstruction acutely, but its effect on obstructive sleep apnea is not known. OBJECTIVE: To determine the response in obstructive sleep apnea to electrical stimulation of the hypoglossal nerve. METHODS: Eight patients with obstructive sleep apnea were implanted with a device that stimulated the hypoglossal nerve unilaterally during inspiration. Sleep and breathing patterns were examined at baseline before implantation and after implantation at 1, 3, and 6 months and last follow-up. RESULTS: Unilateral hypoglossal nerve stimulation decreased the severity of obstructive sleep apnea throughout the entire study period. Specifically, stimulation significantly reduced the mean apnea-hypopnea indices in non-rapid eye movement (mean +/- SD episodes per hour, 52.0 +/- 20.4 for baseline nights and 22.6 +/- 12.1 for stimulation nights; P<.001) and rapid eye movement (48.2 +/- 30.5 and 16.6 +/- 17.1, respectively; P<.001) sleep and reduced the severity of oxyhemoglobin desaturations. With improvement in sleep apnea, a trend toward deeper stages of non-rapid eye movement sleep was observed. Moreover, all patients tolerated long-term stimulation at night and did not experience any adverse effects from stimulation. Even after completing the study protocol, the 3 patients who remained free from stimulator malfunction continued to use this device as primary treatment. CONCLUSION: The findings demonstrate the feasibility and therapeutic potential for hypoglossal nerve stimulation in obstructive sleep apnea.

Adult↗
PubMed2001

A model of sleep-disordered breathing in the C57BL/6J mouse.

To investigate the pathophysiological sequelae of sleep-disordered breathing (SDB), we have developed a mouse model in which hypoxia was induced during periods of sleep and was removed in response to arousal or wakefulness. An on-line sleep-wake detection system, based on the frequency and amplitude of electroencephalograph and electromyograph recordings, served to trigger intermittent hypoxia during periods of sleep. In adult male C57BL/6J mice (n = 5), the sleep-wake detection system accurately assessed wakefulness (97.2 +/- 1.1%), non-rapid eye movement (NREM) sleep (96.0 +/- 0.9%) and rapid eye movement (REM) sleep (85.6 +/- 5.0%). After 5 consecutive days of SDB, 554 +/- 29 (SE) hypoxic events were recorded over a 24-h period at a rate of 63.6 +/- 2.6 events/h of sleep and with a duration of 28.2 +/- 0.7 s. The mean nadir of fraction of inspired O(2) (FI(O(2))) on day 5 was 13.2 +/- 0.1%, and 137.1 +/- 13.2 of the events had a nadir FI(O(2)) <10% O(2). Arterial blood gases confirmed that hypoxia of this magnitude lead to a significant degree of hypoxemia. Furthermore, 5 days of SDB were associated with decreases in both NREM and REM sleep during the light phase compared with the 24-h postintervention period. We conclude that our murine model of SDB mimics the rate and magnitude of sleep-induced hypoxia, sleep fragmentation, and reduction in total sleep time found in patients with moderate to severe SDB in the clinical setting.

Animals↗
PubMed2001

The impact of insulin-dependent diabetes on ventilatory control in the mouse.

Insulin-dependent diabetes mellitus (IDDM) can lead to ventilatory depression and decreased sensitivity to hypercapnia. We examined relationships between ventilation, plasma insulin, leptin, ketones, and blood glucose levels in two mouse models of IDDM: (1) streptozotocin-induced diabetes in C57BL/6J mice on a regular diet or with induced obesity from a high fat diet; and (2) spontaneous diabetes mellitus in NOD-Ltj mice. In both mouse models, IDDM resulted in depression of the hypercapnic ventilatory response (HCVR). This ventilatory depression was not associated with decreases in plasma insulin or leptin levels. There was, however, a strong association between the duration of hyperglycemia, the decline in HCVR, and increased glycosylation of the diaphragm. Hyperventilation was observed in only six of 14 C57BL/6J obese wild-type mice, despite a significant degree of diabetic ketoacidosis (DKA) in all 14 animals. In mice with DKA, there was a significant correlation between the increase in baseline minute ventilation (V E) and hyperleptinemia (r = 0.77, p < 0.01). In leptin-deficient C57BL/6J-Lep(ob) mice, low levels of both V E and ketones were observed. These results suggest that: (1) depression of the HCVR in IDDM is associated with hyperglycemia and glycosylation of the diaphragm; and (2) the hyperventilation of DKA is leptin dependent.

Animals↗
PubMed2001

Long-term monitoring of respiration with a mediastinal pressure sensor in dogs.

The ability of an implanted mediastinal pressure sensor to produce a stable respiratory signal that could be used to trigger stimulation of upper airway muscles was examined. In 6 dogs, a pressure sensor was secured to the manubrium (4 by wires and 2 by transmanubrial placement). In 6 other dogs, the pressure sensor was placed in the upper anterior mediastinum. The animals were monitored for a minimum of 8 weeks (2 transmanubrial sensors for 12 months). Sensors that were able to maintain a midline position, high in the mediastinum, had the best signals. A caudal sensor position or abutment against an intrathoracic structure caused signal inversion (unusable signals). Transmanubrial placement resulted in a stable signal for 1 year. We conclude that long-term monitoring of respiration with a mediastinal pressure sensor can be successfully performed in dogs, providing an adequate signal for nerve-muscle stimulation. Separation from cardiovascular structures improves signal quality.

Animals↗
PubMed2000

Leptin, obesity, and respiratory function.

Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. The importance of this single peptide is vividly demonstrated by the profound obesity exhibited by the ob/ob mouse (C57BL/6J-Lep(ob)) which is unable to produce functional leptin. The measurement of respiratory function in the ob/ob mouse shows that the profound obesity is associated with impaired respiratory mechanics and depressed respiratory control, particularly during sleep. Longitudinal studies and leptin replacement studies in the ob/ob mouse indicate that leptin may act as both as a growth factor in the lung and as a neurohumoral modulator of central respiratory control mechanisms. Moreover, wildtype mice with diet-induced obesity have normal respiratory function associated with markedly elevated leptin levels. Human obesity, similar to obesity in wildtype mice, also causes an elevation in circulating leptin. However, unlike the tight relationship between obesity and elevated leptin present in an inbred strain of wildtype mice, human obesity is associated with more variable leptin levels for a given degree of adiposity. Thus, the possibility exists that a relative deficiency in leptin, or a leptin resistance, may play a role in obesity-related breathing disorders such as obesity hypoventilation syndrome (OHS) or obstructive sleep apnea (OSA).

Animals↗
PubMed2000

Usefulness of continuous oxygen insufflation into trachea for management of upper airway obstruction during anesthesia.

BACKGROUND: Severe complications associated with upper airway obstruction often occur during the perioperative period. Development of a simple and reliable technique for reversing the impaired airway patency may improve airway management. The purpose of the current study is to evaluate the usefulness of transtracheal oxygen insufflation (TTI) for management of upper airway obstruction during anesthesia and to explore the mechanisms of TTI in detail. METHODS: During propofol anesthesia in eight spontaneously breathing patients, the upper airway cross-sectional area and pressure-flow measurements during neck flexion with TTI were compared with those during triple airway maneuvers (TAM) without TTI. Blood gas analyses assessed efficacy of CO2 elimination during TTI in an additional nine patients. RESULTS: TTI achieved adequate PaCO2 and PaO2 levels equivalent to those during TAM. In addition to a significantly smaller cross-sectional area during TTI, the location and slope of the pressure-flow relation during TTI completely differed from those during TAM, indicating that upper airway resistance was much higher during TTI. Notably, minute ventilation during TTI was significantly smaller than that during TAM, suggesting reduced dead space or other mechanisms for CO2 elimination. CONCLUSIONS: TTI is capable of maintaining adequate blood gases through mechanisms different from those of conventional airway support in anesthetized subjects with upper airway obstruction.

Adult↗
PubMed2000

Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea.

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model (n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 +/- 1.7% decrease after apnea with arousal (P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 +/- 1.0 vs. 4.1 +/- 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 +/- 2.3 mmHg vs. 10.3 +/- 1.6 mmHg, REM vs. non-REM, respectively, P < 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation.

Animals↗
PubMed2000

Neural and local effects of hypoxia on cardiovascular responses to obstructive apnea.

Obstructive sleep apnea (OSA) acutely increases systemic (Psa) and pulmonary (Ppa) arterial pressures and decreases ventricular stroke volume (SV). In this study, we used a canine model of OSA (n = 6) to examine the role of hypoxia and the autonomic nervous system (ANS) in mediating these cardiovascular responses. Hyperoxia (40% oxygen) completely blocked any increase in Ppa in response to obstructive apnea but only attenuated the increase in Psa. In contrast, after blockade of the ANS (20 mg/kg iv hexamethonium), obstructive apnea produced a decrease in Psa (-5.9 mmHg; P < 0.05) but no change in Ppa, and the fall in SV was abolished. Both the fall in Psa and the rise in Ppa that persisted after ANS blockade were abolished when apneas were induced during hyperoxia. We conclude that 1) hypoxia can account for all of the Ppa and the majority of the Psa response to obstructive apnea, 2) the ANS increases Psa but not Ppa in obstructive apnea, 3) the local effects of hypoxia associated with obstructive apnea cause vasodilation in the systemic vasculature and vasoconstriction in the pulmonary vasculature, and 4) a rise in Psa acts as an afterload to the heart and decreases SV over the course of the apnea.

Animals↗
PubMed2000

High-flow transtracheal insufflation treats obstructive sleep apnea. A pilot study.

To determine the effect of transtracheal insufflation (TTI) on obstructive sleep apnea (OSA), we examined breathing patterns in five tracheostomized patients with OSA at varying TTI flow rates when breathing with a closed tracheostomy. The breathing patterns and polysomnographic responses to air insufflation were studied as TTI was increased from 0 to 15 L/min for brief periods of non-rapid eye movement (NREM) sleep (Experiment 1). The frequency of sleep-disordered breathing episodes remained high at 0 and 5 L/min (87.0 +/- 33.7 and 79.4 +/- 24.4 episodes per hour NREM) and decreased significantly to 41.3 +/- 31.5 and 43.4 +/- 31.4 episodes/h NREM sleep at rates of 10 and 15 L/min, respectively (p = 0.003). At high levels of TTI (10 and 15 L/min), obstructive apneas and hypopneas decreased but periodic laryngeal obstructions were induced during stage 1 NREM sleep. To prevent laryngeal obstructions, a servo-control system was used to briefly interrupt TTI during these events. When this system was implemented for more prolonged periods of sleep (Experiment 2, total sleep time 176.6 +/- 12.5 min), high-flow TTI (hf-TTI, 15 L/min) led to an overall reduction in the combined frequency of obstructive apneas and laryngeal obstructions from 63.8 +/- 21.8 to 10.7 +/- 9.1 (p < 0.03) and was associated with a marked reduction in arousal frequency from 60.0 +/- 26.0 to 8. 3 +/- 5.4/h in NREM sleep, and from 67.5 +/- 3.5 to 0 +/- 0/h in rapid eye movement (REM) sleep. Our findings demonstrate that hf-TTI stabilized breathing patterns in apneic patients, and was safe and efficacious for prolonged periods of sleep.

Adult↗
PubMed2000

A model of obstructive sleep apnea in normal humans. Role of the upper airway.

We determined whether upper airway obstruction in normal individuals with intact reflexes could produce the syndrome of obstructive sleep apnea. Upper airway obstruction was produced in 12 normal individuals by lowering nasal pressure to -10 cm H(2)O during sleep. Full night polysomnography was performed during two consecutive nights of sleep with subatmospheric nasal pressure and compared with control nights before and after the negative pressure nights. We found that the application of negative pressure was associated with the development of recurrent obstructive apneas (non-REM-disordered breathing rate, 32.6 +/- 34.8 and 37.8 +/- 29.1 events/h during each of two negative pressure nights; p < 0.001) that were associated with oxyhemoglobin desaturation, arousals from sleep, and alterations in sleep stage distribution. Moreover, the median daytime sleep latency after two nights of sleep with subatmospheric pressure fell from 6.9 +/- 1.1 to 3.4 +/- 0.6 min, and rose significantly again to 8.1 +/- 1.5 min (p < 0.03) after the control night following subatmospheric pressure nights. Our findings suggest that a decrease in the pharyngeal transmural pressure alone is a sufficient condition for the production of the sleep apnea syndrome in normal individuals.

Adult↗