Electrical stimulation of the whole hypoglossal nerve in patients with obstructive sleep apnea.

PURPOSE: Electrical stimulation of the whole hypoglossal nerve (HGp-ES) has been demonstrated to enlarge the pharynx and improve pharyngeal stability and patency to airflow in all animals studied, but not in humans. The present study was undertaken to better understand the effect of HGp-ES on the human pharynx. METHODS: Eight patients with obstructive sleep apnea who had implanted stimulators with electrodes positioned proximally on the main truck of the hypoglossus were studied under propofol sedation. Pharyngoscopy and air flow measurements at multiple levels of continuous positive airway pressure (CPAP) were performed before and during Hgp-ES. RESULTS: HGp-ES that activates both tongue protrusors and retractors narrowed the pharyngeal lumen at the site of collapse (velopharynx in all subjects) from 1.38 ± 0.79 to 0.75 ± 0.44 cm2, p < 0.05 (measured at mid-range of CPAP levels) and lowered airflow (from 8.88 ± 2.08 to 6.69 ± 3.51 l/min, p < 0.05). Changes in critical pressure (Pcrit) and velopharyngeal compliance were not significant, but oropharyngeal compliance decreased (from 0.43 ± 0.18 to 0.32 ± 0.13 cm2/cmH2O, p < 0.05). No correlation was found between the pattern of change in luminal shape (determined as the ratio of a-p vs. lateral diameter when lowering CPAP) or changes in cross-sectional area and airflow during Hgp-ES. CONCLUSIONS: Our findings indicate that human retractors dominate when stimulated together with the protrusors during HGp-ES. While co-activation of retractors may be beneficial, it should be limited. We speculate that exercises that augment protrusor force may improve the response to hypoglossal stimulation. The exclusion of patients with concentric pharyngeal obstruction should be re-evaluated.

Inspiratory duty cycle responses to flow limitation predict nocturnal hypoventilation.

Upper airway obstruction (UAO) can elicit neuromuscular responses that mitigate and/or compensate for the obstruction. It was hypothesised that flow-limited breathing elicits specific timing responses that can preserve ventilation due to increases in inspiratory duty cycle rather than respiratory rate. By altering nasal pressure during non-rapid eye movement (non-REM) sleep, similar degrees of UAO were induced in healthy males and females (n = 10 each). Inspiratory duty cycle, respiratory rate and minute ventilation were determined for each degree of UAO during non-REM sleep and compared with the baseline nonflow-limited condition. A dose-dependent increase in the inspiratory duty cycle and respiratory rate was observed in response to increasing severity of UAO. Increases in the inspiratory duty cycle, but not respiratory rate, helped to acutely maintain ventilation. Heterogeneity in these responses was associated with variable degrees of ventilatory compensation, allowing for the segregation of individuals at risk for hypoventilation during periods of inspiratory airflow limitation. Upper airway obstruction constitutes a unique load on the respiratory system. The inspiratory duty cycle, but not the respiratory rate, determine the individual's ability to compensate for inspiratory airflow limitation during sleep, and may represent a quantitative phenotype for obstructive sleep apnoea susceptibility.

Differential effects of respiratory and electrical stimulation-induced dilator muscle contraction on mechanical properties of the pharynx in the pig.

Respiratory stimulation (RS) during sleep often fails to discontinue flow limitation, whereas electrical stimulation (ES) of the hypoglossus (HG) nerve frequently prevents obstruction. The present work compares the effects of RS and HG-ES on pharyngeal mechanics and the relative contribution of tongue muscles and thoracic forces to pharyngeal patency. We determined the pressure-area relationship of the collapsible segment of the pharynx in anesthetized pigs under the following three conditions: baseline (BL), RS induced by partial obstruction of the tracheostomy tube, and HG-ES. Parameters were obtained also after transection of the neck muscles and the trachea (NMT) and after additional bilateral HG transection (HGT). In addition, we measured the force produced by in situ isolated geniohyoid (GH) during RS and HG-ES. Intense RS was recognized by large negative intrathoracic pressures and triggered high phasic genioglossus and GH EMG activity. GH contraction produced during maximal RS less than a quarter of the force obtained during HG-ES. The major finding of the study was that RS and ES differed in the mechanism by which they stabilized the pharynx: RS lowered the pressure-area slope, i.e., reduced pharyngeal compliance (14.1 ± 2.9 to 9.2 ± 1.9 mm(2)/cmH2O, P < 0.01). HG-ES shifted the slope toward lower pressures, i.e., lowered the calculated extraluminal pressure (17.4 ± 5.8 to 9.2 ± 7.4 cmH2O, P < 0.01). Changes during RS and HG-ES were not affected by NMT, but the effect of RS decreased significantly after HGT. In conclusion, HG-ES and RS affect the pharyngeal site of collapse differently. Tongue muscle contraction contributes to pharyngeal stiffening during RS.

The effect of leptin replacement on sleep-disordered breathing in the leptin-deficient ob/ob mouse.

Obese leptin-deficient (ob/ob) mice demonstrate defects in upper airway structural and neuromuscular control. We hypothesized that these defects predispose to upper airway obstruction during sleep, and improve with leptin administration. High-fidelity polysomnographic recordings were conducted to characterize sleep and breathing patterns in conscious, unrestrained ob/ob mice (23 wk, 67.2 ± 4.1 g, n = 13). In a parallel-arm crossover study, we compared responses to subcutaneous leptin (1 µg/h) vs. vehicle on respiratory parameters during NREM and REM sleep. Upper airway obstruction was defined by the presence of inspiratory airflow limitation (IFL), as characterized by an early inspiratory plateau in airflow at a maximum level (V̇Imax) with increasing effort. The severity of upper airway obstruction (V̇Imax) was assessed along with minute ventilation (V̇E), tidal volume (VT), respiratory rate (RR), inspiratory duty cycle, and mean inspiratory flow at each time point. IFL occurred more frequently in REM sleep (37.6 ± 0.2% vs. 1.1 ± 0.0% in NREM sleep, P < 0.001), and leptin did not alter its frequency. V̇Imax (3.7 ± 1.1 vs. 2.7 ± 0.8 ml/s, P < 0.001) and V̇E increased (55.4 ± 22.0 vs. 39.8 ± 16.4 ml/min, P < 0.001) with leptin vs. vehicle administration. The increase in V̇E was due to a significant increase in VT (0.20 ± 0.06 vs. 0.16 ± 0.05 ml, P < 0.01) rather than RR. Increases in V̇E were attributable to increases in mean inspiratory flow (2.5 ± 0.8 vs. 1.8 ± 0.6 ml/s, P < 0.001) rather than inspiratory duty cycle. Similar increases in V̇E and its components were observed in non-flow-limited breaths during NREM and REM sleep. These responses suggest that leptin stabilized pharyngeal patency and increased drive to both the upper airway and diaphragm during sleep.

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.

Structural basis for alterations in upper airway collapsibility.

To determine the structural basis for alterations in upper airway (UA) collapsibility, the pharyngeal critical pressure (Pcrit) was measured in an isolated feline upper airway preparation. The effect of airway elongation and dilation was explored by displacing the trachea caudally and the tongue anteriorly, respectively. With caudal-tracheal displacement, Pcrit fell progressively, a result that can be attributed to increased tension within the pharyngeal mucosa. In contrast, anterior-tongue displacement decreased Pcrit when the trachea had been caudally displaced but not with the trachea in the neutral position. These findings suggest that longitudinal tension within the airway mucosa modulates both Pcrit and the response in Pcrit to dilating forces. A mechanical model to account for these findings is discussed.

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.

Electrical stimulation of upper airway musculature.

Investigators have postulated that pharyngeal collapse during sleep in patients with obstructive sleep apnea (OSA) may be alleviated by stimulating the genioglossus. The effect of electrical stimulation (ES) of the genioglossus on pharyngeal patency was examined in an isolated feline upper airway preparation and in apneic humans during sleep. We found that stimulation of the genioglossus (n = 8) and of the hypoglossal nerve (n = 1) increased maximum airflow through the isolated feline upper airway in humans during sleep. Additional findings in the isolated feline upper airway suggest that such increases in airflow were due to decreases in pharyngeal collapsibility. The evidence suggests that improvements in airflow dynamics with electrical stimulation are due to selective recruitment of the genioglossus, rather than due to nonspecific activation of the pharyngeal musculature or arousal from sleep. The implications of these results for future therapy with ES are discussed.

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.

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.

Pulmonary function and respiratory chemosensitivity in moderately obese patients with sleep apnea.

To determine whether moderately obese, normocapnic, sleep apnea patients are distinguished from normal obese individuals by differences in waking pulmonary function and respiratory chemosensitivity, we compared the waking pulmonary function, hypercapnic, and hypoxic ventilatory responses of 35 nonhypercapnic sleep apnea patients (32 men and 3 women) with those of 17 age-, sex-, weight-, and obesity-matched nonapneic control subjects (16 men and 1 woman). The waking ventilatory response to hypercapnia was lower among sleep apnea patients (mean +/- SD, 2.05 +/- 1.29 L/min/mm Hg) than control subjects (3.02 +/- 2.05 L/min/mm Hg, p < 0.05). Patients with sleep apnea demonstrated a higher waking PaCO2 (40.4 +/- 2.9 vs 37.0 +/- 2.7 mm Hg, p < 0.001), and a lower waking PaO2 (81.4 +/- 11.7 vs 89.7 +/- 10.4 mm Hg, p < 0.03). The waking hypoxic ventilatory response, however, was not significantly different between the groups. Moreover, control subjects had a higher total lung capacity than sleep apnea patients (6.99 +/- 1.12 L and 6.27 +/- 1.09 L, respectively, p < 0.05). The lower hypercapnic ventilatory response, higher waking PaCO2, and lower total lung capacity in the sleep apnea patients resemble the pattern observed in patients with pickwickian syndrome. This suggests that disturbances in pulmonary function and ventilatory control in moderately obese sleep apnea patients are intermediate along a continuum from normal obesity to the pickwickian syndrome.

Abbreviated method for assessing upper airway function in obstructive sleep apnea.

STUDY OBJECTIVES: Previous studies have shown that the level of flow through the upper airway in patients with obstructive sleep apnea (OSA) is determined by the critical closing pressure (Pcrit) and the upstream resistance (RN). We developed a standardized protocol for delineating quasisteady-state pressure-flow relationships for the upper airway from which these variables could be derived. In addition, we investigated the effect of body position and sleep stage on these variables by determining Pcrit and RN, and their confidence intervals (CIs), for each condition. DESIGN: Pressure-flow relationships were constructed in the supine and lateral recumbent positions (nonrapid eye movement [NREM] sleep, n = 10) and in the supine position (rapid eye movement [REM] sleep, n = 5). SETTING: University Hospital Antwerp, Belgium. PATIENTS: Ten obese patients (body mass index, 32.0+/-5.6 kg/m(2)) with severe OSA (respiratory disturbance index, 63.0+/-14.6 events/h) were studied. INTERVENTIONS: Pressure-flow relationships were constructed from breaths obtained during a series of step decreases in nasal pressure (34.1+/-6.5 runs over 3.6+/-1.2 h) in NREM sleep and during 7.8+/-2.2 runs over 0.8+/-0.6 h in REM sleep. RESULTS: Maximal inspiratory airflow reached a steady state in the third through fifth breaths following a decrease in nasal pressure. Analysis of pressure-flow relationships derived from these breaths showed that Pcrit fell from 1.8 (95% CI, -0.1 to 2.7) cm H(2)O in the supine position to -1.1 cm H(2)O (95% CI, -1.8 to 0.4 cm H(2)O; p = 0.009) in the lateral recumbent position, whereas RN did not change significantly. In contrast, no significant effect of sleep stage was found on either Pcrit or RN. CONCLUSIONS: Our methods for delineating upper airway pressure-flow relationships during sleep allow for multiple determinations of Pcrit within a single night from which small yet significant differences can be discerned between study conditions.

A modified leukocyte nitroblue tetrazolium test in acute bacterial infection.

The increased ability to leukocytes to reduce nitroblue tetrazolium (NBT) has been used to detect the presence of systemic bacterial infection. This test has been utilized to evaluate infections and leukocyte dysfunction in children, but has not been extensively applied to traumatized patients or infected volunteers. Moreover, the technic as originally described presented methodologic difficulties. In this study of 889 such patients, a modified NBT test provided excellent differentiation of 63 systemic bacterial infections (NBT score greater than or equal to 10%) from non-infectious fevers, local enteric diseases, and certain viral and plasmodial infections (NBT score less than or equal to 9%). Splenectomy was associated with a transient false-positive score and clinical typhoid fever with a false-negative response

Recognition of diabetes insipidus in postpartum hypopituitarism.

The association of diabetes insipidus with postpartum hypopituitarism is unusual. This report presents a patient with both conditions. Evidence pointing to the pathogenesis of the diabetes insipidus is discussed. This case and selected others illustrate the wide spectrum in the severity of diabetes insipidus encountered in postpartum hypopituitarism, as well as the masking of symptoms caused by concomitant glucocorticoid insufficiency. Histopathologic and experimental evidence suggests that patients with hypopituitarism occurring postpartum might also display mild diabetes insipidus if challenged with antidiuretic stimuli. Diabetes insipidus may be a feature of postpartum hypopituitarism that is infrequently recognized.

Effect of alae nasi activation on maximal nasal inspiratory airflow in humans.

The upper airway is a complicated structure that is usually widely patent during inspiration. However, on inspiration during certain physiological and pathophysiological states, the nares, pharynx, and larynx may collapse. Collapse at these locations occurs when the transmural pressure (Ptm) at a flow-limiting site (FLS) falls below a critical level (Ptm'). On airway collapse, inspiratory airflow is limited to a maximal level (VImax) determined by (-Ptm')/Rus, where Rus is the resistance upstream to the FLS. The airflow dynamics of the upper airway are affected by the activity of its associated muscles. In this study, we examine the modulation of VImax by muscle activity in the nasal airway under conditions of inspiratory airflow limitation. Each of six subjects performed sniffs through one patent nostril (pretreated with an alpha agonist) while flaring the nostril at varying levels of dilator muscle (alae nasi) EMG activity (EMGan). For each sniff, we located the nasal FLS with an airway catheter and determined VImax, Ptm', and Rus. Activation of the alae nasi from the lowest to the highest values of EMGan increased VImax from 422 +/- 156 to 753 +/- 291 ml/s (P < 0.01) and decreased Ptm' from -3.6 +/- 3.0 to -6.0 +/- 4.7 cmH2O (P < 0.05). Activation of the alae nasi had no consistent effect on Rus. VImax was positively correlated with EMGan, and Ptm' was negatively correlated with EMGan in all subjects. Our findings demonstrate that alae nasi activation increases VImax through the nasal airway by decreasing airway collapsibility.

The study of maximal nasal inspiratory flow in humans.

During inspiration through one nostril, airflow becomes limited to a maximal level (VImax) when the transmural pressure (Ptm) at a flow-limiting site (FLS) falls below a critical level (Ptm'). We compared two methods for measuring the Ptm' of the nasal FLS. Each of six subjects (four normal and two with allergic rhinitis out of season) performed multiple inspirations through one nostril as we varied the resistance at the nasal opening. Studies were performed after application of a topical decongestant without activation of the alae nasi. We determined Ptm' by regressing the resulting values of VImax on the corresponding transnasal pressure gradients (Regression Method). We also measured Ptm' directly using pressure catheters to measure the pressure surrounding the FLS and the lateral pressure near the FLS at VImax (Catheter Method). The mean value of Ptm' by the Regression Method was -3.8 +/- 3.2 (SD) cmH2O. The value by the Catheter Method with the catheter just downstream from the nasal FLS was -3.5 +/- 2.9 cmH2O, which correlated closely with the Ptm by the Regression Method (r = 0.98). Our findings suggest that the Ptm' of the nasal airway can be determined by either method. The Catheter Method, however, requires only one inspiratory effort for each determination and simultaneously localizes the nasal FLS.

Tracheal and neck position influence upper airway airflow dynamics by altering airway length.

Upper airway obstruction during sleep is characterized by inspiratory airflow limitation and reductions in maximal inspiratory airflow (VImax). To determine how mechanical factors modulate VImax, we analyzed pressure-flow relationships obtained in the isolated upper airway of paralyzed cats. VImax and its determinants, the pharyngeal critical pressure (Pcrit) and the nasal resistance (Rn) upstream to the flow-limiting site (FLS), were measured as caudal tracheal displacement, neck position, and airway length were systematically varied. As the proximal tracheal stump was displaced caudally, graded increases in VImax from 145.3 +/- 90.8 (SD) to 285.9 +/- 117.5 ml/s (P < 0.02) and decreases in Pcrit from -3.0 +/- 3.0 to -9.5 +/- 3.4 cmH2O (P < 0.002) were seen without any significant change in Rn. During neck flexion, significant decreases in VImax from 192.1 +/- 68.5 to 87.2 +/- 48.4 ml/s (P = 0.001), increases in Pcrit from -5.3 +/- 2.03 cmH2O to -1.6 +/- 1.4 cmH2O (P < 0.001), and decreases in Rn from 29.7 +/- 12.2 cmH2O.l-1.s to 16.2 +/- 8.9 cmH2O.l-1.s (P < 0.001) were noted compared with the neutral or extended neck position. Relative to the neutral airway length, upper airway length was found to decrease by 1.15 +/- 0.14 cm during neck flexion and to lengthen by 0.45 +/- 0.12 cm during neck extension. When tracheal displacement and neck position were altered, VImax and Rn correlated directly and Pcrit correlated inversely with airway length (P < 0.001). We conclude that alterations in airflow mechanics with caudal tracheal displacement and changes in neck positions are primarily due to alterations in airway length.

Effect of sleep deprivation on responses to airway obstruction in the sleeping dog.

The effect of sleep deprivation on sleep architecture and respiratory responses to repetitive airway obstruction during sleep was investigated in four chronically instrumented tracheostomized dogs during 12-h nocturnal experiments. A 24-h period of prior sleep deprivation increased (P < 0.05) the rate at which airway obstruction could be induced from 20 +/- 3 (SE) to 37 +/- 10 times/h compared with non-sleep-deprived dogs. During non-rapid-eye-movement sleep the duration of obstruction, minimum arterial hemoglobin saturation, and peak negative inspiratory effort at arousal were 20.5 +/- 1.0 s, 91.7 +/- 0.5%, and 28.4 +/- 1.8 mmHg, respectively, in non-sleep-deprived dogs. Sleep deprivation increased (P < 0.01) the duration of obstruction to 28.0 +/- 0.9 s, worsened (P < 0.05) the minimal arterial hemoglobin desaturation to 85.4 + 3.1%, and increased (P < 0.025) the peak negative inspiratory effort at arousal to 36.1 +/- 1.6 mmHg. Sleep deprivation also caused increases (P < 0.025) in total sleep time, rapid-eye-movement (REM) sleep time, and percentage of time in REM sleep in a 2-h recovery period without airway obstruction at the end of the study. We conclude that airway obstruction in the sleeping dog can reproduce the disturbances in sleep architecture and respiration that occur in obstructive sleep apnea and that prior sleep deprivation will increase apnea severity, degree of somnolence, and REM sleep rebound independent of change in upper airway collapsibility.

Relationship between blood pressure and airway obstruction during sleep in the dog.

The relationship between airway obstruction during sleep and changes in mean arterial pressure (MAP) was investigated in four chronically instrumented tracheostomized dogs during 12-h nocturnal experiments. The MAP response was determined 1) during experimental airway obstruction whenever sleep occurred, 2) over each 12-h experiment, and 3) during a 2-h recovery period at the end of each experiment. The effects of 24 h of sleep deprivation and changes in plasma levels of renin and atrial natriuretic peptide were assessed. In non-rapid-eye-movement sleep, a period of airway obstruction caused MAP to increase (P < 0.002) from 95 +/- 3 (SE) mmHg to 112 +/- 3 mmHg, and this difference was enhanced (P < 0.04) by sleep deprivation. There was an increase of 12 +/- 2 mmHg in the overall MAP over time (P < 0.001) in non-rapid-eye-movement sleep that was sustained in the 2-h recovery period. Plasma levels of renin and atrial natriuretic peptide were constant and unrelated to changes in MAP. We conclude that in the sleeping dog airway obstruction causes an increase in MAP that can be accentuated by prior sleep deprivation and that repetitive airway obstruction will cause an increase in MAP over time that is sustained for > or = 2 h when normal airway patency is restored.

Mechano- and chemoreceptor modulation of respiratory muscles in response to upper airway negative pressure.

To investigate the influence of phasic pulmonary stretch receptors (n = 6) and chemoreceptors (n = 7) on the reflex response of the genioglossus (GG) muscle and diaphragm (DIA) to upper airway (UAW) negative pressure, we measured the response of the GG and DIA electromyogram (EMG) to three challenges: 1) negative pressure applied to the UAW during normoxia and hypercapnia, 2) end-expiratory tracheal occlusion, and 3) application of UAW negative pressure simultaneous with tracheal occlusion in spontaneously breathing tracheotomized anesthetized cats. Peak GG EMG was greatest when UAW negative pressure and end-expiratory tracheal occlusion were combined. No GG EMG activity was seen when UAW negative pressure was applied alone unless the animal was vagotomized or hypercapnic. DIA EMG increased in response to UAW negative pressure combined with occlusion. However, the increase in peak GG EMG was significantly greater than for the DIA with the same challenge. DIA EMG amplitude increased in response to occlusion alone but did not change when UAW negative pressure was applied alone. In the cat, phasic feedback from phasic pulmonary stretch receptors is a potent inhibitor of reflex activation of the GG in response to negative pressure applied to the UAW, which can be overridden by an increase in chemoreceptor drive.