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Effect of coactivation of tongue protrusor and retractor muscles on pharyngeal lumen and airflow in sleep apnea patients

¹Bnai Zion Medical Center, Technion, Haifa, Israel; and ²The Johns Hopkins Sleep Disorders Center, Baltimore, Maryland

Submitted 10 June 2007 ; accepted in final form 27 July 2007

	ABSTRACT

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The present study evaluated the effect of coactivation of tongue protrusors and retractors on pharyngeal patency in patients with obstructive sleep apnea. The effect of genioglossus (GG), hyoglossus (HG), and coactivation of both on nasal pressure (Pn):flow relationships was evaluated in a sleep study (SlS, n = 7) and during a propofol anesthesia study (AnS, n = 7). GG was stimulated with sublingual surface electrodes in SlS and with intramuscular electrodes in AnS, while HG was stimulated with surface electrodes in both groups. In the AnS, the cross-sectional area (CSA):Pn relationships was measured with a pharyngoscope to estimate velopharyngeal compliance . In the SlS, surface stimulation of GG had no effect on the critical pressure (Pcrit), HG increased Pcrit from 2.8 ± 1.7 to 3.7 ± 1.6 cmH₂O, but coactivation lowered Pcrit to 0.2 ± 1.9 cmH₂O (P < 0.01 for both). In the AnS, intramuscular stimulation of GG lowered Pcrit from 2.6 ± 1.3 to 1.0 ± 2.8 cmH₂O, HG increased Pcrit to 6.2 ± 2.5 cmH₂O (P < 0.01), and coactivation had a similar effect to that of GG (Pcrit = 1.2 ± 2.4 cmH₂O, P < 0.05). None of the interventions affected significantly velopharyngeal compliance. We conclude that the beneficial effect of coactivation depends on the pattern of GG fiber recruitment: although surface stimulation of GG failed to protrude the tongue, it prevented the occlusive effect of the retractor, thereby improving pharyngeal patency during coactivation. Stimulation of deeper GG fibers with intramuscular electrodes enlarged the pharynx, and coactivation had no additive effect.

tongue muscles; sleep apnea; pharynx; genioglossus; hyoglossus

While evaluating the electromyographic and mechanical activity of the muscles that retract the tongue, Fregosi, Fuller and coworkers (9, 10) reported that these retractors were always activated in parallel with the GG. This coactivation of tongue retractors and protrusors was thought to improve the mechanical stability and, therefore, the functional efficacy of these muscles. In a later study the same researchers reported that electrical coactivation of these muscles in the rat improved pharyngeal stability compared with isolated protrusor stimulation (11).

The mechanical effects of GG stimulation in laboratory animals seem to exceed substantially the results obtained in OSA patients, suggesting that the upper airway of the latter and/or its dilator muscles act differently from those of healthy mammals. Nevertheless, we hypothesized that coactivation of tongue protrusors and retractors can improve upper airway patency also in OSA patients. To evaluate the effect of coactivation on pharyngeal mechanics, two studies were performed and are presented herewith. In the first, patients were studied during sleep, and a surface electrode was used to stimulate both the GG and/or tongue retractors. In the second study, propofol anesthesia was used to enable the use of pharyngoscopy, the same surface electrode was used to stimulate the retractors, but GG stimulation was performed with intramuscular electrodes. Accordingly, the response to coactivation was assessed with two different modes of GG fiber recruitment, coupled with the same mode of retractor stimulation.

	METHODS

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Subjects.   Patients with OSA (more than 5 episodes of obstructive or mixed apneas or hypopneas per hour of sleep), previously documented on a conventional overnight polysomnographic sleep study, were recruited for these studies. The studies were approved by the Human Investigations Review Boards of the respective institutions, and written informed consent was obtained from each patient.

Two studies were performed in two groups of patients, all men. 1) The first study (sleep study, SlS) was performed in seven OSA patients during sleep in the Johns Hopkins Sleep Disorder Center Laboratory, Baltimore, MD. 2) The second study (anesthesia study, AnS) was performed in the Respiratory Research Laboratory of Bnai-Zion Medical Center, Haifa, Israel, on seven patients anesthetized with propofol. Patients with any disease that could pose a risk for anesthesia, including ischemic heart disease, any lung disease, severe or uncontrolled hypertension, and body mass index (BMI) > 35 kg/m², as well as subjects with known side effects to any previous anesthesia, were excluded from the AnS. In both studies, patients were studied in the supine position. In the SlS study, the patients were video-observed and returned to the supine position whenever they changed position.

Recording procedures.   The same instrumentation was used in the two studies, but in the AnS, pharyngoscopy and intramuscular GG electrodes were added (Fig. 1). Standard polysomnographic techniques, including submental surface EMG, C3-O1 and C3-A2 EEG, right and left electrooculogram (EOG), ECG, and oxygen saturation, were employed to monitor sleep or anesthesia and exclude arousal. Subjects breathed through a tight-fitting nasal mask and a pneumotachometer, connected to a Validyne ±2 cmH₂O pressure transducer, with the mouth carefully and tightly sealed. The pneumotachometer was connected to a digitized variable pressure-source at the inflow port, enabling variation of nasal pressure (Pn) between 20 and –10 cmH₂O. Pn was monitored with a catheter connected to a side port of the mask. Intrathoracic pressure was measured with an esophageal balloon catheter (Ackrad Laboratories, Cranford NJ), used to recognize upper airway airflow limitation, as well as to distinguish between inspiration and expiration during complete apneas. In the SlS, all parameters were both recorded continuously on a polygraph recorder (no. 780; Grass Instruments, Quincy, MA) and digitized for monitoring and data storage. In the AnS, analog-to-digital acquisition of all parameters was performed on a digital polygraphic data acquisition system (LabVIEW, National Instruments, Austin TX).

View larger version (49K): [in this window] [in a new window]   Fig. 1. Schematic illustration of the instrumentation used in the study performed under anesthesia. The same instrumentation was used in the sleep study, without the endoscope and the intramuscular electrodes. Note that the anterior part of the sublingual surface electrode is positioned above the vertically oriented genioglossus fibers, while the intramuscular electrodes are positioned in the longitudinally oriented fibers. The posterior portion of the sublingual surface electrodes is positioned over the hyoglossus muscle. CPAP, continuous positive airway pressure.

Pharyngoscopy.   In the AnS, a flexible fiber-optic endoscope (Olympus BF-3C40, 3.3 mm OD) was inserted through an adequately sealed port in the nose mask. The pharynx was photographed and video-recorded continuously on videotape throughout the evaluation of the pressure:flow relationships. The endoscope was positioned above the velopharyngeal site of collapse, as this was the primary site of collapse in all AnS patients.

Anesthesia.   Propofol anesthesia was delivered in the AnS by an anesthesiologist, with a loading dose of 2.5 mg/kg, and continuous drip of 6–12 mg·kg^–1·h^–1. Using Pn levels that prevented flow limitation, we aimed to maintain the patient under stable anesthesia, that eliminated any reaction to pain, ES, and other manipulations, while maintaining adequate spontaneous ventilation, as monitored by the pneumotachometer and pulse oxymetry.

Site of collapse.   To determine the site of pharyngeal collapse (velo- or oropharynx) in the SlS, we measured the pharyngeal pressure at Pn < Pcrit with an occluded tube whose sidehole was positioned before sleep at the lower rim of the soft palate. In the AnS, the site of collapse was determined visually, lowering Pn until occlusion was observed with the endoscope positioned first above and than below the velopharynx.

Experimental procedure.   Patients were prepared with EEG, EOG, submental EMG, and esophageal balloon and placed in the supine position, and the primary site of collapse was determined. The upper airway pressure:flow relationships was delineated as previously described (30). Pn was maintained at high levels that prevented flow limitation (holding pressure) and, during stable phase 2 sleep or anesthesia, was lowered intermittently to encompass pressure levels associated with flow limitation and the level below which airflow ceased as the upper airway occluded completely (Pcrit). ES was applied just before inspiratory onset of the 3rd or 4th breath after lowering Pn, for one inspiration. Pn was lowered to each level repeatedly to evaluate separately the effect of ES of the GG, the HG, and combined stimulation of both muscles.

Data analysis.   In both studies, maximal inspiratory flow was measured at the level when inspiratory flow reached a maximal level and plateaued while esophageal pressure fell progressively, indicating the presence of flow limitation. The Pn:flow relationships was determined with least-squares linear regression. This relationship was used to calculate Pcrit as the level of Pn below which airflow became zero, as well as the Pn:flow slope, as previously described (20). Pcrit (Pcrit during ES minus baseline Pcrit) was used to quantify the mechanical effect of ES.

In the AnS, video movies of the pharyngeal lumen, taken during the evaluation of the flow:Pn relationships, before and during ES, were digitized and viewed, and single pictures from the end-expiratory pause (i.e., no flow condition, Pn = intraluminal pressure) were captured and stored. The pharyngeal cross-sectional area (CSA) in each digitized frame was outlined manually and calculated digitally using computer software. The esophageal pressure tube, marked at regular levels, was used as a landmark, in addition to pharyngeal structures, to help measure the CSA perpendicular to the pharyngeal axis and at the same distance from the endoscope, and as a reference for calculating the CSA in absolute units. The CSA:Pn relationship was determined for the quasi-linear portion of this relationships only, with least-squares linear regression, as the Pn range over which flow limitation occurs is always within this range (see DISCUSSION).

Data are presented as means ± SD. Paired t-test was used for comparison of baseline and stimulation results. P values below 0.05 were considered significant.

	RESULTS

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The anthropometric and polysomnographic characteristics of the two patient groups are given in Table 1. All patients were men, and eight of them had a BMI > 30. Four patients were hypertensive, and none had any other significant disease. The subjects had a wide range of apnea-hypopnea index (AHI), but both groups were similar with respect to their mean AHI, BMI, and age. The primary site of collapse was the velopharynx in five of the SlS and all the AnS patients.

View larger version (10K): [in this window] [in a new window]   Fig. 2. Nasal pressure (Pn):flow relationships in a patient studied during sleep (A) and a patient studied under anesthesia, with genioglossus (GG) intramuscular electrodes (B). The response to retractor stimulation and coactivation is similar in both patients. Surface stimulation of the anterior part of the GG in the sleep study (A) had no effect on the Pn:flow relationships [slope during GG stimulation, represented by the dashed line, same as during baseline (BL)], while stimulation with the intramuscular electrodes (B) produced a similar effect (slope during GG stimulation represented again by the dashed line) to that of coactivation. GG, genioglossus stimulation with the surface sublingual electrode in A and with the fine-wire intramuscular electrode in B. HG, retractor (hyoglossus) stimulation with the surface sublingual electrode. GG + HG, coactivation of the 2 extrinsic muscles.

View larger version (15K): [in this window] [in a new window]   Fig. 3. Changes in the critical pressure (Pcrit, Pcrit during stimulation – baseline Pcrit) observed during electrical stimulation of the tongue muscles. GG stimulation was performed with the sublingual surface electrode in the sleep study and with the fine-wire intramuscular electrode in the anesthesia study. *P < 0.05 for the comparison between surface and intramuscular stimulation of the GG.

View larger version (12K): [in this window] [in a new window]   Fig. 4. Cross-sectional area (CSA):Pn relationships at the level of the velopharyngeal occlusion area in one of the anesthesia study subjects. Both GG stimulation and coactivation enlarge the velopharynx and decrease Pcrit. HG stimulation obstructs the velopharynx and increases Pcrit.

	DISCUSSION

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The lack of flow response to surface stimulation of the GG occurred despite clearly visible and palpable contraction of the muscle adjacent to the anterior part of the sublingual surface electrode, associated with depression of the anterior part of the tongue. In the first three AnS patients, we tried to stimulate the GG with the anterior segment of the surface electrode, using higher stimulation intensities than those possible during sleep but could not produce any movement at the posterior side of the tongue. As seen in Fig. 1, due to the fanlike orientation of the GG fibers, surface stimulation of the GG activates primarily the superior, vertically oriented fibers that are not expected to produce anterior displacement of the tongue. Only the inferior and middle fibers, reached by the intramuscular electrodes, pass backward, blend with the posterior body of the tongue, attach to the hyoid bone, and can pull the posterior part of the tongue forward. The different responses to the two modes of GG stimulation in our studies emphasize that mechanically the GG has at least two different actions, namely depression and flattening of the tongue, and tongue protrusion, and only the latter one is likely to have an independent respiratory role.

It was, therefore, rather surprising to find that combining surface GG stimulation with retractor stimulation enlarged the pharynx, although when applied alone, the first had no effect and the latter occluded the airways. A possible explanation to this finding, which also provides a common denominator to our findings in the two studies, is modeled in Fig. 5, on the basis of the specific position and attachments of the HG and the two functional components of the GG. The vertical fibers of the GG depress the tongue, without affecting pharyngeal CSA (Fig. 5A). The longitudinal fibers of the GG protrude the posterior part of the tongue and enlarge the pharyngeal CSA (Fig. 5C). Although the HG is an extrinsic tongue muscle (with an external bony origin and insertion into the tongue base), its external insertion is to the hyoid bone, an unstable bony structure suspended between the pharyngeal and neck muscles, whose position and stability depend largely on the activity of the surrounding muscles. For the HG to act as a tongue retractor, the hyoid bone needs to be stable (Fig. 5B). However, if the other muscles inserting into the hyoid bone are relaxed, and contraction of the vertically oriented GG fibers prevents retraction of the tongue, the HG is expected to move the hyoid bone (including the structures attached to it) anteriorly, thereby advancing the posterior side of the tongue and enlarging the pharyngeal airways (Fig. 5D). Contraction of the longitudinal GG fibers has the same effect on the "free-floating" HG. However, as this part of the GG already advances the tongue, the concomitant contraction of the HG has no additive effect on the pharyngeal CSA (Fig. 5E). Considering the extensive interdigitation of extrinsic and intrinsic tongue muscles, the HG may be considered, like the intrinsic longitudinal tongue fibers, to act in series with the GG, and when both contract together unopposed by other muscles (as was the case in our study during coactivation), the HG may help advancing the tongue, i.e., act as a tongue protrusor. In addition, it is possible that the posterior portion of the surface electrode activated also longitudinal intrinsic tongue fibers, and coactivation of these fibers with the GG assisted the beneficial effect observed in the SlS, by the same mechanism suggested for the HG. Interestingly, a similar phenomenon was reported by Fuller et al. (11), who observed that retractor stimulation improved pharyngeal flow and Pcrit when the tip of the tongue was anchored to a force transducer but obstructed the pharynx when the tongue was free to retract. The second tongue retractor, the styloglossus, is attached to the bony structure of the skull and is expected to be a pure tongue retractor. With the mode of stimulation used in our studies, this muscle was not activated. Our findings indicate, therefore, that coactivation may or may not enlarge the pharynx and improve patency, depending on the retractor and protrusor muscle (or muscle part) activated.

View larger version (29K): [in this window] [in a new window]   Fig. 5. Schematic presentation of the forces applied by the GG and the HG on the tongue. GG1, longitudinal GG fibers that advance and protrude the tongue. GG2, vertically oriented GG fibers that depress the tongue. A, B, and C illustrate the isolated effects of GG2, HG, and GG1 contraction, respectively. D and E show effects of coactivation. To enable tongue retraction by the HG, the hyoid bone has to be stable, and the GG relaxed. However, when the HG contracts together with the GG, and the muscles that stabilize the hyoid bone are relaxed, coactivation is expected to move the hyoid bone (and the tongue) anteriorly. See text for additional explanations.

As in previous studies (16, 17), we used the slope of the CSA:Pn curve in the AnS as an indicator of the compliance of the area of collapse. This method has the advantage of focusing on the collapsible segment of the pharynx, rather than measuring compliance of the whole isolated upper airway, possible only in animals. On the other hand, this method includes confounders like lung volume effects on pharyngeal size and compliance and changes in muscles length-tension relationships associated with alterations in pharyngeal size. Therefore, the CSA:Pn relationships results from a complex interaction of multiple effects (17). It should also be noted that the complete CSA:Pn relationships of the pharynx is typically exponential, with little dilation occurring at high Pn levels (15). However, as we were interested only in the CSA:Pn range close to Pcrit, which is associated with flow limitation (14), we limited our measurements to this nearly linear portion of the curve, as previously suggested (16, 17). The lack of response of velopharyngeal CSA:Pn to tongue muscle stimulation in our study is similar to the response observed by Isono et al. (16) during whole tongue stimulation, and responses in animals (17).

The results of the present study provide additional evidence on the effect of tongue muscle contraction on velopharyngeal patency and collapsibility. Although the exact mechanism by which the tongue affects the soft palate cannot be determined from our experiments, it is likely due to changes in the external tissue pressure at the site of collapse, as previously suggested (27). The close relationships between the direction of movement of the tongue and the size of the velopharynx observed in the present study, as well as the correlation between the magnitude of tongue advancement and enlargement of the retropalatal space during GG stimulation in our recent study (24), suggest that the tongue compresses the site of collapse. Anterior tongue advancement may unload the velopharyngeal area and decrease the pressure exerted by the tongue on the ventral surface of the soft palate, thereby increasing the transmural pressure (i.e., intraluminal minus external pressure). The possibility that palatoglossal and/or palatopharyngeal fibers near the posterior edge of the sublingual electrode could have been activated during retractor muscle stimulation cannot be excluded. These fibers, which pull the anterior palatal arch, could possibly enlarge the retropalatal airway. However, as this potential effect did not prevent velopharyngeal obstruction during retractor stimulation, their effect, if present, was probably minimal. On the other hand, displacement of the tongue may exert a direct mechanical effect on the soft palate, as the tongue connects anatomically to the soft palate by the palatoglossus muscle and arch.

Previous studies that evaluated the effects of tongue protrusor and retractor coactivation on the pharynx used nerve stimulation and compared stimulation of the median hypoglossus branch, which activates the GG (and intrinsic muscles), with stimulation of the whole hypoglossus, which activates all intrinsic and extrinsic (i.e., both retractor and protrusor) tongue muscles (1, 3, 8, 11, 17, 18, 32). Taken together, the animal studies indicated that the mechanical effects of tongue muscle stimulation depend on a complex interaction between the muscles stimulated, the pharyngeal region (i.e., caudal and rostral oropharynx and nasopharynx), and the transmural pressure. In addition, results depended also on the mechanical parameter evaluated (i.e., size, compliance, resistance, or Pcrit). Most studies found no advantage to coactivation by stimulating the whole hypoglossus nerve over stimulation of its medial branch (1, 3, 17, 18). On the other hand, pharyngeal resistance decreased during coactivation more than during GG stimulation (32). In patients with OSA, a similar increase in airflow was found during whole hypoglossus nerve and medial branch stimulation (8). Although differing substantially from our study in the mode of stimulation and, therefore, in the pattern of muscle recruitment, these results corroborate our finding that once the transverse GG fibers are activated, coactivation of the retractors provides little or no additional mechanical advantage. However, isolated supramaximal stimulation of the GG is unlikely to occur under physiological conditions. Our findings suggest that tongue retractors may provide a mechanical advantage during specific muscle recruitment patterns. The coactivation observed regularly when EMG of the retractor and protrusor muscles is recorded (10) suggests that such specific patterns of recruitment are likely to be the norm during physiological, central activation of the tongue muscles.

In conclusion, our findings emphasize the importance of discerning the mechanical action of the deeper, transversely oriented GG fibers, which advance the tongue and enlarge the pharynx, from "nonadvancing" GG fibers, which have other mechanical effects. Similarly, tongue retractors function differently, and the HG may help advancing the base of the tongue when pulled by the GG, unopposed by muscles that stabilize the hyoid bone. Accordingly, a beneficial effect of tongue retractor and protrusor coactivation depends on the pattern of muscle recruitment. Coactivation may enlarge the pharynx and improve flow dynamics during specific modes of tongue muscle activation (for example, contraction of the HG + nonadvancing GG fibers), while little or no benefit of coactivation is observed when the transverse GG fibers are activated.

	GRANTS

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This study was supported by Binational USA-Israel Science Foundation (BSF) Grant 2000234 and by National Heart, Lung, and Blood Institute Grants HL-50381 and HL-37379.

	FOOTNOTES

 

Address for reprint requests and other correspondence: A. Oliven, Dept. of Internal Medicine, Bnai Zion Medical Center, 47 Golomb St., Haifa, Israel (e-mail: oliven{at}tx.technion.ac.il)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

	REFERENCES

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1. Brennick MJ, Trouard TP, Gmitro AF, Fregosi RF. MRI study of pharyngeal airway changes during stimulation of the hypoglossal nerve branches in rats. J Appl Physiol 90: 1373–1384, 2001.[Abstract/Free Full Text]
2. Block AJ, Faukner JA, Huges Rl Remmers JE, Thach BT. Factors influencing upper airway closure. Chest 86: 114–122, 1984.[CrossRef][Web of Science][Medline]
3. Brennick MJ, Trouard TP, Gmitro AF, Fregosi RF. MRI study of pharyngeal airway changes during stimulation of the hypoglossal nerve branches in rats. J Appl Physiol 90: 1373–1384, 2001.[Abstract/Free Full Text]
4. Decker MJ, Haaga J, Arnold JL, Atzberger D, Strohl KP. Functional electrical stimulation and respiration during sleep. J Appl Physiol 75: 1053–1061, 1993.[Abstract/Free Full Text]
5. Eastwood PR, Szollosi I, Platt PR, Hillman DR. Comparison of upper airway collapse during general anaesthesia and sleep. Lancet 359: 1207–1209, 2002.[CrossRef][Web of Science][Medline]
6. Eastwood PR, Platt PR, Shepherd K, Maddison K, Hillman DR. Collapsibility of the upper airway at different concentrations of Propofol anesthesia. Anesthesiology 103: 453–454, 2005.[CrossRef][Web of Science][Medline]
7. Edmonds LC, Daniels BK, Stanson AW, Sheedy PF, Shepard JWJ. The effects of transcutaneous electrical stimulation during wakefulness and sleep in patients with obstructive sleep apnea. Am Rev Respir Dis 146: 1030–1036, 1992.[Web of Science][Medline]
8. Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 123: 57–61, 1997.[Abstract/Free Full Text]
9. Fregosi RF, Fuller DD. Respiratory-related control of extrinsic tongue muscle activity. Respir Physiol 110: 295–306, 1997.[CrossRef][Web of Science][Medline]
10. Fuller DD, Mateika JH, Fregosi RF. Co-activation of tongue protrudor and retractor muscles during chemoreceptor stimulation in the rat. J Physiol 507: 265–276, 1998.[Abstract/Free Full Text]
11. Fuller DD, Williams JS, Janssen PL, Fregosi RF. Effect of co-activation of tongue protrudor and retractor muscle on tongue movements and pharyngeal airflow mechanics in the rat. J Physiol 519: 601–613, 1999.[Abstract/Free Full Text]
12. Ginz HF, Zorzato F, Iaizzo PA, Urwyler A. Effect of three anaesthetic techniques on isometric skeletal muscle strength. Br J Anaesth 92: 367–372, 2004.[Abstract/Free Full Text]
13. Guilleminault C, Powell N, Bowman B, Stoohs R. The effect of electrical stimulation on obstructive sleep apnea syndrome. Chest 107: 67–73, 1995.[CrossRef][Web of Science][Medline]
14. Isono S, Feroah TR, Hajduk EA, Brant R, Whitelaw WA, Remmers JE. Interaction of cross-sectional area, driving pressure, and airflow of passive velopharynx. J Appl Physiol 83: 851–859, 1997.[Abstract/Free Full Text]
15. Isono S, Remmers JE, Tanaka A, Sho Sato JY, Nishino T. Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol 82: 1319–1326, 1997.[Abstract/Free Full Text]
16. Isono S, Tanaka A, Nishino T. Effects of tongue electrical stimulation on pharyngeal mechanics in anaesthetized patients with obstructive sleep apnoea. Eur Respir J 14: 1258–1265, 1999.[Abstract]
17. Kuna ST, Brennick M. Effects of pharyngeal muscle activation on airway pressure-area relationships. Am J Respir Crit Care Med 166: 972–977, 2002.[Abstract/Free Full Text]
18. Kuna ST. Regional effects of selective pharyngeal muscle activation on airway shape. Am J Respir Crit Care Med 169: 1063–1069, 2004.[Abstract/Free Full Text]
19. Miki H, Hida W, Chonan T, Kikuchi Y, Takishima T. Effects of submental electrical stimulation during sleep on upper airway patency in patients with obstructive sleep apnea. Am Rev Respir Dis 140: 1285–1289, 1989.[Web of Science][Medline]
20. Odeh M, Schnall R, Gavriely N, Oliven A. Effect of upper airway muscle contraction on supraglottic resistance and stability. Respir Physiol 92: 139–150, 1993.[CrossRef][Web of Science][Medline]
21. Odeh M, Schnall R, Gavriely N, Oliven A. Dependency of upper airway patency on head position: the effect of muscle contraction. Respir Physiol 100: 239–244, 1995.[CrossRef][Web of Science][Medline]
22. Oliven A, Schnall RP, Pillar G, Gavriely N, Odeh M. Sublingual electrical stimulation of the tongue during wakefulness and sleep. Respir Physiol 127: 217–226, 2001.[CrossRef][Web of Science][Medline]
23. Oliven A, O'Hearn DJ, Boudewyns A, Odeh M, De Backer W, van de Heyning P, Smith PL, Eisele DW, Allan L, Schneider H, Testerman R, Schwartz AR. Upper airway response to electrical stimulation of the genioglossus in obstructive sleep apnea. J Appl Physiol 95: 2023–2029, 2003.[Abstract/Free Full Text]
24. Oliven A, Tov N, Geitini L, Steinfeld U, Oliven R, Schwartz AR, Odeh M. Effect of genioglossus contraction on pharyngeal lumen and airflow in sleep apnea patients. Eur Respir J 30: 1–11, 2007.[Free Full Text]
25. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 44: 931–938, 1978.[Free Full Text]
26. Schnall R, Pillar G, Kelsen SG, Oliven A. Dilatory effects of upper airway muscle contraction induced by electrical stimulation in awake humans. J Appl Physiol 78: 1950–1956, 1995.[Abstract/Free Full Text]
27. Schwartz AR, Thut DC, Russ B, Seelagy M, Yuan X, Brower RG, Permutt S, Wise RA, Smith PL. Effect of electrical stimulation of the hypoglossal nerve on airflow mechanics in the isolated upper airway. Am Rev Respir Dis 147: 1144–1150, 1993.[Web of Science][Medline]
28. Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith PL. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 81: 643–652, 1996.[Abstract/Free Full Text]
29. Schwartz AR, Bennett ML, Smith PL, De Backer WA, Hedner J, Boudewyns A, Van de Heyning PH, Ejnell H, Hochban W, Knaack L, Podszus T, Penzel T, Peter JH, Goding GS, Erickson DJ, Testerman R, Ottenhoff F, Eisele DW. Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 127: 1216–1223, 2001.[Abstract/Free Full Text]
30. Smith PL, Wise RA, Gold AR, Schwartz AR, Permutt S. Upper airway pressure-flow relationships in obstructive sleep apnea. J Appl Physiol 64: 789–795, 1988.[Abstract/Free Full Text]
31. White DP. The pathogenesis of obstructive sleep apnea: advances in the past 100 years. Am J Respir Cell Mol Biol 34: 1–6, 2006.[Free Full Text]
32. Yoo PB, Durand DM. Effects of selective hypoglossal nerve stimulation on canine upper airway mechanics. J Appl Physiol 99: 937–943, 2005.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Free All Versions of this Article: 103/5/1662    most recent 00620.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Oliven, A. Articles by Tov, N. Search for Related Content PubMed PubMed Citation Articles by Oliven, A. Articles by Tov, N.