Mechanical effects of genioglossus muscle stimulation on the pharyngeal airway by MRI in cats
Introduction
Airway obstruction in patients with obstructive sleep apnea (OSA) is believed to arise from neuromuscular factors related to the reduction in upper airway muscle activity during sleep and predisposing anatomical factors such as decreased pharyngeal airway size and increased pharyngeal airway compliance (Schwab et al., 2005). The most commonly used treatments for patients with OSA, including nasal continuous positive airway pressure, oral mandibular advancement devices, and pharyngeal airway surgery, are not efficacious in all patients (Rodenstein, 1992, Launois et al., 1993, Isono et al., 1999a, Hicklin et al., 2000, Senior et al., 2000, Weaver, 2002, Barnes et al., 2004). Several studies have demonstrated the feasibility of electrical stimulation of tongue muscles as a possible treatment for patients with OSA (Schwartz et al., 1996, Oliven et al., 2001, Oliven et al., 2003, Schwartz et al., 2001). In those studies, stimulation of the lingual muscles increased airflow and reduced the number of obstructions during sleep. However, progress and development of muscle stimulation methods for OSA therapy or indeed any novel pharmacological therapies (Veasey, 2001) will benefit and rely on more complete knowledge as to which muscles or muscle combinations can reduce collapsibility either through airway dilation or reduced compliance of the pharyngeal airway during sleep.
Previous investigators have examined the mechanical effects of tongue muscle activation on the pharyngeal airway using a variety of techniques with somewhat conflicting results. The relative contribution of muscle groups innervated by the hypoglossus nerve (Getty, 1975, Williams, 1995) have been studied by selective nerve stimulation whereby, “whole nerve” stimulation of both medial and lateral branches has been used to stimulate the genioglossus geniohyoid, styloglossus, hyoglossus and intrinsic tongue muscles, while medial branch stimulation was used to selectively stimulate only the genioglossus, geniohyoid and intrinsic tongue muscles (Fregosi and Fuller, 1997, Fuller et al., 1998, Kuna and Brennick, 2002). Using a Starling resistor model of flow in the upper airway, Fregosi and Fuller (1997) and Fuller et al. (1998) found that ‘whole’ hypoglossal nerve stimulation decreased critical pressure (Pcrit, collapsing pressure of the flow limiting segment) but had little effect on maximal inspiratory airflow (VImax), while stimulation of just the medial branch of the hypoglossal nerve increased VImax but had a minimal effect on Pcrit. These results were interpreted to suggest that selective stimulation of the medial hypoglossus merely dilates the airway, while stimulation of both medial and lateral hypoglossus branches may reduce airway collapsibility by dilation and by altering pharyngeal airway tissue characteristics (reduced Pcrit) (Eisele et al., 1995, Fregosi and Fuller, 1997, Fuller et al., 1999, Kuna and Brennick, 2002). In contrast to those results, Kuna and Brennick (Kuna and Brennick, 2002) measured static compliance (using a fiberoptic method in the isolated airways in decerebrate cats) and found that pharyngeal compliance, as the slope of airway pressure versus cross-sectional area (CSA) relationship, was reduced during stimulation of either the whole hypoglossal nerve or just its medial branch.
Pharyngeal compliance was also measured in a fiberoptic study in anesthetized paralyzed patients with OSA by Isono et al. (1999b), who reported that transmucosal stimulation of tongue muscles of the oropharyngeal segment near the epiglottis decreased pharyngeal airway compliance. Finally, in a comparison study of genioglossus muscle stimulation using fine wire intramuscular electrodes or unilateral stimulation of the medial branch of the hypoglossal nerve in OSA patients during sleep, Oliven et al. (2003) reported that both intramuscular and nerve stimulation methods increased airflow, reduced Pcrit, and reduced apnea severity. They noted however, that with either method of stimulation, the increase in maximal inspiratory airflow (VImax) occurred without a change in upstream resistance and suggested that the lowered Pcrit in these patients occurred without a reduction in compliance.
The purpose of this study was to examine the regional mechanical effects of selective genioglossus muscle activation on pharyngeal airway size and function in paralyzed, anesthetized cats. We used magnetic resonance imaging (MRI) with and without genioglossal stimulation over a range of applied positive and negative pressures in an isolated, sealed upper airway and measured airway cross-sectional area (CSA) versus airway at multiple rostral to caudal regions of the pharynx. We reasoned that a reduction in the slope of the resulting airway pressure versus CSA relationships with genioglossus stimulation would indicate that stimulation decreased airway compliance, whereas a parallel shift would indicate that airway compliance was unchanged. If there were no change in compliance but an increase in CSA across pressure levels then the upward shift of the pressure versus CSA curve would be reflected in a reduced closing pressure (Pclose or pressure at 0 CSA). The ratio of the lateral to anteroposterior (AP) airway diameters was also examined in each region to determine what shape changes, if any, occurred due to genioglossus stimulation and the different levels of pressure.
Section snippets
Surgical preparation
The methods were approved by the University of Pennsylvania Institutional Animal Care and Use Committee (IACUC). Five cats of either sex, weighing 3.2 ± 0.2 kg (mean ± S.E.M., throughout text) were pre-anesthetized using intramuscular Ketamine (15 mg/kg) with intramuscular diazepam (2 mg/kg) for muscle relaxation and atropine (0.05 mg/kg) for reduction of secretions and to aid anesthetic induction. Within 15–30 min of anesthetic induction, isoflurane vapor (1.5–2.0% by volume in pure O2) was
Results
Fig. 3 (left image) shows the pharyngeal regions that were analyzed on the axial images. Pharyngeal enlargement during stimulation (Fig. 3, right image) is evident in the mid and caudal pharyngeal regions. The circular inset in the right panel shows the location of the stimulating electrodes, where the image distortion is a susceptibility artifact that was due to the great difference in T1 relaxation time between the metal electrodes and surrounding tongue muscle tissue. In most animals, this
Discussion
Extending previous results from this laboratory on pharyngeal airway compliance under passive, unstimulated conditions (Brennick et al., 1998), the current study determined the mechanical effects of selective activation of the genioglossus muscle on pharyngeal CSA, shape and compliance in anesthetized, paralyzed cats. This is the first study to use stimulus-gated MRI to examine the regional effects of intramuscular genioglossus muscle stimulation on pharyngeal pressure–area relationships in
Acknowledgements
The authors gratefully acknowledge Dr. Sam Kuna for advice in reviewing the manuscript. Support by: NIH HL07713, NIH HL42236, NIH EB1780 and NIH HL27520.
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- 1
Present address: Ground Flr. Founders, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
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Present address: 105 Hayden Hall, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, United States.