In-Situ Mechanical Characteristics of the Tongue are not Altered in the Obese Zucker Rat

OBSTRUCTIVE SLEEP APNEA (OSA) IS A COMMON DISORDER OFTEN CORRELATED WITH CARDIOVASCULAR DISEASE AND INCREASES IN MORBIDITY AND mortality.1,2 Obesity is a primary risk factor in the development of OSA, as has been demonstrated by the observation that the majority of patients with OSA are indeed obese.3 OSA is associated with multiple episodes of upper airway collapse (apnea) during sleep. Termination of each apnea is associated with arousal from sleep and vigorous activation of the pharyngeal muscles to restore airway patency. It has been suggested that pharyngeal muscle strength and the ability of these muscles to support upper airway patency may decline as a result of their repetitive intense stimulation.4 Thus, even if peak force is initially normal, the ability to sustain force (fatigability) or recover from muscle contraction (recovery) may be decreased and could be an important factor contributing to the decline of upper airway muscle function and airway occlusion. Because of its primary role as a tongue protrudor and upper airway stabilizer, the genioglossus muscle has received considerable attention, especially in clinical trials attempting to relieve OSA through external electrical stimulation of the genioglossus muscle.5–11 Concurrent activation of tongue retractor and protrudor muscles via electrical stimulation of the common branch of the hypoglossal nerve (cnXII) has been shown to provide a mechanical advantage (decreasing upper airway collapse), as compared with only a protrusive force.12–14 We have shown reductions in upper airway collapsibility with cnXII (common branch) electrical stimulation in both lean and obese Zucker rats.15–17 These previous studies firmly established the functional importance of retractor and protrudor muscle coactivation, especially when studying upper airway mechanics. Few studies have investigated pharyngeal muscle (genioglossus, geniohyoid, sternothyroid, and sternohyoid) contractile properties, almost all having utilized an in-vitro approach.16,18–21 According to these studies, pharyngeal muscle fatigue was increased following repetitive stimulation (fatiguing protocol). On the other hand, in-situ stimulation of the tongue muscles produced limited or no fatigue,22 despite using fatiguing paradigms known to produce fatigue in-vitro. Thus, current knowledge regarding the ability of pharyngeal muscles to produce and sustain force (fatigability) is unresolved and may be dependent on the protocol (in-situ vs in-vitro). Moreover, there is a paucity of data regarding the in-situ performance of the tongue muscle, especially with respect to obesity. As compared with nonobese Zucker rats, the obese Zucker rat, an animal model of obesity, has a more collapsible isolated upper airway15–17 and many of the same respiratory deficits commonly observed in obese humans, including reduced lung volumes, reduced chest wall compliance, a blunted hypoxic ventilatory response, and an anatomically altered upper airway.23,24 Although the isolated upper airway of obese rats is more collapsible than that of the nonobese rat, no evidence to date has been provided that any rodents, obese or not, exhibit any spontaneous airway obstructions awake or asleep. Based on the multiple similarities to obese humans, studying the in-situ characteristics of the tongue in obese Zucker rats may help elucidate the functional role of the tongue in airway collapse and the impact of obesity. Therefore, the purpose of the current study was to assess the in-situ mechanical characteristics, fatigability, and recovery of the tongue muscle in lean and obese Zucker rats. Consistent with the observation that obese Zucker rats have a more collapsible upper airway, we hypothesized that repetitive stimulation of cnXII (common branch) would reduce force-generating capacity and increase tongue fatigue more so in obese than in lean Zucker rats.