Respiratory-related activity of the UAW motor outputs plays an important role in the upper airway patency. Dysfunction of these UAW motor activities may contribute to the OSAHS. Young et al. (2002) estimated that there are about 20 % adults having been suffered from mild OSAHS. Patients with OSAHS usually also suffer from a variety of the cardiovascular and pulmonary disorders (Malhorta and White, 2002;
Qureshi and Ballard, 2003; Young et al., 2002). In addition, some studies report that OSAHS are associated with the impairment of cognition (Engleman and Douglas, 2004; Peng et al., 2004). Furthermore, patients with OSAHS have higher traffic accident rates (George, 2004). These consequences of OSAHS will consume many medical resources and society costs. Hence, it is critical to understand the pathogenesis of OSAHS. Several clinic studies have indicated that reduction of respiratory-related activities of the tongue muscles might be a risk factor for OSAHS (Deegan and McNicholas, 1995; Harper and Sauerland, 1978; Remmers et al., 1978;
Ryan and Bradley, 2005). These observations suggested that the tongue muscles play an important role in the maintenance of UAW patency. PCF receptors are the main chemosensitive afferents in the lung and could be excited and/or sensitized by various external irritants and internal chemicals. Activation of PCF receptors induces central-mediated pulmonary chemoreflex, characterized by apnea, hypotension and bradycardia (Coleridge and Coleridge, 1986). In addition, our previous studies also indicated that activation of PCF receptors could evoke the glottal closure by shifting post-inspiratory activity to discharge earlier during inspiration and inhibiting inspiratory activity of the recurrent laryngeal nerve (Lu et al., 2002; Lu et al., 2005;
Lu et al., 2006). However, it is unclear whether PCF receptor activation could modulate the pharyngeal patency by influencing activities of the hypoglossal nerve or tongue muscles. It is critical to understand the response of the hypoglossal nerve
and/or other UAW motor nerves to the activation of pulmonary vagal afferents. To reveal the effect of activation of pulmonary vagal afferents on hypoglossal activity or other UAW motor discharge, there are six projects conducted in this dissertation.
The first project was to investigate responses of the hypoglossal nerve to capsaicin-induced pulmonary vagal C-fiber receptors activation. Since inspiratory activity of the recurrent laryngeal and superior laryngeal nerve was inhibited by PCF receptors activation, I therefore proposed that inspiratory-related activity of the hypoglossal nerve might be also reduced by intra-jugular capsaicin administration. To test this hypothesis, the whole hypoglossal nerve and phrenic nerve were simultaneously recorded in response to capsaicin treatment. The second project was to examine whether response of two hypoglossal branches to capsaicin-induced activation of PCF receptor was similar or dissimilar. Many reports indicated that inspiratory-related activity of the tongue protrudor and retractor muscles responded similarly to the activation of the chemoreceptors and pulmonary stretch receptors. My hypothesis was that capsaicin administration may also produce a similar inhibition on the neural drives to the tongue protrudor and retractor muscles. The third project was to study the alterations of hypoglossal motoneuron discharge in response to capsaicin-induced activation of PCF receptors in rats. There are two mechanisms, the increase in discharge rate and recruited principle, for the motor increase to various stimuli. According to my hypothesis in the first two projects, activation of PCF receptors might produce reflexive inhibition on inspiratory activity of both hypoglossal branches, this effect would reflect from their decrease in motoneuron discharges. Therefore, data from single fiber recording on the hypoglossal branches might underlie the response of the hypoglossal branches to PCF receptor activation.
My hypothesis was that discharge rate of the hypoglossal motoneurons might decrease if the whole hypoglossal nerves or two branches were inhibited by capsaicin
administration. The fourth project was to examine whether response of the hypogloosal nerves to PCF receptor activation might reflect on the tongue force development. Since the hypoglossal nerve innervates the tongue muscles, reflex response of the hyplgossal nnerve to PCF receptor activation should reflect on the development of the tongue muscle force. This is very important to understand if PCF activation produced an advantage or disadvantage for UAW patency. Therefore, changes of the protrusive and retractive tongue force development were induced by airway occlusion and then evaluated with capsaicin-induced PCF receptor activation in this project. When tongue muscle force development was inhibited by PCF receptor activation, a disadvantage for UAW patency might be concluded and vice versa.
In addition, modulatory effects of other pulmonary vagal afferents, the SARs and RARs, on rhythmic activity of the UAW motor nerves were also examined in my dissertation. SARs-mediated Hering-Breuer reflexes have been well documented since 1868. Most of the previous studies focused on alterations in the amplitude of the UAW motor outputs during Hering-Breuer reflexes. These studies considered that rhythm of the UAW motor nerve are synchronized with the phrenic nerve. However, if the phrenic nerve and the UAW motor nerves receive a single rhythmic input, then rhythmic activity of the phrenic nerve and UAW motor nerves should commence at the same time. Indeed, discharge onset of the UAW motor nerves precedes the phrenic nerve bursting and has been established the notion that rhythmic hypoglossal activity can be uncoupled from the phrenic burst during elevation of PEEP, which may activate both SARs and RARs activity (Ezure et al., 2003). These observations mean that hypoglossal rhythm remains during phrenic apnea induced by PEEP, suggesting a possibility that respiratory rhythm of the hypoglossal nerve and the phrenic nerve bursting may have been differentially modulated by peripheral inputs. Therefore, neural control of rhythmic hypoglossal activity may differ from the phrenic bursting
when SARs and RARs are activated by changing lung volume. I proposed herein that uncoupling might be a common property for UAW motor outputs and thus respiratory rhythmic activity of the UAW motor nerves could be also uncoupled during phrenic apnea induced by increase of PEEP. If true, mechanism for uncoupled activity of the UAW motor nerves was studied by single motoneuron discharge to reveal whether uncoupling was due to the recruitment of expiratory motoneurons or a persistent discharge of inspiratory motoneuron activity. Hence, the fifth project was undertaken to examine my hypothesis that UAW motor activity could be uncoupled during phrenic apnea by positive end-expired pressure in the rat by simultaneous recording of discharge of the facial, hypoglossal, superior laryngeal, and recurrent laryngeal nerve and also of their motoenurons during application of PEEP.
Uncoupling is primarily because PEEP produced inhibition on the phrenic bursting and also on the inspiratory activity of the hypoglossal nerve (Ezure et al., 2003) and is probably contributed by the preceding activity, termed Pre-I, of the hypoglossal nerve. Pre-I UAW motor activity may play a role in the maintenance of UAW patency. However, which neurotransmitter is responsible for Pre-I activity of UAW motor nerves is still unclear. It has been well documented that glycinergic inhibition participated in modulating respiratory rhythm and also coordinating respiratory activity of the cranial and spinal nerve. Blockade of glycine receptor or reduction of chloride concentration induced shift forward of post-inspiratory activity of the recurrent laryngeal nerve from expiratory stage to inspiratory duration. In other words, reduction of synaptic inhibition may synchronize the inspiratory and expiratory activity at inspiratory phase. Accordingly, I proposed that glycinergic inhibition might participate in regulating Pre-I activity. The sixth project was designed to examine this possibility that glycinergic transmission plays a role in modulating pre-inspiratory hypoglossal nerve activity in the rat. The result obtained
showed that application of strychnine not only attenuated Pre-I activity of the hypoglossal nerve during control condition and also the earlier onset of hypoglossl activity induced by sustained lung inflation and PEEP manipulation.
Tables Table 1-1
Origin and insertion of the nasal muscles
Name Origin Insertion M. nasalis, pars transversa Maxilla Aponeurosis on nasal
dorsum
M. nasalis, pars alaris Maxilla Alar skin, minor alar cartilages
M. depressor septi Maxilla Greater alar cartilage M. levator labii superioris
alaeque nasi
Maxilla Upper lip, nasolabial fold
M. procerus Occipitofrontalis muscle Aponeurosis on nasal dorsum
M. dilatator naris Greater alar cartilage Alar skin
M. apicis nasi Greater alar cartilage Skin of nasal tip From Laryngoscope 108(7): 1025-1032, 1998.
B A
Figures
Fig. 1-1
Anatomy of the extrinsic tongue muscles (A) and hypoglossal nerve (B). MHN and LHN represented medial and lateral branch of the hypoglossal nerve, respectively. GG:
genioglossus; HG: hyoglossus; SG: styloglossus; GH: geniohyoid muscle. Panel A is from Respir. Physiol. 110: 295-306, 1997.
Fig. 1-2
Organization of the hypoglossal nucleus in the rat. Left and right side of the figure represent location of the hypoglossal motoneurons supply to the intrinsic and extrinsic tongue muscles, respectively. Location of each subnuclei is expressed in μm anterior to the obex.X: dorsal motor nucleus of the vagus; sol: tractus solitarius; AP: area postrema; CC: central canal. (from Respir. Physiol. Neurobiol. 147: 159-176, 2005)
Fig. 1-3
Scheme showing the relative position of the intrinsic laryngeal muscles and laryngeal cartilage in a horizontal plan. CT: cricothyroid; TA: thyroarytenoid muscle; PCA:
posterior cricoarytenoid muscle; AC: arytenoid cartilage; CC: cricoid cartilage; TC:
thryoid cartilage (TC). (from J. Appl. Physiol. 101: 609-617, 2006)