Dilation of the oropharynx via selective stimulation of the hypoglossal nerve

Obstructive sleep apnea (OSA) is caused by the retraction of the tongue to occlude the upper airway (UAW). Electrical stimulation of the tongue protrudor and retractor muscle has been demonstrated as an effective technique to alleviate UAW obstructions and is considered to be a potential treatment for OSA. Recent studies have shown that selective stimulation of the hypoglossal nerve (HG) to activate tongue muscles using a single implantable device presents an attractive approach for treating OSA. In this study, the functional outcome of selective hypoglossal nerve stimulation with a multi-contact peripheral nerve electrode was studied by imaging the airway in anesthetized beagles. A pulse train of varying amplitude was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired via a video grabber into a computer. For the open mouth positions, the tongue activation patterns were also viewed and videotaped with a digital camcorder through the mouth. The percent dilation of the pharyngeal opening for each contact was calculated. The images show that stimulations delivered through the electrode contacts placed around the HG nerve trunk can generate several different activation patterns of the tongue muscles. Some of these patterns translate into a substantial increase in the oropharyngeal size, while others do not have any effect on the pharynx. The activation patterns vary as a function of the head position and the lower jaw. These results suggest that selective nerve stimulation can be a useful technique to maximize the effects of HG nerve stimulation in removing the obstructions in sleep apnea patients

Submandibular mechanical stimulation of upper airway muscles to treat obstructive sleep apnea

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during wakefulness. The genioglossus activity is recorded with custom-made sublingual EMG electrode molded out of silicone. Mechanical vibrations are applied to the lower jaw at 8 and 12 Hz with an amplitude of 5 mm in the first experiment, and to the sub-mandibular area at three different intensities (0.2-0.9 mm, 21-33 Hz) in the second experiment. The effects of sub-mandibular mechanical vibrations are also investigated in severe obstructive sleep apnea patients during a whole night sleep study. The major findings of this study are that the genioglossus reflexively responds to the mechanical vibrations applied to the mandible and the sub-mandibular skin surface in healthy subjects during wakefulness and the sub-mandibular stimulations during sleep terminate the apnea earlier and decrease the level of hypoxia with smaller micro arousals

Functional Electrical Stimulation of Intrinsic Laryngeal Muscles under Varying Loads in Exercising Horses

Bilateral vocal fold paralysis (BVCP) is a life threatening condition and appears to be a good candidate for therapy using functional electrical stimulation (FES). Developing a working FES system has been technically difficult due to the inaccessible location and small size of the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle. A naturally-occurring disease in horses shares many functional and etiological features with BVCP. In this study, the feasibility of FES for equine vocal fold paralysis was explored by testing arytenoid abduction evoked by electrical stimulation of the PCA muscle. Rheobase and chronaxie were determined for innervated PCA muscle. We then tested the hypothesis that direct muscle stimulation can maintain airway patency during strenuous exercise in horses with induced transient conduction block of the laryngeal motor nerve. Six adult horses were instrumented with a single bipolar intra-muscular electrode in the left PCA muscle. Rheobase and chronaxie were within the normal range for innervated muscle at 0.55±0.38 v and 0.38±0.19 ms respectively. Intramuscular stimulation of the PCA muscle significantly improved arytenoid abduction at all levels of exercise intensity and there was no significant difference between the level of abduction achieved with stimulation and control values under moderate loads. The equine larynx may provide a useful model for the study of bilateral fold paralysis

Effect of acute and chronic pressure-threshold inspiratory muscle training on upper and lower airway function

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.There is evidence to suggest that inspiratory muscle training (IMT) may influence the functional properties of the muscles of the upper (UA) and lower (LA) airway. However, the nature and functional relevance of this influence is currently unclear. This thesis examined the effect of acute and chronic IMT in the context of UA and LA function. The ability of IMT to activate the UA dilator muscles, genioglossus (GG) and geniohyoid (GH), was examined using magnetic resonance imaging (MRI), as was the effect of chronic training on these muscles. In addition, the effect of acute and chronic IMT upon LA resistance (Rrs) and function was investigated in people with asthma using the Forced Oscillation Technique and conventional spirometry. For the UA, an acute bout of IMT at 60% maximal inspiratory mouth pressure (MIP) resulted in significant GG and GH activation (P < 0.001) as demonstrated by increases in the transverse relaxation time of muscle water (T2). Despite this, MRI was unable to detect any effect of chronic IMT upon UA function. For the LA, the usual increase in Rrs, following deep inhalation (DI) in people with asthma was attenuated with both single and multiple breaths against a pressure-threshold load equal to 50% MIP. However, six weeks IMT had no effect on baseline airway function or response to DI. In conclusion, an acute effect of pressure-threshold IMT upon UA and LA function was demonstrated. A strong rationale for a beneficial influence of chronic pressure-threshold IMT was therefore demonstrated. However, the data were insufficient to either reject, or accept the hypothesis that IMT exerts more than a transient influence upon UA and LA function, but insights are presented that support the need for further investigations.This work is funded by Harry Brar and HaB International Ltd

Respiratory Control: Central and Peripheral Mechanisms

Understanding of the respiratory control system has been greatly improved by technological and methodological advances. This volume integrates results from many perspectives, brings together diverse approaches to the investigations, and represents important additions to the field of neural control of breathing. Topics include membrane properties of respiratory neurons, in vitro studies of respiratory control, chemical neuroanatomy, central integration of respiratory afferents, modulation of respiratory pattern by peripheral afferents, respiratory chemoreception, development of respiratory control, behavioral control of breathing, and human ventilatory control. Forty-seven experts in the field report research and discuss novel issues facing future investigations in this collection of papers from an international conference of nearly two hundred leading scientists held in October 1990. This research is of vital importance to respiratory physiologists and those in neurosciences and neurobiology who work with integrative sensory and motor systems and is pertinent to both basic and clinical investigations. Respiratory Control is destined to be widely cited because of the strength of the contributors and the dearth of similar works. The four editors are affiliated with the University of Kentucky: Dexter F. Speck is associate professor of physiology and biophysics, Michael S. Dekin is assistant professor of biological sciences, W. Robert Revelette is research scientist of physiology and biophysics, and Donald T. Frazier is professor and chairman of physiology and biophysics. Experts in the field report current research and discuss novel issues facing future investigations. —SciTech Book Newshttps://uknowledge.uky.edu/upk_biology/1002/thumbnail.jp

Effect of acute and chronic pressure-threshold inspiratory muscle training on upper and lower airway function

There is evidence to suggest that inspiratory muscle training (IMT) may influence the functional properties of the muscles of the upper (UA) and lower (LA) airway. However, the nature and functional relevance of this influence is currently unclear. This thesis examined the effect of acute and chronic IMT in the context of UA and LA function. The ability of IMT to activate the UA dilator muscles, genioglossus (GG) and geniohyoid (GH), was examined using magnetic resonance imaging (MRI), as was the effect of chronic training on these muscles. In addition, the effect of acute and chronic IMT upon LA resistance (Rrs) and function was investigated in people with asthma using the Forced Oscillation Technique and conventional spirometry. For the UA, an acute bout of IMT at 60% maximal inspiratory mouth pressure (MIP) resulted in significant GG and GH activation (P < 0.001) as demonstrated by increases in the transverse relaxation time of muscle water (T2). Despite this, MRI was unable to detect any effect of chronic IMT upon UA function. For the LA, the usual increase in Rrs, following deep inhalation (DI) in people with asthma was attenuated with both single and multiple breaths against a pressure-threshold load equal to 50% MIP. However, six weeks IMT had no effect on baseline airway function or response to DI. In conclusion, an acute effect of pressure-threshold IMT upon UA and LA function was demonstrated. A strong rationale for a beneficial influence of chronic pressure-threshold IMT was therefore demonstrated. However, the data were insufficient to either reject, or accept the hypothesis that IMT exerts more than a transient influence upon UA and LA function, but insights are presented that support the need for further investigations.EThOS - Electronic Theses Online ServiceHarry BrarHaB International LtdGBUnited Kingdo

Swallow, breathing and survival: sex-specific effects of opioids.

This dissertation presents a series of studies examining mechanisms of deglutition and respiration, and how these vital processes are impacted by opioids. The experiments in Chapter Two investigated the role of the upper esophagus in airway protection through systematic activation of pharyngeal and esophageal mechanoreceptors in a cat electromyography model. Chapter Three compared effects of opioid administration on breathing and swallowing between male and female rats, and found that females are more susceptible to opioid-induced depression of breathing and swallow than males. Findings from Chapters Two and Three led to the development of a translational model of opioid-induced dysphagia using videofluoroscopy. Chapter Four demonstrated that opioid administration resulted in a significant decline in airway protection during swallow in freely feeding, unrestrained cats. This work has advanced knowledge of the regulation of the upper aerodigestive tract, and its dual roles in breathing and swallowing. An improved understanding of the neural control of deglutition will facilitate the development of effective treatments for dysphagia. This dissertation includes the first study to compare effects of opioids on pharyngeal swallow between sexes, and provides mechanistic and clinically-translatable insights into opioid-induced dysphagia. Elucidating the actions of opioids on the brainstem breathing and swallowing networks will aid the prevention and treatment of opioid-induced respiratory depression and dysphagia related complications such as aspiration pneumonia

Respiratory muscle strength and ventilatory failure in neuromuscular diseases: Myotonic dystrophy and motor neurone disease

This thesis has explored the use of pulmonary function tests, sleep studies, volitional and nonvolitional respiratory muscle strength assessment techniques in the evaluation of patients with neuromuscular diseases. I have particularly concentrated on patients with myotonic dystrophy and motor neurone disease, which comprised the largest group of patients apart from Duchenne muscular dystrophy, referred for assessment to Glasgow Respiratory units with expertise in non-invasive ventilation. In a group of 20 myotonic dystrophy (MyD) and 5 subjects with MND, I went on to establish that spirometry remains a useful basic tool. Supplemented with mouth pressures, we can derive useful information regarding global respiratory muscle strength. Additional routine evaluation of static lung volumes and diffusion capacity did not add in useful information that would be useful in routine clinical care. It is well known that sleep worsens respiratory failure. The use of screening sleep studies in assessing patients with neuromuscular diseases remains debatable. 25 subjects with MyD and 12 with MND were studied. Routine sleep studies did not seem to add any useful information that could not be predicted from the daytime pulmonary function tests apart from 12% of MyD patients where it was useful in identifying nocturnal respiratory disturbance. However it is debatable whether treating these abnormalities affects prognosis in the long term. There has been significant contribution to our understanding of respiratory muscle strength in various circumstances such as in children and intensive care setting with the introduction of magnetic phrenic nerve stimulation technique. After establishing the methodology at the laboratory, in a group of 10 patients with myotonic dystrophy, we found this to be useful in providing nonvolitional diaphragm strength. It would be immensely useful in this group as mouth pressures are frequently reduced due to facial muscle weakness. We showed that underestimation of respiratory muscle strength using volitional methods is common in MyD [Mean (sd) Sniff Pdi of 67.1(30.7)cm H2O vs bilateral Tw Pdi of 17.1(9.4) cm H2O]. BAMPS was also a useful daytime marker of nocturnal respiratory disturbances and low Tw Pdi identified 75% (3 out of 4) subjects with sleep related breathing disorder during daytime. Repeat volitional and nonvolitional tests 4-6 months' apart confirmed stable respiratory muscle strength. Lastly, I studied patients with motor neurone disease. This group had severe respiratory muscle weakness even at the outset with marked symptoms. Non-invasive ventilation improved symptoms in its users. Interestingly, we found that the inspiratory and expiratory positive airway pressures required for these patients were significantly lower compared to patients with hypventilation due to obesity and post-polio syndromes