Ansa cervicalis stimulation increases pharyngeal patency in patients with obstructive sleep apnea.

Hypoglossal nerve stimulation (HNS) is an alternative treatment option for obstructive sleep apnea (OSA) that reduces pharyngeal collapsibility, but HNS nonresponders often demonstrate continued retropalatal and lateral pharyngeal wall collapse. Recent evidence suggests that caudal pharyngeal traction with sternothyroid muscle contraction via ansa cervicalis stimulation (ACS) can also stabilize the pharynx, but the underlying mechanisms have not been elucidated. Our objective was to evaluate the effect of ACS on pharyngeal patency during expiration when the airway is most hypotonic. Eight participants with OSA underwent sustained ultrasound-guided fine-wire stimulation of the medial branch of the right hypoglossal nerve with and without transient stimulation of the branch of the ansa cervicalis nerve plexus innervating the right sternothyroid muscle during drug-induced sleep endoscopy. Airway cross-sectional area and expiratory airflow (V̇e) were measured from endoscopy video with ImageJ and pneumotachometry, respectively. ACS significantly increased retropalatal cross-sectional area (CSARP) to 211% [159-263] of unstimulated CSARP (P < 0.05). Adding ACS to HNS increased CSARP from baseline by 341% [244-439] (P < 0.05), a 180% [133-227] increase over isolated HNS (P < 0.05). ACS increased V̇e from baseline by 177% [138-217] P < 0.05). Adding ACS to HNS increased V̇e by 254% [207-301], reflecting decreases in pharyngeal collapsibility. Combining ACS with HNS increased retropalatal cross-sectional area and increased expiratory airflow, suggesting decreases in pharyngeal collapsibility. Our findings suggest that ACS exerts caudal traction on the upper airway through sternothyroid muscle contraction and that it may augment HNS efficacy in patients with OSA.NEW & NOTEWORTHY Ansa cervicalis stimulation (ACS) is a recently proposed neurostimulation mechanism for generating caudal pharyngeal traction that may benefit patients with obstructive sleep apnea. Here, we document endoscopic findings with ACS during drug-induced sleep endoscopy and additionally detail the effects of ACS on expiratory airflow, when the pharynx is known to be most hypotonic.

Ultrasound Localization and Percutaneous Electrical Stimulation of the Hypoglossal Nerve and Ansa Cervicalis.

OBJECTIVE: Hypoglossal nerve stimulation for obstructive sleep apnea (OSA) can be effective for appropriately selected patients, but current patient selection criteria are complex and still result in a proportion of nonresponders. Ansa cervicalis stimulation of the infrahyoid cervical strap muscles has recently been proposed as a new form of respiratory neurostimulation (RNS) therapy for OSA treatment. We hypothesized that percutaneous stimulation of both nerves in humans with temporary electrodes would make testing of the physiologic response to different RNS strategies possible. STUDY DESIGN: Nonrandomized acute physiology study. SETTING: Tertiary care hospital. METHODS: Fifteen participants with OSA underwent ultrasonography and placement of percutaneous electrodes proximal to the medial division of the hypoglossal nerve and the branch of the ansa cervicalis innervating the sternothyroid muscle (ACST). Procedural success was documented in each participant, as were any failures or procedural complication. RESULTS: The hypoglossal nerve was successfully localized in 15 of 15 (100%) participants and successfully stimulated in 13 of 15 (86.7%). The ACST was successfully localized in 15 of 15 (100%) participants and successfully stimulated in 14 of 15 (93.3%). Stimulation failure of the hypoglossal nerve was due to suboptimal electrode placement in 1 participant and electrode displacement in the other 2 cases. No complications occurred. CONCLUSIONS: The hypoglossal nerve and ACST can be safely stimulated via percutaneous electrode placement. Larger trials of percutaneous stimulation may help to identify responders to different RNS therapies for OSA with temporary or permanent percutaneous electrodes. Techniques for electrode design, nerve localization, and electrode placement are described.

Ansa Cervicalis Stimulation: A New Direction in Neurostimulation for OSA.

BACKGROUND: Hypoglossal nerve stimulation (HNS) is an alternative treatment option for patients with OSA unable to tolerate positive airway pressure but implant criteria limit treatment candidacy. Previous research indicates that caudal tracheal traction plays an important role in stabilizing upper airway patency. RESEARCH QUESTION: Does contraction of the sternothyroid muscle with ansa cervicalis stimulation (ACS), which pulls the pharynx caudally via thyroid cartilage insertions, increase maximum inspiratory airflow (VImax)? STUDY DESIGN AND METHODS: Hook-wire percutaneous electrodes were used to stimulate the medial branch of the right hypoglossal nerve and right branch of the ansa cervicalis innervating the sternothyroid muscle during propofol sedation. VImax was assessed during flow-limited inspiration with a pneumotachometer. RESULTS: Eight participants with OSA were studied using ACS with and without HNS. Compared with baseline, the mean VImax increase with isolated ACS was 298%, or 473 mL/s (95% CI, 407-539). Isolated HNS increased mean VImax from baseline by 285%, or 260 mL/s (95% CI, 216-303). Adding ACS to HNS during flow-limited inspiration increased mean VImax by 151%, or 205 mL/s (95% CI, 174-236) over isolated HNS. Stimulation was significantly associated with increase in VImax in both experiments (P < .001). INTERPRETATION: ACS independently increased VImax during propofol sedation and drove further increases in VImax when combined with HNS. The branch of the ansa cervicalis innervating the sternothyroid muscle is easily accessed. Confirmation of the ansa cervicalis as a viable neurostimulation target may enable caudal pharyngeal traction as a novel respiratory neurostimulation strategy for treating OSA.

An Implantable System For Chronic In Vivo Electromyography.

Electromyography (EMG) measures the muscle response to electrical stimulation or spontaneous activity of motor units and plays an important role in assessing neuromuscular function. Chronic recording of EMG activity reflecting a muscle's reinnervation status after nerve injury has been limited, due to the invasive nature of traditional EMG recording techniques. In this regard, an implantable system is designed for long-term, in vivo EMG recording and nerve stimulation. It has been applied and tested in a study on reinnervation of laryngeal muscles. This system consists of 1) two bipolar electrode nerve cuffs and leads for stimulating each of two nerves: the recurrent laryngeal nerve (RLN) and internal branch of the superior laryngeal nerve (SLN); 2) two EMG recording electrodes and leads for each of the two laryngeal muscles: posterior cricoarytenoid (PCA) muscle and thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex; and 3) a skin receptacle interfacing all implanted lead terminals to an external recording preamplifier and stimulator using a connection cable. The wire leads are Teflon-coated, multi-filament, type 316 stainless steel. They are coiled and can stretch during body movement of the awake animal to prevent lead breakage and electrode migration. This system is implanted during an aseptic surgery. Afterwards, baseline EMG recordings are performed before the RLN is transected in the second surgery to study muscle reinnervation. Throughout the study, multiple physiological sessions are conducted in the anesthetized animal to obtain evoked and spontaneous EMG activity that reflects the reinnervation status of laryngeal muscles. The system is compact, free of infection over the course of the study, and highly durable. This implantable system can provide a reliable platform for research in which long-term recording or nerve stimulation is required in an anesthetized or freely moving animal.

Unilateral and Bilateral Laryngeal Pacing for Bilateral Vocal Fold Paralysis.

PURPOSE OF REVIEW: Present the state-of-the-art overview of laryngeal pacing for treatment of bilateral vocal fold paralysis. A minimally invasive unilateral pacing system and a fully implantable bilateral pacing system are currently in clinical trials. The relative advantages and disadvantages of each are discussed. RECENT FINDINGS: Research in functional electrical stimulation for the reanimation of the posterior cricoarytenoid muscle has successfully translated from animal models to human clinical trials for unilateral pacing and bilateral pacing. Current findings suggest unilateral pacing in humans significantly improves ventilation but only marginally better than cordotomy. Bilateral pacing in canines increases glottal opening greater than 2-fold over unilateral pacing and restores exercise tolerance to normal. SUMMARY: Unilateral pacing can be considered a breathing assist device and may not be appropriate for active individuals. Bilateral pacing may be preferable for patients who wish to engage in strenuous exercise. Minimally invasive systems may be ideal for patients who prefer less invasive implantation and are not concerned with cosmesis. Fully implantable pacing systems offer greater electrode redundancy and stability, resulting in a system that is robust against electrode migration or damage.

Current Treatment Options for Bilateral Vocal Fold Paralysis: A State-of-the-Art Review.

Vocal fold paralysis (VFP) refers to neurological causes of reduced or absent movement of one or both vocal folds. Bilateral VFP (BVFP) is characterized by inspiratory dyspnea due to narrowing of the airway at the glottic level with both vocal folds assuming a paramedian position. The primary objective of intervention for BVFP is to relieve patients' dyspnea. Common clinical options for management include tracheostomy, arytenoidectomy and cordotomy. Other options that have been used with varying success include reinnervation techniques and botulinum toxin (Botox) injections into the vocal fold adductors. More recently, research has focused on neuromodulation, laryngeal pacing, gene therapy, and stem cell therapy. These newer approaches have the potential advantage of avoiding damage to the voicing mechanism of the larynx with an added goal of restoring some physiologic movement of the affected vocal folds. However, clinical data are scarce for these new treatment options (i.e., reinnervation and pacing), so more investigative work is needed. These areas of research are expected to provide dramatic improvements in the treatment of BVFP.

An implantable system for In Vivo chronic electromyographic study in the larynx.

INTRODUCTION: Electromyography (EMG) plays an important role in exploring the mechanisms of selective reinnervation. An implantable system can help provide chronological information regarding reinnervation of laryngeal muscles. This study was designed to develop an implantable system for repeated recordings of spontaneous and evoked EMG from laryngeal muscles. METHODS: This implantable system has 4 bipolar stimulus cuffs for bilateral recurrent laryngeal nerves (RLNs) and superior laryngeal nerves (SLNs), and 4 EMG recording electrodes for bilateral vocal fold adductors (thyroarytenoid-lateral cricoarytenoid, TA-LCA) and abductor (posterior cricoarytenoid, PCA) muscles. The system was implanted in 8 canines for up to 41 weeks. RESULTS: The system showed good compatibility. Consistent EMG signals were recorded from both PCA and TA-LCA muscles. CONCLUSION: We developed a long-term implantable EMG system that is simple and capable of obtaining stable EMG recordings from canine laryngeal muscles with minimal risk of device breakage, trauma, or infection. Muscle Nerve 55: 706-714, 2017.

Stimulation of denervated muscle promotes selective reinnervation, prevents synkinesis, and restores function.

OBJECTIVES/HYPOTHESIS: Previously, electrical stimulation of denervated canine laryngeal muscle was shown to promote reinnervation by native over foreign motoneurons. The goal of this study was to assess the effect of different stimulus paradigms on reinnervation quality and functional recovery. STUDY DESIGN: A prospective study of six canines over 8 to 20 months. METHODS: A clinical model of laryngeal paralysis was used, where recurrent laryngeal nerves of the animals were sectioned and ventilation compromised. The abductor, posterior cricoarytenoid (PCA) muscles were implanted bilaterally with electrodes from an implantable pulse generator. Animals were randomly assigned to three groups to assess the effect of different stimulus paradigms: 1) 40 pulses per second (pps) train, 2) 10 pps train, 3) no stimulation. Spontaneous vocal fold movement was measured endoscopically during hypercapnia. Exercise tolerance was measured on a treadmill using pulse oximetry. In the terminal session, electromyography (EMG) potentials were recorded during superior laryngeal nerve stimulation to index foreign reinnervation of the PCA by reflex glottic closure (RGC) motoneurons. RESULTS: After reinnervation started, nonstimulated and stimulated 40 pps animals displayed paradoxical closure of the glottis during hypercapnia and severely decreased exercise tolerance due to faulty reinnervation. In contrast, stimulated 10 pps animals displayed minimal paradoxical closure and normal exercise tolerance (12 minutes up to 8 mph). EMG findings in this group demonstrated significantly less PCA reinnervation by foreign RGC motoneurons. CONCLUSION: PCA stimulation with low frequency reduced synkinetic reinnervation by foreign RGC motoneurons. Paradoxical closure of the glottis with inspiration was reduced and exercise tolerance restored to normal.

Comparison of ventilation and voice outcomes between unilateral laryngeal pacing and unilateral cordotomy for the treatment of bilateral vocal fold paralysis.

BACKGROUND/AIMS: Rehabilitation of the bilaterally paralyzed human larynx remains a complex clinical problem. Conventional treatment generally involves surgical enlargement of the compromised airway, but often with resultant dysphonia and risk of aspiration. In this retrospective study, we compared one such treatment, posterior cordotomy, with unilateral laryngeal pacing: reanimation of vocal fold opening by functional electrical stimulation of the posterior cricoarytenoid muscle. METHODS: Postoperative peak inspiratory flow (PIF) values and overall voice grade ratings were compared between the two surgical groups, and pre- and postoperative PIF were compared within the pacing group. RESULTS: There were 5 patients in the unilateral pacing group and 12 patients in the unilateral cordotomy group. Within the pacing group, postoperative PIF values were significantly improved from preoperative PIF values (p = 0.04) without a significant effect on voice (grade; p = 0.62). Within the pacing group, the mean postoperative PIF value was significantly higher than that in the cordotomy group (p = 0.05). Also, the mean postoperative overall voice grade values in the pacing group were significantly lower (better) than those of the cordotomy group (p = 0.03). CONCLUSION: Unilateral pacing appears to be an effective treatment superior to posterior cordotomy with respect to postoperative ventilation and voice outcome measures.

Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats.

INTRODUCTION: Age-related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age-related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found after NMES. METHODS: Fifty-four young, middle-aged, and old 344/Brown Norway rats were included in this study. Twenty-four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG), and hyoglossus (HG) muscles were examined. RESULTS: Compared with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half-decay times, and increased twitch and tetanic tension. Increased type I MHC was found, except for in GG in old and middle-aged rats. CONCLUSION: Transitions in tongue muscle contractile properties and phenotype were found after NMES.

Bilateral motion restored to the paralyzed canine larynx with implantable stimulator.

OBJECTIVES/HYPOTHESIS: Bilateral stimulation of posterior cricoarytenoid (PCA) muscles offers a physiologic approach to restore ventilation to a normal level in case of bilateral laryngeal paralysis. The objective of this study was to evaluate the long-term efficacy and safety of a new generation stimulator in restoring ventilation and exercise tolerance. STUDY DESIGN: A prospective study of four canines over 8-20 months. METHODS: A Genesis XP stimulator and electrodes were implanted and recurrent laryngeal nerves were sectioned and repaired bilaterally. In bimonthly sessions, vocal fold movement resulted from PCA stimulation or induced hypercapnea, was measured endoscopically in the anesthetized animal. Exercise tolerance was measured on a treadmill and swallowing function was examined endoscopically and radiographically. RESULTS: During the denervation phase, there was minimal ventilatory compromise and near-normal exercise tolerance. PCA stimulation produced only nominal abduction. During the reinnervation phase, synkinetic reinnervation became significant, resulting in a narrowed passive airway and paradoxical glottic closure during hypercapnea. Animals were stridorous and could walk for only 1-2 minutes. Bilateral PCA stimulation increased glottal area, equaling that of a normally innervated animal. Exercise tolerance was also normal. The optimal stimulus paradigm for the synkinetically reinnervated larynx was not different from that for the innervated larynx. Stimulation remained efficacious over the study period. Lead integrity could be maintained by prevention of device migration. There was no evidence of aspiration. CONCLUSIONS: This study demonstrates that ventilatory compromise only occurs following faulty reinnervation. Bilateral PCA stimulation can restore ventilation and exercise tolerance completely without aspiration over the long term.

Botulinum toxin injections for new onset bilateral vocal fold motion impairment in adults.

OBJECTIVES/HYPOTHESIS: Review of clinical experience and results using botulinum toxin type A (BTX) for the management of adult patients with respiratory compromise due to new onset bilateral vocal fold motion impairment (BVFMI). STUDY DESIGN: Retrospective case series. METHODS: The records of 11 patients from two institutions with respiratory compromise due to bilateral vocal fold motion impairment were reviewed. Age, sex, etiology of motion impairment, subjective response to BTX injections, changes in pulmonary function studies pre- and postinjection when available, the dosage of botulinum toxin required to achieve response, the number of injections per patient, and complications were reported. RESULTS: All patients were over 18 years old. There were three male and eight female subjects. The etiology of BVFMI was due to previous anterior cervical surgery in nine patients and prolonged intubation in two. Ten patients reported symptomatic improvement and returned for an average of nine injections over the 10-year period of study. The most common interval between injections was 3 months. In all patients the dose required to achieve symptomatic improvement was at least 2.5 mouse units injected into each vocal fold. One patient without relief of symptoms had bilateral cricoarytenoid joint fixation. Complications were limited to moderate dysphagia in one patient and breathy dysphonia in all patients. CONCLUSIONS: BTX injection into the vocal folds provides temporary relief of symptoms in airway obstruction in adult patients with BVFMI. Patients require an average of 2.5 units of botulinum injection into each vocal fold and have an average length of response of 3 months. BTX injection may be used as a form of temporary relief of airway obstruction in patients wishing to avoid ablative surgery or tracheotomy.

Rehabilitation of bilaterally paralyzed canine larynx with implantable stimulator.

OBJECTIVES/HYPOTHESIS: Bilateral stimulation of the posterior cricoarytenoid (PCA) muscles offers a physiologic approach to rehabilitate ventilation to a normal level in case of bilateral laryngeal paralysis. The objective was to evaluate the safety and efficacy of a new generation stimulator in restoring glottal opening, ventilation, and exercise tolerance. STUDY DESIGN: A prospective study in three canines over 6 to 17 months. METHODS: A Genesis XP stimulator and electrodes were surgically implanted, and the recurrent laryngeal nerves sectioned/repaired bilaterally. In bimonthly sessions, vocal fold movement was measured endoscopically in the anesthetized animal. The movement resulted from PCA stimulation or hypercapnea during spontaneous breathing. Exercise tolerance was measured on a treadmill using pulse oximetry and swallowing function examined by videofluoroscopy. RESULTS: During the denervation phase, there was minimal ventilatory compromise and near normal exercise tolerance with the device off (12 minutes, up to 8 mph). PCA stimulation produced only nominal abduction. During the reinnervation phase, synkinetic reinnervation became significant with narrowed passive airway and paradoxical closure of the glottis during hypercapnea. Animals were stridorous and could walk for only 1 to 2 minutes at 4 mph. With the device activated, bilateral PCA stimulation increased glottal area from 50 mm(2) to 250 mm(2), even during hypercapnea, equaling that of a normally innervated animal. Exercise tolerance was normal. There was no evidence of aspiration during deglutition. CONCLUSIONS: This study demonstrates that severe ventilatory compromise only occurs following faulty reinnervation of laryngeal muscles. Bilateral PCA stimulation can result in complete rehabilitation of ventilation and exercise tolerance without impairment of swallowing.

Characterization of raised phonation in an evoked rabbit phonation model.

OBJECTIVES/HYPOTHESIS: Our laboratory has developed an in vivo rabbit model to investigate the effects of phonation on expression and turnover of the vocal fold extracellular matrix. As a logical outgrowth of this research to include phonotrauma in the present study, we investigated the hypothesis that an increase in airflow rate delivered to the glottis produces a change in glottal configuration and an increase in mean phonation intensity. STUDY DESIGN: Prospective animal study. METHODS: Six New Zealand white breeder rabbits weighing 3 to 5 kg were used in this study. A rigid endoscope and camera were used to document glottal configuration. Acoustic signals of modal and raised phonation were recorded and digitized. Two separate one-way repeated measures analysis of variance (ANOVA) tests were used to investigate within subject differences in phonation intensity and fundamental frequency between modal and raised phonation. RESULTS: Phonation intensity was 54.19 dB SPL (6.21 standard deviations [SD]) during modal phonation, and 60.31 dB SPL (5.68 SD) during raised phonation. Endoscopic images revealed a convergent glottis, with greater separation of the vocal folds during raised phonation. Results of ANOVA revealed a significant within subjects effect for phonation intensity (P = .011). Pairwise comparisons revealed that phonation intensity increased significantly during raised phonation, compared to modal phonation (P = .008). No differences in mean fundamental frequency were observed between phonation conditions. CONCLUSIONS: Improved understanding of factors that control phonation output in the in vivo rabbit model will result in improved capabilities to match phonation dose across animals and provide immediate direction to future biochemical studies.

Toward an implantable functional electrical stimulation device to correct strabismus.

PURPOSE: To investigate the feasibility of electrically stimulating the lateral rectus muscle to recover its physiologic abduction ability in cases of complete sixth cranial (abducens) nerve palsy. METHODS: In the feline lateral rectus muscle model, the effects of a charge-balanced, biphasic, current-controlled stimulus on the movement of the eye were investigated while stimulation frequency, amplitude, and pulse duration was varied. Eye deflection was measured with a force transducer. Denervated conditions were simulated by injection of botulinum toxin A. RESULTS: Three chemically denervated and 4 control lateral rectus muscles were analyzed. In control lateral rectus muscles, the minimum fusion frequency was approximately 170 Hz, and the maximum evoked abduction was 27 degrees. The minimum fusion frequency was unchanged after 4 weeks of chemical denervation. Stimulation of chemically denervated lateral rectus muscle resulted in 17 degrees of abduction. For both innervated and chemically denervated lateral rectus muscle, frequencies greater than 175 Hz yielded very little increase in abduction. Modulating amplitude produced noticeable movement throughout the tested range (0.2 to 9 mA). CONCLUSIONS: Results from the feline lateral rectus muscle showed that electrical stimulation is a feasible approach to evoke a contraction from a denervated lateral rectus muscle. The degree of denervation of the feline lateral rectus muscle was indeterminate. Varying the stimulation amplitude allowed greater eye movement. It is very likely that both frequency and amplitude must be modulated for finer control of static eye position.

Model of evoked rabbit phonation.

OBJECTIVES: We describe a method for eliciting phonation in an in vivo rabbit preparation using low-frequency, bipolar pulsed stimulation of the cricothyroid muscles with airflow delivered to the glottis. METHODS: Ten New Zealand White breeder rabbits weighing 3 to 5 kg were used in this study. The cricothyroid muscles were isolated bilaterally, and separate pairs of anode-cathode hooked-wire electrodes were inserted into each muscle. A Grass S-88 stimulator and 2 constant-current PSIU6 isolation units were used to deliver bipolar square wave pulses to each cricothyroid muscle, with airflow delivered to the glottis through a cuffed endotracheal tube. RESULTS: Phonation was evoked with a 50-Hz, 4-mA stimulus train of 1-ms pulses delivered to each cricothyroid muscle. The pulse trains were on for 2 seconds and were repeated every 5 seconds over a period of 180 minutes. Airflow was delivered at 143 cm3/s, producing phonation measuring 71 to 85 dB sound pressure level. CONCLUSIONS: Evoked phonation is feasible in rabbits by use of bipolar stimulation of the cricothyroid muscles with airflow delivered to the glottis. The in vivo rabbit preparation described may provide a useful small animal option for studies of evoked phonation. From the level and consistency of the adduction observed, we hypothesize that current spreading to the underlying adductor muscles and nerves resulted in neural pathway involvement beyond discrete activation of the cricothyroid muscle, providing sufficient approximation of the vocal folds for phonation.

Evaluation of a deep brain stimulation electrode for laryngeal pacing.

OBJECTIVES: The purpose of the present study was to evaluate the suitability of a deep brain stimulation electrode for laryngeal pacing. Of interest was whether the smaller and more closely spaced channels could provide sufficient channel redundancy, controlled current distribution, and discrete activation of the posterior cricoarytenoid (PCA) muscle. METHODS: A study was conducted in dogs under differing states of PCA muscle innervation representing complete denervation to complete synkinetic reinnervation. In 3 animals, stimulated glottal opening was assessed in the innervated state and after chemical denervation by pancuronium bromide. In 3 additional dogs, the left side of the larynx was surgically denervated and compared to the innervated, right side to study an anatomic model of clinical paralysis. RESULTS: The thresholds were lower and the maximum level of abduction was greater for the innervated state. The stimulated glottal opening equaled that of a spontaneously breathing animal. Abductory responses were obtained across all channels in the array, demonstrating its anatomic and physiological compatibility for this application. In the denervated state, responses were only 20% of that of the innervated state with a pulse duration of 0.5 ms. The response could be enhanced to 40% and 60% by increasing the pulse duration to 1 and 2 ms. CONCLUSIONS: A deep brain stimulation electrode could effectively reanimate the PCA muscle to a normal level in a case of synkinetic reinnervation and to as much as 60% of the normal level in a case of complete denervation.

Experimentally induced phonation increases matrix metalloproteinase-1 gene expression in normal rabbit vocal fold.

OBJECTIVES: An in vivo rabbit model was used to study the effect of 3 hours of experimentally induced phonation on messenger RNA expression of the normal vocal fold. STUDY DESIGN: Prospective; animal model. SUBJECTS AND METHODS: Ten rabbits received experimental phonation for 3 hours, followed by 1 hour of recovery. A separate group of 5 rabbits served as no-phonation controls. We measured messenger RNA expression of matrix metalloproteinase-1, MMP-9, and interleukin-1beta using real-time reverse-transcribed polymerase chain reaction. Gene expression ratios from phonation and control animals were assessed with the Mann-Whitney U test. RESULTS: Phonation (77 +/- 3 dB; 429 +/- 141 Hz) resulted in increased matrix metalloproteinase-1 gene expression from rabbits receiving experimental phonation compared with controls, and a nonsignificant increase in matrix metalloproteinase-9 and interleukin-1beta gene expression. CONCLUSION: Matrix metalloproteinases play a role in maintaining tissue homeostasis. Investigation of cellular responses to experimental phonation may provide insight into how matrix metalloproteinases and other extracellular matrices contribute to maintenance of the vocal fold and development of pathology.