Current treatments for bilateral laryngeal paralysis employ destructive surgical procedures that improve ventilation at the expense of voice production and airway protection. Functional electrical stimulation (FES) of the posterior cricoarytenoid (PCA) muscle restores vocal fold abduction, and offers a more dynamic and physiologic alternative to present treatment. The primary objective of the proposed research are: 1) to restore abduction in animals with bilateral vocal fold paralysis using a transcutaneous or indwelling stimulation device, 2) to determine the effects of chronic electrical stimulation on the eventual reinnervation of the PCA. Preliminary studies in the canine have suggested that FES not only restores laryngeal mobility, but prevents denervation atrophy while maintaining the viability and contractility of PCA muscle fibers. Surprisingly, FES has been observed to influence reinnervation of the PCA by selectively encouraging neural reconnection of intrinsic nerve fibers, while repressing reinnervation from foreign sources. Studies from the proposed research will span a four year period during which the effects of chronic FES on nerve and muscle will be fully documented. Such information is critical before studies of laryngeal pacing can be pursued in the implanted patient. Of particular interest is whether FES can reverse denervation atrophy if intervention is delayed. The timing of FES intervention and its capacity to rescue PCA fibers from atrophy and fibrosis will be assessed in terms of changes in muscle physiology and biochemistry. The effects of chronic FES on the extent and quality of PCA reinnervation following Recurrent Laryngeal Nerve (RLN) section and/or repair will be determined using physiological observations of laryngeal behaviors, HRP tracing studies, and muscle histochemistry. If FES is found to prevent or reverse denervation atrophy while promoting appropriate neural reconnection, a clinical model for bilateral paralysis in the canine will be used to study FES as a therapeutic approach. Commercially available devices will be evaluated for adaptation to laryngeal pacing. Further research toward the development of an injectable microstimulator will be pursued in an animal model. This new technology may offer significant advantage over emergency tracheotomy in cases acute bilateral paralysis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001149-07
Application #
2700940
Study Section
Sensory Disorders and Language Study Section (CMS)
Program Officer
Shekim, Lana O
Project Start
1990-09-30
Project End
2002-03-31
Budget Start
1998-05-01
Budget End
2002-03-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Zealear, David L; Mainthia, Rajshri; Li, Yike et al. (2014) Stimulation of denervated muscle promotes selective reinnervation, prevents synkinesis, and restores function. Laryngoscope 124:E180-7
Li, Yike; Pearce, Elizabeth C; Mainthia, Rajshri et al. (2013) Comparison of ventilation and voice outcomes between unilateral laryngeal pacing and unilateral cordotomy for the treatment of bilateral vocal fold paralysis. ORL J Otorhinolaryngol Relat Spec 75:68-73
Nomura, Kenichiro; Kunibe, Isamu; Katada, Akihiro et al. (2010) Bilateral motion restored to the paralyzed canine larynx with implantable stimulator. Laryngoscope 120:2399-409
Zealear, David L; Kunibe, Isamu; Nomura, Kenichiro et al. (2009) Rehabilitation of bilaterally paralyzed canine larynx with implantable stimulator. Laryngoscope 119:1737-44
Katada, Akihiro; Van Himbergen, Daniel; Kunibe, Isamu et al. (2008) Evaluation of a deep brain stimulation electrode for laryngeal pacing. Ann Otol Rhinol Laryngol 117:621-9
Katada, Akihiro; Vos, Jeremy D; Swelstad, Brad B et al. (2006) A sequential double labeling technique for studying changes in motoneuronal projections to muscle following nerve injury and reinnervation. J Neurosci Methods 155:20-7
Zealear, David L; Swelstad, Matthew R; Fortune, Scott et al. (2005) Evoked electromyographic technique for quantitative assessment of the innervation status of laryngeal muscles. Ann Otol Rhinol Laryngol 114:563-72
Zealear, David L; Billante, Cheryl R (2004) Neurophysiology of vocal fold paralysis. Otolaryngol Clin North Am 37:1-23, v
Zealear, David L; Billante, Cheryl R; Courey, Mark S et al. (2003) Reanimation of the paralyzed human larynx with an implantable electrical stimulation device. Laryngoscope 113:1149-56
Billante, Cheryl R; Zealear, David L; Billante, Mark et al. (2002) Comparison of neuromuscular blockade and recovery with botulinum toxins A and F. Muscle Nerve 26:395-403

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