Importance

Scientific understanding of human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. To our knowledge, direct experimentation of human voice production has previously not been possible owing to its invasive nature. The feasibility of an ex vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation.

Objective

To investigate the association between adductor muscle group stimulation and the open quotient (OQ) (the fraction of the cycle during which the glottis remains open) of vocal fold vibration.

Design, setting, and participants

An ex vivo perfused human tissue study was conducted at a physiology laboratory. Human larynx recovered from organ donors within 2 hours of cardiac death was used. The study was performed on May 19, 2014; data analysis took place from June 1, 2014, to December 15, 2014.

Interventions

Perfusion with donated human blood was reestablished shortly after cardiac death. Ex vivo perfused human phonation was then achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles.

Main outcomes and measures

Phonation resulting from the graded states of neuromuscular stimulation was evaluated using high-speed vibratory imaging; the OQ was derived through digital kymography and glottal area waveform analysis.

Results

During constant glottal flow, a stepwise increase in adductor muscle group stimulation decreased the OQ. Quantitatively, OQ values decreased with increased stimulation levels from 2 V (OQ, 1) to 5 V (OQ, 0.68) and reached a lower limit of 8 V (OQ, 0.42). Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit.

Conclusions and relevance

To our knowledge, a negative association between adductor muscle group stimulation and phonatory OQ has been demonstrated for the first time in a neuromuscularly activated human larynx. Further experience with the ex vivo perfused human phonatory model will aid in systematically defining this causal relationship.

Objectives/hypothesis

An animal vocal fold replacement model is needed to investigate treatments for vocal fold scarring. We developed a rabbit surgical model, hypothesizing that orthotopic vocal fold cover implants would attach and survive. We further hypothesized that superficial scarring would be limited, allowing unimpeded vibration.

Study design

Translational research: animal surgical study.

Methods

Rabbit vocal fold covers were excised and immediately reimplanted. After 4 weeks, rabbits were phonated and vibration was recorded with high-speed videography. Larynges were then excised, elastic moduli measured by indentation, and covers sectioned for histology.

Results

Five of six rabbits survived. Phonation was achieved in all, with mucosal waves evident. Elastic modulus did not differ significantly from contralateral uninjured control vocal folds. Histology demonstrated epithelial integrity, partial preservation of elastic fibers, and variable degrees of collagen deposition.

Conclusions

Vocal fold cover implantation in rabbits is feasible, and grafts survived. Attachment onto the thyroarytenoid muscle prevented excessive scarring, maintained tissue mechanics, and preserved mucosal vibration.

Level of evidence

NA.