Despite improved life expectancy compared to medical management alone, Ventricular Assist Device (VAD) recipients show survival rates of 80% at 12 months and 70% at 24 months. A large portion of VAD-associated mortality results from increased risk of stroke with an event frequency reported between 14-47%. Recent concerns have been raised about unprecedented increases of thrombus formation in VAD recipients with subsequent reports pointing towards implantation techniques as a critical contributor to these events. Thus, the overall prognosis with mechanical support can improve by advancing the surgeon’s approach to VAD implantation. Previous studies using Computational Fluid Dynamics (CFD) were aimed at reducing stroke rates by tailoring the VAD outflow graft (VAD-OG) angle to direct any circulating emboli away from the cerebral vessels. In-vitro, or benchtop, models are often developed as computational counterparts. In order to accurately model the hemodynamics in the cardiovascular system, pulsatile flow must be mimicked. This is achieved in the computational domain by what is called a Windkessel model. This project seeks to develop a physical analogy to the Windkessel model for use in the benchtop experiments.

The purpose of the present study was to examine the effects of external laryngeal vibration on voice function. The current study was based on a recent pilot study using silicone vocal folds that demonstrated a decrease in phonation threshold pressure (PTP; cmH2O) when an external oscillation was applied to the vocal folds. Using a within-subjects experimental design, a custom external oscillatory device was fitted to the posterior portion of 12 excised pig larynges using a traditional benchtop phonation setup. For each larynx, phonation was elicited during 30 repeated trials, including 15 with and 15 without external oscillation. During the phonation trials, aerodynamic measures were collected. The outcome measure for this study was PTP, which has been established in the literature as being correlated with physiologic and self-perceived vocal effort. Furthermore, PTP is used routinely as an aerodynamic indicator of voice function, vocal efficiency, and the nature and severity of voice disorders. Although the aim was to quantify either positive (i.e., PTP decrease) or negative (i.e., PTP increase) effects of external oscillation on PTP, it was hypothesized that external oscillation would result in a reduction in average PTP values. The results of the study indicate that application of an external oscillatory device results in significantly lower PTP. These findings have important clinical implications for PTP signal acquisition and the potential use of external oscillation as a therapeutic tool to improve voice function.

Animal models are used extensively in voice research to study aspects of phonation, including physiology, kinematics, structure, and histology. Animals such as dog, cow, pig, sheep, deer, monkey, ferret, and rabbit have been used in voice research, with pig being one of the most common models. It is thought that the pig larynx is highly similar to the human larynx and one of the best models used in animal translational research. As with any model, however, the pig larynx does have some limitations. Perhaps a limitation most important to the rationale of this investigation is that pigs are difficult animals to study in vivo. Maintenance for a pig is challenging due to its large size and the variability of phonation use in the animal. Therefore, viable and practical alternatives are needed for in vivo voice research. The current study collected preliminary normative data from an alternate animal model, the rabbit, which has been used more recently in studies to model human phonation. The rabbit model was chosen due to its histological similarities to humans, in vivo phonation patterns, size, and practicality. The rabbit represents a more practical model for some longitudinal designs, as well as ex vivo phonatory models with aerodynamic measures as the primary variables. The current study involved a comparison of two aerodynamic measures, specifically phonation threshold pressure (PTP) and phonation threshold flow (PTF) between two groups, pig and rabbit larynges. The purpose of this study was to determine normative aerodynamic values for rabbits and to compare these with normative values for pigs during excised larynx benchtop phonation. Each group consisted of 15 larynges that were finely dissected to reveal the true vocal folds. Each larynx was then connected to a pseudolung and humidified air was passed through it. Fifteen phonation trials were elicited and the results averaged for each larynx. The results indicated that PTP and PTF were significantly different between the two groups, with PTP and PTF being lower for the rabbit group. Additionally, PTP values for rabbits were closer than pigs to the typical human value; however, some methodological challenges to rabbit benchtop models, including size and structural integrity, also exist. But the results from this study indicate that rabbits should be considered a viable option for voice research that would be more feasible with a small animal option that translates well to humans than a large animal option.

This thesis examined the effects of combination inhaled corticosteroids (ICs) on the stability of six aerodynamic measures of phonation utilizing a traditional benchtop model with leporine larynges. The motivation for this study was based on the increase of voice disorders associated with IC use in recent years. The aerodynamic measures examined were phonation threshold pressure (PTP), phonation threshold flow (PTF), onset resistance, sustained pressure, sustained flow, and sustained resistance. Leporine larynges were selected as the model for this study due to histological similarities between leporine and human vocal folds that make them ideal for translational research. Rabbits were either exposed to saline solution or ICs for 8 weeks before being sacrificed. After being sacrificed, larynges were excised and dissected. After dissection, the larynges were mounted on a benchtop, the aerodynamic data were gathered, and stability over multiple phonation trials was calculated. The results indicate that the variation between individual rabbits across the measures did not differ significantly. However, after controlling for trial, the average variation of the groups across all trials did differ significantly. PTP and sustained pressure were more variable for the inhaler group, while PTF, sustained flow, onset resistance, and sustained resistance were more variable for the control group. These results suggest that some level of variability in aerodynamic measures both within and between subjects is to be expected when using the leporine benchtop model. Furthermore, while IC exposure does not seem to impact within-subject variability, it does influence between-subjects variability.

This thesis is part of a larger series of studies being conducted by Kristine Tanner, PhD, Associate Professor in the Department of Communication Disorders at Brigham Young University (BYU). The larger project is funded by the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health. This thesis primarily investigated the effects of combination inhaled corticosteroids (ICs) on aerodynamic measures of the voice. In recent years, an increase in the localized laryngeal side effects from IC treatment, including dysphonia, have been reported. This study employed a between-groups experimental design, with two groups of rabbit larynges having been exposed to either ICs or nebulized isotonic saline two times each day for eight weeks at The University of Utah. For this study, the independent variable is group condition (i.e., IC versus saline) and the dependent variables are two aerodynamic measurements made at the onset of phonation using a benchtop experimental setup, namely phonation threshold pressure (PTP; cmH2O) and phonation threshold flow (PTF; L/min). The results of this study indicate a significant difference in PTP and PTF between vocal folds treated with IC as compared to vocal folds treated with nebulized isotonic saline solution. Implications of this study suggest negative changes in the voice due to IC treatment.

Combination corticosteroid inhalers are the primary treatment option for long-term pulmonary disorders including asthma, persistent bronchitis, and chronic obstructive pulmonary disease. Common side effects of these medications are xerostomia in the mouth and throat, hoarseness, and soreness in the oropharynx. Research indicates that a large percentage of the inhaler particles are deposited onto laryngeal tissue, leaving an alteration of laryngeal mucosal properties. As the first stage in a long-term project, this thesis addresses the need for baseline phonatory data that will lay groundwork for quantifying inhaler-induced phonatory changes. Excised larynx research is a powerful tool for assessing aerodynamic alterations that accompany laryngeal pathology. Porcine (pig) larynges are a traditional species employed in voice disorder research, though leporine (rabbit) larynges are an emerging species that lends itself to histologic vocal fold studies as they have the most similar vocal fold cover structure to humans compared to any other animal to date. The purpose of this study was to examine the measurement stability of six aerodynamic parameters in a traditional excised larynx benchtop model. Specifically, the current author assessed measurement stability of leporine larynges compared to porcine larynges with the following aerodynamic metrics: phonation onset pressure (PTP; cmH2O), phonation onset flow (PTF; L/m), sustained pressure (cmH2O), sustained flow (L/m), onset laryngeal resistance (cmH2O/L/m), and sustained laryngeal resistance (cmH2O/L/m). A total of 30 larynges—15 leporine and 15 porcine—were mounted on a benchtop setup; phonation was sampled over 15 trials for each larynx. Measurement stability for the above six tokens was examined using coefficient of variation (%) analyses. Leporine larynges demonstrated significantly less variation across all six aerodynamic parameters when compared to porcine larynges. The leporine PTP values were most stable as compared to leporine and porcine pressure and airflow values. Leporine airflow values were also more stable than porcine PTP and PTF values. These results indicate that leporine larynges might be a preferred excised larynx specimen for certain benchtop phonation studies. These findings are important for establishing expected measurement variability in porcine and leporine larynges, particularly when translating benchtop research to laryngeal pathology.

The purpose of this study was to examine external laryngeal oscillation and its potential effects on phonation threshold pressure (PTP; cm H2O) and phonation threshold flow (PTF; L/sec). Measures of PTP and PTF have inherent limitations due to the nonlinear nature of phonation, influencing their clinical and experimental utility. This is true particularly for tracking relatively small changes in voice function because variability in the measure itself can be larger than that resulting from voice change. Elevated PTP and PTF are associated with a variety of voice disorders and correlate with self-reported vocal effort and fatigue. Prior studies involving silicone and excised animal larynges have demonstrated PTP reduction in response to external oscillation. In an extension of this work, this thesis examined external laryngeal oscillation and aerodynamic voice measures in two experiments including a translational benchtop to human approach. Experiment 1 used a within-subjects counterbalanced design to examine PTF in 12 porcine larynges. Larynges were fitted with a custom oscillation device and 30 phonation trials were conducted for each larynx, 15 with external oscillation and 15 without. Although summary statistics indicated that PTF was lower with external oscillation, differences were not significant. Experiment 2 applied a within-subjects counterbalanced design to examine PTP in four healthy adult females and one healthy adult male. Individuals produced repeated syllable strings of /pi/ productions at comfortable pitch with and without external oscillation using an electrolarynx and the second and third syllables were averaged. Descriptive analysis indicated that PTP was lowered for female participants but not the male participant. Taken together, the results of these studies offer preliminary evidence that external oscillation influences voice onset aerodynamic measures. The effects of external oscillation seem to be more evident in PTP. These findings have important clinical and research applications for PTP measurement and the potential positive influence on voice function. These preliminary results indicate the need for further research in this area.

Subglottic stenosis (SGS) is a narrowing of the airway below the vocal folds and above the trachea. This narrowing may be idiopathic or caused by scarring in the airway due to prolonged endotracheal intubation, radiation therapy, trauma, or gastroesophageal reflux disease. People who present with SGS often experience respiratory difficulty both at rest and during exertion. Breathing difficulty increases with stenosis severity. SGS is also associated with voice problems. Research has identified relationships among stenosis severity, voice function and certain types of surgical management; however, many aspects of these relationships are not fully understood due to the complexities of studying human phonation in this population. The purpose of the present study was to examine the effects of SGS on aerodynamic features of voice function using an excised larynx benchtop mechanical model. Specifically, this research involved the comparison of excised porcine vocal fold vibration at baseline and under experimental conditions of 50% and 75% stenosed. The dependent variable was phonation threshold pressure (PTP), the minimum pressure needed to initiate and maintain vocal fold vibration. PTP was analyzed for nine excised porcine larynges, sampled three times each, at baseline and the two stenosis conditions. The results of this study revealed no differences in PTP based on within-subjects comparisons. Because airflow changes with airway narrowing, this finding might indicate that other factors are responsible for the voice problems associated with SGS that were not accounted for in the current mechanical model. Vocal fold tone is not easily simulated in a benchtop setup and might be an important consideration for future studies. The quantification and manipulation of vocal fold adduction, as well as the study of high-speed imaging, could be useful in future work involving excised larynx mechanical models for the study of SGS. The results from this pilot work represent an important step toward optimizing the experimental setup for studying aerodynamic features of SGS.

Although combination inhaled corticosteroids (ICs) are known to cause voice disorders in otherwise vocally healthy individuals, it is unknown whether those adverse effects can be reversed by the cessation of treatment. Quantitative aerodynamic measures such as phonation threshold pressure (PTP) and phonation threshold flow (PTF) can be used to identify the development of, and recovery from, vocal pathologies. We examined the effects and reversibility of ICs on laryngeal aerodynamics. This study was a mid-project investigation as part of a larger ongoing project. The 18 larynges were from rabbits that received ICs, a control condition, or no treatment. Experimental group rabbits received ICs twice per day until inflammatory changes (e.g., erythema, edema) became visible through endoscopic observation. One experimental group (i.e., the induction group) received treatment until symptoms were observed and then larynges were harvested. The other experimental group (i.e., the reversibility group) had ICs withdrawn once visible changes were detected via endoscopy; larynges were harvested only after these changes no longer differed from baseline. Both experimental groups had corresponding control rabbits that received twice-daily nebulized saline and followed the same withdrawal and larynx harvest schedule. A final group received no treatment. During benchtop phonation trials, PTP and PTF values were determined. All data were analyzed using descriptive and parametric statistics. No significant between-group differences were observed. Descriptively, however, average PTP and PTF values for the reversibility group were lower than the induction group. Additionally, average PTP and PTF values for the reversibility group were slightly lower than the induction group. Both experimental groups had higher PTP and PTF values than the control larynges. The results of this study indicate a trend in recovery for larynges afforded a recovery period from ICs. Further testing is needed to substantiate these preliminary findings.