Dr. Rudolph L. Gleason (Advisor) - Department of Mechanical Engineering, GT
Dr. J. Brandon Dixon (Co-Advisor) - Department of Mechanical Engineering, GT
Dr. J. Alexander Alexeev - Department of Mechanical Engineering, GT
Dr. J. Wei Sun - Department of Biomedical Engineering, GT
Dr. David C. Zawieja - Department of Medical Physiology, Texas A&M
Mechanically Mediated Growth and Remodeling of Collecting Lymphatic Vessels
Lymphatic dysfunction plays a key role in pathologies such as immune disorders, infection, cancer, obesity, and cardiovascular disease; regarding the latter, lymphatic dysfunction may exacerbate edema in myocardial infarction (MI) and chronic heart failure. Secondary lymphedema is a progressive and debilitating disease characterized by fluid retention and tissue swelling that arises due to dysfunction in lymphatic pumping. Secondary lymphedema is a common complication in breast cancer treatment where the surgical removal of lymphatic vessels/lymph nodes can induce overloads that triggers lymphatic pathologies that can present months or even years after surgery. Although the local mechanical environment is known to regulate lymphatic function, the role of sustained mechanical overloads (e.g., high pressure and high flow) in lymphatic dysfunction has yet to be established. Towards this end, our long-term goal was to develop a mechanistic understanding of mechanically-mediated growth and remodeling (G&R) of collecting lymphatic vessels in health and disease and to ultimately identify novel therapeutic interventions to minimize the risk of occurrence, severity, or complications of lymphatic dysfunction. This PhD thesis focuses on developing a novel rat tail model to study lymphatic G&R and to employ a combined experimental-computational approach to quantify the modes by which sustained high pressure and high flow compromise the normal function of the lymphatic system via maladaptive remodeling. First, we introduced and used a novel rat tail model to study the effect of mechanical loads (specifically axial stretch) on the lymphatic contractility. Second, we developed a computational framework to study lymphatic pumping in the context of a lymphangion chain. Third, we developed and tested the feasibility of a novel lymphatic ligation model to study lymphatic remodeling post-surgery. Lastly, the methods and results from this study can pave the way for future studies of lymphatic remodeling in health and disease.