Sydney Ginn
BME PhD Defense Presentation

Date: 2024-12-12
Time: 9:00-11:00
Location / Meeting Link: HSRB II N100 Seminar Room; https://emory.zoom.us/j/94864850528

Committee Members:
Rebecca Levit, MD (advisor); Michael Burke, MD; Brandon Dixon, PhD; Andres Garcia, PhD; Susan Thomas, PhD


Title: Lymphatic Impairment Following Heart Transplantation

Abstract:
Lymphatics play a role in every vascularized organ yet are often overlooked in research as a potential therapeutic target. Their ability to modulate tissue homeostasis and immune cell trafficking holds promise in influencing a variety of disease states. Heart transplantation (HTx) is particularly intriguing as the lymphatic network is severed upon donor heart excision and not surgically reconstructed. The consequence resulting from severed lymphatic vessels in transplanted hearts is unknown. This thesis aimed to address gaps in cardiac lymphatic research from both a clinical and basic science perspective. Our clinical study investigated lymphatic variations in transplant patients with and without late graft dysfunction to assess the impact of lymphatics on metrics of transplant rejection and survival. These data correlated lower lymphatic areas to higher mortality in this patient population. Our findings validate lymphatics as a promising biomarker to evaluate mortality risks or even organs prior to procurement. We believe our work will not only stimulate new avenues of research in this field, but also inspire reflection on current surgical techniques, immune suppression, and organ procurement processes. The outcomes of our clinical study motivated us to do more detailed investigations through animal modeling. We established a heterotopic abdominal heart transplant model (HAHT) to assess longitudinal changes in lymphatic vasculature after HTx and its effect on graft function and survival. These data demonstrated significant increases in lymphatic number and luminal area for extended periods of time post-HAHT and some degree of functional lymphatic drainage at day 14. The period between day 14 and 28 was identified as a critical turning point in pathologic cardiac remodeling with vast therapeutic implications. These findings improve our understanding on lymphatic adaptations after HAHT but more importantly provide a characterized platform to study induced lymphangiogenic responses intended to rescue transplant function. Understanding pathologic conditions associated with lymphatic dysfunction in HTx will provide novel therapeutic targets that enhance the longevity of donor grafts and reduce mortality among the transplant community.

Graduate Academic Office 

Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology & Emory University