Innovating Organ Shipment by Studying Environmental Factors which Affect Organs During Cold Preservation

Abstract: There is an urgent and critical need to innovate shipment methods for human organs. While much has been done in the last three decades to improve transplant survival rates and immunologic outcome, little has been done to understand how to optimally care for organs during shipment. As the field of transplantation

smartly rethinks organ allocation, more work needs to be done to help improve the process of organ shipment. In prior work, we questioned if on-demand organ shipment with unmanned aircraft, or drones, might improve access to transplantable organs. Organ drones may decrease CIT and improve organ availability.

During initial drone experiments, novel telemetry devices showed significant differences in the pressure, temperature, and when drone flight was compared with traditional fixed wing flight. This is particularly interesting because recent publications have revealed differences in organ transplant outcome when organs are moved by

air versus ground. Further, it is well known that low-pressure exposure from airline flight negatively impact organ function after trauma. There are no studies addressing these factors or their impact on transplantable organs. We then modeled environmental factors affecting organs in a small model of heterotopic cardiac

transplant model. We found that mid-range vibration led to reduced survival when compared with non-vibrated hearts. Explanted hearts showed increases in apoptosis and F-actin derangement. More work is needed to determine the most appropriate way to care for organs in transit and mitigate potential risks during shipment.

This proposal builds on our expertise with innovating organ shipment. We hypothesize that CIT is comprised of more than just time alone, and that environmental factors may impact graft survival. We will separate pressure, temperature, and vibration to learn how each factor individually affects transplanted organs

with the greater goal of implementing strategies to mitigate each of these risks and improve organ function. In Aim 1 we will determine, presently unmeasured, actual environmental factors that affect hearts during transport by car, helicopter, airplane, and drone. We will calculate temperature, pressure, and vibration, and

compare telemetry findings for each shipment modality. We will then assess pre-and-post shipment biopsies for changes cellular adhesion molecules (ICAM-1, VCAM-1) and cytoskeletal actin. In Aim 2, we will model these forces in an animal model of heart transplant. Donor hearts will be pre-treated with pressure, temperature, or

vibration. The primary outcome measure will be graft survival. The secondary outcome measure will be non- invasive transthoracic echocardiographic and histology for adhesion molecules and actin as in Aim 1. Here, we will learn for the first time how the environment has been affecting thousands of human organs

during shipment. We will then learn how each component of a multi-variable cold ischemia time contributes to organ function, immunological response, and graft survival. Together these findings will launch the field of organ perseveration into the next decade.