Determining the Etiologies for Post-Operative Xenotransplanted Porcine Cardiac Growth

Abstract

The shortage of donor organs is a major challenge in healthcare, with over 100,000 patients on the national transplant waiting list in the United States alone. Xenotransplantation, the transplantation of animal organs or tissues into humans, is a promising approach to address this issue. However, this innovative field also raises technical challenges, such as incongruencies in organ growth in the donor and the recipient, resulting in organ failure within 1 month after the surgery. Pig hearts have been a promising organ to use, but it has been shown that their hearts continue to grow at alarming rates in recipients. Cardiac growth is concerning as the organ will outgrow the recipient’s chest cavity, resulting in consequential compression complications and a lower survival rate. Certain exposures to the pig heart, such as hypertension and a functioning growth hormone pathway, predispose the heart to hypertrophy, resulting in failed transplantation. The objective of this project is to explore a multifactorial explanation for observed post- transplant cardiac hypertrophy, focusing on the effects of an intact growth hormone receptor (GHR) and hypertensive conditions. We retrospectively analyze telemetry and ultrasound data of six baboons and their corresponding transplanted hearts: two have received hearts with a 9-gene modification and intact GHR; four have received hearts with a 10-gene modification and GHR knockout (GHRKO)