Candidate Biomarkers YES1, Troponin I, Lactate, and Ammonia for Evaluation of Cardiac Function Post Hypothermic Oxygenated Perfusion

Abstract

Hypothermic oxygenated perfusion (HOPE) is a promising method for donor heart preservation, but the hypothermic conditions reduce metabolic activity, making cardiac evaluation challenging, and necessitating prognostic biomarkers to monitor graft quality. This study aims to identify biomarkers during HOPE that predict cardiac function. Seven porcine slaughterhouse hearts underwent 4 hours of HOPE followed by 4 hours of normothermic machine perfusion (NMP) with continuous functional assessment, including measurements of cardiac output (CO), cardiac index (CI), coronary flow (CF), coronary flow index (CFI), left ventricular pressure (LVP), left atrial pressure (LAP), and mean aortic pressure (MAP). Perfusate samples collected at baseline and after 4 hours of HOPE were analyzed for damage markers. Correlations were found between ammonia and CI (r = 0.86), troponin I and CI (r = 0.79), and lactate and CFI (r = -0.81). Mitochondrial and nuclear cell-free DNA decreased during HOPE but did not correlate with function. Olink data indicated that tyrosine-protein kinase Yes (YES1) was negatively correlated with CI (r = -0.86), CF (r = -0.79), and CFI (r = -0.86). These findings suggest YES1, troponin I, ammonia, and lactate as potential prognostic biomarkers during HOPE that may predict cardiac function post-reperfusion, warranting further research to validate their translational potential.