P141. Multi-omics Analysis of Coronary Sinus Blood at Reperfusion to Characterize Donor Heart Metabolism and Early Graft Injury
University of Colorado Anschutz Medical Center
Aurora, CO
United States - Contact Me
Dr. Bo Chang Wu is a General Surgery Resident at University of Colorado with a passion for pursuing cardiothoracic surgery training. Dr. Wu earned his medical degree from Fu-Jen Catholic University School of Medicine in Taiwan and completed an internship at National Taiwan University Hospital. Following his academic success, Dr. Wu embarked on a journey of rigorous training and learning. He first participated in esophageal cancer research with Johns Hopkins Bayview surgical research team and subsequently received two years of general surgery training at Johns Hopkins Hospital. He has joined the aortic surgery research team at the University of Colorado since 2023.
Dr. Wu's dedication to advancing the field of cardiothoracic surgery is further exemplified by his broad research plans focusing on reducing the complications associated with cardiac and aortic surgery during the academic time of residency. Notably, Dr. Wu is a recipient of the prestigious Stimulating Access to Research in Residency (StARR) R38 award, a testament to his potential to make significant contributions to the field.
Description
Methods: Adult heart transplant recipients undergoing either DBD or DCD transplantation were enrolled. Coronary sinus blood (CSB) was collected to capture metabolites reflective of myocardial metabolism at time of graft implantation. Samplels were processed using standardized protocols and analyzed by institutional metabolomics and lipidomics core using mass-spectrometry based profiling. DCD samples were further stratified by NRP vs EVMP. Data were pre-processed, normalized, and analyzed using partial least-squares discriminant analysis (PLS-DA) to assess clustering by donor type and recovery method. Variable importance in projection (VIP) scores identified key metabolites and lipid species contributing to group discrimination.
Results: 29 CSB samples were analyzed (16 DCD, 13 DBD). Among 9 DCD donors, there were 9 NRP and 7 EVMP donors. PLS-DA demonstrated clear metabolic separation between DCD and DBD profiles in metabolomics and lipidomics datasets. Variable importance in projection (VIP) scores identified key metabolites driving this distinction. Compared with DBD grafts, DCD grafts showed lower levels of included D-arabitiol/xylitol/ribitol (DC 0.54, p<0.01), L-glutamine (FC 0.67, p<0.01), thymidine (FC 0.48, p<0.01), L-arginine (FC 0.55, p=0.006), markers linked to energy metabolism, cellular repair, and nitric oxide synthesis. DCD grafts also showed higher levels of mannitol/sorbitol/glucitol/iditol (FC 12.53, p<0.01), associated with oxidative stress during reperfusion.
Lipidomic analysis revealed significant changes in triglycerides and fatty acid species, including TG(22:1_16:0_18:0) (FC 0.42, p<0.05) and FA(20:1)(FC 1.51, p<0.05).
Within the DCD cohort, multivariate modeling with PLS-DA showed distinct clustering between NRP and EVMP grafts. Discriminatory metabolites included D-rhamnose (FC 0.012, p<0.001) and DG(P-6:0_16:0) (FC 0.35, p<0.001), reflecting divergent reperfusion metabolism between groups.
Conclusion: Distinct metabolomic and lipidomic profiles were observed in DCD compared to DBD, and NRP vs EVMP. Metabolic profiling at time of reperfusion may enable identification of at-risk grafts and guide optimization of recovery.
Authors
Elizabeth Bashian (1), Sariah Hyacinth (2), Nicholas Teman (3), Michael Cain (4), Benjamin Kopecky (2)
Institutions
(1) University of Colorado Anschutz Medical Center, Aurora, CO, (2) University of Colorado Anschutz Medical Campus, Aurora, CO, (3) University of Colorado School of Medicine, CO, (4) University of Colorado Hospital, Denver, CO