HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death

• Published in: International journal of molecular sciences Vol. 25; no. 4; p. 2262
• Main Authors: Saemann, Lars, Wächter, Kristin, Gharpure, Nitin, Pohl, Sabine, Hoorn, Fabio, Korkmaz-Icöz, Sevil, Karck, Matthias, Veres, Gábor, Simm, Andreas, Szabó, Gábor
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2024
• Subjects: Animals; B cells; Cardiovascular disease; Cold storage; Comparative analysis; Computer industry; coronary endothelium; Coronary vessels; Coronary Vessels - physiology; Developmental biology; donation after circulatory death; Endothelium; Genes; Heart; heart transplantation; Heart Transplantation - methods; Heart transplants; Humans; Ischemia; Kinases; machine perfusion; organ preservation; Organ Preservation - methods; Oxidative stress; Perfusion; Ribonucleic acid; RNA; Scientific equipment and supplies industry; Smooth muscle; Swine; Tissue Donors; Vein & artery diseases; United States; Massachusetts; Germany; endothelium; Custodiol; machine perfusion; heart transplantation; Custodiol-N; coronary endothelium; donation after circulatory death; Bretschneider; organ preservation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25042262

Protection of the coronary arteries during donor heart maintenance is pivotal to improve results and prevent the development of coronary allograft vasculopathy. The effect of hypothermic, oxygenated perfusion (HOP) with the traditional HTK and the novel HTK-N solution on the coronary microvasculature of donation-after-circulatory-death (DCD) hearts is known. However, the effect on the coronary macrovasculature is unknown. Thus, we maintained porcine DCD hearts by HOP with HTK or HTK-N for 4 h, followed by transplantation-equivalent reperfusion with blood for 2 h. Then, we removed the left anterior descending coronary artery (LAD) and compared the endothelial-dependent and -independent vasomotor function of both groups using bradykinin and sodium-nitroprusside (SNP). We also determined the transcriptome of LAD samples using microarrays. The endothelial-dependent relaxation was significantly better after HOP with HTK-N. The endothelial-independent relaxation was comparable between both groups. In total, 257 genes were expressed higher, and 668 genes were expressed lower in the HTK-N group. Upregulated genes/pathways were involved in endothelial and vascular smooth muscle cell preservation and heart development. Downregulated genes were related to ischemia/reperfusion injury, oxidative stress, mitochondrion organization, and immune reaction. The novel HTK-N solution preserves the endothelial function of DCD heart coronary arteries more effectively than traditional HTK.