Lautner-Csorba Orsolya, Gorur Roopa, Major Terry, Wu Jianfeng, Sheet Partha, Hill Joseph, Yu Minzhi, Xi Chuanwu, Bartlett Robert H, Schwendeman Steven P, Lautner Gergely, Meyerhoff Mark E
From the Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Department of Chemistry, University of Michigan, Ann Arbor, Michigan.
ASAIO J. 2025 Feb 1;71(2):177-185. doi: 10.1097/MAT.0000000000002276. Epub 2024 Jul 22.
This study presents the utilization of a novel, highly lipophilic nitric oxide (NO) donor molecule, S -nitroso-1-adamantanethiol (SNAT), for developing an NO-emitting polymer surface aimed at preventing thrombus formation and bacterial infection in extracorporeal circuits (ECCs). S -nitroso-1-adamantanethiol, a tertiary nitrosothiol-bearing adamantane species, was synthesized, characterized, and used to impregnate polyvinyl chloride (PVC) tubing for subsequent in vivo evaluation. The impregnation process with SNAT preserved the original mechanical strength of the PVC. In vitro assessments revealed sustained NO release from the SNAT-impregnated PVC tubing (iSNAT), surpassing or matching endothelial NO release levels for up to 42 days. The initial NO release remained stable even after 1 year of storage at -20°C. The compatibility of iSNAT with various sterilization techniques (OPA Plus, hydrogen peroxide, EtO) was tested. Acute in vivo experiments in a rabbit model demonstrated significantly reduced thrombus formation in iSNAT ECCs compared with controls, indicating the feasibility of iSNAT to mitigate coagulation system activation and potentially eliminate the need for systemic anticoagulation. Moreover, iSNAT showed substantial inhibition of microbial biofilm formation, highlighting its dual functionality. These findings underscore the promising utility of iSNAT for long-term ECC applications, offering a multifaceted approach to enhancing biocompatibility and minimizing complications.
本研究介绍了一种新型的、高度亲脂性的一氧化氮（NO）供体分子S-亚硝基-1-金刚烷硫醇（SNAT）的应用，旨在开发一种能释放NO的聚合物表面，以防止体外循环（ECC）中的血栓形成和细菌感染。合成并表征了含叔亚硝基硫醇的金刚烷类物质S-亚硝基-1-金刚烷硫醇，并将其用于浸渍聚氯乙烯（PVC）管材，随后进行体内评估。用SNAT浸渍的过程保留了PVC原有的机械强度。体外评估显示，经SNAT浸渍的PVC管材（iSNAT）能持续释放NO，在长达42天的时间里超过或达到内皮细胞释放NO的水平。即使在-20°C下储存1年后，初始NO释放仍保持稳定。测试了iSNAT与各种灭菌技术（OPA Plus、过氧化氢、环氧乙烷）的兼容性。在兔模型中进行的急性体内实验表明，与对照组相比，iSNAT ECCs中的血栓形成明显减少，这表明iSNAT可减轻凝血系统激活，并有可能消除全身抗凝的必要性。此外，iSNAT对微生物生物膜形成有显著抑制作用，突出了其双重功能。这些发现强调了iSNAT在长期ECC应用中的潜在效用，为提高生物相容性和减少并发症提供了多方面的方法。
