Hocking Kyle M, Luo Weifeng, Li Fan Dong, Komalavilas Padmini, Brophy Colleen, Cheung-Flynn Joyce
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tenn.
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tenn.
J Vasc Surg. 2016 Jul;64(1):210-8. doi: 10.1016/j.jvs.2014.12.059. Epub 2015 Feb 19.
Injury to saphenous vein grafts during surgical preparation may contribute to the subsequent development of intimal hyperplasia, the primary cause of graft failure. Surgical skin markers currently used for vascular marking contain gentian violet and isopropanol, which damage tissue and impair physiologic functions. Brilliant blue FCF (FCF) is a nontoxic dye alternative that may also ameliorate preparation-induced injury.
Porcine saphenous vein (PSV) was used to evaluate the effect of FCF on physiologic responses in a muscle bath. Cytotoxicity of FCF was measured using human umbilical venous smooth muscle cells. Effect of FCF on the development of intimal hyperplasia was evaluated in organ culture using PSV. Intracellular calcium fluxes and contractile responses were measured in response to agonists and inhibitors in rat aorta and human saphenous vein.
Marking with FCF did not impair smooth muscle contractile responses and restored stretch injury-induced loss in smooth muscle contractility of PSV. Gentian violet has cytotoxic effects on human umbilical venous smooth muscle cells, whereas FCF is nontoxic. FCF inhibited intimal thickening in PSV in organ culture. Contraction induced by 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate and intracellular calcium flux were inhibited by FCF, oxidized adenosine triphosphate, KN-62, and brilliant blue G, suggesting that FCF may inhibit the purinergic receptor P2X7.
Our studies indicated that FCF is a nontoxic marking dye for vein grafts that ameliorates vein graft injury and prevents intimal thickening, possibly due to P2X7 receptor inhibition. FCF represents a nontoxic alternative for vein graft marking and a potentially therapeutic approach to enhance outcome in autologous transplantation of human saphenous vein into the coronary and peripheral arterial circulation.
手术准备过程中隐静脉移植物的损伤可能会导致内膜增生的后续发展,而内膜增生是移植物失败的主要原因。目前用于血管标记的手术皮肤标记物含有龙胆紫和异丙醇,它们会损害组织并损害生理功能。亮蓝FCF(FCF)是一种无毒的染料替代品,也可能改善准备过程中引起的损伤。
使用猪隐静脉(PSV)评估FCF对肌肉浴中生理反应的影响。使用人脐静脉平滑肌细胞测量FCF的细胞毒性。在器官培养中使用PSV评估FCF对内膜增生发展的影响。测量大鼠主动脉和人隐静脉对激动剂和抑制剂的细胞内钙通量和收缩反应。
用FCF标记不会损害平滑肌收缩反应,并恢复了拉伸损伤引起的PSV平滑肌收缩力丧失。龙胆紫对人脐静脉平滑肌细胞具有细胞毒性作用,而FCF无毒。FCF在器官培养中抑制了PSV中的内膜增厚。2'(3')-O-(4-苯甲酰苯甲酰基)腺苷5'-三磷酸诱导的收缩和细胞内钙通量受到FCF、氧化三磷酸腺苷、KN-62和亮蓝G的抑制,表明FCF可能抑制嘌呤能受体P2X7。
我们的研究表明,FCF是一种用于静脉移植物的无毒标记染料,可改善静脉移植物损伤并防止内膜增厚,这可能是由于抑制了P2X7受体。FCF是静脉移植物标记的无毒替代品,也是一种潜在的治疗方法,可提高人隐静脉自体移植到冠状动脉和外周动脉循环中的效果。