Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, University of Florida, Gainesville, FL 32611, USA.
Alucent Biomedical Inc., Salt Lake City, UT 84108, USA.
Int J Mol Sci. 2023 Apr 20;24(8):7571. doi: 10.3390/ijms24087571.
Rates of arteriovenous fistula maturation failure are still high, especially when suboptimal size veins are used. During successful maturation, the vein undergoes lumen dilatation and medial thickening, adapting to the increased hemodynamic forces. The vascular extracellular matrix plays an important role in regulating these adaptive changes and may be a target for promoting fistula maturation. In this study, we tested whether a device-enabled photochemical treatment of the vein prior to fistula creation facilitates maturation. Sheep cephalic veins were treated using a balloon catheter coated by a photoactivatable molecule (10-8-10 Dimer) and carrying an internal light fiber. As a result of the photochemical reaction, new covalent bonds were created during light activation among oxidizable amino acids of the vein wall matrix proteins. The treated vein lumen diameter and media area became significantly larger than the contralateral control fistula vein at 1 week ( = 0.035 and = 0.034, respectively). There was also a higher percentage of proliferating smooth muscle cells in the treated veins than in the control veins ( = 0.029), without noticeable intimal hyperplasia. To prepare for the clinical testing of this treatment, we performed balloon over-dilatation of isolated human veins and found that veins can tolerate up to 66% overstretch without notable histological damage.
动静脉瘘成熟失败的发生率仍然很高，特别是在使用非最佳尺寸静脉时。在成功成熟过程中，静脉经历管腔扩张和中膜增厚，以适应增加的血流动力学力。血管细胞外基质在调节这些适应性变化中起着重要作用，可能是促进瘘成熟的靶点。在这项研究中，我们测试了在创建瘘之前使用设备对静脉进行光化学处理是否有助于成熟。使用涂有光活化分子（10-8-10 二聚体）和内置光纤的球囊导管对羊头静脉进行处理。作为光化学反应的结果，在光激活期间，在血管壁基质蛋白的可氧化氨基酸之间产生了新的共价键。与对侧对照瘘静脉相比，处理后的静脉管腔直径和中膜面积在 1 周时明显增大（=0.035 和=0.034）。处理后的静脉中增殖的平滑肌细胞也多于对照静脉（=0.029），而内膜增生不明显。为了准备对这种治疗方法进行临床测试，我们对离体人静脉进行了球囊过度扩张，发现静脉可以耐受高达 66%的过度拉伸而不会造成明显的组织学损伤。
