Photochemically Aided Arteriovenous Fistula Creation to Accelerate Fistula Maturation

Abstract

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 (p = 0.035 and p = 0.034, respectively). There was also a higher percentage of proliferating smooth muscle cells in the treated veins than in the control veins (p = 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.

Building a Scaffold for Arteriovenous Fistula Maturation: Unravelling the Role of the Extracellular Matrix

“…Less collagen deposition was observed, although not significant, and the collagen fibres were organised more perpendicular [ 145 ], which seems favourable in AVFs [ 106 ]. The same treatment was also tested in sheep after cephalic veins were dilated through a balloon catheter [ 146 ]. This led to an increase in wall thickness and luminal diameter.…”

Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance

“… c Goldstone et al 75 ; Salinas et al 76 ; Goldstone et al 77 ; Goldstein et al 78 . d Shiu et al ( 79 ); He et al ( 80 ). e Arbanasi et al ( 81 ).…”

“…It was also surmised that the changes detected in the structure of native collagen might have a beneficial effect on AVF maturation. In a recent in vivo study ( 80 ), the method was applied to sheep cephalic veins using a balloon catheter coated with the photosensitizer and carrying a light fiber through which 450-nm radiation was delivered. The resulting luminal area was larger in the treated animals, where an increased number of SMCs was also observed, without noticeable NIH.…”

“…It can be seen from the above overview (and also shown in Table 1 ) that three of the methods developed to inhibit NIH in venous grafts are relying on the mechanical reinforcement of the venous wall induced by photochemical crosslinking of tissular collagen, while exposed either to visible radiation, like in PTP ( 75 – 78 , 104 ) or Alucent technique ( 79 , 80 ), or to UV-A radiation, like in adventitial crosslinking method ( 81 ). The underlying hypothesis was that the reduction of vascular compliance in the venous component (equivalent to the increase of its stiffness), intended to also reduce the compliance mismatch between the two different conduits, lowers the risk of endothelial injury induced by an abnormal distension of the vein following its grafting to an artery.…”