Utilization of shape memory in external vein-graft meshes allows extreme diameter constriction for suppressing intimal hyperplasia: A non-human primate.

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Utilization of shape memory in external vein-graft meshes allows extreme diameter constriction for suppressing intimal hyperplasia: A non-human primate study  Peter Zilla, MD, PhD, Michael Wolf, BSc, Nasser Rafiee, BSc, Loven Moodley, MBChB, Deon Bezuidenhout, PhD, Melanie Black, DipMedTech, Paul Human, PhD, Thomas Franz, PhD  Journal of Vascular Surgery  Volume 49, Issue 6, Pages 1532-1542 (June 2009) DOI: 10.1016/j.jvs.2009.01.068 Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 1 Mesh-constricted grafts at implantation: macroscopic appearance of the anastomotic region of reversed interposition vein grafts in the superficial femoral artery of senescent Chacma baboons. Braided Nitinol meshes were used to constrict the diameter of the vein grafts by 50% to match the size of the artery (a). By longitudinally pleating the Nitinol meshes (b) a distinct further constriction could be achieved without affecting the circumference of the vein graft. In order to prevent diameter changes of the meshes through longitudinal constriction, meshes extended across the anastomoses () and were fixed to the artery with suspension stitches. Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 2 Mesh-constricted grafts at explantation: mid sections of vein grafts externally supported by non-pleated (a and b) and pleated (c and d) Nitinol meshes. Samples represent 6 weeks (a and c) and 6 months (b and d) explants. Although all mesh-supported grafts showed thin and delicate walls, it is obvious that the wall thickness further diminished between 6 weeks and 6 months. In longitudinally opened grafts, the Nitinol mesh appears to lie directly underneath the blood surface in the 6-month explants. Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 3 Histology of mid sections of vein grafts after 6 months of implantation: The size comparison between control grafts (a and b) and mesh supported grafts (c and d) illustrates the degree of constriction achieved by the placement of the external Nitinol meshes (Elastin Masson's Trichrome stain; original magnification 40×). Compared with un-treated controls (a) fibrin glue-sprayed control grafts (b) had a slightly smaller diameter and a thicker fibrotic adventitia. In spite of the dramatic constriction, hardly any of the mesh supported grafts showed folds protruding into the lumen (c and d). Although the crowns of the pleated meshes had flattened out at 6 months, the overall star-shape of the grafts was well preserved (d). At higher enlargement, (original magnification 200×; Masson's Elastin-Trichrome stain [a1 to d1] and Movat [a2 to d2]) both control groups showed similar degrees of intimal hyperplasia (a1 and a2/b1 and b2), clearly discernable from the media by an internal elastic lamella (IEL ⇐). The blue areas in the neointima on Movat stains (a2 and b2) represent extracellular matrix areas rich in glycosaminoglykanes. In both mesh-supported groups, the compacted atrophic media borders directly on the endothelium without a neointima (c1; d1). The accumulation of densely packed elastic fibers in the adventitia of mesh-supported grafts (black) is well recognizable on Movat stains (c2 and d2). Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 4 Image-analytical measurement of neointimal thickness: while intimal hyperplasia was largely immeasurable in both mesh-supported groups (- - - non-pleated; — pleated) it was distinctly pronounced in the two control groups (– – non-treated; – – – fibrin glue-sprayed). (Means ± standard error of the mean [SEM]). Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 5 Control graft fibrosis: Picro-Sirius stains of collagen fibers in control (a) and fibrin glue-sprayed (b) vein grafts. Collagen formation was distinctly more pronounced in the fibrin glue-sprayed group (original magnification 40×). Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 6 Resin-embedded mid-graft sections: at implantation non-pleated (a and b) and pleated (c and d) Nitinol meshes measured the same inner circumference but pleated meshes had a 39% smaller cross-sectional area. Between 6 weeks (a and c) and 6 months (b and d) the walls of the vein grafts became significantly thinner due to the almost complete disappearance of the loose elastin-rich adventitial layer between media and mesh (⇐). None of the 6-months implants (b and d) and none of the pleated 6-week implants (c) showed any signs of folding in spite of the constriction leading to a more than 50% redundancy in vein wall circumference (original magnification 40×). Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions

Fig 7 Rare vein wall redundance in mesh-constricted graft: of all the implants only one mesh-constricted vein graft showed signs of longitudinal folding at 6 weeks. Interestingly, the media had undergone the same changes as in areas where it rested directly on the Nitinol mesh. While the compacted atrophied media lies directly underneath the surface endothelium, the fold contains only the loose adventitial tissue typically filling the space between media and mesh. The empty voids which contained the Nitinol struts are surrounded by fibrous issue (resin sections after de-resining; Masson's trichrome stain; original magnification 40×). Journal of Vascular Surgery 2009 49, 1532-1542DOI: (10.1016/j.jvs.2009.01.068) Copyright © 2009 Society for Vascular Surgery Terms and Conditions