Cellular survival in rat vein-to-artery grafts

Abstract

Microsurgical models of vein-to-artery graft surgery have been developed in rats as a means of assessing vein graft adaptation and neo-intimal hyperplasia. Neo-intimal hyperplasia in these grafts is often attributed, at least in part, to an adaptive response by venous smooth muscle cells to the increased intraluminal pressure of the arterial pressure. However, considerable evidence suggests complete or near-complete cellular replacement in these grafts. A series of experiments were undertaken in which male vein or artery grafts were placed into either allogeneic female nude rat hosts or into syngeneic WKy female hosts as a means of determining donor cell survival. Grafts were removed at postsurgery week 2 or week 6 and the fate of the donor male cells assessed by PCR amplification of the testis-determining gene Sry. The Sry gene was undetectable in 2-week male to female vein grafts. When left for 6 weeks, donor cells were detectable in vein grafts only after multiple 50-cycle PCR analyses. Minimal donor cell survival was not due to an allograft response, as donor male cells were readily detectable in WKy male to female nude rat artery-to-artery grafts. These data were not nude rat specific, as poor donor cell survival was also evidenced in syngeneic male to female vein-to-artery grafts. In conclusion, we demonstrate only marginal survival of donor cells in rat vein-to-artery grafts. Neo-intimal hyperplasia in these grafts was not a consequence of donor venous smooth muscle cell proliferation.

Murine Model of Neointimal Formation and Stenosis in Vein Grafts

“…Furthermore, the low level of arterial graft neointima/stenosis is also consistent with clinical outcomes of low stenotic risk with arterial anastomosis or grafting. [3][4][5][6] The findings of this study contrast with those of Redwood and Tennant 16 in which a lack of evidence for rat vein graft cell survival was found. These investigators used a similar cross-transplantation model, using male grafts placed into female recipients, with polymerase chain reaction analysis of DNA isolated from grafts to identify an SRY (Y chromosome) target to determine male cell presence.…”

“…Whereas the relative contribution of neointimal growth to wall thickness is small for rat, rabbit, and larger animal models, [7][8][9][10][11]16 the proximal portion of the vein graft in the current model had a stenotic area that greatly reduced the luminal area (Figure 2b), even to apparent occlusion at the anastomotic site ( Figure IIb). This finding of severe luminal stenosis at 1 month differs from the milder degrees of neointimal formation found in other vein graft models and is directly analogous to clinical graft stenotic occlusion.…”

“…[11][12][13][14][15] Studies using vein graft models have supported adjacent arterial media as a major source for neointimal cells. 7,16 Arterial and organ allotransplantation models have found that circulating progenitor cells and adjacent (recipient) arterial media are the major contributors to transplant-associated neointimal formation. 15,[17][18][19] A recent study using a murine vein graft model demonstrated that the neointimal cells within the graft arise from both the vein graft and the recipient artery.…”

Clinical Outcome of Aortic Root Replacement With Cryopreserved Aortic Valve Allografts

“…Cellular viability of grafts is important in that it preserves the long term viability of grafts [O'Brien et al, 1987], and numerous studies have addressed the status of endothelial cell viability in cryopreserved heart valves and vascular allografts [Oei et al, 2002]. The importance of preserving endothelial cell viability after cryopreservation is a matter of controversy, since there are two opposite interpretations; one being that graft endothelial cell viability is decreased after cryopreservation and also after transplantation because of depletion of donor cellular population [Armiger,1995;Mitchell et al, 1995;Neves et al, 1997;Niwaya et al, 1995;O'Brien et al,1987;Redwood and Tennant, 2001], and the other that graft cell viability is maintained to a certain degree even after cryopreservation, from morphological, metabolic, and chromosomal perspectives [Fischlein et al, 1995;Lang et al, 1994;Oei et al, 2001]. Duration of warm ischemic time (i.e., the period from cardiac arrest of the donor and retrieval of the heart valve tissues to insertion in medium with antibiotic cocktail at 4°C), differences in the graft preparation method, and the antibiotic treatment regimen, may influence the outcome.…”