Preservation of Arterial Grafts with Duragraft Alleviates Endothelial Dysfunction in a Rat Model of Bypass

Background: Ischemia/reperfusion injury (IRI) is the main contributor to failure of vascular graft during bypass surgery, causing endothelial dysfunction and leading to an enhanced rate of unfavorable early and late complications. DuraGraft has been shown to preserve structural viability and integrity of saphenous vein grafts during ischemia. We tested the hypothesis that Duragraft protects arterial grafts against IRI in a rat model of aortic transplantation (TX).

Method: Male Lewis rats (n = 9/group) were divided into control, TX + placebo, and TX + Duragraft groups. While the aortic arches of the control group were harvested and immediately mounted in organ baths, those of TX + placebo and TX + Duragraft groups were stored for 1 hour either in saline or Duragraft, then transplanted into the abdominal aorta of the recipients. One hour after transplantation, the implanted grafts were explanted and mounted in organ bath chambers. Endothelium-dependent vasorelaxation to acetylcholine (ACh) was studied ex vivo. The expression of 88 genes was analyzed using polymerase chain reaction (PCR) array and immunohistochemistry was performed.

Results: Impaired maximal relaxation (Rmax) to ACh in the TX + placebo group compared with controls was significantly ameliorated in the TX + Duragraft aortic rings (control 89 ± 2%; TX + placebo 24 ± 1%; TX + Duragraft 48 ± 1%, p < 0.05), indicating an improvement in endothelial function. According to the PCR array analysis, TX altered the expression of 25 genes compared with controls and mRNA expression of bad, caspase-8, and jun were upregulated in the TX + Duragraft compared with TX + placebo group. Furthermore, increased immunoreactivity of intercellular adhesion molecule-1 (score: control 1.5 ± 0.2, TX + placebo 8.2 ± 0.5, TX + Duragraft 2.9 ± 0.2, p < 0.001), 4-hydroxy-2-nonenal, an indicator of oxidative stress (score: control 1.7 ± 0.2, TX + placebo 7.9 ± 0.5, TX + Duragraft 4.2 ± 0.4, p < 0.05), caspase-3 (score: control 1.7 ± 0.3, TX + placebo 4.8 ± 0.8, TX + Duragraft 2.6 ± 0.4, p < 0.001), and caspase-8 (score: control: 1.1 ± 0.3, TX + placebo 8.3 ± 0.5, TX + Duragraft 2.3 ± 0.3, p < 0.001) in the TX + placebo group compared with controls, were significantly decreased in the TX + Duragraft aortic rings.

Conclusion: Preservation of arterial grafts with Duragraft alleviates endothelial dysfunction following IRI in a rat bypass model. Duragraft can exert its protective effects, at least in part, by lowering inflammatory response, oxidative stress, and apoptosis.

Publication History

Article published online:
03 February 2022