Aspirin Reduces Ischemia-Reperfusion Injury Induced Endothelial Cell Damage of Arterial Grafts in a Rodent Model

Abstract

Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a nonsteroidal anti-inflammatory drug improves the long-term patency of vein grafts. Whether aspirin has the same effect on arterial grafts is questionable. We aimed to characterize the beneficial effects of aspirin on arterial bypass grafts in a rodent revascularization model. We gave Lewis rats oral pretreatment of either aspirin (n = 8) or saline (n = 8) for 5 days, then aortic arches were explanted and stored in cold preservation solution. The third group (n = 8) was a non-ischemia-reperfusion control. Afterwards the aortic arches were implanted into the abdominal aorta of recipient rats followed by 2 h of reperfusion. Endothelium-dependent vasorelaxation was examined with organ bath experiments. Immunohistochemical staining were carried out. Endothelium-dependent maximal vasorelaxation improved, nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the aspirin preconditioned group, compared to the transplanted control group. Significantly improved endothelial function and reduced I/R injury induced structural damage were observed in free arterial grafts after oral administration of aspirin. Aspirin preconditioning before elective CABG might be beneficial on free arterial graft patency.

Zinc-aspirin preconditioning reduces endothelial damage of arterial grafts in a rodent model of revascularization

“…Our group has identified some promising drugs for this aim in experimental models ( 8 , 9 ). We have shown in a rat model that treatment with aspirin prior to arterial revascularization significantly reduced the functional and morphological damage suffered by free arterial grafts ( 10 ). As many patients take aspirin prior to CABG and there is a debate whether or not this medication should be discontinued before the operation, the findings of our experiment could be clinically highly relevant.…”

“…The rats were randomly divided into the following groups: (1) non-transplanted control group (ntCo, n = 8): rats received 1% methylcellulose vehicle, aortic transplantation was not carried out; (2) transplanted control group (tCo, n = 8): donor rats received 1% methylcellulose vehicle followed by aortic arch transplantation into the recipient rats ( n = 8); (3) aspirin group (Asp): donor rats ( n = 8) were treated with Asp (115 mg/kg), then aortic arches were transplanted into the recipient rats ( n = 8); (4) zinc-aspirin (ZnAsp) group: donor rats ( n = 8) were treated with zinc-aspirin (100 mg/kg), with subsequent aortic arch transplantation into the recipient rats ( n = 8) ( Figure 1 ). As we have hypothesized an add on effect of zinc to the already demonstrated beneficial effect of aspirin in graft protection ( 10 ), and previous results have shown that zinc-aspirin complex exerts a more beneficial effect than zinc alone against the endothelial damage-driven neointima formation ( 13 ), we have decided not to include a group with zinc treatment alone.…”

“…Aspirin and zinc-aspirin were suspended in 1% methylcellulose vehicle. The dosage of the applied substances was determined based on literature data ( 10 , 14 ).…”

“…To achieve this, some promising storage solutions ( 3 , 7 ) as well as drugs for pharmacological conditioning ( 8 , 9 ) have been identified in preclinical studies. Our research group has shown the protective effect of aspirin preconditioning on the structural and functional integrity of free arterial grafts in a rodent model of arterial revascularization ( 10 ).…”

Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation

“…The antioxidant property was also related to the ability of aspirin to enhance the transcription of genes encoding for these antioxidant enzymes (CAT, SOD) [ 126 ]. In two models of ischemia-reperfusion injury administration, aspirin led to a significant reduction in nitro-oxidative stress and an improvement of endothelial function [ 128 , 129 ]. Moreover, in one study, aspirin antioxidant properties protected from oxidative stress-induced DNA strand breaks [ 130 ].…”