Endothelial injury and acquired aspirin resistance as promoters of regional thrombin formation and early vein graft failure after coronary artery bypass grafting

ObjectiveThe predominant mechanism of early graft failure after coronary artery bypass grafting remains in doubt. Aspirin administered in the initial hours after coronary artery bypass grafting improves graft patency, implicating prostanoid synthesis in the pathogenesis. We hypothesized that synergy between endothelial disruption in the venous conduit and aspirin resistance would cause vein graft failure.MethodsAspirin resistance, defined by diagnostic findings on at least two of three separate assays, was serially assessed in 225 patients undergoing off-pump coronary artery bypass grafting. Endothelial cell integrity was determined in surplus segments obtained from 408 vein grafts. The deposition of intraluminal thrombin within the vein was determined by comparing serum F1.2 levels between the coronary sinus and the aorta after grafting. Intraoperative blood flow in the grafts was measured with transit-time technology, and patency was assessed with electrocardiographically gated multichannel computed tomographic coronary angiography on day 5. Aspirin was the sole antithrombotic agent used during the study.ResultsThrombosed grafts (16/408) showed more endothelial cell loss at the time of grafting than did those grafts that remained patent (10.8% ± 21.5% vs 51.4% ± 39.1% integrity, P < .01). Aspirin resistance occurred in 67 patients (30%). Graft thrombosis was associated with aspirin resistance (P < .04) and reduced endothelial integrity (P < .01). These factors coexisted in 14 of 16 grafts that failed and were associated with elevated coronary sinus F1.2 levels.ConclusionAspirin resistance and relatively compromised venous endothelial cell integrity together marked patients whose vein grafts failed within days after off-pump coronary artery bypass grafting. These observations form a basis for identifying patients at risk and developing approaches to prevent vein injury or to selectively intervene in high-risk circumstances.