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Objective: Off-pump coronary artery bypass (OPCAB) is believed to be linked to a “hypercoagulable state” that promotes attrition of conduits with endothelial injury, e.g. saphenous vein (SV). Addressing this concern depends on establishing an exact definition of this state. Shed microparticles (MP) derived from activated platelets are a hallmark of thrombosis. To establish MP as a marker of hypercoagulability after OPCAB, we quantified MP in coronary sinus blood downstream of SV grafts placed during a pig model and human patients.
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Robert S. Poston, Junyan Gu, Seeta Kallam, James Brown.
Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Methods: Harvested porcine SV were prepared by saline distension with and without use of a syringe designed to control infusion pressure to <125 mmHg (n=8 per group) and then grafted off-pump from the aorta to the LAD. Tracts of SV from clinical patients were prepared with (n=25) and without (n=35) pressure control (according to attending preference) and used for grafting during OPCAB. Luminal tissue factor (TF) activity (chromogenic assay) and endothelial integrity (immunohistochemistry) were determined in biopsies obtained from each SV. Thirty minutes after grafting and protamine administration, porcine and human coronary sinus blood was obtained and %MP/total CD41+ events was quantified using flow cytometry. Data is presented in aggregate because of similar findings in both models.
Results: Compared to the controlled pressure group, pigs and humans that were in the uncontrolled distension group showed SV with significantly increased luminal TF activity and decreased endothelial integrity prior to grafting and CS blood with significantly increased MP levels after grafting (table). TF activity in the grafted SV showed a strong correlation with %MP in the CS (R=0.82, p<0.001).
Conclusions: The degree of SV injury during procurement, an established predictor of early graft failure after OPCAB, was directly related to the production of MP immediately after bypass grafting in our porcine and clinical models. Given the potent thrombogenecity of MP, incorporation of this marker into the protocols of future clinical trials may provide a pathophysiologically important surrogate for determining the efficacy of novel antithrombotic therapies after OPCAB.Uncontrolled distension (n=8 pigs, 35 humans) Controlled distension (n=8 pigs, 25 humans) luminal TF activity (U/cm2) 13.8±6.7 2.2±2.8* endothelial integrity 14±28 65±12* MP levels (%MP/total CD41+events) 23±4 10±6*
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