Abstract
Standard harvest and preparation of human saphenous vein (HSV) for autologous coronary and peripheral arterial bypass procedures is associated with injury and increased oxidative stress that negatively affect graft performance. In this study we investigated the global metabolomic profiles of HSV before (unprepared; UP) and after standard vein graft preparation (AP). AP-HSV showed impaired vasomotor function that was associated with increased oxidative stress, phospholipid hydrolysis and energy depletion that are characteristic of mechanical and chemical injury. A porcine model (PSV) was utilized to validate these metabolomic changes in HSV and to determine the efficacy of an improved preparation technique (OP) using pressure-regulated distension, a non-toxic vein marker, and graft storage in buffered PlasmaLyte solution in limiting metabolic decompensation due to graft preparation. Deficits in vasomotor function and metabolic signature observed in AP-PSV could be largely mitigated with the OP procedure. These findings suggest that simple strategies aimed at reducing injury during graft harvest and preparation represents a straightforward and viable strategy to preserve conduit function and possibly improve graft patency.
Highlights
The after standard preparation (AP) technique contributes to reduced viability, impaired vasomotor function, increased oxidative stress, and in vitro intimal thickening of the HSV1,4,15–17, suggesting that vein graft preparation injury prior to implantation plays in role in eliciting the ‘response to injury’
porcine saphenous vein (PSV) prepared with the optimized preparation (OP) technique maintain normal vasomotor function and viscoelastic properties suggesting that changes in vein graft preparation could reduce injury to the HSV17,18
The clinical demographic variables for the patients are typical for patients undergoing CABG procedures
Summary
The AP technique contributes to reduced viability, impaired vasomotor function, increased oxidative stress, and in vitro intimal thickening of the HSV1,4,15–17, suggesting that vein graft preparation injury prior to implantation plays in role in eliciting the ‘response to injury’. Advances in analytical technologies and bioinformatics capabilities have enabled the identification and measurement of thousands of metabolites simultaneously using targeted or untargeted “metabolomics” analyses Such analyses reflect the true functional endpoints of biological events and may plausibly establish correlations between vein graft injury and metabolic changes. There is great utility in defining the early metabolic changes in response to vascular injury Such findings may guide strategies to prevent injury during vein graft preparation. We implemented untargeted, discovery-based metabolomics analyses to identify differences between the metabolic profiles of HSV conduits that were collected before (UP) and after standard preparation (AP) from the same patients To validate these findings we utilized the porcine saphenous vein (PSV) model of vein graft preparation which allows for standardization of graft preparation approaches[17]. We characterized functional responses and compared metabolomic signatures of UP- and AP-PSV to those generated after the optimized preparation (OP)
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