Abstract 116: Enhanced Systemic Inflammation Results in Loss of Vein Graft Lumen and Augments Adaptation to Increased Wall Shear

Abstract

Introduction: Unlike animal models which are highly reproducible, human vascular remodeling demonstrates marked heterogeneity both within and between patients. Studying human vein grafts (VG), we hypothesize that the local wall shear stress (WSS), modulated by the systemic inflammatory milieu, dictates vascular adaptation and preservation (or loss) of VG lumen. Methods: Following infrainguinal VG placement, 33 patients were evaluated with ultrasound duplex, CT scanning and computational fluid dynamic modeling (at 1 week (1w), 1 month (1m), and 6 months (6m) post-op) to determine the WSS and cross-sectional area at 1 mm intervals along the entire VG. Plasma samples were collected (pre-op, 2 hours, 1 day, 1 week, 1 month) and analyzed for 28 pro- and anti-inflammatory cytokines and chemokines. Results: Regions of reduced shear (< 5 dynes/cm 2 ) demonstrated a loss of VG lumen area in the 1w-1m (-6.5% ± 3.2%) and 1m-6m (-8.2% ± 4.8%) timeframe; elevated shear areas (> 50 dynes/cm 2 ) led to an expansion in lumen area (1w-1m: 27% ± 8%; 1m-6m: 36% ± 14%). Patients with pre- and early post-op elevations in the pro-inflammatory cytokines IL-12, -13, -15 demonstrated enhanced loss of VG lumen between 1 w and 1m ( A ). Increased levels of IL-1b, -2, -3, -4, -6 at 1 month were associated with late reductions in VG lumen area ( B ). In contrast, early elevations in MMP-9, E-selectin, and VCAM-1 were accompanied by enhanced outward remodeling, most prominently in high shear regions ( C , p<0.05). Conclusions: Human VG remodeling are highly responsive to the local WSS, and specific cytokines patterns appear to modulate this process in both early and late vein graft remodeling. Using this information, therapeutic manipulation of the peri-operative inflammatory state may be used to improve VG survival.