The correlation of early flow disturbances with the development of infrainguinal graft stenosis: A 10-year study of 341 autogenous vein grafts

AbstractPurpose: Although duplex surveillance of infrainguinal bypass grafts is widely accepted, the optimal frequency and intensity of graft surveillance remains controversial. Earlier reports have suggested that grafts can be stratified into high-risk and low-risk groups based on the presence or absence of early graft flow disturbances. The purpose of this study was to provide long-term data in determining whether early graft flow disturbances detected by means of duplex scanning can predict the development of intrinsic vein graft stenosis. Methods: We reviewed a series of patients undergoing prospective duplex graft surveillance after autogenous infrainguinal bypass grafting procedures from 1987 to 1997. Patients included in the study underwent at least one duplex scan within 3 months of graft implantation and were observed for a minimum of 6 months. Grafts were categorized as abnormal when a focal flow disturbance with a peak systolic velocity greater than 150 cm/s was identified within 3 months of graft implantation. Results: Of 341 vein grafts in 296 patients who met inclusion criteria, 89 grafts (26%) required revision for intrinsic stenosis; the mean follow-up period was 35 months (range, 6 months to 10 years). Early flow disturbances were detected in 84 (25%) grafts. Grafts with early flow disturbances were more likely to ultimately require revision (43% vs 21%; P = .0001) and required initial revision earlier (8 months vs 16 months; P = .019). Eighty-two percent of initial graft revisions occurred in the first 2 postoperative years; 69% occurred in the first year. However, an annual 2% to 4% incidence of late-appearing graft stenosis persisted during long-term follow-up. An additional 24 patients (7% of grafts) required an inflow or outflow reconstruction. Conclusion: Grafts with early postoperative flow disturbances detected by means of duplex scanning have nearly three times the incidence of graft-threatening stenosis and an earlier requirement for revision, when compared with normal grafts. This suggests that the biology and etiology of these lesions may differ. These data support not only aggressive efforts to detect early graft lesions to stratify grafts at highest risk, but also continued lifelong graft surveillance to detect late-appearing lesions, inflow and outflow disease progression, and maximize graft patency. (J Vasc Surg 1999;30:8-15.

Temporal Network Based Analysis of Cell Specific Vein Graft Transcriptome Defines Key Pathways and Hub Genes in Implantation Injury

Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC) and medial smooth muscle cells (SMC) from canine vein grafts, 2 hours (H) to 30 days (D) following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12–24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1) signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR) as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1), a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention

Arterial flow induces changes in venous endothelium which are modified by calcium channel blockers

Introduction: adaptation of saphenous vein to arterial flow may be critical to the results of bypass. The present paper summarizes work recently presented as a Hunterian Lecture. Work includes in vitro investigation of the response of saphenous vein endothelium to arterial flow and assessment of its clinical importance using a cohort of patients undergoing vein bypass surgery.\ud \ud Methods: freshly excised human saphenous vein segments were placed in an in vitro flow circuit to simulate arterial and venous flow conditions. Changes in the endothelial expression of proteins were assessed using a combination of immunohistochemistry and Western blotting. The role of ion channels in the changes seen induced by arterial flow in the saphenous vein endothelium was assessed by addition of ion channel blocking medication to the medium perfusing vein segments. A cohort of patients undergoing vein bypass surgery were followed to assess graft patency and the influence of prescribed medication on its outcome.\ud \ud Results: after arterial flow conditions, the staining area for the endothelial adhesin ICAM-1 and nitric oxide synthase were increased, while that of the anticoagulant protein thrombomodulin was decreased. The concentration of the important stimulant of the clotting cascade tissue factor was unaffected by arterial flow. These changes were modulated by the addition of ion channel blocking drugs to the vein perfusate. In particular, nifedipine abolished the reduction in thrombomodulin, but increased the amount of tissue factor. In a series of 236 patients undergoing primary infra-inguinal vein grafts, prescription of calcium channel blocker was associated with improved primary patency.\ud \ud Conclusions: important changes in the venous endothelium are induced by arterial flow. Ion channel blocking drugs have the potential to modulate these responses