title: Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting.
abstract: OBJECTIVE
  Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting.
  
  
  METHODS
  Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C-C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P < 0.01).
  
  
  CONCLUSIONS
  Perivenous application of α-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Longsheng
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Chengxiong
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China heartyuyang@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000601:surgery; D003487:Cyanoacrylates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D007601:Jugular Veins / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D014014:Tissue Adhesives / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects* / Q000473:pathology; D058017:Vascular Grafting / Q000379:methods
chemical_list: D003487:Cyanoacrylates; D014014:Tissue Adhesives
keywords: Cyanoacrylate; Intimal and medial thickening; Perivenous support; Vein graft failure