Research of "Autologous fibrin coated small caliber vascular prostheses improve the antithrombogenicity by less immunological response"

• Project/Area Number: 15591473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kobe University
• Principal Investigator: OKADA Kenji Kobe University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (90284356)
• Co-Investigator(Kenkyū-buntansha): OKITA Yutaka Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40322193)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: small caliber vascular prostheses / fibrin / CABG / autologous blood / antithrombogenicity

Research Abstract

Introduction : Development of small caliber vascular prostheses is still challenging. Recently we have developed a new technique of fibrin coatings for vascular grafts. We hypothesized that autologous fibrin coatings could improve the antithrombogenicity of grafts by less immunological response. We also examine the graft healing characteristics after implantation.
Methods : Knitted polyester fabric vascular prostheses, 2mm in internal diameter, were coated with autologous (rabbit, A-graft) or xenologous (human, X-graft) fibrin by modified ethanol method from plasma. Fifty Japanese white rabbits were implanted with the grafts in bilateral carotid arteries and divided into three groups by the selection of grafts in the individual rabbit : A&X-grafts (group I, n40), A&A-grafts (group II, n=5), X&X-grafts (group III, n=5). To evaluate graft patency, anti-graft serum antibody, ^<111>Indium platelet scintigraphy and histology, the grafts in group I were explanted on postoperative days (PODs) 1, 3, 7, 10, 14, 30, 60, 180 (n=5 for each). Serum levels of immunoglobulin G (IgG) and M (IgM), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in group II and III were measured serially to compare immunological, coagulative and fibrinolytic reactions.
Rsults : All of grafts except one X-graft on POD 10 were patent without stenosis and thrombus. Monolayer endothelial-like cells were covered on the entire surface of the A-grafts on POD 60. In group I, the maximal anti-graft serum antibodies (0.17±0.02 optical density at 490 nm [O.D.]) and the maximal platelet deposition (10.3±1.6x10^6/mm^2) in A-grafts were significantly less than those in X-grafts (0.46±0.06 O.D. and 17.4±1.4x10^6/mm^2, respectively ; p<0.0001 in both). Although serum levels of IgG, IgM, tPA and PAI-1 were increased at the time of fibrin degradation of grafts during POD 7 to 14, those in group II were significantly less than those in group III (p<0.O1, ANOVA). The PAI-1/tPA ratio in both groups was decreased as platelet deposition of the grafts was increased.
Conclusion : These findings suggest that autologous fibrin coatings improve the antithrombogenicity by less immunological response and have a potential use for hybrid small caliber vascular prostheses.