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J Thorac Cardiovasc Surg 2007;133:1268-1276
© 2007 The American Association for Thoracic Surgery

Evolving Technology

Autologous fibrin-coated small-caliber vascular prostheses improve antithrombogenicity by reducing immunologic response

Tomomi Hasegawa, MD, PhD, Kenji Okada, MD, PhD*, Yoshihito Takano1, Yoshiaki Hiraishi1, Yutaka Okita, MD, PhD

Division of Cardiovascular, Thoracic, and Pediatric Surgery, Department of Cardio-Pulmonary and Vascular Medicine, Kobe University Graduate School of Medicine, Kobe, and R & D Center, Terumo Corporation, Kanagawa, Japan.

Received for publication June 3, 2006; revisions received December 14, 2006; accepted for publication December 18, 2006.

* Address for reprints: Kenji Okada, MD, PhD, Division of Cardiovascular, Thoracic, and Pediatric Surgery, Department of Cardio-Pulmonary and Vascular Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Objective: We have recently developed a thrombin-free fibrin-coated vascular prosthesis that has a high performance rate in producing graft antithrombogenicity. We hypothesized that autologous, compared with xenologous, fibrin coatings could improve the antithrombogenicity of grafts by reducing immunologic response.

Methods: Autologous fibrin-coated vascular prostheses and/or xenologous fibrin-coated vascular prostheses (internal diameter, 2 mm; length, 2.5 cm) were implanted in the bilateral carotid arteries of 50 Japanese white rabbits. They were classified into 2 groups by the selection of grafts in the individual: group I (autologous fibrin-coated vascular prosthesis and xenologous fibrin-coated vascular prosthesis); and group II (group IIa: both autologous fibrin-coated vascular prostheses, or group IIx: both xenologous fibrin-coated vascular prostheses). During a maximum of 180 days after implantation, we evaluated the thrombotic, inflammatory, and immunologic responses associated with both types of graft.

Results: All grafts were patent at each end point. In group I, both platelet deposition and anti-graft antibodies in autologous fibrin-coated vascular prostheses were significantly less than those in xenologous fibrin-coated vascular prostheses until postoperative day 30. At postoperative day 10, there were significantly fewer CD45-positive infiltrating cells in autologous fibrin-coated vascular prostheses, and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and nuclear factor-kappa B expression in autologous fibrin-coated vascular prostheses were less than those in xenologous fibrin-coated vascular prostheses. The neointimal hyperplasia in autologous fibrin-coated vascular prostheses was significantly decreased at postoperative day 180. In group II, serial changes of serum levels of immunoglobulin M, immunoglobulin G, interleukin-1ß, and tissue-type plasminogen activator/plasminogen activator inhibitor-1 ratio in autologous fibrin-coated vascular prostheses were significantly less than those in xenologous fibrin-coated vascular prostheses. In both grafts, platelet deposition significantly correlated with serum immunoglobulin G level and tissue-type plasminogen activator/plasminogen activator inhibitor-1 ratio.

Conclusion: These findings suggest that autologous fibrin coating in thrombin-free fibrin-coated vascular prostheses improve antithrombogenicity by reducing immunologic response and have a potential for clinical use in hybrid small-caliber vascular grafts.

Abbreviations and Acronyms ACD = acid-citrate-dextrose; A-graft = autologous fibrin-coated vascular prostheses; ANOVA = analysis of variance; ELISA = enzyme-linked immunosorbent assay; ICAM-1 = intercellular adhesion molecule-1; NCS = newborn calf serum; NF{kappa}B = nuclear factor-kappa B; PAI-1 = plasminogen activator inhibitor-1; PBS = phosphate-buffered saline; POD = postoperative day; SEM = scanning electron microscopic; tPA = tissue-type plasminogen activator; VCAM-1 = vascular cell adhesion molecule-1; X-graft = xenologous fibrin-coated vascular prostheses






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