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Eur J Cardiothorac Surg 2006;30:568
© 2006 Elsevier Science NL


Letter to the Editor

Reply to Schachner

Song Wan*

Division of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, PR China

Jamie Y. Jeremy

Bristol Heart Institute, University of Bristol, Bristol, UK

Received 31 May 2006; accepted 1 June 2006.

* Corresponding author. Tel.: +852 2632 2629; fax: +852 2637 7974. (Email: swan{at}cuhk.edu.hk).

Key Words: Coronary artery bypass grafting • Fibrin glue • Medial thickness • Neointima • Vein graft

We thank Dr Schachner for his interest and comments on our recent experimental findings [1]. The first facet of our study was that although initially (at 1 month), neointima formation in vein grafts was inhibited by perivenous application of fibrin glue at the time of implantation, at 4 months neointimal formation was not significantly different from controls [1]. Dr Schachner has implied that this is of no consequence. It is a widely held view that neointima formation is axiomatic in promoting vein graft failure [2]. The study therefore demonstrates that there may be a rebound effect that is manifest over the longer term. This also indicates that with acute or pulse treatments of vein grafts with fibrin glue or indeed cytostatic drugs or even gene transfer, care should be exercised when assessing effects at one month only and that potential rebound effects at later time points should be taken into account.

Secondly, Dr Schachner has also suggested that increased medial thickening but no change in luminal area in response to fibrin glue at 4 months could be perceived as a "positive remodeling" effect. We accept that medial thickening is a necessary adaptive response of saphenous vein grafts to arterial conditions and have stated so on many occasions [3,4]. However, excessive thickening of the media may be equally as deleterious as neointima formation. Since medial thickening involves the proliferation of vascular smooth muscle cells and the deposition of matrix proteins, our data at 4 months indicate that these key events are actively occurring in these vein grafts at this time point. Although we did not study effect of fibrin glue in the longer term, it is reasonable to suggest that the trend toward excessive thickening may continue. Indeed, graft thickening in man has long been recognized to become clinically significant at 12–24 months after surgery [2], that is, over more prolonged time courses. Furthermore, vein graft hyperplasia is more aggressive at the anastomoses of vein into artery grafts, sites at which fibrin glue may be applied by surgeons to prevent bleeding. Fibrin glue may be particularly deleterious at these sites by augmenting hyperplasia. Such effects are perhaps not surprising since fibrin is a potent mitogen for vascular smooth muscle cells [5].

Thus, despite the interesting views of Dr Schachner, we re-affirm our conclusions that the application of fibrin glue may elicit untoward effects on vein graft thickening that in the long term may compromise vein graft patency.

References

  1. Wan S, Arifi AA, Chan MC, Yip JH, Ng CS, Chow LT, Yim AP, Jeremy JY. Differential, time-dependent effects of perivenous application of fibrin glue on medial thickening in porcine saphenous vein grafts. Eur J Cardiothorac Surg 2006;29:742-747.[Abstract/Free Full Text]
  2. Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998;97:916-931.[Abstract/Free Full Text]
  3. Wan S, Yim A, Shukla N, Johnson JL, Angelini GD, Jeremy JY. The endothelin-1A receptor antagonist, BSF 302146, is a potent inhibitor of neointimal and medial thickening in porcine saphenous vein-carotid artery interposition grafts. J Thorac Cardiovasc Surg 2004;127:1317-1322.[Abstract/Free Full Text]
  4. Mehta D, George SJ, Jeremy JY, Bryan AJ, Newby AC, Angelini GD. External stenting reduces long-term medial and neointimal thickening in a pig model of arteriovenous bypass grafting. Nat Med 1998;4:235-239.[CrossRef][Medline]
  5. Miller DD, Karim MA, Edwards WD, Schwatrz RS. Relationship of vascular thrombosis and inflammatory leukocyte infiltration to neointimal growth following porcine coronary artery stent placement. Atherosclerosis 1996;124:145-155.[CrossRef][Medline]

Related Article

Remodeling of vein grafts after local application of fibrin glue
Thomas Schachner
Eur. J. Cardiothorac. Surg. 2006 30: 567-568. [Extract] [Full Text] [PDF]




This Article
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Right arrow Author home page(s):
Song Wan
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Right arrow Cardiac - physiology
Right arrow Coronary disease
Right arrowRelated Article


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