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J Thorac Cardiovasc Surg 2008;135:1245-1246
© 2008 The American Association for Thoracic Surgery
Invited Commentary |
Dr Ishii. Regarding the endothelialization, in the SEM variations we can see it occurring beautifully inside the graft wall. When compared with a non-sirolimus graft, sirolimus might therefore facilitate good endothelialization. However, although both heparin and heparin-sirolimus grafts had a 100% patency rate during the 6 months after surgery, the heparin-sirolimus grafts showed less neointima formation than the heparin grafts.
Dr Poston. Maybe it is not just understood how that works. The second question is related to your model. The main concern that people have regarding the use of small prosthetic grafts as bypass conduit for the heart would be acute thrombosis. Your control grafts in your model didn't acutely thrombose, even the PTFE graft without heparin. So do you think that this model is adequately testing the key limitation of these grafts?
Dr Ishii. Actually you are right. This is a good question, Dr Poston. We didn't see any acute thrombosis in either the control grafts without drugs or in the heparin and sirolimus grafts. However, half of the ePTFE grafts in this study occluded during the 6 months after surgery. When compared with our microporous polyurethane grafts, the ePTFE grafts showed less endothelialization. As I showed you with the SEM data, out of all the grafts the heparin-sirolimus grafts had the most beautiful layer of endothelial cells.
Dr Beat H. Walpoth (Geneva, Switzerland). I think what are you doing is a bit controversial. Our series on rapamycin-treated grafts was published in the European Journal of Cardiothoracic Surgery in 2000, and we showed that there is a significant reduction of intimal hyperplasia. I think your data were not significant. In addition, we had no endothelialization; we had much more thrombus formation. So this goes along with what is now seen in the drugeluting stents. In medicine, everything is a question of dosage. I am not sure if eventually your dosage was not potent enough to achieve this goal. Anyhow, they are some interesting results.
Dr Valavanur Subramanian (New York, NY). Just a brief comment to bring you up to date. There are drug-eluting wraps around the grafts that have already been in clinical use in arteriovenous fistula. Our colleagues in endovascular cardiology have now taken a different form of wrap around the distal anastomosis with a PTFE or saphenous vein graft. The first feasibility trial will soon be done in coronary bypass grafts pretty, and the 6-month patency in the arteriovenous fistula has been excellent. So there is already a clinical movement on this approach.
Dr Cliff Choong (Cambridge, United Kingdom). Do you have any data on longer-term results, and are you planning to do any long-term experimental studies?
Dr Ishii. Actually this is just a preliminary rabbit model. We don't have any longer-term data yet. As you mentioned, we should do a larger animal study and longer-term study before attempting any clinical applications. We are planning that now.
Related Article
J. Thorac. Cardiovasc. Surg. 2008 135: 1237-1246.
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