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Eur J Cardiothorac Surg 2005;27:302-306
© 2005 Elsevier Science NL

Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts

Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria

Received 2 September 2004; received in revised form 10 November 2004; accepted 11 November 2004.

^* Corresponding author. Tel.: +43 512 504 80820; fax: +43 512 504 22528. (E-mail: thomas.schachner{at}uibk.ac.at).

Objective: Rapamycin is an immunosuppressive agent with marked antiproliferative properties and is effective in reducing in stent restenosis and vein graft neointimal hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the role of apoptosis in rapamycin treated vein grafts in a mouse model. Methods: C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200µg of rapamycin were applied locally in pluronic gel. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL). Results: In grafted veins without treatment (controls) neointimal thickness was 50 (12–58) µm at 4 weeks postoperatively. In 200µg rapamycin treated grafts the neointimal thickness was 17 (5–55) µm. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was lower in both groups with no significant difference between rapamycin treated grafts and controls. Conclusion: We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease.

Key Words: Neointimal hyperplasia • Vein graft • Apoptosis • Bypass

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