| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ann Thorac Surg 2002;74:1166
© 2002 The Society of Thoracic Surgeons
a Division of Cardiac Surgery, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4
Vein graft atherosclerosis remains a formidable problem limiting long-term effectiveness of conventional coronary artery bypass graft surgery (CABG). Developing simple and efficient strategies to effectively counter the mechanisms and mediators of vein graft atherosclerosis is an area of intense investigation. Vein graft atherosclerosis can be targeted through a number of approaches, both systemically and locally. The systemic use of drugs that modify endothelial function, attenuate platelet-endothelial cell interaction, and counter smooth muscle proliferation are routinely employed following CABG surgery; yet the patency rates of saphenous veins remain an imminent problem. This has led to a renewed interest in developing strategies to efficiently treat saphenous veins perioperatively, in the period following harvest and prior to use as an aortocoronary bypass conduit. One such approach is the "local" delivery of antiproliferative and antithrombotic molecules by adenoviral-mediated gene transfer strategies.
The present study by Chiu-Pinheiro and colleagues documents a technique for adenoviral-mediated endothelial transfection, which could assist in the clinical application of agents intended to modify vascular remodeling. They employed a limited (one hour), pressurized (75 mm Hg) exposure of canine saphenous vein grafts and were able to achieve good transfection efficiency. A similar technique has been employed by Mann and colleagues to deliver an E2F decoy to limit cell cycling after vein grafting in the leg. Although adenoviral-mediated gene transfer is well documented in a variety of experimental and clinical settings, the results of the present study are novel since they demonstrate effective adenoviral vector transfection within the time constraints of an operative procedure. This important paper marks the beginning of a series of studies, which will be performed to determine the optimal conditions for modifying the response to local vascular intervention. Studies defining the appropriate conditions as well as the optimal targets for perioperative manipulation may result in novel approaches to counter vein graft remodeling, intimal hyperplasia, thrombogenicity, and atherosclerotic failure. Future studies must focus on identifying the duration and extent of gene expression, as well as evaluating the risks adenoviral-mediated immunological reaction by the host.
Modifying the endothelial response to vascular injury has the potential to provide complete vascular resuscitation. A number of targets for modifying conduit endothelial function have been tested in small studies, and require large-scale evaluation. Some of these approaches include antagonism of the potent endothelium-derived vasoconstrictor, endothelin-1, and augmentation of the L-arginine-nitric oxide pathway with cofactors like tetrahydrobiopterin. Developing effective gene-transfer methods to locally deliver these interventions at the time of surgery may improve long-term graft resilience. Surgical techniques may be modified to change not only the endothelial responses of the conduit, but also of the recipient arteries, which may be injured by local compression in off-pump coronary surgery. Clearly, modifying the local vascular milieu will have a large impact on graft survival, and sirolimus-eluting drug stents are a testament to this fact.
Footnotes
Drs Weisel and Li disclose that they have a financial relationship with Genzyme Inc.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
