This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cable, D. G. Articles by Schaff, H. V. Search for Related Content PubMed PubMed Citation Articles by Cable, D. G. Articles by Schaff, H. V. Related Collections CV surgery: coronary artery disease Gene therapy

(Circulation. 1999;100:II-392.)
© 1999 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

The Role of Gene Therapy for Intimal Hyperplasia of Bypass Grafts

David G. Cable, MD; James A. Caccitolo, MD; Noel Caplice, MD, PhD; Timothy O’Brien, MD; Robert D. Simari, MD; Richard C. Daly, MD; Joseph A. Dearani, MD; Charles J. Mullany, MD; Thomas A. Orszulak, MD; Hartzell V. Schaff, MD

From the Division of Thoracic and Cardiovascular Surgery (D.G.C., J.A.C., R.C.D., J.A.D., C.J.M., T.A.O., H.V.S.), the Division of Endocrinology, Metabolism, Nutrition, and Internal Medicine (T.O.), and the Division of Cardiovascular Diseases and Internal Medicine (N.C., R.D.S.), Mayo Clinic and Mayo Foundation, Rochester, Minn.

Background—Proliferation of the intima is an early lesion of saphenous vein graft disease. Early patency rates of radial artery grafts are acceptable, but little is known about their risk of intimal hyperplasia.

Methods and Results—To develop a model of intimal hyperplasia, we incubated human saphenous veins, internal mammary arteries, and radial arteries (n=6, 8, and 10, respectively) in an organ culture with Rosewell Park Memorial Institute 1640 (30% serum) for 0, 4, 7, 10, and 14 days. Quantitative histological studies were performed, and the average intimal-to-medial (I/M) ratio was calculated for each incubation interval. After 10 and 14 days of culture, the I/M ratio increased in the saphenous veins (P=0.03, P=0.04 versus 0 day, respectively). No significant increase occurred in the I/M ratio in either the internal mammary or radial arteries. Next, the ability of adenoviral gene transfers to inhibit intimal hyperplasia in the saphenous veins was evaluated. Adenoviral-mediated gene transfer of nitric oxide synthase significantly reduced the I/M ratio at 14 days compared with vehicle (P=0.001) and virus (P=0.004) controls.

Conclusions—The human saphenous vein has a greater propensity for intimal hyperplasia than arterial grafts; the human radial artery behaves similarly to the internal mammary artery. In the future, gene therapy may augment nitric oxide synthase, limiting vein graft disease.

Key Words: gene transfer • mammary arteries • nitric oxide • organ culture • radial artery • saphenous vein