HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Add to Personal Folders Download to citation manager Author home page(s): Matthew L. Williams Carmelo A. Milano Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Petrofski, J. A. Articles by Milano, C. A. Search for Related Content PubMed PubMed Citation Articles by Petrofski, J. A. Articles by Milano, C. A. Related Collections Coronary disease

J Thorac Cardiovasc Surg 2004;127:27-33
© 2004 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Gene delivery to aortocoronary saphenous vein grafts in a large animal model of intimal hyperplasia

^a Department of Surgery, Durham, NC, USA
^b Department of Medicine, Duke University Medical Center, Durham, NC, USA

Read at the Eighty-third Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 4-7, 2003.

Received for publication April 10, 2003; revisions received June 12, 2003; accepted for publication July 22, 2003.

^* Address for reprints: Carmelo A. Milano, MD, Box 3043, Department of Surgery, Duke University Medical Center, Durham, NC 27703, USA
milan002{at}mc.duke.edu

OBJECTIVE: More than 50% of aortocoronary saphenous vein grafts are occluded 10 years after surgery. Intimal hyperplasia is an initial, critical step in the progression toward occlusion. To date, no clinically relevant large animal models of aortocoronary saphenous vein graft intimal hyperplasia have been fully characterized. Gene therapy holds promise as a novel treatment for aortocoronary saphenous vein graft intimal hyperplasia. The 2 objectives of this study are to characterize a canine model of aortocoronary saphenous vein graft intimal hyperplasia and to demonstrate that ex vivo gene delivery is possible in these grafts using adenoviral vectors.

METHODS: Ten dogs underwent aortocoronary bypass grafting using saphenous veins. Six dogs underwent serial arteriograms to monitor graft patency. On postoperative day 90, the dogs were killed and their grafted and nongrafted saphenous veins were studied histologically. Four dogs underwent the same procedure, but their saphenous veins were treated with 1 x 10¹² total viral particles of a replication-deficient, recombinant adenovirus containing ß-galactosidase (n = 2) or the ß-adrenergic receptor kinase carboxyl terminus (n = 2). These animals were killed on postoperative day 7 for determination of transgene expression.

RESULTS: All grafts were demonstrated patent by arteriogram before the animals were killed. The mean intimal area of the saphenous vein grafts was increased when compared with that of the nongrafted saphenous veins (2.83 mm² vs 0.09 mm², P < .0008). Adenoviral-treated saphenous vein grafts demonstrated positive transgene expression either by X-gal staining (ß-galactosidase) or Northern analysis (ß-adrenergic receptor kinase carboxyl terminus).

CONCLUSION: This study characterizes a clinically relevant canine model of aortocoronary saphenous vein graft intimal hyperplasia. In addition, it demonstrates that adenoviral vectors can be delivered ex vivo to the saphenous vein graft vessel wall at subphysiologic distension pressures. This model may be used in future studies to manipulate molecular targets critical in aortocoronary saphenous vein graft intimal hyperplasia.

This article has been cited by other articles:

				T. Schachner, G. Laufer, and J. Bonatti In vivo (animal) models of vein graft disease. Eur. J. Cardiothorac. Surg., September 1, 2006; 30(3): 451 - 463. [Abstract] [Full Text] [PDF]

				J. A. Petrofski, J. A. Hata, M. L. Williams, C. J. Parsa, R. B. Thompson, S. I. Hanish, T. R. Gehrig, W. J. Koch, and C. A. Milano A G{beta}{gamma} inhibitor reduces intimal hyperplasia in aortocoronary saphenous vein grafts J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1683 - 1690. [Abstract] [Full Text] [PDF]

				J. A. Hata, J. A. Petrofski, J. N. Schroder, M. L. Williams, S. H. Timberlake, A. Pippen, M. T. Corwin, A. K. Solan, A. Jakoi, T. R. Gehrig, et al. Modulation of phosphatidylinositol 3-kinase signaling reduces intimal hyperplasia in aortocoronary saphenous vein grafts J. Thorac. Cardiovasc. Surg., June 1, 2005; 129(6): 1405 - 1413. [Abstract] [Full Text] [PDF]