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): Gianni D. Angelini Raimondo Ascione Sudath Talpahewa Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shukla, N. Articles by Jeremy, J. Y. Search for Related Content PubMed PubMed Citation Articles by Shukla, N. Articles by Jeremy, J. Y. Related Collections Coronary disease

Ann Thorac Surg 2003;75:1437-1442
© 2003 The Society of Thoracic Surgeons

---

Original article: cardiovascular

Nitric oxide donating aspirins: novel drugs for the treatment of saphenous vein graft failure

^a Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol, United Kingdom

Accepted for publication November 22, 2002.

^* Address reprint requests to Dr Jeremy, Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol BS2 8HW, UK.
e-mail: j.y.jeremy{at}bristol.ac.uk

BACKGROUND: A new class of nitric oxide donating aspirin (NO-ASA) drugs may increase the therapeutic impact of aspirin in saphenous vein coronary artery bypass grafting (CABG) not only through the inhibition of thrombosis but also through a reduction of vasospasm and inhibition of vascular smooth muscle cell (VSMC) proliferation (effects that are inhibited by NO but not ASA). In order to test this proposal the effect of three NO-ASA drugs (NCX 4040, NCX4050, and NCX4060) on in vitro relaxation and cyclic guanosine monophosphate (cGMP) formation in the human isolated saphenous vein and the proliferation of human VSMCs was investigated.

METHODS: Saphenous vein segments were obtained from 30 patients undergoing CABG (median age, 59 years; range, 49 to 68). The effect of the NO-ASA adducts, ASA alone, and sodium nitroprusside (NO donor) were investigated on (1) relaxation of phenylephrine-stimulated contraction using an organ bath, (2) cyclic guanosine monophosphate (cGMP) formation using an enzyme-linked immunosorbent assay, and (3) the proliferation of VSMCs derived from saphenous vein using bromo-deoxyuridine (BRDU) incorporation.

RESULTS: All three NO-ASA adducts (at concentrations that inhibited responses by 50% [IC₅₀s] between 1 µmol/L and 100 µmol/L) and nitroprusside (at IC₅₀s between 0.5 and 10 µmol/L) elicited relaxation of isolated human saphenous vein, promoted cGMP formation, and inhibited VSMC proliferation whereas ASA alone (up to 100 µmol/L) had no effect on any variable.

CONCLUSIONS: These data indicate that the NO-ASA adducts by virtue of their capacity to release NO and stimulate guanylyl cyclase may be useful not only in the prevention of thrombosis following CABG but also the reduction of saphenous vein graft spasm and neointima formation.

This article has been cited by other articles:

				S. Wan, N. Shukla, G. D. Angelini, A. P.C. Yim, J. L. Johnson, and J. Y. Jeremy Nitric oxide-donating aspirin (NCX 4016) inhibits neointimal thickening in a pig model of saphenous vein-carotid artery interposition grafting: A comparison with aspirin and morpholinosydnonimine (SIN-1). J. Thorac. Cardiovasc. Surg., October 1, 2007; 134(4): 1033 - 1039. [Abstract] [Full Text] [PDF]

				D. S.R. Souza, B. Johansson, L. Bojo, R. Karlsson, H. Geijer, D. Filbey, L. Bodin, M. Arbeus, and M. R. Dashwood Harvesting the saphenous vein with surrounding tissue for CABG provides long-term graft patency comparable to the left internal thoracic artery: Results of a randomized longitudinal trial. J. Thorac. Cardiovasc. Surg., August 1, 2006; 132(2): 373 - 378.e5. [Abstract] [Full Text] [PDF]

				S. Wan, A. A. Arifi, M. C.W. Chan, J. H.Y. Yip, C. S.H. Ng, L. T.C. Chow, A. P.C. Yim, and J. Y. Jeremy Differential, time-dependent effects of perivenous application of fibrin glue on medial thickening in porcine saphenous vein grafts. Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 742 - 746. [Abstract] [Full Text] [PDF]

				T. Schachner Pharmacologic inhibition of vein graft neointimal hyperplasia J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 1065 - 1072. [Abstract] [Full Text] [PDF]

				A. Morelli, S. Filippi, R. Mancina, M. Luconi, L. Vignozzi, M. Marini, C. Orlando, G. B. Vannelli, A. Aversa, A. Natali, et al. Androgens Regulate Phosphodiesterase Type 5 Expression and Functional Activity in Corpora Cavernosa Endocrinology, May 1, 2004; 145(5): 2253 - 2263. [Abstract] [Full Text] [PDF]