Local effects of nitric oxide supplementation and suppression in the development of intimal hyperplasia in experimental vein grafts

G. J. Fulton, M. G. Davies, L. Barber, J. L. Gray, E. Svendsen, P. O. Hagen

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The universal response of vein grafts after insertion into the arterial circulation is the development of intimal hyperplasia; smooth muscle cell proliferation and connective tissue deposition, which may be modulated in part by dysfunctional endothelial nitric oxide (NO) metabolism. This study examines the effects of single dose, local application by pluronic gel of a NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and an NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) on the formation of intimal hyperplasia. Materials: Forty New Zealand white rabbits underwent jugular vein interpostion grafting of the common carotid artery. Design: Ten animals were controls, 10 animals had the outer surface of the vein graft coated with 30% pluronic gel (2.5 ml), and 10 each were immersed for 15 min prior to insertion in Ringer lactate containing 10-3M of SNAP of L-NAME and then had their vein grafts coated with 2.5 ml of gel containing either SNAP (10-3M)) or L-NAME (10-3M), which allows for sustained delivery for up to 6 h. On the 28th post operative day, the animals were sacrificed and vein grafts were harvested for morphology by electron microscopy (SEM and TEM) and dimensional analysis by videomorphometry. Results: All vein grafts developed intimal hyperplasia. On SEM the vein grafts had a confluent layer of endothelial cells with multiple layers of smooth muscle cells representing intimal hyperplasia in TEM. There were no demonstrable morphological differences between the four groups. Local treatment with SNAP produced a significant 36% decrease in mean intimal thickness (72 ± 4 μm vs. 45 ± 4 μm; mean ± S.E.M.; p < 0.01) without a change in medial thickness compared to gel-only treated groups (58 ± 6 μm vs. 61 ± 7 μm; p = ns); medial thickness was also unchanged. Conclusion: These data confirm the protective effect of No in vascular injury and suggest that No synthase activity is either absent or reduced to such a level that further inhibition is this short time course is not relevant to the pathophysiology of vein graft intimal hyperplasia.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalEuropean Journal of Vascular and Endovascular Surgery
Volume15
Issue number4
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Keywords

  • Endothelium
  • Intimal hyperplasia
  • Morphology
  • Nitric oxide
  • Smooth muscle cells
  • SNAP
  • Vein grafts

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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