Endothelial dysfunction and restenosis following percutaneous coronary intervention ☆ Panuratn Thanyasiri, Krishna Kathir, David S. Celermajer, Mark R. Adams ⁎ Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown 2050, Sydney, Australia Department of Medicine, University of Sydney, Sydney, Australia Received 14 March 2006; received in revised form 31 July 2006; accepted 2 August 2006 Available online 7 November 2006 Abstract Background: Restenosis remains an important limitation of PCI. Although local factors such as small vessel diameter and systemic factors such as diabetes explain some of its incidence, it nevertheless also occurs in low-risk patients. We hypothesize that endothelial dysfunction may be an independent risk factor in some of these cases. Methods: 20 patients who had previously undergone PCI were studied at cardiac catheterization (10 with restenotic lesions were matched to 10 without restenosis). Infusion of multiple concentrations of acetylcholine (ACh) and nitroglycerine (GTN) were made via a 3F infusion catheter into the target artery. Following infusion, changes in diameter of segments proximal and distal to the PCI site were measured. Results: There was a significant impairment in endothelium-dependent dilatation at the maximal dose of acetylcholine in those with restenosis compared to those without restenosis, both proximal and distal to the stented area (proximal; 11.5 ± 7.0% versus - 20.9 ± 9.0% p b 0.001, distal; 12.0 ± 3.1% versus - 17.8 ± 8.1% p b 0.001), but there was no difference in the response to GTN. There was a significant correlation between the endothelium-dependent dilatation response and the percent restenosis (r = - 0.65, p = 0.003). Conclusions: Coronary endothelium-dependent dilatation is reduced in subjects with restenosis in arterial segments separate from the stented lesion. This supports a hypothesis that endothelial dysfunction contributes to the development of restenosis, following percutaneous coronary intervention. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Coronary intervention; Restenosis; Nitric oxide; Endothelium 1. Introduction Restenosis following percutaneous coronary intervention (PCI) is common and continues to limit the long-term success of the procedure [1,2]. The process of “in-stent” restenosis is likely precipitated by the endothelial disruption and intimal and medial vascular injury that occurs at the time of balloon inflation [3]. This vascular injury results in exposure of the thrombogenic subendothelium, platelet and vascular smooth muscle cell activation, thrombosis, and the release of a number of growth factors that mediate VSMC migration and proliferation and the production of abundant extracellular matrix [4,5]. The vascular endothelium is responsible for the mainte- nance of the balance between the inhibition and promotion of vascular growth, vasoconstriction and vasodilation, and antithrombotic and fibrinolytic mechanisms [6]. Endothelial cell dysfunction or removal following percutaneous coro- nary intervention may influence the long-term sequelae of this procedure. Specifically, the nitric oxide pathway is an important determinant of neointimal hyperplasia after experimental angioplasty [7,8]. Loss of coronary endothelial nitric oxide production has correlates with future risk of developing coronary artery lesions and of clinical coronary events [9]. Recently it has been shown that brachial artery International Journal of Cardiology 119 (2007) 362 – 367 www.elsevier.com/locate/ijcard ☆ This work is supported in part by the National Heart Foundation, Australia. ⁎ Corresponding author. Tel.: +61 2 95156111; fax: +61 2 9550 6262. E-mail address: mark.adams@email.cs.nsw.gov.au (M.R. Adams). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.08.015