Stent magic! The genie has escaped from the bottle.

A response to injury leading to intimal thickening and subsequent " restenosis " has limited the clinical eYciency of percutaneous coronary interventions ever since they have been used to treat symptomatic coronary artery disease. During the recent two decades a lot has been learned about the pathophysiology of the response to injury following different kinds of interventions. The predominant mechanism is activation of cells within the arterial wall, the adventitial layer, and the blood, namely arterial smooth muscle cells, fibroblasts, endothelial cells, monocytes, lymphocytes, and leucocytes. Once activated by arterial injury, most of these cells will undergo a change of phenotype and express a variety of growth factors and hormones leading to complex interactions, which result in cellular migration and proliferation. As a result, much research has focused on modulation or inhibition of cell proliferation and, although some compounds were eVective in animal models, they were not successful in human restenosis trials. One explanation for this failure is a lack of appropriate animal models, with species related specific diVerences in cell activation and cellular responses, which negates comparison with human atherosclerotic coronary arteries. Nevertheless, we have learned from this experimental work that the response to injury is rather specific for each kind of injury. The time course might be quite diVerent—for example, a short burst of proliferation ensues after conventional balloon angioplasty, while a long lasting proliferative response is induced by implantation of metallic stents. Multiple attempts had been made to ameliorate the arterial response to injury by using diVerent mechanical techniques for ablating or debulking atherosclerotic tissue before dilatation of the vessel was performed. Although attractive in theory, these techniques, like excimer laser angioplasty and directional or rotational atherectomy, have not influenced restenosis rates and hence have not led to a major change in practice in the interventional catheterisa-tion laboratories. By contrast, a technique which has had a tremendous impact during recent years is the implantation of stents, despite the well known experimental data showing , in nearly all animal species, that no other technique is better at provoking a response to injury and neointimal thickening. Vessel wall response to stenting The arterial vessel wall response following stent implanta-tion is predominantly a result of exaggerated cellular migration, proliferation, and expression of extracellular matrix constituents by vascular smooth muscle cells. Once it has occurred, this process is diYcult to reverse, not only in experimental animals models but also in human …