Early and late effects of radiation treatment for prevention of coronary restenosis: a critical appraisal

Radiation treatment represents a new and promising approach for prevention of restenosis after coronary intervention. 1 2 Restenosis results from a complex interplay between thrombosis, vessel remodeling, and neointima formation. Although the exact contribution of each process is still debated, neointima formation has been shown to play a major role in humans after balloon angioplasty and more recently after stent implantation. It is now admitted that vessel shrinkage plays a predominant role in restenosis after catheter based coronary interventions, whereas in-stent restenosis seems exclusively caused by neointima formation. 3 4 Neointima formation results mainly from the accumulation of proliferating smooth muscle cells (SMCs) and extracellular matrix (ECM) secretion. Adventitial myofibroblast proliferation and ECM deposition may also play a role in vessel shrinkage in a way similar to scar retraction after skin injury. 5 Radiation treatment holds the promise to reduce or prevent SMC and myofibroblast proliferation and thus to interfere with vessel remodeling and neointima formation. There are currently two diVerent approaches to deliver endovascular irradiation. One is based on or sources which are positioned locally through a catheter, to deliver single doses at high dose rate in a limited period of time. The other uses radioactive stents for continuous low dose rate treatment. Both techniques have undergone extensive animal testing and initial pilot studies have confirmed the potential. However, in addition to cytoxicity, ionising radiations have a number of biological eVects that complicate the prediction of an optimal dose for restenosis prevention. In this article, we apply fundamental concepts and recent findings in radiation biology to the interpretation of the early and late consequences of radiation treatment used for restenosis prevention.