New Frontiers in Interventional Cardiology

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Abstract
Any antirestenosis therapy under consideration must contend with the two basic mechanisms of vessel renarrowing following coronary intervention.1 The first renarrowing mechanism is vascular contraction, which can be mechanically blocked with a typical balloon expandable stent. The second renarrowing mechanism, neointimal proliferation, is a complex cellular reaction to the injury caused by the actions of mechanical devices such as balloons, stents, and atherectomy catheters. The search for an effective antiproliferative agent has been long and frustrating. Over 100 drugs and devices have been tested resulting in preclinical or clinical failures.2 This legacy of previous failures has made the recent successes of radiotherapy particularly gratifying. The treatment of restenosis with vascular radiation appears to work through inhibition of smooth muscle cell proliferation. The energy emitted from an active isotope is believed to block mitosis by causing a double-stranded break in the cell’s DNA (Figure 1).3,4 Thus, by performing surgery on the vascular smooth muscle cell’s DNA, radiation prevents the proliferative ingrowth of tissue that often reblocks the vessel lumen after a successful angioplasty. The United States Food and Drug Administration’s recent premarket approval of two radiation devices has now propelled this first effective antiproliferative treatment into the mainstream of patient care. This report provides an overview of the basic laboratory and clinical data supporting the effectiveness of brachytherapy as well as some of the challenges and controversies surrounding its integration into clinical practice. Figure 1. Diagram of single- and double-stranded DNA breaks caused by radiation. A, Two-dimensional representation of the normal DNA double helix. B, A break in one strand is of little significance because it is readily repaired using the opposite strand as a template. C, Breaks in both strands, while separated, are repaired as independent breaks (from Eric J. Hall). A fundamental component of any …