INTRACORONARY LOW-DOSE BETA-IRRADIATION INHIBITS NEOINTIMA FORMATION AFTER CORONARY-ARTERY BALLOON INJURY IN THE SWINE RESTENOSIS MODEL

Background Neointima formation contributing to recurrent stenosis rema ins a major limitation of percutaneous transluminal angioplasty. Endov ascular low-dose gamma-irradiation has been shown to reduce intimal th ickening (hyperplasia) after balloon overstretch injury in pig coronar y arteries, a model of restenosis. The objective of this study was to determine whether the use of a beta-emitting radioisotope for this app lication would have similar effects and to examine the dose-response r elations with this approach. Methods and Results Normal domestic pigs underwent balloon overstretch injury in the left anterior descending a nd left circumflex and coronary arteries. A flexible catheter was intr oduced by random assignment into one of these arteries and was afterlo aded with a 2.5-cm ribbon of encapsulated (90)Strontium/(99)Yttrium so urces (Sr-90/Y, a pure beta-emitter). it was left in place for a perio d of time sufficient to deliver one of four doses: 7, 14, 28, or 56 Gy , to a depth of 2 mm. Animals were killed 14 days after balloon injury , the coronary vasculature was pressure-perfusion fixed, and histomorp hometric analysis of arterial cross sections was performed. All arteri es treated with radiation demonstrated significantly decreased neointi ma formation compared with control arteries. The ratio of intimal area to medial fracture length was inversely correlated with increasing ra diation dose: control (no radiation), 0.47; 7 Gy, 0.34; 14 Gy, 0.20; 2 8 Gy, 0.08; and 56 Gy, 0.02 (r=-.78, P<.000001). Scanning electron mic roscopy demonstrated a confluent layer of endothelium-like cells both in control and in 14 Gy-irradiated arteries. There was neither evidenc e of significant necrosis nor excess fibrosis in the media, adventitia , or perivascular space of the coronary arteries or adjacent myocardiu m in the irradiated groups. Furthermore, the exposure to the staff and the total body exposure to the pig with the beta source was a small f raction of the dose previously measured and calculated with Ir-192, a gamma-emitting radioisotope. Conclusions Administration of endovascula r beta-radiation to the site of coronary arterial overstretch balloon injury in pigs with Sr-90/Y is technically feasible and safe. Radiatio n doses between 7 and 56 Gp showed evidence of inhibition of neointima formation. A dose-response relation was demonstrated, but no further inhibitory effect was seen beyond 28 Gy. These data suggest that intra coronary gamma-irradiation is practical and feasible and may aid in pr eventing clinical restenosis.