The Effect of External Beam Radiation on Neointimal Formation in the Rat Carotid Injury Model

Abstract

Background : Restenosis after successful percutaneous transluminal coronary angioplasty remains a major obstacle to the long-term success of the procedure. Uncontrolled proliferation and extracellular matrix synthesis in response to mechanical injury are important contributors to this process. External beam radiation or gamma radiation affects self-renewing tissues by arresting cell division, and therefore limits proliferation by reducing the number of clonal progenitors. The purpose of this study was to determine whether external beam radiation(EBR) could reduce the extent of neointimal formation after balloon injury in the rat carotid injury model and, if it could, to define the minimum effective dose.

Method : 32 Sprague-Dawley rats(mean weight : 370±78g) underwent carotid injury by using 2F Fogarty balloon and EBR with doses ranging from 5 to 20 Gy. Rats were sacrificed after 2 weeks. The arteries were perfusion-fixed in paraformaldehyde. EBR was performed with 6 MeV electrons in a field of 3 x 5cm using a linear accelerator. The dose was specified to a depth of 15mm. Histomorphometry was performed to compare external elastic lamina(EEL) area(mm2), lumen area(mm2) and neointimal area(mm2) of the injured segments.

Results : EEL area showed no significant difference in each different radiation group. Low dose EBR(5 Gy and 10 Gy) had no siginificant impact on neointimal hyperplasia in rat carotid injury model. However, in high dose group(l5Gy and 20 Gy) neointimal area was significantly reduced(p X0.01) indicating high dose EBR markedly prevented neointimal hyperplasia.

Conclusion : Radiation therapy may be an effective adjunctive method for reducing the restenosis rate after successful angioplasty in the rat carotid injury model.