Endovascular Low-Dose Irradiation Inhibits Neointima Formation After Coronary Artery Balloon Injury in Swine

Abstract

Low-dose intracoronary irradiation delivered to the site of coronary arterial overstretch balloon injury in pigs inhibited subsequent intimal thickening (hyperplasia). A dose-response relationship was demonstrated, and delay of treatment for 48 hours appeared to augment the inhibitory effect. Six months of follow-up without fibrosis or arteriosclerosis demonstrated the durability of the beneficial effect in the treated group. These data suggest that intracoronary irradiation therapy may aid in preventing clinical restenosis.

<b>Irradiation and Postangioplasty Restenosis</b>

“…6,7,70,71,75) Wiedermann and co-workers found suppression of neointima 4 weeks after angioplasty when 20 Gy was delivered at a radial depth of 1.5 mm just before arterial injury and demonstrated that this effect persisted at 6 months. Similarly, Waksman and co-workers demonstrated profound suppression of neointima using 192 Ir with a doseresponse effect in vessels treated with 3.5, 7, and 14 Gy at a radial depth of 2 mm.…”

“…Thus, radiation may effectively inhibit neointima formation by killing more rapidly dividing, synthetic smooth muscle cells. 7) Regarding vasomotor function, one early study evaluated the effects of high-dose intracoronary irradiation, 20 Gy, using the gamma emitter 192 Ir, on intimal hyperplasia and vasomotor function. Intracoronary irradiation acutely impaired both endothelium-dependent and independent vasomotor function.…”

“…To evaluate the proper method to apply this new modality of treatment, several investigators have used both externally delivered X ray-irradiation as well as various catheter-based and radioactive stent endovascular approaches with various isotopes in experimental studies primarily using pigs and rabbits. 6,7,70,71) …”

“…Since the discovery of X-rays by Roentgen in 1895 and of radium by Madame Curie in 1898, ionizing radiation is well known as a potent antiproliferative agent for both malignant and benign disorders and the use of radiation to modify the wound healing response has also been well-documented. 6,7) Low dose external radiation is currently used for a number of different problems including the prevention of keloid formation after surgery and recurrence of pterygium after surgical removal. [8][9][10][11] Restenosis may be considered as a type of exuberant wound healing.…”

Increased Expression of Macrophage Colony–Stimulating Factor After Coronary Artery Balloon Injury Is Inhibited by Intracoronary Brachytherapy

“…[7][8][9][10][11][12][13][14] The mechanism by which ICBT inhibits restenosis is not fully understood, but it appears to involve reduced smooth muscle cell (SMC) proliferation and delayed healing responses to vascular injury. 14,15 Macrophage colony-stimulating factor (M-CSF) is a multifunctional proinflammatory protein that regulates the differentiation, proliferation, and survival of mononuclear phagocytic lineage cells such as macrophages and SMCs. 16 -23 Increasing evidence has suggested an important role for M-CSF in de novo human atherosclerotic lesions 1,2,18,19 and experimental animal models.…”