Long-term effects of intracoronary β-radiation in balloon-and stent-injured porcine coronary arteries

• Published in: Circulation (New York, N.Y.) Vol. 103; no. 16; pp. 2108 - 2113
• Main Authors: KALUZA, Grzegorz L, RAIZNER, Albert E, MAZUR, Wojciech, SCHULZ, Daryl G, BUERGLER, John M, FAJARDO, Luis F, TIO, Fermin O, ALI, Nadir M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24-04-2001
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Beta Particles - adverse effects; Biological and medical sciences; Brachytherapy - adverse effects; Coronary Restenosis - complications; Coronary Restenosis - pathology; Coronary Restenosis - radiotherapy; Coronary Thrombosis - etiology; Coronary Thrombosis - pathology; Coronary Vessels - diagnostic imaging; Coronary Vessels - pathology; Coronary Vessels - radiation effects; Death, Sudden, Cardiac - etiology; Death, Sudden, Cardiac - pathology; Disease Models, Animal; Disease Progression; Diseases of the cardiovascular system; Female; Male; Medical sciences; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Stents - adverse effects; Survival Rate; Swine, Miniature; Time; Ultrasonography, Interventional; Vascular Patency - radiation effects; Cuffed tube; Cardiovascular disease; Stent; Arterial disease; Vascular disease; Prevention; Local administration; Beta irradiation; Ungulata; Endoprosthesis; Treatment efficiency; Coronary artery; Instrumentation therapy; Exploration; Instrumental dilatation; Coronary heart disease; Long term; Pig; Restenosis; Pathology; Vertebrata; Mammalia; Treatment; Animal; Artiodactyla; Lesion
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.103.16.2108

The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited.
A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen.
In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.