Supplemental oxygen does not synergize with intracoronary radiation for the prevention of restenosis in porcine coronary arteries

Purpose. Recurrence of obstructive coronary arterial lesions (restenosis) after angioplasty remains a significant clinical problem. Ionizing radiation, at doses >10 Gy administered locally to the angioplasty site, has been shown to inhibit restenosis in porcine coronary arteries, but lower doses are ineffective. Methods that will allow delivery of lower doses of radiation while retaining the antirestenotic efficacy observed at the higher doses are desirable. Hypoxic cells are known to be radioresistant; accordingly, we hypothesized that increasing blood oxygenation through the use of the TherOx Aqueous Oxygen™ system would lower the doses of endovascular radiation required for the prevention of restenosis. Materials and Methods. Five swine were studied as follows: balloon injury + oxygen alone was performed in two swine. Each swine had a balloon overstretch injury in two arteries, left anterior descending (LAD) and either right coronary artery (RCA) or left circumflex (LCX) artery (three arteries total). Balloon injury + oxygen followed by intracoronary irradiation was performed in a further three swine (six arteries). Controls consisted of arteries treated with 0, 5, or 15 Gy of ¹⁹²Ir alone. Results. Arteries treated with the TherOx Aqueous Oxygen™ system alone were indistinguishable from arteries treated without oxygenation except for a larger adventitial area (5.29 ± 0.20 vs. 2.77 ± 0.28 mm²; p < 0.05). Arteries treated with the TherOx Aqueous Oxygen™ system along with 5 Gy of ¹⁹²Ir exhibited a greater injury-corrected intimal area than arteries treated with radiation alone (0.76 ± 0.18 vs. 0.33 ± 0.08 mm²; p < 0.05). Neither thrombosis rate nor thrombus area was significantly different in arteries receiving the TherOx Aqueous Oxygen™ as compared with controls. Conclusions. The TherOx Aqueous Oxygen™ system is safe in the context of balloon overstretch injury, but decreases the antirestenotic efficacy of 5 Gy of ¹⁹²Ir. These findings suggest that hypoxia does not seem to be a major contributor to the dose of radiation required for suppression of neointima, at least when using noncentered γ radiation delivery systems.