Influence of Postangioplasty β-Irradiation on Endothelial Function in Porcine Coronary Arteries

Abstract

Background —Postangioplasty (PTCA) intracoronary radiation therapy (ICRT) has been demonstrated to limit restenosis. The consequences of these procedures on coronary reactivity are unknown. Methods and Results —Porcine coronary arteries were studied after PTCA immediately (n=5) and 6 weeks (n=5) after ICRT (n=5 and 5, respectively), after combined PTCA+ICRT (n=5 and 7, respectively), and after no intervention (n=11). A 3-cm-long source train of Sr/Y 90 was used in vivo to deliver 16 Gy at a depth of 2 mm from the source center, as used in clinical trials. Arterial rings were mounted on myographs to record isometric tension. After achieving steady-state contraction to depolarizing physiological solution containing 40 mmol/L KCl, measured baseline tension was significantly elevated immediately after all interventions. It returned to normal levels 6 weeks after PTCA and ICRT alone but was significantly reduced if combined. Active contractions induced by 40 mmol/L KCl were maintained after combined therapy both immediately after and at 6 weeks. In these depolarizing conditions, nitric oxide–dependent relaxation to substance P was trivial after PTCA+ICRT and reduced after ICRT, whereas in the presence of physiological solution and N ω -nitro- l -arginine, substance P–induced relaxation was reduced after PTCA and abolished after PTCA+ICRT 6 weeks after intervention. In rings without endothelium, the relaxation mediated by sodium nitroprusside (0.1 μmol/L) was reduced immediately after PTCA and at 6 weeks. Conclusions —PTCA+ICRT altered the passive mechanical properties of porcine coronary arterial wall. Furthermore, at 6 weeks, receptor-operated release of endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor was reduced by ICRT and PTCA alone, respectively, and was prevented by their combination.