Intracoronary irradiation with ^186/188rhenium following balloon overstretch injury reduces neointima but does not impair vasoreactivity of porcine coronary arteries

Abstract

Objective: The purpose of this study was to assess the effect of ^186/188rhenium (^186/188Re) on the neointimal proliferation and on the vasomotion of irradiated porcine coronary arteries following balloon injury. Background: Intracoronary radiation (IR) at doses of 10–25 Gy reduces intimal hyperplasia in animal models and lowers restenosis in clinical trials. The response of coronary arteries to acetylcholine (ACh) has been used to examine endothelial function, but this has not been reported in porcine coronary arteries subjected to overstretch balloon injury (BI) and subsequent IR. Methods: Vasomotor response was studied at baseline and at 2 weeks in 20 swine. Baseline vasomotor study without BI was carried out in six animals (12 arteries; Group I, no injury, no radiation). Subsequently the left anterior descending (LAD) and the left circumflex (LCX) arteries of 11 animals were subjected to BI. Eight of these animals (15 arteries) were subjected to IR with ^186/188Re in the LAD and LCX arteries in doses of 15 Gy followed by vasomotor studies at 2 weeks (Group II, BI, radiation). Three animals, (six arteries) of the BI group were not subjected to IR and their vasomotor functions assessed two weeks later (Group HI, BI, no radiation). Endothelium dependent vasomotion was assessed by Doppler flow wire and by quantitative coronary angiography (QCA) following selective infusion of serial doses of ACh proximal to the injured and irradiated segments. Nitroglycerin (200 μg) was injected intracoronary to detect endothelium independent vasodilatation. Histomorphometry and QCA analysis was performed to confirm the effect of IR on intimal area (IA), and IA corrected for fracture length (IA/FL). Results: Responses to ACh infusion and coronary flow reserve were similar at baseline before injury and at 2 weeks following injury with and without radiation. The irradiated vessels demonstrated normal vasodilatation responses to nitroglycerin. The irradiated vessels showed a marked reduction in IA and IA/FL. Conclusion: The vasoreactivity of irradiated coronary arteries is preserved at doses that inhibit neointima formation in the porcine model.