Radiation therapy impairs endothelium-dependent vasodilation in humans

OBJECTIVES The objective of this study was to test the hypothesis that exte rnal-beam radiation induces a chronic impairment of endothelium-dependent v asodilation. BACKGROUND Radiation therapy is used commonly in the treatment of cancer an d is associated with an increased incidence of adverse vascular events rela ted to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction. METHODS Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before en rollment and ten healthy women were studied. Vascular ultrasonography was u sed to image both the artery exposed to radiation and the contralateral art ery. Flow-mediated, endothelium-dependent vasodilation and endothelium-inde pendent vasodilation to nitroglycerin of both axillary arteries were measur ed. RESULTS Endothelium-dependent vasodilation was significantly impaired in th e irradiated axillary arteries compared with the contralateral, nonirradiat ed arteries (-0.4 +/- 0.4% vs. 3.2 +/- 0.8%, p < 0.001) and also compared w ith control subjects' arteries (-0.4 +/- 0.4% vs. 2.5 +/- 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arter ies that received radiation compared with the contralateral arteries (3.8 /- 0.5% vs. 2.0 +/- 0.4%, p < 0.05) and also compared with control arteries (3.8 +/- 0.5% vs. 2.5 +/- 0.4%, P < 0.05). CONCLUSIONS External beam radiation therapy impairs endothelium-dependent v asodilation of conduit arteries, implicating a decrease in the bioavailabil ity of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events. CT Am Coil Ca rdiol 2001;37:761-5) (C) 2001 by the American College of Cardiology.