Effect of Steroid on Impaired Vascular Function Induced by Irradiation

ABSTRACT

BACKGROUND AND OBJECTIVES: Intracoronary irradiation has been proven to reduce restenosis following percutaneous transluminal coronary angioplasty, however late thrombosis is another recurring problem. We evaluated the sequential changes of vascular dysfunction and morphological changes according to the radiation dosage in rats. The effects of dexamethasone on these changes were also evaluated. MATERICAL AND METHODS: Female Sprague-Dawley rats were randomized into 4 groups (n=20, each group), and were irradiated with 0, 5, 10, 20 Gray (Gy). The rats were sacrificed at 1 hour, 1, 3 and 7 days after irradiation. The physiographic responses and morphologic changes of the arterial rings were evaluated. After the time- and dose-response relationship was determined, an additional 40 rats were pretreated with dexamethasone for 3 days and irradiated with 10 or 20 Gy to evaluate the effects of the dexamethasone. 5 Gy irradiation did not induce endothelial dysfunction. 10 Gy irradiation induced an impairment of endothelium dependent relaxation (EDR) only 7days after irradiation. 20 Gy caused an impairment of EDR from the very time of irradiation, although endothelium independent relaxation (EIDR) was not affected irrespective of dose or time. On immuno-histochemistry of vWF, all irradiated arteries showed mild de-endothelialization in acute phase and subsequent re-endothelialization. However, after 20 Gy irradiation, re-endothelialization did not occur. With dexamethasone treatment, all of these vascular dysfunctions were prevented, and re-endothelialization was promoted. CONCLUSION: Irradiation induced the impairment of EDR as well as de-endothelialization, in a time- and dose-response relationship in rats. Pretreatment with dexamethasone may partly prevent radiation-induced vascular dysfunction and de-endothelialization.