S-nitrosoglutathione reduces nonocclusive thrombosis rate following balloon overstretch injury and intracoronary irradiation of porcine coronary arteries

Purpose: Intracoronary radiation (IR) suppresses neointima formation follow ing balloon injury in animal models. High doses of radiation exacerbate thr ombosis and delay re-endothelialization. The free radical nitric oxide (NO) has been reported to inhibit platelet aggregation, reduce neointimal hyper plasia, and stimulate re-endothelialization. This study examined the effect s of a chemical NO donor on neointima formation, thrombosis, and healing of irradiated porcine coronary arteries. Methods and Materials: Vascular lesions were created in the coronary arteri es of 59 domestic swine by overstretch balloon injury. Arteries were then l eft untreated or were treated with intracoronary gamma -radiation using Iri dium-192 in each artery to deliver 5 or 15 Gy at 2 mm from the center of th e source, The chemical NO donor S-nitrosoglutathione (GSNO) was infused i.v . at a rate of 250 mug/min for 10 min before injury, followed by a continuo us infusion for 60 min, Animals were euthanized at 14 days and their arteri es were analyzed for histomorphometric indices of proliferation and thrombo sis. Results: A dose of 15 Gy reduced the ratio of intimal area to medial fractu re length (IA/FL) versus control (0.06 +/- 0.05 0.54 +/- 0.10 [p < 0.001]) but increased the nonocclusive thrombosis rate compared to controls (85% vs , 30%; p < 0.05). A low dose of 5 Gy did not affect neointima formation, Tr eatment with GSNO reduced thrombosis in all treated groups: control, 15%; 5 Gy, 18%; and 15 Gy, 35% (p < 0.05) without affecting neointima formation, Conclusion: Systemic administration of GSNO during balloon injury and IR wa s tolerated well by the sine and resulted in reduction of the thrombosis ra te, especially at high doses, without apparent effect on neointima formatio n. (C) 2000 Elsevier Science Inc.