A comparison of local and systemic angiotensin at1 receptor antagonism on the development of experimental vein graft intimal hyperplasia

Bm-liyrminrt: Vein grafts (VO) develop intimai hyperplasia (IH) which can lead to graft stenosis and failure. Following grafting, responsiveness to angiotensin II increases through angiotensin ATI receptor activation. This study compares local versus systemic ATI receptor inhibition of VG IH using the specific ATI receptor inhibitor L 158.809. Mehtods Thirty-two NZW rabbits underwent jugular vein interposition grafting of their right common carotid artery. Ten animals were controls, six received L 158.809 orally (10mg/lcg/day 5 days prior to surgery until harvest), ten had the outer surface of the graft coated with 30% pluronic gel (2.5ml). and six had 2.5 ml of gel containing L 158.809 ( lO-'mol/l). At 28 days the animals were sacrificed, and grafts fixed, sectioned and stained. Medial and intimai dimensions were quantified by videomorphometry. The data are expressed as the mean ±SEM. Résulte! There was a 40% reduction in IH in those animals treated with oral L 158.809 and a 33% reduction with gel delivered antagonist when compared to control and gel only groups. Medial thickness was increased in the gel/L 158,809 group only. Intimai Thickness Media] Thickness Intimai Ratio Control 70 ±4 μm 65 ±5 μm 0.52 ±0.02 30% Pluronic Gel 72 ±4 μm 58 ±6 μm 0.55 ±0.03 L 158,809 /Gel 48 ±3 μm 83±5 μm 0.36 ±0.01 Oral L 158,809 43± 7 μm 42±6 μm 0.50 ±0.08 Intimai Ratio=Int Area/Int+Med Areas: p< 0.01 compared to control only by ANOVA; p< 0.05 compared to control/gel only. Cnnrlmdons: The results of this study show that both local and systemic angiotensin ATI receptor inhibition can significantly reduce VG IH, although continued systemic therapy appears to be required to control media] hypertrophy.