Perivascular delivery of losartan with surgical fibrin glue prevents neointimal hyperplasia after arterial injury

Journal of Vascular Surgery
Michael C MoonP Zahradka

Abstract

Long-term success of revascularization procedures is limited by recurrent stenosis, a reduction in vascular lumen area that results from neointimal hyperplasia. Inhibitors of the renin-angiotensin system, such as losartan, have potential to prevent recurrent stenosis; however, to date, efficacy has not been demonstrated in either animal models or human beings. While we have previously reported that treatment with a satisfactory dose may be an important element in obtaining efficacy, oral delivery cannot achieve the required concentration. We therefore tested the ability of losartan to restrict neointimal hyperplasia after local delivery of an elevated dose in a fibrin glue. The porcine saphenous artery was subjected to balloon angioplasty. Losartan (25 micromol/mL) was applied directly to the adventitial surface of the injured vessel after mixing with 1.0 mL of Tisseel. Neointimal formation was quantified after 14 days with morphometry, and immunologic staining was used to monitor expression of proteins associated with cell proliferation, migration, and phenotypic modulation. A statistically significant decrease of 82% (n = 5) in neointimal area was obtained with losartan, and cell proliferation, as defined by proliferating cel...Continue Reading

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Citations

Sep 16, 2008·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Nancy E MartinDavid H Abramson
Feb 21, 2006·Clinical and Experimental Pharmacology & Physiology·James E Faber, Nengyu Yang
Jun 20, 2008·Advanced Drug Delivery Reviews·Misara HamoudehHatem Fessi
Nov 30, 2006·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Urs O HäfeliRichard A Prayson
Apr 23, 2013·Journal of Vascular Surgery·Stephen M SeedialK Craig Kent
Aug 7, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Peter ZahradkaNatalia Yurkova
Apr 28, 2010·Archives of Pharmacal Research·Inseon YiChang-Seon Myung
Aug 27, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sunghou LeeKathryn Sandberg
Dec 12, 2013·Journal of Cell Communication and Signaling·Peter MolnarPeter Zahradka
Jun 5, 2008·The Journal of Pharmacology and Experimental Therapeutics·Lorraine YauPeter Zahradka

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