Abstract 555: Technique For Testing Drug-coated Balloons In Deep Veins In Vivo

Abstract

Background: Chronic deep venous occlusions, leading to outflow obstruction in dialysis patients and post thrombotic syndrome (PTS) in DVT patients, are often treated with balloon venoplasty and stenting to restore flow and improve limb outcomes. In stent restenosis and occlusion are primary reasons for late intervention failure. mTOR inhibitors might impact thrombotic and fibrotic pathways on venous endothelial cells (VEC). Methods: Immortalized murine VEC (EOMA, ATTC #CRL-2586) were stimulated with sirolimus (1ng) and vehicle (DMSO) performing quantitative real-time PCR (qRT-PCR). Sprague Dawley rats (n=4, 250-400g) were anesthetized (isoflurane). IVC diameter measured by ultrasound. Infrarenal IVC was exposed using a midline laparotomy, side branches ligated, posterior venous branches cauterized, and micro-clips temporarily placed. A 0.014 sharpened guidewire with a DCB back-loaded was inserted retrograde into the infrarenal IVC. After DCB inflation/deflation, the entire system was removed and U-stitch tightened for hemostasis. Results: Sirolimus blunted transcription of cellular adhesion molecules (CAMs) and mediators of EndMT. (Fig 1) We achieved total stasis to replicate a vein wall reaction to thrombosis and further EndMT changes, with 75% survival in initial proof-of-concept experiments. (Fig 2) Conclusion: IVC retrograde cannulation via U-stitch and sharpened guidewire is a viable animal model for testing venous DCBs. Sirolimus inhibits VEC CAMs critical for thrombus initiation and EndMT mediators involved in PTS remodeling. Future DCB research on adhesive and fibrotic phenotypes is required.