Abstract 1154: Length And Proximal Extent Of Occlusion Dictates Severity Of Disease In A Mini-swine Model Of PAD

Abstract

Background: There is ongoing need for large animal models of peripheral artery disease (PAD) that replicate human disease. We present mild (MI), moderate (MD) and Severe (S) phenotypes of PAD in an Ossabaw mini-swine platform. Methods: Metabolic syndrome was induced in swine (N=16; age= 4 mo) with a high fat/fructose/sodium diet for 8 weeks. Ischemia induction (T0) consisted of: (1) open ligation and resection of R Superficial Femoral Artery (SFA) for MI(N=4); (2) endovascular coil occlusion of R External Iliac Artery (REIA), RSFA and popliteal artery for MD (N=9); and (3) coil occlusion of REIA, RSFA, and right internal iliac artery (RIIA) for S (N=4). At 4 weeks (T4) and 8 (T8), all swine underwent angiography via carotid access, and bilateral gastrocnemius biopsy. All swine had measurements of ankle brachial indices (ABIs), and calf muscle tissue oximetry (STO 2 ) measurements at T0, T4 and T8, along with weekly measurement of walking performance on a treadmill (WP). Results: At T4 and T8 R ABI were increasingly decreased from MI to MD to S (table 1). Mean STO 2 difference between R and L calf at T4 and T8 had no changes in MI, while the differences were larger in S compared to MD (table 1). WP was increasingly decreased from MI to MD to S (table 1). The artery that grew the most on angiography at T4 and T8 were R profunda artery (RPFA) in MI; RIIA in MD; and LIIA in S (table 1). In MI, R PFA had faster flow at T4 and T8 compared to L PFA. At T4, MD and S had similar delays of RPFA reconstitution, this improved at T8 in MD but did not in S (table 1). On histology, MI had no obvious myopathy, MD and S had moderate and severe myopathy respectively. All S subjects developed poorly-healing ischemic ulcers. Conclusion: Length and proximal extent of occlusion dictated the characteristics and severity of phenotypes in our Ossabaw swine model of PAD. This mirrors PAD in humans and can be used to develop therapies for different disease severities.