Abstract 717: Sequential Inflow Occlusion and Walking Capacity in Large Animal Model of PAD

Abstract

Introduction: Peripheral artery disease (PAD) affects over 8 million Americans over 40 years of age. PAD patients are heavily burdened by pain and walking dysfunction. Treatment paradigms for PAD are evolving, but optimal medical therapy, risk factor modification, and supervised exercise therapy (SET) are the first line therapies for these persons. SET improves walking time and may improve skeletal muscle perfusion. However, the mechanisms by which SET and other treatments are not well understood. Translational models of PAD may be useful in developing novel therapeutics for PAD patients. Objective: The objective of this work is to introduce a large animal (porcine) model of PAD that includes sequential occlusion of inflow that can be used on patient-like treadmills for SET or quantification of walking distance and dysfunction. Methods: Two female Yorkshire swine were accommodated to our treadmill one week prior to procedure. On day 0, swine underwent endovascular placement of a covered stent (GORE® VIABAHN® endoprosthesis) into the right external iliac artery followed by placement of a vascular plug (AMPLATZER, St. Jude Medical) inside this stent was used in the initial procedure. In order to mimic the common presentation of PAD patients having one leg more severely ischemic than the other, we performed a sequential occlusion of the ipsilateral internal iliac artery and contralateral external iliac artery one week later. Vascular flow were quantified by arteriogram, a modified ankle brachial index, and duplex ultrasound. Animals were walked weekly on a large animal treadmill with a 3.5 KM/HR pace and 10 degree incline until failure (pigs would slide to end of treadmill). Results: There were no technical failures or complications. One and three weeks after the initial procedure, pigs walked 40% and 45% of pre-procedural maximal walking time. There was sustained depression of the blood pressure ratio of ischemic hindlimb to unaffected forelimb (hindlimb index or HLI), which was significantly inhibited out to 6 weeks ( HLI of 0.4-0.63 ). Conclusion: We have created a pilot model of PAD that can be used for both SET testing and quantifying maximal walking time/distance. This model may be useful in testing novel therapeutics and validating promising mechanistic findings from small animals.