Abstract 17160: Quantitative Characterization of Porcine Peripheral Artery Disease Models

Abstract

Listen

Translate article

Introduction: Peripheral artery disease (PAD) is a significant age-related medical condition affecting over 200 million patients worldwide. PAD cell therapy clinical trials have shown minimal benefits, and questions remain regarding the optimal cell type, dose, and delivery method. A large animal preclinical PAD model has not been standardized nor quantitatively characterized, potentially contributing to the lack of success in these trials. Hypothesis: We hypothesize that a durable model of PAD can be created in swine to test cell therapy efficacy as determined through quantitative measurements of microvascular muscle perfusion and limb functionality while walking. Methods: Swine were divided into three cohorts and underwent unilateral ligation of 1) the external iliac and circumflex iliac arteries, 2) the external, internal, and circumflex iliac arteries, or 3) distal hind limb arteries to create models of PAD. Automated gait analysis with a pressure-sensitive walkway was performed at various time points pre- and post-model creation to quantify functional deficits of trotting animals. Objective calculation of various gait parameters was performed by walkway software. A pulsed arterial spin labeling (ASL) MRI sequence was used to measure perfusion in pig hind limbs during cuff-induced reactive hyperemia. Fluoroscopy-based angiography was performed during model creation and sixth week terminal procedures, and fluorescent microsphere perfusion measurements were obtained for limb muscles at study conclusions. Results: The most severe, durable functional deficits were exhibited in Cohort 2. Cohort 1 exhibited transient functional abnormalities in ischemic vs. non-ischemic hind limbs that returned to baseline in one week. Animals in Cohort 3 also displayed slight deficits early that quickly resolved. ASL MRI successfully quantified microvascular perfusion in hind limb skeletal muscle. Extensive collateral formation in ischemic hind limbs was detected at the end of each study. Conclusions: External and internal iliac artery ligation is a promising strategy to establish a durable model of hind limb ischemia in which to test the efficacy of cell and other therapeutics, better facilitating the transition of PAD therapies from bench to bedside.