Porcine Model of Thoracic Aortic Aneurysms Created by a Novel Retrievable Drug Delivery Stent Graft

The mechanisms of aneurysm growth remain ill-defined. One limitation is the absence of appropriate models. Murine models are too small, while open surgical exposure to apply toxic enzymes impacts recovery and aneurysm behavior. A retrievable drug delivery stent graft (RDDS) was developed to deliver a drug to the vascular wall while preventing systemic exposure. The objective was to use an RDDS to deliver aneurysm promoting enzymes toward creation of a porcine model of thoracic aneurysms. Retrievable stent grafts were assembled from nitinol frames, covered with polymer, and affixed to a delivery wire and drug infusion catheter. Institutional Animal Care and Use Committee-approved pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the descending thoracic aorta followed by 30-minute exposure to an enzyme cocktail. After drug aspiration, stent removal, and femoral artery repair, animals were recovered, with follow-up angiograms and magnetic resonance angiography followed by 4 week explant. Histology and multiplex assays were performed on aneurysms and untreated aorta. The RDDS isolated a segment of aorta for drug infusion (Figure), while the center lumen preserved distal mean arterial pressure (baseline: 70 ± 14 vs after RDDS placement: 75 ± 12; P = .55). Animals tolerated endovascular induction of thoracic aneurysms without the need for prior mechanical injury and without external evidence of toxicity. Within 1 week, significant aneurysmal growth (baseline: 1.5 ± 0.1 cm to 1 week: 2.9 ± 0.7 cm; P = .045) was observed in all five, which persisted to 4 weeks (2.6 ± 0.5 cm). Hematoxylin and eosin staining demonstrated thinning of the aortic wall without perforation. Cytokine analysis (n = 3; P < .003) revealed robust peaks in four proinflammatory cytokines in the mid-portion of the aneurysm. This study demonstrated a reproducible porcine model of thoracic aneurysms, without mechanical injury or open aortic exposure, using an RDDS to focally deliver a toxic drug to an isolated segment of vessel wall. This model may have value for surgical training in open aortic repair, device testing, and to better understand aneurysm pathogenesis. Most importantly, this approach offers future avenues for potentially therapeutic drug delivery directly to aneurysms and even locoregional drug delivery in other contexts.