Abstract Body: Introduction: Porcine models of aortic aneurysm (AA) often rely on open surgical exposures and extraluminal application of elastolytic agents. These methods induce significant surgical trauma and create biological noise reducing experimental effectiveness. We developed a minimally invasive, endovascular porcine model of AA that utilizes intramural delivery of elastolytic agents to mimic human AA pathophysiology. We hypothesized that direct endovascular injection of a proteolytic cocktail into the aortic wall would reliably induce aneurysms with morphological, histological, and biomechanical features resembling human AA.
Methods: AA induction was performed in four domestic swine (baseline weight 41±3 kg). Using fluoroscopy, a microneedle infusion catheter was advanced to the infrarenal aorta, and a proteolytic cocktail of porcine elastase (25-200 units) and calcium chloride (40-50 mg) was injected directly into the aortic wall. Aortic dimensions were monitored via Duplex Ultrasound (DUS) and CT Angiography (CTA). Animals were sacrificed at four weeks for histological and biomechanical analysis.
Results: Aneurysm formation was observed in all animals without mortality or dissection. DUS at one week revealed a 30-60% increase in maximal aortic diameter. CTA confirmed sustained dilation, with mean aortic diameter increasing 20-56%, depending on cocktail composition. Histology demonstrated degradation of elastic lamellae and medial calcification. Immunohistochemistry, zymography, and broad-spectrum matrix metalloproteinases (MMPs) analysis demonstrated elevated MMPs expression and activity, particularly MMP-2 and 9. Biomechanical testing revealed increased stiffness in the aneurysmal tissue compared to healthy control aorta.
Conclusions: Endovascular proteolytic cocktail delivery into swine aortas produces medial degeneration, inflammation, and aneurysm morphology without surgical trauma. Aortic calcification is a prominent feature, as it is in human aortic aneurysms. This large animal model may provide a valuable preclinical platform for evaluating endovascular devices and pharmacological therapies.