Large animal model of controlled peripheral artery calcification

Area of Science:

• Vascular Biology and Disease
• Preclinical Animal Models
• Biomedical Engineering

Background:

• Peripheral artery disease (PAD) involving lower extremity arteries causes significant morbidity and mortality.
• Arterial calcification in PAD is linked to poor outcomes and increased amputation risk.
• Existing treatments for calcific lesions are limited and often yield suboptimal results.

Purpose of the Study:

• To create a large animal model of late-stage arterial calcification that mimics human PAD.
• To establish a platform for testing the efficacy and safety of surgical interventions for calcific PAD.
• To accommodate human-sized devices for advanced therapy development.

Main Methods:

• Induction of arterial calcification in swine using targeted CaCl2 injections into iliac, femoral, and popliteal arteries via a micro-needle catheter.
• Varied injection sites to create eccentric and concentric lesions, with adjacent non-calcified segments as controls.
• Assessment of lesions using Computed Tomography Angiography, Intravascular Ultrasound, mechanical testing, and histological analysis.

Main Results:

• The model demonstrated ring-like calcification patterns and loss of pulsatility as early as 4 weeks post-induction.
• Mechanical properties of excised arteries mirrored human calcified vessels, showing characteristic stiffening.
• Histological analysis confirmed resemblance to human femoropopliteal vessels, with inflammation, ECM changes, and smooth muscle cell loss.

Conclusions:

• This porcine model accurately replicates key pathological features of human calcific PAD.
• It provides a robust platform for evaluating calcium-modifying treatments and devices.
• The model can advance the development of therapies to improve PAD outcomes and reduce amputation rates.