# A novel translational model of atherosclerosis, the ex vivo pump-perfused amputated human limb model

## TL;DR

Researchers developed a new model using amputated human limbs to study atherosclerosis, enabling advanced imaging and drug testing in a realistic human system.

## Contribution

The first ex vivo pump-perfused human limb model for studying atherosclerosis, allowing real-time imaging and molecular targeting.

## Key findings

- The model maintains oxygen saturation above 99% for up to 6 hours of perfusion.
- Clinical imaging techniques like X-ray angiography and optical coherence tomography were successfully applied.
- Indocyanine green dye localized to atherosclerotic plaque, confirming molecular targeting potential.

## Abstract

The preclinical study of atherosclerosis has traditionally centred around the use of small animal models, translating to large animal models, prior to first-in-man studies. We propose to disrupt this paradigm by designing an ex vivo pump perfused human limb model. The novel model consists of taking a freshly amputated limb and incorporating it into an ex situ pump-perfused bypass system (akin to extracorporeal membrane oxygenation), circulating warmed, oxygenated blood. The circuit incorporates an introducer sheath and guiding catheter for intravascular imaging and X-ray angiography. Regular monitoring is performed using blood gas analysis, aiming for physiological parameters. The model maintains oxygen saturations > 99% for the length of perfusion (up to 6-h). Clinical grade X-ray angiography, intravascular ultrasound and optical coherence tomography have been successfully performed. Indocyanine green, a near-infrared fluorescent dye that localises to atherosclerotic plaque, has been injected into the system and left to circulate for 90-min. Fluorescence reflectance imaging of the dissected arterial bed confirmed uptake in areas of calcific atherosclerotic plaque on intravascular imaging. This is the first demonstration of an ex vivo pump-perfused “living” limb experimental model of atherosclerosis, which shows promise for future studies in translational interventional imaging and molecular targeting.