Development of an Atherosclerotic Rabbit Model for Blood Flow Analyses under Extracorporeal Circulation

Background: The choice of the optimal extracorporeal circulation (ECC) cannulation strategy especially in atherosclerotic patients is still under debate. To allow for exact measurements and visualization of different ECC scenarios, magnetic resonance imaging (MRI) is required. Therefore, the present study aims at developing an atherosclerotic rabbit model, which shall be combined with our previously published miniaturized MRI-compatible rabbit ECC system to demonstrate blood flow profiles, wall shear stress and turbulences in dependency on different ECC scenarios.

Method: A total of 15 New Zealand white rabbits received either a pro-atherosclerotic diet (n = 5) containing 0.3% cholesterol and 3% coconut oil (group diet), or a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury (n = 5, group BI), or served as controls (n = 5, group control). After 3 months, the aortas were explanted and analyzed by histology.

Results: Macroscopic analyses showed ubiquity lumen-narrowing aortic plaques with irregular surface. Significantly increased intima hyperplasia, quantified by the intima-to-media ratio, occurred in group diet (0.54 ± 0.15 vs. 0.08 ± 0.01, p = 0.009) and in group BI (p = 0.58 ± 0.09 vs. 0.08 ± 0.01, p < 0.0001) each when compared with controls after 3 months. In contrast to controls, group diet as well as group BI showed remarkable areas of glycosaminoglycans accumulation in the intima and media, as assessed by Movat Pentachrome staining. Calcification of the intima, as assessed by a von Kossa staining score, was significantly increased in group diet (0.98 ± 0.20 vs. 0.00 ± 0.00, p < 0.0001) and in group BI (1.15 ± 0.07 vs. 0.00 ± 0.00, p < 0.0001) each when compared with controls after 3 months. Likewise, media calcification was significantly increased in group diet (1.08 ± 0.18 vs. 0.06 ± 0.03, p < 0.0001) and in group BI (1.38 ± 0.11 vs. 0.06 ± 0.03, p < 0.0001) each when compared with controls after 3 months. There were no significant differences between group diet and group BI.

Conclusion: The developed rabbit model of high calcific aortic plaque burden is suitable to be used for future studies on the interaction between atherosclerotic plaques and the blood flow under ECC. Particularly the generation of turbulences, changes in wall shear stress, and potential subsequent plaque rupture will be investigated.

Publication History

Article published online:
03 February 2022