**5. Conclusion**

*Animal Models in Medicine and Biology*

consecutive weekly measurements.

challenging to perform.

vessel lumen (stenosis) and reduction of the blood flow.

Mechanical endothelium injury is a standard strategy to induce hyperplasia in various animal models such as mice, rabbits or minipigs [9, 10, 17]. In the present study, the endothelial injury was induced by two different approaches in rabbits: first by overexpansion of a BMS in the right iliac artery and second with an inflated balloon in the contralateral left iliac artery. Stenting and balloon injury resulted in a respective permanent and transient overexpansion of the vessel inducing a well-recognised vascular response [11]. An acute inflammation rapidly follows the induced endothelium injury or denudation and peaks after a few days; then, the inflammation temporally declines during the resolution phase. Acute inflammation is accompanied by the proliferation of smooth muscle cells that results in hyperplasia. Consequent thickening of the wall (hyperplasia) may induce a narrowing of the

In the present study, we showed that the rabbit iliac arteries and the distal abdominal aorta could be successfully monitored using high-resolution ultrasound for longitudinal and non-invasive investigation. The quality of the images acquired allowed rigorous measurements of the wall and vessel sizes. It is important to note that for some measurements, the possible presence of oedema could impair the quality of the image acquisition and may explain variations of the parameters in

Besides, the metallic structures of the BMS were visualised as shadows. Although the presence of the metallic stent did not impair the wall thickness and vessel diameters' quantification, the blood flow velocity measurements were often

lumen size followed by a reduction suggesting a weakening of the artery. Notably, the overexpansion of the stent affected the wall thickness that increased rapidly and remained elevated. Histology analysis revealed the formation of neointimal hyperplasia. In contrast, balloon injury results in a transient wall thickening recorded 2 weeks post-intervention with a successive return to the initial dimensions. Transient inflammatory response to the balloon injury may explain the wall. Accordingly, Welt et al. [12] reported a transient inflammation following a balloon injury model as compared with a sustained accumulation of inflammatory

cells such as monocytes in stented iliac arteries of rabbits up to 14 days.

Furthermore, Virmani et al. [13] reviewed the temporal vascular response to BMS implanted in the rabbit iliac artery. Between 7 and 14 days, the intimal thickness increased due to inflammation and cell proliferation and then peaked at 1 month with a return of the cell proliferation to the basal level. Further shrinkage has been reported from 3 to 6 months due to the extracellular matrix remodelling. In agreement, we also report the shrinkage of the wall thickness observed at day

As far as the evaluation of the blood flow is concerned, the VTI and the calculated changes in flow revealed notable individual variations. Nevertheless, the longitudinal evaluation showed that in all animals, the VTI decreased overtime in the left and right segments but remained stable in the proximal segments. Meanwhile, the calculated blood flow was significantly reduced at the site of the balloon injury

and the distal segment but maintained unchanged in the stented segment.

Comparing the acute balloon injury with the chronic injury associated with stent implantation, we reported that the response of the vessel differed with the type of intervention. The primary function of the BMS stent is to provide mechanical support. As expected, the stent allowed the maintenance of increased vessel diameter in all animals. In contrast, balloon inflation induced a short-term increase in the

**4. Discussion**

**190**

28 in the left artery.

The non-invasive, real-time imaging of the rabbit iliac arteries and the distal abdominal aorta for the quantification of lumen diameter and wall thickness using high-resolution ultrasound permit the monitoring of the progression of the wall and vessel following balloon angioplasty and endovascular stent implantation. Conveniently combined with the blood flow analysis, this methodological approach would be essential to evaluate novel therapeutic approaches to prevent hyperplasia.
