**4. Discussion**

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

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 consecutive weekly measurements.

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 challenging to perform.

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 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 28 in the left artery.

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.

**191**

*High-Resolution Ultrasound Imaging System for the Evaluation of the Vascular Response to Stent…*

Despite the neointimal hyperplasia developed within the stent, the blood flow was maintained due to the diameter enlargement resulting from the stent overexpansion. Nevertheless, it is essential to note a maximal 72% reduction of the blow flow, although the statistical significance was not reached due to the small number

The aorta underwent twice the passage of the catheter, once with the crimped stent followed by its retraction and second with the successive introduction into the contralateral artery. The vessel structure remained similar in all the animals, suggesting the absence of injury due to the procedure. An exception was observed for one animal that showed a continuous increase in the wall thickness. These effects may be explained by the large stent diameter and the placement site, close to the aortic bifurcation. Notably, the variations observed in the right artery and the aorta might be dependent on the size and location of the stents that varied between

Moreover, we provide evidence that the wall thickness and the vessel diameter significantly correlated with the histological evaluation. Besides, histology provides evidence that the wall thickening in the stented area resulted in intimal hyperplasia. Neointimal hyperplasia was also observed in the left and right proximal control segments of two animals. Our results corroborate the well-established proliferation of smooth muscle cells resulting in the wall artery thickening induced by the stent

In agreement with the literature, under conventional diet and following injury, rabbits developed wall hyperplasia that is known to be associated with inflammation and smooth muscle proliferation rather than atherosclerotic plaques that can be

Although histological analysis is essential to evaluate wall composition, inflammation and smooth muscle proliferation, longitudinal study provides a useful tool

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.

The study was supported by the Swiss National Science Foundation (SNF

316030\_157658), the University of Fribourg and the Fonds Scientifique

*DOI: http://dx.doi.org/10.5772/intechopen.88656*

of animal and large variability.

and balloon injury [14–16].

**5. Conclusion**

**Acknowledgements**

Cardiovasculaire FSC, Fribourg Hospital.

observed in hyperlipidemic rabbits [9, 17].

to record transient variation in the vessel dimensions.

animals.

*High-Resolution Ultrasound Imaging System for the Evaluation of the Vascular Response to Stent… DOI: http://dx.doi.org/10.5772/intechopen.88656*

Despite the neointimal hyperplasia developed within the stent, the blood flow was maintained due to the diameter enlargement resulting from the stent overexpansion. Nevertheless, it is essential to note a maximal 72% reduction of the blow flow, although the statistical significance was not reached due to the small number of animal and large variability.

The aorta underwent twice the passage of the catheter, once with the crimped stent followed by its retraction and second with the successive introduction into the contralateral artery. The vessel structure remained similar in all the animals, suggesting the absence of injury due to the procedure. An exception was observed for one animal that showed a continuous increase in the wall thickness. These effects may be explained by the large stent diameter and the placement site, close to the aortic bifurcation. Notably, the variations observed in the right artery and the aorta might be dependent on the size and location of the stents that varied between animals.

Moreover, we provide evidence that the wall thickness and the vessel diameter significantly correlated with the histological evaluation. Besides, histology provides evidence that the wall thickening in the stented area resulted in intimal hyperplasia. Neointimal hyperplasia was also observed in the left and right proximal control segments of two animals. Our results corroborate the well-established proliferation of smooth muscle cells resulting in the wall artery thickening induced by the stent and balloon injury [14–16].

In agreement with the literature, under conventional diet and following injury, rabbits developed wall hyperplasia that is known to be associated with inflammation and smooth muscle proliferation rather than atherosclerotic plaques that can be observed in hyperlipidemic rabbits [9, 17].

Although histological analysis is essential to evaluate wall composition, inflammation and smooth muscle proliferation, longitudinal study provides a useful tool to record transient variation in the vessel dimensions.
