The Role of the Mechanical Characteristics and Microstructure of the Porcine Aortic Wall: Implications for Abdominal Aortic Aneurysm Rupture Risk

Aneurysmal disease is a condition in which the arterial wall bulges, causing the diameter to increase by more than 50% compared to the proximal vessel.¹ This can occur in various areas such as extracranial arteries,² visceral arteries,3 arteriovenous fistulas for dialysis,^4,5 and most commonly in the thoracic and abdominal aorta.^6,7 The guideline of the European Society of Vascular and Endovascular Surgery (ESVS) states that surgical or endovascular treatment is required for an abdominal aortic aneurysm (AAA) with a diameter greater than 5 cm in women and 5.5 cm in men.¹ Deprived of surgical or endovascular intervention, the risk of rupture and, therefore, mortality increase significantly.^8,9,10

Numerous studies have been recently published on the porcine aorta^11,12,13 and a limited number of human aortic tissues harvested from the deceased or during surgery to better understand the biomechanical process behind the onset and development of AAA, as well as the risk of rupture.^14,15 Histologically, the arterial wall consists of three layers: intima, media, and adventitia, with different structures and functions.¹⁶ Mechanically, the intima only becomes significant with age,¹⁷ whereas the media primarily consists of smooth muscle cells and has a pivotal role in the wall's mechanical characteristics.¹⁶ Finally, the adventitia envelops the vessel and provides resistance to high pressure, preventing rupture.¹⁸ Niestrawska et al.¹⁹ demonstrated that the development of AAA involves several stages from a histological and biomechanical perspective, including remodeling of collagen fibers, elastin, and smooth muscle cells, and deposition of adipose cells.

The modern management of aortic aneurysms, whether thoracic or abdominal, depends on the risk-to-benefit ratio, or whether the risk of rupture justifies the risks associated with surgical repair. The current surgical decision-making process is largely based on the maximum diameter of the aneurysm.¹ However, it is known that aneurysms with diameters smaller than the threshold specified in the current guidelines²⁰ can also lead to dissection or rupture, and they may represent an alarming 40–60% of cases.^21,22 In a recent study, Arbănași et al.⁷ have shown that the ratio between the maximum diameter of an aneurysm and the diameter of the aorta at the level of the renal arteries or the celiac trunk is a better predictor of the risk of AAA rupture than the maximum diameter of the aneurysm alone. In contrast, Columbo et al.²³ found that for patients with an average age of 60 years, the optimal maximum diameter of the aorta to reduce the risk of postoperative mortality is 6.1 cm for women and 6.9 cm for men. Therefore, it is essential to develop more precise techniques to predict the rupture of an aneurysm, rather than relying on the aortic diameter, and more biomechanical analyses are necessary because aneurysm rupture occurs when the stresses on the vessel wall surpass the strength of the wall tissue.²⁴

The aim of this study is to determine the layer-specific mechanical properties of the porcine abdominal aorta under physiological stress until failure for a better understanding of the role of the microstructural elements of the arterial wall in the development and risk of AAA rupture.

In this study, eight tubular segments of the abdominal porcine aorta were taken from a local slaughterhouse from animals slaughtered exclusively for commercial purposes. Immediately after sampling, the porcine aorta segments were transported and stored at 4 °C, and they were processed and analyzed in less than 6 h.

In this experimental study, we examined the biomechanical behavior of the porcine abdominal aorta using eight tissue samples from the anterior wall. We analyzed the mechanical characteristics of the tissues under physiological stress, as well as their ability to withstand stretching until failure. We recorded an average thickness of 1.82 ± 0.34 cm for the arterial wall, 1.13 ± 0.24 cm for the media, 0.43 ± 0.056 cm for the adventitia, and 0.12 ± 0.054 cm for the intima (Figure 1).

FIGURE 1.

In the first part of the experiment, we applied a physiological stretch of 25% to each aortic wall sample. Then, we individually analyzed each layer using the same protocol. The results showed that in the circumferential axis (Figure 2A), the Cauchy stress of the adventitia (0.233 MPa) was higher than that of the media (0.182 MPa, p = 0.007), intima (0.171 MPa, p = 0.008), and the intact wall (0.192 MPa, p = 0.045). In the longitudinal axis (Figure 2B), the adventitia (0.199 MPa) was stronger than the intima (0.117 MPa, p <0.001), and the intact wall (0.156 MPa, p = 0.045), but there was no statistically significant difference compared to the media. However, the intima exhibited the lowest Cauchy stress (0.117 MPa) compared to the intact wall (0.156 MPa, p = 0.01) and the media (0.142 MPa, p <0.001). Furthermore, the media was stronger than the intact wall (0.142 MPa vs. 0.156 MPa, p = 0.03).

FIGURE 2.

FIGURE 3.

Regarding the stiffness of each layer of the arterial wall, we found the same pattern for the circumferential axis. Thus, the adventitia had a greater stiffness than the other two layers (p <0.05 for both) and the intact wall (1.75 MPa vs. 1.32 MPa, p = 0.03). In the longitudinal axis, the adventitia showed the highest rigidity, but with the mention that the intima showed greater compliance than the media (1.02 MPa vs. 1.24 MPa, p = 0.014) and the intact wall (1.02 MPa vs. 1.32 MPa, p = 0.006). These findings suggest that the shear stress on the arterial wall caused by arterial pressure affects all three layers in physiological stress. Furthermore, the adventitia has a higher concentration of collagen fibers, which makes it more rigid than the other layers.

We analyzed 15 × 5 mm samples from the circumferential axis uniaxially and subjected them to stretching until failure. As seen in Figure 4A, the adventitia was the strongest compared to the other layers and the intact wall (p <0.001 for all), and it also presented better compliance with the highest stretch ratio, as seen in Figure 4B.

FIGURE 4.

Next, we assessed the relationship between the thickness of the vascular tissue (for the intact wall and the three layers together, n = 32 samples) and mechanical characteristics at uniaxial analysis. The results showed a strong positive correlation between the thickness of vascular tissue and ultimate stress (r = 0.738, p <0.001). Additionally, there was a positive correlation between the thickness of vascular tissue and the stretch ratio (r = 0.422, p = 0.016) (Figure 5).

FIGURE 3.

The main result of this experimental biomechanical study is the presentation of the biomechanical behavior of vascular tissue and its specific layers when subjected to physiological stretching until failure for a better understanding of the role of each layer of the vascular wall in the development and risk of AAA rupture.

Many previous studies have considered the aortic wall to be a uniform, consistent structure.^30,31,32 However, it is important to acknowledge that certain structural variations in biomechanical features exist between the longitudinal and circumferential directions, as well as between different regions of the aorta for all three layers of the arterial wall.^32,33 This was observed by Weisbecker et al.³² and similar results were obtained by Noble et al.³³ The isotropic response of the intima and adventitia of the descending aorta contrasts with the similar anisotropic responses of intact wall and media samples, indicating that the mechanical response of the descending thoracic artery is primarily dominated by the behavior of the media.³⁴

The aortic wall is a biological material comprised of elastin, collagen, and smooth muscle cells. According to Peña et al.,³⁵ the media is softer than the adventitia, regardless of their position along the aorta. Additionally, samples from the abdominal aorta are stiffer than those from the descending thoracic aorta, the most significant differences in their behavior being observed in the circumferential direction. This is consistent with our results and those of previous studies that have shown that aortic stiffness increases with the distance from the heart.^36,37,38,39

Understanding the uniaxial and biaxial biomechanical behavior of the arterial wall can help in developing new therapeutic strategies to strengthen the early aneurysmal wall. Our team has recently proposed a new method for photocrosslinking adventitial collagen fibers. This involves exposing the wall to UV-A irradiation.^{25,26,27,28,29} Chirila et al.²⁷ have presented preliminary results of this new therapeutic strategy, demonstrating an increase in strength (p = 0.0015) and stiffness (p = 0.0012) of the porcine aortic adventitia. Additionally, the same team has shown the effectiveness of exposure to UV-A in the case of enzymatically degraded aortic adventitia.^26,28 Most recently, our team has demonstrated that UV-A irradiation increases the mechanical characteristics of the vascular wall on samples of normal and aneurysmal human abdominal aorta.²⁵

It is important to mention that the current study has some limitations. First, it did not include the histological analysis of the samples, and collagen and elastin fiber content was not measured. Second, it is important to consider that there are significant structural differences between porcine and human vascular tissue. Therefore, the results of this study cannot be extrapolated to human tissue. Last, the samples were not subjected to the same stress, which makes it difficult to compare the degree of anisotropy of each layer and the intact aortic wall.

The results of this study indicate that the porcine aortic wall presents the highest stiffness and strength in the adventitia when subjected to physiological stretch. The adventitia is also the strongest and most compliant layer in the uniaxial failure analysis, thus being the last mechanical resistance structure of the arterial wall. In addition, the samples’ thickness is correlated with the mechanical characteristics of the tissue when stretched to failure. It is crucial to avoid injuring and aggressively manipulating the adventitia during surgery to maintain the resistance structure of the vascular wall and prevent post-operative complications like anastomotic pseudoaneurysm and anastomotic rupture.