Loci minoris resistentiae of the cerebral arterial network
In our study, the presence of single unruptured sIA did not influence the rupture pressure values of specific CA segments. Moreover, bifurcation regions displayed high strength, and the rupture pressure did not significantly differ based on location of the rupture of the analyzed CAs, specifically at the wall or bifurcation region. Nevertheless, based on the study of Mitchell and Jakubowski, the average rupture pressure of branched CA specimens was significantly lower than the rupture pressure of straight CA specimens.11 Alternatively, Ciszek et al. did not observe a significant difference in rupture pressure values between straight and branched CA specimens.12 In our study, rupture occurred most frequently at the wall of the analyzed CAs. During the pressure-inflation tests, the bifurcation region ruptured in 40% of MCAs from the aneurysm group and in 25% of MCAs and 12.5% of ICAs from the non-aneurysm group. However, such high strength of CA bifurcations may be counter-intuitive when considering that bifurcation regions are histologically characterized by a discontinuity of the media13 and enlarged fenestrations within the IEL.3 Finlay et al. indicated that the arrangement of adventitial collagen fibers at the bifurcation apex differs from that in the straight arterial segments. In the bifurcation region, collagen fibers are densely co-aligned and form a strong, tendon-like band that provides high strength of the CA bifurcation.14
The sIA development comprises a sequence of overlapping adaptive and degenerative processes induced by specific hemodynamic factors. Only when degenerative processes prevail over adaptive processes does wall strength decrease, leading to sIA rupture.8 Thus, not all sIAs correspond to regions of low wall strength. In a study by Ciszek et al., one sIA ruptured under pressure markedly exceeding physiological blood pressure, while another sIA sustained high intraluminal pressure values.12 Additionally, during the experiments conducted by Mitchell and Jakubowski, the sIA specimen was pressurized up to 1.6 bar (1200 mmHg) and the rupture occurred within the wall of adjacent CA.11 Similarly, in our study, none of the analyzed sIAs ruptured at physiological pressures. Furthermore, in the case of five sIA specimens, the rupture occurred remotely from the sIA, indicating its high wall strength. According to the lifelong Finnish cohort follow-up study, approximately 70% of sIAs did not rupture during the lifetime observation15 which is in line with the results of our study, as well as the aforementioned CAs pressure-inflation test studies.
Specific CA segments that are prone to sIA formation simultaneously predispose to an increased risk of sIA rupture. In a retrospective epidemiological study by Carter et al., ruptured sIAs were most frequently located in the ACommA complex. Additionally, the mean size of sIAs involving ACommA or distal branches of major CAs was smaller than that of sIAs observed at larger CAs, such as the ICA or MCA bifurcation. Carter et al. hypothesized that there is a decrease in sIA wall thickness along with a decrease in the caliber of the parent artery.16 It may be reasonable to consider Laplace’s law applied to this context: when assuming similar pressure conditions and the same diameter, sIAs with thin walls experience remarkably higher intramural stress than their thick-wall counterparts. Likewise, in our study, ACommA displayed significantly lower mean rupture pressure than the ICA and MCA bifurcation in both the aneurysm and non-aneurysm groups. However, in a study by Ciszek et al., as well as in a study by Mitchell and Jakubowski, the authors did not observe significant differences between rupture pressure values depending on the CA segment location.11,12 Further investigations, including histological studies with the measurement of wall thickness, are required to clarify whether caliber of CAs is related to the strength of their wall.
Mechanobiology of the CAs
The rupture pressure values of CAs in both analyzed groups markedly exceeded the maximal in vivo arterial blood pressure17 which is consistent with the results of earlier pressure-inflation tests of CAs. In a study of Mitchell and Jakubowski, the average rupture pressure of all analyzed CAs was 1.848 bar (1386 mmHg), while the mean CAs rupture pressure presented in a study conducted by Ciszek et al. was 2.35 atm (1786 mmHg).11,12 Such discrepancies in the literature data regarding rupture pressure values may result from the diverse age distribution of CAs donors. The mean age at the time of death of autopsy subjects was 69 years in the former study and 47 years in the latter study. Additionally, both studies revealed a significant negative dependency of CA rupture pressure with age. Thus, the relatively higher mean CA rupture pressure obtained by Ciszek et al. may be explained by the predominance of CAs harvested from younger autopsy subjects.
Gradual decrease of the rupture pressure of CAs with age, similar to the gradual increase with age of CA stiffness, may be attributable to age-related arterial wall remodeling, including IEL degeneration.4 Specifically, elastin is the main load-bearing material at low strain conditions, while collagen fibers maintain structural integrity of the CA during further increase of mechanical loadings. Progressive elastin degradation results in an age-related increase in CA stiffness at low strain regimes, indicating early recruitment of collagen fibers. Since collagen fibers are capable of slight deformations prior to failure, once the elastin function is impaired, the intramural stress within the CA wall increases under the same pressure conditions.18 Therefore, it may be conjectured that a significant decrease in rupture pressure values with age exclusively among CAs in the aneurysm group indicates more pronounced progression of elastin degradation within the arterial wall compared to CAs in the non-aneurysm group. However, we did not find a significant difference between the experimental and control groups in terms of mean CA rupture pressure. This discrepancy may be explained by the narrow range of age distribution of CAs donors. If CAs from younger and older autopsy subjects had been pressurized, then CAs from the non-aneurysm group may have presented similar negative dependency of rupture pressure with age.
Limitations
The comparison of rupture pressure values between sIAs and corresponding CA segments was limited by the small number of ruptured sIAs during the pressure-inflation tests. Also, all the analyzed CA and sIA specimens were obtained from the autopsy subjects and the experiments were conducted within 36 hours postmortem. Furthermore, in the case of CAs harvested from human autopsy subjects, the smooth muscles of the wall are consequently without tone. Due to differences between biomechanical properties of CAs collected during surgery and autopsy, presented results may not completely reflect in vivo wall strength of both CAs and sIAs.19 Alternatively, only in the case of pressure-inflation tests conducted on the specimens harvested from the autopsy subjects, rupture pressure values of sIAs and major CAs may be assessed.