- Email: [email protected]
Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection
Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Contents lists available at ScienceDirect
Journal of Biomechanics journal homepage: www.elsevier.com/locate/jbiomech www.JBiomech.com
Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection Hiroshi Yamada a,n, Noriyuki Sakata b, Hideichi Wada c, Tadashi Tashiro c, Eiki Tayama d a Department of Biological Functions Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan b Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan c Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan d Department of Cardiovascular Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan
art ic l e i nf o
a b s t r a c t
Article history: Accepted 21 June 2015
Degradation and fragmentation of elastic fibers in the media dilate the aortic wall excessively in patients with acute Stanford type A aortic dissection (AD). Such dilatation occurs not via aortic stiffening, which is diagnosed using imaging under physiological loading, but due to the abovementioned intrinsic changes in elastic fibers, which can be detected at the low-stress region of the stress–strain relationship. Our objective is to determine an age-related correlation between distensibility and histology. We conducted uniaxial stretching tests and a histological evaluation of the ascending aorta (AA) using AD samples obtained at surgery from 9 elderly patients (aged 52–85 yr), with no heritable connective tissue disorders, and control (CN) samples from 10 subjects at autopsy (aged 56–86 yr). We compared the distensibility, or an increase in strain for the uniaxial tensile stress of 0–50 kPa, between the AD and CN groups, and correlated it with age and histology. Distensibility was significantly greater in the AD than that in the CN group (p ¼0.030), but elastin content was significantly lower (p ¼0.0025). The positive correlation between distensibility and elastin content in CN samples suggests that the distensibility increases with elastic fiber histological abnormalities. The age-matched collagen content decreased with the age of the patients, and did not differ between the AD and CN groups. The age-matched distensibility in the AD and CN groups decreased and became closer with aging. Such intrinsic properties should be considered during imaging to assess distensibility in patients with AD. & 2015 Elsevier Ltd. All rights reserved.
Keywords: Aortic dissection Ascending aorta Stress–strain relationship Elastin Collagen
1. Introduction Emergency surgery is conducted frequently in patients over 50 years of age with acute Stanford type A aortic dissection (AD), which usually accompanies a wall rupture. The aorta is subjected to longitudinal tension and repeated intraluminal pressure, and rupture or excess dilatation in patients with AD is caused by degradation and fragmentation of medial elastic fibers (Nakashima et al. 1990a; Tsai et al. 2005). Nakashima et al. (1990b) observed an AA with a Stanford type A AD by electron microscopy and reported that the interlaminar fibers between the elastic laminae were arranged irregularly and had decreased in number, particularly in the outer media in 6 of 10 cases. Fritze et al. (2012) reported that the proximal AA in patients (40–86 yr of age) undergoing coronary artery bypass grafting exhibited a dramatic decrease in the number of interlaminar fibers n
Corresponding author. Tel./fax: þ 81 93 695 6031. E-mail address: [email protected] (H. Yamada).
and an increase in laminae distance with aging. A review by Tsamis et al. (2013) showed that collagen content increases with age both in the normal AA and in cases of AD. Aging results in dilation of the aortic wall in people 20–94 years of age (Sawabe et al., 2011) and stiffens in those over 50 (Hayashi, 1993). Aging also decreases AA distensibility (Redheuil et al. 2010; Martin et al. 2013), which has been studied for the AA with heritable connective tissue disorders such as Marfan syndrome under physiological loading (Okamoto et al., 2003; Baumgartner et al., 2006), as well as for the AA with dilated bicuspid aortic valve under low strain (Choudhury et al., 2009). Here we focus on the effects of aging on the mechanical properties of the AA in patients with AD and without connective tissue disorders. The intrinsic mechanical properties of the aorta can be described by the stress–strain relationship. Changes in the intrinsic mechanical properties of the AA with histologic abnormalities and aging cannot be obtained by clinical imaging under physiological loading conditions. Rather than the pressure– diameter relationship between diastolic and systolic pressures, we
http://dx.doi.org/10.1016/j.jbiomech.2015.06.025 0021-9290/& 2015 Elsevier Ltd. All rights reserved.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
2
Subject ID AD-1 AD-2 AD-3 AD-4 AD-5 AD-6 AD-7 AD-8 AD-9 Mean (SD)
Age (yr)
Sex
52 58 78 77 79 85 79 62 67 70.8 (11.4)
De Bakey classification
M M F F M F M M M
I I II I I II I I I
Max. dia. of ascending aorta (mm)
Store (days) a
48 55 40 39 46 52 51 44 67 49.1 (8.6)
1 24 4 85 46 68 7 123 3 40.1 (43.7)
Thickness of specimen (mm) 2.1 1.7b 2.1 1.2 1.7 1.2 1.1 1.8 1.9 1.66 (0.38)
Subject ID
Age (yr)
Sex
Pathological diagnosis
Store (days)
Thickness of specimen (mm)
CN-1 CN-2 CN-3 CN-4 CN-5 CN-6 CN-7 CN-8 CN-9 CN-10 Mean (SD)
86 75 68 63 78 59 58 56 61 75 67.9 (10.1)
F M M F F M M M F F
Acute interstitial pneumonia Bronchopneumoia Acute myeloid leukemia Polycystic kidney disease Nephrotic syndrome Idiopathic interstitial pneumonia Chronic myocardial infarction Alcoholic liver cirrhosis Breast cancer Acute pancreatitis
6 32 5 68 0a 84 59 6 1 1 26.2 (32.4)
1.3 1.7 1.5 1.3 1.4 1.8 1.5 1.5 1.5 1.3 1.46 (0.17)
AD: aortic dissection, CN: control, M: male, F: female. a b
Refrigerated at 5 °C. A thin surface tissue of false lumen was removed to prepare the specimen.
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
Table 1 Clinicopathological characteristics of the subjects and attributes of the specimens.
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
3
Fig. 1. Example collagen content (area fraction) measurement. Collagen was extracted from a Picosirus red-stained (left image) AA section using the Microanalyzer software (green regions in the right image). Bar, 500 μm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
should use the pressure–diameter relationship between zero pressure and systolic pressure to determine the intrinsic deformation characteristics of the nonlinear elastic aorta (Yamada and Momii, 2004). In this study, we investigated age-related distensibility and its correlation with histology; i.e., elastin and collagen, using AA specimens from patients with AD and autopsy control (CN) to reveal the intrinsic changes in the AA in patients with AD aged over 50 years by focusing on the stress–strain relationship at low stresses, which reflects abnormalities of the elastic fibers. 2. Materials and methods 2.1. Materials AD samples were obtained from the AAs of nine patients with AD (52–85 yr of age) without Marfan syndrome during emergency surgery at Fukuoka University Hospital from January 2012 to November 2012 (Table 1). CN samples were excised from atherosclerosis-free regions of the AAs in 10 subjects (56–86 yr of age) without AD at postmortem examinations within 24 h after death at the hospital between January 2012 and November 2012. The aortic tissues were frozen at 40 °C or at 5 °C for the periods shown in Table 1. All samples were examined by a senior pathologist (N. S.) with an interest in cardiovascular disease. This research protocol was approved by the Research Ethics Committee of University Hospital, Fukuoka University (no. 11-11-11). Informed consent was obtained from the patients or from relatives before obtaining samples. 2.2. Mechanical testing 2.2.1. Specimen preparation Stored tissue was thawed at room temperature. The adventitia or thin surfacelayer of the false lumen was removed from the samples (see footnote b in Table 1). The specimens were cut into a strip-like shape along the circumferential direction at a length of 20 mm and width of 3 mm. Diameter-related indices of wall distensibility have been evaluated in medical image analyses of the ascending aorta of non-ruptured patients (Redheuil et al. 2010; Martin et al. 2013). Therefore, we focused on the circumferential direction to obtain a measure of distensibility as an index of the diameter-related deformation characteristics. 2.2.2. Experimental setup The uniaxial stretching system consisted of a loading component, two sensor components, specimen-mount components, an A/D converter, and a personal computer. The loading component was a stepping-motor driven stage (SGSP20-20(Z), SIGMA KOKI, Tokyo, Japan) with a stage controller (SHOT-302GS, SIGMA KOKI) to stretch the
specimen vertically with a fine pitch of 8 nm per pulse. The sensor components consisted of a vertical load cell with a capacity of 2N (LVS-200GA, Kyowa, Tokyo, Japan), which was fixed on the stage and connected to a strain amplifier (DAS-405C, Minebea, Tokyo, Japan) and a laser displacement sensor (ZX-SD41 0.5M, Omron, Kyoto, Japan) with a beam on the top surface of the load cell to measure vertical displacement of the upper specimen grip (clip type, mass 20 g, Shimadzu, Kyoto, Japan). A fine polishing mesh (Polinet Sheet A-150, KOYO, Japan) was attached to each surface of the specimengrips to obtain sufficient friction for a slippery specimen. The SGTERM software package (SIGMA KOKI) was used to apply a linear reciprocating motion from the computer (Latitude D620, Dell) to the stage through the controller. Synchronized output of the load cell and the displacement sensor was transmitted to the computer through a 12-bitA/D converter (ADI12-8(USB), Contec, Osaka, Japan) with a 50-ms sampling time. The specimen-mount components consisted of a saline bath and a pair of specimen grips. An acrylic rectangular bath was filled with physiological saline, and the temperature was kept at 37 °C by circulating hot water in a rolled tube in the bottom of the bath. The upper specimen grip hung on a jig connected to the load cell, which held the upper region of specimens over 5 mm in length. The lower region of the specimen was held with a lower specimen grip placed on the bottom of the bath to maintain a grip-to-grip distance of 10 mm. 2.2.3. Uniaxial stretching test Photographs of the specimen were obtained from the front and side before mounting, and initial specimen thickness, width, and cross-sectional area were measured using the ImageJ software (National Institutes of Health, Bethesda, MD, USA). Nominal strain was calculated using a reference length of the grip-to-grip distance when the specimen had no slack. Dead load was measured before mounting a specimen to the specimen grips. After mounting the specimen, the upper position of the specimen was adjusted vertically to obtain the dead load as an unloaded state of the specimen. The specimen was preconditioned with six cycles of stretching and unstretching with a 2-mm range and velocity of 0.1 mm/s. Then, the specimen was stretched vertically with a velocity of 0.1 mm/s. The side view of the specimen was video recorded during stretching with a digital camera (EOS 60D, Canon, Tokyo, Japan) equipped with a macro lens (EF50mm F2.5, Canon). Nominal stress was obtained by dividing load by the initial cross-sectional area. The strain increase in the low-stress range of 0–50 kPa was used as an index of distensibility of the aortic wall to reflect the mechanical properties of elastic fibers. 2.3. Histology Aortic samples adjacent to those used for the stretching test were fixed in 10% buffered formalin for microscopic observations. After dehydration with ethanol, the tissues were embedded in paraffin. The paraffin sections were deparaffinized and stained with hematoxylin and eosin, Picosirus red staining for collagen, and modified Movat staining for elastin and proteoglycans. Images of the aortic sections were recorded with a digital camera. As shown in Fig. 1, the area of collagen and elastin was measured as a percentage of total area examined using the Microanalyzer 1.1 software (Japan
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
4
Poladigital, Tokyo, Japan). The area fractions measured at the three sites were averaged for each component. The morphometric analysis was performed by a pathologist (N. S.) who was blinded to the stretching test data. 2.4. Statistical analysis Welch’s t-test was used to compare the numerical data, including patient age, thickness of specimen, distensibility and elastin and collagen contents between the AD and CN groups. A linear regression analysis was carried out between two continuous variables. The relationship among the distensibility, elastin and collagen contents of aorta, and age was assessed using Pearson correlation analysis. A logistic regression analysis was carried out to calculate the contribution of elastin and collagen to distinguish the distensibility between AD and CN and between groups younger than 70 years and older than 70 years. A p-valueo 0.05 was considered to indicate significance. All analyses were conducted using the StatFlex 6.0 software (Artech, Osaka, Japan).
3. Results The AD patient group was aged 70.87 11.4 years (mean7 standard deviation), and the CN group was 67.9710.1 years (see Table 1). There were no statistically significant differences between the AD and CN groups in terms of age (p ¼0.57) and the thickness of the specimen (p ¼0.34; where AD-2 was excluded from statistical analysis) using Welch’s t-test. Linear regression between the age in years x and the thickness in millimeters y gave y¼3.39x–0.02 for the AD group and y¼ 1.95x–0.01 for the CN group, showing that the AD group was thicker than the CN group patients aged less than 70 years. The multiple correlation coefficients between the storage time and the distensibility were 0.0096 for the AD group and 0.47 for the CN group, showing no correlation between the storage time and the distensibility. The modified Movat-stained sections of AA in CN subjects showed high elastic fiber content in the entire wall, which appeared as separate wavy continuous fibers throughout the media (Fig. 2A, and C). In contrast, those of the AAs in patients
with AD showed a slight irregular arrangement and decreased elastic fiber content in the wall, which was disrupted in parts (Fig. 2B, and D). Fig. 3a compares the elastin and collagen contents (area fraction) of the AD and CN groups. The AD group showed significantly decreased elastin content compared to that in the CN group (p ¼0.0025). In contrast, no significant difference was found in collagen content between the groups. Table 2a shows a logistic regression model to distinguish between the AD and CN groups by elastin or collagen content. The regression coefficient for percent elastin, but not that for percent collagen, was statistically significant (p ¼0.020). Fig. 3b compares elastin and collagen contents (area fraction) between the o70 yr of age (YT70) and 470 yr of age (OT70) groups. The OT70 group had a significantly higher collagen content compared to the YT70 group (p ¼0.0086). However, no significant difference was found in elastin content. Table 2b lists a logistic regression model to distinguish between the YT70 and OT70 groups by elastin or collagen content. The regression coefficient for the collagen fraction was statistically significant (p ¼0.034), but that for the elastin fraction was not. Fig. 4a and b shows the stress–strain relationships in theo70 yr and470 yr age AD and CN subgroups, respectively. The maximum point of each stress–strain curve corresponded to remarkable specimen damage or a slip of the specimen by the specimen grip, both of which caused irregular specimen deformation. The AA became stiffer with age in both the AD and CN groups. Fig. 5 compares the age-related distensibility between the AD and CN groups. There was a statistically significant difference between AD and CN groups in the distensibility (p¼ 0.044) using Welch’s t-test. The slope of the regression line for AD, ( 0.008/yr of age) was double that for CN ( 0.004/yr of age). A comparison of the regression lines showed steady recovery of abnormal distensibility with aging in patients with AD compared to the control group.
Fig. 2. Modified Movat-stained sections of the AA in a CN subject (images A, C) and a patient with AD (images B, D). Bar, 500 μm (A, B), 200 μm (C, D).
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Fig. 6a and b shows age-related elastin and collagen contents (area fraction), respectively, in the AD and CN groups. Elastin content had a negative relationship with age in the CN group (r ¼ 0.66, p ¼0.036), but no relationship in the AD group (p ¼0.20). Collagen content tended to increase with age, and no difference in age-matched content was detected between the CN and AD groups. Fig. 7a and b shows the correlations between distensibility and elastin and collagen contents (area fraction), respectively, in the AD and CN groups. The AD group tended to be more distensible than the CN at the same elastin or collagen content.
5
4. Discussion As aforementioned, Welch’s t-test revealed no statistical difference in age and statistically significant difference in distensibility between the AD and CN groups. Fig. 5 shows that the intrinsic distensibility of the AA tended to be larger in patients with AD than that in age-matched CN subjects at low stress levels. We think that the aorta of patients with AD is clinically assessed as stiff because a dilated aortic wall due to its elastin abnormalities is inflated to a steep range of the stress–strain relationship by blood
Fig. 3. (a) Comparisons of elastin and collagen contents (area fraction) (a) between the AD and CN groups and (b) between theo 70 yr (YT70) and 470 yr of age (OT70) groups. Asterisks denote statistically significant differences: ** p o 0.01.
Table 2 (a) Logistic regression model to distinguish between AD and CN groups by elastin or collagen content (area fraction). (b) Logistic regression model to distinguish betweeno 70 yr (YT70) and 4 70 yr of age (OT70) groups by elastin or collagen content (area fraction). (a) Model parameter
Regression coefficient
SE
p-value
Odds ratio
%Elastin %Collagen Intercept
0.268 0.011 9.564
0.115 0.067 4.758
0.020 0.868
0.764 0.988
Model parameter
Regression coefficient
SE
p-value
Odds ratio
%Elastin %Collagen Intercept
0.137 0.178 0.220
0.086 0.084 2.939
0.110 0.034
0.871 1.195
(b)
Fig. 4. Stress–strain relationships of individual AD and CN specimens in patients (a) o 70 yr and (b)470 yr of age. Note that an irregularity in the stress–strain curve was observed at the maximum stress point due to mechanical damage to the specimen or a slip of the specimen in the specimen grip.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
6
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
pressure, and the diameter changes due to the small difference between diastolic and systolic pressures. The elastin content (area fraction) was lower in the AD samples than in the CN samples (Fig. 3a), which appeared to contradict the positive correlation between distensibility and elastin content in the CN samples (Fig. 7a), while the collagen contents were similar. We speculate that the increase in distensibility with AD was correlated with elastic fiber abnormalities. Nakashima et al. (1990b) showed an apparent irregularity in arrangement and shape and a decrease in the number of interlaminar elastic fibers in the AA media in six of 10 cases of type A AD. Klima et al. (1983) found elastic fragmentation in 94% of patients with ascending aortic aneurysm, which was not associated with Marfan syndrome. Fritze et al. (2012) showed destruction of elastic laminae and loss of interlaminar crosslinks in AD-free AAs with aging.
Wang et al. (2005) reported a reduction in the elastin content in the aorta with AD for patients aged 60 yr on average, which is in agreement with the data shown in Fig. 3a. Andreotti et al. (1985) reported increased collagen content with aging, but no change in the elastin content. These trends are consistent with our data (see Figs. 3b and 6 and Table 2b), which lead to a decrease in the distensibility with aging (see Fig. 5). The initiation and progress of the tear and rupture of the AA wall in patients with AD are also important issues. Iliopoulos et al. (2009) carried out a uniaxial tensile loading test for strip-like specimens of non-dissecting AA aneurysms in 12 patients (age 6979 yr) and showed that the failure stress in the circumferential direction was almost 2 MPa but varied considerably. The maximum stress of o500 kPa in our results (Fig. 3) was almost out of the range of the failure stress in their experiment. Pasta et al.
Fig. 5. Age-related distensibility in the stress range of 0–50 kPa for the AD and CN groups.
Fig. 6. Age-related (a) elastin and (b) collagen contents (area fraction) in the AD and CN groups.
Fig. 7. Correlations between the distensibility and (a) elastin and (b) collagen contents (area fraction) in the AD and CN groups.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
(2012) conducted a peeling test on AAs obtained from patients with TAV and BAV to investigate delamination tissue strength. Such shear is another means by which the initiation and progress of AD can be understood. Our statistical analysis on the storage time showed no effect on the distensibility at low stress levels. However, a better control of the storage time for the specimens would suppress the effects of freezing on the distensibility (Langerak et al., 2001; Goh et al., 2010; Sugita and Matsumoto, 2013). The uniaxial loading test with 20 mm strip-like specimens was a study limitation. Biaxial loading tests reproduce a physiological loading condition by controlling the stress/strain state not only in the circumferential direction, but also in the longitudinal direction, as performed for 20–25 mm square specimens (Okamoto et al. 2003) and 15 mm square ones (Choudhury et al. 2009). In conclusion, we revealed age-related distensibility and aortic wall content in elderly patients with acute AD and CN. The correlation results showed that the distensibility of the AA in patients with acute AD was greater than that in age-matched CN subjects, and that it became more similar to that of the CN subjects with aging, which was accompanied by increased collagen content. The increase in collagen content as a consequence of vascular wall remodeling with aging likely suppresses the increasing rate of distensibility for acute AD candidate patients, and therefore may delay emergency surgery for acute AD in patients older than 50 years of age. Our results provide data on intrinsic mechanical properties that underlie the deformation characteristics of the aorta and cannot be detected using clinical imaging of the AD.
Conflict of interest statement None of the authors has a conflict of interest to disclose.
Acknowledgments This research was supported in part by funds from the Mitsui Life Social Welfare Foundation (2011/7) and the Central Research Institutes of Fukuoka University (No. 117008). The authors thank Ms. Hiroyo Fukagawa for technical assistance with the histological observations.
References Andreotti, L., Bussotti, A., Cammelli, D., di Giovine, F., Sampognaro, S., Sterrantino, G., Varcasia, G., Arcangeli, P., 1985. Aortic connective tissue in ageing–a biochemical study. Angiology 36, 872–879.
7
Baumgartner, D., Baumgartner, C., Schermer, E., Engl, G., Schweigmann, U., Matyas, G., Steinmann, B., Stein, J.I., 2006. Different patterns of aortic wall elasticity in patients with Marfan syndrome: a noninvasive follow-up study. J. Thorac. Cardiovasc. Surg. 132, 811–819. Choudhury, N., Bouchot, O., Rouleau, L., Tremblay, D., Cartier, R., Butany, J., Mongrain, R., Leask, R.L., 2009. Local mechanical and structural properties of healthy and diseased human ascending aorta tissue. Cardiovasc. Pathol. 18, 83–91. Fritze, O., Romero, B., Schleicher, M., Jacob, M.P., Oh, D.Y., Starcher, B., Schenke-Layland, K., Bujan, J., Stock, U.A., 2012. Age-related changes in the elastic tissue of the human aorta. J. Vasc. Res. 49, 77–86. Goh, K.L., Chen, Y., Chou, S.M., Listrat, A., Bechet, D., Wess, T.J., 2010. Effects of frozen storage temperature on the elasticity of tendons from a small murine model. Animal 4, 1613–1617. Hayashi, K., 1993. Experimental approaches on measuring the mechanical properties and constitutive laws of arterial walls. J. Biomech. Eng. 115, 481–488. Iliopoulos, D.C., Deveja, R.P., Kritharis, E.P., Perrea, D., Sionis, G.D., Toutouzas, K., Stefanadis, C., Sokolis, D.P., 2009. Regional and directional variations in the mechanical properties of ascending thoracic aortic aneurysms. Med. Eng. Phys. 31, 1–9. Klima, T., Spjut, H.J., Coelho, A., Gray, A.G., Wukasch, D.C., Reul Jr., G.J., Cooley, D.A., 1983. The morphology of ascending aortic aneurysms. Hum. Pathol. 14, 810–817. Langerak, S.E., Groenink, M., van der Wall, E.E., Wassenaar, C., Vanbavel, E., van Baal, M.C., Spaan, J.A., 2001. Impact of current cryopreservation procedures on mechanical and functional properties of human aortic homografts. Transpl. Int. 14, 248–255. Martin, C., Sun, W., Primiano, C., McKay, R., Elefteriades, J., 2013. Age-dependent ascending aorta mechanics assessed through multiphase CT. Ann. Biomed. Eng. 41, 2565–2574. Nakashima, Y., Kurozumi, T., Sueishi, K., Tanaka, K., 1990a. Dissecting aneurysm: a clinicopathologic and histopathologic study of 111 autopsied cases. Hum. Pathol. 21, 291–296. Nakashima, Y., Shiokawa, Y., Sueishi, K., 1990b. Alterations of elastic architecture in human aortic dissecting aneurysm. Lab. Investig. 62, 751–760. Okamoto, R.J., Xu, H., Kouchoukos, N.T., Moon, M.R., Sundt 3rd, T.M., 2003. The influence of mechanical properties on wall stress and distensibility of the dilated ascending aorta. J. Thorac. Cardiovasc. Surg. 126, 842–850. Pasta, S., Phillippi, J.A., Gleason, T.G., Vorp, D.A., 2012. Effect of aneurysm on the mechanical dissection properties of the human ascending thoracic aorta. J. Thorac. Cardiovasc. Surg. 143, 460–467. Redheuil, A., Yu, W.C., Wu, C.O., Mousseaux, E., de Cesare, A., Yan, R., Kachenoura, N., Bluemke, D., Lima, J.A.C., 2010. Reduced ascending aortic strain and distensibility earliest manifestations of vascular aging in humans. Hypertension 55, 319–326. Sawabe, M., Hamamatsu, A., Chida, K., Mieno, M.N., Ozawa, T., 2011. Age is a major pathobiological determinant of aortic dilatation: a large autopsy study of community deaths. J. Atheroscler. Thromb. 18, 157–165. Sugita, S., Matsumoto, T., 2013. Novel biaxial tensile test for studying aortic failure phenomena at a microscopic level. Biomed. Eng. Online 12, 3. Tsai, T.T., Nienaber, C.A., Eagle, K.A., 2005. Acute aortic syndromes. Circulation 112, 3802–3813. Tsamis, A., Krawiec, J.T., Vorp, D.A., 2013. Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review. J. R. Soc. Interface 10, 20121004. Wang, X., LeMaire, S.A., Chen, L., Carter, S.A., Shen, Y.H., Gan, Y., Bartsch, H., Wilks, J.A., Utama, B., Ou, H., Thompson, R.W., Coselli, J.S., Wang, X.L., 2005. Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection. Surgery 138, 352–359. Yamada, H., Momii, S., 2004. Evaluation of possible stress distributions in abdominal aorta on the basis of physiologically loading data. In: Proceedings of the ASME 2004 International Mechanical Engineering Congress and Exposition. Anaheim.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
Contents lists available at ScienceDirect
Journal of Biomechanics journal homepage: www.elsevier.com/locate/jbiomech www.JBiomech.com
Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection Hiroshi Yamada a,n, Noriyuki Sakata b, Hideichi Wada c, Tadashi Tashiro c, Eiki Tayama d a Department of Biological Functions Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan b Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan c Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan d Department of Cardiovascular Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan
art ic l e i nf o
a b s t r a c t
Article history: Accepted 21 June 2015
Degradation and fragmentation of elastic fibers in the media dilate the aortic wall excessively in patients with acute Stanford type A aortic dissection (AD). Such dilatation occurs not via aortic stiffening, which is diagnosed using imaging under physiological loading, but due to the abovementioned intrinsic changes in elastic fibers, which can be detected at the low-stress region of the stress–strain relationship. Our objective is to determine an age-related correlation between distensibility and histology. We conducted uniaxial stretching tests and a histological evaluation of the ascending aorta (AA) using AD samples obtained at surgery from 9 elderly patients (aged 52–85 yr), with no heritable connective tissue disorders, and control (CN) samples from 10 subjects at autopsy (aged 56–86 yr). We compared the distensibility, or an increase in strain for the uniaxial tensile stress of 0–50 kPa, between the AD and CN groups, and correlated it with age and histology. Distensibility was significantly greater in the AD than that in the CN group (p ¼0.030), but elastin content was significantly lower (p ¼0.0025). The positive correlation between distensibility and elastin content in CN samples suggests that the distensibility increases with elastic fiber histological abnormalities. The age-matched collagen content decreased with the age of the patients, and did not differ between the AD and CN groups. The age-matched distensibility in the AD and CN groups decreased and became closer with aging. Such intrinsic properties should be considered during imaging to assess distensibility in patients with AD. & 2015 Elsevier Ltd. All rights reserved.
Keywords: Aortic dissection Ascending aorta Stress–strain relationship Elastin Collagen
1. Introduction Emergency surgery is conducted frequently in patients over 50 years of age with acute Stanford type A aortic dissection (AD), which usually accompanies a wall rupture. The aorta is subjected to longitudinal tension and repeated intraluminal pressure, and rupture or excess dilatation in patients with AD is caused by degradation and fragmentation of medial elastic fibers (Nakashima et al. 1990a; Tsai et al. 2005). Nakashima et al. (1990b) observed an AA with a Stanford type A AD by electron microscopy and reported that the interlaminar fibers between the elastic laminae were arranged irregularly and had decreased in number, particularly in the outer media in 6 of 10 cases. Fritze et al. (2012) reported that the proximal AA in patients (40–86 yr of age) undergoing coronary artery bypass grafting exhibited a dramatic decrease in the number of interlaminar fibers n
Corresponding author. Tel./fax: þ 81 93 695 6031. E-mail address: [email protected] (H. Yamada).
and an increase in laminae distance with aging. A review by Tsamis et al. (2013) showed that collagen content increases with age both in the normal AA and in cases of AD. Aging results in dilation of the aortic wall in people 20–94 years of age (Sawabe et al., 2011) and stiffens in those over 50 (Hayashi, 1993). Aging also decreases AA distensibility (Redheuil et al. 2010; Martin et al. 2013), which has been studied for the AA with heritable connective tissue disorders such as Marfan syndrome under physiological loading (Okamoto et al., 2003; Baumgartner et al., 2006), as well as for the AA with dilated bicuspid aortic valve under low strain (Choudhury et al., 2009). Here we focus on the effects of aging on the mechanical properties of the AA in patients with AD and without connective tissue disorders. The intrinsic mechanical properties of the aorta can be described by the stress–strain relationship. Changes in the intrinsic mechanical properties of the AA with histologic abnormalities and aging cannot be obtained by clinical imaging under physiological loading conditions. Rather than the pressure– diameter relationship between diastolic and systolic pressures, we
http://dx.doi.org/10.1016/j.jbiomech.2015.06.025 0021-9290/& 2015 Elsevier Ltd. All rights reserved.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
2
Subject ID AD-1 AD-2 AD-3 AD-4 AD-5 AD-6 AD-7 AD-8 AD-9 Mean (SD)
Age (yr)
Sex
52 58 78 77 79 85 79 62 67 70.8 (11.4)
De Bakey classification
M M F F M F M M M
I I II I I II I I I
Max. dia. of ascending aorta (mm)
Store (days) a
48 55 40 39 46 52 51 44 67 49.1 (8.6)
1 24 4 85 46 68 7 123 3 40.1 (43.7)
Thickness of specimen (mm) 2.1 1.7b 2.1 1.2 1.7 1.2 1.1 1.8 1.9 1.66 (0.38)
Subject ID
Age (yr)
Sex
Pathological diagnosis
Store (days)
Thickness of specimen (mm)
CN-1 CN-2 CN-3 CN-4 CN-5 CN-6 CN-7 CN-8 CN-9 CN-10 Mean (SD)
86 75 68 63 78 59 58 56 61 75 67.9 (10.1)
F M M F F M M M F F
Acute interstitial pneumonia Bronchopneumoia Acute myeloid leukemia Polycystic kidney disease Nephrotic syndrome Idiopathic interstitial pneumonia Chronic myocardial infarction Alcoholic liver cirrhosis Breast cancer Acute pancreatitis
6 32 5 68 0a 84 59 6 1 1 26.2 (32.4)
1.3 1.7 1.5 1.3 1.4 1.8 1.5 1.5 1.5 1.3 1.46 (0.17)
AD: aortic dissection, CN: control, M: male, F: female. a b
Refrigerated at 5 °C. A thin surface tissue of false lumen was removed to prepare the specimen.
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
Table 1 Clinicopathological characteristics of the subjects and attributes of the specimens.
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
3
Fig. 1. Example collagen content (area fraction) measurement. Collagen was extracted from a Picosirus red-stained (left image) AA section using the Microanalyzer software (green regions in the right image). Bar, 500 μm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
should use the pressure–diameter relationship between zero pressure and systolic pressure to determine the intrinsic deformation characteristics of the nonlinear elastic aorta (Yamada and Momii, 2004). In this study, we investigated age-related distensibility and its correlation with histology; i.e., elastin and collagen, using AA specimens from patients with AD and autopsy control (CN) to reveal the intrinsic changes in the AA in patients with AD aged over 50 years by focusing on the stress–strain relationship at low stresses, which reflects abnormalities of the elastic fibers. 2. Materials and methods 2.1. Materials AD samples were obtained from the AAs of nine patients with AD (52–85 yr of age) without Marfan syndrome during emergency surgery at Fukuoka University Hospital from January 2012 to November 2012 (Table 1). CN samples were excised from atherosclerosis-free regions of the AAs in 10 subjects (56–86 yr of age) without AD at postmortem examinations within 24 h after death at the hospital between January 2012 and November 2012. The aortic tissues were frozen at 40 °C or at 5 °C for the periods shown in Table 1. All samples were examined by a senior pathologist (N. S.) with an interest in cardiovascular disease. This research protocol was approved by the Research Ethics Committee of University Hospital, Fukuoka University (no. 11-11-11). Informed consent was obtained from the patients or from relatives before obtaining samples. 2.2. Mechanical testing 2.2.1. Specimen preparation Stored tissue was thawed at room temperature. The adventitia or thin surfacelayer of the false lumen was removed from the samples (see footnote b in Table 1). The specimens were cut into a strip-like shape along the circumferential direction at a length of 20 mm and width of 3 mm. Diameter-related indices of wall distensibility have been evaluated in medical image analyses of the ascending aorta of non-ruptured patients (Redheuil et al. 2010; Martin et al. 2013). Therefore, we focused on the circumferential direction to obtain a measure of distensibility as an index of the diameter-related deformation characteristics. 2.2.2. Experimental setup The uniaxial stretching system consisted of a loading component, two sensor components, specimen-mount components, an A/D converter, and a personal computer. The loading component was a stepping-motor driven stage (SGSP20-20(Z), SIGMA KOKI, Tokyo, Japan) with a stage controller (SHOT-302GS, SIGMA KOKI) to stretch the
specimen vertically with a fine pitch of 8 nm per pulse. The sensor components consisted of a vertical load cell with a capacity of 2N (LVS-200GA, Kyowa, Tokyo, Japan), which was fixed on the stage and connected to a strain amplifier (DAS-405C, Minebea, Tokyo, Japan) and a laser displacement sensor (ZX-SD41 0.5M, Omron, Kyoto, Japan) with a beam on the top surface of the load cell to measure vertical displacement of the upper specimen grip (clip type, mass 20 g, Shimadzu, Kyoto, Japan). A fine polishing mesh (Polinet Sheet A-150, KOYO, Japan) was attached to each surface of the specimengrips to obtain sufficient friction for a slippery specimen. The SGTERM software package (SIGMA KOKI) was used to apply a linear reciprocating motion from the computer (Latitude D620, Dell) to the stage through the controller. Synchronized output of the load cell and the displacement sensor was transmitted to the computer through a 12-bitA/D converter (ADI12-8(USB), Contec, Osaka, Japan) with a 50-ms sampling time. The specimen-mount components consisted of a saline bath and a pair of specimen grips. An acrylic rectangular bath was filled with physiological saline, and the temperature was kept at 37 °C by circulating hot water in a rolled tube in the bottom of the bath. The upper specimen grip hung on a jig connected to the load cell, which held the upper region of specimens over 5 mm in length. The lower region of the specimen was held with a lower specimen grip placed on the bottom of the bath to maintain a grip-to-grip distance of 10 mm. 2.2.3. Uniaxial stretching test Photographs of the specimen were obtained from the front and side before mounting, and initial specimen thickness, width, and cross-sectional area were measured using the ImageJ software (National Institutes of Health, Bethesda, MD, USA). Nominal strain was calculated using a reference length of the grip-to-grip distance when the specimen had no slack. Dead load was measured before mounting a specimen to the specimen grips. After mounting the specimen, the upper position of the specimen was adjusted vertically to obtain the dead load as an unloaded state of the specimen. The specimen was preconditioned with six cycles of stretching and unstretching with a 2-mm range and velocity of 0.1 mm/s. Then, the specimen was stretched vertically with a velocity of 0.1 mm/s. The side view of the specimen was video recorded during stretching with a digital camera (EOS 60D, Canon, Tokyo, Japan) equipped with a macro lens (EF50mm F2.5, Canon). Nominal stress was obtained by dividing load by the initial cross-sectional area. The strain increase in the low-stress range of 0–50 kPa was used as an index of distensibility of the aortic wall to reflect the mechanical properties of elastic fibers. 2.3. Histology Aortic samples adjacent to those used for the stretching test were fixed in 10% buffered formalin for microscopic observations. After dehydration with ethanol, the tissues were embedded in paraffin. The paraffin sections were deparaffinized and stained with hematoxylin and eosin, Picosirus red staining for collagen, and modified Movat staining for elastin and proteoglycans. Images of the aortic sections were recorded with a digital camera. As shown in Fig. 1, the area of collagen and elastin was measured as a percentage of total area examined using the Microanalyzer 1.1 software (Japan
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
4
Poladigital, Tokyo, Japan). The area fractions measured at the three sites were averaged for each component. The morphometric analysis was performed by a pathologist (N. S.) who was blinded to the stretching test data. 2.4. Statistical analysis Welch’s t-test was used to compare the numerical data, including patient age, thickness of specimen, distensibility and elastin and collagen contents between the AD and CN groups. A linear regression analysis was carried out between two continuous variables. The relationship among the distensibility, elastin and collagen contents of aorta, and age was assessed using Pearson correlation analysis. A logistic regression analysis was carried out to calculate the contribution of elastin and collagen to distinguish the distensibility between AD and CN and between groups younger than 70 years and older than 70 years. A p-valueo 0.05 was considered to indicate significance. All analyses were conducted using the StatFlex 6.0 software (Artech, Osaka, Japan).
3. Results The AD patient group was aged 70.87 11.4 years (mean7 standard deviation), and the CN group was 67.9710.1 years (see Table 1). There were no statistically significant differences between the AD and CN groups in terms of age (p ¼0.57) and the thickness of the specimen (p ¼0.34; where AD-2 was excluded from statistical analysis) using Welch’s t-test. Linear regression between the age in years x and the thickness in millimeters y gave y¼3.39x–0.02 for the AD group and y¼ 1.95x–0.01 for the CN group, showing that the AD group was thicker than the CN group patients aged less than 70 years. The multiple correlation coefficients between the storage time and the distensibility were 0.0096 for the AD group and 0.47 for the CN group, showing no correlation between the storage time and the distensibility. The modified Movat-stained sections of AA in CN subjects showed high elastic fiber content in the entire wall, which appeared as separate wavy continuous fibers throughout the media (Fig. 2A, and C). In contrast, those of the AAs in patients
with AD showed a slight irregular arrangement and decreased elastic fiber content in the wall, which was disrupted in parts (Fig. 2B, and D). Fig. 3a compares the elastin and collagen contents (area fraction) of the AD and CN groups. The AD group showed significantly decreased elastin content compared to that in the CN group (p ¼0.0025). In contrast, no significant difference was found in collagen content between the groups. Table 2a shows a logistic regression model to distinguish between the AD and CN groups by elastin or collagen content. The regression coefficient for percent elastin, but not that for percent collagen, was statistically significant (p ¼0.020). Fig. 3b compares elastin and collagen contents (area fraction) between the o70 yr of age (YT70) and 470 yr of age (OT70) groups. The OT70 group had a significantly higher collagen content compared to the YT70 group (p ¼0.0086). However, no significant difference was found in elastin content. Table 2b lists a logistic regression model to distinguish between the YT70 and OT70 groups by elastin or collagen content. The regression coefficient for the collagen fraction was statistically significant (p ¼0.034), but that for the elastin fraction was not. Fig. 4a and b shows the stress–strain relationships in theo70 yr and470 yr age AD and CN subgroups, respectively. The maximum point of each stress–strain curve corresponded to remarkable specimen damage or a slip of the specimen by the specimen grip, both of which caused irregular specimen deformation. The AA became stiffer with age in both the AD and CN groups. Fig. 5 compares the age-related distensibility between the AD and CN groups. There was a statistically significant difference between AD and CN groups in the distensibility (p¼ 0.044) using Welch’s t-test. The slope of the regression line for AD, ( 0.008/yr of age) was double that for CN ( 0.004/yr of age). A comparison of the regression lines showed steady recovery of abnormal distensibility with aging in patients with AD compared to the control group.
Fig. 2. Modified Movat-stained sections of the AA in a CN subject (images A, C) and a patient with AD (images B, D). Bar, 500 μm (A, B), 200 μm (C, D).
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Fig. 6a and b shows age-related elastin and collagen contents (area fraction), respectively, in the AD and CN groups. Elastin content had a negative relationship with age in the CN group (r ¼ 0.66, p ¼0.036), but no relationship in the AD group (p ¼0.20). Collagen content tended to increase with age, and no difference in age-matched content was detected between the CN and AD groups. Fig. 7a and b shows the correlations between distensibility and elastin and collagen contents (area fraction), respectively, in the AD and CN groups. The AD group tended to be more distensible than the CN at the same elastin or collagen content.
5
4. Discussion As aforementioned, Welch’s t-test revealed no statistical difference in age and statistically significant difference in distensibility between the AD and CN groups. Fig. 5 shows that the intrinsic distensibility of the AA tended to be larger in patients with AD than that in age-matched CN subjects at low stress levels. We think that the aorta of patients with AD is clinically assessed as stiff because a dilated aortic wall due to its elastin abnormalities is inflated to a steep range of the stress–strain relationship by blood
Fig. 3. (a) Comparisons of elastin and collagen contents (area fraction) (a) between the AD and CN groups and (b) between theo 70 yr (YT70) and 470 yr of age (OT70) groups. Asterisks denote statistically significant differences: ** p o 0.01.
Table 2 (a) Logistic regression model to distinguish between AD and CN groups by elastin or collagen content (area fraction). (b) Logistic regression model to distinguish betweeno 70 yr (YT70) and 4 70 yr of age (OT70) groups by elastin or collagen content (area fraction). (a) Model parameter
Regression coefficient
SE
p-value
Odds ratio
%Elastin %Collagen Intercept
0.268 0.011 9.564
0.115 0.067 4.758
0.020 0.868
0.764 0.988
Model parameter
Regression coefficient
SE
p-value
Odds ratio
%Elastin %Collagen Intercept
0.137 0.178 0.220
0.086 0.084 2.939
0.110 0.034
0.871 1.195
(b)
Fig. 4. Stress–strain relationships of individual AD and CN specimens in patients (a) o 70 yr and (b)470 yr of age. Note that an irregularity in the stress–strain curve was observed at the maximum stress point due to mechanical damage to the specimen or a slip of the specimen in the specimen grip.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
6
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
pressure, and the diameter changes due to the small difference between diastolic and systolic pressures. The elastin content (area fraction) was lower in the AD samples than in the CN samples (Fig. 3a), which appeared to contradict the positive correlation between distensibility and elastin content in the CN samples (Fig. 7a), while the collagen contents were similar. We speculate that the increase in distensibility with AD was correlated with elastic fiber abnormalities. Nakashima et al. (1990b) showed an apparent irregularity in arrangement and shape and a decrease in the number of interlaminar elastic fibers in the AA media in six of 10 cases of type A AD. Klima et al. (1983) found elastic fragmentation in 94% of patients with ascending aortic aneurysm, which was not associated with Marfan syndrome. Fritze et al. (2012) showed destruction of elastic laminae and loss of interlaminar crosslinks in AD-free AAs with aging.
Wang et al. (2005) reported a reduction in the elastin content in the aorta with AD for patients aged 60 yr on average, which is in agreement with the data shown in Fig. 3a. Andreotti et al. (1985) reported increased collagen content with aging, but no change in the elastin content. These trends are consistent with our data (see Figs. 3b and 6 and Table 2b), which lead to a decrease in the distensibility with aging (see Fig. 5). The initiation and progress of the tear and rupture of the AA wall in patients with AD are also important issues. Iliopoulos et al. (2009) carried out a uniaxial tensile loading test for strip-like specimens of non-dissecting AA aneurysms in 12 patients (age 6979 yr) and showed that the failure stress in the circumferential direction was almost 2 MPa but varied considerably. The maximum stress of o500 kPa in our results (Fig. 3) was almost out of the range of the failure stress in their experiment. Pasta et al.
Fig. 5. Age-related distensibility in the stress range of 0–50 kPa for the AD and CN groups.
Fig. 6. Age-related (a) elastin and (b) collagen contents (area fraction) in the AD and CN groups.
Fig. 7. Correlations between the distensibility and (a) elastin and (b) collagen contents (area fraction) in the AD and CN groups.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i
H. Yamada et al. / Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎
(2012) conducted a peeling test on AAs obtained from patients with TAV and BAV to investigate delamination tissue strength. Such shear is another means by which the initiation and progress of AD can be understood. Our statistical analysis on the storage time showed no effect on the distensibility at low stress levels. However, a better control of the storage time for the specimens would suppress the effects of freezing on the distensibility (Langerak et al., 2001; Goh et al., 2010; Sugita and Matsumoto, 2013). The uniaxial loading test with 20 mm strip-like specimens was a study limitation. Biaxial loading tests reproduce a physiological loading condition by controlling the stress/strain state not only in the circumferential direction, but also in the longitudinal direction, as performed for 20–25 mm square specimens (Okamoto et al. 2003) and 15 mm square ones (Choudhury et al. 2009). In conclusion, we revealed age-related distensibility and aortic wall content in elderly patients with acute AD and CN. The correlation results showed that the distensibility of the AA in patients with acute AD was greater than that in age-matched CN subjects, and that it became more similar to that of the CN subjects with aging, which was accompanied by increased collagen content. The increase in collagen content as a consequence of vascular wall remodeling with aging likely suppresses the increasing rate of distensibility for acute AD candidate patients, and therefore may delay emergency surgery for acute AD in patients older than 50 years of age. Our results provide data on intrinsic mechanical properties that underlie the deformation characteristics of the aorta and cannot be detected using clinical imaging of the AD.
Conflict of interest statement None of the authors has a conflict of interest to disclose.
Acknowledgments This research was supported in part by funds from the Mitsui Life Social Welfare Foundation (2011/7) and the Central Research Institutes of Fukuoka University (No. 117008). The authors thank Ms. Hiroyo Fukagawa for technical assistance with the histological observations.
References Andreotti, L., Bussotti, A., Cammelli, D., di Giovine, F., Sampognaro, S., Sterrantino, G., Varcasia, G., Arcangeli, P., 1985. Aortic connective tissue in ageing–a biochemical study. Angiology 36, 872–879.
7
Baumgartner, D., Baumgartner, C., Schermer, E., Engl, G., Schweigmann, U., Matyas, G., Steinmann, B., Stein, J.I., 2006. Different patterns of aortic wall elasticity in patients with Marfan syndrome: a noninvasive follow-up study. J. Thorac. Cardiovasc. Surg. 132, 811–819. Choudhury, N., Bouchot, O., Rouleau, L., Tremblay, D., Cartier, R., Butany, J., Mongrain, R., Leask, R.L., 2009. Local mechanical and structural properties of healthy and diseased human ascending aorta tissue. Cardiovasc. Pathol. 18, 83–91. Fritze, O., Romero, B., Schleicher, M., Jacob, M.P., Oh, D.Y., Starcher, B., Schenke-Layland, K., Bujan, J., Stock, U.A., 2012. Age-related changes in the elastic tissue of the human aorta. J. Vasc. Res. 49, 77–86. Goh, K.L., Chen, Y., Chou, S.M., Listrat, A., Bechet, D., Wess, T.J., 2010. Effects of frozen storage temperature on the elasticity of tendons from a small murine model. Animal 4, 1613–1617. Hayashi, K., 1993. Experimental approaches on measuring the mechanical properties and constitutive laws of arterial walls. J. Biomech. Eng. 115, 481–488. Iliopoulos, D.C., Deveja, R.P., Kritharis, E.P., Perrea, D., Sionis, G.D., Toutouzas, K., Stefanadis, C., Sokolis, D.P., 2009. Regional and directional variations in the mechanical properties of ascending thoracic aortic aneurysms. Med. Eng. Phys. 31, 1–9. Klima, T., Spjut, H.J., Coelho, A., Gray, A.G., Wukasch, D.C., Reul Jr., G.J., Cooley, D.A., 1983. The morphology of ascending aortic aneurysms. Hum. Pathol. 14, 810–817. Langerak, S.E., Groenink, M., van der Wall, E.E., Wassenaar, C., Vanbavel, E., van Baal, M.C., Spaan, J.A., 2001. Impact of current cryopreservation procedures on mechanical and functional properties of human aortic homografts. Transpl. Int. 14, 248–255. Martin, C., Sun, W., Primiano, C., McKay, R., Elefteriades, J., 2013. Age-dependent ascending aorta mechanics assessed through multiphase CT. Ann. Biomed. Eng. 41, 2565–2574. Nakashima, Y., Kurozumi, T., Sueishi, K., Tanaka, K., 1990a. Dissecting aneurysm: a clinicopathologic and histopathologic study of 111 autopsied cases. Hum. Pathol. 21, 291–296. Nakashima, Y., Shiokawa, Y., Sueishi, K., 1990b. Alterations of elastic architecture in human aortic dissecting aneurysm. Lab. Investig. 62, 751–760. Okamoto, R.J., Xu, H., Kouchoukos, N.T., Moon, M.R., Sundt 3rd, T.M., 2003. The influence of mechanical properties on wall stress and distensibility of the dilated ascending aorta. J. Thorac. Cardiovasc. Surg. 126, 842–850. Pasta, S., Phillippi, J.A., Gleason, T.G., Vorp, D.A., 2012. Effect of aneurysm on the mechanical dissection properties of the human ascending thoracic aorta. J. Thorac. Cardiovasc. Surg. 143, 460–467. Redheuil, A., Yu, W.C., Wu, C.O., Mousseaux, E., de Cesare, A., Yan, R., Kachenoura, N., Bluemke, D., Lima, J.A.C., 2010. Reduced ascending aortic strain and distensibility earliest manifestations of vascular aging in humans. Hypertension 55, 319–326. Sawabe, M., Hamamatsu, A., Chida, K., Mieno, M.N., Ozawa, T., 2011. Age is a major pathobiological determinant of aortic dilatation: a large autopsy study of community deaths. J. Atheroscler. Thromb. 18, 157–165. Sugita, S., Matsumoto, T., 2013. Novel biaxial tensile test for studying aortic failure phenomena at a microscopic level. Biomed. Eng. Online 12, 3. Tsai, T.T., Nienaber, C.A., Eagle, K.A., 2005. Acute aortic syndromes. Circulation 112, 3802–3813. Tsamis, A., Krawiec, J.T., Vorp, D.A., 2013. Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review. J. R. Soc. Interface 10, 20121004. Wang, X., LeMaire, S.A., Chen, L., Carter, S.A., Shen, Y.H., Gan, Y., Bartsch, H., Wilks, J.A., Utama, B., Ou, H., Thompson, R.W., Coselli, J.S., Wang, X.L., 2005. Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection. Surgery 138, 352–359. Yamada, H., Momii, S., 2004. Evaluation of possible stress distributions in abdominal aorta on the basis of physiologically loading data. In: Proceedings of the ASME 2004 International Mechanical Engineering Congress and Exposition. Anaheim.
Please cite this article as: Yamada, H., et al., Age-related distensibility and histology of the ascending aorta in elderly patients with acute aortic dissection. Journal of Biomechanics (2015), http://dx.doi.org/10.1016/j.jbiomech.2015.06.025i