Ann Thorac Surg 2003;75:1210-1214
© 2003 The Society of Thoracic Surgeons
Original article: cardiovascular
Effect of aneurysm on the tensile strength and biomechanical behavior of the ascending thoracic aorta
David A. Vorp, PhDa,b*,
Brian J. Schiro, BSa,
Marek P. Ehrlich, MDc,
Tatu S. Juvonen, MDc,
M.Arisan Ergin, MDc,
Bartley P. Griffith, MDa
a Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
b Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
c Department of Cardiothoracic Surgery, Mount Sinai Medical Center, New York, New York, USA
Accepted for publication October 25, 2002.
* Address reprint requests to Dr Vorp, Department of Surgery, University of Pittsburgh, Suite 200, McGowan Institute for Regenerative Medicine, 100 Technology Drive, Pittsburgh, PA 15219, USA
e-mail: vorpda{at}msx.upmc.edu
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Abstract
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BACKGROUND: Rupture of an ascending thoracic aortic aneurysm (ATAA), which is associated with significant mortality, occurs when the mechanical forces acting on the aneurysm exceed the strength of the degenerated aortic wall. The purpose of this study was to evaluate changes in biomechanical properties of the aortic wall related to ATAA formation.
METHODS: Ascending thoracic aortic aneurysm tissue was obtained from surgery; control (nonaneurysmal) aorta was obtained from autopsy. Tissue strips with longitudinal (LONG) or circumferential (CIRC) orientation were stretched to failure. Maximum tissue stiffness and tensile strength were determined from plots of stress (normalized force) versus strain (normalized deformation). Student’s t test was used for all comparisons.
RESULTS: Tensile strength of LONG (nATAA = 17, ncontrol = 7) and CIRC (nATAA = 23, ncontrol = 7) ATAA specimens were 29% and 34% less than that of control tissue, respectively (p < 0.05). Maximum tissue stiffness was 72% stiffer for LONG ATAA (p < 0.05) and 44% stiffer for CIRC ATAA (p = 0.06) than for control tissue, respectively.
CONCLUSIONS: The data suggest that ATAA formation is associated with stiffening and weakening of the aortic wall, which may potentiate aneurysm rupture.
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Introduction
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Aneurysm of the thoracic aorta is relatively rare; only 0.0059% of a given population is diagnosed with this condition each year [1]. However, the condition is also particularly lethal. Joyce and colleagues [2] estimated the 5-year mortality rate of patients with an ascending thoracic aortic aneurysm (ATAA) to be 39% for lesions 6 cm or less in diameter, and 62% for ATAA more than 6 cm in diameter. Except for aortic aneurysm associated with a connective tissue disorder (eg, Marfan syndrome or Ehlers Danlos syndrome), the typical patient is elderly [3]. Therefore, surgical correction is often contraindicated by a variety of age-related risk factors. Moreover, the cost of surgical repair of thoracic aortic aneurysms is relatively high. If left untreated, however, spontaneous aortic rupture or dissection may occur, and these are associated with a 94% mortality rate [1].
Aneurysm rupture occurs when the strength of the degenerating aortic wall is insufficient to withstand the physiologic forces exerted on it. In a sense, reduction of aortic aneurysm wall strength is self-propagating. In general, the forces acting on the aneurysm are directly related to the local diameter or radius of curvature of the wall [4]. An aneurysm enlarges as it weakens, thereby resulting in greater forces acting on the wall and increasing the risk of rupture considerably. Therefore, knowledge of the strength of the aneurysm wall, and the forces acting on the wall, could potentially provide diagnostic identification of aneurysms for which the risk of rupture exceeds the risks of repair [5]. Investigations of the tensile strength and biomechanical behavior of thoracic aortic aneurysms may help direct development of such a clinical tool.
The purpose of the present study was to evaluate and compare the tensile strength and biomechanical properties of ATAA with those of nonaneurysmal ascending thoracic aorta. We found a significant decrease in tensile strength, as well as a modification of the biomechanical behavior of the aortic wall.
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Material and methods
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Human aortic tissue specimens
All human aortic tissue specimens were obtained under informed consent following guidelines of our Institutional Review Board. Segments of degenerative (nondissecting) ATAA were obtained fresh from the operating room from patients undergoing surgical repair. The aneurysm diameter as assessed radiologically was obtained from the patient’s hospital chart. Segments of control (nonaneurysmal) ascending thoracic aorta were obtained within 24 hours of death from subjects undergoing autopsy. Immediately after excision, the aortic segments were placed in saline and refrigerated at 4°C. Within 48 hours of death for the autopsy samples, or of harvest for the ATAA samples, the recovered tissue was equilibrated to room temperature by immersion in fresh phosphate-buffered saline and tested as described below.
Tensile testing
The aortic segments were cut into long, thin, rectangular (about 3 cm x 8 mm) strips of tissue with either longitudinal (LONG) or circumferential (CIRC) orientation. When possible, strips of both orientations were obtained from the same aortic segment and individually tested. The tissue specimens were placed in a previously described [6] uniaxial tensile testing system and continuously wetted with phosphate-buffered saline. The width and thickness were measured at three locations along the length of each specimen using a dial caliper, averaged, and recorded. The force and deformation applied to each specimen were measured continuously as the specimen was stretched to failure.
Data analysis
As previously described [6], the Cauchy stress (T) within the specimen at any given time was calculated as the applied force normalized by deformed cross-sectional area, and strain (
) was calculated as deformation normalized by original specimen length. From the stress–strain curve generated for each specimen tested, the maximum tangential stiffness (MTS) was taken as the maximum slope (ie, maximum resistance to deformation), while the tensile strength was taken as the peak stress obtained before failure (Fig 1).
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Fig 1. Schematic stress-strain curve demonstrating definitions of tensile strength and maximum tangential stiffness (MTS) used in this study.
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To further characterize the biomechanical response of the aneurysm wall, we used a mathematical model previously described for abdominal aortic tissue [7]. In short, the model relates the stress in the uniaxially loaded specimen to the stretch (
) through the Equation
 | (1) |
Here, 
and ß are model parameters that are indicative of the mechanical properties of the tissue; is equal to the deformed length of the specimen divided by the original length; ie, = + 1. The mathematical model was fit to each individual experimentally derived T - data set by minimizing the sum of square errors based on the Simplex-Quasi Newton nonlinear regression algorithm (STATISTICA, v.4.5, Statsoft Inc, Tulsa, OK). The best-fit model parameters (ie, and ß) were determined for each specimen tested.
Student’s t test was performed to compare measures of tensile strength (MTS), and the biomechanical model parameters and ß between groups. Significance was assumed for p less than 0.05.
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Results
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Twenty-six patients (aged 66 ± 2 years; mean ± SEM) with ATAA (diameter 5.8 ± 0.3 cm) provided 17 LONG-oriented specimens and 23 CIRC-oriented specimens for tensile testing. Seven LONG and 7 CIRC control (nonaneurysmal) tissue specimens were obtained from 10 subjects (aged 51 ± 6 years; estimated aortic diameter 3.3 ± 0.2 cm). No significant difference was noted in wall thickness between ATAA and control specimens: 1.9 ± 0.1 mm compared with 1.8 ± 0.2 mm.
The tensile strength of ATAA tissue was found to be significantly (p < 0.05) lower than that for the control tissue for both the CIRC and LONG orientations (Fig 2;
118 ± 12 N/cm2 versus 180 ± 24 N/cm2, and 121 ± 9 N/cm2 versus 171 ± 14 N/cm2, respectively). No significant difference in strength was noted between CIRC and LONG specimens for either aneurysmal or control tissue. A comparison of tensile strength versus diameter for the ATAA specimens (Fig 3)
revealed no correlation for either the LONG (R = 0.008) or CIRC (R = 0.086) specimens.
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Fig 3. Strength versus diameter for longitudinal (LONG; A) and circumferential (CIRC; B) specimens of ascending thoracic aortic aneurysm. No correlation was found between strength and diameter for either orientation (R = 0.008 and R = 0.086, respectively).
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The MTS of LONG ATAA specimens was greater than that for the control tissue (Fig 4;
448 ± 59 N/cm2 versus 261 ± 26 N/cm2, p < 0.05). A similar finding was noted for CIRC specimens, but the difference was not statistically significant (Fig 4; 467 ± 42 N/cm2 versus 325 ± 63 N/cm2, p = 0.06). No significant difference in MTS was noted between CIRC and LONG specimens for either aneurysmal or control tissue.
The biomechanical model given in Equation 1 fit the stress-stretch data well for all specimens analyzed (R2 > 0.97). A representative fit is shown in Figure 5.
The mean values of for LONG and CIRC specimens were not significantly different between ATAA and control tissue (10 ± 2 N/cm2 versus 11 ± 4 N/cm2, and 8 ± 1 N/cm2 versus 15 ± 5 N/cm2, respectively; Fig 6A).
However, the values of ß for both the LONG and CIRC specimens were significantly greater for ATAA specimens as compared with control tissue (53 ± 15 N/cm2 versus 9 ± 3 N/cm2, p = 0.04 and 17 ± 4 N/cm2 versus 4 ± 1 N/cm2, p = 0.03, respectively; Fig 6B). A significant difference was noted in ß for LONG versus CIRC ATAA specimens (53 ± 15 N/cm2 versus 17 ± 4 N/cm2, p = 0.04), but not for control tissue (9 ± 3 N/cm2 versus 4 ± 1 N/cm2, p = 0.12,). And no significant difference was noted in for CIRC versus LONG for either the ATAA (p = 0.25) or the control (p = 0.29) tissue.
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Fig 5. Fit of mathematical model given by Equation 1 (black line curve), to stress-strain data (x) for representative ascending thoracic aortic aneurysm (ATAA; A) and control (B) specimens.
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Fig 6. Model parameters (A) and ß (B) as defined by Equation 1 for longitudinal (LONG) and circumferential (CIRC) specimens of ascending thoracic aortic aneurysm (solid bar) and control (nonaneurysmal) (open bar) aortic tissue. Values shown are mean ± SEM.
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Comment
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Management of patients with thoracic aortic aneurysms is a substantial problem in cardiovascular surgery. Ideally, surgical intervention should take place only when the risk of aneurysm rupture exceeds the risks associated with the surgery. Rupture of ATAA is a biomechanical phenomenon that occurs when the tensile strength of the wall is exceeded by the wall stresses placed on the diseased aortic wall during the cardiac cycle. Therefore, knowledge of the strength of the normal and diseased aorta may offer insights to help assess the risk of ATAA rupture. We measured the biomechanical properties of aneurysmal ascending thoracic aorta and compared them with those of nonaneurysmal control tissue. Our results indicated that ATAA is approximately 30% weaker and appreciably stiffer than nonaneurysmal ascending thoracic aorta.
We previously reported similar findings for the biomechanical properties of human abdominal aortic aneurysm [6–8]. Previous research has also been published on the biomechanical properties of nonaneurysmal human descending thoracic aorta [9–11]. Mohan and Melvin [10] used uniaxial testing to report tensile strength values of 172 ± 22 N/cm2 and 147 ± 22 N/cm2 for CIRC and LONG specimens, respectively, values that are slightly lower than our control values. As did our data for ascending thoracic aorta, their data for descending thoracic aorta suggested no significant difference in strength between the two directions. Similarly, Groenink and coworkers [9] determined the rupture strength of intact segments, and their values are also similar to our control values. Sherebrin and associates [11] found that LONG-oriented tissue samples of descending thoracic aorta were stiffer than CIRC-oriented tissue samples. This result is consistent with our findings for the two stiffness measurements of MTS and ß (Figs 4 and 6).
The biomechanical behavior of arterial tissue is generally attributed to the status of the structural proteins present. Elastin provides distensibility and recoil at lower pressures, whereas collagen provides tensile strength and stiffness at higher pressures. To our knowledge, no data exist in the literature regarding the state of elastin and collagen in degenerative ATAA. Therefore, it is not possible to analyze our data in light of known microstuctural differences between normal and aneurysmal tissues. However, similar biomechanical changes have been noted for abdominal aorta as were found in this study; namely, a weakening and stiffening due to aneurysm formation [6–8]. Those observed changes are consistent with the known loss of elastic fibers and derangements in collagen cross-linking that is associated with abdominal aortic aneurysm [12, 13]; this loss likely occurs with ATAA as well.
As with all experimental research, this study contains several limitations. For example, Equation 1 is a simple constitutive model that was actually derived using similar uniaxial tensile testing data for abdominal aortic aneurysm [7]. A similar procedure could be used to derive a distinct constitutive model specific for ATAA. However, this previous constitutive model was used simply to provide a means to compare the uniaxial, nonlinearly elastic properties of ATAA with those for nonaneurysmal tissue; ie, and ß. A possible limitation to our data is the difference in mean age between the ATAA and control groups. However, previous work—albeit on descending thoracic aorta—suggests that these differences are not appreciable vis-à-vis biomechanics. Data collected by Sherebrin and associates [11] suggested little difference in mechanical properties of nonaneurysmal descending thoracic aorta between subjects 51 and 66 years, the mean ages of the two groups studied here. They used a two-parameter mathematical expression similar to our Equation 1 and showed a linear correlation between the parameters and age. The value of one measurement, similar to our ß, was 18% lower for a 51-year-old subject than for an individual who was 66 years. Their other measurement, more akin to our , was 6% higher. Correction of our values of and ß to account for similar age differences would not alter our results because we found no significant difference in and a difference in ß of much more than 18%. The limitations associated with the tensile testing of aortic tissue have been discussed previously [6, 7]. For example, the use of Equation 1 in our data analysis is valid for a mechanically isotropic material. The fact that we found a statistically significant difference in ß between LONG and CIRC ATAA tissue suggests that this material is anisotropic. To evaluate the anisotropic nature of aortic tissue, multiaxial testing methods are necessary. Therefore, further characterization of ATAA tissue should be performed using biaxial testing methods (eg, Sacks [14]), and such research is indeed the focus of ongoing work at our institution [15]. Nonetheless, uniaxial testing methods offer the advantage of allowing measurement of the tensile strength of the tissue, which is not possible with biaxial testing methods. A more appropriate comparison of ATAA tissue would be with freshly excised, nonaneurysmal aortic tissue and not tissue obtained from autopsy. However, freshly excised, nonaneurysmal tissue is difficult to obtain in the sizes necessary for testing both LONG and CIRC specimens. Before testing, the ATAA and control tissues were stored in refrigerated saline, which has been shown to not alter the biomechanical properties of vascular tissue [16]. Regardless, because both tissues were stored similarly, any changes would theoretically occur to both types of tissues so that comparisons would remain valid. Despite these limitations, we believe that the present analysis reveals useful and novel information about the biomechanical behavior of ATAA.
One possible application of the data generated by the present study is toward the development of a new paradigm in the prediction of ATAA rupture. Aneurysm rupture results from mechanical failure of the aortic wall, which occurs when the acting wall stresses exceed the tensile strength of the tissue. One widely accepted indicator for risk of rupture is ATAA diameter. However, our data suggest that ATAA wall strength is not related to diameter (Fig 3). Therefore, risk of rupture may be best assessed by evaluation of the wall stresses acting on ATAA. The mathematical model given by Equation 1 was developed previously [7] to allow accurate computational stress analyses of abdominal aortic aneurysm [5]. Therefore, the present study offers insight into the tensile strength of ATAA and the biomechanical properties used in one possible mathematical model required for stress analysis. Future research might include the development of such a noninvasive, biomechanical tool to evaluate wall stress distribution (and hence rupture potential) for ATAA on a patient-specific basis.
In conclusion, our data suggest that ATAA formation is associated with alterations in biomechanical properties, including aortic wall weakening and stiffening, changes that may potentiate aneurysm rupture.
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Acknowledgments
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The authors thank Dr David H.-J. Wang for his technical assistance with data collection. We also acknowledge Dr Lawrence C. Nichols and the staff of the autopsy suite at Presbyterian University Hospital, University of Pittsburgh Medical Center, for supplying us with autopsy tissue. This project was supported in part by a grant from the National Institutes of Health (RO1 HL 060670-01A2), Bethesda, MD, and by a Biomedical Engineering Grant from The Whitaker Foundation, Washington, DC.
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Abstract
Introduction
) and control (nonaneurysmal) aortic tissue (
). Values shown are mean ± SEM.