An experimental study on the ultimate strength of the adventitia and media of human atherosclerotic carotid arteries in circumferential and axial directions
Introduction
Atherosclerosis is the most common disease of the arterial wall. The abrupt closure of an artery by an occlusive thrombus is the main cause of myocardial infarction and other thrombotic consequences of atherosclerosis. The thrombosis is often associated with rupture of fibrous cap covering a large lipid-rich necrotic core (Rekhter et al., 1998; Cullen et al., 2003). Histology has shown that most rupture sites are also sites of increased mechanical stress (Cullen et al., 2003; Li et al., 2006). It has been widely accepted that atherosclerosis leads to locally increased stresses in the region of lesions. However, validation of this hypothesis has been impeded by a lack of experimental data on ultimate strength (i.e. the maximum value of stress at failure) of atherosclerotic tissues. Knowledge of ultimate strength of human atherosclerotic tissues is essential for understanding plaque rupture mechanisms and assessing the risk of possible ruptures (Tang et al., 2005). It is also of great importance in predicting the outcome of interventional treatments such as balloon angioplasty (Holzapfel et al., 2002).
Available experimental data for the ultimate strength of human atherosclerotic arteries is very limited. Most research efforts have focused on quantifying the stress–strain relationship of atherosclerotic tissues over physiological loading ranges. Lee et al. (1991) and Loree et al. (1994) performed dynamic and static tensile tests on plaque caps from abdominal and thoracic aortas. These results indicated that stiffness of cap increased with loading frequency, calcified cap was stiffest and the circumferential tangential modulus at 25 kPa did not depend on the cap type. Lendon et al., 1991, Lendon et al., 1993 showed that the weaker plaque caps appear to be associated with increased macrophage activity. Holzapfel et al. (2004) investigated layer- and direction-dependent ultimate tensile stress and stretch ratio of human atherosclerotic iliac arteries. Anisotropic and highly nonlinear tissue properties were observed as well as interspecimen differences. The adventitia demonstrated the highest strength and fibrous cap in circumferential direction showed low fracture stress. Using in vivo medical screening approaches, Nagaraj et al. (2005) observed stiffening elastic modulus with lesion progression in porcine carotid artery. Using noninvasive echotracking system, Paini et al. (2007) found plaque region in human carotid artery was associated with larger bending and stiffer material properties. Walraevens et al. (2008) used uniaxial unconfined compression tests to distinguish the mechanical properties of healthy tissue from calcified tissue in aorta. More recently, Ebenstein et al. (2008) used nanoindentation to measure the mechanical properties of blood clots, fibrous tissue, partially calcified fibrous tissue and bulk calcifications of human atherosclerotic plaque tissue. The results demonstrated that the stiffness of plaque tissue largely depends on the mineral content. Most of these previous studies focused on the fibrous cap and are based on tests in one direction. It is well known that atherosclerotic plaques also have fiber-oriented multi-layered structures. Different layers display different direction-dependent mechanical behaviors (Holzapfel et al., 2000, Holzapfel et al., 2004). Layer- and direction-dependent experimental data are crucial for realistic computational models and accurate stress–strain predictions (Holzapfel et al., 2002).
Accurate knowledge of ultimate strength of arteries will provide the mechanical loading threshold for plaque vulnerability assessment based on computational stress/strain predictions (Cheng et al., 1993; Li et al., 2006). While image-based computational models are capable of representing the mechanical loading in the plaque (Tang et al., 2005; Yang et al., 2007), it is hard to assess the risk of plaque rupture without knowing the local material strength of the blood vessel. In this paper, we will quantify the ultimate strength of human atherosclerotic carotid arteries by direct mechanical testing.
Section snippets
Methods
Three pairs of human carotid arteries were tested (69.3±17.7 yr; 1 female and 2 males). Carotid arteries were obtained from the Department of Pathology, Washington University School of Medicine. Specimens were obtained and de-identified under the auspices of a Washington University Institutional Review Board Protocol. Each pair of arteries was obtained at autopsy and fresh frozen in PBS. On the day of testing, each sample was thawed at room temperature and dissected. In order to investigate the
Results
Tissue ultimate strength can be captured by the sudden drop of the stress–stretch curve (Fig. 4). The recorded data set for each specimen consisted of about 1000 stress–stretch data points. To minimize the possible effect of signal noise, the ultimate strength value for each specimen was determined by averaging 5 data points centered at the peak stress value and the corresponding value of stretch ratio was taken as the extensibility.
Ultimate strength of human atherosclerotic carotid arteries
The ultimate strength of atherosclerotic tissues in human carotid artery was layer- and direction-dependent. The adventitia was much stronger than the media. The same phenomenon was observed by Holzapfel et al. (2004) in human atherosclerotic iliac artery. The media in axial direction had the lowest rupture stress. For the extensibility, except for the pair of CA vs. AM, no significant difference was found between any other two groups. The media had relatively lower extensibility (Table 1).
Conflict of interest
The authors declare that there are no conflicts of interest associated with this research.
Acknowledgement
This research was supported in part by NIH Grant NIH/NIBIB R01 EB004759 and NSF/NIGMS DMS-0540684.
References (22)
- et al.
Atherosclerotic plaque caps are locally weakened when macrophage density is increased
Atherosclerosis
(1991) - et al.
Testing of small connective tissue specimens for the determination of the mechanical behavior of atherosclerotic plaques
Journal of Biomedical Engineering
(1993) - et al.
Stress analysis of carotid plaque rupture based on in vivo high resolution MRI
Journal of Biomechanics
(2006) - et al.
Static circumferential tangential modulus of human atherosclerotic tissue
Journal of Biomechanics
(1994) - et al.
Porcine carotid arterial material property alterations with induced atheroma: an in vivo study
Medical Engineering and Physics
(2005) - et al.
Correlation between compression, tensile and tearing tests on healthy and calcified aortic tissues
Medical Engineering & Physics
(2008) - et al.
Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging
Circulation
(2002) - et al.
Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation
Circulation
(1993) - et al.
Rupture of the atherosclerotic plaque: does a good animal model exists?
Arteriosclerosis, Thrombosis, and Vascular Biology
(2003) - et al.
Nanomechanical properties of calcification, fibrous tissue, and hematoma from atherosclerotic plaques
Journal of Biomedical Materials Research (Part A)
(2008)
The vulnerable atherosclerotic plaque: understanding, identification, and modification
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