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a Department of Surgery, University of California, San Francisco, California
b Department of Bioengineering, University of California, San Francisco, California
c Department of Anesthesia, University of California, San Francisco, California
d Department of Radiology, University of California, San Francisco, California
e Veterans Affairs Medical Center, San Francisco, California
Accepted for publication June 29, 2010.
* Address correspondence to Dr Ratcliffe, Surgical Service (112), San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121 (Email: mark.ratcliffe{at}med.va.gov).
| Abstract |
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Methods: Magnetic resonance imaging scans with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace).
Results: First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the Young-Laplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress.
Conclusions: The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling
| Introduction |
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An alternative approach to quantifying ventricular wall stress and stiffness is mathematical modeling based on the conservation laws of continuum mechanics, the most versatile of which is the finite element (FE) method [11]. The FE method used in this study for continuum analysis of the heart includes several features that are uncommon in conventional FE methods. First, the constitutive relationship is nonlinear and anisotropic [12, 13], with direction based directly on measured three-dimensional myofiber angle distributions [14, 15]. Next, the models undergo large or finite deformation with a difference in dimensions between end diastole and end systole that is greater than 10%. More recent models now also include the transmural heterogeneity of cellular excitation-contraction coupling mechanisms [16].
We calculated stress with the assumption that wall thickness is very much less than the radius of curvature with large deformation FE methods (Young-Laplace law) and without the assumption (modified Laplace) using data collected from sheep after anteroapical MI and after Dor procedure. We tested the hypothesis that stress in the circumferential direction calculated with Laplace law is equal to values obtained with the FE method. Since stress in the cross-fiber direction is likely to cause volume overload hypertrophy and stress in the fiber direction is likely to cause pressure overload hypertrophy, we also compared stress calculated using force balance with the magnitude of stress in the fiber and cross fiber directions calculated with the FE method.
| Material and Methods |
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Magnetic resonance (MRI) images with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical MI and in 1 of those sheep 6 weeks after Dor procedure (Fig 1) [17]. These experimental results were previously reported [17, 18].
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Modified Laplace law
Throughout the paper, we refer to Equation 3 as "Young-Laplace" and to Equation 2 as "modified Laplace."
Finite Element Model
Analysis of borderzone function using FE models has been previously reported [20].
Finite element method
Animal-specific FE models were created from MRI images at the early diastole, which was considered as the initial unloaded reference state [21]. Representative surface and FE meshes are seen in Figure 3. Myofiber angles of –37 degrees, 23 degrees, and 83 degrees were assigned at the epicardium, midwall, and endocardium, respectively, in the remote and borderzone regions [22]. At the aneurysm region, fiber angles were set to 0 degrees [23]. Circumferential displacement of basal epicardial nodes was constrained.
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Constitutive relationship
Passive [13] and active myocardial [24] constituitive relationships have been previously described. The active myocardial material property law was implemented using a user-defined material subroutine in LS-DYNA (Livermore Software Technology Corporation, Livermore, CA). Diastolic [25] and systolic [24] material variables have been previously reported.
Material property optimization
The method of myocardial material property optimization was previously described by Sun and colleagues [26]. Specifically, the commercial FE optimization software, LS-OPT [27], was used to find the optimal value of T
max for each region.
Simulations were performed on a small Linux cluster (seven nodes; each node with two AMD Opteron 240 processors and 1 gB memory).
Statistical Analysis
All values are expressed as mean ± SD and compared by repeated measures analysis using a mixed model to test for both fixed and random effects (Systat Software, Chicago, IL). The statistical model was as follows:
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| Results |
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Average Circumferential Stress
Table 1
shows average LV wall stress in the circumferential direction calculated using the Young-Laplace law, the modified Laplace law, and the FE method. The average wall thickness to radius of curvature ratio was 0.22 ± 0.022 at end diastole and 0.24 ± 0.030 at end systole. As a consequence, circumferential stress calculated with the Young-Laplace law and the modified Laplace law is significantly different.
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Regional Variation
There were significant regional differences. Stress calculated with the modified Laplace was higher than circumferential stress calculated with the FE method in the remote (37%, p = 0.048) but not borderzone regions (Fig 4A), and higher than circumferential stress calculated with the FE method in the endocardial layer (93%, p < 0.001) at end diastole (Fig 4B).
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Once again, there were significant regional differences. Stress calculated with the modified Laplace law was higher than cross-fiber stress calculated with the FE method in the remote region (22%, p = 0.012) at end diastole (Fig 4A). Stress calculated with both the modified Laplace law was substantially lower than fiber stress calculated with the FE method in both remote (modified Laplace 64%, p < 0.001) and borderzone regions (modified Laplace 35%, p = 0.012) at end systole (Fig 5A). Finally, stress calculated with the modified Laplace law was lower than fiber stress at all layers (p < 0.001) at end systole (Fig 5B).
Change in Stress After Dor Procedure
Stress at end systole calculated with the Young-Laplace law, modified Laplace law, and FE method in the infarct borderzone before and after Dor procedure is seen in Table 2. The reduction in average borderzone stress calculated with the Young-Laplace and modified Laplace law was –23.5% and –26.2%, respectively. However, the change in regional stress calculated with the FE method was quite different, with a substantial increase in stress in the inner layer (
in circumferential stress +196.7%;
in fiber stress +15%) and a more pronounced decrease in the outer layer (
in circumferential stress –70.4%;
in fiber stress –49.7%).
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| Comment |
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Finite Element Method as the Gold Standard
The decision to use the large deformation FE method as the reference or gold standard is reasonable given that the FE models were optimized using measured myocardial strain in addition to end-diastolic and end-systolic volumes. A comparison of Laplace's law with the FE method in a physical model constructed from materials with known material properties, such as silicone [28] or silicone with embedded elastic fibers, and one that has simplified geometry would be interesting, and we propose to carry out this study in the future. However, even when completed, physical models of that sort will lack the ability to simulate active contraction.
Limitations of the Young-Laplace Law
There are a number of inaccuracies and limitations associated with the application of Laplace type calculations of LV wall stress [29] An inaccuracy specific to the Young-Laplace law is the restriction that the wall thickness (h) be very much less than the radius of curvature (r). However, the h/r ratio in this study was 0.22 ± 0.022 at end diastole and 0.24 ± 0.030 at end systole. This suggests that Equation 2 (modified Laplace), which does not have the h << r restriction, is more reasonable. In fact, we found in all cases that stress calculated with Equation 2 was closer to FE-based calculation of circumferential stress than stress calculated with the Young-Laplace law.
Stress Variation Across the LV Wall
When a thick-walled pressure vessel is inflated, most of the deformation in the circumferential and longitudinal directions occurs at the inner surface and decreases monotonically toward the outer surface. Thus, we would expect circumferential and longitudinal stress to vary transmurally in a similar manner, although the actual transmural variation in these stress components will depend on the relationship between stress and strain (constitutive relation) of the myocardium. For instance, Guccione and colleagues [30] previously measured fiber stress in the left ventricle of a normal dog using a finite deformation FE method similar to that used in the current study [30]. The investigators found the transmural gradient in fiber stress was 3.3 kPa at the base and 4.6 kPa at the apex at end diastole [30]. The transmural gradients were small near the LV base during systole and were as high as 43 kPa between the midventricle and apex [30]. In the present study, transmural gradients in fiber stress were smaller but still significant with a gradient of 1.55 kPa in the remote myocardium at end diastole and 7.23 kPa at end systole. The Young-Laplace law is based on a global force balance, which ignores myocardial material properties. Thus, the Young-Laplace law can be used to estimate only average stress across the full wall thickness in the circumferential and longitudinal directions.
Importance of Fiber and Cross-Fiber Stress
Another limitation of the Young-Laplace and modified Laplace laws is that they cannot be used to calculate stress in the local muscle fiber or cross-fiber direction as stress in the fiber and cross-fiber directions are probably the causes of hypertrophy. There is increasing evidence that stress in the cross-fiber direction causes eccentric or volume overload type hypertrophy [31, 32]. Although evidence is less clear, it is probable that end-systolic fiber stress causes concentric or pressure overload type hypertrophy.
Implications for the Dor Procedure
Regional differences between stress calculated the Young-Laplace law and FE methods occurs especially in the inner and outer layers of the infarct borderzone. When coupled with inability of Laplace type methods to measure fiber and cross-fiber stress, this leads the Young-Laplace and modified Laplace laws to miscalculate the change in stress in the infarct borderzone after the Dor procedure. Since the rationale for the Dor procedure in specific and surgical ventricular remodeling in general is reduction in wall stress [33], accurate knowledge of stress in the fiber and cross-fiber directions is of obvious importance. Furthermore, in our opinion, improvement in borderzone contractility is the primary therapeutic target of the Dor procedure [20].
Utility of Finite Deformation Type FE Model of the Left Ventricle
The FE method can be used to simulate the effect of surgical ventriculoplasty [34] and passive constraint on the left ventricle. For instance, Dang and colleagues [34] previously used a FE model of the finite deformation type to calculate the effect of surgical remodeling on stroke volume and mean fiber stress. Force balance methods such as the Young-Laplace law can only calculate stress from an existing left ventricle image obtained during animal experiments or from patients. Thus, it cannot be used as a predictive theoretical tool. In our opinion, this is the greatest limitation of the Young-Laplace law.
Conclusions
Circumferential stress calculated with the modified Laplace law was superior to the Young-Laplace law, although stress calculated with the modified Laplace law remained statistically different (higher) than FE-based calculation of circumferential stress at end diastole.
Conversely, the magnitude of stress calculated with the modified Laplace law is very different than stress in the fiber and cross-fiber directions calculated with the FE method. Also, there are pronounced regional differences, with the largest differences between the modified Laplace and FE methods occurring in the inner and outer layers of the infarct borderzone. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress. The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling.
| Acknowledgments |
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| References |
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