Myocardial injury among participants in endurance sports—a model to study myocardial regeneration?

Track 14. Cardiovascular Mechanics revealing the most influential factors that determine these mechanical properties. We believe that collagen alignment in combination with cross-linking is the major determinant for the mechanical properties of the cardiovascular engineered tissues. References [1] Hoerstrup et al. Circulation 2000; 102(19): 11144-49. [2] Boerboom et al. Annals of Biomedical Engineering 2003; 31: 1040-1053. [3] Billiar and Sacks. Journal of Biomedical Engineering 2000; 122: 327-335. [4] Driessen et al. Journal of Theoretical Biology 2004; 226: 53-64. [5] Mol et al. Thoracic and Cardiovascular Surgeon 2003; 51: 78-83. 5166 Th, 15:00-15:15 (P44) Effect o f circumferential and shear stress on collagen synthesis in arteries in organ culture B. Wayman, R.P. Vito, A. Rachev. Georgia Institute ef Technology, The George W. Woodruff School of Mechanical Engineering, Atlanta, GA, USA Arteries respond to sustained changes in global mechanical parameters, such as arterial pressure, flow rate and axial force, by growth and remodeling. The growth and remodeling result from the altered proliferative and synthetic activity of vascular smooth muscle cells, which, in turn are sensitive to changes in the combined effect of the local mechanical parameters such as the mean and cyclic circumferential and axial stresses in the media and the flow-induced shear stress at the intima. The global and the local parameters are related via the equations of equilibrium, the flow equation, and the constitutive equations of the vascular tissue. In contrast to in vivo and organ culture studies based on controlled changes in a single global parameter, this study focuses on organ culture experiments in which a single local mechanical parameter is perturbed, while the rest are kept at a baseline value. The results obtained could be beneficial for design of optimal mechanical conditioning in bioreactors for tissue engineered arteries and for experimentally motivated selection of growth laws for mathematical modeling of growth and remodeling. To illustrate the novel approach, the remodeling response of porcine carotid arteries was investigated in organ culture for 72 hours. Arteries were subjected to super-physiologic (150 kPa) or sub-physiologic (50 kPa) circumferential stress maintaining in both cases the intimal shear stress at physiologic levels (l.5Pa). The pressure and flow were adjusted in a step-wise manner every 24 hours accordingly. In separate experiments, arteries were subjected to super-physiologic (2.25 Pa) or sub-physiologic (0.75 Pa) shear stress and physiologic hoop stress (100 kPa). Collagen synthesis was measured using a 3H-proline incorporation assay. Collagen synthesis was significantly greater at super-physiologic hoop stress, whereas no significant difference was found between arteries when the shear stress was perturbed. 4982 Th, 15:15-15:30 (P44) Myocardial injury among participants in endurance sports - a model to study myocardial regeneration? A. Koller 1, C. Haid 2. 1Department of Sports and Circulatory Medicine, Medical University of Innsbruck, Innsbruck, Austria, 2 University Department of Orthopedics, Medical University of Innsbruck, Innsbruck, Austria Rare deaths have been reported with marathon running.While some deaths have been attributed to hyponatremia, the contribution of myocardial injury remains unclear. We sought to determine whether biochemical evidence of myocardial injury could be demonstrated following completition of a marathon. Moreover, we have started to address the question whether exercise-induced injury is a suitable model to study myocardial regeneration. We recruited 30 marathon runners. Testing, including cardiac troponin T (cTnT), serum N-terminal pro-BNP (NT-proBNP) and ischemia modified albumin (IMA), was performed prior to (Pre) and immediately post (Post) marathon. The group included 18 males and 12 females with a mean age of 32.4±7.2 years and a mean finishing time of 4 hours 18±42 min. Significant increases in cTnT (Pre: <0.01 ngm1-1 , Post: 0.13±0.2 ngml-1; p <0.0001 ), NT-proBNP (Pre: 32.7±20.1 pgm1-1, Post: 154.3±92.8pgml-1; p<0.0001) and a decrease in IMA (Pre: 89.4±6.6 units, Post: 67.3±7.7 units; p<0.0001) were observed. Age was positively correlated with the post NT-proBNP. Finishing time did not correlate with cTnT, NT-proBNP or IMA. Biochemical evidence of myocardial injury was demonstrated in marathon runners. Although the mechanisms underlying myocardial injury are unclear, most of these data suggest that this model can be used to study myocardial regeneration. The mechanism of cardiac injury, however, may not be due to myocardial ischemia, as IMA, a sensitive marker of ischemia, fell following exercise.

14.12. Tissue Adaptation and Remodelling

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4518 Th, 16:00-16:15 (P46) Stress-driven collagen fiber remodeling in arterial walls I. Hariton 1, G. deBotton 1, T.C. Gasser 2, G.A. Holzapfel 2,3. 1The Pearlstone Center for Aeronautical Studies, Department of Mechanical Engineering, Ben-Gurion University, Beer-Sheva, Israel, 2School of Engineering Sciences, Royal Institute of Technology, Stockholm, Sweden, 3Computational Biomechanics, Graz University of Technology, Graz, Austria A stress-driven model for the relation between the collagen morphology and the loading conditions in arterial walls is proposed. We assume that the two families of collagen fibers in arterial walls are aligned along preferred directions, located between the directions of the two maximal principal stresses. For the determination of these directions an iterative finite element based procedure is developed. As an example the remodeling of a section of a human common carotid artery is simulated. We find that the predicted fiber morphology correlates well with experimental observations. Interesting outcomes of the model including local shear minimization and the possibility of axial compressions due to high blood pressure are revealed and discussed. 5700 Th, 16:15-16:30 (P46) A 3-D constrained mixture model for vascular growth and remodeling R.L. Gleason. Mechanical and Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA Despite the explosion of information on vascular growth and remodeling (G&R), from the molecular level to the tissue level, attempts at integrating these data into a predictive multi-scale model are still in their infancy. We submit that vascular G&R is controlled largely by production, removal, and reorganization of structural proteins at multiple hierarchical levels: first via turnover of intracellular proteins (e.g., F-actin), then via regulation of cell-cell, celI-ECM, and ECM-ECM interactions (e.g., cadherins, integrins, and matrix cross-linking enzymes), and finally via growth and turnover of cells and ECM. Given the need to track individual load bearing constituent, and the states in which they are produced and remodeled, we model the constitutive behavior of the vessel wall as a constrained mixture. We consider three constituent- (elastin-, collagen-, and smooth muscle-) dominated behaviors and model each with the strain-energy function of Holzapfel et al. [1]. In addition, we include an active contractile contribution for smooth muscle directed along its fiber direction; we adopt the work of Rachev and Hayashi [2] with this regard. Whereas each constituent is 'constrained' to move together, each constituent can possess its own natural (i.e., stress-free) configuration. Data suggest that the volume fraction and organization (i.e., fiber directions) of individual constituents can vary with position. Opening angle data suggest that the stress-free (natural) configurations of the tissue on the whole (i.e., the mixture), too, can vary with position. We submit that the natural configurations of individual constituents can also vary with position; here we consider radial variations in constituent and mixture natural configuration (i.e., we model a thick axisymmetric tube). We present illustrative results on the evolution of wall stresses and opening angle during flow-, pressure-, and axial stretch-induced growth and remodeling, by prescribing radial variation in the evolution of volume fractions, fiber directions, and natural configurations of individual constituents. References [1] Holzapfel GA, Gasser TC, Ogden RW. J Elast 2000; 61: 1-48. [2] Rachev A, Hayashi K. Ann Biomed Eng 1999; 27: 459-468. 4599 Th, 16:30-16:45 (P46) Remodeling o f the collagen fiber architecture in cardiovascular tissues N.J.B. Driessen, R.A. Boerboom, C.V.C. Bouten, EP.T. Baaijens. Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands Living tissues show an adaptive response to mechanical loading by remodeling their internal structure and morphology. Understanding this response is desired for successful tissue engineering of load-bearing cardiovascular tissues, such as aortic valves [1] and arteries [2]. In addition, it may give further insight into the effects of mechanical factors on the pathophysiology of cardiovascular diseases, such as atherosclerosis and the formation of aneurysms. In this study, mechanically induced remodeling of the collagen fiber architecture in cardiovascular tissues is investigated. A recently developed computational framework [3] is extended to study remodeling of the collagen fiber distribution. A structurally-based constitutive model that incorporates the angular fiber distribution is employed to describe the mechanics of the cardiovascular tissues [4]. It is assumed that the collagen fibers are distributed according to a periodic normal distribution, with a main fiber angle alpha and a dispersity beta. We hypothesize that, for uniaxial loading conditions, the fibers align with the tensile principal direction and the dispersity of the fiber distribution decreases (i.e. fibers become more aligned). For biaxial loading conditions, on the other hand, it is assumed that the collagen fibers align with preferred directions situated in between the principal directions and the dispersity of the distribution