Abstract
Fibrosis is a significant component of cardiac remodeling in heart failure. However, such remodeling has not been fully quantified across a range of scales and the functional impacts on arrhythmogenesis are still poorly understood. Transmural ventricular tissue samples from WKY and SHR rats are imaged and analyzed structurally at the scale of myocardial laminae. New imaging protocols and immunohistochemical labeling are investigated for 3D reconstructions of cell distributions and interconnectivity. At larger scales, there are obvious structural differences between WKY and SHR tissue in fiber rotation and tissue connectivity. Electrical activation models show less significant differences in functional behavior between the two tissue types. Imaging extended volume 3D cell connectivity provides promising insights and will be used in the future to inform modeling at larger scales.
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Zipes, D.P., Wellens, H.J.J.: Sudden cardiac death. Circulation 98, 2334–2351 (1998)
Schaper, J., Kostin, S., Hein, S., Elsässer, A., Arnon, E., Zimmermann, R.: Structural remodelling in heart failure. Exp. Clin. Cardiol. 7, 64–68 (2002)
Houser, S.R., Margulies, K.B., Murphy, A.M., Spinale, F.G., Francis, G.S., Prabhu, S.D., Rockman, H.A., Kass, D.A., Molkentin, J.D., Sussman, M.A., Koch, W.J.: Animal models of heart failure: a scientific statement from the American heart association. Am. Heart Assoc. Counc. Basic Cardiovasc. Sci. Counc. Clin. Cardiol. Counc. Funct. Genomics Transl. Biol. 111, 131–150 (2012)
Smaill, B.H., Zhao, J., Trew, M.L.: Three-dimensional impulse propagation in myocardium: arrhythmogenic mechanisms at the tissue level. Circ. Res. 112, 834–848 (2013)
Kawara, T., Derksen, R., de Groot, J.R., Coronel, R., Tasseron, S., Linnenbank, A.C., Hauer, R.N.W., Kirkels, H., Janse, M.J., de Bakker, J.M.T.: Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation 104, 3069–3075 (2001)
Pertsov, A.M.: Scale of geometric structures responsible for discontinuous propagation in myocardial tissue. In: Spooner, P.M., Joyner, R.W., Jalife, J. (eds.) Discontinuous Conduction in the Heart, pp. 273–293. Futura Press, Armonk (1997)
Tanaka, K., Zlochiver, S., Vikstrom, K.L., Yamazaki, M., Moreno, J., Klos, M., Zaitsev, A.V., Vaidyanathan, R., Auerbach, D.S., Landas, S., Guiraudon, G., Jalife, J., Berenfeld, O., Kalifa, J.: Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure. Circ. Res. 101, 839–847 (2007)
TenTusscher, K.H.W.J., Panfilov, A.V.: Influence of diffuse fibrosis on wave propagation in human ventricular tissue. Europace 9, vi38–vi45 (2007)
Cingolani, O.H., Yang, X.-P., Cavasin, M.A., Carretero, O.A.: Increased systolic performance with diastolic dysfunction in adult spontaneously hypertensive rats. Hypertension 41, 249–254 (2003)
Slama, M., Ahn, J., Varagic, J., Susic, D., Frohlich, E.D.: Long-term left ventricular echocardiographic follow-up of SHR and WKY rats: effects of hypertension and age. Am. J. Physiol. Heart Circ. Physiol. 286, H181–H185 (2004)
Rutherford, S.L., Trew, M.L., Sands, G.B., LeGrice, I.J., Smaill, B.H.: High-resolution 3-dimensional reconstruction of the infarct border zone: impact of structural remodeling on electrical activation. Circ. Res. 111, 301–311 (2012)
Seidel, T., Draebing, T., Seemann, G., Sachse, F.B.: A semi-automatic approach for segmentation of three-dimensional microscopic image stacks. Funct. Imaging Model. Heart 7945, 300–307 (2013)
Jähne, B.: Digital Image Processing. Springer, Heidelberg (2005)
Hoare, C.A.R.: Quicksort. Comput. J. 5, 10–16 (1962)
Faber, G.M., Rudy, Y.: Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study. Biophys. J. 78, 2392–2404 (2000)
LeGrice, I.J., Pope, A.J., Sands, G.B., Whalley, G., Doughty, R.N., Smaill, B.H.: Progression of myocardial remodeling and mechanical dysfunction in the spontaneously hypertensive rat. Am. J. Physiol. Heart Circ. Physiol. 303, H1353–H1365 (2012)
Boluyt, M.: Matrix gene expression and decompensated heart failure: the aged SHR model. Cardiovasc. Res. 46, 239–249 (2000)
Jansen, J.A., van Veen, T.A.B., de Jong, S., van der Nagel, R., van Stuijvenberg, L., Driessen, H., Labzowski, R., Oefner, C.M., Bosch, A.A., Nguyen, T.Q., Goldschmeding, R., Vos, M.A., de Bakker, J.M.T., van Rijen, H.V.M.: Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast activity. Circ. Arrhythmia Electrophysiol. 5, 380–390 (2012)
Van Rijen, H.V.M., Eckardt, D., Degen, J., Theis, M., Ott, T., Willecke, K., Jongsma, H.J., Opthof, T., de Bakker, J.M.T.: Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation 109, 1048–1055 (2004)
Schwab, B.C., Seemann, G., Lasher, R.A., Torres, N.S., Wulfers, E.M., Arp, M., Carruth, E.D., Bridge, J.H.B., Sachse, F.B.: Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling. IEEE Trans. Med. Imaging 32, 862–872 (2013)
Dodt, H.-U., Leischner, U., Schierloh, A., Jährling, N., Mauch, C.P., Deininger, K., Deussing, J.M., Eder, M., Zieglgänsberger, W., Becker, K.: Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain. Nat. Methods 4, 331–336 (2007)
Young, A.A., Legrice, I.J., Young, M.A., Smaill, B.H.: Extended confocal microscopy of myocardial laminae and collagen network. J. Microsc. 192, 139–150 (1998)
Dickie, R., Bachoo, R.M., Rupnick, M.A., Dallabrida, S.M., Deloid, G.M., Lai, J., Depinho, R.A., Rogers, R.A.: Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy. Microvasc. Res. 72, 20–26 (2006)
Seidel, T., Draebing, T., Seemann, G., Sachse, F.B.: A semi-automatic approach for segmentation of three-dimensional microscopic image stacks of cardiac tissue. In: Ourselin, S., Rueckert, D., Smith, N. (eds.) FIMH 2013. LNCS, vol. 7945, pp. 300–307. Springer, Heidelberg (2013)
Saffitz, J.E., Kanter, H.L., Green, K.G., Tolley, T.K., Beyer, E.C.: Tissue-specific determinants of anisotropic conduction velocity in canine atrial and ventricular myocardium. Circ. Res. 74, 1065–1070 (1994)
Khwaounjoo, P., Rutherford, S.L., Scrcek, Ma., LeGrice, I.J., Trew, M.L., Smaill, B.H.: Image-based motion correction for optical mapping of cardiac electrical activity. Ann. Biomed. Eng., 1–12 (2014)
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Khwaounjoo, P., LeGrice, I.J., Trew, M.L., Smaill, B.H. (2015). Quantifying Structural and Functional Differences Between Normal and Fibrotic Ventricles. In: van Assen, H., Bovendeerd, P., Delhaas, T. (eds) Functional Imaging and Modeling of the Heart. FIMH 2015. Lecture Notes in Computer Science(), vol 9126. Springer, Cham. https://doi.org/10.1007/978-3-319-20309-6_6
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