Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Emily R. Pfeiffer; Jared R. Tangney; Jeffrey H. Omens; Andrew D. McCulloch

doi:10.1115/1.4026221

Journal of Biomechanical Engineering | Volume 136 | Issue 2 | research-article

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Research Papers

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Emily R. Pfeiffer, Jared R. Tangney, Jeffrey H. Omens and Andrew D. McCulloch ¹

[+] Author and Article Information

Emily R. Pfeiffer, Jared R. Tangney

Department of Bioengineering
Cardiac Biomedical Science and
Engineering Center,
University of California,
San Diego 9500 Gilman Drive,
La Jolla, CA 92093-0412

Jeffrey H. Omens

Department of Bioengineering and Department of Medicine, Cardiac Biomedical
Science and Engineering Center,
University of California,
San Diego 9500 Gilman Drive,
La Jolla, CA 92093-0412

Andrew D. McCulloch

Department of Bioengineering and Department of Medicine, Cardiac Biomedical
Science and Engineering Center,
University of California,
San Diego 9500 Gilman Drive,
La Jolla, CA 92093-0412
e-mail: amcculloch@ucsd.edu

¹Corresponding author.

Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received September 4, 2013; final manuscript received December 2, 2013; accepted manuscript posted December 12, 2013; published online February 5, 2014. Editor: Victor H. Barocas.

J Biomech Eng 136(2), 021007 (Feb 05, 2014) (11 pages) Paper No: BIO-13-1409; doi: 10.1115/1.4026221 History: Received September 04, 2013; Revised December 02, 2013; Accepted December 12, 2013

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Abstract

Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation–contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation–contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.

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References

Prinzen, F. W., and Peschar, M., 2002, “Relation Between the Pacing Induced Sequence of Activation and Left Ventricular Pump Function in Animals,” Pacing Clin. Electrophysiol., 25(4 Pt 1), pp. 484–498. [CrossRef] [PubMed]

Quinn, T. A., Bayliss, R. A., and Kohl, P., 2011, “Mechano-electric Feedback in the Heart: Effects on Heart Rate and Rhythm,” Heart Rate and Rhythm, O. N.Tripathi, U.Ravens, and M. C.Sanguinetti, Eds., Springer, Berlin, pp. 133–151.

Leclercq, C., and Kass, D. A., 2002, “Retiming the Failing Heart: Principles and Current Clinical Status of Cardiac Resynchronization,” J. Am. Coll. Cardiol., 39(2), pp. 194–201. [CrossRef] [PubMed]

Pogwizd, S. M., and Bers, D. M., 2002, “Calcium Cycling in Heart Failure: The Arrhythmia Connection,” J. Cardiovasc. Electrophysiol., 13(1), pp. 88–91. [CrossRef] [PubMed]

Prinzen, F. W., Augustijn, C. H., AllessieM. a., Arts, T., Delhaas, T., and Reneman, R. S., 1992, “The Time Sequence of Electrical and Mechanical Activation During Spontaneous Beating and Ectopic Stimulation,” Eur. Heart J., 13(4), pp. 535–543. [PubMed]

Hoffman, B., Cranefield, P., Stuckey, J., Amer, N., Cappelletti, R., and Domingo, R., 1959, “Direct Measurement of Conduction Velocity in In Situ Specialized Conducting System of Mammalian Heart,” Proc. Soc. Exp. Biol. Med., 102, pp. 55–57. [CrossRef] [PubMed]

Myerburg, R. J., Nilsson, K., and Gelband, H., 1972, “Physiology of Canine Intraventricular Conduction and Endocardial Excitation,” Circ. Res., 30(2), pp. 217–243. [CrossRef] [PubMed]

Scher, A. M., Young, A. C., Malmgren, A. L., and Erickson, R. V., 1955, “Activation of the Interventricular Septum,” Circ. Res., 3(1), pp. 56–64. [CrossRef] [PubMed]

Sodi-Pallares, D., Bisteni, A., Medrano, G., and Cisneros, F., 1955, “The Activation of the Free Left Ventricular Wall in the Dog's Heart; In Normal Conditions and in Left Bundle Branch Block,” Am. Heart J., 49(4), pp. 587–602. [CrossRef] [PubMed]

Durrer, D., Van Dam, R. T., Freud, G. E., Janse, M. J., Meijler, F. L., and Arzbaecher, R. C., 1970, “Total Excitation of the Isolated Human Heart,” Circulation, 41(6), pp. 899–912. [CrossRef] [PubMed]

Badke, F., Boinay, P., and Covell, J. W., 1980, “Effects of Ventricular Pacing on Regional Left Ventricular Performance in the Dog,” Am. J. Physiol., 238, pp. H858–867. [PubMed]

Gurev, V., Constantino, J., Rice, J. J., and Trayanova, N. A., 2010, “Distribution of Electromechanical Delay in the Heart: Insights From a Three-Dimensional Electromechanical Model,” Biophys. J., 99(3), pp. 745–754. [CrossRef] [PubMed]

Ashikaga, H., Coppola, B. A., Hopenfeld, B., Leifer, E. S., McVeigh, E. R., and Omens, J. H., 2007, “Transmural Dispersion of Myofiber Mechanics: Implications for Electrical Heterogeneity in vivo,” J. Am. Coll. Cardiol., 49(8), pp. 909–916. [CrossRef] [PubMed]

Usyk, T., and McCulloch, A. D., 2003, “Relationship Between Regional Shortening and Asynchronous Electrical Activation in a Three-Dimensional Model of Ventricular Electromechanics,” J. Cardiovasc. Electrophysiol., 14(10 Suppl), pp. S196–S202. [CrossRef] [PubMed]

Russell, K., SmisethO. a., Gjesdal, O., Qvigstad, E., Norseng, P. A., Sjaastad, I., Opdahl, A., Skulstad, H., Edvardsen, T., and Remme, E. W., 2011, “Mechanism of Prolonged Electromechanical Delay in Late Activated Myocardium During Left Bundle Branch Block,” Am. J. Physiol. Heart Circ. Physiol., 301(6), pp. H2334–H243. [CrossRef] [PubMed]

Wyndham, C. R., Smith, T., Meeran, M. K., Mammana, R., Levitsky, S., and Rosen, K. M., 1980, “Epicardial Activation in Patients With Left Bundle Branch Block,” Circulation, 61(4), pp. 696–703. [CrossRef] [PubMed]

Grines, C. L., Bashore, T. M., Boudoulas, H., Olson, S., Shafer, P., and Wooley, C. F., 1989, “Functional Abnormalities in Isolated Left Bundle Branch Block. The Effect of Interventricular Asynchrony,” Circulation, 79(4), pp. 845–853. [CrossRef] [PubMed]

Uusimaa, P., Risteli, J., Niemelä, M., Lumme, J., Ikäheimo, M., Jounela, A., and Peukhurinen, K., 1997, “Collagen Scar Formation After Acute Myocardial Infarction: Relationships to Infarct Size, Left Ventricular Function, and Coronary Artery Patency,” Circulation, 96, pp. 2565–2572. [CrossRef] [PubMed]

van Oosterhout, M. F. M., Prinzen, F. W., Arts, T., Schreuder, J. J., Vanagt, W. Y. R., Cleutjens, J. P. M., Reneman, R. S., and Ward, Y. R., 1998, “Asynchronous Electrical Activation Induces Asymmetrical Hypertrophy of the Left Ventricular Wall,” Circulation, 98(6), pp. 588–595. [CrossRef] [PubMed]

Vassallo, J. a., Cassidy, D. M., Marchlinski, F. E., Buxton, a. E., Waxman, H. L., Doherty, J. U., and Josephson, M. E., 1984, “Endocardial Activation of Left Bundle Branch Block,” Circulation, 69(5), pp. 914–923. [CrossRef] [PubMed]

Prinzen, F., Cheriex, E., Delhaas, T., van Oosterhout, M., Arts, T., Wellens, H., and Reneman, R., 1995, “Asymmetric Thickness of the Left Ventricular Wall Resulting From Asynchronous Electric Activation: A Study in Dogs With Ventricular Pacing and in Patients With Left Bundle Branch Block,” Am. Heart J., 130(5), pp. 1045–1053. [CrossRef] [PubMed]

Sweeney, M. O., and Prinzen, F. W., 2006, “A New Paradigm for Physiologic Ventricular Pacing,” J. Am. Coll. Cardiol., 47(2), pp. 282–288. [CrossRef] [PubMed]

Delhaas, T., Arts, T., Prinzen, F., and Reneman, R., 1993, “Relation Between Regional Electrical Activation Time and Subepicardial Fiber Strain in the Canine Left Ventricle,” Pflügers Arch., 423(1–2), pp. 78–87. [CrossRef]

Prinzen, F. W., Augustijn, C. H., Arts, T., Allessie, M. a., and Reneman, R. S., 1990, “Redistribution of Myocardial Fiber Strain and Blood Flow by Asynchronous Activation,” Am. J. Physiol., 259(2 Pt 2), pp. H300–H308. [PubMed]

Wyman, B. T., Hunter, W. C., Prinzen, F. W., Faris, O. P., and McVeigh, E. R., 2002, “Effects of Single- and Biventricular Pacing on Temporal and Spatial Dynamics of Ventricular Contraction,” Am. J. Physiol. Heart Circ. Physiol., 282(1), pp. H372–H379. [PubMed]

Prinzen, F., and Hunter, W., 1999, “Mapping of Regional Myocardial Strain and Work During Ventricular Pacing: Experimental Study Using Magnetic Resonance Imaging Tagging,” J. Am. Coll. Cardiol., 33(6), pp. 1735–1742. [CrossRef] [PubMed]

Ghio, S., Constantin, C., Klersy, C., Serio, A., Fontana, A., Campana, C., and Tavazzi, L., 2004, “Interventricular and Intraventricular Dyssynchrony Are Common in Heart Failure Patients, Regardless of QRS Duration,” Eur. Heart J., 25(7), pp. 571–578. [CrossRef] [PubMed]

Maron, B. J., Doerer, J. J., Haas, T. S., Estes, N. A. M., and Link, M. S., 2006, “Historical Observation on Commotio Cordis,” Heart Rhythm, 3(5), pp. 605–606. [CrossRef] [PubMed]

Kohl, P., Hunter, P., and Noble, D., 1999, “Stretch-Induced Changes in Heart Rate and Rhythm: Clinical Observations, Experiments and Mathematical Models,” Prog. Biophys. Mol. Biol., 71, pp. 91–138. [CrossRef] [PubMed]

Maron, B. J., Haas, T. S., Ahluwalia, A., Garberich, R. F., Estes, N. A. M., and Link, M. S., 2013, “Increasing Survival Rate From Commotio Cordis,” Heart Rhythm, 10(2), pp. 219–223. [CrossRef] [PubMed]

Madias, C., Maron, B. J., Alsheikh-ali, A. A., Estes, N. A. M., and Link, M. S., 2007, “Commotio Cordis,” Indian Pacing Electrophysiol. J., 7(4), pp. 235–245. [PubMed]

TrayanovaN. a., Constantino, J., and Gurev, V., 2010, “Models of Stretch-Activated Ventricular Arrhythmias,” J. Electrocardiol., 43(6), pp. 479–485. [CrossRef] [PubMed]

Hansen, D. E., Craig, C. S., and Hondeghem, L. M., 1990, “Stretch-Induced Arrhythmias in the Isolated Canine Ventricle. Evidence for the Importance of Mechanoelectrical Feedback,” Circulation, 81(3), pp. 1094–1105. [CrossRef] [PubMed]

Wang, Z., Taylor, L. K., Denney, W. D., and Hansen, D. E., 1994, “Initiation of Ventricular Extrasystoles by Myocardial Stretch in Chronically Dilated and Failing Canine Left Ventricle,” Circulation, 90(4), pp. 2022–2031. [CrossRef] [PubMed]

Berdowski, J., Tijssen, J. G. P., and Koster, R. W., 2010, “Chest Compressions Cause Recurrence of Ventricular Fibrillation After the First Successful Conversion by Defibrillation in Out-of-Hospital Cardiac Arrest,” Circ. Arrhythmia Electrophysiol., 3(1), pp. 72–78. [CrossRef]

Janse, M. J., Coronel, R., Wilms-Schopman, F. J., and de Groot, J. R., 2003, “Mechanical Effects on Arrhythmogenesis: From Pipette to Patient,” Prog. Biophys. Mol. Biol., 82(1–3), pp. 187–195. [CrossRef] [PubMed]

Pellis, T., Kette, F., Lovisa, D., Franceschino, E., Magagnin, L., Mercante, W. P., and Kohl, P., 2009, “Utility of Pre-cordial Thump for Treatment of Out of Hospital Cardiac Arrest: A Prospective Study,” Resuscitation, 80(1), pp. 17–23. [CrossRef] [PubMed]

Pellis, T., and Kohl, P., 2010, “Extracorporeal Cardiac Mechanical Stimulation: Precordial Thump and Precordial Percussion,” Br. Med. Bull., 93, pp. 161–177. [CrossRef] [PubMed]

Bainbridge, F. A., 1915, “The Influence of Venous Filling Upon the Rate of the Heart,” J. Physiol., 50(2), pp. 65–84. [PubMed]

Crystal, G. J., and Salem, M. R., 2012, “The Bainbridge and the ‘Reverse’ Bainbridge Reflexes: History, Physiology, and Clinical Relevance,” Anesth. Analg., 114(3), pp. 520–532. [CrossRef] [PubMed]

Cui, J., Gao, Z., BlahaC. a., Herr, M. D., Mast, J. L., and Sinoway, L. I., 2013, “Distension of Central Great Vein Decreases Sympathetic Outflow in Humans,” Am. J. Physiol. Heart Circ. Physiol., 305(3), pp. H378–H385. [CrossRef] [PubMed]

Lab, M. J., 1982, “Contraction-Excitation Feedback in Myocardium. Physiological Basis and Clinical Relevance,” Circ. Res., 50(6), pp. 757–766. [CrossRef] [PubMed]

Marrus, S. B., and Nerbonne, J. M., 2008, “Mechanisms Linking Short- and Long-Term Electrical Remodeling in the Heart… Is It a Stretch?,” Channels, 2(2), pp. 117–124. [CrossRef] [PubMed]

Eckardt, L., Kirchhof, P., Monnig, G., Breithardt, G., Borggrefe, M., and Haverkamp, W., 2000, “Modification of Stretch-Induced Shortening of Repolarization by Streptomycin in the Isolated Rabbit Heart,” J. Cardiovasc. Pharmacol., 36(6), pp. 1–17. [PubMed]

Franz, M. R., and Bode, F., 2003, “Mechano-electrical Feedback Underlying Arrhythmias: The Atrial Fibrillation Case,” Prog. Biophys. Mol. Biol., 82(1–3), pp. 163–174. [CrossRef] [PubMed]

Kiseleva, I., Kamkin, A., Wagner, K.-D., Theres, H., Ladhoff, A., Scholz, H., Günther, J., and Lab, M. J., 2000, “Mechanoelectric Feedback After Left Ventricular Infarction in Rats,” Cardiovasc. Res., 45(2), pp. 370–378. [CrossRef] [PubMed]

McNary, T. G., Sohn, K., Taccardi, B., and Sachse, F. B., 2008, “Experimental and Computational Studies of Strain-Conduction Velocity Relationships in Cardiac Tissue,” Prog. Biophys. Mol. Biol., 97(2–3), pp. 383–400. [CrossRef] [PubMed]

Sung, D., Mills, R. W., Schettler, J., Narayan, S. M., Omens, J. H., and McCulloch, A. D., 2003, “Ventricular Filling Slows Epicardial Conduction and Increases Action Potential Duration in an Optical Mapping Study of the Isolated Rabbit Heart,” J. Cardiovasc. Electrophysiol., 14(7), pp. 739–749. [CrossRef] [PubMed]

Mills, R. W., Narayan, S. M., and McCulloch, A. D., 2008, “Mechanisms of Conduction Slowing During Myocardial Stretch by Ventricular Volume Loading in the Rabbit,” Am. J. Physiol. Heart Circ. Physiol., 295(3), pp. H1270–H1278. [CrossRef] [PubMed]

Satoh, T., and Zipes, D. P., 1996, “Unequal Atrial Stretch in Dogs Increases Dispersion of Refractoriness Conducive to Developing Atrial Fibrillation,” J. Cardiovasc. Electrophysiol., 7(9), pp. 833–842. [CrossRef] [PubMed]

Mills, R. W., Wright, A. T., Narayan, S. M., and McCulloch, A. D., 2011, “The Effects of Wall Stretch on Ventricular Conduction and Refractoriness in the Whole Heart,” Cardiac Mechano-Electric Coupling and Arrhythmias, P.Kohl, F.Sachs, and M. R.Franz, Eds., Oxford University Press, Oxford, pp. 180–186.

López-López, J., Shacklock, P., Balke, C., and Wier, W., 1995, “Local Calcium Transients Triggered by Single L-Type Calcium Channel Currents in Cardiac Cells,” Science, 268(5213), pp. 1042–1045. [CrossRef] [PubMed]

Bers, D., 2002, “Cardiac Excitation-Contraction Coupling,” Nature, 415(6868), pp. 198–205. [CrossRef] [PubMed]

Endo, M., Tanaka, M., and Ogawa, Y., 1970, “Calcium Induced Release of Calcium From the Sarcoplasmic Reticulum of Skinned Skeletal Muscle Fibres,” Nature, 228(5266), pp. 34–36. [CrossRef] [PubMed]

Cordeiro, J. M., Greene, L., Heilmann, C., Antzelevitch, D., and Antzelevitch, C., 2004, “Transmural Heterogeneity of Calcium Activity and Mechanical Function in the Canine Left Ventricle,” Am. J. Physiol. Heart Circ. Physiol., 286(4), pp. H1471–H1479. [CrossRef] [PubMed]

Bers, D. M., 2008, “Calcium Cycling and Signaling in Cardiac Myocytes,” Annu. Rev. Physiol., 70, pp. 23–49. [CrossRef] [PubMed]

Holroydes, M. J., Robertson, S. P., Johnsong, J. D., Solarosgl, R. J., James, D., Solaro, R. J., and Potter, J. D., 1980, “The Calcium and Magnesium Binding Sites on Cardiac Troponin and Their Role in the Regulation of Myofibrillar Adenosine Triphosphatase,” J. Biol. Chem., 255(24), pp. 11688–11693. [PubMed]

Kobayashi, T., and Solaro, R. J., 2005, “Calcium, Thin Filaments, and the Integrative Biology of Cardiac Contractility,” Annu. Rev. Physiol., 67, pp. 39–67. [CrossRef] [PubMed]

Gordon, A. M., Homsher, E., and Regnier, M., 2000, “Regulation of Contraction in Striated Muscle,” Physiol. Rev., 80(2), pp. 853–924. [PubMed]

de Tombe, P. P., Mateja, R. D., Tachampa, K., Ait Mou, Y., Farman, G. P., and Irving, T. C., 2010, “Myofilament Length Dependent Activation.,” J. Mol. Cell. Cardiol., 48(5), pp. 851–858. [CrossRef] [PubMed]

Campbell, S. G., Lionetti, F. V., Campbell, K. S., and McCulloch, A. D., 2010, “Coupling of Adjacent Tropomyosins Enhances Cross-Bridge-Mediated Cooperative Activation in a Markov Model of the Cardiac Thin Filament,” Biophys. J., 98(10), pp. 2254–2264. [CrossRef] [PubMed]

Hofmann, P. A., and Fuchs, F., 1988, “Bound Calcium and Force Development in Skinned Cardiac Muscle Bundles: Effect of Sarcomere Length,” J. Mol. Cell. Cardiol., 20(8), pp. 667–677. [CrossRef] [PubMed]

Allen, D. G., Kurihara, S., and Allen, B. Y. D. G., 1982, “The Effects of Muscle Length on Intracellular Calcium Transients in Mammalian Cardiac Muscle,” J. Physiol., 327, pp. 79–94. [PubMed]

Bett, G. C., and Sachse, F. B., 1997, “Cardiac Mechanosensitivity and Stretch-Activated Ion Channels,” Trends Cardiovasc. Med., 7(1), pp. 4–8. [CrossRef] [PubMed]

Bowman, C. L., Gottlieb, P. a., Suchyna, T. M., Murphy, Y. K., and Sachs, F., 2007, “Mechanosensitive Ion Channels and the Peptide Inhibitor GsMTx-4: History, Properties, Mechanisms and Pharmacology,” Toxicon, 49(2), pp. 249–270. [CrossRef] [PubMed]

Dyachenko, V., Husse, B., Rueckschloss, U., and Isenberg, G., 2009, “Mechanical Deformation of Ventricular Myocytes Modulates Both TRPC6 and Kir2.3 Channels,” Cell Calcium, 45(1), pp. 38–54. [CrossRef] [PubMed]

Hu, H., and Sachs, F., 1997, “Stretch-Activated Ion Channels in the Heart,” J. Mol. Cell. Cardiol., 29, pp. 1511–1523. [CrossRef] [PubMed]

Spassova, M. a., Hewavitharana, T., Xu, W., Soboloff, J., and Gill, D. L., 2006, “A Common Mechanism Underlies Stretch Activation and Receptor Activation of TRPC6 Channels,” Proc. Natl. Acad. Sci. U.S.A., 103(44), pp. 16586–16591. [CrossRef] [PubMed]

Suchyna, T. M., Johnson, J. H., Hamer, K., Leykam, J. F., Gage, D. a., Clemo, H. F., Baumgarten, C. M., and Sachs, F., 2000, “Identification of a Peptide Toxin From Grammostola Spatulata Spider Venom That Blocks Cation-Selective Stretch-Activated Channels,” J. Gen. Physiol., 115(5), pp. 583–598. [CrossRef] [PubMed]

Eder, P., and Molkentin, J. D., 2011, “TRPC Channels As Effectors of Cardiac Hypertrophy,” Circ. Res., 108(2), pp. 265–272. [CrossRef] [PubMed]

Friedrich, O., Wagner, S., Battle, A. R., Schürmann, S., and Martinac, B., 2012, “Mechano-regulation of the Beating Heart at the Cellular Level—Mechanosensitive Channels in Normal and Diseased Heart,” Prog. Biophys. Mol. Biol., 110(2–3), pp. 226–238. [CrossRef] [PubMed]

Quinn, T. A., and Kohl, P., 2012, “Mechano-sensitivity of Cardiac Pacemaker Function: Pathophysiological Relevance, Experimental Implications, and Conceptual Integration With Other Mechanisms of Rhythmicity,” Prog. Biophys. Mol. Biol., 110(2–3), pp. 257–268. [CrossRef] [PubMed]

Healy, S. N., and McCulloch, A. D., 2005, “An Ionic Model of Stretch-Activated and Stretch-Modulated Currents in Rabbit Ventricular Myocytes,” Europace, 7, pp. S128–S134. [CrossRef]

Kong, C.-R., Bursac, N., and Tung, L., 2005, “Mechanoelectrical Excitation by Fluid Jets in Monolayers of Cultured Cardiac Myocytes,” J. Appl. Physiol., 98(6), pp. 2328–2336. [CrossRef] [PubMed]

Weise, L. D., and Panfilov, A. V., 2013, “A Discrete Electromechanical Model for Human Cardiac Tissue: Effects of Stretch-Activated Currents and Stretch Conditions on Restitution Properties and Spiral Wave Dynamics,” PLoS One, 8(3), p. e59317. [CrossRef] [PubMed]

Clapham, D. E., Shrier, A., and DeHaan, R. L., 1980, “Junctional Resistance and Action Potential Delay Between Embryonic Heart Cell Aggregates,” J. Gen. Physiol., 75(6), pp. 633–654. [CrossRef] [PubMed]

Elfgang, C., Eckert, R., Lichtenberg-Fraté, H., Butterweck, A., Traub, O., Klein, R. a., Hülser, D. F., and Willecke, K., 1995, “Specific Permeability and Selective Formation of Gap Junction Channels in Connexin-Transfected HeLa Cells,” J. Cell Biol., 129(3), pp. 805–817. [CrossRef] [PubMed]

Gourdie, R. G., 1995, “A Map of the Heart: Gap Junctions, Connexin Diversity and Retroviral Studies of Conduction Myocyte Lineage,” Clin. Sci., 88, pp. 257–262. [PubMed]

Severs, N. J., Bruce, A. F., Dupont, E., and Rothery, S., 2008, “Remodelling of Gap Junctions and Connexin Expression in Diseased Myocardium,” Cardiovasc. Res., 80(1), pp. 9–19. [CrossRef] [PubMed]

Weingart, R., 1986, “Electrical Properties of the Nexal Membrane Studied in Rat Ventricular Cell Pairs,” J. Physiol., 370, pp. 267–284. [PubMed]

Fontes, M. S. C., van Veen, T. a., B., de Bakker, J. M. T., and van Rijen, H. V. M., 2011, “Functional Consequences of Abnormal Cx43 Expression in the Heart,” Biochim. Biophys. Acta, 1818(8), pp. 2020–202. [CrossRef] [PubMed]

Saffitz, J. E., Laing, J. G., and Yamada, K. a., 2000, “Connexin Expression and Turnover: Implications for Cardiac Excitability,” Circ. Res., 86, pp. 723–728. [CrossRef] [PubMed]

Saffitz, J. E., 2005, “Dependence of Electrical Coupling on Mechanical Coupling in Cardiac Myocytes: Insights Gained From Cardiomyopathies Caused by Defects in Cell-Cell Connections,” Ann. N.Y. Acad. Sci., 1047, pp. 336–344. [CrossRef] [PubMed]

Cherian, P. P., Siller-Jackson, A. J., Gu, S., Wang, X., Bonewald, L. F., Sprague, E., and Jiang, J. X., 2005, “Mechanical Strain Opens Connexin 43 Hemichannels in Osteocytes: A Novel Mechanism for the Release of Prostaglandin,” Mol. Biol. Cell, 16(7), pp. 3100–3106. [CrossRef] [PubMed]

Gopalan, S. M., Flaim, C., Bhatia, S. N., Hoshijima, M., Knoell, R., Chien, K. R., Omens, J. H., and McCulloch, A. D., 2003, “Anisotropic Stretch-Induced Hypertrophy in Neonatal Ventricular Myocytes Micropatterned on Deformable Elastomers,” Biotechnol. Bioeng., 81(5), pp. 578–587. [CrossRef] [PubMed]

Zhuang, J., Yamada, K. a., Saffitz, J. E., and Kléber, A. G., 2000, “Pulsatile Stretch Remodels Cell-to-Cell Communication in Cultured Myocytes,” Circ. Res., 87(4), pp. 316–322. [CrossRef] [PubMed]

Kontogeorgis, A., Kaba, R. a., Kang, E., Feig, J. E., Gupta, P. P., Ponzio, M., Liu, F., Rindler, M. J., Wit, A. L., Fisher, E. a., Peters, N. S., and Gutstein, D. E., 2008, “Short-Term Pacing in the Mouse Alters Cardiac Expression of Connexin43,” BioMed Cent. Physiol., 8, p. 8.

Poelzing, S., and Rosenbaum, D. S., 2004, “Altered Connexin43 Expression Produces Arrhythmia Substrate in Heart Failure,” Am. J. Physiol. Heart Circ. Physiol., 287(4), pp. H1762–H1770. [CrossRef] [PubMed]

Rhett, J. M., Veeraraghavan, R., Poelzing, S., and Gourdie, R. G., 2013, “The Perinexus: Sign-Post on the Path to a New Model of Cardiac Conduction?,” Trends Cardiovasc. Med., 23(6), pp. 222–228. [CrossRef] [PubMed]

Hand, P. E., and Peskin, C. S., 2010, “Homogenization of an Electrophysiological Model for a Strand of Cardiac Myocytes With Gap-Junctional and Electric-Field Coupling,” Bull. Math. Biol., 72(6), pp. 1408–1424. [CrossRef] [PubMed]

Lin, J., and Keener, J. P., 2013, “Ephaptic Coupling in Cardiac Myocytes,” IEEE Trans. Biomed. Eng., 60(2), pp. 576–582. [CrossRef] [PubMed]

Roberts, S. F., Stinstra, J. G., and Henriquez, C. S., 2008, “Effect of Nonuniform Interstitial Space Properties on Impulse Propagation: A Discrete Multidomain Model,” Biophys. J., 95(8), pp. 3724–3737. [CrossRef] [PubMed]

Kohl, P., Cooper, P. J., and Holloway, H., 2003, “Effects of Acute Ventricular Volume Manipulation on In Situ Cardiomyocyte Cell Membrane Configuration,” Prog. Biophys. Mol. Biol., 82(1–3), pp. 221–227. [CrossRef] [PubMed]

McNary, T. G., Spitzer, K. W., Holloway, H., Bridge, J. H. B., Kohl, P., and Sachse, F. B., 2012, “Mechanical Modulation of the Transverse Tubular System of Ventricular Cardiomyocytes,” Prog. Biophys. Mol. Biol., 110(2–3), pp. 218–225. [CrossRef] [PubMed]

Suchyna, T. M., Tape, S. E., Koeppe, R. E., Andersen, O. S., Sachs, F., and Gottlieb, P. A., 2004, “Bilayer-Dependent Inhibition of Mechanosensitive Channels by Neuroactive Peptide Enantiomers,” Nature, 430(6996), pp. 235–240. [CrossRef] [PubMed]

Maleckar, M. M., Greenstein, J. L., Giles, W. R., and Trayanova, N. A., 2009, “Electrotonic Coupling Between Human Atrial Myocytes and Fibroblasts Alters Myocyte Excitability and Repolarization,” Biophys. J., 97(8), pp. 2179–2190. [CrossRef] [PubMed]

Miragoli, M., Gaudesius, G., and Rohr, S., 2006, “Electrotonic Modulation of Cardiac Impulse Conduction by Myofibroblasts,” Circ. Res., 98(6), pp. 801–810. [CrossRef] [PubMed]

Rook, M., Jongsma, H., and Jonge, B., 1989, “Single Channel Currents of Homo- and Heterologous Gap Junctions Between Cardiac Fibroblasts and Myocytes,” Pflügers Arch. Eur. J. Physiol., 414(1), pp. 95–98. [CrossRef]

Rudy, Y., 2005, “Electrotonic Cell-Cell Interactions in Cardiac Tissue: Effects on Action Potential Propagation and Repolarization,” Ann. N.Y. Acad. Sci., 1047, pp. 308–313. [CrossRef] [PubMed]

100

Kohl, P., Kamkin, A., Kiseleva, I. S., and Streubel, T., 1992, “Mechanosensitive Cells in the Atrium of Frog Heart,” Exp. Physiol., 77(1), pp. 213–216. [PubMed]

101

Kohl, P., Kamkin, A., Kiseleva, I. S., and Noble, D., 1994, “Mechanosensitive Fibroblasts in the Sino-Atrial Node Region of Rat Heart: Interaction With Cardiomyocytes and Possible Role,” Exp. Physiol., 79(6), pp. 943–956. [PubMed]

102

Haraguchi, Y., Shimizu, T., Yamato, M., and Okano, T., 2010, “Electrical Interaction Between Cardiomyocyte Sheets Separated by Non-cardiomyocyte Sheets in Heterogeneous Tissues,” Tissue Eng., 4, pp. 291–299.

103

Rohr, S., 2009, “Myofibroblasts in Diseased Hearts: New Players in Cardiac Arrhythmias?,” Heart Rhythm, 6(6), pp. 848–856. [CrossRef] [PubMed]

104

Vasquez, C., Benamer, N., and Morley, G. E., 2011, “The Cardiac Fibroblast: Functional and Electrophysiological Considerations in Healthy and Diseased Hearts,” J. Cardiovasc. Pharmacol., 57(4), pp. 380–388. [CrossRef] [PubMed]

105

Thompson, S. a., Copeland, C. R., Reich, D. H., and Tung, L., 2011, “Mechanical Coupling Between Myofibroblasts and Cardiomyocytes Slows Electric Conduction in Fibrotic Cell Monolayers,” Circulation, 123(19), pp. 2083–2093. [CrossRef] [PubMed]

106

Suchyna, T. M., and Sachs, F., 2007, “Mechanosensitive Channel Properties and Membrane Mechanics in Mouse Dystrophic Myotubes,” J. Physiol., 581(1), pp. 369–387. [CrossRef] [PubMed]

107

Sokabe, M., Sachs, F., and Jing, Z. Q., 1991, “Quantitative Video Microscopy of Patch Clamped Membranes Stress, Strain, Capacitance, and Stretch Channel Activation,” Biophys. J., 59(3), pp. 722–728. [CrossRef] [PubMed]

108

Morris, C., and Homann, U., 2001, “Cell Surface Area Regulation and Membrane Tension,” J. Membr. Biol., 179, pp. 79–102. [PubMed]

109

Gómez, A. M., Guatimosim, S., Dilly, K. W., Vassort, G., Lederer, W. J., and Gómez, A. M., 2001, “Heart Failure After Myocardial Infarction: Altered Excitation-Contraction Coupling,” Circulation, 104(6), pp. 688–693. [CrossRef] [PubMed]

110

Isenberg, G., Kondratev, D., Dyachenko, V., Kazanski, V., and Gallitelli, M. F., 2005, “Isolated Cardiomyocytes: Mechanosensitivity of Action Potential, Membrane Current and Ion Concentration,” Mechanosensitivity in Cells and Tissues, A.Kamkin, and I.Kiseleva, Eds., Academia, Moscow.

111

Camelliti, P., Al-Saud, S. A., Smolenski, R. T., Al-Ayoubi, S., Bussek, A., Wettwer, E., Banner, N. R., Bowles, C. T., Yacoub, M. H., and Terracciano, C. M., 2011, “Adult Human Heart Slices Are a Multicellular System Suitable for Electrophysiological and Pharmacological Studies,” J. Mol. Cell. Cardiol., 51(3), pp. 390–398. [CrossRef] [PubMed]

112

Seo, K., Inagaki, M., Nishimura, S., Hidaka, I., Sugimachi, M., Hisada, T., and Sugiura, S., 2010, “Structural Heterogeneity in the Ventricular Wall Plays a Significant Role in the Initiation of Stretch-Induced Arrhythmias in Perfused Rabbit Right Ventricular Tissues and Whole Heart Preparations,” Circ. Res., 106, pp. 176–184. [CrossRef] [PubMed]

113

de Boer, T. P., Camelliti, P., Ravens, U., and Kohl, P., 2009, “Myocardial Tissue Slices: Organotypic Pseudo-2D Models for Cardiac Research & Development,” Future Cardiol., 5(5), pp. 425–430. [CrossRef] [PubMed]

114

Engler, A. J., Carag-Krieger, C., Johnson, C. P., Raab, M., Tang, H.-Y., Speicher, D. W., Sanger, J. W., Sanger, J. M., and Discher, D. E., 2008, “Embryonic Cardiomyocytes Beat Best on a Matrix With Heart-Like Elasticity: Scar-Like Rigidity Inhibits Beating,” J. Cell Sci., 121(Pt 22), pp. 3794–802. [CrossRef] [PubMed]

115

Jacot, J. G., McCulloch, A. D., and Omens, J. H., 2008, “Substrate Stiffness Affects the Functional Maturation of Neonatal Rat Ventricular Myocytes,” Biophys. J., 95(7), pp. 3479–3487. [CrossRef] [PubMed]

116

Yeung, T., Georges, P. C., Flanagan, L. A., Marg, B., Ortiz, M., Funaki, M., Zahir, N., Ming, W., Weaver, V., and Janmey, P. A., 2005, “Effects of Substrate Stiffness on Cell Morphology, Cytoskeletal Structure, and Adhesion,” Cell Motil. Cytoskeleton, 60(1), pp. 24–34. [CrossRef] [PubMed]

117

Alford, P. W., Feinberg, A. W., Sheehy, S. P., and Parker, K. K., 2010, “Biohybrid Thin Films for Measuring Contractility in Engineered Cardiovascular Muscle,” Biomaterials, 31(13), pp. 3613–3621. [CrossRef] [PubMed]

118

Aubin, H., Nichol, J. W., Hutson, C. B., Bae, H., Sieminski, A. L., Cropek, D. M., Akhyari, P., and Khademhosseini, A., 2010, “Directed 3D Cell Alignment and Elongation in Microengineered Hydrogels,” Biomaterials, 31(27), pp. 6941–6951. [CrossRef] [PubMed]

119

Sarig, U., and Machluf, M., 2011, “Engineering Cell Platforms for Myocardial Regeneration,” Expert Opin. Biol. Ther., 11(8), pp. 1055–1077. [CrossRef] [PubMed]

120

Nawroth, J. C., Lee, H., Feinberg, A. W., Ripplinger, C. M., McCain, M. L., Grosberg, A., Dabiri, J. O., and Parker, K. K., 2012, “A Tissue-Engineered Jellyfish With Biomimetic Propulsion,” Nat. Biotechnol., 30, pp. 792–797. [CrossRef] [PubMed]

121

Davis, J., Westfall, M. V., Townsend, D., Blankinship, M., Herron, T. J., Guerrero-serna, G., Wang, W., Devaney, E., and Metzger, J. M., 2008, “Designing Heart Performance by Gene Transfer,” Physiol. Rev., 88, pp. 1567–1651. [CrossRef] [PubMed]

122

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., and Koch, W. J., 2012, “Animal Models of Heart Failure: A Scientific Statement From the American Heart Association,” Circ. Res., 111, pp. 131–150. [CrossRef] [PubMed]

123

Arrenberg, A. B., Stainier, D. Y., Baier, H., and Huisken, J., 2010, “Optogenetic Control of Cardiac Function,” Science, 330(6006), pp. 971–974. [CrossRef] [PubMed]

124

Kaushik, G., Fuhrmann, A., Cammarato, A., and Engler, A. J., 2011, “In Situ Mechanical Analysis of Myofibrillar Perturbation and Aging on Soft, Bilayered Drosophila Myocardium,” Biophys. J., 101(11), pp. 2629–2637. [CrossRef] [PubMed]

125

Rohr, S., Scholly, D., and Kleber, A. G., 1991, “Patterned Growth of Neonatal Rat Heart Cells in Culture. Morphological and Electrophysiological Characterization,” Circ. Res., 68, pp. 114–130. [CrossRef] [PubMed]

126

Bursac, N., Parker, K. K., Iravanian, S., and Tung, L., 2002, “Cardiomyocyte Cultures With Controlled Macroscopic Anisotropy: A Model for Functional Electrophysiological Studies of Cardiac Muscle,” Circ. Res., 91(12), p. e45–e54. [CrossRef] [PubMed]

127

Camelliti, P., McCulloch, A. D., and Kohl, P., 2005, “Microstructured Cocultures of Cardiac Myocytes and Fibroblasts: A Two-Dimensional In Vitro Model of Cardiac Tissue,” Microsc. Microanal., 11(3), pp. 249–259. [CrossRef] [PubMed]

128

Costa, K. D., Lee, E. J., and Holmes, J. W., 2003, “Creating Alignment and Anisotropy in Engineered Heart Tissue: Role of Boundary Conditions in a Model Three-Dimensional Culture System,” Tissue Eng., 9(4), pp. 567–577. [CrossRef] [PubMed]

129

Kuo, P.-L., Lee, H., Bray, M.-A., Geisse, N. a., Huang, Y.-T., Adams, W. J., Sheehy, S. P., and Parker, K. K., 2012, “Myocyte Shape Regulates Lateral Registry of Sarcomeres and Contractility,” Am. J. Pathol., 181(6), pp. 2030–2037. [CrossRef] [PubMed]

130

McDevitt, T., Angello, J., Whitney, M., Reinecke, H., Hauschka, S., Murry, C., and Stayton, P., 2002, “In Vitro Generation of Differentiated Cardiac Myofibers on Micropatterned Laminin Surfaces,” J. Biomed. Mater. Res., 60(3), pp. 472–479. [CrossRef] [PubMed]

131

Barbee, K. A., Macarak, E. J., and Thibault, L. E., 1994, “Strain Measurements in Cultured Vascular Smooth Muscle Cells Subjected to Mechanical Deformation,” Ann. Biomed. Eng., 22(1), pp. 14–22. [CrossRef] [PubMed]

132

Lee, A. A., Delhaas, T., McCulloch, A. D., and Villarreal, F. J., 1999, “Differential Responses of Adult Cardiac Fibroblasts to In Vitro Biaxial Strain Patterns,” J. Mol. Cell. Cardiol., 31(10), pp. 1833–183. [CrossRef] [PubMed]

133

Camelliti, P., Gallagher, J. O., Kohl, P., and McCulloch, A. D., 2006, “Micropatterned Cell Cultures on Elastic Membranes As an In Vitro Model of Myocardium,” Nat. Protoc., 1(3), pp. 1379–1391. [CrossRef] [PubMed]

134

Zhang, Y., Sekar, R. B., McCulloch, A. D., and Tung, L., 2008, “Cell Cultures As Models of Cardiac Mechanoelectric Feedback,” Prog. Biophys. Mol. Biol., 97(2–3), pp. 367–382. [CrossRef] [PubMed]

135

Eschenhagen, T., Fink, C., Remmers, U., Scholz, H., Watfchow, J., Well, J., Zimmermann, W., Dohmen, H. H., Schafer, H., Bishopric, N., Wakatsuki, T., and Elson, E., 1997, “Three-Dimensional Reconstitution of Embryonic Cardiomyocytes in a Collagen Matrix: A New Heart Muscle Model System,” FASEB J., 11(8), pp. 683–694. [PubMed]

136

Asnes, C. F., Marquez, J. P., Elson, E. L., and Wakatsuki, T., 2006, “Reconstitution of the Frank-Starling Mechanism in Engineered Heart Tissues,” Biophys. J., 91(5), pp. 1800–1810. [CrossRef] [PubMed]

137

de Lange, W. J., et al. , 2011, “Neonatal Mouse-Derived Engineered Cardiac Tissue: A Novel Model System for Studying Genetic Heart Disease,” Circ Res, 109(1), pp. 8–19. [CrossRef] [PubMed]

138

Ralphe, J. C., and de Lange, W. J., 2013, “3D Engineered Cardiac Tissue Models of Human Heart Disease: Learning More From Our Mice,” Trends Cardiovasc Med, 23(2), pp. 27–32. [PubMed]

139

Raman, S., Kelley, M. A., and Janssen, P. M., 2006, “Effect of Muscle Dimensions on Trabecular Contractile Performance Under Physiological Conditions,” Pflugers Arch, 451(5), pp. 625–630. [CrossRef] [PubMed]

140

Tong, C. W., Gaffin, R. D., Zawieja, D., and Muthuchamy, M., 2004, “Roles of Phosphorylation of Myosin Binding Protein-C and Troponin I in Mouse Cardiac Muscle Twitch Dynamics,” J. Physiol., 558(Pt 3), pp. 927–41. [CrossRef] [PubMed]

141

ter Keurs, H. E., Rijnsburger, W. H., van Heuningen, R., and Nagelsmit, M. J., 1980, “Tension Development and Sarcomere Length in Rat Cardiac Trabeculae. Evidence of Length-Dependent Activation,” Circ. Res., 46(5), pp. 703–714. [CrossRef] [PubMed]

142

Backx, P. H., and Ter Keurs, H. E., 1993, “Fluorescent Properties of Rat Cardiac Trabeculae Microinjected With Fura-2 Salt,” Am. J. Physiol., 264(4 Pt 2), pp. H1098–H1110. [PubMed]

143

Stull, L. B., Leppo, M. K., Marbán, E., and Janssen, P. M. L., 2002, “Physiological Determinants of Contractile Force Generation and Calcium Handling in Mouse Myocardium,” J. Mol. Cell. Cardiol., 34(10), pp. 1367–1376. [CrossRef] [PubMed]

144

ter Keurs, H., Schouten, V., Bucx, J., Mulder, B., and de Tombe, P., 1987, “Excitation-Contraction Coupling in Myocardium: Implications of Calcium Release and Na+-Ca2+ Exchange,” Can. J. Physiol. Pharmacol., 65(4), pp. 619–626. [CrossRef] [PubMed]

145

Tyberg, J. V., Parmley, W. W., and Sonnenblick, E. H., 1969, “In-Vitro Studies of Myocardial Asynchrony and Regional Hypoxia,” Circ. Res., 25(5), pp. 569–579. [CrossRef] [PubMed]

146

Liu, T., Brown, B. S., Wu, Y., Antzelevitch, C., Kowey, P. R., and Yan, G. X., 2006, “Blinded Validation of the Isolated Arterially Perfused Rabbit Ventricular Wedge in Preclinical Assessment of Drug-Induced Proarrhythmias,” Heart Rhythm, 3(8), pp. 948–956. [CrossRef] [PubMed]

147

Di Diego, J. M., Sicouri, S., Myles, R. C., Burton, F. L., Smith, G. L., and Antzelevitch, C., 2013, “Optical and Electrical Recordings From Isolated Coronary-Perfused Ventricular Wedge Preparations,” J. Mol. Cell Cardiol., 54, pp. 53–64. [CrossRef] [PubMed]

148

Glukhov, A. V., Fedorov, V. V., Lou, Q., Ravikumar, V. K., Kalish, P. W., Schuessler, R. B., Moazami, N., and Efimov, I. R., 2010, “Transmural Dispersion of Repolarization in Failing and Nonfailing Human Ventricle,” Circ. Res., 106, pp. 981–991. [CrossRef] [PubMed]

Figures

Fig. 1

The relationship between excitation–contraction coupling and MEF from the scale of the myocyte to the whole heart

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Fig. 2

The first step in the initiation of contraction begins with an influx of sodium ions, which depolarizes the membrane and opens the voltage-gated L-type calcium channels. This causes an influx of calcium into the cell, some of which binds to ryanodine receptors (RyR) located on surface of the sarcoplasmic reticulum (SR), which allows for a large scale release of calcium from inside the SR; a process referred to as calcium induced calcium release. There is then an abundance of free calcium in the cell that can bind to troponin (Tn), in particular troponin-C. This binding causes tropomyosin (Tm) to shift, exposing the myosin binding site on actin. Once the myosin head binds to actin, force is generated. At the end of the crossbridge cycle, calcium is released from troponin-C and is then either pumped out of the cell by the sodium-calcium exchanger (NCX) or resequestered into the SR via the sarcoplasmic reticulum calcium ATPase (SERCA) pump. Resulting changes in the mechanical context of the cell can alter the dynamics of conduction of electrical excitation throughout the tissue and the duration of cell action potential, by modulating channels, junctions, and cell capacitances and resistances; thus feeding back between cardiac mechanics and electrophysiology.

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Fig. 4

Layout of a computer-controlled system designed for measuring cardiac muscle mechanics. The system is capable of measuring force, calcium transients, sarcomere length (in trabeculae), muscle length, and local muscle strain. The high-speed servomotor performs very precise stretches.

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Fig. 3

Combined apparatus for biaxial stretch of micropatterned neonatal cardiomyocytes and optical mapping of cell membrane potential permits study of conduction through multicellular preparations. (a) Diagram of optical mapping and micropatterned stretch equipment; (b) representative map of electrical activation, spatial scale 2 mm; (c) example stretch experiment result, showing that conduction in the longitudinal and transverse directions of the micropatterned cell culture slows with biaxial stretch, scale 2 mm; and (d) Example activation map in a transgenic mouse model of arrhythmia associated with mechanoelectric junctions, in collaboration with Dr. Farah Sheikh, UCSD.

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Fig. 5

(a) Measured strain in a mouse papillary muscle due to a 20% prestretch with a timing in relation to activation (vertical line) that is similar to (b) measured strain in the late activated region of a ventricularly paced dog heart

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Pfeiffer ER, Tangney JR, Omens JH, McCulloch AD. Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback. ASME. J Biomech Eng. 2014;136(2):021007-021007-11. doi:10.1115/1.4026221.

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Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

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