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Model-Based Design of Mechanical Therapies for Myocardial Infarction

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Abstract

The mechanical properties of healing myocardial infarcts are a critical determinant of pump function and the transition to heart failure. Recent reports suggest that modifying infarct mechanical properties can improve function and limit ventricular remodeling. However, little attempt has been made to identify the specific infarct material properties that would optimize left ventricular (LV) function. We utilized a finite-element model of a large anteroapical infarct in a dog heart to explore a wide range of infarct mechanical properties. Isotropic stiffening of the infarct reduced end-diastolic (EDV) and end-systolic (ESV) volumes, improved LV contractility, but had little effect on stroke volume. A highly anisotropic infarct, with high longitudinal stiffness but low circumferential stiffness coefficients, produced the best stroke volume by increasing diastolic filling, without affecting contractility or ESV. Simulated infarcts in two different locations displayed different transmural strain patterns. Our results suggest that there is a general trade-off between acutely reducing LV size and acutely improving LV pump function, that isotropically stiffening the infarct is not the only option of potential therapeutic interest, and that customizing therapies for different infarct locations may be important. Our model results should provide guidance for design and development of therapies to improve LV function by modifying infarct mechanical properties.

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Acknowledgments

This work was funded by a Coulter Foundation Translational Research Grant (JWH, GA) and by NIH R01 HL-075639 (JWH). The authors wish to thank Dr. Roy Kerckhoffs at the University of California, San Diego, for his advice and assistance.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Health System, University of Virginia, Box 800759, Charlottesville, VA, 22908, USA

    Gregory M. Fomovsky, Jesse R. Macadangdang, Gorav Ailawadi & Jeffrey W. Holmes

  2. Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA

    Jeffrey W. Holmes

  3. Department of Surgery, University of Virginia, Charlottesville, VA, 22908, USA

    Gorav Ailawadi

  4. Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA

    Gorav Ailawadi & Jeffrey W. Holmes

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  1. Gregory M. Fomovsky
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  2. Jesse R. Macadangdang
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  3. Gorav Ailawadi
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  4. Jeffrey W. Holmes
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Correspondence to Jeffrey W. Holmes.

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Fomovsky, G.M., Macadangdang, J.R., Ailawadi, G. et al. Model-Based Design of Mechanical Therapies for Myocardial Infarction. J. of Cardiovasc. Trans. Res. 4, 82–91 (2011). https://doi.org/10.1007/s12265-010-9241-3

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