Skip to main content
SpringerLink
Log in

Effect of Scar Compaction on the Therapeutic Efficacy of Anisotropic Reinforcement Following Myocardial Infarction in the Dog

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Cardiac restraint devices have been used following myocardial infarction (MI) to limit left ventricular (LV) dilation, although isotropic restraints have not been shown to improve post-MI LV function. We have previously shown that anisotropic reinforcement of acute infarcts dramatically improves LV function. This study examined the effects of chronic, anisotropic infarct restraint on LV function and remodeling. Hemodynamics, infarct scar structure, and LV volumes were measured in 28 infarcted dogs (14 reinforced, 14 control). Longitudinal restraint reduced 48-h LV volumes, but no differences in LV volume, function, or infarct scar structure were observed after 8 weeks of healing. All scars underwent substantial compaction during healing; we hypothesize that compaction negated the effects of restraint therapy by mechanically unloading the restraint device. Our results lend support to the concept of adjustable restraint devices and suggest that scar compaction may explain some of the variability in published studies of local infarct restraint.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

MI:

Myocardial infarction

LV:

Left ventricle

LAD:

Left anterior descending coronary artery

MR:

Magnetic resonance

SA:

Short axis

Db:

Dobutamine

CSA:

Cross sectional area

ED:

End diastole

ES:

End systole

SV:

Stroke volume

CO:

Cardiac output

EDP:

End-diastolic pressure

Max dPdt:

Maximum rate of LV pressure generation

Ees:

End-systolic elastance

EDV:

End-diastolic volume

ESV:

End-systolic volume

References

  1. Go, A. S., Mozaffarian, D., Roger, V. L., et al. (2013). Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation, 129, e28–e292.

  2. Roger, V. L., Go, A. S., Lloyd-Jones, D. M., et al. (2011). Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation, 125, e2–e220.

  3. Bristow, M. R., Ginsburg, R., Minobe, W., Cubicciotti, R. S., Sageman, S., Lurie, K., et al. (1982). Decreased catecholamine snsitivity and β-adrenergic-receptor density in failing human hearts. The New England Journal of Medicine, 307(4), 205–211.

  4. Thomas, J. A., & Marks, B. H. (1978). Plasma norepinephrine in congestive heart failure. The American Journal of Cardiology, 41(2), 233–243.

    Article  CAS  PubMed  Google Scholar 

  5. Clarke, S. A., Ghanta, R. K., Ailawadi, G., & Holmes, J. W. (2014). Cardiac restraint and support following myocardial infarction. In T. Franz (Ed.), Cardiovascular and cardiac therapeutic devices (pp. 169–206). Berlin Heidelberg: Springer.

  6. Bogen, D. K., Rabinowitz, S. A., Needleman, A., McMahon, T. A., & Abelmann, W. H. (1980). An analysis of the mechanical disadvantage of myocardial infarction in the canine left ventricle. Circulation Research, 47(5), 728–741.

  7. Fomovsky, G. M., Macadangdang, J. R., Ailawadi, G., & Holmes, J. W. (2011). Model-based design of mechanical therapies for myocardial infarction. Journal of Cardiovascular Translational Research, 4(1), 82–91.

  8. Fomovsky, G. M., Clark, S. A., Parker, K. M., Ailawadi, G., & Holmes, J. W. (2012). Anisotropic reinforcement of acute anteroapical infarcts improves pump function. Circulation: Heart Failure, 5, 515–522.

  9. Jugdutt, B. I. (2002). The dog model of left ventricular remodeling after myocardial infarction. Journal of Cardiac Failure, 8(6 Suppl), S472–S475.

    Article  PubMed  Google Scholar 

  10. Jugdutt, B. I., Schwarz-Michorowski, B. L., & Khan, M. I. (1992). Effect of long-term captopril therapy on left ventricular remodeling and function during healing of canine myocardial infarction. Journal of the American College of Cardiology, 19(3), 713–721.

    Article  CAS  PubMed  Google Scholar 

  11. Shapiro, E. P., Rogers, W. J., Beyar, R., Soulen, R. L., Zerhouni, E. A., Lima, J. A., & Weiss, J. L. (1989). Determination of left ventricular mass by magnetic resonance imaging in hearts deformed by acute infarction. Circulation, 79(3), 706–711.

  12. Kim, R. J., Fieno, D. S., Parrish, T. B., Harris, K., Chen, E., Simonetti, O., et al. (1999). Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation, 100, 1992–2002.

  13. Heiberg, E., Sjogren, J., Ugander, M., Carlsson, M., Engblom, H., & Arheden, H. (2010). Design and validation of segment—a freely available software for cardiovascular image analysis. BMC Medical Imaging, 10, 1.

  14. Ginsburg, R., Bristow, M. R., Billingham, M. E., Stinson, E. B., Schroeder, J. S., & Harrison, D. C. (1983). Study of the normal and failing isolated human heart: decreased response of failing heart to isoproterenol. American Heart Journal, 106(3), 535–540.

  15. Fowler, M. B., Laser, J. A., Hopkins, G. L., Minobe, W., & Bristow, M. R. (1986). Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation, 74(6), 1290–1302.

  16. Dolber, P. C., Beyer, E. C., Junker, J. L., & Spach, M. S. (1992). Distribution of gap junctions in dog and rat ventricle studied with a double-label technique. Journal of Molecular and Cellular Cardiology, 24, 1443–1457.

  17. Luna, L. G. (1992). Histopathologic methods and color atlas of special stains and tissue artifacts. Gaithersburg: American Histolabs.

  18. Dolber, P. C., & Spach, M. S. (1987). Picrosirius red staining of cardiac muscle following phosphomolybdic acid treatment. Stain Technology, 62(1), 23–26.

    CAS  PubMed  Google Scholar 

  19. Junqueira, L. C., Bignolas, G., & Brentani, R. R. (1979). Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochemical Journal, 11(4), 447–455.

    Article  CAS  PubMed  Google Scholar 

  20. Whittaker, P., Kloner, R. A., Boughner, D. R., & Pickering, J. G. (1994). Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light. Basic Research in Cardiology, 89(5), 397–410.

  21. Karlon, W. J., Covell, J. W., McCulloch, A. D., Hunter, J. J., & Omens, J. H. (1998). Automated measurement of myofiber disarray in transgenic mice with ventricular expression of ras. The Anatomical Record, 252(4), 612–625.

  22. Fomovsky, G. M., & Holmes, J. W. (2010). Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat. American Journal of Physiology: Heart and Circulatory Physiology, 298(1), H221–H228.

  23. Richardson, W. J., & Holmes, J. W. (2013). Do infarcts really expand or compact? Relationship between changing material properties and apparent infarct remodeling. Abstract No. SBC2013-14411. Presented at the ASME 2013 Summer Bioengineering Conference, June 26–29, 2013, Sunriver, Oregon.

  24. Eghbali, M., Blumenfeld, O. O., Seifter, S., Buttrick, P. M., Leinwand, L. A., Robinson, T. F., et al. (1989). Localization of types I, III and IV collagen mRNAs in rat heart cells by in situ hybridization. The Journal of Molecular and Cellular Cardiology, 21, 103–113.

  25. Lee, E. J., Holmes, J. W., & Costa, K. D. (2008). Remodeling of engineered tissue anisotropy in response to altered loading conditions. Annals of Biomedical Engineering, 36(8), 1322–1334.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Thomopoulos, S., Fomovsky, G. M., & Holmes, J. W. (2005). The development of structural and mechanical anisotropy in fibroblast populated collagen gels. Journal of Biomechanical Engineering, 127(5), 742.

    Article  PubMed  Google Scholar 

  27. Canty, E. G., Lu, Y., Meadows, R. S., Shaw, M. K., Holmes, D. F., & Kadler, K. E. (2004). Coalignment of plasma membrane channels and protrusions (fibropositors) specifies the parallelism of tendon. Journal of Cell Biology, 165(4), 553–563.

  28. Petroll, W. M., Ma, L., & Jester, J. V. (2003). Direct correlation of collagen matrix deformation with focal adhesion dynamics in living corneal fibroblasts. Journal of Cell Science, 116(Pt 8), 1481–1491.

    Article  CAS  PubMed  Google Scholar 

  29. Fomovsky, G. M., Rouillard, A. D., & Holmes, J. W. (2012). Regional mechanics determine collagen fiber structure in healing myocardial infarcts. Journal of Molecular and Cellular Cardiology, 52(5), 1083–1090.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Rouillard, A. D., & Holmes, J. W. (2012). Mechanical regulation of fibroblast migration and collagen remodeling in healing myocardial infarcts. The Journal of Physiology, 18, 4585–4602.

    Article  Google Scholar 

  31. Jugdutt, B. I., & Amy, R. W. M. (1986). Healing after myocardial infarction in the dog: changes in infarct hydroxyproline and topography. Journal of the American College of Cardiology, 7(1), 91–102.

    Article  CAS  PubMed  Google Scholar 

  32. Theroux, P., Ross, J., Franklin, D., Kemper, W. S., & Sasyama, S. (1976). Regional myocardial function in the conscious dog during acute coronary occlusion and responses to morphine, propranolol, nitroglycerin, and lidocaine. Circulation, 53(2), 302–314.

  33. Gerdes, A. M., & Kasten, F. H. (1980). Morphometric study of endomyocardium and epimyocardium of the left ventricle in adult dogs. The American Journal of Anatomy, 159(4), 389–394.

    Article  CAS  PubMed  Google Scholar 

  34. Komamura, K., Shannon, R. P., Ihara, T., Shen, Y. T., Mirsky, I., Bishop, S. P., & Vatner, S. F. (1993). Exhaustion of Frank-Starling mechanism in conscious dogs with heart failure. The American Journal of Physiology, 265(4 Pt 2), H1119–H1131.

  35. Volders, P. G., Sipido, K. R., Vos, M. A., Kulcsár, A., Verduyn, S. C., & Wellens, H. J. (1998). Cellular basis of biventricular hypertrophy and arrhythmogenesis in dogs with chronic complete atrioventricular block and acquired torsade de pointes. Circulation, 98(11), 1136–1147.

  36. Ghanta, R. K., Rangaraj, A., Umakanthan, R., Lee, L., Laurence, R. G., Fox, J. A., et al. (2007). Adjustable, physiological ventricular restraint improves left ventricular mechanics and reduces dilatation in an ovine model of chronic heart failure. Circulation, 115(10), 1201–1210.

  37. Lee, L. S., Ghanta, R. K., Mokashi, S. A., Coelho-Filho, O., Kwong, R. Y., Kwon, M., et al. (2012). Optimized ventricular restraint therapy: adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy. The Journal of Thoracic and Cardiovascular Surgery, 145(3), 824–831.

  38. Koomalsingh, K. J., Witschey, W. R. T., McGarvey, J. R., Shuto, T., Kondo, N., Xu, C., et al. (2013). Optimized local infarct restraint improves left ventricular function and limits remodeling. The Annals of Thoracic Surgery, 95(1), 155–162.

  39. Fomovsky, G. M. (2010). Scar structure, mechanics, and ventricular function in healing myocardial infarction (Doctoral Dissertation). Columbia University.

Download references

Acknowledgments

The authors would like to acknowledge Jeremy Gatesman, John Christopher, Joseph Dimaria, Kevin Foley, and Wade Zhang for their assistance in performing surgeries, conducting MR scans, and analyzing data for this study. Funding for this work was provided by the National Institutes of Health (R21 HL111546) and National Science Foundation Graduate Research Fellowship (DGE-00809128).

Compliance with Ethical Standard

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the University of Virginia Animal Care and Use Committee.

Conflict of Interest

The authors have no conflicts of interest to report.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA

    Samantha A. Clarke, Gorav Ailawadi & Jeffrey W. Holmes

  2. Center for Comparative Medicine, University of Virginia, Charlottesville, VA, USA

    Norman C. Goodman

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

    Gorav Ailawadi

  4. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Jeffrey W. Holmes

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

    Gorav Ailawadi & Jeffrey W. Holmes

Authors
  1. Samantha A. Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norman C. Goodman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gorav Ailawadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey W. Holmes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey W. Holmes.

Additional information

Editor-in-Chief Jennifer L. Hall oversaw the review of this article

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Clarke, S.A., Goodman, N.C., Ailawadi, G. et al. Effect of Scar Compaction on the Therapeutic Efficacy of Anisotropic Reinforcement Following Myocardial Infarction in the Dog. J. of Cardiovasc. Trans. Res. 8, 353–361 (2015). https://doi.org/10.1007/s12265-015-9637-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-015-9637-1

Keywords

Search

Navigation