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A Multidisciplinary Assessment of Remote Myocardial Fibrosis After Reperfused Myocardial Infarction in Swine and Patients

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Abstract

In extensive nonreperfused myocardial infarction (MI), remote fibrosis has been documented. Early reperfusion by primary angioplasty represents the gold standard method to minimize the extension of the infarction. We aimed to ascertain whether fibrosis also affects remote regions in reperfused MI in swine and patients. Swine were subjected to a transient occlusion of the left anterior descending artery followed by 1-week or 1-month reperfusion. Collagen content in the remote area macroscopically, microscopically, by magnetic resonance microimaging, and at the molecular level was similar to controls. In patients with previous MI, samples from autopsies displayed a significant increase in collagen content only in the infarct region. In patients with previous MI submitted to cardiac magnetic resonance-T1 mapping, the extracellular volume fraction in remote segments was similar to that for controls. In all scenarios, the remote region did not show a significant increase of collagen content in comparison with controls.

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Abbreviations

α-SMA:

Alpha-smooth muscle actin

CMR:

Cardiac magnetic resonance

COL1A1:

Collagen type I alpha 1

COL1A2:

Collagen type I alpha 2

COL3A1:

Collagen type III alpha 1

ECV:

Extracellular volume fraction

MI:

Myocardial infarction

TGF-β:

Transforming growth factor-β

TS:

Thioflavin-S

TTZ:

2,3,5-Triphenyltetrazolium chloride

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Authors and Affiliations

  1. Cardiology Department, Hospital Clinico Universitario, INCLIVA, University of Valencia, Blasco Ibanez 17, 46010, Valencia, Spain

    Arantxa Hervas, Jose Gavara, Elena de Dios, Cesar Rios-Navarro, Nerea Perez-Sole, Gema Minana, Julio Nunez, Clara Bonanad, Francisco J. Chorro & Vicente Bodi

  2. Pathology Department, School of Medicine, University of Valencia, Blasco Ibanez 17, 46010, Valencia, Spain

    Amparo Ruiz-Sauri

  3. ERESA, Valencia, Spain

    Jose V. Monmeneu

  4. CBIT, Polytechnic University of Valencia, Valencia, Spain

    Itziar Perez

  5. Laboratory of Metabolomics, University of Valencia, INCLIVA, Valencia, Spain

    Daniel Monleon & Jose M. Morales

  6. UCIM, University of Valencia, Valencia, Spain

    Jose M. Morales

  7. SCSIE, Universidad de Valencia, Valencia, Spain

    Ana Diaz

  8. Physiology Department, School of Medicine, University of Valencia, Valencia, Spain

    Jose M. Vila

Authors
  1. Arantxa Hervas
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  2. Amparo Ruiz-Sauri
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  3. Jose Gavara
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  4. Jose V. Monmeneu
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  5. Elena de Dios
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  6. Cesar Rios-Navarro
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  7. Nerea Perez-Sole
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  8. Itziar Perez
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  9. Daniel Monleon
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  10. Jose M. Morales
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  11. Gema Minana
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  12. Julio Nunez
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  13. Clara Bonanad
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  14. Ana Diaz
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  15. Jose M. Vila
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  16. Francisco J. Chorro
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  17. Vicente Bodi
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Corresponding authors

Correspondence to Amparo Ruiz-Sauri or Vicente Bodi.

Ethics declarations

Human Subjects Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committees and conform to the ethical guidelines of the 1975 Declaration of Helsinki as revised in 2000.

Animal Studies Statement

The local Animal Care and Use Committee approved the study, and it conforms to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1993).

Conflict of Interest

The authors declare that they have no conflicts of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Sources of Funding

This work was supported by the ‘Instituto de Salud Carlos III’ and co-funded by ‘FEDER’ [grant numbers PI14/00271, PIE15/00013] and by the ‘Generalitat Valenciana’ [grant number PROMETEO/2013/007].

Additional information

Associate Editor Enrique Lara-Pezzi oversaw the review of this article

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Online Resource 1

Expanded methodology used in the study. (PDF 443 kb)

Online Resource 2

Table of risk factors and baseline characteristics of controls and patients with previous myocardial infarcts submitted to cardiac magnetic resonance-T1 mapping. (PDF 53 kb)

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Cite this article

Hervas, A., Ruiz-Sauri, A., Gavara, J. et al. A Multidisciplinary Assessment of Remote Myocardial Fibrosis After Reperfused Myocardial Infarction in Swine and Patients. J. of Cardiovasc. Trans. Res. 9, 321–333 (2016). https://doi.org/10.1007/s12265-016-9698-9

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  • DOI: https://doi.org/10.1007/s12265-016-9698-9

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