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The physiological significance of a coronary stenosis differentially affects contractility and mitochondrial function in viable chronically dysfunctional myocardium

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Abstract

The reversibility of viable dysfunctional myocardium after revascularization is variable and the reasons for this are unknown. Using 2D-DIGE, we tested the hypothesis that this could reflect the extent of molecular remodeling of myocardial tissue in the absence of infarction. Swine with a progressive left anterior descending (LAD) stenosis were studied 2 months (n = 18) or 3 months (n = 22) post-instrumentation. Coronary flow reserve (vasodilated/rest) was severely reduced at 2 months (LAD 2.6 ± 0.4 versus 5.1 ± 0.4 in normal, p < 0.05) and became critically impaired after 3 months (LAD 1.1 ± 0.2, p < 0.05 vs. 2 months). Despite progression in stenosis severity, reductions in wall thickening at 2 months (LAD 37 ± 4 % vs. remote 86 ± 9 %, p < 0.05) were unchanged at 3 months (LAD 32 ± 3 %, p = ns). Contractile dysfunction was primarily related to reductions (LAD/normal) in contractile proteins which were not affected by stenosis severity (e.g., troponin T, 2 months 0.82 ± 0.03 vs. 0.74 ± 0.03 at 3 months, p-ns). In contrast, mitochondrial function and proteins were normal at 2 months but declined with progression to a critical stenosis (state 3 respiration at 3 months 145 ± 13 vs. 216 ± 5 ng-atoms O2 mg−1 min−1 at 2 months, p < 0.05). In a similar fashion, increases in stress (e.g., αB-crystalline 2.13 ± 0.2 vs. 1.17 ± 0.13 at 2 months, p < 0.05) and cytoskeletal proteins (e.g., desmin 1.63 ± 0.12 vs. 1.24 ± 0.10 at 2 months, p < 0.05) only developed with more advanced remodeling from a critical stenosis. We conclude that similar degrees of chronic contractile dysfunction can have diverse intrinsic molecular adaptations to ischemia. This spectrum of adaptations may underlie variability in the time course and extent of reversibility in viable chronically dysfunctional myocardium after revascularization.

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Abbreviations

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

EGTA:

Ethylene glycol tetraacetic acid

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

HSP:

Heat shock protein

IM:

Intramuscular

IV:

Intravenous

KCl:

Potassium chloride

MOPS:

3-(N-morpholino)propanesulfonic acid

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Acknowledgments

We would like to thank Anne Coe, Deana Gretka, Elaine Granica and Beth Palka for technical assistance.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest. Supported by HL-55324, HL61610 and the Albert and Elizabeth Rekate Fund.

Author information

Authors and Affiliations

  1. VA WNY Health Care System, University at Buffalo, Buffalo, USA

    James A. Fallavollita & John M. Canty Jr.

  2. The Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, USA

    Brian J. Page, Rebeccah F. Young, Gen Suzuki, James A. Fallavollita & John M. Canty Jr.

  3. The Center for Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, USA

    Brian J. Page, Rebeccah F. Young, Gen Suzuki, James A. Fallavollita & John M. Canty Jr.

  4. Department of Medicine, University at Buffalo, Buffalo, USA

    Brian J. Page, Gen Suzuki, James A. Fallavollita & John M. Canty Jr.

  5. Department of Biomedical Engineering, University at Buffalo, Buffalo, USA

    John M. Canty Jr.

  6. Department of Physiology and Biophysics, University at Buffalo, Buffalo, USA

    John M. Canty Jr.

  7. Division of Cardiovascular Medicine, Clinical and Translational Research Centre, University at Buffalo, Suite 7030, 875 Ellicott Street, Buffalo, NY, 14203, USA

    John M. Canty Jr.

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  1. Brian J. Page
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Correspondence to John M. Canty Jr..

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Page, B.J., Young, R.F., Suzuki, G. et al. The physiological significance of a coronary stenosis differentially affects contractility and mitochondrial function in viable chronically dysfunctional myocardium. Basic Res Cardiol 108, 354 (2013). https://doi.org/10.1007/s00395-013-0354-0

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  • DOI: https://doi.org/10.1007/s00395-013-0354-0

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