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Reversal of Maladaptive Gene Program in Left Ventricular Myocardium of Dogs with Heart Failure Following Long-Term Therapy with the Acorn Cardiac Support Device

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Abstract

Progressive left ventricular (LV) dilation is a characteristic feature of heart failure and is associated with poor long-term prognosis. One of the characteristic changes that occur in the failing heart is a change in gene expression wherein fetal genes that were turned off shortly after birth are re-activated in heart failure and may play a key role in the progressive worsening of the heart failure state. This review discusses reversal of maladaptive gene expression in dogs with chronic heart failure treated long-term with the Acorn Cardiac Support Device (CSD); a passive mechanical device designed to prevent progressive LV enlargement and to restore normal LV chamber geometry. Studies in our laboratories have shown that, in addition to preventing LV dilation and improving LV ejection fraction, long-term therapy with the CSD reverses the maladaptive gene program observed in LV myocardium of dogs with heart failure. Therapy with the CSD was associated with up-regulated mRNA expression for α-myosin heavy chain and down-regulated mRNA expression of A- and B- type natriuretic peptides, cytokines and favorably modulated cytoskeletal proteins. These findings provide an explanation for mechanisms that may be partly responsible for the improvement in LV systolic and diastolic function seen in dogs with heart failure after long-term CSD therapy.

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Authors and Affiliations

  1. Departments of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan

    Sharad Rastogi MD, Sudhish Mishra PhD, Ramesh C. Gupta PhD & Hani N. Sabbah PhD (Director)

  2. Cardiovascular Research, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan, 48202

    Hani N. Sabbah PhD (Director)

Authors
  1. Sharad Rastogi MD
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  2. Sudhish Mishra PhD
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  3. Ramesh C. Gupta PhD
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  4. Hani N. Sabbah PhD
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Correspondence to Hani N. Sabbah PhD.

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Rastogi, S., Mishra, S., Gupta, R.C. et al. Reversal of Maladaptive Gene Program in Left Ventricular Myocardium of Dogs with Heart Failure Following Long-Term Therapy with the Acorn Cardiac Support Device. Heart Fail Rev 10, 157–163 (2005). https://doi.org/10.1007/s10741-005-4643-z

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  • DOI: https://doi.org/10.1007/s10741-005-4643-z

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