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      Varying Degrees of Ventricular Unloading in the Heterotopic Rat Heart Transplant Model Demonstrated by Magnetic Resonance Imaging

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          Abstract

          Objective:

          Left ventricular assist device placement is an increasingly common treatment for cardiac failure, resulting in cardiac unloading and potentially reversing the remodelling changes seen in heart failure. A popular animal model for human ventricular unloading is the rodent heterotopic non-working heart transplant; the volume loading status of this preparation is important to interpreting the resulting reverse remodelling yet has not been previously investigated. This study was designed to assess the variability of left ventricular volume loading in the rodent transplant model.

          Methods:

          Heterotopic abdominal heart transplant was performed on syngeneic rats; high resolution cine magnetic resonance imaging was subsequently performed on the heterotopic transplanted hearts in anesthetised rats, after variable post-transplant recovery times, in order to assess ventricular loading status.

          Results:

          Highly variable left ventricular volume loading status was demonstrated, with some hearts exhibiting considerable ventricular filling and ejection.

          Conclusions:

          These observations call into question the assumption that studies using this model are consistently examining fully unloaded ventricles, and indicate the desirability of in vivo imaging of such hearts to quantify the degree of ventricular loading.

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          Most cited references27

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          NIH Image to ImageJ: 25 years of image analysis.

          For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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            Myocardial fatty acid metabolism in health and disease.

            There is a constant high demand for energy to sustain the continuous contractile activity of the heart, which is met primarily by the beta-oxidation of long-chain fatty acids. The control of fatty acid beta-oxidation is complex and is aimed at ensuring that the supply and oxidation of the fatty acids is sufficient to meet the energy demands of the heart. The metabolism of fatty acids via beta-oxidation is not regulated in isolation; rather, it occurs in response to alterations in contractile work, the presence of competing substrates (i.e., glucose, lactate, ketones, amino acids), changes in hormonal milieu, and limitations in oxygen supply. Alterations in fatty acid metabolism can contribute to cardiac pathology. For instance, the excessive uptake and beta-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. Furthermore, alterations in fatty acid beta-oxidation both during and after ischemia and in the failing heart can also contribute to cardiac pathology. This paper reviews the regulation of myocardial fatty acid beta-oxidation and how alterations in fatty acid beta-oxidation can contribute to heart disease. The implications of inhibiting fatty acid beta-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed.
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              Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy.

              The cardiac response to increased work includes a reactivation of fetal genes. The response to a decrease in cardiac work is not known. Such information is of clinical interest, because mechanical unloading can improve the functional capacity of the failing heart. We compared here the patterns of gene expression in unloaded rat heart with those in hypertrophied rat heart. Both conditions induced a re-expression of growth factors and proto-oncogenes, and a downregulation of the 'adult' isoforms, but not of the 'fetal' isoforms, of proteins regulating myocardial energetics. Therefore, opposite changes in cardiac workload in vivo induce similar patterns of gene response. Reactivation of fetal genes may underlie the functional improvement of an unloaded failing heart.
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                Author and article information

                Journal
                Int J Biomed Sci
                Int J Biomed Sci
                IJBS
                International Journal of Biomedical Science : IJBS
                Master Publishing Group
                1550-9702
                1555-2810
                December 2014
                : 10
                : 4
                : 223-228
                Affiliations
                [1 ]Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, South Parks Road, Oxford OX1 3PT, U.K.;
                [2 ]Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, U.K.
                Author notes
                Corresponding author: Rhys D. Evans, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, South Parks Road, Oxford OX1 3PT, U.K. Tel: +44 (0)1865 272445; Fax: +44 (0) 1865 282272; E-mail: rhys.evans@ 123456dpag.ox.ac.uk .

                Funding: British Heart Foundation grant PG/030/22667.

                Article
                IJBS-10-223
                4289694
                25598751
                6ade627b-43f4-401f-a9de-6490ad5de6df
                © Carolyn A. Carr et al. Licensee Master Publishing Group

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 August 2014
                : 20 November 2014
                Categories
                Original Article

                heart failure,heart transplant,heterotopic,magnetic resonance imaging,unloading

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