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Reduced Myocardial Mitochondrial ROS Production in Mechanically Unloaded Hearts

  • Daniel Scheiber
  • Elric Zweck
  • Tomas Jelenik
  • Patrick Horn
  • Sophie Albermann
  • Maryna Masyuk
  • Udo Boeken
  • Diyar Saeed
  • Malte Kelm
  • Michael Roden
  • Julia Szendroedi
  • Ralf Westenfeld
Original Article
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Abstract

Mechanical ventricular unloading in advanced heart failure (HF) has been shown to induce reverse remodeling in myocardial tissues. Little is known about the impact of ventricular unloading on myocardial energy metabolism. We hypothesized that left ventricular unloading reduces myocardial mitochondrial reactive oxygen species (ROS) production and improves mitochondrial coupling efficiency in patients suffering from advanced HF. Left ventricular tissue specimens were harvested from explanted hearts at the time of transplantation. We compared myocardial metabolism in explanted hearts supported with an unloading ventricular assist device prior to transplantation (LVAD-HTX; n = 9) with tissue specimens of unsupported failing hearts (HTX; n = 6). Myocardial mitochondrial ROS production was decreased by 40% in LVAD-HTX compared to HTX patients (1.5 ± 0.3 vs. 0.9 ± 0.1 pmol/(s/mg); p < 0.05). High-resolution respirometry revealed increased mitochondrial coupling efficiency in LVAD-HTX patients (respiratory/control ratio 1.7 ± 0.2 vs. 1.2 ± 0.2; p < 0.05). In conclusion, ventricular unloading is related to decreased mitochondrial ROS production and increased coupling efficiency in myocardium of human failing hearts, suggesting a novel pathomechanism of unloading-associated cardioprotection.

Keywords

Heart failure Left ventricular unloading Left ventricular assist device Heart transplantation Myocardial energy metabolism High-resolution respirometry Mitochondrial respiration Reactive oxygen species 
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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Daniel Scheiber
    • 1
    • 2
    • 3
  • Elric Zweck
    • 1
    • 2
    • 3
  • Tomas Jelenik
    • 2
    • 3
  • Patrick Horn
    • 1
  • Sophie Albermann
    • 1
    • 2
    • 3
  • Maryna Masyuk
    • 1
  • Udo Boeken
    • 4
  • Diyar Saeed
    • 4
  • Malte Kelm
    • 1
    • 5
  • Michael Roden
    • 2
    • 3
    • 6
  • Julia Szendroedi
    • 2
    • 3
    • 6
  • Ralf Westenfeld
    • 1
  1. 1.Division of Cardiology, Pulmonology and Vascular Medicine, Medical FacultyHeinrich Heine UniversityDüsseldorfGermany
  2. 2.Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes ResearchHeinrich Heine UniversityDüsseldorfGermany
  3. 3.German Center for Diabetes Research (DZD e.V.)DüsseldorfGermany
  4. 4.Clinic for Cardiovascular Surgery, Medical FacultyHeinrich Heine UniversityDüsseldorfGermany
  5. 5.Cardiovascular Research Institute Duesseldorf, Medical FacultyHeinrich Heine UniversityDüsseldorfGermany
  6. 6.Department of Endocrinology and Diabetology, Medical FacultyHeinrich Heine UniversityDüsseldorfGermany

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