Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling.
Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MIadjacent) and less so in the remote, nonischemic myocardium (MIremote). We used a pig model of chronic coronary stenosis and MI (n = 13). Functional and perfusion MR imaging 6 wk after intervention showed reduced ejection fraction and increased global wall stress compared with sham-operated animals (Sham; n = 14). Regional strain in MIadjacentwas reduced with reduced contractile reserve; in MIremotestrain was also reduced but responsive to dobutamine and perfusion was normal compared with Sham. Capillary density was unchanged. Cardiac myocytes isolated from both regions had reduced basal and maximal oxygen consumption rate, as well as through complex I and II, but complex IV activity was unchanged. Reduced respiration was not associated with detectable reduction of mitochondrial density. There was no significant change in AMPK or glucose transporter expression levels, but glycogen content was significantly increased in both MIadjacentand MIremoteGlycogen accumulation was predominantly perinuclear; mitochondria in this area were smaller but only in MIadjacentwhere also subsarcolemmal mitochondria were smaller. In conclusion, after MI reduction of mitochondrial respiration and glycogen accumulation occur in all LV regions suggesting that reduced perfusion does not lead to additional specific changes and that increased hemodynamic load is the major driver for changes in mitochondrial function.
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Diogo T
DT
Galan
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Virginie
V
Bito
Cardiovascular Imaging and Dynamics, Department of Cardiovascular Sciences, KU Leuven, University of Leuven, Leuven, Belgium; and.
Piet
P
Claus
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Patricia
P
Holemans
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Joëlle
J
Abi-Char
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Chandan K
CK
Nagaraju
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Eef
E
Dries
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Kristel
K
Vermeulen
INSERM UMR-S 769 Université Paris-Sud, Châtenay-Malabry, France.
Renée
R
Ventura-Clapier
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium; Karin.Sipido@kuleuven.be.
Karin R
KR
Sipido
Division of Experimental Cardiology, KU Leuven, University of Leuven, Leuven, Belgium.
Ronald B
RB
Driesen
D055372:AMP-Activated Protein Kinases / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019069:Cell Respiration; D002921:Cicatrix; D023921:Coronary Stenosis / Q000150:complications; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006003:Glycogen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008929:Mitochondria, Heart / Q000378:metabolism*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D055414:Myocardial Perfusion Imaging; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013318:Stroke Volume; D034421:Sus scrofa; D013552:Swine; D020257:Ventricular Remodeling
D051246:Glucose Transport Proteins, Facilitative; D012333:RNA, Messenger; D006003:Glycogen; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D055372:AMP-Activated Protein Kinases; D042967:Electron Transport Complex I
chronic ischemia; hemodynamic load; mitochondria; perfusion