Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling

• Published in: American journal of physiology. Heart and circulatory physiology 2016-11, Vol.311 (5), p.H1075-H1090
• Main Authors: Galan, Diogo T, Bito, Virginie, Claus, Piet, Holemans, Patricia, Abi-Char, Joëlle, Nagaraju, Chandan K, Dries, Eef, Vermeulen, Kristel, Ventura-Clapier, Renée, Sipido, Karin R, Driesen, Ronald B
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - genetics; Animals; Blotting, Western; Cardiomyopathies - diagnostic imaging; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cardiomyopathy; Cell Respiration; Cicatrix; Coronary Stenosis - complications; Electron Transport Complex I - metabolism; Electron Transport Complex II - metabolism; Electron Transport Complex IV - metabolism; Glucose Transport Proteins, Facilitative - genetics; Glycogen - metabolism; Heart attacks; Ischemia; Magnetic Resonance Imaging; Microscopy, Electron; Microscopy, Fluorescence; Mitochondria; Mitochondria, Heart - metabolism; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - etiology; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Perfusion Imaging; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Oxygen; Oxygen Consumption; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Stroke Volume; Sus scrofa; Swine; Ventricular Remodeling
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00945.2015

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 (MI ) and less so in the remote, nonischemic myocardium (MI ). 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 MI was reduced with reduced contractile reserve; in MI strain 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 MI and MI Glycogen accumulation was predominantly perinuclear; mitochondria in this area were smaller but only in MI where 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.