Mitochondrial adaptations in the adjacent and remote myocardium of a chronic myocardial infarction

Scarring and remodelling 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 adjacent ) and less so in the remote, nonischemic myocardium (MI remote). 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 adjacent was reduced with reduced contractile reserve; in MI remote 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 a 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 adjacent and MI remote. Glycogen accumulation was predominantly perinuclear; mitochondria in this area were smaller but only in MI adjacent where also subsarcolemmal mitochondria were smaller. PN mitochondria also have different behaviour. They can show oscillation independently from the IMF mitochondria population, suggesting they have a separate network. 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.

Publication year:2019

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