P104Sarcoplasmic reticulum function and energetic metabolism in failing myocardium associated with diabetes mellitus.

Cardiovascular Research

PubMedID: 25020524

Kondrat Eva D, Afanasiev S, Egorova M, Kozlov B, Popov S. P104Sarcoplasmic reticulum function and energetic metabolism in failing myocardium associated with diabetes mellitus. Cardiovasc Res. 2014;103 Suppl 1S18.
PURPOSE
We studied the sarcoplasmic reticulum function and prevailing type of energy production in failing myocardium associated with diabetes mellitus.

METHODS
Cardiac preparations from right atrium of 14 patients with heart failure (HF) following coronary artery disease and 13 patients with heart failure associated with diabetes mellitus (DM) with short duration of the disease were used in experiments. Myocardium strips on 6 mm length and less than 1 mm thick bathed at 37 °C in oxygenated Krebs-Henzelait solution. Muscles were stimulated at a frequency of 0.5 Hz. Post-rest reaction of myocardium assessed for analyze the sarcoplasmic reticulum function. Mechanical restitution curves were drawn by plotting the isometric twitch force of the first beat after rest period against the rest interval (4 - 60 sec). The protein levels of Ca2+-ATP-ase or SERCA2a in myocardium were determined by Western blotting. Oxygen consumption by mitochondria was measured using a Clark-type oxygen electrode at 30°C. The activity of lactate dehydrogenase and succinate dehydrogenase were determined by histochemical method.

RESULTS
We found that the patients with both HF and HF associated with DM included individuals whose myocardium showed positive post-rest response and patients whose myocardium had negative post-rest reaction. The positive myocardial responses in patients with HF associated with DM were significantly higher than in patients with HF only. The protein levels of SERCA2a in the myocardium of patients with HF combined with DM was significantly higher than in patients with HF only. The oxidative phosphorylation prevailed in the myocardium of patients with HF associated with DM. The activity of glycolysis and Krebs cycle in the myocardium of patient with HF was higher than another group.

CONCLUSION
Cardiomyocytes from patients with HF and with HF associated with DM were remodeled either with the preservation the SR function or with disruption of the SR function. In case of preservation of SR function, development of DM in the presence of HF was associated with higher SERCA2a level than in HF alone. Oxidative phosphorylation prevailed in the cardiomyocytes of patients with HF associated with DM with short duration of the disease.