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Post-rest inotropic reaction of the myocardium in dependence on SERCA2a expression level and metabolic enzyme activity in patients with coronary artery disease and diabetes mellitus

Session Poster Session 2

Speaker Dina Kondrat'eva

Congress : Heart Failure 2019

  • Topic : basic science
  • Sub-topic : Basic Science - Cardiac Biology and Physiology: Signal Transduction, Mechano-Transduction
  • Session type : Poster Session
  • FP Number : P1268

Authors : D Kondrat'eva (Tomsk,RU), SA Afanasiev (Tomsk,RU), MV Egorova (Tomsk,RU), SHD Akhmedov (Tomsk,RU), VM Shipulin (Tomsk,RU), SV Popov (Tomsk,RU)

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Authors:
D Kondrat'eva1 , SA Afanasiev1 , MV Egorova2 , SHD Akhmedov1 , VM Shipulin1 , SV Popov1 , 1Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences - Tomsk - Russian Federation , 2Siberian State Medical University - Tomsk - Russian Federation ,

Citation:

Background. Contractile dysfunction in heart failure (HF) and diabetes mellitus is tightly associated with the abnormal excitation-contraction coupling, associated with sarcoplasmic reticulum (SR) dysfunction. The role of changes in the intracellular calcium handling in the pathogenesis of HF associated with diabetes remains poorly understood. The inotropic behavior of isolated preparation of myocardium of patients with coronary artery disease (CAD) and CAD combined with type 2 diabetes mellitus (DM2), its relation with the expression SERCA2a and enzyme activity of the energy suppling metabolism were evaluated.

Methods. The study included patients with chronic CAD and patients with CAD combined with DM2 undergoing coronary artery bypass grafting. Inotropic reaction on rest period was studied on isolated trabeculae of the right auricular myocardium of patients. Post-rest reaction of myocardium assessed for analyze the sarcoplasmic reticulum function (4 - 60 sec). The protein levels of SERCA2a in myocardium were determined by Western blotting. Oxygen consumption by mitochondria was measured using a Clark-type oxygen electrode. The activity of lactate dehydrogenase and succinate dehydrogenase were determined by histochemical method.

Results. It was shown that potentiation and decay of post-rest contraction force of myocardium was observed in both CAD patients with and without DM2. The potentiation of post-rest contractions of myocardium corresponds to the "high content" of the SERCA2a expression, and the decay of post-rest contractions coincides to the "low content" of the SERCA2a. In the combined development of CAD and DM2 with short duration of the disease, the potentiation of post-rest contractions is manifested to a greater degree and corresponds to a higher of SR SERCA2a expression than in CAD patients. Activity of the enzymes of the energy suppling metabolism succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) was higher in the myocardium of CAD patients while the rate of oxygen uptake by cardiomyocyte mitochondria was higher in the myocardium of patients with combined pathology.

Conclusion. In CAD with and without DM2 the potentiation of post-rest contractions of isolated muscle strips of human myocardium corresponds to «high level» of SR SERCA2a expression, while the decay of post-rest contractions is associated with «low level» of SR SERCA2a expression. In combined development of CAD and DM2 with short-term duration of disease the potentiation of post-rest contractions is manifested to a greater degree and corresponds to a higher level of SR SERCA2a expression than in CAD alone patients. In CAD ATP synthesis is realizes mainly in result of glycolytic processes and Krebs cycle and, opposite, the mitochondrial oxidative phosphorylation prevail in comorbid development of CAD and DM2 in the production of ATP.

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