Potential role of mitochondrial dysfunction in arrhythmogenesis in coronary artery disease

Abstract

Introduction. Coronary artery disease (CAD) continues to be the most common pathology in the structure of cardiovascular diseases over the past decades, both in Russia and around the world. In the normal condition, the mitochondria of all body cells have the same function capabilities due to the carriage of the same genome. Therefore, it is possible to assess the respiration activity of cardiomyocyte mitochondria by the respiration of mitochondria from peripheral blood leukocytes.Aim: To compare respiratory activity of mitochondria of peripheral blood leukocytes in patients diagnosed with coronary artery disease and coronary artery disease with developed cardiac rhythm disorders (CRD).Material and methods. The studied groups included 45 patients with CAD without CRD and 39 patients with CAD complicated by CRD. Mitochondria were isolated from peripheral blood leukocytes by differential centrifugation. The rate of oxygen loss in pyruvate-malate and succinate incubation buffers was measured when isolated mitochondria were introduced, as well as when palmitic acid was added to the medium. Oxygen consumption rate for the V3 (active phosphorylating) and V4 (nonphosphorylating) metabolic sates was determined, and on their basis respiratory control coefficient was calculating using the formula V3/V4. Statistical data processing was carried out using STATISTICA 13.0 software.Results. Oxygen consumption rate in mitochondria of patients with uncomplicated CAD and CAD with CRD had no significant differences in either pyruvate-malate or succinate buffers. When palmitic acid was added to the incubation medium, the mitochondria of CAD patients without CRD significantly increased oxygen consumption rate in both incubation media. Mitochondria of CAD patients with CRD did not change oxygen consumption rate in both metabolic states after the addition of palmitic acid in incubation media.Conclusion. On the basis of the data obtained, it can be concluded that the function capabilities of mitochondria in the complicated course of CAD has been exhausted, which manifests itself in the inability to increase ATP synthesis in response to the introduction of additional substrates.