Affect of heart mitochondrial energetic metabolism in remote ischemic and metabolic preconditioning

Authors: Magdaléna Jašová 1    Ivana Kancirová 1    Táňa Ravingerová 1    Jitka Kuncová 2    Michaela Marková 2    Iveta Waczulíková 3    Miroslav Ferko 1   
1 Slovak Academy of Sciences, Institute for Heart Research , Bratislava, Slovak Republic    2 Charles University of Pilsen , Department of Physiology, Biomedical Center, Faculty of Medicine in Pilsen, Pilsen, Czech Republic    3 Comenius University, Faculty of Mathematics, Physics & Informatics, Department of Nuclear Physics, Bratislava, Slovak Republic   
Year: 2018
Section: Cellular metabolism, physiology, molecular biology and genetics
Abstract No.: 1780
ISBN: 978-80-972360-2-1

Background: Biophysical properties of heart mitochondrial membranes may influence their role in adaptation processes in the myocardium. The aim was to elucidate the processes of energetic metabolism, mitochondrial membrane fluidity, pyruvate dehydrogenase activity (PDH) and free oxygen radical (ROS) signalling in myocardial endogenous protection against ischemia-reperfusion injury observed in remote ischemic preconditioning (RIP) and experimental acute diabetes mellitus (DM). For the purpose of elucidating the cardioprotective role of pyruvate dehydrogenase regulation, we proposed a protocol using pyruvate dehydrogenase activator - dichloroacetate (DCA) and anoxia induced in in vitro conditions.

Methods: Male Wistar rats (9-11 weeks old, 220±20 g b. wt.) were used for this study. Heart MIT were isolated by means of differential centrifugation and forwarded to biochemical and biophysical investigation. RIP was triggered by three cycles of 5-min. limb ischemia and reperfusion. Acute DM was induced by a single dose of streptozotocin (STZ, 65 mg/kg b.wt.). Experiment was terminated on the 8th day after STZ application. Isolated hearts were perfused according to Langendorff (30-min ischemia and 40-min reperfusion).

Results: RIP and acute DM preserved ATP synthase activity after I/R injury, without significant influence in mitochondrial respiratory function. RIP increased membrane fluidity due to inhibition of ROS probably. We demonstrated the positive effect of DCA on the mitochondrial respiratory activity.

Conclusion: Since mitochondria of streptozotocin acute diabetes hearts show reduced capability of oxygen consumption, cardiomyocytes can experience the state of pseudo-hypoxia and exhibit increased expression of genes involved in adaptation to hypoxia. RIP induced endogenous protective mechanisms by increase in membrane fluidity, thereby improving the energy demand during ischemia. The process of short-term adaptation, such as the RIP induced positive signal is sufficient enough to start the process of myocardial protection against ischemia-reperfusion injury.

Funding Acknowledgements : APVV-15-0119; VEGA 2/0121/18; ITMS 26230120006