Mitochondrial function in myocardial injury due to ischemia-reperfusion and in cardioprotection

ZAOBORNYJ T

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2018

Cardiovascular diseases are the main cause of morbidity and mortality in the modern world. Among ischemic heart diseases, acute myocardial infarction is the most frequent ant it is characterized not only by cell death but also by a progressive impairment of the ventricular function. As a fine control of respiration is essential to meet energy demands of cardiomyocytes, during the development of heart disease, the loss of mitochondrial function is a key mediator of cell injury and death. Indeed, mitochondria have a critical role in the control of heart metabolism since they are the cellular source of ATP, as well asCa2+ reservoirs and production sites of reactive O2 and nitrogen species (ROS/RNS). The interplay between mitochondria and other cellular components is considered to regulate the cellular energy levels and redox state. When ischemia takes place, reperfusion is implemented to avoid cell damage. Paradoxically, this maneuver also results in myocardial injury known as reperfusion injury. The absence of O2 during ischemia determines a state of maximum reduction of the mitochondrial respiratory chain. Upon reperfusion, the escape of electrons from the respiratory chain is accelerated, increasing ROS and RNS generation. In this setting, cellular bioenergetics result impaired and this is evidenced by a reduction in mitochondrial respiration, uncoupling and impaired ATP production; as well as by changes in redox balance. Many studies have investigated strategies to reduce ischemia/reperfusion injury through the so called cardioprotective procedures. The approaches that have been fostered include endogenous and pharmacological conditioning. The mechanism involved in the majority of cardioprotective interventions comprises the preservation of mitochondrial integrity and function, together with the maintenance of ROS within physiological levels compatible with signaling and reliable energy supply.