Hemorrhagic Shock and Mitochondria: Pathophysiology and Therapeutic Approaches

Severe injuries and some pathologies associated with massive bleeding, such as maternal hemorrhage, gastrointestinal and perioperative bleeding, and rupture of an aneurysm, often lead to major blood loss and the development of hemorrhagic shock. A sharp decrease in circulating blood volume triggers a vicious cycle of vasoconstriction and coagulopathy leading to ischemia of all internal organs and, in severe decompensated states, ischemia of the brain and heart. The basis of tissue damage and dysfunction in hemorrhagic shock is an interruption in the supply of oxygen and substrates for energy production to the cells, making the mitochondria a source and target of oxidative stress and proapoptotic signaling. Based on these mechanisms, different strategies are proposed to treat the multiple organ failure that occurs in shock. The main direction of such treatment is to provide the cells with a sufficient amount of substrates that utilize oxidative phosphorylation at different stages and increase the efficiency of energy production by the mitochondria. These strategies include restoring the efficiency of mitochondrial complexes, for example, by restoring the nicotinamide adenine dinucleotide (NAD) pool. Another direction is approaches to minimize oxidative stress as well as apoptosis, which are primarily dependent on the mitochondria. There are also a number of other methods to reduce mitochondrial dysfunction and improve the quality of the mitochondrial population. In this review, we consider such strategies for the treatment of hemorrhagic shock and show the promise of therapeutic approaches aimed at restoring the bioenergetic functions of the cell and protecting mitochondria.