Phospholipids in mitochondrial dysfunction during hemorrhagic shock

Abstract

Energy deficiency plays a key role in the development of irreversible shock conditions. Therefore, identifying mitochondrial functional disturbances during hemorrhagic shock should be considered a prospective direction for studying its pathogenesis. Phospholipid (PL)-dependent mechanisms of mitochondrial dysfunction in the brain (i.e., in the frontal lobes of the cerebral hemispheres and medulla oblongata) and liver, which, when damaged, leads to an encephalopathy, are examined in this review. These mechanisms show strong regional specificity. Analyzing the data presented in this review suggests that the basis for mitochondrial functional disturbances is cholinergic hyperactivation, accompanied by a choline deficiency and membrane phosphatidylcholine (PC) depletion. Stabilization of the PL composition in mitochondrial membranes using "empty" PC liposomes could be one of the most important methods for eliminating energy deficiency during massive blood loss.

Cerebrospinal fluid metabolite alterations in patients with different etiologies, diagnoses, and prognoses of disorders of consciousness

“…The level of PCs is directly linked to the levels of choline and acetylcholine (Javaid et al., 2021 ). Research on hemorrhagic shock showed that membrane PC depletion was present after shock as the result of cholinergic hyperactivation (Leskova, 2017 ). Cholinergic hyperactivation is the basis of mitochondrial functional disturbances (Leskova, 2017 ), which lead to energy deficiency and neuron death.…”

“…Research on hemorrhagic shock showed that membrane PC depletion was present after shock as the result of cholinergic hyperactivation (Leskova, 2017 ). Cholinergic hyperactivation is the basis of mitochondrial functional disturbances (Leskova, 2017 ), which lead to energy deficiency and neuron death. The supplementation of PCs through drugs, including alpha‐glyceryl phosphorylcholine, Fortasyn Connect, or lecithin alone, has shown the potential to slow the progression of AD and dementia and to improve cognition and remyelination after controlled cortical impact injury (Javaid et al., 2021 ).…”

Whole Blood Redox Potential Correlates With Progressive Accumulation of Oxygen Debt and Acts as A Marker of Resuscitation in A Swine Hemorrhagic Shock Model

“…This corresponds to increasing tissue hypoxia and increasing O 2 ER, with an accumulation of reduced redox species and thus the potential for the blood to be subsequently oxidized on reperfusion. This systemic reduction (gain of electrons and/or decreased oxidation state) is likely multifactorial, and may be influenced by decreased oxygen delivery and progressive mitochondrial dysfunction occurring during hemorrhagic shock, with an associated loss of mitochondrial membrane potential that significantly reduces the ability to utilize NADH, increasing its concentration, which subsequently decreases the NAD+/NADH ratio (26, 27). Through transhydrogenation, NADPH levels increase as well, and although NADPH may not leave the cell, other reduced species carrying excess hydrogen, such as sulfhydryls and ascorbic acid, may cross the cell membrane and decrease the overall redox potential as measured in whole blood (28).…”