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Review
. 2018 Dec 4:9:1739.
doi: 10.3389/fphys.2018.01739. eCollection 2018.

Oxidative Stress and Neonatal Respiratory Extracorporeal Membrane Oxygenation

Genny Raffaeli  1   2 , Stefano Ghirardello  1 , Sofia Passera  1   2 , Fabio Mosca  1   2 , Giacomo Cavallaro  1
Affiliations
Review

Oxidative Stress and Neonatal Respiratory Extracorporeal Membrane Oxygenation

Genny Raffaeli et al. Front Physiol. .

Abstract

Oxidative stress is a frequent condition in critically ill patients, especially if exposed to extracorporeal circulation, and it is associated with worse outcomes and increased mortality. The inflammation triggered by the contact of blood with a non-endogenous surface, the use of high volumes of packed red blood cells and platelets transfusion, the risk of hyperoxia and the impairment of antioxidation systems contribute to the increase of reactive oxygen species and the imbalance of the redox system. This is responsible for the increased production of superoxide anion, hydrogen peroxide, hydroxyl radicals, and peroxynitrite resulting in increased lipid peroxidation, protein oxidation, and DNA damage. The understanding of the pathophysiologic mechanisms leading to redox imbalance would pave the way for the future development of preventive approaches. This review provides an overview of the clinical impact of the oxidative stress during neonatal extracorporeal support and concludes with a brief perspective on the current antioxidant strategies, with the aim to focus on the potential oxidative stress-mediated cell damage that has been implicated in both short and long-term outcomes.

Keywords: CRRT; ECMO; antioxidants; cardiopulmonary bypass; extracorporeal circulation; oxidative stress.

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Figures

FIGURE 1
FIGURE 1
Redox Biology and Oxidative stress. The production of O2- mainly occurs with the oxidation of NADPH into NADP+ in the presence of O2 and NOX, and partly from an electron’s loss during the combustion of carbohydrates, amino acids, and lipids for the production of energy in mitochondria. Superoxide dismutases (SOD) immediately transforms O2− into H2O2 which is converted in OH● in the presence of iron, if not degraded by antioxidant enzymes in H2O. Furthermore, the excess of O2− reacting with NO produces ONO2−, which in turn participates in oxidative damage with OH●. Contrarily, the standard production of O2- contributes to the homeostasis of the redox signal. CAT, catalase; Cys–S-, cysteine thiolate anion; Cys-SO2H, cysteine sulfinic acid; Cys-SO3H, cysteine sulfonic acid; Cys–SOH, cysteine sulfenic acid; Fe2+, ferrous ions; Fe3+, ferric ions; GPx, glutathione peroxidases; Grx, glutaredoxin; H2O2, hydrogen peroxide; NADP+, nicotinamide adenine dinucleotide phosphate oxidated form; NADPH, nicotinamide adenine dinucleotide phosphate reduced form; NO, Nitric oxide; NOS, nitric oxide synthase; NOX, NADPH oxidase; O2, oxygen; O2-, superoxide anion; OH, hydroxyl radicals; ONO2-, peroxynitrite; PRx, peroxiredoxins; SOD, superoxide dismutases; Trx, thioredoxin.
FIGURE 2
FIGURE 2
Thioredoxin and Peroxiredoxin system. Reduced Trx-SH catalyzes the reduction of disulfide (s–s) bridges within oxidized cell proteins. This process causes the oxidation of Trx-SH to Trx-disulfide which is subsequently reduced by TR at the expense of NADPH. The TR in its catalytic Trx reduction process uses Se as a cofactor. Reduced PRx-SH promotes the separation of two H2O molecules from H2O2 through a “two-step mechanism.” The peroxidic cysteine sulfhydryl group of a Prx subunit is oxidized to sulfenic acid (–SOH). Subsequently, sulfenic acid condenses with the reduced cysteine group present in the other subunit to form a disulfide bond between the units. This two-step process releases two H2O molecules from H2O2 with the oxidation of PRx-SH to PRx-SOH to PRx-disulfide. The oxidized PRx is in turn reduced by the Trx-SH. H2O2, hydrogen peroxide; NADP+, nicotinamide adenine dinucleotide phosphate oxidated form; NADPH, nicotinamide adenine dinucleotide phosphate reduced form; PRx, peroxiredoxin; TR, thioredoxin reductase; Trx, thioredoxin.
FIGURE 3
FIGURE 3
Main determinants of ECMO-induced oxidative stress. Graphical representation of the interaction between the coagulation cascade, the immune response, and the endothelium in the multifactorial amplification process of the ECMO-related redox unbalance. ICAM, intercellular adhesion molecule. VCAM, vascular cell adhesion molecule.
FIGURE 4
FIGURE 4
Clinical relevance of ECMO-induced oxidative stress. AF, atrial fibrillation; ARDS, acute respiratory distress syndrome; ECC, extracorporeal circuit; IBD, intestinal bowel disease; MOF, multi-organ failure; SIRS, systemic inflammatory response syndrome.
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