Skip Navigation LinksHome > July 2011 - Volume 39 - Issue 7 > Postresuscitation syndrome: Potential role of hydroxyl radic...
Critical Care Medicine:
doi: 10.1097/CCM.0b013e3182186d42
Laboratory Investigations

Postresuscitation syndrome: Potential role of hydroxyl radical-induced endothelial cell damage*

Huet, Olivier MD, PhD; Dupic, Laurent MD; Batteux, Frédéric MD, PhD; Matar, Corine PhD; Conti, Marc MD; Chereau, Christiane PharmD; Lemiale, Virginie MD; Harrois, Anatole MD; Mira, Jean-Paul MD, PhD; Vicaut, Eric MD, PhD; Cariou, Alain MD; Duranteau, Jacques MD, PhD

Collapse Box

Abstract

Objective: After out of hospital cardiac arrest, it has been reported that endothelium dysfunction may occur during the postresuscitation syndrome. However, the consequences of the reperfusion phase on endothelial reactive oxygen species production and redox homeostasis have not been explored in out of hospital cardiac arrest patients.

Design: Prospective, observational study.

Setting: Medical intensive care unit in a university hospital.

Patients: Twenty successfully resuscitated out of hospital cardiac arrest patients, seven septic shock patients, and ten healthy volunteers.

Intervention: Plasma was collected from patients at admission and 12, 24, 36, 48, and 72 hrs after cardiac arrest. We studied the production of reactive oxygen species and cell survival during plasma perfusion using perfused endothelial cells (human umbilical vein endothelial cells) as a model. Cell antioxidant response was studied by measuring superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and reduced and oxidized glutathione levels. Mitochondrial respiratory chain activity was assessed by measuring complex I, II, III, and IV activities and anaerobic glycolysis by measuring glucose-6-phosphate dehydrogenase activity.

Measurements and Main Results: Using perfused endothelial cells as a model, we demonstrate that plasma from out of hospital cardiac arrest patients induced on naive human umbilical vein endothelial cells a significant and massive cell death compared to plasma from septic shock patients and healthy volunteers. An increase of reactive oxygen species production with a decrease in antioxidant defenses (superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, reduced and oxidized glutathione levels) was observed. The metabolic consequence of plasma exposure showed that mitochondrial respiratory chain activity was significantly impaired and anaerobic glycolysis was significantly increased. Inhibiting hydroxyl radical production significantly decreased cell death, suggesting that plasma from out of hospital cardiac arrest induced significant cell death by triggering the Fenton reaction.

Conclusion: Plasma from out of hospital cardiac arrest induces major endothelial toxicity with an acute pro-oxidant state in the cells and impairment of mitochondrial respiratory chain activity. This toxicity could be due to hydroxyl radical production by activation of the Fenton reaction.

© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

Article Tools

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.