Affiliation:
1. The Feinstein Institutes for Medical ResearchNorthwell Manhasset NY
2. Department of Emergency Medicine Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Hempstead NY
3. Nihon Kohden Innovation Center Cambridge MA
4. Elmezzi Graduate School of Molecular Medicine Manhasset NY
Abstract
Background
Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post‐resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen‐sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia‐induced oxidative stress.
Methods and Results
Sprague–Dawley rats were subjected to 10‐minute asphyxia‐induced CA with a fraction of inspired O
2
of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%,
P
<0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85,
P
<0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5,
P
<0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03,
P
<0.01). After CA, mitochondrial reactive oxygen species increased by ≈2‐fold under hyperoxia. Heme oxygenase expression was also oxygen‐sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB‐1 (high mobility group box‐1) protein was not oxygen‐sensitive and was induced by CA.
Conclusions
Post‐resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post‐CA organ injury, oxygen metabolism, and survival. Additionally, post‐CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine