Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats

Anesth Analg. 2014 Aug;119(2):368-380. doi: 10.1213/ANE.0000000000000303.

Abstract

Background: Sudden cardiac arrest is a leading cause of death worldwide. Three-fourths of cardiac arrest patients die before hospital discharge or experience significant neurological damage. Hydrogen-rich saline, a portable, easily administered, and safe means of delivering hydrogen gas, can exert organ-protective effects through regulating oxidative stress, inflammation, and apoptosis. We designed this study to investigate whether hydrogen-rich saline treatment could improve survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation, and the mechanism responsible for this effect.

Methods: Sprague-Dawley rats were subjected to 8 minutes of cardiac arrest by asphyxia. Different doses of hydrogen-rich saline or normal saline were administered IV at 1 minute before cardiopulmonary resuscitation, followed by injections at 6 and 12 hours after restoration of spontaneous circulation, respectively. We assessed survival, neurological outcome, oxidative stress, inflammation biomarkers, and apoptosis.

Results: Hydrogen-rich saline treatment dose dependently improved survival and neurological function after cardiac arrest/resuscitation. Moreover, hydrogen-rich saline treatment dose dependently ameliorated brain injury after cardiac arrest/resuscitation, which was characterized by the increase of survival neurons in hippocampus CA1, reduction of brain edema in cortex and hippocampus, preservation of blood-brain barrier integrity, as well as the decrease of serum S100β and neuron-specific enolase. Furthermore, we found that the beneficial effects of hydrogen-rich saline treatment were associated with decreased levels of oxidative products (8-iso-prostaglandin F2α and malondialdehyde) and inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and high-mobility group box protein 1), as well as the increased activity of antioxidant enzymes (superoxide dismutase and catalase) in serum and brain tissues. In addition, hydrogen-rich saline treatment reduced caspase-3 activity in cortex and hippocampus after cardiac arrest/resuscitation.

Conclusions: Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Injuries / blood
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Cardiopulmonary Resuscitation*
  • Caspase 3 / metabolism
  • Cytokines / blood
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fluid Therapy / methods*
  • Heart Arrest / diagnosis
  • Heart Arrest / therapy*
  • Hydrogen / administration & dosage*
  • Inflammation Mediators / blood
  • Male
  • Malondialdehyde / blood
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Oxidative Stress / drug effects
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • S100 Calcium Binding Protein beta Subunit / blood
  • Sodium Chloride / administration & dosage*
  • Time Factors

Substances

  • Antioxidants
  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Neuroprotective Agents
  • S100 Calcium Binding Protein beta Subunit
  • S100b protein, rat
  • 8-epi-prostaglandin F2alpha
  • Sodium Chloride
  • Malondialdehyde
  • Hydrogen
  • Dinoprost
  • Casp3 protein, rat
  • Caspase 3
  • Phosphopyruvate Hydratase