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Inhalation of high concentration hydrogen gas improves short-term outcomes in a rat model of asphyxia induced-cardiac arrest.

ABSTRACT: Cardiogenic global brain hypoxia-ischemia is a devastating medical problem that is associated with unfavorable neurologic outcomes. Low dose hydrogen gas (up to 2.9%) has been shown to be neuroprotective in a variety of brain diseases. In the present study, we investigated the protective effect of water by electrolysis-derived high concentration hydrogen gas (60%) in a rat model of asphyxia induced-cardiac arrest and global brain hypoxia-ischemia. High concentration hydrogen gas was either administered starting 1 hour prior to cardiac arrest for 1 hour and starting 1 hour post-resuscitation for 1 hour (pre- & post-treatment) or starting 1 hour post-resuscitation for 2 hours (post-treatment). In animals subjected to 9 minutes of asphyxia, both therapeutic regimens tended to reduce the incidence of seizures and neurological deficits within 3 days post-resuscitation. In rats subjected to 11 minutes of asphyxia, significantly worse neurological deficits were observed compared to 9 minutes asphyxia, and pre- & post-treatment had a tendency to improve the success rate of resuscitation and to reduce the seizure incidence within 3 days post-resuscitation. Findings of this preclinical study suggest that water electrolysis-derived 60% hydrogen gas may improve short-term outcomes in cardiogenic global brain hypoxia-ischemia.

SUBMITTER: Huang L

PROVIDER: S-EPMC6178639 | biostudies-literature | 2018 Jul-Sep

REPOSITORIES: biostudies-literature

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Inhalation of high concentration hydrogen gas improves short-term outcomes in a rat model of asphyxia induced-cardiac arrest.

Huang Lei L Applegate Richard L RL Applegate Patricia M PM Boling Warren W Zhang John H JH

Medical gas research 20180701 3

Cardiogenic global brain hypoxia-ischemia is a devastating medical problem that is associated with unfavorable neurologic outcomes. Low dose hydrogen gas (up to 2.9%) has been shown to be neuroprotective in a variety of brain diseases. In the present study, we investigated the protective effect of water by electrolysis-derived high concentration hydrogen gas (60%) in a rat model of asphyxia induced-cardiac arrest and global brain hypoxia-ischemia. High concentration hydrogen gas was either admin ...[more]

PMID: 30319760

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Project description:BackgroundDespite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats.MethodsRats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated.ResultsThe survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan-Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in D-glutamine and D-glutamate metabolism.ConclusionsH2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia-reperfusion injury in critically ill patients who require ECMO support.

Project description:Ischemia-reperfusion injury is common in critically ill patients, and directed therapies are lacking. Inhaled hydrogen gas diminishes ischemia-reperfusion injury in models of shock, stroke, and cardiac arrest. The purpose of this study was to investigate the safety of inhaled hydrogen gas at doses required for a clinical efficacy study.DesignProspective, single-arm study.SettingTertiary care hospital.Patients/subjectsEight healthy adult participants.InterventionsSubjects underwent hospitalized exposure to 2.4% hydrogen gas in medical air via high-flow nasal cannula (15 L/min) for 24 (n = 2), 48 (n = 2), or 72 (n = 4) hours.Measurements and main resultsEndpoints included vital signs, patient- and nurse-reported signs and symptoms (stratified according to clinical significance), pulmonary function testing, 12-lead electrocardiogram, mini-mental state examinations, neurologic examination, and serologic testing prior to and following exposure. All adverse events were verified by two clinicians external to the study team and an external Data and Safety Monitoring Board. All eight participants (18-30 yr; 50% female; 62% non-Caucasian) completed the study without early termination. No clinically significant adverse events occurred in any patient. Compared with baseline measures, there were no clinically significant changes over time in vital signs, pulmonary function testing results, Mini-Mental State Examination scores, neurologic examination findings, electrocardiogram measurements, or serologic tests for hematologic (except for clinically insignificant increases in hematocrit and platelet counts), renal, hepatic, pancreatic, or cardiac injury associated with hydrogen gas inhalation.ConclusionsInhalation of 2.4% hydrogen gas does not appear to cause clinically significant adverse effects in healthy adults. Although these data suggest that inhaled hydrogen gas may be well tolerated, future studies need to be powered to further evaluate safety. These data will be foundational to future interventional studies of inhaled hydrogen gas in injury states, including following cardiac arrest.

Dataset Information

Inhalation of high concentration hydrogen gas improves short-term outcomes in a rat model of asphyxia induced-cardiac arrest.

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Inhalation of high concentration hydrogen gas improves short-term outcomes in a rat model of asphyxia induced-cardiac arrest.

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