Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
Yin T, Becker LB, Choudhary RC, Takegawa R, Shoaib M, Shinozaki K, Endo Y, Homma K, Rolston DM, Eguchi S, Ariyoshi T, Matsumoto A, Oka K, Takahashi M, Aoki T, Miyara SJ, Nishikimi M, Sasaki J, Kim J, Molmenti EP, Hayashida K. · Journal of Translational Medicine. 2021;19:462.
Study at a glance
Preclinical
Male Sprague-Dawley rats after 20 minutes of asphyxial cardiac arrest and extracorporeal cardiopulmonary resuscitation.
2% H₂ with 98% O₂ supplied through both the ECMO membrane oxygenator and mechanical ventilator from ECPR initiation through the first hour after return of spontaneous circulation. · Gas concentrations were reported, but source flow through the oxygenator and ventilator was not. ECMO blood-flow values are not gas-supply flows and are not used to infer H₂/O₂ mL/min.
Experimental gas during ECPR and for the first 60 minutes after return of spontaneous circulation; total follow-up four hours.
Four-hour survival was 7/9 with H₂ versus 2/9 with placebo, and EEG recovery and several cerebral, hemodynamic, endothelial and metabolic measures favored H₂. MAP, heart rate, temperature, arterial lactate, PaO₂, PaCO₂ and pH did not show confirmed between-group differences in the reported early period.
Very small lethal male-rat model, unblinded H₂ administration, only four-hour follow-up, limited behavioral neurological assessment, multiple exploratory biomarkers and no dose/timing comparison. Institutional/departmental funds and a ZOLL Foundation grant were reported; several authors were affiliated with Miyarisan Pharmaceutical, although authors declared no competing interests.
What kind of evidence is this?
Preclinical
Randomized rat cardiac-arrest/ECPR experiment with blinded laboratory assays
Critical care and ischemia-reperfusion
Inhaled H₂
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Male Sprague-Dawley rats after 20 minutes of asphyxial cardiac arrest and extracorporeal cardiopulmonary resuscitation.
Survival groups used n=9 each. Outcome-specific subgroups used n=3 for EEG, n=7 for brain oxygenation and n=8 for mediator/metabolomic analyses.
Experimental gas during ECPR and for the first 60 minutes after return of spontaneous circulation; total follow-up four hours.
2% H₂ with 98% O₂ supplied through both the ECMO membrane oxygenator and mechanical ventilator from ECPR initiation through the first hour after return of spontaneous circulation.
2% H₂ with 98% O₂ — not Brown's gas because the H₂:O₂ proportions were not 2:1.
Gas concentrations were reported, but source flow through the oxygenator and ventilator was not. ECMO blood-flow values are not gas-supply flows and are not used to infer H₂/O₂ mL/min.
Not reported — gas-supply flow is absent.
98% O₂; mL/min flow not reported because gas-supply flow is absent.
ECPR and mechanical ventilation with 100% O₂, followed in both groups by 60% O₂ for the remaining three hours.
Outcomes and reported result
Four-hour survival, coma reflexes, EEG recovery, brain tissue oxygenation, hemodynamics, endothelial-injury marker syndecan-1, cytokines and plasma metabolomics.
Four-hour survival was 7/9 with H₂ versus 2/9 with placebo, and EEG recovery and several cerebral, hemodynamic, endothelial and metabolic measures favored H₂. MAP, heart rate, temperature, arterial lactate, PaO₂, PaCO₂ and pH did not show confirmed between-group differences in the reported early period.
The complete free PMC article and supplements were checked for randomization, all exposure paths/timing, missing gas flow, outcome-specific samples, positive and null physiological results, assay blinding, funding and conflicts.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Very small lethal male-rat model, unblinded H₂ administration, only four-hour follow-up, limited behavioral neurological assessment, multiple exploratory biomarkers and no dose/timing comparison. Institutional/departmental funds and a ZOLL Foundation grant were reported; several authors were affiliated with Miyarisan Pharmaceutical, although authors declared no competing interests.
Experimental cardiac arrest treated with ECPR in rats; it does not establish survival benefit in human ECMO/ECPR care.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 34781966 · DOI: 10.1186/s12967-021-03129-1
Free full article in PubMed Central.
Complete PMC article, supplementary methods/tables and PubMed metadata; full-text extraction checked 9 August 2026.
10 August 2026
Help people check the facts before they buy.
Hydrogenology keeps 665 source-checked records accessible without advertising or product promotion.
Help us correct the recordReport a discrepancy
Send the exact difference between this page and the linked source. The study reference is attached automatically.