Conflicting findings on the effectiveness of hydrogen therapy for ameliorating vascular leakage in a 5-day post hypoxic-ischemic survival piglet model
Htun Y, Nakamura S, Nakao Y, Mitsuie T, Ohta K, Arioka M, Yokota T, Inoue E, Inoue K, Tsuchiya T, Koyano K, Konishi Y, Miki T, Ueno M, Kusaka T. · Scientific Reports. 2023;13:10486.
Study at a glance
Preclinical
Newborn piglets exposed to a controlled hypoxic-ischemic insult and followed for five days.
After resuscitation, H₂ ventilation was given for 24 hours, either with normothermia or with whole-body therapeutic hypothermia at 33.5±0.5°C. · A cylinder containing 3.8% H₂/96.2% N₂ was blended with 100% O₂. Delivered H₂ varied from 2.1% to 2.7% as each piglet's FiO₂ was adjusted from 0.21 to 0.40.
Twenty-four hours of H₂ ventilation; neurological recovery was observed for five days and brains were assessed on day five.
The prespecified albumin-leakage outcome was numerically lower with H₂ alone but did not differ significantly among the four groups. Neurological and physiological measures produced mixed secondary findings; the article therefore explicitly reports conflicting rather than uniformly positive evidence.
Preclinical piglet model, only 26 analyzed animals, seven post-randomization exclusions based on insult duration, four small groups and a histological surrogate primary outcome. H₂ concentration varied with oxygen requirement and total gas flow was not reported. Japanese JSPS KAKENHI grants funded the study; sponsors reportedly had no study role and the authors declared no competing interests.
What kind of evidence is this?
Preclinical
Randomized four-group newborn-piglet hypoxic-ischemic survival experiment
Other neurological conditions
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
Newborn piglets exposed to a controlled hypoxic-ischemic insult and followed for five days.
33 piglets were randomized; 26 met the prespecified insult-duration analysis range: normothermia n=7, H₂ n=7, therapeutic hypothermia n=6 and H₂ plus hypothermia n=6.
Twenty-four hours of H₂ ventilation; neurological recovery was observed for five days and brains were assessed on day five.
After resuscitation, H₂ ventilation was given for 24 hours, either with normothermia or with whole-body therapeutic hypothermia at 33.5±0.5°C.
H₂ alone diluted in nitrogen and clinical oxygen — not Brown's gas.
A cylinder containing 3.8% H₂/96.2% N₂ was blended with 100% O₂. Delivered H₂ varied from 2.1% to 2.7% as each piglet's FiO₂ was adjusted from 0.21 to 0.40.
Not reported — the article gives H₂ concentration and ventilator duration but not total ventilation flow, so mL/min cannot be calculated.
FiO₂ was adjusted from 21% to 40%; O₂ flow in mL/min was not reported.
Normothermia without H₂ and therapeutic hypothermia without H₂, creating four randomized groups.
Outcomes and reported result
Albumin immunohistochemistry as a marker of cerebral vascular leakage, neurological scores, physiological and blood-gas variables, cerebral blood volume and cerebral hemoglobin oxygenation.
The prespecified albumin-leakage outcome was numerically lower with H₂ alone but did not differ significantly among the four groups. Neurological and physiological measures produced mixed secondary findings; the article therefore explicitly reports conflicting rather than uniformly positive evidence.
The complete open-access publisher article, exclusions, group sizes, gas preparation, positive and null outcomes, funding, sponsor role and conflict statement were checked.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Preclinical piglet model, only 26 analyzed animals, seven post-randomization exclusions based on insult duration, four small groups and a histological surrogate primary outcome. H₂ concentration varied with oxygen requirement and total gas flow was not reported. Japanese JSPS KAKENHI grants funded the study; sponsors reportedly had no study role and the authors declared no competing interests.
Newborn-piglet hypoxic-ischemic encephalopathy model; the null vascular-leakage result does not establish benefit in human newborns.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 37380745 · DOI: 10.1038/s41598-023-37577-0
Open-access Scientific Reports article and PubMed Central copy.
Scientific Reports publisher article, PubMed Central copy and PubMed metadata; full-text extraction checked 9 August 2026.
10 August 2026
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