重症新生児低酸素性虚血性脳症ブタモデルにおける吸入H₂およびCO₂が低体温療法の神経保護効果に与える影響
Using a 48-hour piglet model of severe neonatal hypoxic-ischemic encephalopathy (HIE), this study examined whether 4 hours of 2.1% H2 inhalation or graded CO2 administration following asphyxia could enhance the neuroprotective benefit of therapeutic hypothermia (33.5°C). Asphyxia produced severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10), confirmed by abnormal cerebral electrical activity and neuropathology. Hypothermia provided significant neuroprotection in the caudate nucleus but minimal protection in the hippocampus, where mRNA levels of apoptosis-inducing factor and caspase-3 rose approximately 10-fold compared to naive animals. Neither H2 nor CO2 augmented hypothermia-induced neuroprotection in any brain region; moreover, CO2 abolished the protective effect of hypothermia in the caudate nucleus. These findings indicate that neither medical gas reinforces hypothermia-based neuroprotection in this HIE model.
Hippocampal apoptosis-inducing factor and caspase-3 mRNA increased approximately 10-fold after asphyxia under hypothermia, correlating with region-specific neuroprotective failure. H2 did not modulate these apoptotic markers, and CO2 abolished hypothermia-mediated protection in the caudate nucleus.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/32948011