Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management

Background-We have previously shown that hydrogen (H₂) inhalation, begun at the start of hyperoxic cardiopulmonary resuscitation, significantly improves brain and cardiac function in a rat model of cardiac arrest. Here, we examine the effectiveness of this therapeutic approach when ₂ inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM).

Methods and Results-Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, postcardiac arrest rats were randomized into 4 groups: mechanically ventilated with 26% O₂ and normothermia (control); mechanically ventilated with 26% O₂, 1.3% H₂, and normothermia (H₂); mechanically ventilated with 26% O₂ and TTM (TTM); and mechanically ventilated with 26% O₂, 1.3% H2, and TTM (TTM+H₂). Animal survival rate at 7 days after ROSC was 38.4% in the control group, 71.4% in the H₂ and TTM groups, and 85.7% in the TTM+H₂ group. Combined therapy of TTM and H₂ inhalation was superior to TTM alone in terms of neurological deficit scores at 24, 48, and 72 hours after ROSC, and motor activity at 7 days after ROSC. Neuronal degeneration and microglial activation in a vulnerable brain region was suppressed by both TTM alone and H2 inhalation alone, with the combined therapy of TTM and H₂ inhalation being most effective.

Conclusions-H₂ inhalation was beneficial when begun after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H₂ inhalation was more effective than TTM alone.