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 (H-2) 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 H-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, post-cardiac arrest rats were randomized into 4 groups: mechanically ventilated with 26% O-2 and normothermia (control); mechanically ventilated with 26% O-2, 1.3% H-2, and normothermia (H-2); mechanically ventilated with 26% O-2 and TTM (TTM); and mechanically ventilated with 26% O-2, 1.3% H-2, and TTM (TTM+H-2). Animal survival rate at 7 days after ROSC was 38.4% in the control group, 71.4% in the H-2 and TTM groups, and 85.7% in the TTM+H-2 group. Combined therapy of TTM and H-2 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 H-2 inhalation alone, with the combined therapy of TTM and H-2 inhalation being most effective. Conclusions-H-2 inhalation was beneficial when begun after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H-2 inhalation was more effective than TTM alone.