Hydrogen Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest, Independent of Targeted Temperature Management
Background—We have previously shown that hydrogen (H2) inhalation, commenced at the start of hyperoxic cardiopulmonary resuscitation (CPR), significantly improves brain and cardiac function in a rat model of cardiac arrest (CA). Here, we examine the effectiveness of this therapeutic approach when H2 inhalation is commenced upon 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 min VF CA followed by CPR. Five min after achieving ROSC, post-CA rats were randomized into four groups: mechanically ventilated (MV) with 26% O2 and normothermia (control); MV with 26% O2, 1.3% H2 and normothermia (H2); MV with 26% O2 and TTM (TTM); MV with 26% O2, 1.3% H2 and TTM (TTM + H2). Animal survival rate at 7 d 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 h post-ROSC, and motor activity at 7 d post-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 commenced after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H2 inhalation was more effective than TTM alone.
- hydrogen gas
- cardiopulmonary resuscitation
- heart arrest
- ischemia/reperfusion injury/neuroprotection
- Received June 20, 2014.
- Revision received September 20, 2014.
- Accepted September 26, 2014.