Hydrogen Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest Independently of Targeted Temperature Management

Abstract

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.