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. (Circulation. 2014;130:2173-2180.)

Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats

“…Transient global cerebral ischemia could lead to delayed neuronal loss and activation of microglia and astrocytes in selectively vulnerable areas, such as the hippocampal CA1 22. As indicated in the histological analysis of the hippocampal CA1 region in Figure 4, TTM or GBC alone significantly recovered numbers of neurons by NeuN staining compared to NT treatment, with their combination resulted in a further recovery (Figure 4A and 4E).…”

“…In humans, TTM is suggested to be maintained for at least 24 hours after achieving target temperature 2. However, shorter duration of TTM was commonly utilized in animal studies, because of the high metabolic rate of rodents and shorter time in reaching target temperature 22, 29, 30. Ye et al 31.…”

Hydrogen Gas Attenuates Myocardial Ischemia Reperfusion Injury Independent of Postconditioning in Rats by Attenuating Endoplasmic Reticulum Stress-Induced Autophagy

“…In 2007, Ohsawa et al [24], found that hydrogen act as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, especially hydroxyl radical (OH·), the most cytotoxic reactive oxygen species (ROS). In recent years, hydrogen gas (H 2 ) or hydrogen-rich saline are widely accepted to exert protective effects in many diseases including myocardial ischemia-reperfusion injury, neuropathic Pain, brain injury via regulating oxidative stress, inflammatory response and apoptosis [25-28]. Except in rat model, the protective effects of inhaling H 2 in myocardial ischemia-reperfusion injury also have been reported in dog model and patients experiencing ST-elevated myocardial infarction [29, 30].…”

Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome – First-in-Human Pilot Study –

“…Recent proof-of-concept studies in animal models have demonstrated the therapeutic effect of molecular hydrogen (H2) on neurological outcomes after cardiac arrest (CA). 3, 4 In this study, we sought to evaluate the feasibility and safety of H2 inhalation (HI) for PCAS.…”