Influence of oxygen concentration on the neuroprotective effect of hydrogen inhalation in a rat model of cardiac arrest

Background: Post-cardiac arrest (CA) brain injury is the main cause of death in patients resuscitated from CA. Previous studies demonstrated that hydrogen inhalation mitigates post-CA brain injury. However, factors affecting the efficacy of hydrogen remain unknown. In the present study, we investigated the influence of oxygen concentration and targeted temperature on neuroprotective effect in a CA rat model of ventricular fibrillation (VF). Methods: Cardiopulmonary resuscitation (CPR) was initiated after 7 min of untreated VF in adult male Sprague-Dawley rats. Immediately following successful resuscitation, animals were randomized to be ventilated with 21% oxygen and 79% nitrogen (21%O2); 2% hydrogen, 21% oxygen, and 77% nitrogen (2%H2 + 21%O2); 2% hydrogen, 50% oxygen, and 48% nitrogen (2%H2 + 50%O2); or 2% hydrogen and 98% oxygen (2%H2 + 98%O2) for 3 h. For each group, the target temperature was 37.5°C for half of the animals and 35.0°C for the other half. Results: No statistical differences in baseline measurements and CPR characteristics were observed among groups. For animals with normothermia, 2%H2 + 50%O2 (123 [369] vs. 500 [393], p = 0.041) and 2%H2 + 98%O2 (73 [66] vs. 500 [393], p = 0.002) groups had significantly lower neurological deficit scores (NDSs) at 96 h and significantly higher survival (75.0 vs. 37.5%, p = 0.033 and 81.3 vs. 37.5%, p = 0.012) than 21%O2 group. For animals with hypothermia, no statistical difference in NDS among groups but 2%H2 + 98%O2 has significantly higher survival than the 21%O2 group (93.8 vs. 56.3%, p = 0.014). Conclusion: In this CA rat model, inhaling 2% hydrogen combined with a high concentration of oxygen improved 96-h survival, either under normothermia or under hypothermia.

Hydrogen Inhalation is Superior to Mild Hypothermia for Improving Neurological Outcome and Survival in a Cardiac Arrest Model of Spontaneously Hypertensive Rat

Background: Postcardiac arrest syndrome is the consequence of whole-body ischemia-reperfusion events that lead to multiple organ failure and eventually to death. Recent animal studies demonstrated that inhalation of hydrogen greatly mitigates postresuscitation myocardial dysfunction and brain injury. However, the influence of underlying heart disease on the efficacy of hydrogen is still unknown. In the present study, we investigated the effects of hydrogen inhalation on neurological outcome and survival in a cardiac arrest model of spontaneously hypertensive rat (SHR). Methods: Cardiopulmonary resuscitation was initiated after 4 min of untreated ventricular fibrillation in 40 SHRs. Immediately after successful resuscitation, animals were randomized to be ventilated with 98% oxygen and 2% nitrogen under normothermia (Ctrl), 2% nitrogen under hypothermia (TH), 2% hydrogen under normothermia (H2), or 2% hydrogen under hypothermia (H2+TH) for 2 h. Hypothermia was maintained at 33°C for 2 h. Animals were observed up to 96 h for assessment of survival and neurologic recovery. Results: No statistical differences in baseline measurements were observed among groups and all the animals were successfully resuscitated. Compared with Ctrl, serum cardiac troponin T measured at 5 h and myocardial damage score measured at 96 h after resuscitation were markedly reduced in H2, TH, and H2+TH groups. Compared with Ctrl and TH, astroglial protein S100 beta measured during the earlier postresuscitation period, and neurological deficit score and neuronal damage score measured at 96 h were considerably lower in both H2 and H2+TH groups. Ninety-six hours survival rates were significantly higher in the H2 (80.0%) and H2+TH (90.0%) groups than TH (30.0%) and to Ctrl (30.0%). Conclusions: Hydrogen inhaling was superior to mild hypothermia for improving neurological outcome and survival in cardiac arrest and resuscitation model of systemic hypertension rats.

Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model

Background: Electroencephalography (EEG) is commonly used to assess the neurological prognosis of comatose patients after cardiac arrest (CA). However, the early prognostic accuracy of EEG may be affected by postresuscitation interventions. Recent animal studies found that hydrogen inhalation after CA greatly improved neurological outcomes by selectively neutralizing highly reactive oxidants, but the effect of hydrogen inhalation on EEG recovery and its prognostication value are still unclear. The present study investigated the effects of hydrogen inhalation on early postresuscitation EEG characteristics in an asphyxial CA rat model. Methods: Cardiopulmonary resuscitation was initiated after 5 min of untreated CA in 40 adult female Sprague-Dawley rats. Animals were randomized for ventilation with 98% oxygen plus 2% hydrogen (H2) or 98% oxygen plus 2% nitrogen (Ctrl) under normothermia for 1 h. EEG characteristics were continuously recorded for 4 h, and the relationships between quantitative EEG characteristics and 96 h neurological outcomes were investigated. Results: No differences in baseline and resuscitation data were observed between groups, but the survival rate was significantly higher in the H2 group than in the Ctrl group (90% vs. 40%, P < 0.01). Compared to the Ctrl group, the H2 group showed a shorter burst onset time (21.85 [20.00-23.38] vs. 25.70 [22.48-30.05], P < 0.01) and time to normal trace (169.83 [161.63-208.55] vs. 208.39 [186.29-248.80], P < 0.01). Additionally, the burst suppression ratio (0.66 ± 0.09 vs. 0.52 ± 0.17, P < 0.01) and weighted-permutation entropy (0.47 ± 0.16 vs. 0.34 ± 0.13, P < 0.01) were markedly higher in the H2 group. The areas under the receiver operating characteristic curves for the 4 EEG characteristics in predicting survival were 0.82, 0.84, 0.88, and 0.83, respectively. Conclusions: In this asphyxial CA rat model, the improved postresuscitation EEG characteristics for animals treated with hydrogen are correlated with the better 96 h neurological outcome and predicted survival.