H2 Gas Improves Functional Outcome After Cardiac Arrest to an Extent Comparable to Therapeutic Hypothermia in a Rat Model

Background-All clinical and biological manifestations related to postcardiac arrest (CA) syndrome are attributed to ischemia-reperfusion injury in various organs including brain and heart. Molecular hydrogen (H-2) has potential as a novel antioxidant. This study tested the hypothesis that inhalation of H-2 gas starting at the beginning of cardiopulmonary resuscitation (CPR) could improve the outcome of CA. Methods and Results-Ventricular fibrillation was induced by transcutaneous electrical epicardial stimulation in rats. After 5 minutes of the subsequent CA, rats were randomly assigned to 1 of 4 experimental groups at the beginning of CPR: mechanical ventilation (MV) with 2% N-2 and 98% O-2 under normothermia (37 degrees C), the control group; MV with 2% H-2 and 98% O-2 under normothermia; MV with 2% N-2 and 98% O-2 under therapeutic hypothermia (TH), 33 degrees C; and MV with 2% H-2 and 98% O-2 under TH. Mixed gas inhalation and TH continued until 2 hours after the return of spontaneous circulation (ROSC). H-2 gas inhalation yielded better improvement in survival and neurological deficit score (NDS) after ROSC to an extent comparable to TH. H-2 gas inhalation, but not TH, prevented a rise in left ventricular end-diastolic pressure and increase in serum IL-6 level after ROSC. The salutary impact of H-2 gas was at least partially attributed to the radical-scavenging effects of H-2 gas, because both 8-OHdG- and 4-HNE-positive cardiomyocytes were markedly suppressed by H-2 gas inhalation after ROSC. Conclusions-Inhalation of H-2 gas is a favorable strategy to mitigate mortality and functional outcome of post-CA syndrome in a rat model, either alone or in combination with TH.