Abstract 9: Hydrogen Sulfide Improves Outcome after Cardiac Arrest and Cardiopulmonary Resuscitation in Mouse
Introduction: Administration of hydrogen sulfide (H2S) donor has been shown to attenuate ischemia-reperfusion injury. The aim of this study was to evaluate the effect of an H2S donor sodium sulfide (Na2S, IK-1001, Ikaria) on the outcome after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in mouse.
Methods: Male wild-type C57BL/6 mice were subjected to potassium-induced CA for 8 min with normothermia (37±0.5°C) whereupon CPR was attempted with chest compression and mechanical ventilation. After CA, mice received administration of Na2S (0.55 mg/kg i.v.) 1 min before CPR (pre-Na2S, n=8) or 10 min after CPR (post-Na2S, n=5) or vehicle of Na2S (vehicle, n=6). Survival rate and neurological and cardiac function were examined at 24h after CPR and compared to sham-operated mice (n=6). Calcium-induced mitochondrial permeability transition (MPT) was examined in mitochondria isolated from LV 15 min after CPR. Phosphorylation of Akt and caspase-3 activation was assessed by immunoblot in protein extracts from brain cortex and LV 15 min after CPR.
Results: There was no difference in the rate of return of spontaneous circulation (ROSC), CPR time to ROSC, and HR and MAP at ROSC between groups. Survival rate at 24h after CPR was markedly higher in the pre-Na2S (14/15) than in the post-Na2S (5/11) or vehicle group (8/21) (P<0.01 for both vs pre- Na2S). Pre-Na2S, but not post-Na2S, prevented CA-induced LV dysfunction assessed by dP/dtmax, preload-recruitable stroke work (PRSW), and end-systolic elastance (Ees) (Table⇓). CA-induced neurological dysfunction was more marked in post-Na2S and vehicle than in pre-Na2S. Pre-Na2S increased Akt phosphorylation in LV and brain cortex and prevented CA-induced caspase-3 activation in brain cortex and MPT in LV mitochondria.
Conclusion: These results suggest that administration of an H2S donor at the time of CPR improves outcome after CA at least in part via activation of Akt-dependent cell survival signaling and prevention of MPT.