Abstract 177: Hydrogen Sulfide Prevents the Disruption of Blood Brain Barrier After Cardiac Arrest and CPR in Mice
Introduction: Global cerebral ischemia and reperfusion after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) disrupts blood-brain barrier (BBB) and induces brain edema. Recently, we reported that hydrogen sulfide donor sodium sulfide (Na2S) improves neurological function and survival rate after CA/CPR. The aim of this study was to examine the mechanisms responsible for the neuroprotective effect of hydrogen sulfide in a mouse model of CA/CPR.
Methods: Male mice were subjected to potassium-induced CA for 7.5 min with normothermia whereupon CPR was performed with chest compression and mechanical ventilation. After CA, mice received administration of Na2S (Na2S, 0.55 mg/kg i.v.; n=12) or vehicle (vehicle, n=12) 1 min before CPR. Survival was observed for 10 days after CA/CPR. Neurological function was assessed 4 days after CA/CPR by neurological function scoring system. Diffusion-Weighted Imaging (DWI) of the brain was performed 1 day after CA/CPR. For detection of BBB leakage, gadolinium (Gd)-DTPA was administrated intravenously and detected by Gd-enhanced T1 imaging 2 days after CA/CPR.
Results: Cardiac arrest and CPR induced abnormal water diffusion and ion homeostasis in the hippocampus and cerebellum 24h after CA, as demonstrated by the presence of hyperintense DWI (hDWI) in vehicle-treated mice. Administration of Na2S prevented the development of the brain lesions with hDWI and neurological dysfunction and markedly improved long-term survival after CA (P<0.05). The calculated cortical and striatal volume of hDWI were markedly decreased by administration of Na2S compared to vehicle (p<0.01). Disruption of BBB indicated by Gd-leakage was detected in vehicle but not in Na2S-treated mice in brain areas overlapping with areas with hDWI.
Conclusions: These results suggest that administration of a hydrogen sulfide donor at the time of CPR prevents the disruption of BBB and improves neurological outcome and long-term survival after CA/CPR.
- © 2010 by American Heart Association, Inc.