Hypothermia and neuroprotection by sulfide after cardiac arrest and cardiopulmonary resuscitation

Background Poor neurological outcome remains a major problem in patients suffering cardiac arrest. Recent data have demonstrated potent neuroprotective effects of the administration of sulfide donor compounds after ischaemia/reperfusion injury following cardiac arrest and resuscitation. Therefore, we sought to evaluate the impact of sodium sulfide (Na 2 S), a liquid hydrogen sulfide donor on core body temperature and neurological outcome after cardiac arrest in rats. Methods Fifty male Wistar rats were randomized into two groups (sulfide vs. placebo, n =25 per group). Cardiac arrest was induced by transoesophageal ventricular fibrillation during general anaesthesia. After 6min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. An investigator blinded bolus of either Na 2 S (0.5mg/kgbody weight) or placebo 1min before the beginning of CPR, followed by a continuous infusion of Na 2 S (1mg/kgbody weight/h) or placebo for 6h, was administered intravenously. 1 day, 3 days, and 7 days after restoration of spontaneous circulation, neurological outcome was evaluated by a tape removal test. After 7 days of reperfusion, coronal brain sections were analyzed by TUNEL- and Nissl-staining. A caspase activity assay was used to determine antiapoptotic properties of Na 2 S. Results Temperature course was similar in both groups (mean minimal temperature in the sulfide group 31.3±1.2°C vs. 30.8±1.9°C in the placebo group; p =0.29). Despite significant neuroprotection demonstrated by the tape removal test after 3 days of reperfusion in the sulfide treated group, there was no significant difference in neuronal survival at day 7. Likewise results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups after 7 days of reperfusion. Conclusion In our rat model of cardiac arrest, sulfide therapy was associated with only a short term beneficial effect on neurological outcome.