Hypothermia and neuroprotection by sulfide after cardiac arrest and cardiopulmonary resuscitation

BackgroundPoor 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 (Na2S), a liquid hydrogen sulfide donor on core body temperature and neurological outcome after cardiac arrest in rats.MethodsFifty 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 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. An investigator blinded bolus of either Na2S (0.5 mg/kg body weight) or placebo 1 min before the beginning of CPR, followed by a continuous infusion of Na2S (1 mg/kg body weight/h) or placebo for 6 h, 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 Na2S.ResultsTemperature 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.ConclusionIn our rat model of cardiac arrest, sulfide therapy was associated with only a short term beneficial effect on neurological outcome.