title: Hypothermia and neuroprotection by sulfide after cardiac arrest and cardiopulmonary resuscitation.
abstract: 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 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. An investigator blinded bolus of either Na(2)S (0.5 mg/kg body weight) or placebo 1 min before the beginning of CPR, followed by a continuous infusion of Na(2)S (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 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.
  
  
  CONCLUSIONS
  In our rat model of cardiac arrest, sulfide therapy was associated with only a short term beneficial effect on neurological outcome.
authors.affiliation: Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. juergen.knapp@urz.uni-heidelberg.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Knapp
authors.forename: Anna
authors.initials: A
authors.lastname: Heinzmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneider
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Padosch
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Böttiger
authors.forename: Peter
authors.initials: P
authors.lastname: Teschendorf
authors.forename: Erik
authors.initials: E
authors.lastname: Popp
mesh_terms: D000818:Animals; D017209:Apoptosis; D001831:Body Temperature; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D016887:Cardiopulmonary Resuscitation; D006323:Heart Arrest / Q000150:complications* / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000379:methods*; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D013440:Sulfides; C033479:sodium sulfide