title: Hydrogen sulfide does not increase resuscitability in a porcine model of prolonged cardiac arrest.
abstract: Treatment options to improve resuscitability and neurological prognosis after cardiac arrest (CA) are limited. Hydrogen sulfide has demonstrated remarkable improvements in outcomes in small animal models of severe hypoxia or hemorrhage. We investigated the influence of sodium sulfide (Na2S), a liquid hydrogen sulfide donor, on resuscitability, postresuscitation hemodynamics, and neurological performance in a porcine model of prolonged CA and cardiopulmonary resuscitation. Twenty-four male pigs were instrumented with arterial and pulmonary artery catheters before 10 min of CA was induced. During resuscitation, animals were randomized to receive either high-dose (1 mg/kg; n = 8) or low-dose (0.3 mg/kg; n = 8) Na2S (IK-1001; Ikaria, Clinton, NJ) or control (saline placebo; n = 8) i.v. injection and consecutive infusion. Cardiopulmonary resuscitation was performed for 6 min before defibrillation was attempted. Hemodynamic variables were taken at baseline and 10, 30, 60, 120, and 240 min after successful resuscitation. Neurological outcome was evaluated on 4 postoperative days before brains and hearts were harvested for histopathologic analysis. No differences in hemodynamic parameters were observed at baseline. Initial resuscitability was not improved by Na2S. Animals exposed to high- and low-dose Na2S showed significantly reduced cardiac output, heart rate, and pulmonary arterial pressure compared with control animals during the early postresuscitation period. Strikingly, two of the high-dose Na2S animals died during the postresuscitation period, whereas all other animals survived. High-dose Na2S significantly decreased microglial activation in striatal areas, although this did not translate into improved neurological outcome. Although animals receiving Na2S developed higher troponin T serum levels, these differences remained insignificant. In this investigation, Na2S did not improve resuscitability but significantly compromised postresuscitation hemodynamics.
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Derwall
authors.forename: Maren
authors.initials: M
authors.lastname: Westerkamp
authors.forename: Céline
authors.initials: C
authors.lastname: Löwer
authors.forename: Jan
authors.initials: J
authors.lastname: Deike-Glindemann
authors.forename: Nora Katharina
authors.initials: NK
authors.lastname: Schnorrenberger
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
authors.forename: Kay Wilhelm
authors.initials: KW
authors.lastname: Nolte
authors.forename: Nadine
authors.initials: N
authors.lastname: Gaisa
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Katharina
authors.initials: K
authors.lastname: Siepmann
authors.forename: Martin
authors.initials: M
authors.lastname: Häusler
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Michael
authors.initials: M
authors.lastname: Fries
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D006323:Heart Arrest / Q000628:therapy*; D006339:Heart Rate / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D008297:Male; D013440:Sulfides / Q000627:therapeutic use; D034421:Sus scrofa
chemical_list: D013440:Sulfides; C033479:sodium sulfide; D006862:Hydrogen Sulfide