title: High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep.
abstract: BACKGROUND
  Severe H2S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication.
  
  
  OBJECTIVE
  To determine the time course and the nature of H2S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure.
  
  
  METHODS
  NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H2S in the blood, which was previously found to lead to cardiac arrest within minutes following the cessation of H2S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion.
  
  
  RESULTS
  All animals were still alive at the cessation of H2S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H2S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H2S trapping.
  
  
  CONCLUSIONS
  In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H2S exposure. Very high dose of hydroxocobalamin (5 g), injected very early after the cessation of H2S exposure, improved cardiac contractility and prevented PEA.
authors.affiliation: Division of Pulmonary and Critical Medicine, Pennsylvania State University College of Medicine , Hershey, PA , USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Haouzi
authors.forename: Bruno
authors.initials: B
authors.lastname: Chenuel
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000139:chemically induced / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000506:poisoning*; D006879:Hydroxocobalamin / Q000494:pharmacology*; D007275:Injections, Intravenous; D012756:Sheep
chemical_list: D006879:Hydroxocobalamin; D006862:Hydrogen Sulfide
keywords: Cardiac contractility; H2S; antidotes