Endogenous H₂S in hemorrhagic shock: innocent bystander or central player?

The role of the gaseous mediator hydrogen sulfide (H₂S) in hemorrhagic shock is still a matter of debate. This debate is emphasized by the fact that available literature data on blood and tissue H₂S concentrations vary by three orders of magnitude, both under physiological conditions as well as during stress states. Therefore, in a rat model of unresuscitated, lethal hemorrhagic shock, Van de Louw and Haouzi tested the two hypotheses of whether blood and tissue H₂S levels would increase due to the shock-related tissue hypoxia, and whether vitamin B12 would attenuate organ injury and improve survival as a result of enhanced H₂S oxidation. Hemorrhage did not affect the blood and tissue H₂S content, and, despite the increased capacity to oxidize H₂S, vitamin B12 did not affect any parameter of shock severity. The authors concluded that H₂S concentrations cannot be used as a marker of shock, most probably as a result of tissue's capacity to oxidize H₂S even under conditions of severe oxygen debt. This research paper elegantly re-adjusts the currently available data on blood and tissue H₂S levels, and thereby adds an important piece to the puzzle of whether H₂S release should be enhanced or lowered during stress conditions associated with tissue hypoxia.