Surviving blood loss using hydrogen sulfide.
BACKGROUND
Reduced metabolic activity improves outcome in many clinical and experimental models of injury and diseases that result in insufficient blood supply. Recently, we demonstrated that inhaled hydrogen sulfide gas can be used to reversibly reduce metabolic activity in mice. We hypothesize that hydrogen sulfide will confer benefit in injuries and diseases related to insufficient blood supply.


METHODS
Sprague-Dawley rats were subjected to controlled hemorrhage to remove 60% of total blood. Hydrogen sulfide was administered to rats either via airway as gas, or intravenous infusion as liquid. Outcome was assayed by survival.


RESULTS
Using inhaled hydrogen sulfide gas, 75% of treated and 23% of untreated rats survived longer than 24 hours. Using intravenous administered sulfide, 67% of treated and 14% of untreated rats survived longer than 24 hours. Using log-rank analysis, p < 0.001. Surviving rats showed no functional or behavioral abnormalities. Blood chemistry analysis at the end of hemorrhage showed minor but significant differences between treated and control animals. Respirometry results show that hydrogen sulfide stabilized metabolic output during and after hemorrhage.


CONCLUSIONS
These data indicate that sulfide can protect rats from lethal hemorrhage. Future studies are needed to analyze the mechanism of benefit as well as whether sulfide is beneficial in other models of human injury and disease.
Morrison
Michael L
ML
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Blackwood
Jennifer E
JE
Lockett
Summer L
SL
Iwata
Akiko
A
Winn
Robert K
RK
Roth
Mark B
MB
D000280:Administration, Inhalation; D000393:Air Pollutants; D000818:Animals; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000188:drug therapy*; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000627:therapeutic use*; D020896:Hypovolemia / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000393:Air Pollutants; D006862:Hydrogen Sulfide