Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock*.
OBJECTIVE
Controversial data are available on the effects of hydrogen sulfide during hemorrhage. Because the clinical significance of hydrogen sulfide administration in rodents may not be applicable to larger species, we tested the hypothesis whether intravenous Na2S (sulfide) would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation.


METHODS
Prospective, controlled, randomized study.


METHODS
University animal research laboratory.


METHODS
Forty-five domestic pigs of either gender.


METHODS
Anesthetized and instrumented animals underwent 4 hrs of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Sulfide infusion was started 2 hrs before hemorrhage, simultaneously with blood removal or at the beginning of retransfusion of shed blood, and continued for 12 hrs. Resuscitation comprised hydroxyethyl starch and norepinenephrine infusion titrated to maintain mean arterial pressure at preshock values.


RESULTS
Before, immediately at the end of and 12 and 22 hrs after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, nitric oxide and cytokine production (nitrate+nitrite, interleukin-6, tumor necrosis factor-α levels). Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and DNA damage (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining). The progressive kidney (creatinine levels, creatinine clearance), liver (transaminase activities, bilirubin levels), and cardiocirculatory (norepipnehrine requirements, troponin I levels) dysfunction was attenuated in the simultaneous treatment group only, which coincided with reduced lung, liver, and kidney histological damage. Sulfide reduced mortality, however, irrespective of the timing of its administration.


CONCLUSIONS
While the sulfide-induced protection against organ injury was only present when initiated simultaneously with blood removal, it was largely unrelated to hypothermia. The absence of sulfide-mediated protection in the pretreatment protocol may be due to the accumulation of sulfide during low flow states. In conclusion, sulfide treatment can be effective in hemorrhagic shock, but its effectiveness is restricted to a narrow timing and dosing window.
Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Hendrik
H
Bracht
Angelika
A
Scheuerle
Michael
M
Gröger
Balázs
B
Hauser
José
J
Matallo
Oscar
O
McCook
Andrea
A
Seifritz
Ulrich
U
Wachter
Josef A
JA
Vogt
Pierre
P
Asfar
Martin
M
Matejovic
Peter
P
Möller
Enrico
E
Calzia
Csaba
C
Szabó
Wolfgang
W
Stahl
Kerstin
K
Hoppe
Bettina
B
Stahl
Lorenz
L
Lampl
Michael
M
Georgieff
Florian
F
Wagner
Peter
P
Radermacher
Florian
F
Simon
D001663:Bilirubin / Q000378:metabolism; D003404:Creatinine / Q000032:analysis; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010952:Plasma Substitutes / Q000494:pharmacology; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D000637:Transaminases / Q000378:metabolism; D019210:Troponin I / Q000097:blood
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D019210:Troponin I; D003404:Creatinine; D000637:Transaminases; D001663:Bilirubin; D009638:Norepinephrine; D006862:Hydrogen Sulfide