Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock

Hendrik Bracht, Angelika Scheuerle, Michael Gröger, Balázs Hauser, José Matallo, Oscar McCook, Andrea Seifritz, Ulrich Wachter, Josef A. Vogt, Pierre Asfar, Martin Matejovic, Peter Möller, Enrico Calzia, Csaba Szabo, Wolfgang Stahl, Kerstin Hoppe, Bettina Stahl, Lorenz Lampl, Michael Georgieff, Florian WagnerPeter Radermacher, Florian Simon

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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. Design: Prospective, controlled, randomized study. Setting: University animal research laboratory. Subjects: Forty-five domestic pigs of either gender. Interventions: 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. Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)2157-2167
Number of pages11
JournalCritical Care Medicine
Volume40
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Hemorrhagic Shock
Sulfides
Swine
Hemorrhage
Hydrogen Sulfide
Kidney
Resuscitation
Liver
Creatinine
Arterial Pressure
Staining and Labeling
Sus scrofa
Troponin I
DNA Nucleotidylexotransferase
Hematoxylin
Eosine Yellowish-(YS)
Nitrites
Portal Vein
Transaminases
Blood Volume

Keywords

  • Apoptosis
  • heart function
  • heme oxygenase-1
  • hydrogen sulfide
  • hypothermia
  • inducible nitric oxide synthase
  • inflammation
  • kidney function
  • liver function
  • nuclear transcription factor κB
  • oxidative stress
  • suspended animation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Bracht, H., Scheuerle, A., Gröger, M., Hauser, B., Matallo, J., McCook, O., ... Simon, F. (2012). Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock. Critical Care Medicine, 40(7), 2157-2167. https://doi.org/10.1097/CCM.0b013e31824e6b30

Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock. / Bracht, Hendrik; Scheuerle, Angelika; Gröger, Michael; Hauser, Balázs; Matallo, José; McCook, Oscar; Seifritz, Andrea; Wachter, Ulrich; Vogt, Josef A.; Asfar, Pierre; Matejovic, Martin; Möller, Peter; Calzia, Enrico; Szabo, Csaba; Stahl, Wolfgang; Hoppe, Kerstin; Stahl, Bettina; Lampl, Lorenz; Georgieff, Michael; Wagner, Florian; Radermacher, Peter; Simon, Florian.

In: Critical Care Medicine, Vol. 40, No. 7, 07.2012, p. 2157-2167.

Research output: Contribution to journalArticle

Bracht, H, Scheuerle, A, Gröger, M, Hauser, B, Matallo, J, McCook, O, Seifritz, A, Wachter, U, Vogt, JA, Asfar, P, Matejovic, M, Möller, P, Calzia, E, Szabo, C, Stahl, W, Hoppe, K, Stahl, B, Lampl, L, Georgieff, M, Wagner, F, Radermacher, P & Simon, F 2012, 'Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock', Critical Care Medicine, vol. 40, no. 7, pp. 2157-2167. https://doi.org/10.1097/CCM.0b013e31824e6b30
Bracht H, Scheuerle A, Gröger M, Hauser B, Matallo J, McCook O et al. Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock. Critical Care Medicine. 2012 Jul;40(7):2157-2167. https://doi.org/10.1097/CCM.0b013e31824e6b30
Bracht, Hendrik ; Scheuerle, Angelika ; Gröger, Michael ; Hauser, Balázs ; Matallo, José ; McCook, Oscar ; Seifritz, Andrea ; Wachter, Ulrich ; Vogt, Josef A. ; Asfar, Pierre ; Matejovic, Martin ; Möller, Peter ; Calzia, Enrico ; Szabo, Csaba ; Stahl, Wolfgang ; Hoppe, Kerstin ; Stahl, Bettina ; Lampl, Lorenz ; Georgieff, Michael ; Wagner, Florian ; Radermacher, Peter ; Simon, Florian. / Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock. In: Critical Care Medicine. 2012 ; Vol. 40, No. 7. pp. 2157-2167.
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AU - Bracht, Hendrik

AU - Scheuerle, Angelika

AU - Gröger, Michael

AU - Hauser, Balázs

AU - Matallo, José

AU - McCook, Oscar

AU - Seifritz, Andrea

AU - Wachter, Ulrich

AU - Vogt, Josef A.

AU - Asfar, Pierre

AU - Matejovic, Martin

AU - Möller, Peter

AU - Calzia, Enrico

AU - Szabo, Csaba

AU - Stahl, Wolfgang

AU - Hoppe, Kerstin

AU - Stahl, Bettina

AU - Lampl, Lorenz

AU - Georgieff, Michael

AU - Wagner, Florian

AU - Radermacher, Peter

AU - Simon, Florian

PY - 2012/7

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N2 - 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. Design: Prospective, controlled, randomized study. Setting: University animal research laboratory. Subjects: Forty-five domestic pigs of either gender. Interventions: 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. Measurements and Main 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.

AB - 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. Design: Prospective, controlled, randomized study. Setting: University animal research laboratory. Subjects: Forty-five domestic pigs of either gender. Interventions: 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. Measurements and Main 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.

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KW - heart function

KW - heme oxygenase-1

KW - hydrogen sulfide

KW - hypothermia

KW - inducible nitric oxide synthase

KW - inflammation

KW - kidney function

KW - liver function

KW - nuclear transcription factor κB

KW - oxidative stress

KW - suspended animation

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