Effects of intravenous sulfide during porcine aortic occlusion-induced kidney ischemia/reperfusion injury.
In rodents, inhaled H2S and injection of H2S donors protected against kidney ischemia/reperfusion (I/R) injury. During porcine aortic occlusion, the H2S donor Na2S (sulfide) reduced energy expenditure and decreased the noradrenaline requirements needed to maintain hemodynamic targets during early reperfusion. Therefore, we tested the hypothesis whether sulfide pretreatment may also ameliorate organ function in porcine aortic occlusion-induced kidney I/R injury. Anesthetized, ventilated, and instrumented pigs randomly received either sulfide or vehicle and underwent 90 min of kidney ischemia using intraaortic balloon-occlusion, and 8 h of reperfusion. During reperfusion, noradrenaline was titrated to maintain blood pressure at baseline levels. Sulfide attenuated the fall in creatinine clearance and the rise in creatinine blood levels, whereas renal blood flow and fractional Na+ excretion were comparable. Sulfide also lowered the blood IL-6, IL-1β, and nitrite + nitrate concentrations, which coincided with reduced kidney oxidative DNA base damage and iNOS expression, and attenuated glomerular histological injury as assessed by the incidence of glomerular tubularization. While expression of heme oxygenase 1 and cleaved caspase 3 did not differ, sulfide reduced the expression Bcl-xL and increased the activation of nuclear transcription factor κB. During porcine aortic occlusion-induced kidney I/R injury, sulfide pretreatment attenuated tissue injury and organ dysfunction as a result of reduced inflammation and oxidative and nitrosative stress. The higher nuclear transcription factor κB activation was probably due to the drop in temperature.
Simon
Florian
F
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für Anästhesiologie, Universitätsklinikum, Ulm, Germany.
Scheuerle
Angelika
A
Gröger
Michael
M
Stahl
Bettina
B
Wachter
Ulrich
U
Vogt
Josef
J
Speit
Günter
G
Hauser
Balázs
B
Möller
Peter
P
Calzia
Enrico
E
Szabó
Csaba
C
Schelzig
Hubert
H
Georgieff
Michael
M
Radermacher
Peter
P
Wagner
Florian
F
D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D053148:Caspase 3 / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013552:Swine; D051020:bcl-X Protein / Q000378:metabolism
D000393:Air Pollutants; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D051020:bcl-X Protein; D003404:Creatinine; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D053148:Caspase 3; D006862:Hydrogen Sulfide