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Effect of intravenous H2S on porcine aortic occlusion-induced systemic inflammation and kidney ischemia/reperfusion injury
Critical Care volume 14, Article number: P507 (2010)
Both inhaled hydrogen sulfide (H2S)  and intravenous H2S donors protected against kidney ischemia/reperfusion (I/R) injury [2–4], but all these data originate from unresuscitated rodent models. Therefore, we investigated the effect of the H2S donor Na2S in a clinically relevant porcine model of aortic occlusion-induced renal I/R injury.
Anesthetised and ventilated pigs received Na2S (n = 9) or vehicle (n = 10) for 2 hours before and 8 hours after 90 minutes of intra-aortic balloon occlusion-induced kidney ischemia. During reperfusion noradrenaline was titrated to keep blood pressure at baseline levels. Before Na2S, prior to aortic occlusion and at 1, 2, 4 and 8 hours of reperfusion, we measured renal blood flow and function (creatinine clearance and blood levels, fractional Na+ excretion), blood cytokines (TNFα, IL-6, IL-1β) and nitrates, renal tissue DNA damage (comet assay), HO-1 and caspase-3 expression (western blotting), and NF-κB activation (EMSA). Histological damage (glomerular tubularisation ) was assessed immediately post mortem.
Na2S pretreatment was associated with a progressive fall in core temperature and significantly lower noradrenaline infusion rates needed to achieve the hemodynamic targets. While renal blood flow and fractional Na+ excretion were comparable, Na2S attenuated the fall in creatinine clearance and the rise in creatinine blood levels, respectively, which coincided with significantly lower IL-6, IL-1β, and nitrate blood levels. Kidney glomerular and tissue DNA damage were markedly attenuated, whereas NF-κB activation was significantly higher in the Na2S-treated animals.
In a clinically relevant porcine model mimicking aortic cross-clamping-induced kidney I/R injury, Na2S attenuated tissue injury and organ dysfunction as a result of reduced systemic inflammation and oxidative stress. The higher NF-κB activation and the unchanged fractional Na+ excretion were most probably due to the drop in temperature  and the direct effect of H2S on tubular Na+ absorption , respectively.
J Am Soc Nephrol. 2009, 20: 1901-1905. 10.1681/ASN.2008121269
Lab Invest. 2008, 88: 1038-1048. 10.1038/labinvest.2008.73
Eur J Pharmacol. 2009, 606: 205-209. 10.1016/j.ejphar.2009.01.041
Am J Physiol Renal Physiol. 2009, 297: F27-F25. 10.1152/ajprenal.00096.2009
Nephron Exp Nephrol. 2007, 105: e33-e40. 10.1159/000097017
Am J Physiol Gastrointest Liver Physiol. 2007, 292: G201-G207. 10.1152/ajpgi.00186.2006
J Pharmacol Exp Ther. 2009, 329: 1056-1062. 10.1124/jpet.108.149963
Supported by the DFG (SCHE 899/2-3) and Ikaria Inc. (Seattle, WA, USA).
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Wagner, F., Simon, F., Scheuerle, A. et al. Effect of intravenous H2S on porcine aortic occlusion-induced systemic inflammation and kidney ischemia/reperfusion injury. Crit Care 14, P507 (2010). https://doi.org/10.1186/cc8739
- Comet Assay
- Hydrogen Sulfide
- Renal Blood Flow
- Aortic Occlusion