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  • Open Access

Effect of intravenous H2S on porcine aortic occlusion-induced systemic inflammation and kidney ischemia/reperfusion injury

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Critical Care201014 (Suppl 1) :P507

https://doi.org/10.1186/cc8739

  • Published:

Keywords

  • Comet Assay
  • Hydrogen Sulfide
  • Renal Blood Flow
  • Na2S
  • Aortic Occlusion

Introduction

Both inhaled hydrogen sulfide (H2S) [1] and intravenous H2S donors protected against kidney ischemia/reperfusion (I/R) injury [24], 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.

Methods

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 [5]) was assessed immediately post mortem.

Results

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.

Conclusions

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 [6] and the direct effect of H2S on tubular Na+ absorption [7], respectively.

Declarations

Acknowledgements

Supported by the DFG (SCHE 899/2-3) and Ikaria Inc. (Seattle, WA, USA).

Authors’ Affiliations

(1)
Ulm University, Ulm, Germany
(2)
University of Texas Medical Branch, Galveston, TX, USA

References

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  6. Am J Physiol Gastrointest Liver Physiol. 2007, 292: G201-G207. 10.1152/ajpgi.00186.2006Google Scholar
  7. J Pharmacol Exp Ther. 2009, 329: 1056-1062. 10.1124/jpet.108.149963Google Scholar

Copyright

© BioMed Central Ltd. 2010

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