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

Introduction

Both inhaled hydrogen sulfide (H₂S) [1] 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.

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.