Compared effects of inhibition and exogenous administration of Hydrogen Sulfide in ischaemia-reperfusion injury.

Abstract : Purpose. Haemorrhagic shock is associated with an inflammatory response consecutive to ischaemia-reperfusion (I/R) that leads to cardiovascular failure and organ injury. The role of hydrogen sulfide (H2S) remains uncertain. Vascular effects of H2S are mainly mediated through K+ATP -channel activation. Herein, we compared the effects of PAG, an inhibitor of H2S production, as well as sodium hydrosulfide (NaHS), a H2S donor, on hemodynamics, vascular reactivity and cellular pathways in a rat model of I/R. METHODS: Mechanically-ventilated and instrumented rats were bled during 60 minutes in order to maintain mean arterial pressure at 40 +/- 2 mm Hg. Ten minutes prior to retransfusion, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl) or PAG (50 mg/kg). PNU, a pore-forming receptor inhibitor of K+ATP channels, was used to assess the role of K+ATP channels. RESULTS: Shock and I/R induced a decrease in MAP, lactic acidosis and ex-vivo vascular hyporeactivity, which were attenuated by NaHS and PNU but not by PAG. NaHS also prevented aortic iNOS expression and NO production while increasing Akt and eNOS phosphorylation. NaHS reduced JNK activity and p-P38/P38 activation suggesting a decrease in endothelial cell activation without variation in ERK phosphorylation. PNU + NaHS increased MAP when compared to NaHS or PNU alone suggesting a dual effect of NaHS on vascular reactivity. CONCLUSIONS: NaHS protects against the effects of haemorrhage-induced I/R by acting primarily through a decrease in both proinflammatory cytokines and iNOS expression and an upregulation of the Akt/eNOS pathway. el of I/R. We also compared the hemodynamic effects of NaHS administered before and 10 minutes after reperfusion. METHODS: Mechanically-ventilated and instrumented rats were bled during 60 minutes in order to maintain mean arterial pressure at 40 +/- 2 mm Hg. Ten minutes prior to retransfusion, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl) or PAG (50 mg/kg). PNU, a pore-forming receptor inhibitor of K+ATP channels, was used to assess the role of K+ATP channels. RESULTS: Shock and I/R induced a decrease in MAP, lactic acidosis and ex-vivo vascular hyporeactivity, which were attenuated by NaHS administered before reperfusion and PNU but not by PAG and NaHS administered 10 minutes after reperfusion. NaHS also prevented aortic iNOS expression and NO production while increasing Akt and eNOS phosphorylation. NaHS reduced JNK activity and p-P38/P38 activation suggesting a decrease in endothelial cell activation without variation in ERK phosphorylation. PNU + NaHS increased MAP when compared to NaHS or PNU alone suggesting a dual effect of NaHS on vascular reactivity. CONCLUSIONS: NaHS when given before reperfusion protects against the effects of haemorrhage-induced I/R by acting primarily through a decrease in both proinflammatory cytokines and iNOS expression and an upregulation of the Akt/eNOS pathway.
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Critical Care, BioMed Central, 2013, 17 (4), pp.R129. 〈10.1186/cc12808〉
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Khodor Issa, Antoine Kimmoun, Solène Collin, Frederique Ganster, Sophie Fremont-Orlowski, et al.. Compared effects of inhibition and exogenous administration of Hydrogen Sulfide in ischaemia-reperfusion injury.. Critical Care, BioMed Central, 2013, 17 (4), pp.R129. 〈10.1186/cc12808〉. 〈inserm-00852236〉

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