Beneficial effect of a hydrogen sulphide donor (sodium sulphide) in an ovine model of burn‐ and smoke‐induced acute lung injury

Abstract

Background and purpose:The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na2S, a H2S donor. Experimental approach: The study used a total of 16 chronically instrumented, adult female sheep. Na2S was administered 1 h post injury, as a bolus injection at a dose of 0.5 mg·kg -1 and subsequently, as a continuous infusion at a rate of 0.2 mg·kg -1 ·h -1 for 24 h. Cardiopulmonary variables (mean arterial and pulmonary arterial blood pressure, cardiac output, ventricular stroke work index, vascular resistance) and arterial and mixed venous blood gases were measured. Lung wet-to-dry ratio and myeloperoxidase content and protein oxidation and nitration were also measured. In addition, lung inducible nitric oxide synthase expression and cytochrome c were measured in lung homogenates via Western blotting and enzyme-linked immunosorbent assay (ELISA) respectively. Key results: The H2S donor decreased mortality during the 96 h experimental period, improved pulmonary gas exchange and lowered further increase in inspiratory pressure and fluid accumulation associated with burn-and smoke-induced acute lung injury. Further, the H2S donor treatment reduced the presence of protein oxidation and 3-nitrotyrosine formation following burn and smoke inhalation injury. Conclusions and implications: Parenteral administration of the H2S donor ameliorated the pulmonary pathophysiological changes associated with burn-and smoke-induced acute lung injury. Based on the effect of H2S observed in this clinically relevant model of disease, we propose that treatment with H2S or its donors may represent a potential therapeutic strategy in managing patients with acute lung injury.

Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition catalyst in burn and smoke inhalation injury

“…We previously demonstrated that 3-NT, as an indirect measure of ONOO Ϫ formation, is markedly elevated in lung tissue of sheep subjected to combined burn and smoke inhalation injury (6,24,28,36). Formation of ONOO Ϫ may influence the inflammatory response to this injury at multiple levels.…”

H2S during circulatory shock: Some unresolved questions

“…For example: lethal hypoxia [3], ischemia/reperfusion (I/R)-injury [4–30], cardiac arrest [31–36], hemorrhage and resuscitation [37–45], acute lung injury resulting from blunt chest trauma [46,47] and/or injurious mechanical ventilation [48–50], as well as systemic inflammation resulting from endotoxin injection [51–59], acute pancreatitis [60–63], polymicrobial sepsis [64–70], and/or burn injury [71–73]. While the beneficial effect of exogenous H 2 S supplementation and maintaining endogenous H 2 S production, respectively, are well-established in I/R injury, equivocal results were reported after cardiac arrest, hemorrhage and resuscitation, and, in particular, in sepsis: inhaling gaseous H 2 S [33,44,48,50,53,54,65], the injection of the sulfide-containing salts NaSH [31,39,49,51,59,63,64,66–71,120] and Na 2 S [32,34–38,41,42,44,47,48,72,73] or the slow-releasing H 2 S donor GYY4137 [55] as well as of inhibitors of H 2 S production [43,45,58–60,62,63,67–71,120] were associated with attenuation of shock-related organ dysfunction. Consequently, knowledge about vascular sulfide concentrations may assume major importance, in particular in the context of “ acute on chronic disease ”, i.e., during circulatory shock in animals with pre-existing chronic disease, which per se may markedly alter endogenous H 2 S production, e.g., atherosclerosis [74], arterial hypertension [75,76], chronic kidney disease [77,78], and/or chronic obstructive pulmonary disease (COPD) [79–81].…”

Is Pharmacological, H2S-induced ‘Suspended Animation’ Feasible in the ICU?

“…Inhaling H 2 S prior to myocardial ischemia at concentrations that had no metabolic depressant eff ect (10 ppm) attenuated organ damage, but to a lesser degree than concentrations that reduced energy expenditure (100 ppm) [12], suggesting that hypometabolism may indeed enhance the organ-protective properties of H 2 S. Of note, in that study as well as in others demonstrating H 2 S-related organ production coinciding with reduced metabolic activity, hypothermia was prevented [5], [7], [9], [14], [15] in order to elucidate the impact of a simultaneous drop in core temperature. Moreover, organ protection and improved survival were also shown to be in part [12], [13], [15], [34], [35] or even completely [8], [11], [36], [37] independent of any H 2 Sinduced metabolic depression at all. Finally, data obtained in large animal (swine or sheep) models of shock resulting from ischemia/reperfusion [29], [38]- [42], hemorrhage and resuscitation [30], or burn injury [36] also suggested that the benefi cial eff ects of infusing Na 2 S were at least in part independent of metabolic depression and/or a fall in core temperature.…”

“…Moreover, organ protection and improved survival were also shown to be in part [12], [13], [15], [34], [35] or even completely [8], [11], [36], [37] independent of any H 2 Sinduced metabolic depression at all. Finally, data obtained in large animal (swine or sheep) models of shock resulting from ischemia/reperfusion [29], [38]- [42], hemorrhage and resuscitation [30], or burn injury [36] also suggested that the benefi cial eff ects of infusing Na 2 S were at least in part independent of metabolic depression and/or a fall in core temperature. Hence, any moderate hypothermia observed simultaneously with H 2 S-induced organ-protection may also be due to attenuation of systemic infl ammation rather than to reduced energy expenditure per se.…”