Applying gases for microcirculatory and cellular oxygenation in sepsis: effects of nitric oxide, carbon monoxide, and hydrogen sulfide

Purpose of review Nitric oxide, carbon monoxide, and hydrogen sulfide (H2S) are gases that have received attention as signaling molecules regulating many biological processes. All of them were reported to have beneficial effects in inflammatory states, in particular for microcirculatory perfusion and tissue energy balance. Thus, this review will highlight the most important results with a focus on resuscitated, clinically relevant experimental models and, if available, human studies. Recent findings There is ample evidence that nitric oxide, carbon monoxide, and H2S may exert cytoprotective effects in shock states due to their vasomotor, antioxidant, and anti-inflammatory properties as well as their potential to induce a hibernation-like metabolic state called 'suspended animation' resulting from inhibition of cytochrome-c-oxidase. It must be emphasized, however, that the three molecules may also be cytotoxic, not only because of their inhibition of cellular respiration but also because of their marked pro-inflammatory effects. Summary It is still a matter of debate whether manipulating nitric oxide, carbon monoxide, or H2S tissue concentrations, either by using the inhaled gas itself or by administering donor molecules or inhibitors of their endogenous production, is a useful therapeutic approach to improve microcirculatory blood flow, tissue oxygenation, and cellular respiration. This is mainly due to their 'friend and foe character' documented in various experimental models, but also to the paucity of data from long-term, resuscitated large animal experiments that fulfil the criteria of clinically relevant models.