Of mice and men (and sheep, swine etc.): The intriguing hemodynamic and metabolic effects of hydrogen sulfide (H2S)

Whether the hydrogen sulfide (H2S)-induced metabolic depression observed in awake rodents exists in larger species is controversial. Therefore, Derwall and colleagues exposed anesthetized and ventilated sheep to incremental H2S concentrations by means of an extracorporeal membrane oxygenator. H2S caused pulmonary vasoconstriction and metabolic acidosis at the highest concentration studied. Oxygen uptake and carbon dioxide production remained in the physiological range. The authors concluded that, beyond the effect of temperature, H2S hardly modifies metabolism at all. Since the highest H2S concentration caused toxic side effects (possibly due to an inhibition of mitochondrial respiration), the therapeutic use of inhaled H2S should be cautioned

Metabolic, cardiac and renal effects of the slow hydrogen sulfide-releasing molecule GYY4137 during resuscitated septic shock in swine with pre-existing coronary artery disease

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Published Ahead of Print, 19 January 2017Decreased levels of endogenous hydrogen sulfide (H2S) contribute to atherosclerosis, whereas equivocal data are available on H2S effects during sepsis. Moreover, H2S improved glucose utilization in anaesthetized, ventilated, hypothermic mice, but normothermia and/or sepsis blunted this effect. The metabolic effects of H2S in large animals are controversial. Therefore, we investigated the effects of the H2S donor GYY4137 during resuscitated, fecal peritonitis-induced septic shock in swine with genetically and diet-induced coronary artery disease (CAD). 12 and 18 hours after peritonitis induction, pigs received either GYY4137 (10 mg kg, n = 9) or vehicle (n = 8). Before, at 12 and 24 hours of sepsis, we assessed left ventricular (pressure-conductance catheters) and renal (creatinine clearance, blood NGAL levels) function. Endogenous glucose production and glucose oxidation were derived from the plasma glucose isotope and the expiratory CO2/CO2 enrichment during continuous i.v. 1,2,3,4,5,6-C6-glucose infusion. GYY4137 significantly increased aerobic glucose oxidation, which coincided with higher requirements of exogenous glucose to maintain normoglycemia, as well as significantly lower arterial pH and decreased base excess. Apart from significantly lower cardiac eNOS expression and higher troponin levels, GYY4137 did not significantly influence cardiac and kidney function or the systemic inflammatory response. During resuscitated septic shock in swine with CAD, GYY4137 shifted metabolism to preferential carbohydrate utilization. Increased troponin levels are possibly due to reduced local NO availability. Cautious dosing, the timing of GYY4137 administration and interspecies differences most likely account for the absence of any previously described anti-inflammatory or organ-protective effects of GYY4137 in this model