Background and aims Hydrogen sulphide (H2S) can be produced by one of two enzymes: CSE or CBS. H2S is associated with transitional microvascular tone dysregulation in the preterm infant. We have animal model evidence that increases in H2S associated with microvascular dysregulation are driven by CSE-dependent mechanisms. Nitric oxide (NO) and carbon monoxide (CO) also play a role in the transitional circulation of preterm neonates. The aim of this study was to characterise the interrelationships of all 3 gasotransmitters using structural equation modelling analysis.
Methods 90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as total nitrate and nitrite in urine. H2S was measured as urinary thiosulphate by liquid chromatography.
Results We observed a positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = –0.33). No relationship was observed between NO and CO (p = 0.18, r = 0.18). Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit (χ2 = 1.11) is presented.
Conclusions NO production positively related to H2S production. Previous studies report that NO inhibits H2S production via the enzyme CBS but induces CSE expression. These results suggest that in the preterm newborn, CSE expression is significantly modulated by NO. The relationship between NO and CSE/H2S may thus be critical to the deleterious higher microvascular blood flow.