Interactions of the Gasotransmitters Contribute to Microvascular Tone (Dys)regulation in the Preterm Neonate

BACKGROUND & AIMS: Hydrogen sulphide (H(2)S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow. 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 nitrate and nitrite in urine. H(2)S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions. RESULTS: No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H(2)S (p = 0.008, r = 0.28) and an inverse relationship between CO and H(2)S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented. CONCLUSIONS: The relationships between NO and H(2)S, and CO and H(2)S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H(2)S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.