Abstract
Background & AimsHydrogen sulphide (H2S), 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.Methods90 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. H2S 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.ResultsNo relationship was observed between NO and CO (p = 0.18, r = 0.18). 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) 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.ConclusionsThe relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S 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.
Highlights
Endogenous hydrogen sulphide (H2S) is associated with microvascular tone regulation at 24h postnatal age in the preterm infant and production appears to be affected by both gestational age and sex [1]
The relationships between nitric oxide (NO) and H2S, and carbon monoxide (CO) and H2S may be of importance in the preterm newborn, as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation
NO is proposed to play a central role in the maintenance of vascular homeostasis in the perinatal period, urinary excretion of NO metabolites do not correlate with early changes in microvascular blood flow in the preterm neonate [4]
Summary
Endogenous hydrogen sulphide (H2S) is associated with microvascular tone regulation at 24h postnatal age in the preterm infant and production appears to be affected by both gestational age and sex [1]. It has been hypothesised that the rate of NO production in the endothelium of peripheral microvessels (via endothelial nitric oxide synthase (eNOS)) is lower than would be required to activate the downstream sGC pathway in vascular smooth muscle cells responsible for the excessive vasodilatation seen in premature neonates. This has led to the speculation that other mechanisms may be involved in both the production of NO in the microvasculature and its vasoactive effects on vascular smooth muscle cells during the transition from fetal to neonatal circulatory systems, with NO contributing to the maintenance of background tone throughout this period [5,6]. 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
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