title: Interactions of the gasotransmitters contribute to microvascular tone (dys)regulation in the preterm neonate.
abstract: OBJECTIVE
  Hydrogen 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.
  
  
  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. 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.
  
  
  RESULTS
  No 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.
  
  
  CONCLUSIONS
  The 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.
authors: Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia; Illawarra Health and Medical Research Institute and Graduate School of Medicine, University of Wollongong, NSW, 2522, Australia.
authors: Rebecca M
authors: RM
authors: Dyson
authors: Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, 2308, Australia.
authors: Hannah K
authors: HK
authors: Palliser
authors: Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia.
authors: Joanna L
authors: JL
authors: Latter
authors: Illawarra Health and Medical Research Institute and Graduate School of Medicine, University of Wollongong, NSW, 2522, Australia.
authors: Megan A
authors: MA
authors: Kelly
authors: Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, 90-236, Lodz, Poland.
authors: Grazyna
authors: G
authors: Chwatko
authors: Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, 90-236, Lodz, Poland.
authors: Rafal
authors: R
authors: Glowacki
authors: Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia; Illawarra Health and Medical Research Institute and Graduate School of Medicine, University of Wollongong, NSW, 2522, Australia; Kaleidoscope Neonatal Intensive Care Unit, John Hunter Children's Hospital, New Lambton Heights, NSW, 2305, Australia.
authors: Ian M R
authors: IM
authors: Wright
mesh_terms: D002248:Carbon Monoxide / Q000378:metabolism; D005260:Female; D064426:Gasotransmitters / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D064426:Gasotransmitters; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006862:Hydrogen Sulfide