Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: a new paradigm for cardiovascular compromise in the preterm newborn

Dyson, Rebecca, Palliser, Hannah K., Wilding, Nicole, Kelly, Megan A., Chwatko, Grazyna, Glowacki, Rafal, Berry, Mary J., Ni, Xin, and Wright, Ian (2019) Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: a new paradigm for cardiovascular compromise in the preterm newborn. Microcirculation, 26 (2). e12507.

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Abstract

Objective: H 2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H 2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition.

Methods: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H 2 S, was determined by high-performance liquid chromatography. Real-time H 2 S production was assessed using a microrespiration system in fetal and postnatal (10, 24 hours) skin and heart samples. CSE contribution was investigated by inhibition via propargylglycine.

Results: In preterm animals, postnatal H 2 S production capacity in peripheral vasculature increased significantly and was significantly reduced by the inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood flow and capacity of the vasculature to produce H 2 S. H 2 S produced via CSE did not correlate directly with microvascular blood flow.

Conclusions: In preterm neonates, H 2 S production increases during fetal-to-neonatal transition and CSE contribution to total H 2 S increases postnatally. CSE-dependent mechanisms may therefore underpin the increase in H 2 S production over the first 72 hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability.

Item ID: 62775
Item Type: Article (Research - C1)
ISSN: 1549-8719
Keywords: cystathionine γ-lyase, gasotransmitters, hydrogen sulfide, preterm birth, transitional circulation
Copyright Information: © 2018 John Wiley & Sons Ltd.
Funders: John Hunter Hospital Charitable trust grants, Hunter Medical Research Institute (HMRI), Australian Postgraduate Award Scholarship, University of Otago (UO)
Projects and Grants: HMRI Children's Research Exchange Visit Award, UO Health Sciences Career Development Postdoctoral Fellowship
Date Deposited: 15 May 2020 05:15
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3213 Paediatrics > 321303 Neonatology @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9205 Specific Population Health (excl. Indigenous Health) > 920501 Child Health @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
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