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

Abstract

Objective H2S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H2S 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 H2S, was determined by high‐performance liquid chromatography. Real‐time H2S 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 H2S 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 H2S. H2S produced via CSE did not correlate directly with microvascular blood flow. Conclusions In preterm neonates, H2S production increases during fetal‐to‐neonatal transition and CSE contribution to total H2S increases postnatally. CSE‐dependent mechanisms may therefore underpin the increase in H2S production over the first 72 hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability.

COVID-19: can we treat the mother without harming her baby?

“…In sheep models, fetal surgery can be performed to allow collection of paired blood samples from the maternal and fetal circulation and determine the fetal response to maternal drug treatment in real time. [90][91][92][93]99 In guinea pigs, one can comprehensively assess the longer-term effects of fetal drug exposure to primary school age equivalency 97,98,[100][101][102][103] or Fig. 3.…”

The content of gas transmitters in umbilical cord blood and blood of newborns born to mothers with preeclampsia

“…Увеличение содержания сероводорода в крови у новорожденных свидетельствует о развитии дисфункции эндотелия и нарушении микроциркуляции [22]. Высокие концентрации сероводорода также оказывают расслабляющее действие на гладкие мышцы кровеносных сосудов посредством активации АТФ-зависимых К+ [23]. Учитывая данные литературы, следует отметить, что и оксид азота, и сероводород оказывают вазодилататорный эффект, хотя имеют различные механизмы действия.…”

Microcirculation at Mooloolaba

“…The gasotransmitter hydrogen sulfide (H 2 S) contributes to the regulation of microvascular tone during circulatory transition at birth. In this issue, Dyson et al explore the production and possible sources of H 2 S in term and preterm newborn guinea‐pigs. They demonstrate that microcirculatory blood flow is higher in preterm male offspring, a group in which H 2 S production is also increased.…”