Aeration Strategy at Birth Does Not Impact Carotid Blood Flow and Oxygen Delivery in Preterm Lambs

Dahm, S.; Kenna, K.; Stewart, D.; Pereira-Fantini, P.; McCall, K.; Perkins, E.; Sourial, M.; Tingay, D.

doi:10.1101/2022.03.03.482754

Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.03.03.482754

Aeration Strategy at Birth Does Not Impact Carotid Blood Flow and Oxygen Delivery in Preterm Lambs

Dahm, S.·Kenna, K.·Stewart, D.·Pereira-Fantini, P.·McCall, K.·Perkins, E.·Sourial, M.·Tingay, D.

View original source ↗Export metadata ↓

Abstract

BackgroundThe impact of different respiratory strategies at birth on the preterm lung is well understood, however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on cerebral haemodynamics and oxygenation. Methods124-127 day gestation apnoeic intubated preterm lambs (n=68) being studied as part of a larger program primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmH2O (No-RM; n=12), sustained inflation (SI; n=15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmH2O, n=41) at birth, followed by 90 minutes of standardised ventilation. Haemodynamic data was continuously recorded, with intermittent arterial blood gas analysis. Main outcome measures for this study included carotid blood flow, carotid artery oxygen content and carotid oxygen delivery. ResultsOverall carotid blood flow measures were comparable between strategies, with the exception of mean carotid blood flow which was significantly lower for the SI group compared to the No-RM and DynPEEP groups respectively over the first 3 minutes (p<0.0001, mixed-effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP did not alter cerebral haemodynamic measures. ConclusionAlthough there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained. ImpactO_LIDifferent pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics. C_LIO_LIThis is the first study that compares the effect of sustained lung inflation, and dynamic and static positive end-expiratory pressure on cerebral haemodynamics. C_LIO_LIWe found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery. C_LIO_LIThis preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates. C_LI

Explore related subjects

physiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Dahm, S., Kenna, K., Stewart, D., Pereira-Fantini, P., McCall, K., Perkins, E., Sourial, M., Tingay, D.. 2022-03-04. Aeration Strategy at Birth Does Not Impact Carotid Blood Flow and Oxygen Delivery in Preterm Lambs. https://doi.org/10.1101/2022.03.03.482754

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

28S-rsRNA facilitates PASMC proliferation through PKM2 β-hydroxybutyrylation

Ribosomal RNA-derived small RNAs (rsRNAs) are nucleic acid fragments originating from rRNA, the functions and roles of which in diseases remain incompletely understood. We identified 28S rsRNA-CTC_L20, an rsRNA whose expression is upregulated in hypoxic pulmonary artery smooth muscle cells (PASMCs) and in lung tissues of pulmonary hypertension (PH) models. In hypoxic cells, 28S rsRNA-CTC_L20 promotes PASMC proliferation, and its knockdown mitigates SuHx-induced pulmonary hypertension and vascular remodeling. Mechanistically, 28S rsRNA-CTC_L20 modulates {beta}-hydroxybutyrate (BHB) production by maintaining the stability of ketogenic enzyme mRNAs through its "CTGNNGG" motif. Elevated levels of BHB enhance the {beta}-hydroxybutyrylation modification at K166 of pyruvate kinase M2 (PKM2), increasing its activity and driving glycolysis to sustain proliferation. These results link ketone body metabolism to glycolysis in hypoxic cells and define an rsRNA-BHB-PKM2 {beta}-hydroxybutyrylation axis in PH. They also point to 28S rsRNA-CTC_L20 as a potential target for treating vascular remodeling.

physiology↗

bioRxiv2026

Selective activation of estrogen receptors modulates electrical activity and insulin secretion in human EndoC-βH1 cells

Estrogen receptors (ERs), ER and ER{beta} have important roles in the physiology of the endocrine pancreas in animal models, but the effects of ER activation on insulin-secreting human cells are still poorly understood. Here, we investigated the role of ER and ER{beta} as modulators of electrical activity and insulin secretion in the insulin-secreting human cell line EndoC-{beta}H1. Immunocytochemical analysis revealed a widespread cellular distribution of ER, while ER{beta} was predominantly localized outside the nucleus. We observed that both estradiol (E2) and the ER{beta} agonist diarylpropionitrile (DPN) led to a decrease in insulin secretion in the absence of stimulatory glucose concentrations, without affecting insulin content. Patch-clamp experiments revealed that a 48-hour treatment with either the ER agonist PPT or DPN resulted in depolarization of the resting membrane potential, increased action potential firing frequency, and altered the action potential waveform in EndoC-{beta}H1 cells. PPT increased voltage-dependent Ca2+ channel currents, while DPN reduced K+ and Na+ currents. These results suggest that activation of ER and ER{beta} modulates beta-cell electrical activity through distinct pathways involving ion channels. The effects of E2, PPT, and DPN were not caused by altered expression levels of ion channel genes after 48 hours of treatment. This suggests that these receptors act extranuclearly without affecting gene expression. Together, our findings demonstrate that selective activation of ER and ER{beta} modulates beta-cell excitability through distinct electrophysiological mechanisms and that E2 and DPN reduce basal insulin secretion in human EndoC-{beta}H1 cells. These results support ER and ER{beta} as potential targets for modulating human pancreatic beta-cell function.

physiology↗

bioRxiv2026

Body weight modifies the efficacy of lifespan-extending interventions in ad libitum-fed mice

Geroprotective interventions are often assessed by extension of lifespan in ad libitum-fed mice. Increased lifespan could therefore reflect rescue of adverse phenotypes of unhealthy controls. We analysed body weight and survival for 33,780 mice in the Interventions Testing Program (ITP) to test whether treatment effects varied with body weight. In males, each added standard deviation of attained adult weight made treatment 6% more favourable (HR 0.94), more apparent for interventions that lowered body weight (HR 0.90). Median lifespan increase rose from 6.2% in mice in the lightest quartile to 20.2% in the heaviest pre-dosing weight quartile among those experiments, mainly because control survival declined more steeply with weight than that of the intervention group. The effect of body weight was consistent across 13 of 14 compounds and reflected weight attained during adulthood rather than in early life. Weight-dependence of intervention effects was weak in ITP females, possibly because median survival of controls exceeded that of every sampled non-ITP female control group. Amelioration of weight-associated risk is therefore implicated as a major contributor to lifespan increases relative to heavy, short-lived controls. The geroprotective effects of these interventions may thus be less apparent in metabolically healthier mice or humans.

physiology↗