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Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.

Miura Y, Saito M, Usuda H, Woodward E, Rittenschober-Böhm J, Kannan PS, Musk GC, Matsuda T, Newnham JP, Kemp MW - PLoS ONE (2015)

Bottom Line: Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes.There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation.

View Article: PubMed Central - PubMed

Affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan.

ABSTRACT

Introduction: Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume.

Methods: Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups.

Results: Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.

Conclusion: In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.

No MeSH data available.


Related in: MedlinePlus

Representative images for qualitative scoring of airspace infiltration.Images are representative of the indicated inflammatory scores assigned to each field assessed (× 200 total magnification). Scale bar = 100 μm.
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pone.0140701.g001: Representative images for qualitative scoring of airspace infiltration.Images are representative of the indicated inflammatory scores assigned to each field assessed (× 200 total magnification). Scale bar = 100 μm.

Mentions: 5 μm paraffin sections of 10% (pH 7.4) formalin-fixed fetal lung (right upper lobe) were stained with Meyer’s haematoxylin and eosin. Qualitative scoring of airspace infiltration was performed by a single investigator blinded to treatment groups. Six fields (200 x total magnification) were scored for each animal. Airspace infiltration and consolidation were graded as follows: 0 = no inflammatory cells in airspace; 1 = airspace inflammatory cells, no consolidation; 2 = airspace inflammatory cells + limited microconsolidation (1–4 per field) foci; 3 = airspace inflammatory cells + numerous (>4 per field) but predominantly discrete microconsolidation foci; and 4 = airspace inflammatory cells + confluent airspace consolidation (Fig 1).


Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.

Miura Y, Saito M, Usuda H, Woodward E, Rittenschober-Böhm J, Kannan PS, Musk GC, Matsuda T, Newnham JP, Kemp MW - PLoS ONE (2015)

Representative images for qualitative scoring of airspace infiltration.Images are representative of the indicated inflammatory scores assigned to each field assessed (× 200 total magnification). Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608829&req=5

pone.0140701.g001: Representative images for qualitative scoring of airspace infiltration.Images are representative of the indicated inflammatory scores assigned to each field assessed (× 200 total magnification). Scale bar = 100 μm.
Mentions: 5 μm paraffin sections of 10% (pH 7.4) formalin-fixed fetal lung (right upper lobe) were stained with Meyer’s haematoxylin and eosin. Qualitative scoring of airspace infiltration was performed by a single investigator blinded to treatment groups. Six fields (200 x total magnification) were scored for each animal. Airspace infiltration and consolidation were graded as follows: 0 = no inflammatory cells in airspace; 1 = airspace inflammatory cells, no consolidation; 2 = airspace inflammatory cells + limited microconsolidation (1–4 per field) foci; 3 = airspace inflammatory cells + numerous (>4 per field) but predominantly discrete microconsolidation foci; and 4 = airspace inflammatory cells + confluent airspace consolidation (Fig 1).

Bottom Line: Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes.There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation.

View Article: PubMed Central - PubMed

Affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan.

ABSTRACT

Introduction: Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume.

Methods: Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups.

Results: Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.

Conclusion: In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.

No MeSH data available.


Related in: MedlinePlus