Exposure to intrauterine inflammation leads to impaired function and altered structure in the preterm heart of fetal sheep

Tare, Marianne, Bensley, Jonathan G., Moss, Timothy J. M., Lingwood, Barbara E., Kim, Min Y., Barton, Samantha K., Kluckow, Martin, Gill, Andrew W., De Matteo, Robert, Harding, Richard, Black, M. Jane, Parkington, Helena C. and Polglase, Graeme R. (2014) Exposure to intrauterine inflammation leads to impaired function and altered structure in the preterm heart of fetal sheep. Clinical Science, 127 9: 559-569. doi:10.1042/CS20140097

Author Tare, Marianne
Bensley, Jonathan G.
Moss, Timothy J. M.
Lingwood, Barbara E.
Kim, Min Y.
Barton, Samantha K.
Kluckow, Martin
Gill, Andrew W.
De Matteo, Robert
Harding, Richard
Black, M. Jane
Parkington, Helena C.
Polglase, Graeme R.
Title Exposure to intrauterine inflammation leads to impaired function and altered structure in the preterm heart of fetal sheep
Journal name Clinical Science   Check publisher's open access policy
ISSN 0143-5221
Publication date 2014-05-12
Year available 2014
Sub-type Article (original research)
DOI 10.1042/CS20140097
Open Access Status Not yet assessed
Volume 127
Issue 9
Start page 559
End page 569
Total pages 11
Place of publication London, United Kingdom
Publisher Portland Press
Language eng
Subject 2700 Medicine
Abstract Intrauterine inflammation is a major contributor to preterm birth and has adverse effects on preterm neonatal cardiovascular physiology. Cardiomyocyte maturation occurs in late gestation in species such as humans and sheep. We tested the hypothesis that intrauterine inflammation has deleterious effects on cardiac function in preterm sheep which might be explained by altered cardiomyocyte proliferation and maturation. Pregnant ewes received an ultrasound-guided intra-amniotic injection of lipopolysaccharide (LPS) or saline 7 days prior to delivery at day 127 of pregnancy (term 147 days). Cardiac contractility was recorded in spontaneously beating hearts of the offspring, perfused in a Langendorff apparatus. Saline-filled latex balloons were inserted into left (LV) and right ventricles (RV). Responsiveness to isoprenaline and stop-flow/reperfusion was assessed. In other experiments, hearts were perfusion-fixed and cardiomyocyte nuclearity, volume and number determined. β-Adrenoceptor mRNA levels were determined in unfixed tissue. In hearts of LPS-exposed fetuses, contractility in LV and RV was suppressed by ~40% and cardiomyocyte numbers were reduced by ~25%. Immature mono-nucleated cardiomyocytes had lower volumes (~18%), while mature bi-nucleated cardiomyocyte volume was ~77% greater. While basal coronary flow was significantly increased by 21±7% in LPS-exposed hearts, following ischemia-reperfusion, end diastolic pressure was increased 2.4±0.3-fold and infarct area 3.2±0.6-fold versus in controls. Maximum responsiveness to isoprenaline was enhanced by LPS, without an increase in b-adrenoceptor mRNA, suggesting altered second messenger signalling. Intrauterine inflammation altered cardiac growth, suppressed contractile function and enhanced responsiveness to stress. Although these effects may ensure immediate survival, they likely contribute to the increased vulnerability of organ perfusion in preterm neonates.
Keyword Medicine, Research & Experimental
Research & Experimental Medicine
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1026890
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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Created: Thu, 03 Jul 2014, 19:53:48 EST by Dr Barbara Lingwood on behalf of UQ Centre for Clinical Research