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Gestational age at time of in utero lipopolysaccharide exposure influences the severity of inflammation-induced diaphragm weakness in lambs

Citation

Karisnan, K and Mahzabin, T and Bakker, AJ and Song, Y and Noble, PB and Pillow, JJ and Pinniger, GJ, Gestational age at time of in utero lipopolysaccharide exposure influences the severity of inflammation-induced diaphragm weakness in lambs, American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 314, (4) pp. R523-R532. ISSN 0363-6119 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 the American Physiological Society

DOI: doi:10.1152/ajpregu.00150.2017

Abstract

The preterm diaphragm is functionally immature compared with its term counterpart. In utero inflammation further exacerbates preterm diaphragm dysfunction. We hypothesized that preterm lambs are more vulnerable to in utero inflammation-induced diaphragm dysfunction compared with term lambs. Pregnant ewes received intra-amniotic (IA) injections of saline or 10 mg lipopolysaccharide (LPS) 2 or 7 days before delivery at 121 days (preterm) or ∼145 days (term) of gestation. Diaphragm contractile function was assessed in vitro. Plasma cytokines, diaphragm myosin heavy chain (MHC) isoforms, and oxidative stress were evaluated. Maximum diaphragm force in preterm control lambs was significantly lower (22%) than in term control lambs (P < 0.001). Despite similar inflammatory cytokine responses to in utero LPS exposure, diaphragm function in preterm and term lambs was affected differentially. In term lambs, maximum force after a 2-day LPS exposure was significantly lower than in controls (by ~20%, P < 0.05). In preterm lambs, maximum forces after 2-day and 7-day LPS exposures were significantly lower than in controls (by ~30%, P < 0.05). Peak twitch force after LPS exposure was significantly lower in preterm than in controls, but not in term lambs. In term lambs, LPS exposure increased the proportion of MHC-I fibers, increased twitch contraction times, and increased fatigue resistance relative to controls. In preterm diaphragm, the cross-sectional area of embryonic MHC fibers was significantly lower after 7-day versus 2-day LPS exposures. We conclude that preterm lambs are more vulnerable to IA LPS-induced diaphragm dysfunction than term lambs. In utero inflammation exacerbates diaphragm dysfunction and may increase susceptibility to postnatal respiratory failure.

Item Details

Item Type:Refereed Article
Keywords:contractile dysfunction, diaphragm, gestational age, in utero inflammation
Research Division:Medical and Health Sciences
Research Group:Paediatrics and Reproductive Medicine
Research Field:Paediatrics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
UTAS Author:Song, Y (Dr Yong Song)
ID Code:135694
Year Published:2018
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-11-08
Last Modified:2019-12-05
Downloads:0

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