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

Karisnan, K, Mahzabin, T, Bakker, AJ, Song, Y, Noble, PB, Pillow, JJ and Pinniger, GJ 2018 , '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, vol. 314, no. 4 , R523-R532 , doi: 10.1152/ajpregu.00150.2017.

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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 P 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 Type: Article
Authors/Creators:Karisnan, K and Mahzabin, T and Bakker, AJ and Song, Y and Noble, PB and Pillow, JJ and Pinniger, GJ
Keywords: contractile dysfunction, diaphragm, gestational age, in utero inflammation
Journal or Publication Title: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Publisher: Amer Physiological Soc
ISSN: 0363-6119
DOI / ID Number: 10.1152/ajpregu.00150.2017
Copyright Information:

Copyright © 2018 the American Physiological Society

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