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LPS-induced hypotension in pregnancy: the effect of progesterone supplementation

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Title: LPS-induced hypotension in pregnancy: the effect of progesterone supplementation
Authors: Zöllner, J
Howe, LG
Edey, LF
O'Dea, KP
Takata, M
Leiper, J
Johnson, MR
Item Type: Journal Article
Abstract: Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and LPS. The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS.Female CD1 mice had radiotelemetry probes implanted to measure haemodynamic function non-invasively and were time-mated. From day 14 of pregnancy, mice received either 10 mg of P4 or vehicle alone per day and on day 16, intraperitoneal LPS (10 μg of serotype 0111:B4) was injected. In two identically treated cohorts of mice, tissue and serum (for RNA, protein studies) were collected at 6 and 12 hours.Administration of LPS resulted in a fall in blood pressure in vehicle treated, but not P4 supplemented mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors and in both circulating and tissue inflammatory cell numbers, but with reduced left ventricular expression of cytokines in P4-supplemented mice. However, left ventricular expression of markers of cardiac dysfunction and apoptosis were similar.This study demonstrates that P4 supplementation prevented LPS-induced hypotension in pregnant mice in association with reduced myocardial inflammatory cytokine gene expression. These observations suggest that rather than being detrimental, P4 supplementation has a protective effect on the maternal cardiovascular response to sepsis.
Issue Date: 1-Feb-2020
Date of Acceptance: 8-Mar-2019
URI: http://hdl.handle.net/10044/1/71285
DOI: 10.1097/SHK.0000000000001343
ISSN: 1073-2322
Publisher: Lippincott, Williams & Wilkins
Start Page: 199
End Page: 207
Journal / Book Title: Shock
Volume: 53
Issue: 2
Copyright Statement: © 2019 by the Shock Society. This is a non-final version of an article published in final form in Shock: April 14, 2019 - Volume Publish Ahead of Print - Issue - p, https://dx.doi.org/10.1097/SHK.0000000000001343
Keywords: 1103 Clinical Sciences
Emergency & Critical Care Medicine
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-04-14
Appears in Collections:Department of Surgery and Cancer