Major surgery leads to a proinflammatory phenotype: differential gene expression following a laparotomy

Dobson, Geoffrey P., Morris, Jodie L., Biros, Erik, Davenport, Lisa M., and Letson, Hayley L. (2021) Major surgery leads to a proinflammatory phenotype: differential gene expression following a laparotomy. Annals Of Medicine And Surgery, 71. 102970.

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Background: The trauma of surgery is a neglected area of research. Our aim was to examine the differential expression of genes of stress, metabolism and inflammation in the major organs of a rat following a laparotomy.

Materials and methods: Anaesthetised Sprague-Dawley rats were randomised into baseline, 6-hr and 3-day groups (n = 6 each), catheterised and laparotomy performed. Animals were sacrificed at each timepoint and tissues collected for gene and protein analysis. Blood stress hormones, cytokines, endothelial injury markers and coagulation were measured.

Results: Stress hormone corticosterone significantly increased and was accompanied by significant increases in inflammatory cytokines, endothelial markers, increased neutrophils (6-hr), higher lactate (3-days), and coagulopathy. In brain, there were significant increases in M1 muscarinic (31-fold) and α-1A-adrenergic (39-fold) receptor expression. Cortical expression of metabolic genes increased ∼3-fold, and IL-1β by 6-fold at 3-days. Cardiac β-1-adrenergic receptor expression increased up to 8.4-fold, and M2 and M1 muscarinic receptors by 2 to 4-fold (6-hr). At 3-days, cardiac mitochondrial gene expression (Tfam, Mtco3) and inflammation (IL-1α, IL-4, IL-6, MIP-1α, MCP-1) were significantly elevated. Haemodynamics remained stable. In liver, there was a dramatic suppression of adrenergic and muscarinic receptor expression (up to 90%) and increased inflammation. Gut also underwent autonomic suppression with 140-fold increase in IL-1β expression (3-days).

Conclusions: A single laparotomy led to a surgical-induced proinflammatory phenotype involving neuroendocrine stress, cortical excitability, immune activation, metabolic changes and coagulopathy. The pervasive nature of systemic and tissue inflammation was noteworthy. There is an urgent need for new therapies to prevent hyper-inflammation and restore homeostasis following major surgery.

Item ID: 69727
Item Type: Article (Research - C1)
ISSN: 2049-0801
Keywords: Trauma; Surgery; Inflammation; Laparotomy; Stress response; Gene expression
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Copyright Information: © 2021 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY license.
Date Deposited: 25 Oct 2021 00:47
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320226 Surgery @ 80%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3208 Medical physiology > 320803 Systems physiology @ 20%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified @ 100%
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