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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Abstract

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.

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