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

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.

Graphical abstract

Highlights

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  A single laparotomy activated a surgical-induced stress response.

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  This was accompanied by inflammation, immune activation, hypermetabolism and coagulopathy.

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  A standout result was the pervasive nature of systemic and tissue inflammation.

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  Our study highlights the dynamic nature of genetic changes underpinning the body's early response to major surgery.

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  There is an urgent need for new therapies to prevent surgical stress and secondary injury and restore homeostatic balance.