Abstract
SummaryBackground & aimsPostoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation.MethodsFifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis – RA) and remote to the site of surgery (vastus lateralis – VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation.ResultsImmediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4 (7.8-fold, P < 0.05), TNF-α (16.5-fold, P < 0.05) and IL-6 (1058-fold, P < 0.001). A similar, albeit blunted, response was observed in VL. Surgery also increased expression of proteins linked to inflammation (IL-6; 6-fold, P < 0.01), protein degradation (MAFbx; 4.5-fold, P < 0.5), and blunted carbohydrate oxidation (PDK4; 4-fold, P < 0.05) in RA but not VL. Increased systemic inflammation (TNF-α, P < 0.05; IL-6, P < 0.001), and impaired postoperative glucose tolerance (P < 0.001), but not bacteraemia (although gut permeability was increased significantly, P < 0.05) or increased plasma cortisol, were noted 48 h postoperatively.ConclusionsA systemic postoperative proinflammatory response was accompanied by muscle inflammation and metabolic dysregulation both local and remote to the site of surgery, and was not accompanied by bacteraemia.Clinical trial registrationRegistered at http://clinicaltrials.gov (NCT01134809).
Highlights
Increased expression of interleukin-6 (IL-6), IL-6 receptor and tumour necrosis factor a (TNFa) mRNA has been demonstrated in skeletal muscle local to the site of injury in non-septic post-surgery patients [4], but whether these gene transcript changes are accompanied by increases at the protein level and with metabolic dysregulation is unknown
The major findings of the present study were that surgical trauma induced a systemic inflammatory response immediately after surgery that was accompanied by an increase in gut permeability, but there was no evidence of bacteraemia or substantive changes in fasting blood glucose or plasma insulin and cortisol concentrations 48 h later
After surgery, the abundance of mRNAs associated with tissue inflammation, protein breakdown and impaired carbohydrate oxidation was profoundly increased in muscle local to the site of surgical trauma (RA), and was mirrored by similar pattern of mRNA response in muscle distant to the site of injury (VL), albeit to a lesser extent
Summary
The effectors of the systemic response are complex and involve interactions between cytokines, neurohormonal mediators and muscle This metabolic response to major surgery may be exacerbated further by inflammation-related changes in gut permeability and resultant bacterial translocation [3]. Increased expression of interleukin-6 (IL-6), IL-6 receptor and tumour necrosis factor a (TNFa) mRNA has been demonstrated in skeletal muscle local to the site of injury in non-septic post-surgery patients [4], but whether these gene transcript changes are accompanied by increases at the protein level and with metabolic dysregulation is unknown. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation. Results: Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4
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