Abstract
BackgroundOxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile.MethodsAdults patients undergoing elective laparoscopic or open colorectal resections were included. Primary outcomes were serum oxylipin profile quantified by ultra high-performance liquid chromatography-mass spectrometry, serum white cell count and C-reactive protein concentration. Serum samples were taken at three time-points: pre-operative (day zero), early post-operative (day one) and late post-operative (day four/five).ResultsSome 55 patients were included, of which 33 (60%) underwent surgery that was completed laparoscopically. Pre-operative oxylipin profiles were characterised by marked heterogeneity but surgery induced a common shift resulting in more homogeneity at the early post-operative time-point. By the late post-operative phase, oxylipin profiles were again highly variable. This evolution was driven by time-dependent changes in specific oxylipins. Notably, the levels of several oxylipins with anti-inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at the early post-operative point before returning to baseline by the late post-operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the early post-operative phase while levels of anti-thrombotic mediators (9-HODE and 13-HODE) fell; concentrations of all three oxylipins then remained fairly static from early to late post-operative phases. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had lower levels of some anti-inflammatory oxylipins (8,9-DHET and 17-HDoHE) in addition to reduced concentrations of anti-thrombotic mediators (9-HODE and 13-HODE) with increased concentration of their pro-thrombotic counterpart (TxB2).ConclusionsSerum oxylipin profile is modified by surgical intervention and may even be sensitive to the degree of surgical trauma and therefore represents a novel descriptor of the surgical systemic inflammatory response.
Highlights
Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma
Clinicians are generally reliant on the longitudinal assessment of physiological parameters and biomarkers of inflammation, such as C-reactive protein (CRP) and white cell count (WCC)
Eicosanoids, and more generally oxylipins, are potent, locally-acting lipid mediators derived from the metabolism of polyunsaturated fatty acid (PUFA) precursors such as linoleic acid (C18:2, LA), dihomo-γ-linolenic acid (C20:3, DGLA), arachidonic acid (C20:4, AA), eicosapentaenoic acid (C20:5, EPA) and docosahexaenoic acid (C22:6, DHA)
Summary
Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. Complications following colorectal surgery, such as surgical site infection (2–25% [1, 2]) and anastomotic leak (3–15% [3]), frequently induce the systemic inflammatory response syndrome (SIRS) or sepsis which are the major causes of post-operative morbidity and mortality [3,4,5,6] To detect such complications, clinicians are generally reliant on the longitudinal assessment of physiological parameters (e.g. respiratory rate, heart rate, temperature) and biomarkers of inflammation, such as C-reactive protein (CRP) and white cell count (WCC). Eicosanoids, and more generally oxylipins, are potent, locally-acting lipid mediators derived from the metabolism of polyunsaturated fatty acid (PUFA) precursors such as linoleic acid (C18:2, LA), dihomo-γ-linolenic acid (C20:3, DGLA), arachidonic acid (C20:4, AA), eicosapentaenoic acid (C20:5, EPA) and docosahexaenoic acid (C22:6, DHA) These PUFAs are principally converted to biologically active downstream mediators by three enzymatic pathways. Despite the acknowledged importance of oxylipins, there remains an incomplete knowledge of their systemic profiles during acute inflammation in humans due to a lack, until recently, of suitable quantitative bioanalytical platforms
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