Please use this identifier to cite or link to this item: http://hdl.handle.net/1946/10815
The relationship between inflammatory mediators, n-6 and n-3 long-chain polyunsaturated fatty acids in red blood cell membranes and postoperative atrial fibrillation following open heart surgery
Tengsl bólguþátta, ómega-6 og ómega-3 fjölómettaðra fitusýra í himnum rauðra blóðkorna og gáttatifs eftir opna hjartaskurðaðgerð
During open heart surgery, mechanical manipulation of the heart and pericardium leads to a local tissue trauma and local inflammatory response which both increases the risk of postoperative atrial fibrillation (POAF). In clinical studies focus has been on the anti-inflammatory and anti-arrhythmic effect of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but the effect on the incidence of POAF in patients undergoing coronary artery bypass grafting (CABG) has been contradictory. The aims of this study were to examine the association between circulating inflammatory mediators, n-6 and n-3 LC-PUFA in red blood cell (RBC) membrane lipids and the incidence of POAF in patients undergoing open heart surgery.
The study was a part of a prospective, randomized, double-blinded, placebo-controlled clinical trial on the use of n-3 LC-PUFA for a week prior to open heart surgery to prevent postoperative atrial fibrillation. Blood samples were obtained from each patient a week before surgery (baseline), immediately before surgery (perioperatively) and on the third postoperative day. Total lipids were extracted from RBC membrane and the fatty acid composition determined by using a gas chromatograph. Inflammatory mediators were measured at baseline, perioperatively and postoperatively. The study endpoint was defined as an episode of POAF lasting more than five minutes by continuous electrocardiographic monitoring.
Plasma concentrations of IFN-γ and TNF-β were lower than those of IL-6, IL-8, IL-10, IL-18 and hs-CRP were higher on the third postoperative day than perioperatively. The relationship between concentrations of inflammatory mediators and fatty acid levels in plasma phospholipids (PL) and RBC membrane lipids was investigated. In perioperative plasma PL, higher level of eicosapentaenoic acid (EPA) was associated with lower concentration of hs-CRP, and higher docosahexaenoic acid (DHA) level was associated with lower IL-12 and IL-18 concentrations. In RBC, higher arachidonic acid (AA) level was highly associated with higher concentration of TNF-β, whereas higher DHA level was associated with lower IL-18 concentration. In perioperative plasma PL, higher level of AA was associated with more increase in IL-10 and lesser increase in TGF-β, whereas higher level of EPA was associated with lesser increase in IL-10. On the other hand, in RBC higher AA level was associated with more pronounced decrease in TNF-β, and lesser increase in TGF-β, whereas higher level of EPA was associated with more increase in IL-1 β and TGF-β.
Perioperatively the concentration of TGF-β was negatively associated with age (r = -0.165, P = 0.036). On the third postoperative day the concentrations of IL-6 and IL-8 were positively associated (r = 0.179, P = 0.036, and r = 0.180, P = 0.022, respectively), and TGF-β negatively associated (r = -0.168, P = 0.033) with age.
Sixty-two CABG patients (49.6%) developed POAF. The patients who developed POAF (POAF group) were older (69 (45-82) years versus 65 (43-79) years, P=0.001) and their body mass index (BMI) was lower (26.7 (17.2-38.1) kg/m2 versus 28.3 (20.9-41.3) kg/m2, P<0.05) compared with those who did not develop POAF (sinus rhythm (SR) group). In both groups postoperative IL-6, IL-8, IL-18, IL-10 and hs-CRP concentrations were higher (P<0.05), and that of TNF-β was lower (P<0.01) than the perioperative concentrations. Only postoperative concentration of IL-6 was higher in POAF group compared with the SR group. Perioperatively, the SR and POAF groups differed in the n-6 and n-3 LC-PUFA levels of RBC membrane lipids. The POAF group had lower level of AA and higher levels of total n-3 LC-PUFA and DHA compared with the SR group (P < 0.05). Multivariable logistic regression analysis did not reveal inflammatory mediators as independent predictors of POAF. However, the risk of POAF increased with higher perioperative concentration of DHA (OR (95% CI) = 1.506 (1.010-2.246)), and higher postoperative concentrations of EPA (OR (95% CI) = 1.952 (1.043-3.654)), DHA (OR (95% CI) = 1.983 (1.260-3.121)), and total n-3 LC-PUFA (OR (95% CI) = 1.440 (1.119-1.853)) in RBC membrane lipids (P < 0.05). Perioperatively, there was a trend for an increasing incidence of POAF with higher quartiles of DHA and total n-3 LC-PUFA (P = 0.006 and P = 0.010, respectively). Postoperatively, there was a significant difference in POAF incidence between quartiles of DHA and total n-3 LC-PUFA (P = 0.007 and P = 0.034, respectively) with a significant trend for an increasing incidence of POAF with higher quartiles of these fatty acids (P = 0.001 and P = 0.002, respectively).
The study suggests that n-6 and n-3 LC-PUFA in RBC membrane lipids play an important role in modulating the inflammatory response following surgical injury. Further, it indicates that inflammatory mediators are not strongly associated with the development of POAF, and that higher levels of n-3 LC-PUFA in cell membranes may be a risk factor for POAF.