Impaired Myocardium Energetics Associated With The Risk For Postoperative Atrial Fibrillation After Isolated Coronary Artery Bypass Graft Surgery

Background:Postoperative atrial fibrillation (POAF) is among the most common complications occurring in 10% to 40% of patients after coronary artery bypass grafting (CABG) surgery. Most POAF is self-limiting but prone to lead to tachycardia, heart failure, and increased cerebrovascular emboli. Even uncomplicated POAF requires medical and nursing time and can prolong hospital stay. Although many studies have correlated specific risk factors of POAF, the mechanisms underlying its pathophysiology remain to be completely elucidated. Altered myofibrillar energetics may contribute to atrial contractile dysfunction, glycolytic enzymes are compensatory up-regulated during persistent AF, and discordant metabolic alterations are evident in individuals susceptible to POAF. Peroxisome proliferator-activated receptor y coactivator-la (PGC-la) has been demonstrated as a master regulator of myocardial energy metabolism. Activation of the PGC-la regulatory cascade increases cardiac mitochondrial oxidative capacity in the heart. Recently studies suggest that dysmetabolism may contribute to the pathogenesis of atrial fibrillation; however, the relevance of this putative mechanism in patients undergoing CABG surgery is unknown. Glucose transporter 3 (GLUT3) was the third glucose transporter to be discovered, and is preferentially expressed in cells with high-energy demand but in lower proportion as compared with GLUT4 and GLUT1. Little is known about the regulation of heart GLUT3. This carrier is the most efficient among the different GLUTs, as it has the lowest Km. In the present study, we tested the hypothesis that both the maladaptive energy metabolism and diminished capacity of glucose uptake are associated with the risk for postoperative atrial fibrillation after isolated coronary artery bypass graft (CABG) surgery.Objective:In the present study, we tested the novel hypothesis that the maladaptive energy metabolism is associated with the risk of postoperative atrial fibrillation after isolated CABG surgery and evaluated the relationship of impaired energetics and clinic risk factors involved in it.Methods AND Results:Right atrial appendages were obtained from 79 patients who were in normal sinus rhythm and undergoing isolated coronary artery bypass grafting, those who exhibited new-onset POAF (n=22) or remained in sinus rhythm(SR) (n=57) were prospectively matched based on preoperative, intraoperative, and postoperative characteristics. Postoperative atrial fibrillation was assessed by electrocardiogram and must have required initiation of antiarrhythmic therapy or anticoagulatioa Local PGC-la and GLUT3 concentration was quantified by enzyme-linked immunosorbent assay (ELISA) in tissue homo genates. The comparison of mRNA expression was tested by quantitative real-time PCR. PGC-la and GLUT3 levels and the related protein mRNA expression were significantly reduced in POAF patients compared with controls (P< 0.05). This selective reduction in PGC-1α was associated with the presence of diabetes mellitus (n=34) then those without (n=45) (P< 0.05). Binary logistic regression identified PGC-la (P=0.017) as independent predictors for the development of postoperative AF among the 79 patients. Other predictors of postoperative AF that were included in the regression model but did not reach a level of statistical significance were age, history of DM, BMI, total cholesterol.Conclusion:This study in a carefully chosen, well-characterized cohort of patients undergoing isolated coronary artery bypass grafting, surgery, used the mature techniques to provide novel insights into the regulation of myocardial energy metabolism. This is the first prospective study to analyze the role of PGC-la and protein-related mRNA expression in myocardium tissue and demonstrates that a discordant regulation of energy metabolites precedes the postoperative postoperative AF after CABG surgery. We also found that the reduction in PGC-la levels were associated with presence of diabetes mellitus, while the underlying mechanism is unclear. In our study, we first found that the GLUT3 level and protein-related mRNA expression were both lower in patients of the POAF group compared with those who remained in SR, with the difference being statistically significant. This suggested that the impaired capacity of glucose uptake can abate the efficiency of glucose oxidation in the reperfusion heart and can induce the electrical instability to a certain extent.