Impaired myocardium energetics associated with the risk for new-onset atrial fibrillation after isolated coronary artery bypass graft surgery.
BACKGROUND
New-onset postoperative atrial fibrillation (POAF) is one of the most common complications occurring in 10-40% of patients after coronary artery bypass graft (CABG) surgery. Recent studies suggest that dysmetabolism may contribute to the pathogenesis of atrial fibrillation; however, the putative mechanism in patients undergoing CABG surgery is unknown. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) has been demonstrated as a master regulator of myocardial energy metabolism, and glucose transporter 3 (GLUT3) has both a higher affinity for glucose and a much greater transport capacity compared with GLUT1, GLUT2, and GLUT4. We sought to evaluate the role of energy metabolism, especially the glucose metabolism, on patients after isolated CABG surgery.


RESULTS
Right atrial appendages were obtained from 79 patients who were in normal sinus rhythm and undergoing isolated CABG; those who exhibited new-onset POAF (n=22) or remained in sinus rhythm (n=57) were prospectively matched on the basis of preoperative, intraoperative, and postoperative characteristics. POAF was assessed by electrocardiogram and must have required the initiation of antiarrhythmic therapy or anticoagulation. Local PGC-1α and GLUT3 concentrations were quantified by enzyme-linked immunosorbent assay in tissue homogenates. The comparison of mRNA expression was tested by quantitative real-time PCR. PGC-1α 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 (P<0.05).


CONCLUSIONS
Patients who have low PGC-1α and GLUT3 levels are at increased risk for new-onset POAF. The myofibrillar energetic impairment may be important in the pathogenesis of atrial fibrillation.
aPeking Union Medical College, Chinese Academy of Medical Science bFuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing cTEDA International Cardiovascular Hospital, Tianjin, China dCardiac Signaling Center of USC, MUSC & Clemson University, Charleston, South Carolina eMetrowest Medical Center, Framingham, Massachusetts, USA.
Dian-Min
DM
Sun
Xin
X
Yuan
Hua
H
Wei
Shen-Jun
SJ
Zhu
Peng
P
Zhang
Shi-Ju
SJ
Zhang
Hong-Guang
HG
Fan
Yan
Y
Li
Zhe
Z
Zheng
Xiao-Cheng
XC
Liu
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000379:methods; D003324:Coronary Artery Disease / Q000601:surgery*; D004562:Electrocardiography; D004734:Energy Metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D012307:Risk Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D051274:Glucose Transporter Type 3; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators; D014157:Transcription Factors; D005947:Glucose