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. METHODS AND 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). CONCLUSION: 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.

Intramyocardial injection of tannic acid attenuates postinfarction remodeling: a novel approach to stabilize the breaking extracellular matrix.

OBJECTIVE: Myocardial infarction is associated with early matrix metalloproteinase activation and extracellular matrix degradation. We tested the hypothesis that stabilizing the original extracellular matrix of the infarcted left ventricle with local injection of tannic acid would preserve cardiac structure and function. METHODS: In vitro cytotoxicity of tannic acid was performed first; myocardial infarction model was induced by ligation of the left anterior descending branch in rats. Tannic acid was intramyocardially injected into infarcted site 24 hours after myocardial infarction (n = 30), and saline solution was injected in the same way as in the control (n = 30). The matrix metalloproteinase activity from tannic acid/saline solution-treated tissues was assayed by gelatin zymography 24 hours and 1 week after the treatment. The collagen content in the infarcted area was evaluated by hydroxyproline colorimetry assay 1 and 4 weeks after the treatment. Left ventricular structure and function were also evaluated with echocardiography, hemodynamics, and histologic examination. RESULTS: Tannic acid at a concentration of 0.05% had minimal cytotoxic effects on cultured cardiomyocytes and thus was subsequently chosen as the optimal concentration for injection. Compared with the saline solution injection group, tannic acid treatment inhibited the matrix metalloproteinase-2/-9 activity and increased the collagen content at the early post-myocardial infarction stage (48.6 +/- 7.2 vs 37.3 +/- 6 microg/mg dry weight). Tannic acid treatment also significantly reduced infarct expansion (infarct expansion index: 1.04 +/- 0.15 vs 1.42 +/- 0.21) and left ventricular dilatation at 4 weeks after infarction. Although tannic acid treatment improved fractional shortening (26% +/- 2.4% vs 23.3% +/- 3.2%), it failed to alter blood pressure (systolic blood pressure: 93.8 +/- 8.2 vs 90.6 +/- 8.5 mm Hg) and rate of pressure rise. CONCLUSIONS: Local delivery of tannic acid prevents collagen matrix degradation via cross-linking fibrous collagen and inhibiting matrix metalloproteinase activity but does not improve the intrinsic contractile function of myocardium. This treatment may be helpful to attenuate the adverse topographic remodeling after acute myocardial infarction.

Tissue extracts from infarcted myocardium of rats in promoting the differentiation of bone marrow stromal cells into cardiomyocyte-like cells.

OBJECTIVE: To investigate whether cardiac tissue extracts from rats could mimic the cardiac microenvironment and act as a natural inducer in promoting the differentiation of bone marrow stromal cells (BMSCs) into cardiomyocytes. METHODS: Three kinds of tissue extract or cell lysate [infarcted myocardial tissue extract (IMTE), normal myocardial tissue extract (NMTE) and cultured neonatal myocardial lysate (NML)] were employed to induce BMSCs into cardiomyocyte-like cells. The cells were harvested at each time point for reverse transcription-polymerase chain reaction (RT-PCR) detection, immunocytochemical analysis, and transmission electron microscopy. RESULTS: After a 7-day induction, BMSCs were enlarged and polygonal in morphology. Myofilaments, striated sarcomeres, Z-lines, and more mitochondia were observed under transmission electron microscope. Elevated expression levels of cardiac-specific genes and proteins were also confirmed by RT-PCR and immunocytochemistry. Moreover, IMTE showed a greater capacity of differentiating BMSCs into cardiomyocyte-like cells. CONCLUSIONS: Cardiac tissue extracts, especially IMTE, can effectively differentiate BMSCs into cardiomyocyte-like cells.