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.

Left ventricular reconstruction with no-patch technique: early and late clinical outcomes.

BACKGROUND: Few studies have evaluated late clinical outcome of no-patch technique in patients with large left ventricular aneurysms. The objectives of this study were to evaluate a no-patch surgical technique to reconstruct the left ventricle in patients with left ventricular aneurysm and to assess early and late clinical outcomes. METHODS: In 1995, we began using a no-patch technique in patients with dyskinetic left ventricular aneurysms. A total of 145 patients underwent left ventricular reconstruction with this technique and were followed up for (59 ± 29) months (range, 1 - 127 months). Risk factors for early mortality were analyzed by bivariate analyses. Cox's proportional hazards model was used to calculate risk factors for all-cause mortality and hospital readmission. Kaplan-Meier methodology was used to analyze late survival. RESULTS: One week after operation, left ventricular end-diastolic diameter had decreased from (61 ± 8) mm to (55 ± 8) mm, and geometry of the left ventricle was restored to a more normal conical shape. Early mortality was 3% and late mortality 11%. Over a 5-year follow-up period, hospital readmission was 28%. One-, 5-, and 10-year survival estimates were 95% (95% confidence interval (CI) 91% - 99%), 86% (95%CI 78% - 94%), and 74% (95%CI 60% - 88%). Readmission-free survival at 1 and 5 years after operation was 87% (95%CI 81% - 93%) and 60% (95%CI 50% - 70%), respectively. CONCLUSION: The no-patch technique for left ventricular reconstruction is an effective and simple procedure that can achieve satisfactory early and late clinical outcomes in patients with left ventricular aneurysms.

Impact of off-pump techniques on sex differences in early and late outcomes after isolated coronary artery bypass grafts.

BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) is associated with lower early mortality and benefits women disproportionately. The objective of this study was to assess the impact of off-pump techniques on sex differences in late outcomes. METHODS: We reviewed a clinical database of consecutive patients who underwent isolated coronary artery bypass graft surgery (CABG) at FuWai Hospital from 1999 to 2005. Logistic regression analysis and proportional hazards modeling were used to investigate whether sex or surgery type were associated with early mortality and late outcomes (mortality, major cardiac and cerebral event). RESULTS: Female sex was associated with higher rates of early death (adjusted odds ratio, 4.726; p < 0.0001), and OPCAB benefited women disproportionately for early mortality. Odds ratio of death for women versus men was 4.726 (p < 0.0001) in the conventional CABG on cardiopulmonary bypass group; odds ratio of death for women versus men was 1.344 (p = 0.5617) in the OPCAB group. Analysis of late outcomes indicated that OPCAB and cardiopulmonary bypass resulted in similar survival, regardless of sex. The women versus men hazard ratio of late mortality after CABG on cardiopulmonary bypass and OPCAB for women was 0.851 (p = 0.4984) and 0.650 (p = 0.2005), respectively. Women treated with OPCAB were less likely to be free from major cardiac and cerebral events than men treated with OPCAB. The women versus men hazard ratio of major cardiac and cerebral events after CABG on cardiopulmonary bypass and OPCAB for women was 1.079 (p = 0.4992) and 1.299 (p = 0.0387), respectively. CONCLUSIONS: Compared with men, women are a high-risk group and benefit from off-pump operation in terms of early mortality after CABG. Conversely, during follow-up, women have high adjusted risks of major cardiac and cerebral events after OPCAB.

Is it possible to obtain "true endothelial progenitor cells" by in vitro culture of bone marrow mononuclear cells?

In vitro-cultured bone marrow cells have been shown to contain some low-density lipoprotein (LDL) uptake-positive cells. Although a small portion of LDL uptake-positive cells had expression for endothelial markers, all of them demonstrated a phagocytosis function similar to monocyte/macrophages and expression of the panleukocyte surface marker CD45 and monocyte marker CD14. These LDL uptake-positive cells did not show significant proliferative capacity and died out gradually in long-term culture. In contrast, the bone marrow-derived LDL uptake-negative cells showed strong proliferation and expression of typical mesenchymal surface markers CD29 and CD44. Although cultured under endothelial promoting conditions, these mesenchymal stem cells (MSCs) did not show any sign of differentiation toward endothelial cells. In conclusion, adult bone marrow-derived LDL uptake-positive cells that have been reported so far actually are monocytes/macrophages that can express some endothelial markers but are not "true endothelial progenitor cells" (EPCs). MSCs, which are the only cell type that shows strong proliferation during long-term adherent culture for bone marrow cells, do not differentiate toward the endothelial lineage when grown under endothelial promoting conditions.

Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture.

Mononuclear cells (MNCs) isolated from peripheral blood by density gradient centrifugation were plated on human fibronectin-coated culture plates and cultured in EGM-2 medium. Attached spindle-shaped cells, reported as endothelial progenitor cells (EPCs) by some investigators, had elongated from adherent round cells, but had not proliferated from a small number of cells as supposed previously. The growth curve of the primary EPCs showed that the cells had little proliferative capacity. Flow cytometry analysis showed that the cells could express some of the endothelial lineage markers, while they could also express CD14, which is considered a marker of monocyte/macrophage lineages throughout culture. In endothelial function assays, the cells demonstrated a lower level of expression of eNOS than mature endothelial cells in the reverse transcription-polymerase chain reaction and did not show an ability to develop tube-like structures in angiogenesis assay in vitro. In this study, we identified the monocytoid function of EPCs by the combined Dil-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and Indian ink uptake tests. All the cells were double positive for Dil-Ac-LDL and Indian ink uptake at days 4, 14 and 28 of culture, which means the EPCs maintained monocytoid function throughout the culture. Therefore, although adult EPCs from peripheral MNCs have some endothelial lineage properties, they maintain typical monocytic function and have little proliferative capacity.