Electrical Remodeling in Persistent Atrial Fibrillation May Be Mediated by Changes in the IKATP Channel

The goal of this study was to measure the effective refractory period (ERP), the conduction velocity (CV) and the wavelength (WL) after cardioversion in patients with persistent atria] fibrillation (AF) and to determine the effects of the adenosine triphosphate sensitive potassium channel (KATP) opening agent, nicorandil, on those parameters in patients with persistent AF. METHODS: Patients with AF underwent elective cardioversion followed by measurement of ERP and CV before and after administration of nicorandil. Parameters were measured again one week later, and the ERP and the CV was used to calculate WL. RESULTS: ERP was significantly shorter immediately after termination of AF than at the 1-week time point (193.4 vs. 228.7 msec p < 0.01). While there was no significant difference in ERP immediately after termination of AF when comparing measurements taken before and after the administration of nicorandil, ERP at the 1-week time point was shorter after nicorandil administration than before nicorandil administration (193.4 vs. 191.4 msec, n.s.; 228.7 vs. 217.2msec, p < 0.01). Further, WL was higher at the 1-week time point after nicorandil administration than before nicorandil administration. CONCLUSIONS: These data indicate that the electrical remodeling that occurs after cardioversion is at least partially mediated by changes in KATP channel behavior. Further, the electrophysiologic properties, that is, nicorandil prolonging the WL, may be of benefit in reducing the recurrence rate of AF

Atheroprotective Effects of Tumor Necrosis Factor–Stimulated Gene-6

Tumor necrosis factor–stimulated gene-6 (TSG-6), an anti-inflammatory protein, was shown to be localized in the neointima of injury-induced rat arteries. However, the modulatory effect of TSG-6 on atherogenesis has not yet been reported. We aimed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (HECs), human monocyte-derived macrophages (HMDMs), human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in apolipoprotein E–deficient mice, along with expression levels of TSG-6 in coronary lesions and plasma from patients with coronary artery disease (CAD). TSG-6 was abundantly expressed in HECs, HMDMs, and HASMCs in vitro. TSG-6 significantly suppressed cell proliferation and lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular adhesion molecule-1 in HECs. TSG-6 significantly suppressed inflammatory M1 phenotype and suppressed oxidized low-density lipoprotein–induced foam cell formation associated with down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in HMDMs. In HASMCs, TSG-6 significantly suppressed migration and proliferation, but increased collagen-1 and -3 expressions. Four-week infusion of TSG-6 into apolipoprotein E–deficient mice significantly retarded the development of aortic atherosclerotic lesions with decreased vascular inflammation, monocyte/macrophage, and SMC contents and increased collagen fibers. In addition, it decreased peritoneal M1 macrophages with down-regulation of inflammatory molecules and lowered plasma total cholesterol levels. In patients with CAD, plasma TSG-6 levels were significantly increased, and TSG-6 was highly expressed in the fibrous cap within coronary atherosclerotic plaques. These results suggest that TSG-6 contributes to the prevention and stability of atherosclerotic plaques. Thus, TSG-6 may serve as a novel therapeutic target for CAD