Influence of left atrial and ventricular volumes on the relation between mitral valve annulus and coronary sinus.

The aim of this study was to evaluate the anatomic relation between the coronary sinus (CS), mitral annulus, and coronary arteries using 64-multislice computed tomography (MSCT) in patients presenting with a wide range of atrial volumes and left ventricular functions to determine the potential clinical use for percutaneous mitral annuloplasty (PMA). The MSCT data of 165 patients (age 63.65 +/- 12.89 years, 67.3% men) were evaluated. The following variables were measured: CS length, CS ostium area, area of the section of CS when it becomes great cardiac vein, area between CS and atrioventricular groove assessed in volume-rendered 3-dimensional images, axial angle measured as the angle between CS and mitral annulus assessed in axial section, mitral valve annulus (MVA) area, left atrium volume, and left circumflex artery/marginal branch-CS relation referring to mitral annulus. The correlation was inversed between the reduction of the axial angle and all following variables: enlargement of both left ventricular end-systolic (r = -0.429, p <0.001) and end-diastolic (r = -0.428, p <0.001) volumes, left atrial volume (r = -0.361, p <0.001), and MVA (r = -0.324, p <0.001). Similarly, there was inverse correlation between the reduction of the area between CS and atrioventricular groove, and enlargement of both left ventricular end-systolic (r = -0.376, p <0.001) and end-diastolic (r = -0.291, p <0.001) volumes, left atrial volume (r = -0.221, p = 0.001), and MVA (r = -0.155, p = 0.019). Of note, circumflex artery was located between CS and MVA in 77% of the patients, but in patients with severe mitral regurgitation CS crossed circumflex/marginal branch artery more frequently (97% of cases). In conclusion, a close proximity of the CS to the mitral annulus but also to circumflex artery is more likely to occur with left atrial and ventricular enlargement. Thus, MSCT should be considered as part of the selection process of potential candidate to PMA to avoid external compression of circumflex artery/marginal branch by the device.

Ceramide triggers Weibel-Palade body exocytosis.

The sphingolipid ceramide mediates a variety of stress responses, including vascular inflammation and thrombosis. Activated endothelial cells release Weibel-Palade bodies, granules containing von Willebrand factor (vWF) and P-selectin, which induce leukocyte rolling and platelet adhesion and aggregation. We hypothesized that ceramide induces vascular inflammation and thrombosis in part by triggering Weibel-Palade body exocytosis. We added ceramide to human aortic endothelial cells and assayed Weibel-Palade body exocytosis by measuring the concentration of vWF released into the media. Exogenous ceramide induces vWF release from endothelial cells in a dose-dependent manner. Activators of endogenous ceramide production, neutral sphingomyelinase, or tumor necrosis factor-alpha also induce Weibel-Palade body exocytosis. We next studied NO effects on ceramide-induced Weibel-Palade body exocytosis because NO can inhibit vascular inflammation. The NO donor S-nitroso-N-acetylpenicillamine decreases ceramide-induced vWF release in a dose-dependent manner, whereas the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester increases ceramide-induced vWF release. In summary, our findings show that endogenous ceramide triggers Weibel-Palade body exocytosis, and that endogenous NO inhibits ceramide-induced exocytosis. These data suggest a novel mechanism by which ceramide induces vascular inflammation and thrombosis.

Mesenchymal stem cells: future source for reparative medicine.

Current treatments for ischemic cardiomyopathy are aimed toward minimizing the deleterious consequences of damaged myocardium. The possibility of treating heart failure by generating new myocardium and vascular structures has provided major impetus for recent stem cell research. Mesenchymal stem cells (MSCs), also referred to as marrow stromal cells, differentiate into a wide variety of lineages, including myocardial smooth muscle and possibly endothelial cells. The multilineage potential of MSCs, their ability to elude detection by the host's immune system, and their relative ease of expansion in culture make MSCs a very promising source of stem cells for transplantation. This paper reviews animal and human trials studying the role of MSCs in cardiomyogenesis and vasculogenesis in postinfarct myocardium, factors that stimulate MSC differentiation, routes of MSC delivery, and methods of detecting MSC engraftment.