Our findings suggest that loss-of-function SCN5A mutations resulting in Brugada syndrome are distinguished by profound bradyarrhythmias.

No abstract

Few reports have examined the effects of adult bone marrow multipotent stromal cells (MSCs) on large animals, and no useful method has been established for MSC implantation. In this study, we investigate the effects of MSC infusion from the coronary vein in a swine model of chronic myocardial infarction (MI). MI was induced in domestic swine by placing beads in the left coronary artery. Bone marrow cells were aspirated and then cultured to isolate the MSCs. At 4 weeks after MI, MSCs labeled with dye (n ¼ 8) or vehicle (n ¼ 5) were infused retrogradely from the anterior interventricular vein without any complications. Left ventriculography (LVG) was performed just before and at 4 weeks after cell infusion. The ejection fraction (EF) assessed by LVG significantly decreased from baseline up to a follow-up at 4 weeks in the control group (Po0.05), whereas the cardiac function was preserved in the MSC group. The difference in the EF between baseline and follow-up was significantly greater in the MSC group than in the control group (Po0.05). The MSC administration significantly promoted neovascularization in the border areas compared with the controls (Po0.0005), though it had no affect on cardiac fibrosis. A few MSCs expressed von Willebrand factor in a differentiation assay, but none of them expressed troponin T. In quantitative gene expression analysis, basic fibroblast growth factor and vascular endothelial growth factor (VEGF) levels were significantly higher in the MSC-treated hearts than in the controls (Po0.05, respectively). Immunohistochemical staining revealed VEGF production in the engrafted MSCs. In vitro experiment demonstrated that MSCs significantly stimulated endothelial capillary network formation compared with the VEGF protein (Po0.0001). MSC infusion via the coronary vein prevented the progression of cardiac dysfunction in chronic MI. This favorable effect appeared to derive not from cell differentiation, but from enhanced neovascularization by angiogenic factors secreted from the MSCs.

To clarify the role of vascular endothelial growth factor (VEGF) in the process of restenosis, a Palmaz-Schatz stent was implanted in the left anterior descending coronary artery of male pigs at 2 weeks after balloon injury (balloon/artery ratio 1.2:1). The animals were euthanized at 1, 2, and 4 weeks after stenting, and western blot and immunohistochemical analysis were performed using VEGF, fms-like tyrosine kinase (flt)-1, and platelet-derived growth factor (PDGF) antibodies. The expressions of VEGF and flt-1 protein in the neointima were observed as early as 1 week after stenting and remained for up to 4 weeks, while re-endothelialization was complete at 2 weeks. These protein expressions were demonstrated in proliferated smooth muscle cells throughout the entire period after stenting and, in addition, they were observed in the macrophages and endothelial cells of microvessels around stent struts at 4 weeks. The expression pattern of VEGF corresponded with that of PDGF, a growth factor well-known to induce neointimal proliferation. The cell proliferative activity, measured by the proliferating cell nuclear antigen index, around the struts remained high until 4 weeks after stenting, while that in the other areas declined at 4 weeks. These results suggest that VEGF is involved in the process of restenosis not only through its angiogenic properties and induction of monocyte chemotaxis, but also by a synergistic effect with PDGF.

Aims: To investigate the effect of haemodialysis on retinal circulation in patients with end stage renal disease (ESRD). Method: Seventeen consecutive patients with ESRD were recruited into the study. The authors simultaneously measured changes in vessel diameter and blood velocity and calculated the retinal blood flow (RBF) in the retinal veins in patients with ESRD before and after haemodialysis using a laser Doppler velocimetry system. In addition, the relations between the changes in systemic and retinal circulatory parameters were examined.Results: There was a group averaged increase in vessel diameter (p = 0.003) after haemodialysis. However, the blood velocity and RBF values obtained after haemodialysis were not significantly different from those before haemodialysis (p = 0.66 and p = 0.63, respectively). The changes in vessel diameter were negatively (r = 20.549, p = 0.02) correlated with the change in MABP, but the changes in blood velocity and RBF were positively correlated with the change in MABP (r = 0.683, p,0.002 and r = 0.589, p,0.01, respectively). The change in RBF was also inversely correlated with the increase in haematocrit (r = 20.693, p,0.002) and the amount of fluid removed (r = 20.597, p,0.01). Conclusion:The results indicate that haemodialysis and the associated changes in systemic circulatory parameters may affect the retinal circulation in patients with ESRD.